Search results for: blood borne infections

Authors: Milijana N. Miljkovic, Viktorija M. Dragojevic-Simic, Nemanja K. Rancic, Vesna M. Jacevic, Snezana B. Djordjevic, Momir M. Mikov, Aleksandra M. Kovacevic

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Itraconazole (ITZ) is a weak base and extremely lipophilic compound, with water solubility as a rate-limiting step in its absorption from the gastrointestinal tract. Its absolute bioavailability, about 55%, is maximal when its oral formulation, capsules, are taken immediately after a full meal. Peak plasma concentrations (Cmax) are reached within 2 to 5 hrs after their administration. ITZ undergoes extensive hepatic metabolism by human CYP3A4 isoenzyme and more than 30 different metabolites have been identified. One of the main ones is hydroxyitraconazole (HITZ), in which plasma concentrations are almost twice higher than those of ITZ. Gender differences in drug PK (Pharmacokinetics) have already been recognized, but variations in metabolism are believed to be their major cause. The aim of the study was to investigate the influence of gender on ITZ PK parameters after administration of oral capsule formulation, following 100 mg single dosing in healthy adult volunteers under fed conditions. The single-center, open-label PK study was performed. PK analyses included PK parameters obtained after a single 100 mg dose administration of itraconazole capsules to 48 females and 66 males. Blood samples were collected at pre-dose and up to 72.0 h after administration (1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 12.0, 24.0, 36.0 and 72.0 hrs). The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxyitraconazole, were Cmax, AUClast, and AUCtot. Plasma concentrations of ITZ and HITZ were determined using a validated liquid chromatographic method with mass spectrometric detection, while pharmacokinetic parameters were estimated using non-compartmental methods. The pharmacokinetic analyses were performed using Kinetica software version 5.0. The mean value of ITZ Cmaxmen was 74.79 ng/ml, and Cmaxwomen was 51.291 ng/ml (independent samples test; p = 0.005). Hydroxyitraconazole had a mean value of Cmaxmen 106.37 ng/ml, and the mean value Cmaxwomen was 70.05 ng/ml. Women had, on average, lower AUClast and Cmax than men. AUClastmen for ITZ was 736.02 ng/mL*h and AUClastwomen was 566.62 ng/mL*h, while AUClastmen for HITZ was 1154.80 was ng/mL*h and AUClastwomen for HITZ was 708.12 ng/mL*h (independent samples test; p = 0.033). The mean values of ITZ AUCtotmen were 884.73 ng/mL*h and AUCtotwomen was 685.10 ng/mL*h. AUCtotmen for HITZ was 1290.41 ng/mL*h, while AUCtotwomen for HIZT was 788.60 ng/mL*h (p < 0.001). The results could point out to lower oral bioavailability of ITZ in women, since values of Cmax, AUClast, and AUCtot of both ITZ and HITZ were significantly lower in women than in men, respectively. The reason may be higher expression and activity of CYP3A4 in women than in men, but there also may be differences in other PK parameters. High variability of both ITZ and HITZ concentrations in both genders confirmed that ITZ is a highly variable drug. Further examinations of its PK are needed to justify strategies for therapeutic drug monitoring in patients treated by this antifungal agent.

Keywords: itraconazole, gender, hydroxyitraconazole, pharmacokinetics

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Authors: Farah Diab, Mohamad Khalil, Francesca Storace, Francesca Baldini, Piero Portincasaa, Giulio Lupidi, Laura Vergani

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Thymbra spicata is a thyme-like plant belonging to the Lamiaceae family that shows a global distribution, especially in the eastern Mediterranean region. Leaves of T. spicata contain large amounts of phenols such as phenolic acids (rosmarinic acid), phenolic monoterpenes (carvacrol), and flavonoids. In Lebanon, T. spicata is currently used as a culinary herb in salad and infusion, as well as for traditional medicinal purposes. Carvacrol (5-isopropyl-2-methyl phenol), the most abundant polyphenol in the organic extract and essential oils, has a great array of pharmacological properties. In fact, carvacrol is largely employed as a food additive and neutraceutical agent. Our aim is to investigate the beneficial effects of T. spicata ethanolic extract (TE) and its main component, carvacrol, using in vitro models of hepatic steatosis and endothelial dysfunction. As a further point, we focused on investigating if and how the binding of carvacrol to albumin, the physiological transporter for drugs in the blood, might be altered by the presence of high levels of fatty acids (FAs), thus impairing the carvacrol bio-distribution in vivo. For that reason, hepatic FaO cells treated with exogenous FAs such as oleate and palmitate mimic hepatosteatosis; endothelial HECV cells exposed to hydrogen peroxide are a model of endothelial dysfunction. In these models, we measured lipid accumulation, free radical production, lipoperoxidation, and nitric oxide release before and after treatment with carvacrol. The carvacrol binding to albumin with/without high levels of long-chain FAs was assessed by absorption and emission spectroscopies. Our findings show that both TE and carvacrol (i) counteracted lipid accumulation in hepatocytes by decreasing the intracellular and extracellular lipid contents in steatotic FaO cells; (ii) decreased oxidative stress in endothelial cells by significantly reducing lipoperoxidation and free radical production, as well as, attenuating the nitric oxide release; (ii) high levels of circulating FAs reduced the binding of carvacrol to albumin. The beneficial effects of TE and carvacrol on both hepatic and endothelial cells point to a nutraceutical potential. However, high levels of circulating FAs, such as those occurring in metabolic disorders, might hinder the carvacrol transport, bio-distribution, and pharmacodynamics.

Keywords: carvacrol, endothelial dysfunction, fatty acids, non-alcoholic fatty liver diseases, serum albumin

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Authors: Haoming Ma, Guo Yu, Peiru Zhou

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Background: Previous studies show that dysglycemia, mostly hyperglycemia, hypoglycemia and glycemic variability(GV), are associated with excess mortality in critically ill patients, especially those without diabetes. Glycemic variability is an increasingly important measure of glucose control in the intensive care unit (ICU) due to this association. However, there is limited data pertaining to the relationship between different clinical factors and glycemic variability and clinical outcomes categorized by their DM status. This retrospective study of 958 intensive care unit(ICU) patients was conducted to investigate the relationship between GV and outcome in critically ill patients and further to determine the significant factors that contribute to the glycemic variability. Aim: We hypothesize that the factors contributing to mortality and the glycemic variability are different from critically ill patients with or without diabetes. And the primary aim of this study was to determine which dysglycemia (hyperglycemia\hypoglycemia\glycemic variability) is independently associated with an increase in mortality among critically ill patients in different groups (DM/Non-DM). Secondary objectives were to further investigate any factors affecting the glycemic variability in two groups. Method: A total of 958 diabetic and non-diabetic patients with severe diseases in the ICU were selected for this retrospective analysis. The glycemic variability was defined as the coefficient of variation (CV) of blood glucose. The main outcome was death during hospitalization. The secondary outcome was GV. The logistic regression model was used to identify factors associated with mortality. The relationships between GV and other variables were investigated using linear regression analysis. Results: Information on age, APACHE II score, GV, gender, in-ICU treatment and nutrition was available for 958 subjects. Predictors remaining in the final logistic regression model for mortality were significantly different in DM/Non-DM groups. Glycemic variability was associated with an increase in mortality in both DM(odds ratio 1.05; 95%CI:1.03-1.08,p＜0.001) or Non-DM group(odds ratio 1.07; 95%CI:1.03-1.11,p=0.002). For critically ill patients without diabetes, factors associated with glycemic variability included APACHE II score(regression coefficient, 95%CI:0.29,0.22-0.36,p＜0.001), Mean BG(0.73,0.46-1.01,p＜0.001), total parenteral nutrition(2.87,1.57-4.17,p＜0.001), serum albumin(-0.18,-0.271 to -0.082,p＜0.001), insulin treatment(2.18,0.81-3.55,p=0.002) and duration of ventilation(0.006,0.002-1.010,p=0.003).However, for diabetes patients, APACHE II score(0.203,0.096-0.310,p＜0.001), mean BG(0.503,0.138-0.869,p=0.007) and duration of diabetes(0.167,0.033-0.301,p=0.015) remained as independent risk factors of GV. Conclusion: We found that the relation between dysglycemia and mortality is different in the diabetes and non-diabetes groups. And we confirm that GV was associated with excess mortality in DM or Non-DM patients. Furthermore, APACHE II score, Mean BG, total parenteral nutrition, serum albumin, insulin treatment and duration of ventilation were significantly associated with an increase in GV in Non-DM patients. While APACHE II score, mean BG and duration of diabetes (years) remained as independent risk factors of increased GV in DM patients. These findings provide important context for further prospective trials investigating the effect of different clinical factors in critically ill patients with or without diabetes.

Keywords: diabetes, glycemic variability, predictors, severe disease

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Authors: A. Zare Javid, H. Babaee, E. Ashrafzadeh, H. Yousefimanesh, M. Zakerkish, K. Ahmadi Angali, M. Ravanbakhsh

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Introduction: Type 2 diabetes mellitus and periodontal disease hold a physiologically relationship. Periodontal disease, a common widespread chronic disease, is considered as an important complication in diabetes mellitus. The prevalence and severity of periodontal disease are increased among diabetic patients. A balanced nutrition may improve either diabetes or periodontal disease by controlling one of them. The aim of this study was to evaluate the effects of cranberry juice enriched with n-3 PUFA and their individual consumption on glycemic control and antioxidant status in diabetic patients with periodontal disease. Methods: In this randomized clinical trial 41 diabetic patients (35 – 65 y) with chronic adult periodontal disease were recruited from Endocrinology Clinic of Golestan Hospital in Ahvaz city, Iran. Subjects were randomly assigned to four groups as follow: one control group (n=12) and three intervention groups as receiving 1 g n-3 PUFA capsule (n=10), 400 ml cranberry juice (n=9), 400 ml cranberry juice enriched with 1g n-3 PUFA (n=10) for 8 weeks. Non-surgical periodontal therapy was provided for all patients during study. Fasting blood glucose, glycated hemoglobin, plasma and saliva TAOC and MDA, pocket depth and bleeding on probing were measured at baseline and post intervention. Results: There was a significant reduction in glycated hemoglobin observed in intervention groups of receiving n-3 PUFA and cranberry enriched with n-3 PUFA (11 %, P = 0.01 and 7 %, P = 0.01, respectively). The intervention group receiving n-3 PUFA had significantly lower glycated hemoglobin compared with control group. There was no significant difference found in FBS between and within groups. Furthermore, there was a significant increase in plasma TAOC only in cranberry enriched with n-3 PUFA group. Moreover, plasma MDA significantly decreased in intervention groups of receiving cranberry and cranberry enriched with n-3 PUFA. A significant increase was observed in TAOC of salvia in cranberry enriched with n-3 PUFA group compared to control group .The intervention group receiving cranberry enriched with n-3 PUFA had significantly lower MDA of salvia compared with control group. Pocket depth were significantly decreased in all groups, however, bleeding on probing didn’t significantly changed in patients post intervention. Conclusion: It is suggested that consumption of cranberry juice enriched with n-3 PUFA as a nutritional approach in adjunct with non-surgical periodontal therapy may help to improve glycosylated hemogolobin and TAOC in salvia and plasma in diabetic patients with periodontal disease.

Keywords: antioxidant, cranberry, oxidant status, periodontal disease, type 2 diabetes mellitus

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Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

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Authors: Irene Kretchy, Frances Owusu-Daaku, Samuel Danquah

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Hypertension is the leading risk factor for cardiovascular diseases, and a major cause of death and disability worldwide. This study examined whether psychosocial variables influenced patients’ perception and experience of side effects of their medicines, how they coped with these experiences and the impact on mental health and medication adherence to conventional hypertension therapies. Methods: A hospital-based mixed methods study, using quantitative and qualitative approaches was conducted on hypertensive patients. Participants were asked about side effects, medication adherence, common psychological symptoms, and coping mechanisms with the aid of standard questionnaires. Information from the quantitative phase was analyzed with the Statistical Package for Social Sciences (SPSS) version 20. The interviews from the qualitative study were audio-taped with a digital audio recorder, manually transcribed and analyzed using thematic content analysis. The themes originated from participant interviews a posteriori. Results: The experiences of side effects – such as palpitations, frequent urination, recurrent bouts of hunger, erectile dysfunction, dizziness, cough, physical exhaustion - were categorized as no/low (39.75%), moderate (53.0%) and high (7.25%). Significant relationships between depression (x 2 = 24.21, P < 0.0001), anxiety (x 2 = 42.33, P < 0.0001), stress (x 2 = 39.73, P < 0.0001) and side effects were observed. A logistic regression model using the adjusted results for this association are reported – depression [OR = 1.9 (1.03 – 3.57), p = 0.04], anxiety [OR = 1.5 (1.22 – 1.77), p = < 0.001], and stress [OR = 1.3 (1.02 – 1.71), p = 0.04]. Side effects significantly increased the probability of individuals to be non-adherent [OR = 4.84 (95% CI 1.07 – 1.85), p = 0.04] with social factors, media influences and attitudes of primary caregivers further explaining this relationship. The personal adoption of medication modifying strategies, espousing the use of complementary and alternative treatments, and interventions made by clinicians were the main forms of coping with side effects. Conclusions: Results from this study show that contrary to a biomedical approach, the experience of side effects has biological, social and psychological interrelations. The result offers more support for the need for a multi-disciplinary approach to healthcare where all forms of expertise are incorporated into health provision and patient care. Additionally, medication side effects should be considered as a possible cause of non-adherence among hypertensive patients, thus addressing this problem from a Biopsychosocial perspective in any intervention may improve adherence and invariably control blood pressure.

Keywords: biopsychosocial, hypertension, medication adherence, psychological disorders

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Authors: Preet Shah, Om Shrivastav

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Introduction : In India, Leishmania donovani is the only parasite causing Leishmaniasis. The parasite infects the reticuloendothelial system and is found in the bone marrow, spleen and liver. Treatment of choice is amphotericin-B with sodium stibogluconate being an alternative. Miltefosine is useful in refractory cases. In our case, Leishmaniasis occurred in a person residing in western India (which is quite rare) and it failed to respond to two different drugs (again an uncommon feature) before it finally responded to a third one. Description: A 50 year old lady, a resident of western India, with no history of recent travel, presented with an ulcer on the left side of the nose since 8 months. She was apparently alright 8 months back, when she noticed a small ulcerated lesion on the left ala of the nose which was immediately biopsied. The biopsy revealed amastigotes of Leishmania for which she was administered intra-lesional sodium stibogluconate for 1 month (4 doses every 8 days).Despite this, there was no regression of the ulcer and hence she presented to us for further management. On examination, her vital parameters were normal. Barring an ulcer on the left side of the nose, rest of the examination findings were unremarkable. Complete blood count was normal. Ultrasound abdomen showed hepatomegaly. PET-CT scan showed increased metabolic activity in left ala of nose, hepatosplenomegaly and increased metabolic activity in spleen and bone marrow. Bone marrow biopsy was done which showed hypercellular marrow with erythroid preponderance. Considering a diagnosis of leishmaniasis which had so far been unresponsive to sodium stibogluconate, she was started on liposomal amphotericin-B. At the time of admission, her creatinine level was normal, but it started rising with the administration of liposomal amphotericin-B, hence the dose was reduced. Despite this, creatinine levels did not improve, and she started developing hypokalemia and hypomagnesemia as side effects of the drug, hence further reductions in the dosage were made. Despite a total of 3 weeks of liposomal amphotericin-B, there was no improvement in the ulcer. As had so far failed to respond to sodium stibogluconate and liposomal amphotericin-B, it was decided to start her on miltefosine. She received the miltefosine for a total of 12 weeks. At the end of this duration, there was a marked regression of the cutaneous lesion. Conclusion: Refractoriness to amphotericin-B in leishmaniasis may be seen in up to 5 % cases. Here, an alternative drug such as miltefosine is useful and hence we decided to use it, to which she responded adequately. Furthermore, although leishmaniasis is common in the eastern part of India, it is a relatively unknown entity in the western part of the country with the occurrence being very rare. Because of these 2 reasons, we consider our case to be a unique one.

Keywords: amphotericin-b, leishmaniasis, miltefosine, tropical diseases

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Authors: Alberto Alfano, Sergio D’ambrosio, Darshankumar Parecha, Donatella Cimini, Chiara Schiraldi.

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The main objective of this study regards the setup of an efficient small-scale platform for the conversion of local renewable waste materials, such as whey, into added-value products, thereby reducing environmental impact and costs deriving from the disposal of processing waste products. The buffalo milk whey derived from the cheese-making process, called second cheese whey, is the main by-product of the dairy industry. Whey is the main and most polluting by-product obtained from cheese manufacturing consisting of lactose, lactic acid, proteins, and salts, making whey an added-value product. In Italy, and in particular, in the Campania region, soft cheese production needs a large volume of liquid waste, especially during late spring and summer. This project is part of a circular economy perspective focused on the conversion of potentially polluting and difficult to purify waste into a resource to be exploited, and it embodies the concept of the three “R”: reduce, recycle, and reuse. Special focus was paid to the production of health-promoting biomolecules and biopolymers, which may be exploited in different segments of the food and pharmaceutical industries. These biomolecules may be recovered through appropriate processes and reused in an attempt to obtain added value products. So, ultrafiltration and nanofiltration processes were performed to fractionate bioactive components starting from buffalo milk whey. In this direction, the present study focused on the implementation of a downstream process that converts waste generated from food and food processing industries into added value products with potential applications. Owing to innovative downstream and biotechnological processes, rather than a waste product may be considered a resource to obtain high added value products, such as food supplements (probiotics), cosmeceuticals, biopolymers, and recyclable purified water. Besides targeting gastrointestinal disorders, probiotics such as Lactobacilli have been reported to improve immunomodulation and protection of the host against infections caused by viral and bacterial pathogens. Interestingly, also inactivated microbial (probiotic) cells and their metabolic products, indicated as parabiotic and postbiotics, respectively, have a crucial role and act as mediators in the modulation of the host’s immune function. To boost the production of biomass (both viable and/or heat inactivated cells) and/or the synthesis of growth-related postbiotics, such as EPS, efficient and sustainable fermentation processes are necessary. Based on a “zero-waste” approach, wastes generated from local industries can be recovered and recycled to develop sustainable biotechnological processes to obtain probiotics as well as post and parabiotic, to be tested as bioactive compounds against gastrointestinal disorders. The results have shown it was possible to recover an ultrafiltration retentate with suitable characteristics to be used in skin dehydration, to perform films (i.e., packaging for food industries), or as a wound repair agent and a nanofiltration retentate to recover lactic acid and carbon sources (e.g., lactose, glucose..) used for microbial cultivation. On the side, the last goal is to obtain purified water that can be reused throughout the process. In fact, water reclamation and reuse provide a unique and viable opportunity to augment traditional water supplies, a key issue nowadays.

Keywords: biotech process, downstream process, probiotic growth, from waste to product, buffalo whey

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Authors: Irina M. Kolesnikova, Andrey M. Gaponov, Sergey A. Roumiantsev, Tatiana V. Grigoryeva, Alexander V. Laikov, Alexander V. Shestopalov

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Background. Neuropathy is a common complication of obesity. In this regard, the content of neurotrophins in such patients is of particular interest. Neurotrophins are the proteins that regulate neuron survival and neuroplasticity and include brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). However, the risk of complications depends on the metabolic type of obesity. Metabolically unhealthy obesity (MUHO) is associated with a high risk of complications, while this is not the case with metabolically healthy obesity (MHO). Therefore, the aim of our work was to study the effect of the obesity metabolic type on serum neurotrophins levels. Patients, materials, methods. The study included 134 healthy donors and 104 obese patients. Depending on the metabolic type of obesity, the obese patients were divided into subgroups with MHO (n=40) and MUHO (n=55). In the blood serum, the concentration of BDNF and NGF was determined. In addition, the content of adipokines (leptin, asprosin, resistin, adiponectin), myokines (irisin, myostatin, osteocrin), indicators of carbohydrate, and lipid metabolism were measured. Correlation analysis revealed the relationship between the studied parameters. Results. We found that serum BDNF concentration was not different between obese patients and healthy donors, regardless of obesity metabolic type. At the same time, in obese patients, there was a decrease in serum NGF level versus control. A similar trend was characteristic of both MHO and MUHO. However, MUHO patients had a higher NGF level than MHO patients. The literature indicates that obesity is associated with an increase in the plasma concentration of NGF. It can be assumed that in obesity, there is a violation of NGF storage in platelets, which accelerates neurotrophin degradation. We found that BDNF concentration correlated with irisin levels in MUHO patients. Healthy donors had a weak association between NGF and VEGF levels. No such association was found in obese patients, but there was an association between NGF and leptin concentrations. In MHO, the concentration of NHF correlated with the content of leptin, irisin, osteocrin, insulin, and the HOMA-IR index. But in MUHO patients, we found only the relationship between NGF and adipokines (leptin, asprosin). It can be assumed that in patients with MHO, the replenishment of serum NGF occurs under the influence of muscle and adipose tissue. In the MUHO patients only the effect of adipose tissue on NGF was observed. Conclusion. Obesity, regardless of metabolic type, is associated with a decrease in serum NGF concentration. We showed that muscle and adipose tissues make a significant contribution to the serum NGF pool in the MHO patients. In MUHO there is no effect of muscle on the NGF level, but the effect of adipose tissue remains.

Keywords: neurotrophins, nerve growth factor, NGF, brain-derived neurotrophic factor, BDNF, obesity, metabolically healthy obesity, metabolically unhealthy obesity

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Authors: Bonnie Clough, Tamara Ownsworth, Vladimir Estivill-Castro, Matt Stainer, Rene Hexel, Andrew Bulmer, Wendy Moyle, Allison Waters, David Neumann, Jayke Bennett

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The success of global vaccination programs is reliant on the uptake of vaccines to achieve herd immunity. Yet, many individuals do not obtain vaccines or venipuncture procedures when needed. Whilst health education may be effective for those individuals who are hesitant due to safety or efficacy concerns, for many of these individuals, the primary concern relates to blood or injection fear or phobia (BII). BII is highly prevalent and associated with a range of negative health impacts, both at individual and population levels. Exposure therapy is an efficacious treatment for specific phobias, including BII, but has high patient dropout and low implementation by therapists. Whilst virtual reality approaches exposure therapy may be more acceptable, they have similarly low rates of implementation by therapists and are often difficult to tailor to an individual client’s needs. It was proposed that a piloted robot may be able to adequately facilitate fear induction and be an acceptable approach to exposure therapy. The current study examined fear induction responses, acceptability, and feasibility of a piloted robot for BII exposure. A Nao humanoid robot was programmed to connect with a virtual reality head-mounted display, enabling live streaming and exploration of real environments from a distance. Thirty adult participants with BII fear were randomly assigned to robot-pilot or virtual reality exposure conditions in a laboratory-based fear exposure task. All participants also completed a computer-based two-dimensional exposure task, with an order of conditions counterbalanced across participants. Measures included fear (heart rate variability, galvanic skin response, stress indices, and subjective units of distress), engagement with a feared stimulus (eye gaze: time to first fixation and a total number of fixations), acceptability, and perceived treatment credibility. Preliminary results indicate that fear responses can be adequately induced via a robot-piloted platform. Further results will be discussed, as will implications for the treatment of BII phobia and other fears. It is anticipated that piloted robots may provide a useful platform for facilitating exposure therapy, being more acceptable than in-vivo exposure and more flexible than virtual reality exposure.

Keywords: anxiety, digital mental health, exposure therapy, phobia, robot, virtual reality

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Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar

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Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.

Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis

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Authors: Charles Mazhazhate

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This study interrogates and analyses the intricate kin- and- kith network patterns of corruption and mismanagement of resources prevalent in public sector supply chains bedeviling the developing economies of Sub-Saharan Africa with particular reference to Zimbabwe. This is forcing governments to resort to harsh fiscal policies that see their citizens paying high taxes against a backdrop of incomes below the poverty datum line, and this negatively affects their quality of life. The corporate world is also affected by the various tax-regime instituted. Mismanagement of resources and corrupt practices are rampant in state-owned enterprises to the extent that institutional policies, procedures, and practices are often flouted for the benefit of a clique of individuals. This interwoven in kith and kin blood human relations in organizations where appointments to critical positions are based on ascribed status. People no longer place value in their systems to make them work thereby violating corporate governance principles. Greediness and ‘unholy friendship connections’ are instrumental in fueling the employment of people who know each other from their discrete backgrounds. Such employments or socio-metric unions are meant to protect those at the top by giving them intelligent information through spying on what other subordinates are doing inside and outside the organization. This practice has led to the underperforming of organizations as those employees with connections and their upper echelons favorites connive to abuse resources for their own benefit. Even if culprits are known, no draconian measures are employed as a deterrence measure. Public value along public sector supply chains is lost. The study used a descriptive case study research design on fifty organizations in Zimbabwe mainly state-owned enterprises. Both qualitative and quantitative instrumentations were used. Both Snowball and random sampling techniques were used. The study found out that in all the fifty SOEs, there were employees in key positions related to top management, with tentacles feeding into the law enforcement agents, judiciary, security systems, and the executive. Such employees in public seem not to know each other with but would be involved in dirty scams and then share the proceeds with top people behind the scenes. The study also established that the same employees do not have the necessary competencies, qualifications, abilities, and capabilities to be in those positions. This culture is now strong that it is difficult to bust. The study recommends recruitment of all employees through an independent employment bureau to ensure strategic fit.

Keywords: corruption, state owned enterprises, strategic fit, public sector supply chains, efficiency

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Authors: Magdy I. A. Alshourbagi

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Background: The National Institute for Deafness and Communication Disorders defines idiopathic sudden sensorineural hearing loss as the idiopathic loss of hearing of at least 30 dB across 3 contiguous frequencies occurring within 3 days.The most common clinical presentation involves an individual experiencing a sudden unilateral hearing loss, tinnitus, a sensation of aural fullness and vertigo. The etiologies and pathologies of ISSNHL remain unclear. Several pathophysiological mechanisms have been described including: vascular occlusion, viral infections, labyrinthine membrane breaks, immune associated disease, abnormal cochlear stress response, trauma, abnormal tissue growth, toxins, ototoxic drugs and cochlear membrane damage. The rationale for the use of hyperbaric oxygen to treat ISSHL is supported by an understanding of the high metabolism and paucity of vascularity to the cochlea. The cochlea and the structures within it require a high oxygen supply. The direct vascular supply, particularly to the organ of Corti, is minimal. Tissue oxygenation to the structures within the cochlea occurs via oxygen diffusion from cochlear capillary networks into the perilymph and the cortilymph. . The perilymph is the primary oxygen source for these intracochlear structures. Unfortunately, perilymph oxygen tension is decreased significantly in patients with ISSHL. To achieve a consistent rise of perilymph oxygen content, the arterial-perilymphatic oxygen concentration difference must be extremely high. This can be restored with hyperbaric oxygen therapy. Subject and Methods: A 37 year old man was presented at the clinic with a five days history of muffled hearing and tinnitus of the right ear. Symptoms were sudden onset, with no associated pain, dizziness or otorrhea and no past history of hearing problems or medical illness. Family history was negative. Physical examination was normal. Otologic examination revealed normal tympanic membranes bilaterally, with no evidence of cerumen or middle ear effusion. Tuning fork examination showed positive Rinne test bilaterally but with lateralization of Weber test to the left side, indicating right ear sensorineural hearing loss. Audiometric analysis confirmed sensorineural hearing loss across all frequencies of about 70- dB in the right ear. Routine lab work were all within normal limits. Clinical diagnosis of idiopathic sudden sensorineural hearing loss of the right ear was made and the patient began a medical treatment (corticosteroid, vasodilator and HBO therapy). The recommended treatment profile consists of 100% O2 at 2.5 atmospheres absolute for 60 minutes daily (six days per week) for 40 treatments .The optimal number of HBOT treatments will vary, depending on the severity and duration of symptomatology and the response to treatment. Results: As HBOT is not yet a standard for idiopathic sudden sensorineural hearing loss, it was introduced to this patient as an adjuvant therapy. The HBOT program was scheduled for 40 sessions, we used a 12-seat multi place chamber for the HBOT, which was started at day seven after the hearing loss onset. After the tenth session of HBOT, improvement of both hearing (by audiogram) and tinnitus was obtained in the affected ear (right). Conclusions: In conclusion, HBOT may be used for idiopathic sudden sensorineural hearing loss as an adjuvant therapy. It may promote oxygenation to the inner ear apparatus and revive hearing ability. Patients who fail to respond to oral and intratympanic steroids may benefit from this treatment. Further investigation is warranted, including animal studies to understand the molecular and histopathological aspects of HBOT and randomized control clinical studies.

Keywords: idiopathic sudden sensorineural hearing loss (issnhl), hyperbaric oxygen therapy (hbot), the decibel (db), oxygen (o2)

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Authors: Carmiña L. Vargas-Zapata, María A. Conde-Sarmiento, Maria Consuelo Maestre-Vargas

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Calcium is an essential element for good growth and development of the organism, and its requirement is increased at school age. Low socio-economic populations of developing countries such as Colombia may have food deficiency of this mineral in schoolchildren that could be reflected in calcium biochemical indicators, bone alterations and anthropometric indicators. The objective of this investigation was to evaluate some calcium biochemical indicators in a group of schoolchildren of low socioeconomic level from Barranquilla city and to correlate with body mass index. 60 schoolchildren aged 7 to 15 years were selected from Jesus’s Heart Educational Institution in Barranquilla-Atlántico, apparently healthy, without suffering from infectious or gastrointestinal diseases, without habits of drinking alcohol or smoking another hallucinogenic substance and without taking supplementation with calcium in the last six months or another substance that compromises bone metabolism. The research was approved by the ethics committee at Universidad del Atlántico. The selected children were invited to donate a blood and urine sample in a fasting time of 12 hours, the serum was separated by centrifugation and frozen at ˗20 ℃ until analyzed and the same was done with the urine sample. On the day of the biological collections, the weight and height of the students were measured to determine the nutritional status by BMI using the WHO tables. Calcium concentrations in serum and urine (SCa, UCa), alkaline phosphatase activity total and of bone origin (SAPT, SBAP) and urinary creatinine (UCr) were determined by spectrophotometric methods using commercial kits. Osteocalcin and Cross-linked N-telopeptides of type I collagen (NTx-1) in serum were measured with an enzyme-linked inmunosorbent assay. For statistical analysis the Statgraphics software Centurium XVII was used. 63% (n = 38) and 37% (n = 22) of the participants were male and female, respectively. 78% (n = 47), 5% (n = 3) and 17% (n = 10) had a normal, malnutrition and high nutritional status, respectively. The averages of evaluated indicators levels were (mean ± SD): 9.50 ± 1.06 mg/dL for SCa; 181.3 ± 64.3 U/L for SAPT, 143.8 ± 73.9 U/L for SBAP; 9.0 ± 3.48 ng/mL for osteocalcin and 101.3 ± 12.8 ng/mL for NTx-1. UCa level was 12.8 ± 7.7 mg/dL that adjusted with creatinine ranged from 0.005 to 0.395 mg/mg. Considering serum calcium values, approximately 7% of school children were hypocalcemic, 16% hypercalcemic and 77% normocalcemic. The indicators evaluated did not correlate with the BMI. Low values ​​were observed in calcium urinary excretion and high in NTx-1, suggesting that mechanisms such as increase in renal retention of calcium and in bone remodeling may be contributing to calcium homeostasis.

Keywords: calcium, calcium biochemical, indicators, school children, low socioeconomic status

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Authors: John Kosmeh

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Introduction – For years, senior health care and skilled nursing facilities have been plagued with the dilemma of not having the necessary tools and equipment to adequately care for senior residents in their communities. This has led to high transport rates to emergency departments and high 30-day readmission rates, costing billions of unnecessary dollars each year, as well as quality assurance issues. Our Senior care telemedicine program is designed to solve this issue. Methods – We conducted a 1-year pilot program using our technology coupled with our 24/7 telemedicine program with skilled nursing facilities in different parts of the United States. We then compared transports rates and 30-day readmission rates to previous years before the use of our program, as well as transport rates of other communities of similar size not using our program. This data was able to give us a clear and concise look at the success rate of reducing unnecessary transport and readmissions as well as cost savings. Results – A 94% reduction nationally of unnecessary out-of-facility transports, and to date, complete elimination of 30-day readmissions. Our virtual platform allowed us to instruct facility staff on the utilization of our tools and system as well as deliver treatment by our ER-trained providers. Delay waiting for PCP callbacks was eliminated. We were able to obtain lung, heart, and abdominal ultrasound imaging, 12 lead EKG, blood labs, auscultate lung and heart sounds, and collect other diagnostic tests at the bedside within minutes, providing immediate care and allowing us to treat residents within the SNF. Are virtual capabilities allowed for loved ones, family members, and others who had medical power of attorney to virtually connect with us at the time of visit, to speak directly with the medical provider, providing increased confidence in the decision to treat the resident in-house. The decline in transports and readmissions will greatly reduce governmental cost burdens, as well as fines imposed on SNF for high 30-day readmissions, reduce the cost of Medicare A readmissions, and significantly impact the number of patients visiting overcrowded ERs. Discussion – By utilizing our program, SNF can effectively reduce the number of unnecessary transports of residents, as well as create significant savings from loss of day rates, transportation costs, and high CMS fines. The cost saving is in the thousands monthly, but more importantly, these facilities can create a higher quality of life and medical care for residents by providing definitive care instantly with ER-trained personnel.

Keywords: senior care, long term care, telemedicine, technology, senior care communities

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Authors: Allaire Eric, Hauet Pascal, Floresco Jean, Beley Sebastien, Sussman Helene, Virag Ronald

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Background: Caverno-venous leakage (CVL) is devastating, although barely known disease, the first cause of major physical impairment in men under 25, and responsible for 50% of resistances to phosphodiesterase 5-inhibitors (PDE5-I), affecting 30 to 40% of users in this medication class. In this condition, too early blood drainage from corpora cavernosa prevents penile rigidity and penetration during sexual intercourse. The role of conservative surgery in this disease remains controversial. Aim: Assess complications and results of combined open surgery and embolization for CVL. Method: Between June 2016 and September 2021, 133 consecutive patients underwent surgery in our institution for CVL, causing severe erectile dysfunction (ED) resistance to oral medical treatment. Procedures combined vein embolization and ligation with microsurgical techniques. We performed a pre-and post-operative clinical (Erection Harness Scale: EHS) hemodynamic evaluation by duplex sonography in all patients. Before surgery, the CVL network was visualized by computed tomography cavernography. Penile EMG was performed in case of diabetes or suspected other neurological conditions. All patients were optimized for hormonal status—data we prospectively recorded. Results: Clinical signs suggesting CVL were ED since age lower than 25, loss of erection when changing position, penile rigidity varying according to the position. Main complications were minor pulmonary embolism in 2 patients, one after airline travel, one with Factor V Leiden heterozygote mutation, one infection and three hematomas requiring reoperation, one decreased gland sensitivity lasting for more than one year. Mean pre-operative pharmacologic EHS was 2.37+/-0.64, mean pharmacologic post-operative EHS was 3.21+/-0.60, p<0.0001 (paired t-test). The mean EHS variation was 0.87+/-0.74. After surgery, 81.5% of patients had a pharmacologic EHS equal to or over 3, allowing for intercourse with penetration. Three patients (2.2%) experienced lower post-operative EHS. The main cause of failure was leakage from the deep dorsal aspect of the corpus cavernosa. In a 14 months follow-up, 83.2% of patients had a clinical EHS equal to or over 3, allowing for sexual intercourse with penetration, one-third of them without any medication. 5 patients had a penile implant after unsuccessful conservative surgery. Conclusion: Open surgery combined with embolization for CVL is an efficient approach to CVL causing severe erectile dysfunction.

Keywords: erectile dysfunction, cavernovenous leakage, surgery, embolization, treatment, result, complications, penile duplex sonography

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Authors: Michelle Rippy

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Medicolegal death investigation historically is a field that does not receive much research attention or advancement, as all of the subjects are deceased. Public health threats, drug epidemics and contagious diseases are typically recognized in decedents first, with thorough and accurate death investigations able to assist in epidemiology research and prevention programs. One vital component of medicolegal death investigation is determining the decedent’s time of death. An accurate time of death can assist in corroborating alibies, determining sequence of death in multiple casualty circumstances and provide vital facts in civil situations. Popular television portrays an unrealistic forensic ability to provide the exact time of death to the minute for someone found deceased with no witnesses present. The actuality of unattended decedent time of death determination can generally only be narrowed to a 4-6 hour window. In the mid- to late-20th century, liver temperatures were an invasive action taken by death investigators to determine the decedent’s core temperature. The core temperature was programmed into an equation to determine an approximate time of death. Due to many inconsistencies with the placement of the thermometer and other variables, the accuracy of the liver temperatures was dispelled and this once common place action lost scientific support. Currently, medicolegal death investigators utilize three major after death or post-mortem changes at a death scene. Many factors are considered in the subjective determination as to the time of death, including the cooling of the decedent, stiffness of the muscles, release of blood internally, clothing, ambient temperature, disease and recent exercise. Current research is utilizing non-invasive hospital grade tympanic thermometers to measure the temperature in the each of the decedent’s ears. This tool can be used at the scene and in conjunction with scene indicators may provide a more accurate time of death. The research is significant and important to investigations and can provide an area of accuracy to a historically inaccurate area, considerably improving criminal and civil death investigations. The goal of the research is to provide a scientific basis to unwitnessed deaths, instead of the art that the determination currently is. The research is currently in progress with expected termination in December 2018. There are currently 15 completed case studies with vital information including the ambient temperature, decedent height/weight/sex/age, layers of clothing, found position, if medical intervention occurred and if the death was witnessed. This data will be analyzed with the multiple variables studied and available for presentation in January 2019.

Keywords: algor mortis, forensic pathology, investigations, medicolegal, time of death, tympanic

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Authors: Ying Li, Rui Hu, Shizhen Chen, Xin Zhou, Yunhuang Yang

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Prostate cancer is one of the leading causes of cancer-related death among men. Prostate-specific antigen (PSA), a specific product of prostatic epithelial cells, is an important indicator of prostate cancer. Though PSA is not a specific serum biomarker for the screening of prostate cancer, it is recognized as an indicator for prostate cancer recurrence and response to therapy for patient’s post-prostatectomy. Since radical prostatectomy eliminates the source of PSA production, serum PSA levels fall below 50 pg/mL, and may be below the detection limit of clinical immunoassays (current clinical immunoassay lower limit of detection is around 10 pg/mL). Many clinical studies have shown that intervention at low PSA levels was able to improve patient outcomes significantly. Therefore, ultra-sensitive and precise assays that can accurately quantify extremely low levels of PSA (below 1-10 pg/mL) will facilitate the assessment of patients for the possibility of early adjuvant or salvage treatment. Currently, the commercially available ultra-sensitive ELISA kit (not used clinically) can only reach a detection limit of 3-10 pg/mL. Other platforms developed by different research groups could achieve a detection limit as low as 0.33 pg/mL, but they relied on sophisticated instruments to get the final readout. Herein we report a microfluidic platform for point-of-care (POC) detection of PSA with a detection limit of 0.5 pg/mL and without the assistance of any equipment. This platform is based on a previously reported volumetric-bar-chart chip (V-Chip), which applies platinum nanoparticles (PtNPs) as the ELISA probe to convert the biomarker concentration to the volume of oxygen gas that further pushes the red ink to form a visualized bar-chart. The length of each bar is used to quantify the biomarker concentration of each sample. We devised a long reading channel V-Chip (LV-Chip) in this work to achieve a wide detection window. In addition, LV-Chip employed a unique enzyme-free ELISA probe that enriched PtNPs significantly and owned 500-fold enhanced catalytic ability over that of previous V-Chip, resulting in a significantly improved detection limit. LV-Chip is able to complete a PSA assay for five samples in 20 min. The device was applied to detect PSA in 50 patient serum samples, and the on-chip results demonstrated good correlation with conventional immunoassay. In addition, the PSA levels in finger-prick whole blood samples from healthy volunteers were successfully measured on the device. This completely stand-alone LV-Chip platform enables convenient POC testing for patient follow-up in the physician’s office and is also useful in resource-constrained settings.

Keywords: point-of-care detection, microfluidics, PSA, ultra-sensitive

Procedia PDF Downloads 88

Authors: Yael Wolff Sagy, Yiska Loewenberg Weisband, Vered Kaufman Shriqui, Michal Krieger, Arie Ben Yehuda, Ronit Calderon Margalit

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Background: Obesity is both a risk factor and common comorbidity of diabetes. Obesity impedes the achievement of glycemic control, and enhances damage caused by hyperglycemia to blood vessels; thus it increases diabetes-related complications. This study assessed the prevalence of obesity and morbid obesity among Israeli adults with diabetes, and estimated disparities associated with sex and socioeconomic position (SEP). Methods: A cross-sectional study was conducted in the setting of the Israeli National Program for Quality Indicators in Community Healthcare. Data on all the Israeli population is retrieved from electronic medical records of the four health maintenance organizations (HMOs). The study population included all Israeli patients with diabetes aged 20-64 with documented body mass index (BMI) in 2016 (N=180,451). Diabetes was defined as the existence of one or more of the following criteria: (a) Plasma glucose level >200 mg% in at least two tests conducted at least one month apart in the previous year; (b) HbA1c>6.5% at least once in the previous year (c) at least three prescriptions of diabetes medications were dispensed during the previous year. Two measures were included: the prevalence of obesity (defined as last BMI≥ 30 kg/m2 and <35 kg/m2) and the prevalence of morbid obesity (defined as last BMI≥ 35 kg/m2) in individuals aged 20-64 with diabetes. The cut-off value for morbid obesity was set in accordance with the eligibility criteria for bariatric surgery in diabetics. Data were collected by the HMOs and aggregated by age, sex and SEP. SEP was based on statistical areas ranking by the Israeli Central Bureau of Statistics and divided into 4 categories, ranking from 1 (lowest) to 4 (highest). Results: BMI documentation among adults with diabetes was 84.9% in 2016. The prevalence of obesity in the study population was 30.5%. Although the overall rate was similar in both sexes (30.8% in females, 30.3% in males), SEP disparities were stronger in females (32.7% in SEP level 1 vs. 27.7% in SEP level 4; 18.1% relative difference) compared to males (30.6% in SEP level 1 vs. 29.3% in SEP level 4; 4.4% relative difference). The overall prevalence of morbid obesity in this population was 20.8% in 2016. The rate among females was almost double compared to the rate in males (28.1% and 14.6%, respectively). In both sexes, the prevalence of morbid obesity was strongly associated with lower SEP. However, in females, disparities between SEP levels were much stronger (34.3% in SEP level 1 vs. 18.7% in SEP level 4; 83.4% relative difference) compared to SEP-disparities in males (15.7% in SEP level 1 vs. 12.3% in SEP level 4; 27.6% relative difference). Conclusions: The overall prevalence of BMI≥ 30 kg/m2 among adults with diabetes in Israel exceeds 50%; and the prevalence of morbid obesity suggests that 20% meet the BMI-criteria for bariatric surgery. Prevalence rates show major SEP- and sex-disparities; especially strong SEP disparities in morbid obesity among females. These findings highlight the need for greater consideration of different population groups when implementing interventions.

Keywords: diabetes, health disparities, health policy, obesity, socio-economic position

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Authors: Da Yoon Yu, Jeong A. Kim, In Sung Kim, Yeon Hee Hong, Jae Young Kim, Sang Suk Lee, Sung Chan Kim, So Hui Choe, In Soon Choi, Kwang Keun Cho

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The present study was conducted to identify the effects of synbiotics composed of lactic acid (LA) bacteria (LAB) and sea tangle on rat’s intestinal microorganisms and anti-obesity effects. The experiment was conducted for six weeks using an 8-week old male rat as experiment animals and the experimental design was to use six treatments groups of 4 repetitions using three mice per repetition. The treatment groups were organized into a normal fat diet control (NFC), a high fat (HF) diet control (HFC), a prebiotic 0% treatment (HF+LA+sea tangle 0%, ST0), a prebiotic 5% treatment (HF+LA+sea tangle 5%, ST5), a prebiotic 10% treatment (HF+LA+sea tangle 10%, ST10), and a prebiotic 15% treatment group (HF+LA+sea tangle 15%, ST15) to conduct experiments with various levels of prebiotics. According to the results of the experiment, the NFC group showed the highest daily weight gain (22.34g) and the ST0 group showed the lowest daily weight gain (19.41g). However, weight gains during the entire experimental period were the highest in the HFC group (475.73g) and the lowest in the ST0 group (454.23g). Feed efficiency was the highest in the HFC group (0.20). Treatment with synbiotics composed of LAB and sea tangle suppressed weight increases due to HF diet and reduced feed efficiency. Intestinal microorganisms were identified through pyrosequncing and according to the results, Firmicutes phylum (approximately 60%) and Bacteroidetes phylum (approximately 30%) accounted for approximately 90% or more of intestinal microorganisms in all of the treatment groups indicating these bacteria are dominating in the intestines. Firmicutes that is related to weight increases accounted for 64.96% of microorganisms in the NFC group, 75.32% in the HFC group, 59.51% in the ST0 group, 61.29% in the ST5 group, 49.91% in the ST10 group, and 39.65% in the ST15 group. Therefore, Firmicutes showed the highest share the HFC group that showed high weight gains and the lowest share in the group treated with mixed synbiotics composed of LAB and sea tangle. Bacteroidetes that is related to weight gain inhibition accounted for 32.12% of microorganisms in the NFC group, and HFC group 21.57%, ST0 group 37.66%, ST5 group 34.92%, ST10 group 44.46%, and ST15 group 53.22%. Therefore, the share of Bacteroidetes was the lowest in the HFC group with no addition of synbiotics and increased along with the level of treatment with synbiotics. Changes in blood components were not significantly different among the groups and SCFA yields were shown to be higher in groups treated with synbiotics than in groups not added with synbiotics. Through the present study, it was shown that the supply of synbiotics composed of LAB and sea tangle increased feed intake but led to weight losses and that the intake of synbiotics composed of LAB and sea tangle had anti-obesity effects due to decreases in Firmicutes which are microorganisms related to weight gains and increases in Bacteroidetes which are microorganisms related to weight losses. Therefore, synbiotics composed of LAB and sea tangle are considered to have the effect to prevent metabolic disorders in the rat.

Keywords: bacteroidetes, firmicutes, intestinal microbiota, lactic acid, sea tangle, synbiotics

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Authors: Christelle E. Chua, Alicia L. Ho

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The development of a panel of differential gene expression signatures has been of interest in the field of biomarker discovery for radiation exposure. In the absence of the availability of exposed human subjects, lymphocyte cell lines have often been used as a surrogate to human whole blood, when performing ex vivo irradiation studies. The extent of variation between different lymphocyte cell lines is currently unclear, especially with regard to the expression of extracellular miRNA. This study compares the expression profile of extracellular miRNA isolated from different lymphocyte cell lines. It also compares the profile of miRNA obtained when different exosome isolation kits are used. Lymphocyte cell lines were created using lymphocytes isolated from healthy adult males of similar racial descent (Chinese American and Chinese Singaporean) and immortalised with Epstein-Barr virus. The cell lines were cultured in exosome-free cell culture media for 72h and the cell culture supernatant was removed for exosome isolation. Two exosome isolation kits were used. Total exosome isolation reagent (TEIR, ThermoFisher) is a polyethylene glycol (PEG)-based exosome precipitation kit, while ExoSpin (ES, Cell Guidance Systems) is a PEG-based exosome precipitation kit that includes an additional size exclusion chromatography step. miRNA from the isolated exosomes were isolated using miRNEASY minikit (Qiagen) and analysed using nCounter miRNA assay (Nanostring). Principal component analysis (PCA) results suggested that the overall extracellular miRNA expression profile differed between the lymphocyte cell line originating from the Chinese American donor and the cell line originating from the Chinese Singaporean donor. As the gender, age and racial origins of both donors are similar, this may suggest that there are other genetic or epigenetic differences that account for the variation in extracellular miRNA gene expression in lymphocyte cell lines. However, statistical analysis showed that only 3 miRNA genes had a fold difference > 2 at p < 0.05, suggesting that the differences may not be of that great a significance as to impact overall conclusions drawn from different cell lines. Subsequent analysis using cell lines from other donors will give further insight into the reproducibility of results when difference cell lines are used. PCA results also suggested that the method of exosome isolation impacted the expression profile. 107 miRNA had a fold difference > 2 at p < 0.05. This suggests that the inclusion of an additional size exclusion chromatography step altered the subset of the extracellular vesicles that were isolated. In conclusion, these results suggest that extracellular miRNA can be isolated and analysed from exosomes derived from lymphocyte cell lines. However, care must be taken in the choice of cell line and method of exosome isolation used.

Keywords: biomarker, extracellular miRNA, isolation methods, lymphocyte cell line

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Authors: Mohit Kumar, Beklashwar Salona, Shiv Murti, Mukesh Singh

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We report here a case of five-months old male baby, born as second child of non-consanguineous parents with no considerable history of genetic abnormality which was referred to our cytogenetic laboratory for chromosomal analysis. Physical dysmorphic facial features including mongoloid face, cleft palate, simian crease, and developmental delay were observed. We present this case with unique balanced autosomal translocation of t(3;10)(p21;p13). The risk of phenotypic abnormalities based on de novo balanced translocation was estimated to be 7%. The association of balanced chromosomal rearrangement with Down syndrome features such as multiple congenital anomalies, facial dysmorphism and congenital heart anomalies are very rare in a 5-months old male child. Trisomy-21 is not uncommon in chromosomal abnormality with the birth defect and balanced translocations are frequently observed in patients with secondary infertility or recurrent spontaneous abortion (RSA). Two ml heparinized peripheral blood cells cultured in RPMI-1640 for 72 hours supplemented with 20% fetal bovine serum, phytohemagglutinin (PHA), and antibiotics were used for chromosomal analysis. A total 30 metaphases images were captured using Olympus-BX51 microscope and analyzed using Bio-view karyotyping software through GTG-banding (G bands by trypsin and Giemsa) according to International System for Human Cytogenetic Nomenclature 2016. The results showed balanced translocation between short arm of chromosome # 3 and short arm of chromosome # 10. The karyotype of the child was found to be 46,XY,t(3;10)(p21; p13). Chromosomal abnormalities are one of the major causes of birth defect in new born babies. Also, balanced translocations are frequently observed in patients with secondary infertility or recurrent spontaneous abortion. The index case presented with dysmorphic facial features and had a balanced translocation 46,XY,t(3;10)(p21;p13). This translocation with break points at (p21; p13) has not been reported in the literature in a child with facial dysmorphism. To the best of our knowledge, this is the first report of novel balanced translocation t(3;10) with break points in a child with dysmorphic features. We found balanced chromosomal translocation instead of any trisomy or unbalanced aberrations along with some phenotypic abnormalities. Therefore, we suggest that such novel balanced translocation with abnormal phenotype should be reported in order to enable the pathologist, pediatrician, and gynecologist to have a better insight into the intricacies of chromosomal abnormalities and their associated phenotypic features. We hypothesized that dysmorphic features as seen in this case may be the result of change in the pattern of genes located at the breakpoint area in balanced translocations or may be due to deletion or mutation of genes located on the p-arm of chromosome # 3 and p-arm of chromosome # 10.

Keywords: balanced translocation, karyotyping, phenotypic abnormalities, facial dimorphisms

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Authors: K. Azadeh, M. Ghasemi, S. Fazelifar

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Aim: Changes in stress hormones can be modify response of immune system. Cortisol as the most important body corticosteroid is anti-inflammatory and immunosuppressive hormone. Normal levels of cortisol in humans has fluctuated during the day, In other words, cortisol is released periodically, and regulate through the release of ACTH circadian rhythm in every day. Therefore, the aim of this study was to determine the effects of Chamomile on serum levels of inflammatory indexes to a bout of eccentric exercise in young women. Methodology: 32 women were randomly divided into 4 groups: high dose of Chamomile, low dose of Chamomile, ibuprofen and placebo group. Eccentric exercise included 5 set and rest period between sets was 1 minute. For this purpose, subjects warm up 10 min and then done eccentric exercise. Each participant completed 15 repetitions with optional 20 kg weight or until can’t continue moving. When the subject was no longer able to continue to move, immediately decreased 5 kg from the weight and the protocol continued until cause exhaustion or complete 15 repetitions. Also, subjects received specified amount of ibuprofen and Chamomile capsules in target groups. Blood samples in 6 stages (pre of starting pill, pre of exercise protocol, 4, 24, 48 and 72 hours after eccentric exercise) was obtained. The levels of cortisol and adrenocorticotropic hormone levels were measured by ELISA way. K-S test to determine the normality of the data and analysis of variance for repeated measures was used to analyze the data. A significant difference in the p < 0/05 accepted. Results: The results showed that Individual characteristics including height, weight, age and body mass index were not significantly different among the four groups. Analyze of data showed that cortisol and ACTH basic levels significantly decreased after supplementation consumption, but then gradually significantly increased in all stages of post exercise. In High dose of Chamomile group, increasing tendency of post exercise somewhat less than other groups, but not to a significant level. The inter-group analysis results indicate that time effect had a significant impact in different stages of the groups. Conclusion: The results of this study, one session of eccentric exercise increased cortisol and ACTH hormone. The results represent the effect of high dose of Chamomile in the prevention and reduction of increased stress hormone levels. As regards use of medicinal plants and ibuprofen as a pain medication and inflammation has spread among athletes and non-athletes, the results of this research can provide information about the advantages and disadvantages of using medicinal plants and ibuprofen.

Keywords: chamomile, inflammatory indexes, eccentric exercise, young girls

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Authors: Abdullah S. Alghamdi, Khaled Alghamdi, Richard O. Jenkins, Parvez I. Haris

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Background: Physical activity is an important factor in the treatment and prevention of type 2 diabetes mellitus (T2DM). Reduction in HbA1c level, an important diabetes biomarker, was reported in patients who increased their daily physical activity. Although the ambient temperature was reported to be positively correlated to a negative impact on health and increase the incidences of diabetes, the exposure to bright sunlight was recently found to be associated with enhanced insulin sensitivity and improved beta-cell function. How Ramadan alters physical activity, and especially sunlight exposure, has not been adequately investigated. Aim: This study aimed to assess the physical activity and sun exposure of Saudis with T2DM over different periods (before, during, and after Ramadan) and related this to HbA1c levels. Methods: This study recruited 82 Saudis with T2DM, who chose to fast during Ramadan, from the Endocrine and Diabetic Centre of Al Iman General Hospital, Riyadh, Saudi Arabia. Ethical approvals for this study were obtained from De Montfort University and Saudi Ministry of Health. Physical activity and sun exposure were assessed by a self-administered questionnaire. Physical activity was estimated using the International Physical Activity Questionnaire (IPAQ), while the sun exposure was assessed by asking the patients about their hours per week of direct exposure to the sun, and daily hours spent outdoors. Blood samples were collected in each period for measuring HbA1c. Results: Low physical activity was observed in more than 60% of the patients, with no significant changes between periods. There were no significant variances between periods in the daily hours spent outdoors and the total number of weekly hours of direct exposure to the sun. The majority of patients reported only few hours of exposure to the sun (1h or less per week) and time spent outdoors (1h or less per day). The mean HbA1c significantly changed between periods (P = 0.001), with lowest level during Ramadan. There were significant differences in the mean HbA1c between the groups for the level of physical activity (P < 0.001), with significant lower mean HbA1c in the higher-level group. There were no significant variances in the mean of HbA1c between the groups for the daily hours spent outdoors. The mean HbA1c of the patients, who reported never in their total weekly hours of exposure to the sun, was significantly lower than the mean HbA1c of those who reported 1 hour or less (P = 0.001). Conclusion: Physical inactivity was prevalent among the study population with very little exposure to the sun or time spent outdoors. Higher level of physical activity was associated with lower mean HbA1c levels. Encouraging T2DM patients to achieve the recommended levels of physical activity may help them to obtain greater benefits of Ramadan fasting, such as reducing their HbA1c levels. The impact of low direct exposure to the sun and the time spent outdoors needs to be further investigated in both healthy and diabetic patients.

Keywords: diabetes, fasting, physical activity, sunlight, Ramadan

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Authors: Azza El-Medany, Jamila El-Medany

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Residential and agricultural pesticide use is widespread in the world. Their extensive and indiscriminative use, in addition with their ability to interact with biological systems other than their primary targets constitute a health hazards to both humans and animals. The toxic effects of pesticides include alterations in metabolism; there is a lack of knowledge that organophosphates can cause pancreatic toxicity. The primary goal of this work is to study the effects of chronic exposure to Diazinon an organophosphate used in agriculture on pancreatic tissues and evaluate the ameliorating effect of Mesna as antioxidant on the toxicity of Diazinon on pancreatic tissues.40 adult male rats, their weight ranged between 300-350 g. The rats were classified into three groups; control (10 rats) was received corn oil at a dose of 1 0 mg/kg/day by gavage once a day for 2 months. Diazinon (15 rats) was received Diazinon at a dose of 10 mg/kg/day dissolved in corn oil by gavage once a day for 2 months. Treated group (15 rats), were received Mesna 180mg/kg once a week by gavage 15 minutes before administration of Diazinon for 2 months. At the end of the experiment, animals were anesthetized, blood samples were taken by cardiac puncture for glucose and insulin assays and pancreas was removed and divided into 3 portions; first portion for histopathological study; second portion for ultrastructural study; third portion for biochemical study using Elisa Kits including determination of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), myeloperoxidase activity (MPO), interleukin 1β (IL-1β). A significant increase in the levels of MDA, TNF-α, MPO activity, IL-1β, serum glucose levels in the toxicated group with Diazinon were observed, while a significant reduction was noticed in GSH in serum insulin levels. After treatment with Mesna a significant reduction was observed in the previously mentioned parameters except that there was a significant rise in GSH in insulin levels. Histopathological and ultra-structural studies showed destruction in pancreatic tissues and β cells were the most affected cells among the injured islets as compared with the control group. The current study try to spot light about the effects of chronic exposure to pesticides on vital organs as pancreas also the role of oxidative stress that may be induced by them in evoking their toxicity. This study shows the role of antioxidant drugs in ameliorating or preventing the toxicity. This appears to be a promising approach that may be considered as a complementary treatment of pesticide toxicity.

Keywords: Diazinon, reduced glutathione, myeloperoxidase activity, tumor necrosis factor α, Mesna

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Authors: Thaminda Liyanage, Anuga Liyanage, Chamila Kurukulasuriya, Sidath Bandara

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Background: The burden of chronic kidney disease (CKD) is growing rapidly around the world, particularly in Asia. Over the last two decades Sri Lanka has experienced an epidemic of CKD with ever growing number of patients pursuing medical care due to CKD and its complications, specially in the “Mahaweli” river basin in north central region of the island nation. This was apparently a new form of CKD which was not attributable to conventional risk factors such as diabetes mellitus, hypertension or infection and widely termed as “CKD-unknown” or “CKDu”. In the past decade a number of small scale studies were conducted to determine the aetiology, prevalence and complications of CKDu in North Central region. These hospital-based studies did not provide an accurate estimate of the problem as merely 10% or less of the people with CKD are aware of their diagnosis even in developed countries with better access to medical care. Interestingly, similar observations were made on the changing epidemiology of obesity in the region but no formal study was conducted to date to determine the magnitude of obesity burden. Moreover, if increasing obesity in the region is associated with CKD epidemic is yet to be explored. Methods: We will conduct an area wide cross sectional survey among all adult residents of the “Mahaweli” development project area 5, in the North Central Province of Sri Lanka. We will collect relevant medical history, anthropometric measurements, blood and urine for hematological and biochemical analysis. We expect a participation rate of 75%-85% of all eligible participants. Participation in the study is voluntary, there will be no incentives provided for participation. Every analysis will be conducted in a central laboratory and data will be stored securely. We will calculate the prevalence of obesity and chronic kidney disease, overall and by stage using total number of participants as the denominator and report per 1000 population. The association of obesity and CKD will be assessed with regression models and will be adjusted for potential confounding factors and stratified by potential effect modifiers where appropriate. Results: This study will provide accurate information on the prevalence of obesity and CKD in the region. Furthermore, this will explore the association between obesity and CKD, although causation may not be confirmed. Conclusion: Obesity and CKD are increasingly recognized as major public health problems in Sri Lanka. Clearly, documenting the magnitude of the problem is the essential first step. Our study will provide this vital information enabling the government to plan a coordinated response to tackle both obesity and CKD in the region.

Keywords: BMI, Chronic Kidney Disease, obesity, Sri Lanka

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Authors: Ching-Yi Yiu, Hui-Chen Hsu

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Objectives: Head and neck cancer (HNC) is a big global health problem in the world. Despite the development of diagnosis and treatment, the overall survival of HNC is still low. The well recognition of the interaction of the host immune system and cancer cells has led to realizing the processes of tumor initiation, progression and metastasis. Many systemic inflammatory responses have been shown to play a crucial role in cancer progression. The pre and post-treatment nutritional and immunological status of HNC patients is a reliable prognostic indicator of tumor outcomes and survivors. Methods: Between July 2020 to June 2022, We have enrolled 60 HNC patients, including 59 males and 1 female, in Chi Mei Medical Center, Liouying, Taiwan. The age distribution was from 37 to 81 years old (y/o), with a mean age of 57.6 y/o. We evaluated the pre-and post-treatment nutritional and immunological status of these HNC patients with body weight, body weight loss, body mass index (BMI), whole blood count including hemoglobin (Hb), lymphocyte, neutrophil and platelet counts, biochemistry including prealbumin, albumin, c-reactive protein (CRP), with the time period of before treatment, post-treatment 3 and 6 months. We calculated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to assess how these biomarkers influence the outcomes of HNC patients. Results: We have carcinoma of the hypopharynx in 21 cases with 35％, carcinoma of the larynx in 9 cases, carcinoma of the tonsil and tongue every 6 cases, carcinoma soft palate and tongue base every 5 cases, carcinoma of buccal mucosa, retromolar trigone and mouth floor every 2 cases, carcinoma of the hard palate and low lip each 1 case. There were stage I 15 cases, stage II 13 cases, stage III 6 cases, stage IVA 10 cases, and stage IVB 16 cases. All patients have received surgery, chemoradiation therapy or combined therapy. We have wound infection in 6 cases, 2 cases of pharyngocutaneous fistula, flap necrosis in 2 cases, and mortality in 6 cases. In the wound infection group, the average BMI is 20.4 kg/m2; the average Hb is 12.9 g/dL, the average albumin is 3.5 g/dL, the average NLR is 6.78, and the average PLR is 243.5. In the PC fistula and flap necrosis group, the average BMI is 21.65 kg/m2; the average Hb is 11.7 g/dL, the average albumin is 3.15 g/dL, average NLR is 13.28, average PLR is 418.84. In the mortality group, the average BMI is 22.3 kg/m2; the average Hb is 13.58 g/dL, the average albumin is 3.77 g/dL, the average NLR is 6.06, and the average PLR is 275.5. Conclusion: HNC is a big challenging public health problem worldwide, especially in the high prevalence of betel nut consumption area Taiwan. Besides the definite risk factors of smoking, drinking and betel nut related, the other biomarkers may play significant prognosticators in the HNC outcomes. We concluded that the average BMI is less than 22 kg/m2, the average Hb is low than 12.0 g/dL, the average albumin is low than 3.3 g/dL, the average NLR is low than 3, and the average PLR is more than 170, the surgical complications and mortality will be increased, and the prognosis is poor in HNC patients.

Keywords: nutritional, immunological, neutrophil-to-lymphocyte ratio, paltelet-to-lymphocyte ratio.

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Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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Authors: M. S. Raza, A. Kapil, Sonu Tyagi, H. Gautam, S. Mohapatra, R. Chaudhry, S. Sood, V. Goyal, R. Lodha, V. Sreenivas, B. K. Das

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Background: Acute bacterial meningitis remains the major cause of mortality and morbidity. More than half of the survivors develop the significant lifelong neurological abnormalities. Diagnosis of the hospital acquired acute bacterial meningitis (HAABM) is challenging as it appears either in the post operative patients or patients acquire the organisms from the hospital environment. In both the situations, pathogens are exposed to high dose of antibiotics. Chances of getting multidrug resistance organism are very high. We have performed this experiment to find out the etiological agents of HAABM and its antibiotics susceptibility pattern. Methodology: A perspective study was conducted at the Department of Microbiology, All India Institute of Medical Sciences, New Delhi. From March 2015 to April 2018 total 400 Cerebro spinal fluid samples were collected aseptically. Samples were processed for cell count, Gram staining, and culture. Culture plates were incubated at 37°C for 18-24 hours. Organism grown on blood and MacConkey agar were identified by MALDI-TOF Vitek MS (BioMerieux, France) and antibiotic susceptibility tests were performed by Kirby Bauer disc diffusion method as per CLSI 2015 guideline. Results: Of the 400 CSF samples processed, 43 (10.75%) were culture positive for different bacteria. Out of 43 isolates, the most prevalent Gram-positive organisms were S. aureus 4 (9.30%) followed by E. faecium 3 (6.97%) & CONS 2 (4.65%). Similarly, E. coli 13 (30.23%) was the commonest Gram-negative isolates followed by A. baumannii 12 (27.90%), K. pneumonia 5 (11.62%) and P. aeruginosa 4(9.30%). Most of the antibiotics tested against the Gram-negative isolates were resistance to them. Colistin was most effective followed by Meropenem and Imepenim for all Gram-negative HAABM isolates. Similarly, most of antibiotics tested were susceptible to S. aureus and CONS. However, E. faecium (100%) were only susceptible to vancomycin and teicoplanin. Conclusion: Hospital acquired acute bacterial meningitis (HAABM) is becoming the emerging challenge as most of isolates are showing resistance to commonly used antibiotics. Gram-negative organisms are emerging as the major player of HAABM. Great care needs to be taken especially in tertiary care hospitals. Similarly, antibiotic stewardship should be followed and antibiotic susceptibility test (AST) should be performed regularly to update the antibiotic patter and to prevent from the emergence of resistance. Updated information of the AST will be helpful for the better management of the meningitis patient.

Keywords: CSF, MALDI-TOF, hospital acquired acute bacterial meningitis, AST

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Authors: Rashmi Shukla, Yamini Bhusan Tripathi

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Diabetic nephropathy (DN) is characterized as diabetic kidney disease which involves many pathways e.g. hyperactivated protein kinase c (PKC), polyol pathway, excess production of advanced glycation end product (AGEs) & free radical accumulation etc. All of them results to hypoxia followed by apoptosis of podocytes, glomerulosclerosis, extracellular matrix (ECM) accumulation and fibrosis resulting to irreversible changes in kidney. This is continuously rising worldwide and there are not enough specific drugs, to retard its progress. Due to increasing side effects of allopathic drugs, interest in herbal remedies is growing. Earlier, we have reported that PTY-2 (a phytomedicine, derived from Pueraria tuberosa Linn.) inhibits the accumulation of extracellular matrix (ECM) through activation of MMP-9. Present study exhibited the therapeutic potential of Pueraria tuberosa in the prevention of podocytes apoptosis and modulation of nephrin expression in streptozotocin (STZ) induced DN rats. DN rats were produced by maintaining persistent hyperglycemia for 8 weeks by intra-peritoneal injection of 55 mg/kg streptozotocin (STZ). These rats were randomly divided in 2 groups, i.e. DN control, and DN+ water extract of Pueraria tuberosa (PTW). One group of age-matched normal rats served as non-diabetic control (group-1), The STZ induced DN rats (group-2) and DN+PTW treated rats (group-3). The PTW was orally administered (0.3g/kg) daily to group-2 rats and drug vector (1 ml of 10% tween 20) in control rats. The treatments were continued for 20 days and blood and urine samples were collected. Rats were then sacrificed to investigate the expression Bcl2, Bax and nephroprotective protein i.e. nephrin in kidney glomerulus. The effect of PTW was evaluated, we have found that the PTW significantly(p < .001) reversed the raised serum urea, serum creatinine, urine protein and improved the creatinine clearance in STZ induce diabetic nephropathy in rats and also significantly(p < .001) prevented the rise in urine albumin excretion. The Western blot analysis of kidney tissue homogenate showed increased expression of Bcl2 in PTW treated rats. The RT-PCR showed the increased expression and accumulation of nephrin mRNA. The confocal photomicrographs also supported the reduction of Bax and a simultaneous increase in Bcl2 and nephrin in glomerular podocytes. Hence, our finding suggests that the nephroprotective role of PTW is mediated via restoration of nephrin thus prevents the podocytes apoptosis and ameliorates diabetic nephropathy. The clinical trial of PTW would prove to be a potential food supplement/ drug of alternative medicine for patients with diabetic nephropathy in early stage.

Keywords: Pueraria tuberosa, diabetic nephropathy, anti-apoptosis, nephrin

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