Search results for: chronic pulmonary disease

Authors: Mythri G., Manjunath ML, Girish Babu M., Shireen Swaliha Quadri

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Background: The increase in diabetes among the elderly is of concern because in addition to the wide range of traditional diabetes complications, evidence has been growing that diabetes is associated with increased risk of cognitive decline. Aims and Objectives: To find out if there is any association between blood sugar levels and short-term and working memory status in patients of type 2 diabetes. Materials and Methods: The study was carried out in 200 individuals aged between 40-65 years consisting of 100 diagnosed cases of Type 2 Diabetes Mellitus and 100 non-diabetics from OPD of Mc Gann Hospital, Shivamogga. Rye’s Auditory Verbal Learning Test, Verbal Fluency Test and Visual Reproduction Test, Working Digit Span Test and Validation Span Test were used to assess short-term and working memory. Fasting and Post Prandial blood sugar levels were estimated. Statistical analysis was done using SPSS 21. Results: Memory test scores of type 2 diabetics were significantly reduced (p < 0.001) when compared to the memory scores of age and gender matched non-diabetics. Fasting blood sugar levels were found to have a negative correlation with memory scores for all 5 tests: AVLT (r=-0.837), VFT (r=-0.888), VRT(r=-0.787), WDST (r=-0.795) and VST (r=-0.943). Post- Prandial blood sugar levels were found to have a negative correlation with memory scores for all 5 tests: AVLT (r=-0.922), VFT (r=-0.848), VRT(r=-0.707),WDST (r=-0.729) and VST (r=-0.880) Memory scores in all 5 tests were found to be negatively correlated with the FBS and PPBS levels in diabetic patients (p < 0.001). Conclusion: The decreased memory status in diabetic patients may be due to many factors like hyperglycemia, vascular disease, insulin resistance, amyloid deposition and also some of the factor combine to produce additive effects like, type of diabetes, co-morbidities, age of onset, duration of the disease and type of therapy. These observed effects of blood sugar levels of diabetics on memory status are of potential clinical importance because even mild cognitive impairment could interfere with todays’ activities.

Keywords: diabetes, cognition, diabetes, HRV, respiratory medicine

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Authors: T. Schilirò, S. Bonetta, S. Bonetta, E. Ceretti, D. Feretti, I. Zerbini, V. Romanazzi, S. Levorato, T. Salvatori, S. Vannini, M. Verani, C. Pignata, F. Bagordo, G. Gilli, S. Bonizzoni, A. Bonetti, E. Carraro, U. Gelatti

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Air pollution is one of the most important worldwide health concern. In the last years, in both the US and Europe, new directives and regulations supporting more restrictive pollution limits were published. However, the early effects of air pollution occur, especially for the urban population. Several epidemiological and toxicological studies have documented the remarkable effect of particulate matter (PM) in increasing morbidity and mortality for cardiovascular disease, lung cancer and natural cause mortality. The finest fractions of PM (PM with aerodynamic diameter <2.5 µm and less) play a major role in causing chronic diseases. The International Agency for Research on Cancer (IARC) has recently classified air pollution and fine PM as carcinogenic to human (1 Group). The structure and composition of PM influence the biological properties of particles. The chemical composition varies with season and region of sampling, photochemical-meteorological conditions and sources of emissions. The aim of the MAPEC (Monitoring Air Pollution Effects on Children for supporting public health policy) study is to evaluate the associations between air pollution and biomarkers of early biological effects in oral mucosa cells of 6-8 year old children recruited from first grade schools. The study was performed in five Italian towns (Brescia, Torino, Lecce, Perugia and Pisa) characterized by different levels of airborne PM (PM10 annual average from 44 µg/m3 measured in Torino to 20 µg/m3 measured in Lecce). Two to five schools for each town were chosen to evaluate the variability of pollution within the same town. Child exposure to urban air pollution was evaluated by collecting ultrafine PM (PM0.5) in the school area, on the same day of biological sampling. PM samples were collected for 72h using a high-volume gravimetric air sampler and glass fiber filters in two different seasons (winter and spring). Gravimetric analysis of the collected filters was performed; PM0.5 organic extracts were chemically analyzed (PAH, Nitro-PAH) and tested on A549 by the Comet assay and Micronucleus test and on Salmonella strains (TA100, TA98, TA98NR and YG1021) by Ames test. Results showed that PM0.5 represents a high variable PM10 percentage (range 19.6-63%). PM10 concentration were generally lower than 50µg/m3 (EU daily limit). All PM0.5 extracts showed a mutagenic effect with TA98 strain (net revertant/m3 range 0.3-1.5) and suggested the presence of indirect mutagens, while lower effect was observed with TA100 strain. The results with the TA98NR and YG1021 strains showed the presence of nitroaromatic compounds as confirmed by the chemical analysis. No genotoxic or oxidative effect of PM0.5 extracts was observed using the comet assay (with/without Fpg enzyme) and micronucleus test except for some sporadic samples. The low biological effect observed could be related to the low level of air pollution observed in this winter sampling associated to a high atmospheric instability. For a greater understanding of the relationship between PM size, composition and biological effects the results obtained in this study suggest to investigate the biological effect of the other PM fractions and in particular of the PM0.5-1 fraction.

Keywords: airborne PM, ames test, comet assay, micronucleus test

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Authors: Amir Hamed Abd-Elrahman, Mohamed Bessat

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450 fattening cattle and buffaloes aged from 6 to 30 months old were examined clinically to determine patterns of occurrence of hemoparasitic diseases and the efficacy of different anti theilerial drugs. 420 animals examined clinically to determine relation between different outbreak of FMD and LSD in Egypt 2012- 2013 and haemoprotozoal diseases. The clinical pictures of haemoprotozoal diseases are variable, from sever to mild, depending on the endemic situation which governed by frequent previous exposure and tick infestation. B. bigemina is the most common haemoprotozoal diseases in the area of study and the infection rate in a descending manner for B. bigemina, A. marginale and T. annulata were 20%, 9.7% and 6.6% respectively. The species susceptibility of B. bigemina and T. annulata showed a higher incidence in cattle than buffaloes while in A. marginale showed a little difference in cattle and buffaloes susceptibility by 10% and 9.2% respectively. The breed susceptibility of B. bigemina and T. annulata showed a higher incidence in crossbred cattle than native baladi cattle while A. marginale showed a higher incidence in native baladi cattle than crossbred cattle. The maximal infection rates were recorded during summer months. The infection rates of B. bigemina and A. marginale were higher among young animals over 6 months and declined above 2 year old while in T. annulata the infection rates were lower among young animals and increased above 2 year old. The case fatality of T. annulata was higher than A. marginale and B. bigemina. Efficacy of different anti theilerial drugs were studied, cure rate of chlouroquine group and Butalex group were 60% disappearance of schizont in lymph node smear after 9 days and 5 days respectively while cure rate of Oxytetracycline Dihydrate (Alamycine) group 20% with disappearance of schizont in lymph node smear after 14 days. FMD and LSD infection enhancement the occurrence of bovine haemoprotozoal diseases.

Keywords: Babesia bigemina, Anaplasma marginale, Theileria annulata, FMD, LSD, ephemeral fever

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Authors: Hala Raslan, Noha Eltaweel, Hanaa Rasmi, Solaf Kamel, May Magdy, Sherif Ismail, Khalda Amr

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Introduction: Rheumatoid arthritis (RA) is an inflammatory, autoimmune disorder with progressive joint damage. Osteoarthritis (OA) is a degenerative disease of the articular cartilage that shows multiple clinical manifestations or symptoms resembling those of RA. Genetic predisposition is believed to be a principal etiological factor for RA and OA. In this study, we aimed to measure the expression of the top deregulated miRNAs that might be the cause of pathogenesis in both diseases, according to our latest NGS analysis. Six of the deregulated miRNAs were selected as they had multiple target genes in the RA pathway, so they are more likely to affect the RA pathogenesis.Methods: Eighty cases were recruited in this study; 45 rheumatoid arthiritis (RA), 30 osteoarthiritis (OA) patients, as well as 20 healthy controls. The selection of the miRNAs from our latest NGS study was done using miRwalk according to the number of their target genes that are members in the KEGG RA pathway. Total RNA was isolated from plasma of all recruited cases. The cDNA was generated by the miRcury RT Kit then used as a template for real-time PCR with miRcury Primer Assays and the miRcury SYBR Green PCR Kit. Fold changes were calculated from CT values using the ΔΔCT method of relative quantification. Results were compared RA vs Controls and OA vs Controls. Target gene prediction and functional annotation of the deregulated miRNAs was done using Mienturnet. Results: Six miRNAs were selected. They were miR-15b-3p, -128-3p, -194-3p, -328-3p, -542-3p and -3180-5p. In RA samples, three of the measured miRNAs were upregulated (miR-194, -542, and -3180; mean Rq= 2.6, 3.8 and 8.05; P-value= 0.07, 0.05 and 0.01; respectively) while the remaining 3 were downregulated (miR-15b, -128 and -328; mean Rq= 0.21, 0.39 and 0.6; P-value= <0.0001, <0.0001 and 0.02; respectively) all with high statistical significance except miR-194. While in OA samples, two of the measured miRNAs were upregulated (miR-194 and -3180; mean Rq= 2.6 and 7.7; P-value= 0.1 and 0.03; respectively) while the remaining 4 were downregulated (miR-15b, -128, -328 and -542; mean Rq= 0.5, 0.03, 0.08 and 0.5; P-value= 0.0008, 0.003, 0.006 and 0.4; respectively) with statistical significance compared to controls except miR-194 and miR-542. The functional enrichment of the selected top deregulated miRNAs revealed the highly enriched KEGG pathways and GO terms. Conclusion: Five of the studied miRNAs were greatly deregulated in RA and OA, they might be highly involved in the disease pathogenesis and so might be future therapeutic targets. Further functional studies are crucial to assess their roles and actual target genes.

Keywords: MiRNAs, expression, rheumatoid arthritis, osteoarthritis

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Authors: Aliseydi Bozkurt

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Objectives: Benign prostatic hyperplasia (BPH) is the most common benign disease, and prostate cancer (PC) is malign disease of the prostate gland. Transrectal ultrasound-guided biopsy (TRUS-bx) is one of the most important diagnostic tools in PC diagnosis. Identifying men at increased risk for having a biopsy detectable prostate cancer should consider prostate specific antigen density (PSAD), f/t PSA Ratio, an estimate of prostate volume. Method: We retrospectively studied 269 patients who had a prostate specific antigen (PSA) score of 4 or who had suspected rectal examination at any PSA level and received TRUS-bx between January 2015 and June 2018 in our clinic. TRUS-bx was received by 12 experienced urologists with 12 quadrants. Prostate volume was calculated prior to biopsy together with TRUS. Patients were classified as malignant and benign at the end of pathology. Age, PSA value, prostate volume in transrectal ultrasonography, corpuscle biopsy, biopsy pathology result, the number of cancer core and Gleason score were evaluated in the study. The success rates of PV, PSAD, and f/tPSA were compared in all patients and those with PSA 2.5-10 ng/mL and 10.1-30 ng/mL tp foresee prostate cancer. Result: In the present study, in patients with PSA 2.5-10 ng/ml, PV cut-off value was 43,5 mL (n=42 < 43,5 mL and n=102 > 43,5 mL) while in those with PSA 10.1-30 ng/mL prostate volüme (PV) cut-off value was found 61,5 mL (n=31 < 61,5 mL and n=36 > 61,5 mL). Total PSA values in the group with PSA 2.5-10 ng/ml were found lower (6.0 ± 1.3 vs 6.7 ± 1.7) than that with PV < 43,5 mL, this value was nearly significant (p=0,043). In the group with PSA value 10.1-30 ng/mL, no significant difference was found (p=0,117) in terms of total PSA values between the group with PV < 61,5 mL and that with PV > 61,5 mL. In the group with PSA 2.5-10 ng/ml, in patients with PV < 43,5 mL, f/t PSA value was found significantly lower compared to the group with PV > 43,5 mL (0.21 ± 0.09 vs 0.26 ± 0.09 p < 0.001 ). Similarly, in the group with PSA value of 10.1-30 ng/mL, f/t PSA value was found significantly lower in patients with PV < 61,5 mL (0.16 ± 0.08 vs 0.23 ± 0.10 p=0,003). In the group with PSA 2.5-10 ng/ml, PSAD value in patients with PV < 43,5 mL was found significantly higher compared to those with PV > 43,5 mL (0.17 ± 0.06 vs 0.10 ± 0.03 p < 0.001). Similarly, in the group with PSA value 10.1-30 ng/mL PSAD value was found significantly higher in patients with PV < 61,5 mL (0.47 ± 0.23 vs 0.17 ± 0.08 p < 0.001 ). The biopsy results suggest that in the group with PSA 2.5-10 ng/ml, in 29 of the patients with PV < 43,5 mL (69%) cancer was detected while in 13 patients (31%) no cancer was detected. While in 19 patients with PV > 43,5 mL (18,6%) cancer was found, in 83 patients (81,4%) no cancer was detected (p < 0.001). In the group with PSA value 10.1-30 ng/mL, in 21 patients with PV < 61,5 mL (67.7%) cancer was observed while only in10 patients (32.3%) no cancer was seen. In 5 patients with PV > 61,5 mL (13.9%) cancer was found while in 31 patients (86.1%) no cancer was observed (p < 0.001). Conclusions: Identifying men at increased risk for having a biopsy detectable prostate cancer should consider PSA, f/t PSA Ratio, an estimate of prostate volume. Prostate volume in PC was found lower.

Keywords: prostate cancer, prostate volume, prostate specific antigen, free/total PSA ratio

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Authors: Elena Pello, Martin Bobak, Yuri Nikitin

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In current issue we evaluated integration of magnesium with lipids; the attractive findings were obtained in men and women; the crucial ties of magnesium with total cholesterol in hypertensive men, with total cholesterol in concordance with low-density lipoprotein cholesterol in hypertensive women were disclosed; unanswered questions were trapped, difficulties were surmounted, and magnesium deficiency perseverance in pathogenesis of cardiovascular disease development was expressed; nutrients as well as risk factors may contribute to cardiovascular complications.

Keywords: dietary, magnesium, hypertension, lipids

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Authors: Michaela Chovancova, Pavel Niedoba

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For the treatment of acute and chronic lung diseases it is preferred to deliver medicaments by inhalation. The drug is delivered directly to tracheobronchial tree. This way allows the given medicament to get directly into the place of action and it makes rapid onset of action and maximum efficiency. The transport of aerosol particles in the particular part of the lung is influenced by their size, anatomy of the lungs, breathing pattern and airway resistance. This article deals with calculation of airway resistance in the lung model of Horsfield. It solves the problem of determination of the pressure losses in bifurcation and thus defines the pressure drop at a given location in the bronchial tree. The obtained data will be used as boundary conditions for transport of aerosol particles in a central part of bronchial tree realized by Computational Fluid Dynamics (CFD) approach. The results obtained from CFD simulation will allow us to provide information on the required particle size and optimal inhalation technique for particle transport into particular part of the lung.

Keywords: human lungs, bronchial tree, pressure losses, airways resistance, flow, breathing

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Authors: Edidiong Ekefre

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The Nigerian civil war was one of the foremost postcolonial conflicts in West Africa that attracted a serious humanitarian problem due to an unprecedented refugee crisis that affected the Biafran region. Due to its geographical location, the Nigerian government used blockades and starvation as a weapon of war against the Biafran. Faced with strong opposition from the Nigerian government, most humanitarian organizations withdrew their support from Biafra, whose death toll was rapidly growing daily due to starvation, malnutrition, and chronic ailment. Thus, the Catholic Church, a major Christian denomination in Biafra, had to see it as its religious obligation to support the humanitarian needs of the Biafrans. Thus, applying oral history methods with archival research, this paper examines the humanitarian activities of the Catholic Church in the Nigerian civil war. It contends that the Catholic Church was a key player in the humanitarian aspect of the Nigerian civil war. The paper concludes that faith-based humanitarian intervention in the Biafran refugee crisis was essential for the survival of the Biafran war-stricken women and children.

Keywords: refugee crisis, humanitarian intervention, Caritas International, blockades, airlifts, starvation

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Authors: Antonia Egli, Theo Lynn, Pierangelo Rosati, Gary Sinclair

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The World Health Organization (WHO) defines vaccine hesitancy as the postponement or complete denial of vaccines and estimates a direct linkage to approximately 1.5 million avoidable deaths annually. This figure is not immune to public health developments, as has become evident since the global spread of COVID-19 from Wuhan, China in early 2020. Since then, the proliferation of influential, but oftentimes inaccurate, outdated, incomplete, or false vaccine-related information on social media has impacted hesitancy levels to a degree described by the WHO as an infodemic. The COVID-19 pandemic and related vaccine hesitancy levels have in 2022 resulted in the largest drop in childhood vaccinations of the 21st century, while the prevalence of online stigma towards vaccine hesitant consumers continues to grow. Simultaneously, a second disease has risen to global importance: Monkeypox is an infection originating from west and central Africa and, due to racially motivated online hate, was in August 2022 set to be renamed by the WHO. To better understand public reactions towards two viral infections that became global threats to public health no two years apart, this research examines user replies to threads published by the WHO on Twitter. Replies to two Tweets from the @WHO account declaring COVID-19 and Monkeypox as ‘public health emergencies of international concern’ on January 30, 2020, and July 23, 2022, are gathered using the Twitter application programming interface and user mention timeline endpoint. Research methodology is unique in its analysis of stigmatizing, racist, and hateful content shared on social media within the vaccine discourse over the course of two disease outbreaks. Three distinct analyses are conducted to provide insight into (i) the most prevalent topics and sub-topics among user reactions, (ii) changes in sentiment towards the spread of the two diseases, and (iii) the presence of stigma, racism, and online hate. Findings indicate an increase in hesitancy to accept further vaccines and social distancing measures, the presence of stigmatizing content aimed primarily at anti-vaccine cohorts and racially motivated abusive messages, and a prevalent fatigue towards disease-related news overall. This research provides value to non-profit organizations or government agencies associated with vaccines and vaccination programs in emphasizing the need for public health communication fitted to consumers' vaccine sentiments, levels of health information literacy, and degrees of trust towards public health institutions. Considering the importance of addressing fears among the vaccine hesitant, findings also illustrate the risk of alienation through stigmatization, lead future research in probing the relatively underexamined field of online, vaccine-related stigma, and discuss the potential effects of stigma towards vaccine hesitant Twitter users in their decisions to vaccinate.

Keywords: social marketing, social media, public health communication, vaccines

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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Authors: Kenichi Yamahara, Makiko Ohshima, Shunsuke Ohnishi, Hidetoshi Tsuda, Akihiko Taguchi, Toshihiro Soma, Hiroyasu Ogawa, Jun Yoshimatsu, Tomoaki Ikeda

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We have previously reported the therapeutic potential of rat fetal membrane(FM)-derived mesenchymal stem cells (MSCs) using various rat models including hindlimb ischemia, autoimmune myocarditis, glomerulonephritis, renal ischemia-reperfusion injury, and myocardial infarction. In this study, 1) we isolated and characterized MSCs from human amnion and chorion; 2) we examined their differences in the expression profile of growth factors and cytokines; and 3) we investigated the therapeutic potential and difference of these MSCs using murine hindlimb ischemia and acute graft-versus-host disease (GVHD) models. Isolated MSCs from both amnion and chorion layers of FM showed similar morphological appearance, multipotency, and cell-surface antigen expression. Conditioned media obtained from amnion- and chorion-derived MSCs inhibited cell death caused by serum starvation or hypoxia in endothelial cells and cardiomyocytes. Amnion and chorion MSCs secreted significant amounts of angiogenic factors including HGF, IGF-1, VEGF, and bFGF, although differences in the cellular expression profile of these soluble factors were observed. Transplantation of human amnion or chorion MSCs significantly increased blood flow and capillary density in a murine hindlimb ischemia model. In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced T-lymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of GVHD disease. Our results highlight that human amnionand chorion-derived MSCs, which showed differences in their soluble factor secretion and angiogenic/immuno-suppressive function, could be ideal cell sources for regenerative medicine.

Keywords: amnion, chorion, fetal membrane, mesenchymal stem cells

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Authors: Kamel Abdelaziz Mohamed

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Intoduction:Inadequate knowledge about obstetric admission and infrequent dealing with the obstetric patients in ICU results in high mortality and morbidity. Aim of the work:To evaluate the indications, course, severity of illness, and outcome of obstetric patients admitted to the intensive care unit (ICU). Patients and Methods: We collected baseline data and acute physiology and chronic health evaluation II (APACHE II) scores. ICU mortality was the primary outcome. Results: Seventy obstetric patients were admitted to the ICU over 3 years, 36 of these patients (51.4 %) were admitted during the antepartum period. The primary obstetric indication for ICU admission was pregnancy-induced hypertension (22 patients, 31.4%), followed by sepsis (8 patients, 11.4%) as the leading non-obstetric admission. The mean APACHE II score was 19.6. The predicted mortality rate based on the APACHE II score was 22%, however, only 4 maternal deaths (5.7%) were among the obstetric patients admitted to the ICU. Conclusion: Evaluation of obstetric patients by (APACHE II) scores showed higher predicted mortality rate, however the overall mortality was lower. Regular follow up, together with early detection of complications and prompt ICU admission necessitating proper management by specialized team can improve mortality.

Keywords: obstetric, complication, postpartum, sepsis

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Authors: Izabela P. Vatanabe, Rafaela Peron, Patricia Manzine, Marcia R. Cominetti

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Introduction: Considering the increase in life expectancy of world population, there is an emerging concern in health services to allocate better care and care to elderly, through promotion, prevention and treatment of health. It has been observed that frailty syndrome is prevalent in elderly people worldwide and this complex and heterogeneous clinical syndrome consist of the presence of physical frailty associated with cognitive dysfunction, though in absence of dementia. This can be characterized by exhaustion, unintentional weight loss, decreased walking speed, weakness and low level of physical activity, in addition, each of these symptoms may be a predictor of adverse outcomes such as hospitalization, falls, functional decline, institutionalization, and death. Cognitive frailty is a recent concept in literature, which is defined as the presence of physical frailty associated with mild cognitive impairment (MCI) however in absence of dementia. This new concept has been considered as a subtype of frailty, which along with aging process and its interaction with physical frailty, accelerates functional declines and can result in poor quality of life of the elderly. MCI represents a risk factor for Alzheimer's disease (AD) in view of high conversion rate for this disease. Comorbidities and physical frailty are frequently found in AD patients and are closely related to heterogeneity and clinical manifestations of the disease. The decreased platelets ADAM10 levels in AD patients, compared to cognitively healthy subjects, matched by sex, age and education. Objective: Based on these previous results, this study aims to evaluate whether ADAM10 platelet levels of could act as a biomarker of cognitive frailty. Methods: The study was approved by Ethics Committee of Federal University of São Carlos (UFSCar) and conducted in the municipality of São Carlos, headquarters of Federal University of São Carlos (UFSCar). Biological samples of subjects were collected, analyzed and then stored in a biorepository. ADAM10 platelet levels were analyzed by western blotting technique in subjects with MCI and compared to subjects without cognitive impairment, both with and without presence of frailty. Statistical tests of association, regression and diagnostic accuracy were performed. Results: The results have shown that ADAM10/β-actin ratio is decreased in elderly individuals with cognitive frailty compared to non-frail and cognitively healthy controls. Previous studies performed by this research group, already mentioned above, demonstrated that this reduction is still higher in AD patients. Therefore, the ADAM10/β-actin ratio appears to be a potential biomarker for cognitive frailty. The results bring important contributions to an accurate diagnosis of cognitive frailty from the perspective of ADAM10 as a biomarker for this condition, however, more experiments are being conducted, using a high number of subjects, and will help to understand the role of ADAM10 as biomarker of cognitive frailty and contribute to the implementation of tools that work in the diagnosis of cognitive frailty. Such tools can be used in public policies for the diagnosis of cognitive frailty in the elderly, resulting in a more adequate planning for health teams and better quality of life for the elderly.

Keywords: ADAM10, biomarkers, cognitive frailty, elderly

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Authors: Muhammad Fayyaz Nazir, Ellen Wayenberg, Shahzadaah Faahed Qureshi

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Introduction: The study is based on the Contextual Interaction Theory (CIT) constructs to explore the role of policy actors in implementing the COVID-19 Disease Prevention and Control (DP&C) Policy. The study analyzes the role of healthcare workers' contextual factors, such as cognition, motives, and resources, and their interactions in implementing Social Distancing (SD). In this way, we test a two actors policy implementation theory, i.e., the CIT in a three-actor context. Methods: Data was collected through document analysis and semi-structured interviews. For a qualitative study design, interviews were conducted with questions on cognition, motives, and resources from the healthcare workers involved in implementing SD in the local context in Multan – Pakistan. The possible interactions resulting from contextual factors of the policy actors – healthcare workers were identified through framework analysis protocol guided by CIT and supported by trustworthiness criterion and data saturation. Results: This inquiry resulted in theory application, addition, and enrichment. The theoretical application in the three actor's contexts illustrates the different levels of motives, cognition, and resources of healthcare workers – senior administrators, managers, and healthcare professionals. The senior administrators working in National Command and Operations Center (NCOC), Provincial Technical Committees (PTCs), and Districts Covid Teams (DCTs) were playing their role with high motivation. They were fully informed about the policy and moderately resourceful. The policy implementors: healthcare managers working on implementing the SD within their respective hospitals were playing their role with high motivation and were fully informed about the policy. However, they lacked the required resources to implement SD. The target medical and allied healthcare professionals were moderately motivated but lack of resources and information. The interaction resulted in cooperation and the need for learning to manage the future healthcare crisis. However, the lack of resources created opposition to the implementation of SD. Objectives of the Study: The study aimed to apply a two actors theory in a multi actors context. We take this as an opportunity to qualitatively test the theory in a novel situation of the Covid-19 pandemic and make way for its quantitative application by designing a survey instrument so that implementation researchers can apply CIT through multivariate analyses or higher-order statistical modeling. Conclusion: Applying two actors' implementation theory in exploring a complex case of healthcare intervention in three actors context is a unique work that has never been done before, up to the best of our knowledge. So, the work will contribute to the policy implementation studies by applying, extending, and enriching an implementation theory in a novel case of the Covi-19 pandemic, ultimately fulfilling the gap in implementation literature. Policy institutions and other low or middle-income countries can learn from this research and improve SD implementation by working on the variables with weak significance levels.

Keywords: COVID-19, disease prevention and control policy, implementation, policy actors, social distancing

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Authors: Besma Abdeltif, Chebabhi Imen

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Introduction: it is important to define the genital pathologies encountered in Algeria in postpartum dairy cows. The objective was to identify the different pathologies of reproduction in cows found at the communal abattoir of Souk Ahras. Materials and Methods: Our study was carried at the communal slaughterhouse of Souk-Ahras on 63 genital tracts were examined macroscopically after slaughter. Results: The results obtained reveal a high frequency of pregnant females (14.28%), most of the gestations were at their beginning. Uterine anomalies ranked first in the genital lesions of the cow (20.37%). The frequencies of these abnormalities are in ascending order: aplasia of the horns = 1.85%, traumatic cervical = 1.85%, cervical tumors = 1.85%, chronic endometritis = 3.70% and Acute endometritis = 11.11%. The ovarian cyst is the most common lesion, with a frequency of 3.70%, followed by smooth ovaries (1.85%). These are single, thin-walled cysts more present on the right ovary than the left ovary. Salpingitis is the only tubal lesion found on 5.55% of the non-pregnant genital tract. Neoformation is the only vaginal lesion identified in this work (1.85%). Conclusion: Our result, in general, conforms to the data of the literature.

Keywords: genital tract, cow, slaughterhouse, pathology

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Authors: Tahmeena Ali, Andrew Francis, Keong Yap, Sharynn Schuster

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Social anxiety is a chronic and debilitating condition characterized by fear and avoidance of social situations. Several risk factors have emerged, which emphasize the role of early childhood experiences in the development of this condition. As such, the current study tested the hypothesis that early maladaptive schemas (EMSs) mediate the relationship between retrospectively reported parental criticism and social anxiety whilst controlling the effects of depression. Three hundred and thirty-four non-clinical participants completed an online questionnaire consisting of self-report measures of parental criticism, EMSs of disconnection and rejection, and symptoms of social anxiety and depression. The mediation analysis confirmed the hypothesized model, indicating that EMSs mediated the relationship between parental criticism and social anxiety symptoms when controlling for depression. Whilst the current study is limited due to its cross-sectional design, the findings lend support to the developmental formulations of social anxiety and have important therapeutic implications for treatment.

Keywords: early maladaptive schema, parental criticism, schema, social anxiety

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Authors: Vishvas N. Patel, Mehul Chorawala

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Currently, according to the authors best knowledge there are less effective therapeutic agents to limit intestinal mucosa damage associated with inflammatory bowel disease (IBD). Clinical studies have shown beneficial effects of several probiotics in patients of IBD. Probiotics are live organisms; confer a health benefit to the host by modulating immunoinflammation and oxidative stress. Although probiotics in murine and human improve disease severity, very little is known about the specific contribution of cell wall contents of probiotics in IBD. Herein, we investigated the ameliorative potential of cell wall contents of Lactobacillus casei (LC) in lipopolysaccharide (LPS)-induced murine colitis. Methods: Colitis was induced in LPS-sensitized rats by intracolonic instillation of LPS (50 µg/rat) for consecutive 14 days. Concurrently, cell wall contents isolated from 103, 106 and 109 CFU of LC was given subcutaneously to each rat for 21 days, considering sulfasalazine (100 mg/kg, p.o.) as standard. The severity of colitis was assessed by body weight loss, food intake, stool consistency, rectal bleeding, colon weight/length, spleen weight and histological analysis. Colonic inflammatory markers (myeloperoxidase (MPO) activity, C-reactive protein and proinflammatory cytokines) and oxidative stress markers (malondialdehyde, reduced glutathione and nitric oxide) were also assayed. Results: Cell wall contents of isolated from 106 and 109 CFU of LC significantly improved the severity of colitis by reducing body weight loss and diarrhea & bleeding incidence, improving food intake, colon weight/length, spleen weight and microscopic damage to the colonic mucosa. The treatment also reduced levels of inflammatory and oxidative stress markers and boosted antioxidant molecule. However, cell wall contents of isolated from 103 were ineffective. Conclusion: In conclusion, cell wall contents of LC attenuate LPS-induced colitis by modulating immuno-inflammation and oxidative stress.

Keywords: probiotics, Lactobacillus casei, immuno-inflammation, oxidative stress, lipopolysaccharide, colitis

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Balasooriya B. M. C. M., Sujeeva N., Thowfeek Z., Siddiqa Omo, Liyanagunawardana J. E., Jayawardana Saiu, Manathunga S. S., Katulanda G. W.

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Introduction and objectives: Adrenal venous sampling (AVS) is the gold standard to discriminate unilateral primary aldosteronism (UPA) from bilateral disease (BPA). AVS is technically demanding and only performed in a limited number of centers worldwide. To the best of our knowledge, Except for one study conducted in India, no other research studies on this area have been conducted in South Asia. This study aimed to evaluate the effectiveness of AVS in the management of primary aldosteronism. Methods: A total of 32 patients who underwent AVS at the National Hospital of Sri Lanka from April 2021 to April 2023 were enrolled. Demographic, clinical and laboratory data were obtained retrospectively. A procedure was considered successful when adequate cannulation of both adrenal veins was demonstrated. Cortisol gradient across the adrenal vein (AV) and the peripheral vein was used to establish the success of venous cannulation. Lateralization was determined by the aldosterone gradient between the two sides. Continuous and categorical variables were summarized with mean, SD, and proportions, respectively. The mean and standard deviation of the contralateral suppression index (CSI) were estimated with an intercept-only Bayesian inference model. Results: Of the 32 patients, the average age was 52.47 +26.14 and 19 (59.4%) were males. Both AVs were successfully cannulated in 12 (37.5%). Among them, lateralization was demonstrated in 11(91.7%), and one was diagnosed as a bilateral disease. There were no total failures. Right AV cannulation was unsuccessful in 18 (56.25%), of which lateralization was demonstrated in 9 (50%), and others were inconclusive. Left AV cannulation was unsuccessful only in 2 (6.25%); one was lateralized, and the other remained inconclusive. The estimated mean of the CSI was 0.33 (89% credible interval 0.11-0.86). Seven patients underwent unilateral adrenalectomy and demonstrated significant improvement in blood pressure during follow-up. Two patients await surgery. Others were treated medically. Conclusions: Despite failure due to procedural difficulties, AVS remained useful in the management of patients with PA. Moreover, the success of the procedure needs experienced hands and advanced equipment to achieve optimal outcomes in PA.

Keywords: adrenal venous sampling, lateralization, contralateral suppression index, primary aldosteronism

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Authors: Rajiv Jash, Himangshusekhar Maji

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Phytomolecules have long been associated with the effective treatment of various disorders since ages. This study focuses on identifying the immunomodulatory pure molecules isolated from plants, which can be studied for their effect in alleviating IgAN. All the phytomolecules mentioned here have inflammation-reducing properties, and IgAN, being an autoimmune disease, can be a good target of these phytomolecules. Various pathological pathways of IgA nephropathy can be targeted with these phytomolecules, and this study is an effort to find out the rationale behind the choice of the molecules based on their ability to target the effector molecules of those pathological pathways.

Keywords: IgAN, fibrosis, inflammation, ESRD, TGFβ

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Authors: Abdul-Monim Batiha, Manar AlAzzam, Mohammed ALBashtawy, Loai Tawalbeh, Ahmad Tubaishat, Fadwa N. Alhalaiqa

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Background: Obesity is the major modifiable risk factor for many chronic illnesses especially high blood pressure. Objectives: To evaluate the relationship between anthropometric indices and high blood pressure, and which one was most strongly correlated with high blood pressure in Jordanian population. Methods: A cross-sectional study was conducted with a total 622 students and workers from three Jordanian universities. Results: Nearly half of the participant are overweight (34.7%) and obese (15.4%) and hypertension was detected among 138 (22.2%) of the participants. Linear correlation was significant (p<0.01) between both systolic blood pressure and diastolic blood pressure for all anthropometric indices, except for A body shape index and diastolic blood pressure was significant at p< 0.05. Stepwise multiple linear regression analysis was used to assess the influence of age and anthropometric measurements. Conclusions: The waist circumference was the only independent predictor of hypertension, showing that this simple measurement may be an importance marker of high blood pressure in Jordanian population.

Keywords: anthropometric indices, Jordan, blood pressure, cross-sectional study, obesity, hypertension, waist circumference

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Authors: Kadhim Alabady

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Purpose: Mental health problems affect women and men equally, but some are more common among women. To Provide a baseline of the current picture of major mental health challenges among women in Dubai. which can then be used to measure the impact of interventions or service development. Method: We have used mixed methods evaluation approaches. This was used to increase the validity of findings by using a variety of data collection techniques. We have integrated qualitative and quantitative methods in this piece of work. Conducting the two approaches is to explore issues that might not be highlighted enough through one method. Results: The key findings are: The prevalence of people who suffer from different types of mental disorders remains largely unknown, many women are unwilling to seek professional help because of lack of awareness or the stigma attached to it. -It is estimated there were around 2,928–4,392 mothers in Dubai (2014) suffering from postnatal depression of which 858–1,287, early intervention can be effective. -The system for managing health care for women with mental illness is fragmented and contains gaps and duplications. -It is estimated 1,029 girl aged 13–19 years affected with anorexia nervosa and there would be an estimated 1,029 girl aged 13–19 years affected with anorexia nervosa. Recommendations: -Work is required with primary health care in order to identify women with undiagnosed mental illnesses. Further work is undertaken within primary health care to assess disease registries with the aim of helping GP practices to improve their disease registers. -It is important to conduct local psychiatric morbidity surveys in Dubai to obtain data and assess the prevalence of essential mental health symptoms and conditions that are not routinely collected to get a clear sense of what is needed and to assist decision and policy making in getting a complete picture on what services are required. -Emergency Mental Health Care – there is a need for a crisis response team to respond to emergencies in the community. -Continuum of care – a significant gap in the services for women once they diagnosed with mental disorder.

Keywords: mental health, depression, schizophrenia, women

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Authors: Dativa Maria Aliddeki, Fred Monje, Godfrey Nsereko, Benon Kwesiga, Daniel Kadobera, Alex Riolexus Ario

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Background: Cholera is a severe gastrointestinal disease caused by Vibrio cholera. It has caused several pandemics. On 26 February 2018, a suspected cholera outbreak, with one death, occurred in School X in Hoima Municipality, western Uganda. We investigated to identify the scope and mode of transmission of the outbreak, and recommend evidence-based control measures. Methods: We defined a suspected case as onset of diarrhea, vomiting, or abdominal pain in a student or staff of School X or their family members during 14 February–10 March. A confirmed case was a suspected case with V. cholerae cultured from stool. We reviewed medical records at Hoima Hospital and searched for cases at School X. We conducted descriptive epidemiologic analysis and hypothesis-generating interviews of 15 case-patients. In a retrospective cohort study, we compared attack rates between exposed and unexposed persons. Results: We identified 15 cases among 75 students and staff of School X and their family members (attack rate=20%), with onset from 25-28 February. One patient died (case-fatality rate=6.6%). The epidemic curve indicated a point-source exposure. On 24 February, a student brought fried fish from her home in a fishing village, where a cholera outbreak was ongoing. Of the 21 persons who ate the fish, 57% developed cholera, compared with 5.6% of 54 persons who did not eat (RR=10; 95% CI=3.2-33). None of 4 persons who recooked the fish before eating, compared with 71% of 17 who did not recook it, developed cholera (RR=0.0, 95%CIFisher exact=0.0-0.95). Of 12 stool specimens cultured, 6 yielded V. cholerae. Conclusion: This cholera outbreak was caused by eating fried fish, which might have been contaminated with V. cholerae in a village with an ongoing outbreak. Lack of thorough cooking of the fish might have facilitated the outbreak. We recommended thoroughly cooking fish before consumption.

Keywords: cholera, disease outbreak, foodborne, global health security, Uganda

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Authors: Benjamin Osei-Tutu, Henrietta Awewole Kolson

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Background: Acute gastroenteritis is one of the frequently reported Out-Patient Department (OPD) cases. However, the causative pathogens of these cases are rarely identified at the OPD due to delay in laboratory results or failure to obtain specimens before antibiotics is administered. Method: A retrospective review of surveillance data from the Adentan Municipality, Accra, Ghana that were recorded in the National foodborne disease surveillance system of Ghana, was conducted with the main aim of describing the epidemiology and food practice of cases reported from the Adentan Municipality. The study involved a retrospective review of surveillance data kept on patients who visited health facilities that are involved in foodborne disease surveillance in Ghana, from January 2015 to December 2016. Results: A total of 375 cases were reviewed and these were classified as viral hepatitis (hepatitis A and E), cholera (Vibrio cholerae), dysentery (Shigella sp.), typhoid fever (Salmonella sp.) or gastroenteritis. Cases recorded were all suspected case and the average cases recorded per week was 3. Typhoid fever and dysentery were the two main clinically diagnosed foodborne illnesses. The highest number of cases were observed during the late dry season (Feb to April), which marks the end of the dry season and the beginning of the rainy season. Relatively high number of cases was also observed during the late wet seasons (Jul to Oct) when the rainfall is the heaviest. Home-made food and street vended food were the major sources of suspected etiological food, recording 49.01% and 34.87% of the cases respectively. Conclusion: Majority of cases recorded were classified as gastroenteritis due to the absence of laboratory confirmation. Few cases were classified as typhoid fever and dysentery based on clinical symptoms presented. Patients reporting with foodborne diseases were found to consume home meal and street vended foods as their predominant source of food.

Keywords: accra, etiologic food, food poisoning, gastroenteritis, illness, surveillance

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Authors: Katarzyna Palus, Jarosław Całka

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Gastrointestinal disorders, especially acid-related diseases, including peptic and duodenal ulcers, gastroesophageal reflux disease, upper GI bleeding or stress-related mucosal disease, are currently serious health issues encountered very frequently in patients worldwide. However, to date, the response of sympathetic neurons to gastric mucosal injury and local inflammation following hyperacidity is unknown. Thus, the present study was designed to determine possible changes in expression of galanin (GAL) in the CSMG neurons supplying the prepyloric area of the porcine stomach in a physiological state and following experimentally-induced hyperacidity by using combined retrograde tracing and double-labelling immunohistochemistry. The choice of the domestic pig as an experimental model in the present study is not accidental and is justified by the high degree of physiological and anatomical similarity to human digestive system functions. In this experiment ten juvenile female pigs of the Large White Polish breed were used. The animals were divided into two groups: control and animals with hydrochloric acid infusion (HCl). The neuronal retrograde marker Fast Blue (FB) was injected into the anterior prepyloric wall of the stomach of all animals. After 23 days, animals of the HCl-group were reintroduced into a state of general anesthesia and intragastrically given 5 ml/kg of body weight of 0.25 M aqueous solution of hydrochloric acid. On the 28th day, all animals were euthanized. The CSMG complexes were then collected and the CSMG cryostat sections were stained immunocytochemically for GAL and TH (tyrosine hydroxylase). Immunohistochemistry revealed that in the control group 8.40 ± 0.53 % out of 200 FB-positive CSMG neurons contained GAL. In HCl group upregulation of the GAL-IR neurons to 22.52 ± 1.18 % were observed. All GAL-IR neurons in both groups showed the simultaneously TH immunoreactivity. Increase in the expression of GAL in FB-positive neurons of the HCL group may suggest its participation in the protective mechanisms of neurons in different pathological processes, such as gastric hyperacidity.

Keywords: coeliac-superior mesenteric ganglion complex, gastric innervation, hyperacidity, immunohistochemistry

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Authors: Abdou Elhendy

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Numerous study have shown the efficacy of the percutaneous intervention (PCI) and coronary stenting in improving left ventricular function and relieving exertional angina. Furthermore, PCI remains the main line of therapy in acute myocardial infarction. Improvement of procedural techniques and new devices have resulted in an increased number of PCI in those with difficult and extensive lesions, multivessel disease as well as total occlusion. Immediate and late outcome may be compromised by acute thrombosis or the development of fibro-intimal hyperplasia. In addition, progression of coronary artery disease proximal or distal to the stent as well as in non-stented arteries is not uncommon. As a result, complications can occur, such as acute myocardial infarction, worsened heart failure or recurrence of angina. In a stent, restenosis can occur without symptoms or with atypical complaints rendering the clinical diagnosis difficult. Routine invasive angiography is not appropriate as a follow up tool due to associated risk and cost and the limited functional assessment. Exercise and pharmacologic stress testing are increasingly used to evaluate the myocardial function, perfusion and adequacy of revascularization. Information obtained by these techniques provide important clues regarding presence and severity of compromise in myocardial blood flow. Stress echocardiography can be performed in conjunction with exercise or dobutamine infusion. The diagnostic accuracy has been moderate, but the results provide excellent prognostic stratification. Adding myocardial contrast agents can improve imaging quality and allows assessment of both function and perfusion. Stress radionuclide myocardial perfusion imaging is an alternative to evaluate these patients. The extent and severity of wall motion and perfusion abnormalities observed during exercise or pharmacologic stress are predictors of survival and risk of cardiac events. According to current guidelines, stress echocardiography and radionuclide imaging are considered to have appropriate indication among patients after PCI who have cardiac symptoms and those who underwent incomplete revascularization. Stress testing is not recommended in asymptomatic patients, particularly early after revascularization, Coronary CT angiography is increasingly used and provides high sensitive for the diagnosis of coronary artery stenosis. Average sensitivity and specificity for the diagnosis of in stent stenosis in pooled data are 79% and 81%, respectively. Limitations include blooming artifacts and low feasibility in patients with small stents or thick struts. Anatomical and functional cardiac imaging modalities are corner stone for the assessment of patients after PCI and provide salient diagnostic and prognostic information. Current imaging techniques cans serve as gate keeper for coronary angiography, thus limiting the risk of invasive procedures to those who are likely to benefit from subsequent revascularization. The determination of which modality to apply requires careful identification of merits and limitation of each technique as well as the unique characteristic of each individual patient.

Keywords: coronary artery disease, stress testing, cardiac imaging, restenosis

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Authors: Anna Höfer, Johannes Herrmann, Patrick Meybohm, Christopher Lotz

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Mitochondria are pivotal for energy supply and regulation of cellular functions. Deficiencies of mitochondrial metabolism have been implicated in diverse stressful conditions including infections. Platelets are key mediators for thrombo-inflammation during development and resolution of acute respiratory distress syndrome (ARDS). Previous data point to an exhausted platelet phenotype in critically-ill patients with coronavirus 19 disease (COVID-19) impacting the course of disease. The objective of this work was to characterize platelet mitochondrial metabolism in patients suffering from COVID-19 ARDSA longitudinal analysis of platelet mitochondrial metabolism in 24 patients with COVID-19 induced ARDS compared to 35 healthy controls (ctrl) was performed. Blood samples were analyzed at two time points (t1=day 1; t2=day 5-7 after study inclusion). The activity of mitochondrial citrate synthase was photometrically measured. The impact of oxidative stress on mitochondrial permeability was assessed by a photometric calcium-induced swelling assay and the activity of superoxide dismutase (SOD) by a SOD assay kit. The amount of protein carbonylation and the activity of mitochondria complexes I-IV were photometrically determined. Levels of interleukins (IL)-1α, IL-1β and tumor necrosis factor (TNF-) α were measured by a Multiplex assay kit. Median age was 54 years, 63 % were male and BMI was 29.8 kg/m2. SOFA (12; IQR: 10-15) and APACHE II (27; IQR: 24-30) indicated critical illness. Median Murray Score was 3.4 (IQR: 2.8-3.4), 21/24 (88%) required mechanical ventilation and V-V ECMO support in 14/24 (58%). Platelet counts in ARDS did not change during ICU stay (t1: 212 vs. t2: 209 x109/L). However, mean platelet volume (MPV) significantly increased (t1: 10.6 vs. t2: 11.9 fL; p<0.0001). Citrate synthase activity showed no significant differences between ctrl and ARDS patients. Calcium induced swelling was more pronounced in patients at t1 compared to t2 and to ctrl (50µM; t1: 0.006 vs. ctrl: 0.016 ΔOD; p=0.001). The amount of protein carbonylation as marker for irreversible proteomic modification constantly increased during ICU stay and compared to ctrl., without reaching significance. In parallel, superoxid dismutase activity gradually declined during ICU treatment vs. ctrl (t2: - 29 vs. ctrl.: - 17 %; p=0.0464). Complex I analysis revealed significantly stronger activity in ARDS vs. ctrl. (t1: 0.633 vs. ctrl.: 0.415 ΔOD; p=0.0086). There were no significant differences in complex II, III or IV activity in platelets from ARDS patients compared to ctrl. IL-18 constantly increased during the observation period without reaching significance. IL-1α and TNF-α did not differ from ctrl. However, IL-1β levels were significantly elevated in ARDS (t1: 16.8; t2: 16.6 vs. ctrl.: 12.4 pg/mL; p1=0.0335, p2=0.0032). This study reveals new insights in platelet mitochondrial metabolism during COVID-19 caused ARDS. it data point towards enhanced platelet activity with a pronounced turnover rate. We found increased activity of mitochondria complex I and evidence for enhanced oxidative stress. In parallel, protective mechanisms against oxidative stress were narrowed with elevated levels of IL-1β likely causing a pro-apoptotic environment. These mechanisms may contribute to platelet exhaustion in ARDS.

Keywords: acute respiratory distress syndrome (ARDS), coronavirus 19 disease (COVID-19), oxidative stress, platelet mitochondrial metabolism

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Authors: Pouriya Darabiyan, Kourosh Zarea, Saeed Ghanbari, Aseya Temori, Shokreya Ehsani

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Introduction: Diabetes is one of the most common metabolic disorders and is one of the top 10 leading causes of death in adults. Therefore, this study was conducted to investigate the epidemiological prevalence of diabetes in Afghanistan between 2015 and 2019. Methods: This descriptive cross-sectional study was performed using the information of diabetics registered in the system related to the Ministry of Health of Afghanistan from 2015 to 2019. Eventually, people's information, including age, gender, and place of residence, was entered into STATA software version 12 and analyzed using descriptive statistics tests. Results: The study, which was performed on 49,339 people with diabetes in 34 provinces and 8 regions of Afghanistan, found that most of the women studied were 55.2% (272,311) women and had the highest and lowest prevalence in the region. The order is related to South East and South. The average prevalence of diabetes per 10,000 people is about 62.13. Conclusions: The prevalence of diabetes in Afghanistan over a five-year period in men and women is on the rise, requiring more attention from relevant authorities to improve public health and prevent, control and treat chronic diseases such as diabetes. Keywords: Diabetes, Prevalence, Afghanistan, Epidemiology

Keywords: diabetes, prevalence, Afghanistan, epidemiology

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Authors: Alexandra K. Diem, Giles Richardson, Roxana O. Carare, Neil W. Bressloff

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Alzheimer's disease (AD) is the most common form of dementia and although it has been researched for over 100 years, there is still no cure or preventive medication. Its onset and progression is closely related to the accumulation of the neuronal metabolite Aβ. This raises the question of how metabolites and waste products are eliminated from the brain as the brain does not have a traditional lymphatic system. In recent years the rapid uptake of Aβ into cerebral artery walls and its clearance along those arteries towards the lymph nodes in the neck has been suggested and confirmed in mice studies, which has led to the hypothesis that interstitial fluid (ISF), in the basement membranes in the walls of cerebral arteries, provides the pathways for the lymphatic drainage of Aβ. This mechanism, however, requires a net reverse flow of ISF inside the blood vessel wall compared to the blood flow and the driving forces for such a mechanism remain unknown. While possible driving mechanisms have been studied using mathematical models in the past, a mechanism for net reverse flow has not been discovered yet. Here, we aim to address the question of the driving force of this reverse lymphatic drainage of Aβ (also called perivascular drainage) by using multi-scale numerical and analytical modelling. The numerical simulation software COMSOL Multiphysics 4.4 is used to develop a fluid-structure interaction model of a cerebral artery, which models blood flow and displacements in the artery wall due to blood pressure changes. An analytical model of a layer of basement membrane inside the wall governs the flow of ISF and, therefore, solute drainage based on the pressure changes and wall displacements obtained from the cerebral artery model. The findings suggest that an active role in facilitating a reverse flow is played by the components of the basement membrane and that stiffening of the artery wall during age is a major risk factor for the impairment of brain lymphatics. Additionally, our model supports the hypothesis of a close association between cerebrovascular diseases and the failure of perivascular drainage.

Keywords: Alzheimer's disease, artery wall mechanics, cerebral blood flow, cerebral lymphatics

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Authors: Alison C. Essary, Victor Trastek

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Introduction: The current state of the health care system in the U.S. is characterized by an unprecedented number of people living with multiple chronic conditions, unsustainable rise in health care costs, inadequate access to care, and wide variation in health outcomes throughout the country. An estimated two-thirds of Americans are living with two or more chronic conditions, contributing to 75% of all health care spending. In 2013, the School for the Science of Health Care Delivery (SHCD) was charged with redesigning the health care system through education and research. Faculty in business, law, and public policy, and thought leaders in health care delivery, administration, public health and health IT created undergraduate, graduate, and executive academic programs to address this pressing need. Faculty and students work across disciplines, and with community partners and employers to improve care delivery and increase value for patients. Methods: Curricula apply content in health care administration and operations within the clinical context. Graduate modules are team-taught by faculty across academic units to model team-based practice. Seminars, team-based assignments, faculty mentoring, and applied projects are integral to student success. Cohort-driven models enhance networking and collaboration. This observational study evaluated two years of admissions data, and one year of graduate data to assess program outcomes and inform the current graduate-level curricula. Descriptive statistics includes means, percentages. Results: Fall 2013, the program received 51 applications. The mean GPA of the entering class of 37 students was 3.38. Ninety-seven percent of the fall 2013 cohort successfully completed the program (n=35). Sixty-six percent are currently employed in the health care industry (n=23). Of the remaining 12 graduates, two successfully matriculated to medical school; one works in the original field of study; four await results on the MCAT or DAT, and five were lost to follow up. Attrition of one student was attributed to non-academic reasons. Fall 2014, the program expanded to include both on-ground and online cohorts. Applications were evenly distributed between on-ground (n=70) and online (n=68). Thirty-eight students enrolled in the on-ground program. The mean GPA was 3.95. Ninety-five percent of students successfully completed the program (n=36). Thirty-six students enrolled in the online program. The mean GPA was 3.85. Graduate outcomes are pending. Discussion: Challenges include demographic variability between online and on-ground students; yet, both profiles are similar in that students intend to become change agents in the health care system. In the past two years, on-ground applications increased by 31%, persistence to graduation is > 95%, mean GPA is 3.67, graduates report admission to six U.S. medical schools, the Mayo Medical School integrates SHCD content within their curricula, and there is national interest in collaborating on industry and academic partnerships. This places SHCD at the forefront of developing innovative curricula in order to improve high-value, patient-centered care.

Keywords: delivery science, education, health care delivery, high-value care, innovation in education, patient-centered

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