Search results for: cell-based therapy

Authors: Betul Taspinar, Eda O. Okur, Ismail Saracoglu, Ismail Okur, Ferruh Taspinar

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Thoracic hyperkyphosis, is a well-known spinal phenomenon, refers to an excessive curvature (> 40 degrees) of the thoracic spine. The aim of this study was to explore the effectiveness of thrust manipulation on thoracic spine alignment. 31 young adults with hyperkyphosis diagnosed with Spinal Mouse® device were randomly assigned either thrust manipulation group (n=16, 11 female, 5 male) or sham manipulation group (n=15, 8 female, 7 male). Thrust and sham manipulations were performed by a blinded physiotherapist who is a certificated expert in musculoskeletal physiotherapy. Thoracic kyphosis degree was measured after the interventions via Spinal Mouse®. Wilcoxon test was used to analyse the data obtained before and after the manipulation for each group, whereas Mann-Whitney U test was used to compare the groups. The mean of baseline thoracic kyphosis degrees in thrust and sham groups were 50.69 o ± 7.73 and 48.27o ± 6.43, respectively. There was no statistically significant difference between groups in terms of initial thoracic kyphosis degrees (p=0.51). After the interventions, the mean of thoracic kyphosis degree in thrust and sham groups were measured as 44.06o ± 6.99 and 48.93o ± 6.57 respectively (p=0.03). There was no statistically significant difference between before and after interventions in sham group (p=0.33), while the mean of thoracic kyphosis degree in thrust group decreased significantly (p=0.00). Thrust manipulation can attenuate thoracic hyperkyphosis immediately in young adults by not using placebo effect. Manipulation might provide accurate proprioceptive (sensory) input to the spine joints and reduce kyphosis by restoring normal segment mobility. Therefore thoracic manipulation might be included in the physiotherapy programs to treat hyperkyphosis.

Keywords: hyperkyphosis, manual therapy, spinal mouse, physiotherapy

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Authors: Jamie R. Chua, Christina Irene D. Mejia, Regina P. Berba

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Disseminated tuberculosis is an infectious disease caused by Mycobacterium tuberculosis involving two or more non-contiguous sites identified through bacteriologic confirmation or clinical diagnosis. Over the five year period included in the study, the UP-PGH TB DOTS clinic had total of 3,967 referrals, and the prevalence of disseminated tuberculosis is 1% (68/3967). The mean age was 33.9 years (range 19-64 years) with a male: female ratio of 1:1. 67% (52 patients) had no predisposing comorbid illness or immune disorder. The most common presenting symptoms were abdominal pain (19%), back pain (13%), abdominal enlargement (11%) and mass (10.2%). Anemia, leukocytosis, hypoalbuminemia, and high-normal serum calcium were common biochemical and hematologic findings. Around 36% (25) of patients were diagnosed clinically with disseminated tuberculosis despite lacking bacteriologic evidence of multi-organ involvement. The lungs (86%) is still the most commonly involved site, followed by intestinal (22%), vertebral/Pott’s (27%), and pelvic/genital (19%). The mean time from presentation to initiation of therapy was 22 days (SD 32.7). Only 18 patients (29.3%) were properly recorded to have been referred to local TB DOTs facilities. Of the 68 patients, only 16% (11 patients) continued follow-up at PGH, and all had documented treatment completion. Treatment outcomes of the remaining were unknown. Due to the variety of involved sites, a high index of suspicion is required. Knowledge on clinical features, common radiographic findings, and histopathologic characteristics of disseminated TB is important as bacteriologic evidence of infection is not always apparent.

Keywords: disseminated tuberculosis, Mycobacterium tuberculosis, miliary tuberculosis, tuberculosis

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Authors: Michaela Dušková, Kateřina Šimůnková, Martin Hill, Hana Hruškovičová, Hana Pospíšilová, Eva Králíková, Luboslav Stárka

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Smoking represents the most widespread substance dependence in the world. Several studies show the nicotine's ability to alter women hormonal homeostasis. Women smokers have higher testosterone and lower estradiol levels throughout life compared to non-smoker women. We monitored the effect of smoking discontinuation on steroid spectrum with 40 premenopausal and 60 postmenopausal women smokers. These women had been examined before they discontinued smoking and also after 6, 12, 24, and 48 weeks of abstinence. At each examination, blood was collected to determine steroid spectrum (measured by GC-MS), LH, FSH, and SHBG (measured by IRMA). Repeated measures ANOVA model was used for evaluation of the data. The study has been approved by the local Ethics Committee. Given the small number of premenopausal women who endured not to smoke, only the first 6 week period data could be analyzed. A slight increase in androgens after the smoking discontinuation occurred. In postmenopausal women, an increase in testosterone, dihydrotestosterone, dehydroepiandrosterone, and other androgens occurred, too. Nicotine replacement therapy, weight changes, and age does not play any role in the androgen level increase. The higher androgens levels correlated with failure in smoking cessation. Women smokers have higher androgen levels, which might play a role in smoking dependence development. Women successful in smoking cessation, compared to the non-successful ones, have lower androgen levels initially and also after smoking discontinuation. The question is what androgen levels women have before they start smoking.

Keywords: addiction, smoking, cessation, androgens

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Authors: Mario Isaza-Ruget, Claudia C. Colmenares-Mejia, Nancy Yomayusa, Camilo A. González, Andres Cely, Jossie Murcia

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Quantification of risks associated with complications development from chronic kidney disease (CKD) through accurate survival models can help with patient management. A retrospective cohort that included patients diagnosed with CKD from a primary care program and followed up between 2013 and 2018 was carried out. Time-dependent and static covariates associated with demographic, clinical, and laboratory factors were included. Deep Learning (DL) survival analyzes were developed for three CKD outcomes: CKD stage progression, >25% decrease in Estimated Glomerular Filtration Rate (eGFR), and Renal Replacement Therapy (RRT). Models were evaluated and compared with Random Survival Forest (RSF) based on concordance index (C-index) metric. 2.143 patients were included. Two models were developed for each outcome, Deep Neural Network (DNN) model reported C-index=0.9867 for CKD stage progression; C-index=0.9905 for reduction in eGFR; C-index=0.9867 for RRT. Regarding the RSF model, C-index=0.6650 was reached for CKD stage progression; decreased eGFR C-index=0.6759; RRT C-index=0.8926. DNN models applied in survival analysis context with considerations of longitudinal covariates at the start of follow-up can predict renal stage progression, a significant decrease in eGFR and RRT. The success of these survival models lies in the appropriate definition of survival times and the analysis of covariates, especially those that vary over time.

Keywords: artificial intelligence, chronic kidney disease, deep neural networks, survival analysis

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Authors: M. Klimova, O. Semyachkina-Glushkovskaya, J. Kurts, E. Zinchenko, N. Navolokin, A. Shirokov, A. Dubrovsky, A. Abdurashitov, A. Terskov, A. Mamedova, I. Agranovich, T. Antonova, I. Blokhina

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The direction for research of Alzheimer's disease is to find an effective non-invasive and non-pharmacological way of treatment. Here we tested our hypothesis that the opening of the blood-brain barrier (BBB) induces activation of lymphatic drainage and clearing functions that can be used as a method for non-invasive stimulation of clearance of beta-amyloid and therapy of Alzheimer’s disease (AD). To test our hypothesis, in this study on healthy male mice we analyzed the interaction between BBB opening by repeated loud music (100-10000 Hz, 100 dB, duration 2 h: 60 sec – sound; 60 sec - pause) and functional changes in the meningeal lymphatic vessels (MLVs). We demonstrate clearance of dextran 70 kDa (i.v. injection), fluorescent beta-amyloid (intrahippocampal injection) and gold nanorods (intracortical injection) via MLV that significantly increased after the opening of BBB. Our studies also demonstrate that the BBB opening was associated with the improvement of neurocognitive status in mice with AD. Thus, we uncover therapeutic effects of BBB opening by loud music, such as non-invasive stimulation of lymphatic clearance of beta-amyloid in mice with AD, accompanied by improvement of their neurocognitive status. Our data are consistent with other results suggesting the therapeutic effect of BBB opening by focused ultrasound without drugs for patients with AD. This research was supported by a grant from RSF 18-75-10033

Keywords: Alzheimer's disease, beta-amyloid, blood-brain barrier, meningeal lymphatic vessels, repeated loud music

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Authors: Ryuji Yamazaki, Masahiro Kochi, Weiran Zhu, Hiroko Kase

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In care for older adults, behavioral and psychological symptoms of dementia (BPSD) like agitation and aggression are distressing for patients and their caretakers, often resulting in premature institutionalization with increased costs of care. To improve mood and mitigate symptoms, as a non-pharmaceutical approach, emotion-oriented therapy like reminiscence work is adopted in face-to-face communication. Telecommunication support is expected to be provided by robotic media as a bridge for digital divide for those with dementia and facilitate social interaction both verbally and nonverbally. The purpose of this case study is to explore the conditions in which robotic media can effectively attract attention from older adults with dementia and promote their well-being. As a pilot study, we introduced the pillow-phone Hugvie^®, a huggable humanly shaped communication medium to five residents with dementia at a care facility, to investigate how the following conditions work for the elderly when they use the medium; 1) no sound, 2) radio, non-interactive, 3) daily conversation, and 4) reminiscence work. As a result, under condition 4, reminiscence work, the five participants kept concentration in interacting with the medium for a longer duration than other conditions. In condition 4, they also showed larger amount of utterances than under other conditions. These results indicate that providing topics related to personal histories through robotic media could affect communication positively and should, therefore, be further investigated. In addition, the issue of ethical implications by using persuasive technology that affects emotions and behaviors of older adults is also discussed.

Keywords: BPSD, reminiscence, tactile telecommunication, utterances

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Authors: H. M. Imam, H. M. Rezk, A. F. Tohamy

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Background: Human umbilical cord blood (HUCB) is considered as a unique source for stem cells. HUCB contain different types of progenitor cells which could differentiate into hepatocytes. Aims: To investigate the potential of rat's liver damage repair using human umbilical cord mesenchymal stem cells (hUCMSCs). We investigated the feasibility for hUCMSCs in recovery from liver damage. Moreover, investigating fibrotic liver repair and using the CCl4-induced model for liver damage in the rat. Methods: Rats were injected with 0.5 ml/kg CCl4 to induce liver damage and progressive liver fibrosis. hUCMSCs were injected into the rats through the tail vein; Stem cells were transplanted at a dose of 1×106 cells/rat after 72 hours of CCl4 injection without receiving any immunosuppressant. After (6 and 8 weeks) of transplantation, blood samples were collected to assess liver functions (ALT, AST, GGT and ALB) and level of Procollagen III as a liver fibrosis marker. In addition, hepatic tissue regeneration was assessed histopathologically and immunohistochemically using antihuman monoclonal antibodies against CD34, CK19 and albumin. Results: Biochemical and histopathological analysis showed significantly increased recovery from liver damage in the transplanted group. In addition, HUCB stem cells transdifferentiated into functional hepatocytes in rats with hepatic injury which results in improving liver structure and function. Conclusion: Our findings suggest that transplantation of hUCMSCs may be a novel therapeutic approach for treating liver fibrosis. Therefore, hUCMSCs are a potential option for treatment of liver cirrhosis.

Keywords: carbon tetra chloride, liver fibrosis, mesenchymal stem cells, rat

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Authors: Nahashon Mwirigi

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The management of HIV/AIDS is a global challenge, demanding precise tools to predict disease progression and guide tailored treatment. CD4 cell count dynamics, a crucial immune function indicator, play an essential role in understanding HIV/AIDS progression and enhancing patient care through effective modeling. While several models assess disease progression, existing methods often fall short in capturing the complex, non-linear nature of HIV/AIDS, especially across diverse demographics. A need exists for models that balance predictive accuracy with clinical applicability, enabling individualized care strategies based on patient-specific progression rates. This study utilizes patient data from Kenyatta National Hospital (2003–2014) to model HIV/AIDS progression across six CD4-defined states. The Exponential, 2-Parameter Weibull, and 3-Parameter Weibull models are employed to analyze failure rates and explore progression patterns by age and gender. Model selection is based on Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) to identify models best representing disease progression variability across demographic groups. The 3-Parameter Weibull model emerges as the most effective, accurately capturing HIV/AIDS progression dynamics, particularly by incorporating delayed progression effects. This model reflects age and gender-specific variations, offering refined insights into patient trajectories and facilitating targeted interventions. One key finding is that older patients progress more slowly through CD4-defined stages, with a delayed onset of advanced stages. This suggests that older patients may benefit from extended monitoring intervals, allowing providers to optimize resources while maintaining consistent care. Recognizing slower progression in this demographic helps clinicians reduce unnecessary interventions, prioritizing care for faster-progressing groups. Gender-based analysis reveals that female patients exhibit more consistent progression, while male patients show greater variability. This highlights the need for gender-specific treatment approaches, as men may require more frequent assessments and adaptive treatment plans to address their variable progression. Tailoring treatment by gender can improve outcomes by addressing distinct risk patterns in each group. The model’s ability to account for both accelerated and delayed progression equips clinicians with a robust tool for estimating the duration of each disease stage. This supports individualized treatment planning, allowing clinicians to optimize antiretroviral therapy (ART) regimens based on demographic factors and expected disease trajectories. Aligning ART timing with specific progression patterns can enhance treatment efficacy and adherence. The model also has significant implications for healthcare systems, as its predictive accuracy enables proactive patient management, reducing the frequency of advanced-stage complications. For resource limited providers, this capability facilitates strategic intervention timing, ensuring that high-risk patients receive timely care while resources are allocated efficiently. Anticipating progression stages enhances both patient care and resource management, reinforcing the model’s value in supporting sustainable HIV/AIDS healthcare strategies. This study underscores the importance of models that capture the complexities of HIV/AIDS progression, offering insights to guide personalized, data-informed care. The 3-Parameter Weibull model’s ability to accurately reflect delayed progression and demographic risk variations presents a valuable tool for clinicians, supporting the development of targeted interventions and resource optimization in HIV/AIDS management.

Keywords: HIV/AIDS progression, 3-parameter Weibull model, CD4 cell count stages, antiretroviral therapy, demographic-specific modeling

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Authors: M. S. M. Anjalee Umesha Bandara

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Hela Veda Shastra is a science that is an endowment from generation to generation. There is also an individualistic science and indigenous practice of traditional herbs. There are many effective cures for snakes, fractures, head cancer, cuts, lunatics, reflexology, etc. Hela physicians who rescued them from infections caused by snakes have recognized poems to remember the medicines they used to cure the patients. Due to the harmony of the Hela Osu and Hela Knowledge poetry collection, it has become easy for the juniors of the Hela Veda generation to gain medical knowledge. It is a research problem whether it is possible to arrive at a correct conclusion about the patient form of the snake information thread through the existing Dhuta characteristics of Hela Serpa Vedakam. This research was done with the assumption that snake venom can be successfully treated according to its characteristics. In this research, two generations related to the Ratmalavatiya Vedaparamparava and the Vannihatpattu of the Kalla Veda generation have been identified as Veda Paramparas who treat and created Dutha Kavya, including the form of the Serpent Dasthana. They have collected ancient books, documents and interviews related to qualitative research on snake disease treatment. In addition, collecting data by referring to books related to Hela medicine. The ancient indigenous lineage methods that are superior to modern Western science's snake therapy should save the Hela's amazing wealth of wisdom for the future, leaving aside the selfishness of keeping the teaching to themselves.

Keywords: snake venom medicine, vedic genealogy, Dhuta characteristic, snake

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Authors: Małgorzata Drzewiecka, Tomasz Śliwiński, Maciej Radek

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The inhibition of histone deacetyles (HDACs) holds promise as a potential anti-cancer therapy because histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, histone deacetylase inhibitors (HDACi) such as class I HDAC inhibitor - valproic acid (VPA) have been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that, using of VPA in combination with talazoparib (BMN-637 – PARP1 inhibitor – PARPi) and/or Dacarabazine (DTIC - alkylating agent) resulted in increased DNA double strand break (DSB) and reduced survival (while not affecting primary melanocytes )and proliferation of melanoma cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-637. In addition, inhibition of HDAC caused sensitization of melanoma cells to dacarbazine and BMN-637 in melanoma xenografts in vivo. At the mRNA and protein level histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study provides that combining HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is known for being one of the most aggressive malignant tumors. The findings presented here point to a scenario in which HDAC via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies.

Keywords: melanoma, hdac, parp inhibitor, valproic acid

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Authors: Y. V. S. Annapurna, V. V. Lakshmi

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Urinary tract infection (UTI) is one of the most common infectious diseases at the community level with a high rate of morbidity . This is further augmented by increase in the number of resistant and multi resistant strains of bacteria particularly by those producing Extended spectrum of beta lactamases. The present study was aimed at analysis of antibiograms of E.coli and Klebsiella sp causing urinary tract infections. Between November 2011 and April 2013, a total of 1120 urine samples were analyzed,. Antibiotic sensitivity testing was done with 542(48%) isolates of E.coli and 446(39%) of Klebsiella sp using the standard disc diffusion method against eleven commonly used antibiotics .Organisms showed high susceptibility to Amikacin and Netilimicin and low susceptibility to Cephalosporins. MAR index was calculated for the multidrug resistant strains. Maximum MAR index detected among the isolates was 0.9. Phenotypic identification for ESBL production was confirmed by double disk synergy test (DDST) according to CLSI guidelines. Plasmid profile of the isolates was carried out using alkaline hydrolysis method. Agarose-gel electrophoresis showed presence of high-molecular weight plasmid DNA among the ESBL strains. This study emphasizes the importance of indiscriminate use of antibiotics which if discontinued, in turn would prevent further development of bacterial drug resistance. For this, a proper knowledge of susceptibility pattern of uropathogens is necessary before prescribing empirical antibiotic therapy and it should be made mandatory.

Keywords: escherichia coli, extended spectrum of beta lactamase, Klebsiella spp, Uropathogens

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Authors: Nishu Atrey, Priyanka Singh, G. P. Talwar, Jagdish Gupta, Alka Kriplani, Rohini Sehgal, Indrani Ganguli, Soni Sinha

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Background: Vaginosis is a widely prevalent syndrome in India and elsewhere. Recurrence is frequent in women treated with antibiotics, whose vagina pH remains above 5.0 indicative of the loss of resident lactobacilli. The objective of the present trial was to determine whether a Polyherbal microbicide BASANT can regress Vaginosis. Another objective was to determine whether the three selected strains of Probiotics endowed with making high amounts of lactic acid can colonise and restore the pH of the vagina to the acidic healthy range. Materials and Procedure: BASANT, was employed in powder form in veg (cellulose) capsules. TRF#36 strain of Lactobacillus fermentum, TRF#8 strain of L.gasseri, and TRF#30 strain of L.salivarius (combination termed as Pro-vag-Health) were employed at 3x109 bacilli lyophilized, packaged in capsules. The trials were conducted in women suffering from vaginosis with vaginal pH above 5.0. Women were given intravaginally either BASANT, Pro-vag-Health or a combination of the two intravaginally for seven days and thereafter once weekly as a maintenance dose. Results: BASANT cleared vaginosis in 14/20 women and Pro-vag-Health in 13/20 women. Interestingly, the combination of BASANT plus Pro-vag-Health was effective in 19/20 women, in contrast to Placebo capsules effective only in 1/20 women. Interpretation and Conclusion: The combination of BASANT and Pro-veg-Health Probiotics taken together intravaginally for seven days relieves 19 out of 20 women from vaginosis to restore acidic pH and healthy vagina. Extension of trial with this combination in larger number is indicated.

Keywords: microbicide, probiotics, vaginal pH, vaginosis

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Authors: Elin Julianti, Marlia Singgih, Masayoshi Arai, Jianyu Lin, Masteria Yunovilsa Putra, Muhammad Azhari, Agnia S. Muharam

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The search for a source of new medicinal compounds with anticancer activity from natural products has become important to resolve the ineffectiveness problem of pancreatic cancer therapy. Fungal marine microorganisms are prolific sources of bioactive natural products. In this present study, the ethyl acetate extract of cultured broth of Trichoderma longibrachiatum marine sponge-derived fungi exhibited selective cytotoxicity against human pancreatic carcinoma PANC-1 cells cultured under glucose-deficient conditions (IC50 = 98,4 µg/mL). The T. longibrachiatum was fermented by the static method at room temperature for 60 days. The culture broth was extracted using ethyl acetate by liquid-liquid extraction method. The liquid-liquid extraction was conducted toward the ethyl extract by using 90% MeOH-H₂O and n-|Hexane as a solvent. The extract of 90% MeOH-H₂O was fractionated by liquid extraction using by C₁₈ reversed-phase vacuum flash chromatography using mixtures of MeOH-H₂O, from 50:50 to 100:0, and 1% TFA MeOH as the eluents to yield six fractions. The fraction 2 (MeOH-H2O, 70:30) and fraction 3 (MeOH-H2O, 80:20) showed moderate cytotoxicity with IC50 value of 119.3 and 274.7 µg/mL, respectively. Fraction 4 (MeOH-H₂O, 90:10) showed the highest cytotoxicity activity with IC₅₀value of < 10 µg/mL. The chemical compounds of the fractions that are responsible for cytotoxic activity are potent for further investigation.

Keywords: cytotoxic activity, trichoderma longibrachiatum, marine-derived fungi, PANC-1 cell line

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Authors: Stephanie Cheng, Benjamin Poh, Vivyan Tay, Sachin Mathur

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Aim: Diabetes mellitus (DM) is a worldwide pandemic affecting 500 million people. It is known to be associated with increased susceptibility to soft tissue infections (STI). Despite being a major public health burden, the literature relating the effects of DM and the presentation, severity and healing of STIs in general surgical patients remain limited. Methods: We conducted a retrospective review of all patients admitted with STI in a tertiary teaching hospital over a 12-month period. Patient demographics and surgical outcomes were collected and analyzed. Results: During the study period, 1059 patients were admitted for STIs, of which 936 (88%) required surgical intervention. Diabetic patients were presented with a higher body-mass index (BMI) (28 vs 26), larger abscess size (24 vs 14 cm²) and a longer length of stay (LOS)(4.4 days vs 2.9 days). They also underwent a higher proportion of wide debridement as well as application of negative pressure wound therapy (NPWT) (42% vs 35%). More diabetic patients underwent subsequent re-operation within the same sitting (8 vs 4). There were no differences in re-admission rates within 30 days nor subsequent abscess formation in those followed for 6 months. Conclusion: The incidence of STIs among DM patients represents a significant disease burden; surgeons should consider intensive patient counseling and partnering with primary care providers in order to help reduce the incidence of future STI admissions based on lifestyle modification and glucose control.

Keywords: general surgery, emergency general surgery, acute care surgery, soft tissue infections, diabetes mellitus

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Authors: Sara Mohammad Atef Sabaika

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Background: The development of factor VIII (FVIII) inhibitor and hemophilic arthropathy in patients with hemophilia A (PWHA) are a great challenge for hemophilia care. Both genetic and environmental factors led to complications in PWHA. The development of inhibitory antibodies is usually induced by the immune response. Tumor necrosis factor α (TNF-α), one of the cytokines, might contribute to its polymorphism. Aim: Study the association between tumor necrosis alpha level and genotypes in pediatric patients with hemophilia A and its relation to inhibitor development and joint status. Methods: A cross-sectional study was conducted among a sufficient number of PWHA attending the Pediatric Hematology and Oncology Unit, Pediatric department in Menoufia University hospital. The clinical parameters, FVIII, FVIII inhibitor, and serum TNF-α level were assessed. The genotyping of −380G > A TNF-α gene polymorphism was performed using real time polymerase chain reaction. Results: Among the 50 PWHA, 28 (56%) were identified as severe PWHA. The FVIII inhibitor was identified in 6/28 (21.5%) of severe PWHA. There was a significant correlation between serum TNF-α level and the development of inhibitor (p = 0:043). There was significant correlation between polymorphisms of −380G > A TNF-α gene and hemophilic arthropathy development (p = 0:645). Conclusion: The prevalence of FVIII inhibitor in severe PWHA in Menoufia was 21.5%. The frequency of replacement therapy is a risk factor for inhibitor development. Serum TNF-α level and its gene polymorphism might be used to predict inhibitor development and joint status in pediatric patients with hemophilia A.

Keywords: hemophilic arthropathy, TNF alpha., patients witb hemophilia A PWHA, inhibitor

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Authors: Murali Munisamy, Gauthaman Karunakaran, Mubarak Al-Gahtany, Vivekanandhan Subbiah, M. Manjari Tripati

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Background: Sodium valproate is a widely prescribed broad-spectrum anti-epileptic drug. It shows high inter-individual variability in pharmacokinetics and pharmacodynamics and has a narrow therapeutic range. We evaluated the effects of polymorphic uridine diphosphate glucuronosyltransferase (UGT1A9) metabolizing enzyme on the pharmacokinetics of sodium valproate in the patients with epilepsy who showed toxicity to therapy. Methods: Genotype analysis of the patients was made with polymerase chain–restriction fragment length polymorphism (RFLP) with sequencing. Plasma drug concentrations were measured with reversed phase high-performance liquid chromatography (HPLC) and concentration–time data were analyzed by using a non-compartmental approach. Results: The results of this study suggested a significant genotypic as well as allelic association with valproic acid toxicity for UGT1A9 polymorphic enzymes. The elimination half-life (t 1/2=40.2 h) of valproic acid was longer and the clearance rate (CL=937 ml/h) was lower in the poor metabolizers group of UGT1A9 polymorphism who showed toxicity than in the intermediate metabolizers group (t1/2=35.5 h, CL=1042 ml/h) or the extensive metabolizers group (t1/2=26. h, CL=1,302 ml/h). Conclusion: Our findings suggest that the UGT1A9 genetic polymorphism plays a significant role in the steady state concentration of sodium valproate, and it thereby has an impact on the toxicity of the sodium valproate used in the patients with epilepsy.

Keywords: UGT1A9, sodium valporate, pharmacogenetics, polymorphism

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Authors: S. Aberkane, N. Djabali, S. Fafi, A. Baghezza

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Chronic illnesses affect many Algerians. It is possible to investigate the impact of illness representations and coping on quality of life and whether illness representations are indirectly associated with quality of life through their influence on coping. This study aims at investigating the relationship between illness perception, coping strategies and quality of life with chronic illness. Illness perceptions are indirectly associated with the quality of life through their influence on coping mediation. A sample of 316 participants with chronic illness living in the region of Batna, Algeria, has been adopted in this study. A correlation statistical analysis is used to determine the relationship between illness perception, coping strategies, and quality of life. Multiple regression analysis was employed to highlight the predictive ability of the dimensions of illness perception and coping strategies on the dependent variables of quality of life, where mediation analysis is considered in the exploration of the indirect effect significance of the mediator. This study provides insights about the relationship between illness perception, coping strategies and quality of life in the considered sample (r = 0.39, p < 0.01). Therefore, it proves that there is an effect of illness identity perception, external and medical attributions related to emotional role, physical functioning, and mental health perceived, and these were fully mediated by the asking for assistance (c’= 0.04, p < 0.05), the guarding (c’= 0.00, p < 0.05), and the task persistence strategy (c’= 0.05, p < 0.05). The findings imply partial support for the common-sense model of illness representations in a chronic illness population. Directions for future research are highlighted, as well as implications for psychotherapeutic interventions which target unhelpful beliefs and maladaptive coping strategies (e.g., cognitive behavioral therapy).

Keywords: chronic illness, coping, illness perception, quality of life, self- regulation model

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Authors: Ashit Syngle, Nidhi Garg, Pawan Krishan

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Objective: Bone marrow derived stem cells, endothelial progenitor cells (EPCs), protect against atherosclerotic vascular damage. However, EPCs are depleted in AS and contribute to the enhanced cardiovascular risk. Statins have a protective effect in CAD and diabetes by enhancing the proliferation, migration and survival of EPCs. Therapeutic potential of augmenting EPCs to treat the heightened cardiovascular risk of AS has not yet been exploited. We aimed to investigate the effect of rosuvastatin on EPCs population and inflammation in AS. Methods: 30 AS patients were randomized to receive 6 months of treatment with rosuvastatin (10 mg/day, n=15) and placebo (n=15) as an adjunct to existing stable anti-rheumatic drugs. EPCs (CD34+/CD133+) were quantified by Flow Cytometry. Inflammatory measures (BASDAI, BASFI, CRP and ESR), pro-inflammatory cytokines (TNF-α, IL-6 and IL-1) and lipids were measured at baseline and after treatment. Results: At baseline, inflammatory measures and pro-inflammatory cytokines were elevated and EPCs depleted among both groups. EPCs increased significantly (p < 0.01) after treatment with rosuvastatin. At 6 months, BASDAI, BASFI, ESR, CRP, TNF-α, and IL-6 improved significantly in rosuvastatin group. Significant negative correlation was observed between EPCs and BASDAI, CRP and IL-6 after rosuvastatin treatment. Conclusion: First study to show that rosuvastatin augments EPCs population in AS. This defines a novel mechanism of rosuvastatin treatment in AS: the augmentation of EPCs with improvement in proinflammatory cytokines and inflammatory disease activity. The augmentation of EPCs by rosuvastatin may provide a novel strategy to prevent cardiovascular events in AS.

Keywords: ankylosing spondylitis, Endothelial Progenitor Cells, inflammation, pro-inflammatory cytokines, rosuvastatin

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Authors: Somit Dutta, Pallab Kar, Arnab Kumar Chakraborty, Arnab Sen, Tapas Kumar Chaudhuri

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In the present study three species of Clerodendrum; Clerodendrum indicum, Volkameria inermis and Clerodendrum colebrookianum were used to investigate the possible activity against oxidative stress. A detailed in-vivo and in-vitro antioxidant profiling, directly associated with inflammation-related carcinogenesis, has been executed with a motive to evaluate the free radical scavenging activity of Clerodendrum extract. Measurement of cell viability and ROS generation in HEK-293 (Human Embryonic Kidney Cell Line) cells was also estimated. The immune cell proliferative properties (MTT) and in-vitro assay for evaluation of their antioxidant activities including hydroxyl radical, nitric oxide, singlet oxygen, peroxinitrate and hydrogen peroxide, etc. were investigated. GC-MS and FTIR analyses have been performed to identify the active biological compounds. These active biological compounds were further studied to assess their potential medicinal properties, aided by molecular docking and interaction analysis between the active compounds and different proteins related to oxidative stress leading to progression of carcinogenesis. The research article clearly demonstrates the role of ROS in various phases of carcinogenesis. Therefore, the antioxidant and free radical scavenging capacity of all the Clerodendrum species might prove beneficial for the immune system. It might be concluded that this plant species offers great promise for cancer prevention and therapy due to the presence of several bioactive compounds and potent antioxidant capacity of C. colebrookianum.

Keywords: antioxidant, cancer, oxidative stress, reactive oxygen species (ROS)

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Authors: Priyanka Chowdhury, Asitikantha Sarma, Utpal Ghosh

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Hadron therapy using high Linear Energy Transfer (LET) ion beam is producing promising clinical results worldwide. The major advantages are its ability to kill radio-resistant tumor and its anti-metastatic activity. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been widely used as radiosensitizer, but its role in metastasis is unknown. The purpose of our study was to investigate the effect of PARP-1 depletion in combination with either Carbon Ion Beam (CIB) or gamma irradiation on metastatic potential of cultured cancerous cells. A549 cells were irradiated with CIB (0-4Gy) or gamma (0, 2, 4, 6 and 10 Gy) with and without PARP-1 inhibition. The metastatic potential of the cells was determined by cell migratory assay, expression, and activity of MMP-2 and MMP-9, expression of Cadherin, Fibronectin, and Vimentin. CIB exposure reduced migratory property and activity of MMP-2 and MMP-9 significantly. CIB with PARP-1 inhibition reduced cell migration and Matrix Metalloproteinase (MMPs) activity in a synergistic manner. Expression of MMPs was also down-regulated in CIB and combined treatment. On the contrary, MMP- 2 and MMP-9 activity was significantly increased in gamma irradiated cells but decreased upon combined treatment of gamma and PARP-1 inhibitor. MMPs expression and migration was reduced when gamma irradiation was combined with PARP-1 inhibition. Thus, our study clearly demonstrates that PARP-1 inhibition in combination with either high or low LET can significantly suppress metastatic potential in cancer cells and thereby can be a promising tool in controlling metastatic cancers.

Keywords: high LET, low LET, matrix metalloproteinase (MMP), PARP-1

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Authors: Junhong Li, Danni Cheng, Yaxin Luo, Xiaowei Yi, Ke Qiu, Wendu Pang, Minzi Mao, Yufang Rao, Yao Song, Jianjun Ren, Yu Zhao

Abstract:

Background: The number of multiple cancer patients was increasing, and the impact of prior cancer history on salivary gland cancer patients remains unclear. Methods: Clinical, demographic and pathological information on salivary gland cancer patients were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017, and the characteristics and prognosis between patients with a prior cancer and those without prior caner were compared. Univariate and multivariate cox proportional regression models were used for the analysis of prognosis. A risk score model was established to exam the impact of treatment on patients with a prior cancer in different risk groups. Results: A total of 9098 salivary gland cancer patients were identified, and 1635 of them had a prior cancer history. Salivary gland cancer patients with prior cancer had worse survival compared with those without a prior cancer (p<0.001). Patients with a different type of first cancer had a distinct prognosis (p<0.001), and longer latent time was associated with better survival (p=0.006) in the univariate model, although both became nonsignificant in the multivariate model. Salivary gland cancer patients with a prior cancer were divided into low-risk (n= 321), intermediate-risk (n=223), and high-risk (n=62) groups and the results showed that patients at high risk could benefit from surgery, radiation therapy, and chemotherapy, and those at intermediate risk could benefit from surgery. Conclusion: Prior cancer history had an adverse impact on the survival of salivary gland cancer patients, and individualized treatment should be seriously considered for them.

Keywords: prior cancer history, prognosis, salivary gland cancer, SEER

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Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell

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Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.

Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers

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Authors: B. Oral, C. Bal, M. S. Kar, A. Akgürbüz

Abstract:

Loss of maxillary central incisors occurs in many patients, and the treatment of young adults with this problem is a challenge for both prosthodontists and orthodontists. Common treatment alternatives are distalization of adjacent teeth and fabrication of a conventional 3-unit fixed partial denture, a single implant supported crown restoration or a resin-bonded fixed partial denture. This case report describes the indication of a resin-bonded fixed partial denture, preparation of the abutment teeth and the prosthetic procedures. The technique described here represents a conservative, esthetically pleasing and rapid solution for the missing maxillary central incisor when implant placement and/or guided bone regeneration techniques are not feasible because of financial, social or time restrictions. In this case a 16 year-old female patient who lost her maxillary left central incisor six years ago in a bicycle accident applied to our clinic with a major complaint of her unaesthetic appearance associated with the loss of her maxillary left central incisor. Although there was an indication for orthodontic treatment because of the limited space at the traumatized area, the patient did not accept to receive any orthodontic procedure. That is why an implant supported restoration could not be an option for the narrow area. Therefore maryland bridge as a minimal invasive dental therapy was preferred as a retention appliance so the patient's aesthetic appearance was restored.

Keywords: Maryland bridge, single tooth restoration, aesthetics, maxillary central incisors

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Authors: Olusola Olalekan Elekofehinti, Isaac Gbadura Adanlawo, Joao Batista Teixeira Rocha

Abstract:

We evaluated the potential neuroprotective effect of Phyllantus nuriri against Fe2+ and SNP induced oxidative stress in mitochondria of rats brain. Cellular viability was assessed by MTT reduction, reactive oxygen species (ROS) generation was measured using the probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Glutathione content was measured using dithionitrobenzoic acid (DTNB). Fe2+ (10µM) and SNP (5µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, this occurred in parallel with increased glutathione oxidation, ROS production and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with methanolic extract of Phyllantus nuriri (10-100 µg/ml) reduced the disruption of mitochondrial activity, gluthathione oxidation, ROS production as well as the increase in TBARS levels caused by both Fe2+ and SNP in a dose dependent manner. HPLC analysis of the extract revealed the presence of gallic acid (20.54±0.01), caffeic acid (7.93±0.02), rutin (25.31±0.05), quercetin (31.28±0.03) and kaemferol (14.36±0.01). This result suggests that these phytochemicals account for the protective actions of Phyllantus nuriri against Fe2+ and SNP -induced oxidative stress. Our results show that Phyllantus nuriri consist important bioactive molecules in the search for an improved therapy against the deleterious effects of Fe2+, an intrinsic producer of reactive oxygen species (ROS), that leads to neuronal oxidative stress and neurodegeneration.

Keywords: Phyllantus niruri, neuroprotection, oxidative stress, mitochondria, synaptosome

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Authors: Engi E. I. Sarhan, Usama M. Rashad, Ibrahim M. I. Hamoda, Mohammed K. Mohamed

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Background: This study aimed to know the effect of nitrogen-based cryotherapy on the spasticity of calf muscle in stroke patients. Patients were selected from the outpatient clinic of Neurology, Al-Mansoura general hospital, Al-Mansoura University. Subjects and methods: Thirty Stroke Patients of both sexes ranged from 45 to 60 years old were divided randomly into two equal groups, a study group (A) received a nitrogen-based cryotherapy, a selective physical therapy program and ankle foot orthosis (AFO), while as patients in control group (B) received the same program and AFO only. The treatment duration was three times per week for four weeks for both groups. We assessed spasticity of calf muscle before and after treatment subjectively using modified Ashworth scale (MAS) and objectively via measuring H / M ratio on electromyography machine. We also assessed ankle dorsiflexion ROM objectively using two dimensions motion analysis (2D). Results: After treatment, there was a highly significant improvement in the study group compared to the control group regarding the score of MAS, no significant difference in the study group compared to the control group regarding the readings of H / M ratio, highly significant improvement in the study group compared to the control group regarding the 2D motion analysis findings. Conclusion: This modality considers effective in reducing spasticity in the calf muscle and improving ankle dorsiflexion of the affected limb.

Keywords: ankle foot orthosis, nitrogen-based cryotherapy, stroke, spasticity

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Authors: Anushaa A.

Abstract:

In this work, silver nanoparticles (AgNP) were manufactured directly without harmful chemicals utilising methanol extract (SNLME) Solanum nigrume leaves. We are using nigrum leaf extract from Solanum, which converts silver nitrate to silver ions, for synthesization purposes. An examination of the AgNP produced was performed using ultraviolet (UV-VIS) spectroscopy, infrared spectroscopy (FTIR) transformed from Fourier and scanning electrons (SEM). Biological activity was also tested. UV-VIS has proven that biosynthesized AgNP exists (420-450 nm). The FTIR spectrum has been utilised to confirm the presence of different functional groups within the biomolecules, which are a nanoparticular capping agent and the spectroscopic and crystal nature of AgNP. The viability of the silver nanoparticles was evaluated using zeta potential calculations. Negative zeta potential of -33.4 mV demonstrated the stability of silver-nanoparticles. The morphology of AgNP was examined using a scanning electron microscope. Greenly generated AgNP showed significant anti-Staphylococcus aureus, Candida, and Escherichia coli action. The green AgNP demonstration indicated that the IC50 for the human teratocarcinoma cell line was 29.24 μg/ml during 24 hours of therapy (PA1 Ovarian cell line). The dose-dependent effects were reported in both antibacterial and cytotoxicity assays and as an effective agent. Finally, the findings of this research showed that silver nanoparticles generated might serve as a viable therapeutic agent to combat microorganisms killing and curing cancer.

Keywords: antimicrobial activity, PA1 ovarian cancer cell line, silver nanoparticles, Solanum nigrum

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Authors: Oksana Mykytyuk

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Chronic desynchronosis is an important factor of progression of osteoarthritis in shift workers. 80 patients with primary osteoarthritis (female:male ratio = 3:1, average age: 57.6 years, average disease duration: 6.4 years, radiological stage: II-III) were examined, 42% reported systematic night shift-work for more than two years. Full clinical examination was performed, all patients filled in SF-36, WOMAC questonnaries, marked visual analog scales for estimation of pain intensity and general well-being. Patients who had been exposed to night work had significantly worse clinical course of osteoarthritis marked by more (27.5%, p < 0.05) extensive pain syndrome, especially at night hours, (10.00 pm-2.00 am period) and estimated life quality as poorer comparing those working at day time. Osteoarthritis initiation occurred at earlier age in them comparing those who worked in non-shifted regimen. They showed a trend to generalized affliction of bigger quantity of joint groups, higher frequency of synovitis as well. Shift-workers administered higher doses of non-steroid anti-inflammatory drugs (NSAIDs) and estimated their effect as lower (39.6% average daily relief vs 62.5% in non-shift workers after 10 days of regular application of therapy). Frequency of chronic NSAID-induced gastropathy was 25% higher among night-workers. Shift-workers are predisposed to worse course of osteoarthritis with marked clinical symptoms, requiring higher doses on NSAIDs and with inclination towards bigger frequency of complication. That should be kept in mind while developing individual treatment and secondary prophylaxis strategy.

Keywords: desynchronosis, osteoarthritis, questionnaries, shift-work

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Authors: M. McHugh, D. Lillis

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Mobile applications are being used to perform a wide variety of tasks in day-to-day life, ranging from checking email to controlling your home heating. Application developers have recognized the potential to transform a smart device into a medical device, by using a mobile medical application i.e. a mobile phone or a tablet. When initially conceived these mobile medical applications performed basic functions e.g. BMI calculator, accessing reference material etc.; however, increasing complexity offers clinicians and patients a range of functionality. As this complexity and functionality increases, so too does the potential risk associated with using such an application. Examples include any applications that provide the ability to inflate and deflate blood pressure cuffs, as well as applications that use patient-specific parameters and calculate dosage or create a dosage plan for radiation therapy. If an unapproved mobile medical application is marketed by a medical device organization, then they face significant penalties such as receiving an FDA warning letter to cease the prohibited activity, fines and possibility of facing a criminal conviction. Regulatory bodies have finalized guidance intended for mobile application developers to establish if their applications are subject to regulatory scrutiny. However, regulatory controls appear contradictory with the approaches taken by mobile application developers who generally work with short development cycles and very little documentation and as such, there is the potential to stifle further improvements due to these regulations. The research presented as part of this paper details how by adopting development techniques, such as agile software development, mobile medical application developers can meet regulatory requirements whilst still fostering innovation.

Keywords: agile, applications, FDA, medical, mobile, regulations, software engineering, standards

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Authors: M. R. Akshaya, Veena Rao

Abstract:

Pet population in India is increasing phenomenally owing to the changes in urban lifestyle with increasing number of single professionals, single parents, delayed parenthood etc. The animal companionship as a means of reducing stress levels, deriving emotional support, and unconditional love provided by dogs are a few reasons attributed for increasing pet ownership. The consequence is the booming of the pet care products and dog care centers catering to the different requirements of rearing the pets. Dog care centers quite popular in tier 1 metros of India cater to the requirement of the dog owners providing space for the dogs in absence of the owner. However, it is often reported that the absence of the owner leads to destructive and exploratory behavior issues; the main being the anxiety disorders. In the above context, it becomes imperative for a designer to design dog boarding centers that help in reducing the separation anxiety in dogs keeping in mind the different interior design parameters. An exploratory research with focus group discussion is employed involving a group of dog owners, behaviorists, proprietors of day care as well as boarding centers, and veterinarians to understand their perception on the significance of different interior parameters of color, texture, ventilation, aroma therapy and acoustics as a means of reducing the stress levels in dogs sent to the boarding centers. The data collected is organized as thematic networks thus enabling the listing of the interior design parameters that needs to be considered in designing dog boarding centers. 

Keywords: behavioral response, design parameters, dog boarding centers, interior environment

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Authors: Kolja Them, Johannes Salamon, Harald Ittrich, Michael Kaul, Tobias Knopp

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Superparamagnetic iron oxide nanoparticles (SPIONs) are nanoscale magnets which can be biologically functionalized for biomedical applications. Stem cell therapies to repair damaged tissue, magnetic fluid hyperthermia for cancer therapy and targeted drug delivery based on SPIONs are prominent examples where the visualization of a preferably low concentrated SPION distribution is essential. In 2005 a new method for tomographic SPION imaging has been introduced. The method named magnetic particle imaging (MPI) takes advantage of the nanoparticles magnetization change caused by an oscillating, external magnetic field and allows to directly image the time-dependent nanoparticle distribution. The SPION magnetization can be changed by the electron spin dynamics as well as by a mechanical rotation of the nanoparticle. In this work different calibration methods in MPI are investigated for image reconstruction of magnetically labeled stem cells. It is shown that a calibration using rotationally immobilized SPIONs provides a higher quality of stem cell images with fewer artifacts than a calibration using mobile SPIONs. The enhancement of the image quality and the reduction of artifacts enables the localization and identification of a smaller number of magnetically labeled stem cells. This is important for future medical applications where low concentrations of functionalized SPIONs interacting with biological matter have to be localized.

Keywords: biomedical imaging, iron oxide nanoparticles, magnetic particle imaging, stem cell imaging

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