The N1 domain of the peroxisomal AAA-ATPase Pex6 is required for Pex15 binding and proper assembly with Pex1.

The heterohexameric ATPases associated with diverse cellular activities (AAA)-ATPase Pex1/Pex6 is essential for the formation and maintenance of peroxisomes. Pex1/Pex6, similar to other AAA-ATPases, uses the energy from ATP hydrolysis to mechanically thread substrate proteins through its central pore, thereby unfolding them. In related AAA-ATPase motors, substrates are recruited through binding to the motor's N-terminal domains or N terminally bound cofactors. Here, we use structural and biochemical techniques to characterize the function of the N1 domain in Pex6 from budding yeast, Saccharomyces cerevisiae. We found that although Pex1/ΔN1-Pex6 is an active ATPase in vitro, it does not support Pex1/Pex6 function at the peroxisome in vivo. An X-ray crystal structure of the isolated Pex6 N1 domain shows that the Pex6 N1 domain shares the same fold as the N-terminal domains of PEX1, CDC48, and NSF, despite poor sequence conservation. Integrating this structure with a cryo-EM reconstruction of Pex1/Pex6, AlphaFold2 predictions, and biochemical assays shows that Pex6 N1 mediates binding to both the peroxisomal membrane tether Pex15 and an extended loop from the D2 ATPase domain of Pex1 that influences Pex1/Pex6 heterohexamer stability. Given the direct interactions with both Pex15 and the D2 ATPase domains, the Pex6 N1 domain is poised to coordinate binding of cofactors and substrates with Pex1/Pex6 ATPase activity.

Comparative Analysis of Antihypertensive and Anticonvulsant Regimens in Managing Pre-eclampsia and Eclampsia: Insights from a Sudanese Retrospective Study.

BACKGROUND Preeclampsia presents with gestational proteinuria, usually after 20 weeks of gestation, and can be complicated by generalized tonic-clonic seizures of eclampsia. Particularly in countries with limited healthcare resources, preeclampsia and eclampsia are major causes of maternal morbidity and mortality. This retrospective study aimed to evaluate the presentation, management, and outcomes of 185 women with preeclampsia and eclampsia in 2 maternity hospitals in Omdurman, Sudan, between January and December 2020. MATERIAL AND METHODS An analytical retrospective study was conducted in 2 main maternity hospitals in Omdurman, Sudan, between January and December 2020. The study included 185 pregnant women with preeclampsia or eclampsia. Data on clinical and obstetric characteristics (history of the illness, comorbid diseases, parity, gravida, multifetal pregnancy, and laboratory investigations), medications used, and maternal and neonatal outcomes were obtained for the diagnosis. The data were analyzed using the SPSS version 27. RESULTS Results: The mean age was 27.2±6.3 years, with 42.7% primigravida, 30% had a triple-drug regimen, nifedipine was the most common antihypertensive (60.5%), and 17.3% of patients underwent observation only. The seizure rate was 20%, with 92.73% controlled with magnesium sulfate. The antihypertensive regimen before delivery was significantly associated with the mode of delivery (P=0.001) and maternal outcomes (P=0.047); the regimen used after delivery significantly achieved blood pressure control (P=0.043) and improved maternal outcomes (P=0.007), but not fetal outcomes. CONCLUSIONS Maternal outcomes were markedly affected by the antihypertensive drug regimens used and the patient's seizure control status, and use of anti-convulsants successfully controlled all seizures.

Prevalence and Determinants of Self-Medication Among Pregnant Women at an Antenatal Clinic at Soba Teaching Hospital, Sudan: A Cross-Sectional Analysis.

BACKGROUND Rates of self-medication among pregnant women are high, due to the promotion of herbal and dietary supplements and lack of awareness of possible adverse effects. This study evaluated self-medication in pregnant women attending an antenatal clinic at Soba Teaching Hospital, Sudan. MATERIAL AND METHODS A quantitative study was conducted using a pre-tested semi-structured interviewer-administered questionnaire, which consisted of 25 questions divided into 4 sections: demographic and obstetric; self-medication source, recommendations, and conditions; most commonly used medications and herbal medicine; reasons for self-medications. A total of 230 pregnant women were included in the study. The chi-square test was used to test associations between variables and the binary logistic regression model was used to evaluate the relationship between self-medication practice and explanatory variables. A P value of <0.05 was deemed significant in the final model. RESULTS Of the 230 pregnant women interviewed, 67% were multigravida, 184 (80%) practiced self-medication, 45.6% used pharmaceutical products, commonly analgesics (32.5%), and 21.9% used herbal remedies, including peppermint (19.4%) and citrus fruits (17.5%). Self-medication was used for nausea (49.5%) and heartburn (46.2%). Reasons for self-medication included belief in safety (40%) and the expense of physician fees (28.1%). Socio-demographic characteristics and the prevalence of self-medication in pregnant women showed no significant associations. CONCLUSIONS The findings from this study showed that the prevalence of self-medication reported by pregnant women attending antenatal clinics in Sudan was high and included approved drugs and herbal medicines, mainly from pharmacies, and was driven by the perception that all medications supplied by pharmacies were safe.

Statin use and longitudinal changes in quantitative MRI-based biomarkers of thigh muscle quality: data from Osteoarthritis Initiative.

OBJECTIVE: To assess whether changes in MRI-based measures of thigh muscle quality associated with statin use in participants with and without/at-risk of knee osteoarthritis. METHODS: This retrospective cohort study used data from the Osteoarthritis Initiative study. Statin users and non-users were matched for relevant covariates using 1:1 propensity-score matching. Participants were further stratified according to baseline radiographic knee osteoarthritis status. We used a validated deep-learning method for thigh muscle MRI segmentation and calculation of muscle quality biomarkers at baseline, 2nd, and 4th visits. Mean difference and 95% confidence intervals (CI) in longitudinal 4-year measurements of muscle quality biomarkers, including cross-sectional area, intramuscular adipose tissue, contractile percent, and knee extensors and flexors maximum and specific contractile force (force/muscle area) were the outcomes of interest. RESULTS: After matching, 3772 thighs of 1910 participants were included (1886 thighs of statin-users: 1886 of non-users; age: 62 ± 9 years (average ± standard deviation), range: 45-79; female/male: 1). During 4 years, statin use was associated with a slight decrease in muscle quality, indicated by decreased knee extension maximum (mean-difference, 95% CI: - 1.85 N/year, - 3.23 to - 0.47) and specific contractile force (- 0.04 N/cm2/year, - 0.07 to - 0.01), decreased thigh muscle contractile percent (- 0.03%/year, - 0.06 to - 0.01), and increased thigh intramuscular adipose tissue (3.06 mm2/year, 0.53 to 5.59). Stratified analyses showed decreased muscle quality only in participants without/at-risk of knee osteoarthritis but not those with established knee osteoarthritis. CONCLUSIONS: Statin use is associated with a slight decrease in MRI-based measures of thigh muscle quality over 4 years. However, considering statins' substantial cardiovascular benefits, these slight muscle changes may be relatively less important in overall patient care.

Evaluating the Biocontrol Efficacy and Antioxidant Potential of Phellinus caribaeo-quercicola-A First Report Dual-Action Endophyte From Inula racemosa Hook. F.

Phellinus caribaeo-quercicola is a basidiomycetous fungus, isolated as an endophyte in this study from the healthy and symptomless leaves of Inula racemosa Hook. f., an important medicinal herb growing in Kashmir Himalaya. This study combines morphological, molecular and phylogenetic techniques to identify the fungal endophyte, using the ITS sequence of nrDNA. A detached leaf assay was conducted to assess the pathogenicity of the fungal endophyte suggesting its mutually symbiotic relationship with the host. The authors also investigated the antifungal potential of the isolated endophytic strain to ascertain its use as a biocontrol agent. The study shows that P. caribaeo-quercicola INL3-2 strain exhibits biocontrol activity against four key fungal phytopathogens that cause significant agronomic and economic losses: Aspergillus flavus, Aspergillus niger, Fusarium solani, and Fusarium oxysporum. Notably, P. caribaeo-quercicola INL3-2 strain is highly effective against A. flavus, with an inhibition percentage of 57.63%. In addition, this study investigates the antioxidant activity of P. caribaeo-quercicola INL3-2 strain crude extracts using ethyl acetate and methanol as solvents. The results showed that the methanolic fraction of P. caribaeo-quercicola exhibits potential as an antioxidant agent, with an IC50 value of 171.90 ± 1.15 µg/mL. This investigation is first of its kind and marks the initial report of this fungal basidiomycete, P. caribaeo-quercicola, as an endophyte associated with a medicinal plant. The findings of this study highlight the potential of P. caribaeo-quercicola INL3-2 strain as a dual-action agent with both biocontrol and antioxidant properties consistent with the medicinal properties of Inula racemosa. This endophytic fungus could be a promising source of natural compounds for use in agriculture, medicine, and beyond.

Injection therapy in professional footballers.

BACKGROUND: Injection therapy offers a minimally invasive approach for symptomatic relief that allows concurrent training, limiting time loss and providing a faster recovery. However, there is a lack of scientific evidence to support it, and there are controversies about its use. The present narrative review aims to present the available scientific literature on injection therapies in professional footballers (PF), highlighting the advantages and disadvantages of its use in the most common injuries. METHODS: The authors searched and reviewed contemporary literature on injection therapies in PF in electronic databases, summarizing them in a narrative review. RESULTS: Injection therapies such as hyaluronic acid and PRP have shown an adequate safety profile that allows their use. Current evidence suggests that hyaluronic acid injections are a valid option for managing symptomatic cartilage injuries. At the same time, PRP injections have failed to prove beneficial in treating muscle injuries and should be avoided until further evidence proves the opposite. Yet, PRP may have potential use in partial ACL injuries, anterior inferior tibiofibular ligament injuries (ankle syndesmosis), and fifth metatarsal fractures and needs further study. Due to the long-term health repercussions, other injection therapies should be preferred over corticosteroids in PF. CONCLUSIONS: There is a paucity of evidence on the use and benefits of injection therapies in PF despite its extensive use among physicians. Viscosupplementation may have a role in improving symptomatic cartilage injuries. In contrast, PRP injection therapy needs further high-quality clinical trials to assess its role in PF sports injuries.

Do bitcoin electricity consumption and carbon footprint exhibit random walk and bubbles? Analysis with policy implications.

One of the main current focuses of global economies and decision-makers is the efficiency of energy utilization in cryptocurrency mining and trading, along with the reduction of associated carbon emissions. Understanding the pattern of Bitcoin's energy consumption and its bubble frequency can greatly enhance policy analysis and decision-making for energy efficiency and carbon emission reduction. This research aims to assess the validity of the random walk hypothesis for Bitcoin's electricity consumption and carbon footprint. We employed both traditional methods (ADF and KPSS) and recently proposed unit root techniques that account for structural breaks and non-linearity in the data series. Our analysis covers daily data from July 2010 to December 2021. The empirical results revealed that traditional unit root techniques did not confirm the stationarity of both bitcoin's electricity consumption and carbon footprint. However, novel structural break (SB) and linearity tests conducted enabled us to discover five SB episodes between 2012 and 2020 and non-linearity of the variables, which informed our application of the newly developed non-linear unit root tests with structural breaks. With the new methods, the results indicated stationarity after accommodating the SB and non-linearity. Furthermore, based on Phillips and Shi (2019)'s test, we identified certain bubble episodes in the bitcoin energy and carbon variables between 2013 and 2021. The major drivers of the bubbles in bitcoin energy consumption and carbon footprint are variables relating to the bitcoin and financial markets activities and risks, including the global economic and political risks. The study's conclusion based on the above findings informs several policy implications drawn for energy and environmental management including the encouragement of green investments in cryptocurrency mining and trading.

Association of TCF7L2 Gene Variant (rs12255372) with Polycystic Ovary Syndrome and its Effect Modification of the Disease Phenotype.

Polycystic ovary syndrome (PCOS) and type-2 diabetes mellitus (T2DM) share common genetic features. Transcription factor 7-like-2 (TCF7L2) is consistently studied T2DM susceptibility locus. However, limited studies on TCF7L2 have failed to demonstrate any link with the PCOS risk. Therefore, we investigated the association of TCF7L2 polymorphic variant (rs12255372) with the PCOS risk. We recruited 120 PCOS cases, diagnosed as per Rotterdam 2003 criteria, and an equal number of age-matched controls. Besides a detailed clinical assessment, subjects underwent biochemical and hormonal profiling. Genotyping for rs12255372 was done by PCR-RFLP. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of genotype-phenotype correlations. The PCOS cases reported fewer menstrual cycles per year and exhibited signs of hyperandrogenism. The heterozygous genotype of rs12255372 was strongly associated with the PCOS risk (OR = 2.00; 95%CI: 1.07-3.76). Unlike controls, only 3 cases harbored TT genotype, and the PCOS risk persisted in the dominant model (GT + TT) as well. Moreover, we found a synergistic effect modification by the variant genotype in the subjects who had family histories of T2DM, hirsutism, or menstrual irregularities. We report a significant association of the TCF7L2 polymorphic variant rs12255372 with the PCOS risk.

Patient-oriented educational Sports Medicine YouTube videos in Arabic have higher view counts in the Middle East and North Africa than their English versions.

PURPOSE: The present study aims to assess the impact of the local language on the view count of patient-oriented educational Sports Medicine videos in an Orthopaedic and Sports Medicine Hospital in the Middle East and North Africa. METHODS: An observational study on English and Arabic versions of Aspetar's YouTube channel patient-oriented educational video series was conducted in February 2023, comparing the view count and viewer characteristics. Included videos were posted either simultaneously or in English version first, in both languages, and shared on the same media platforms. Collected data of interest included video title, view count in each language, age and sex of the viewers, location, and traffic source. RESULTS: Eleven videos of the patient-oriented educational video series were included in the present study. Except for one, the view count was significantly higher in the Arabic version of all 11 videos (minimum sevenfold, P = 0.03). Viewers were predominantly males (73.9%) and between 18 and 44 years old (81.1%). Eleven out of 19 countries of the Middle East and North Africa region [11] were among the viewers' top 20 countries. Traffic sources included YouTube search (45.9%), YouTube suggested videos (17%), external sources (14.4%), YouTube browse features (8.5%), and YouTube advertising (6%). CONCLUSION: Patient-oriented educational Sports Medicine videos in Arabic yield higher view counts than their English version in young adult viewers from 11 countries in the Middle East and Africa among the top 20. Content creation on languages with limited online representation could effectively reach the targeted population by breaking language barriers.

COVID-19 independently predicts poor outcomes in Acute Ischemic Stroke- Insights from a multicenter study from Pakistan and United Arab Emirates.

BACKGROUND: Ischemic stroke associated with coronavirus 2019 (COVID-19) has been well recognized by now. Few studies have compared COVID related versus unrelated strokes. We intend to report on a large group of Asian patients from two countries and compare COVID with non-COVID strokes admitted during the same time period. METHODS: Consecutive cases of acute ischemic stroke either presenting or developing, between March 2020 and December 2021 in four tertiary care hospitals (1 in Dubai, UAE and 3 in Karachi, Pakistan) and testing positive for COVID-19 were included in the study. Patients admitted with ischemic stroke during the same time period and who tested negative for COVID-19 were also randomly selected from the four hospitals. All data was collected from the medical records of the patients and recorded on a standard questionnaire before it was entered in SPSS version 21 for analysis. RESULTS: There were 139 COVID positive and 271 COVID negative patients with acute ischemic stroke included in the current study. There were significantly more males (80.6% vs 64.9%, p=0.001) and more large vessel strokes in the COVID positive group (41% vs 21.8%, p<0.001). Being COVID positive was an independent predictor of poor outcome at discharge, defined as a modified Rankin score of 3-6 (OR 3.87, 95% CI 2.21-6.77) after adjusting for country, age, sex, vascular comorbid conditions and stroke subtype. CONCLUSIONS: In this largest series of patients with COVID related strokes from Asia, COVID-19 was an independent predictor of poor outcomes at discharge after adjusting for other variables.

The Psychological Antecedents to COVID-19 Vaccination among Community Pharmacists in Khartoum State, Sudan.

Background and Objectives: Little is known regarding the 5C psychological antecedents to COVID-19 vaccination among pharmacists in low- and middle-income countries. This study aimed to assess the acceptance of COVID-19 vaccination and its psychological antecedents among community pharmacists in Khartoum State, Sudan. Materials and Methods: A cross-sectional study was conducted from July to September 2022. A self-administered questionnaire was used to collect data about sociodemographic and health status characteristics, vaccine acceptance, and the 5C psychological antecedents to vaccination. Stepwise logistic regression analysis was conducted, and results were presented using odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Results: A total of 382 community pharmacists participated in the current study, with a mean age of 30.4 ± 5.6 years. Nearly two-thirds of the participants (65.4%) were females, and the majority (74.9%) have received or intended to receive the COVID-19 vaccination. Vaccine acceptance was significantly associated with the following psychological antecedents to vaccination: confidence, complacency, constraints, and calculation (p < 0.001). Results of the logistic regression showed that confidence in vaccines [OR = 6.82 (95% CI = 3.14-14.80)], conspiracy beliefs [OR = 0.44 (95% CI = 0.23-0.85)], and constraints to vaccination [OR = 0.18 (95% CI = 0.06-0.56)] were the significant determinants of vaccine acceptance. Conclusion: The study revealed important predictors of COVID-19 vaccine acceptance that can be used to guide policymakers in designing target-oriented interventions that can improve the vaccine acceptance rate among community pharmacists in Sudan. These findings suggest that interventions to promote vaccine acceptance among pharmacists should focus on building confidence in vaccines and providing accurate information about the safety and efficacy of the COVID-19 vaccine, and reducing constraints to vaccination.

Lateral epicondylitis of the elbow: an up-to-date review of management.

Lateral epicondylitis, also known as tennis elbow, is an overuse tendinopathy of the common extensor origin of the elbow in patients involved in repetitive movement of the wrist and forearm. Lateral epicondylitis is a self-limiting condition, with operative management only recommended in severe, recalcitrant cases. This article reviews the recent updates on operative and non-operative management of lateral epicondylitis.

Real world use of oral treatments in interstitial cystitis/bladder pain syndrome in the UK: Outcome of a cross sectional study.

BACKGROUND: To describe the oral treatments people living with interstitial cystitis/bladder pain syndrome (IC/BPS) are using to treat their urologic condition in the UK. METHOD: A questionnaire hyperlink encompassing current and previous medications taken for IC/BPS with other sociodemographic and diagnostic indices was available to the Bladder Health UK website. Interested and fully consented individuals accessed and completed the survey. RESULTS: A total of 601 accessed the questionnaire of whom 173 participants responded (response rate: 28.7%) with a mean ± SD O'Leary/Sant scores of 20.12 ± 9.38. A sample size of 171 was estimated to be used in the survey. A fifth of the participants were not on any treatment at all. Amitriptyline was the most prevalent medication in use both alone and in combination. A shift in the use of unapproved (for IC/BPS) antidepressant, smooth muscle relaxant, opioids, gabapentenoids, and antibiotics was observed in the sample. There were no significant differences between the mean (SD) O'Leary/Sant scores of cohorts currently taking oral medications and those not taking it. More than two-thirds of the participants had been diagnosed with the disease more than 5 years. Just under a half (47.4%) of participants reported a history of allergy. CONCLUSION: Our study provides contemporary evidence that the treatments used for managing IC/BPS encompass a broad range of medications both recommended and not recommended by current guidelines. The latter suggests patients are willing to try novel treatments when more conventional ones are ineffective.

Vitamin D status among Kashmiri tribal population: A cross-sectional community-based study.

Background & objectives: Vitamin D deficiency (VDD) is prevalent across all age groups in general population of India but studies among tribal populations are scanty. This study aimed to evaluate the prevalence of VDD in the indigenous tribal population of the Kashmir valley and examine associated risk factors. Methods: In this cross-sectional investigation, a total of 1732 apparently healthy tribal participants (n=786 males and n=946 females) were sampled from five districts of Kashmir valley by using probability proportional to size method. Serum 25-hydroxy vitamin D (25(OH)D) levels were classified as per the Endocrine Society (ES) recommendations: deficiency (<20 ng/ml), insufficiency (20-30 ng/ml) and sufficiency (>30 ng/ml). The serum 25(OH)D levels were assessed in relation to various demographic characteristics such as age, sex, education, smoking, sun exposure, body mass index and physical activity. Results: The mean age of the male participants was 43.79±18.47 yr with a mean body mass index (BMI) of 20.50±7.53 kg/m[2], while the mean age of female participants was 35.47±14.92 yr with mean BMI of 22.24±4.73 kg/m2. As per the ES guidelines 1143 of 1732 (66%) subjects had VDD, 254 (14.71%) had insufficient and 334 (19.3%) had sufficient serum 25(OH)D levels. VDD was equally prevalent in male and female participants. Serum 25(OH)D levels correlated positively with serum calcium, phosphorous and negatively with serum alkaline phosphatase. Gender, sun exposure, altitude, physical activity and BMI did not seem to contribute significantly to VDD risk. Interpretation & conclusions: VD deficiency is highly prevalent among Kashmiri tribals, although the magnitude seems to be lower as compared to the general population. These preliminary data are likely to pave way for further studies analyzing the impact of vitamin D supplementation with analysis of functional outcomes.

Return to Sports Following Meniscal Allograft Transplantation Is Possible but Remains Questionable: A Systematic Review.

OBJECTIVE: To evaluate the return to sports rate and time following meniscal allograft transplantation (MAT). METHODS: PubMed, Web of Science, and Embase were searched in December 2020. Eligibility criteria included clinical studies reporting the return to sport rate following MAT with ≥12-month follow-up. RESULTS: A total of 14 case series were included with 670 patients. The bone bridge technique was used for all transplantations in 5 studies, and suture fixations with bone tunnels were used for all transplantations in 5 studies. In 2 studies, bone plugs were used for medial menisci and bone bridge for lateral menisci. In 1 study, suture fixation was used for medial menisci, and bone bridge for lateral menisci. The return to sports rate ranged from 20% to 91.7%, with 2 studies reporting low return to sport rates. The return to sport time ranged between 7.6 and 16.9 months. The return to preinjury level had a rate of 7% to 100%. Return to a higher level of sports was reported in only 2 studies (28.5% to 86%). Return to a lower level of sports was reported in low proportions in most studies. In terms of patient-reported outcomes, the Lysholm knee and subjective International Knee Documentation Committee (IKDC) scores and Knee Osteoarthritis Outcome Score (KOOS) had significant improvements after MAT. The KOOS quality of life subscore did not change significantly in 1 study. The total reoperation rate after MAT ranged between 3.1% and 80%, whereas the total failure ranged between 1.1% and 30.1%. CONCLUSION: Despite that most studies reporting high return to sports rates, the current level of evidence is low, with all studies being case series. There is significant variability in the reported return to sports rate, time, and level. Therefore, high-quality comparative studies are mandated to elucidate whether MAT is associated with higher return to sports rates and levels. LEVEL OF EVIDENCE: IV, systematic review.

The relationship between illness perception and worsening of interstitial cystitis/painful bladder syndrome symptoms: A cross-sectional study.

OBJECTIVE: To evaluate disease perception in a cohort of patients with interstitial cystitis/painful bladder syndrome (IC/PBS) using the Brief Illness Perception-Questionnaire (BIP-Q) and to evaluate how this might relate to disease severity. MATERIALS AND METHODS: The study is a cross-sectional survey amongst members of Bladder Health UK who had previously received a clinical diagnosis of IC/PBS. A hyperlink containing the questionnaire was sent to the patient group's website and interested members accessed and completed the survey. Participants' inclusion was based on a prior clinical diagnosis of IC/PBS, current O'Leary Sant scores supportive of the diagnosis, and age between 18 and 80. A sample size of 171 was used in the study. The Brief Illness Perception Questionnaire (BIP-Q) and the O'Leary/Sant symptoms and problem indices questionnaire were used to collect data. A multivariable logistic regression analysis was used to test the relationship between items of BIP-Q and severity of IC/PBS. Content analysis was used for the causal domain and subsequently analysed as percentages. RESULTS: Six hundred and one members accessed the questionnaire of whom 159 returned completed questionnaires. One hundred and twenty-two of 159 (≥75%) respondents believe that their illness will continue indefinitely. The majority of the respondents indicated that IC/PBS had a negative impact on their daily lives, caused them worry and made them emotionally unstable. Of the 8 BIP-Q items, those most predictive of disease severity were (adjusted odd ratio and confidence intervals): consequence 0.094 (0.023-0.386); treatment control 2.702 (1.256-5.812); identity 0.141 (0.033-0.600); concern 9.363 (1.521-57.632). CONCLUSIONS: Our findings show that IC/PBS negatively impacts participant's quality of life and emotional wellbeing. Higher expectation for treatment benefit and increasing levels of patient concern are predictive for severity of IC/PBS.

A significant association of the CTLA4 gene variants with the risk of autoimmune Graves' disease in ethnic Kashmiri population.

Graves' disease (GD) is the commonest cause of hyperthyroidism in populations with adequate iodine intake. It results from an abnormality in the immune system, which produces unique antibodies causing over production of thyroid hormones and glandular hyperplasia in individuals with genetic susceptibility. The Cytotoxic Lymphocyte Associated Antigen-4 (CTLA4) gene product serves the important function of immunomodulation, thereby helping in maintenance of peripheral self-tolerance. Studies on the association of the CTLA4 SNPs with GD have shown variations in the results from different populations. Since no such study has been carried out in ethnic Kashmiri population, we aimed to study a possible association of the CTLA4 SNPs (+49 A/G, -318C/T, CT 60 A/G and -1661 A/G) with GD. A total of 285 individuals (135 patients with GD and 150 healthy individuals) were genotyped using PCR-RFLP method and the results showed statistically significant differences in genotypic and allelic frequencies of cases and controls for + 49 A/G SNP (p=<0.001; OR = 5.14; CI = 2.17-12.19) and CT 60 A/G SNP (p = < 0.001; OR = 6.9; CI = 2.8-16.6), while -318C/T and -1661 A/G SNPs showed no significant association. We also studied the mRNA expression of the CTLA4 in patients with GD and healthy individuals by Real-Time PCR and found a decreased expression of the CTLA4 mRNA in PBMCs of patients with GD as compared to healthy controls with a -3.71-fold change. We conclude that the CTLA4 + 49 A/G and CT 60 A/G SNPs have a significant association with the risk of GD development in Kashmiri population and CTLA4 mRNA expression is significantly decreased in GD.

Microbiological study of used cosmetic products: highlighting possible impact on consumer health.

AIMS: To investigate the nature and extent of microbial contamination in five categories of used cosmetic products (lipstick, lip gloss, eyeliners, mascaras and beauty blenders) and highlight the potential risk posed to consumers in the UK. METHODS AND RESULTS: Used products were donated and microbial contents were determined by microbial culture and identification. About 79-90% of all used products were contaminated with bacteria, with bacterial loads ranging between 102 and 103  CFU per ml, beauty blenders contained an average load of >106  CFU per ml. Presence of Staphylococcus aureus, Escherichia coli and Citrobacter freundii was detected. Enterobacteriaceae and fungi were detected in all product types, and were prevalent in beauty blenders (26·58 and 56·96% respectively). Ninety-three per cent of beauty blenders had not been cleaned and 64% had been dropped on the floor and continued to be used. CONCLUSIONS: Significant levels of microbial contamination occur during use of cosmetic products and presence of pathogenic organisms pose a potential risk to health. SIGNIFICANCE AND IMPACT OF THE STUDY: The nature and high level of contamination in used cosmetic products indicate that greater user awareness and education are required. Manufacturers should ensure that product expiry dates are prominently displayed and consumers can identify the symbols used on product packaging.

Effects of terlipressin infusion on blood loss and transfusion needs during liver resection: A randomised trial.

BACKGROUND: Blood loss and perioperative blood transfusion requirements affect the long-term survival after liver resection for malignant tumours. Terlipressin is a synthetic vasopressin analogue with relative specificity for the splanchnic circulation where it causes vasoconstriction with subsequent reduction of blood loss during abdominal surgeries. We tried to examine the impact of terlipressin on blood loss and blood transfusion needs during liver resection. METHODS: In this randomised, double-blind placebo-controlled trial 84 patients scheduled for major liver resections were randomly assigned to receive either terlipressin at the onset of surgery as an initial bolus dose of (1 mg over 30 minutes) followed by a continuous infusion of 2 µg/kg/h throughout the procedure (Terlipressin group) or the same volume and rate of 0.9% saline (Placebo group).The primary outcome was the amount of intra-operative blood loss. RESULTS: The mean (SD) of the amount of intra-operative blood loss was 1351 (887) in the terlipressin group versus 1892 (889) mL in the placebo group (P = 0.006). Thirteen (30%) patients received blood transfusion in the terlipressin group compared with t27 (64.2%) in the placebo group (P = 0.002) with a statistically significant difference in the median (range) number of the transfused units of packed RBCs [0 (0-5) units and 1 (0-6) units in the two groups respectively; P = 0.001]. CONCLUSION: Terlipressin infusion during major liver resection was associated with less bleeding compared to placebo. More studies are required to confirm our results especially in patients with normal portal pressure.

Effects of terlipressin infusion during hepatobiliary surgery on systemic and splanchnic haemodynamics, renal function and blood loss: a double-blind, randomized clinical trial.

BACKGROUND: Terlipressin, in general, is a vasopressor which acts via V1 receptors. Its infusion elevates mean blood pressure and can reduce bleeding which has a splanchnic origin. The primary outcome was to assess the impact of intraoperative terlipressin infusion on portal venous pressure during hepatobiliary surgery; the 2ry outcomes included effects upon systemic hemodynamics, estimated blood loss, and postoperative renal functions. METHODS: This prospective randomized study involved 50 patients undergoing hepatobiliary surgery who were randomly and equally allocated into terlipressin group, or a control group. The terlipressin group received an initial bolus dose of (1 mg over 30 min) followed by a continuous infusion of 2 µg/kg/h throughout the procedure and gradually weaned over the first four postoperative hours, whereas the control group received the same volumes of normal saline. The portal venous pressure changes were measured directly through a portal vein angiocatheter. RESULTS: Portal pressure was significantly reduced over time in the terlipressin group only (from 17.88 ± 7.32 to 15.96 ± 6.55 mmHg, p < .001). Mean arterial blood pressure was significantly higher in the terlipressin group. Estimated blood loss was significantly higher in the control group than the terlipressin group (1065.7 ± 202 versus 842 ± 145.5 ml; p = 0.004), and the units of packed RBCs transfused were significantly higher in the control group ((0-2) versus (0-4) p = 0.003). There was no significant difference between groups as regards the incidence of acute kidney injury. CONCLUSION: Intraoperative infusion of terlipressin during hepatobiliary surgery was shown to improve intraoperative portal hemodynamics with subsequent reduction in blood loss. TRIAL REGISTRATION: Clinical trial number and registry URL: Trial registration number: NCT02718599 . Name of registry: ClinicalTrials.gov. URL of registry: https://clinicaltrials.gov/ct2/show/NCT02718599 . Date of registration: March 2016. Date of enrolment of the first participant to the trial: April 2016.