Whole genome sequencing of 4,787 individuals identifies gene-based rare variants in age-related macular degeneration.

Genome-wide association studies have contributed extensively to the discovery of disease-associated common variants. However, the genetic contribution to complex traits is still largely difficult to interpret. We report a genome-wide association study of 2394 cases and 2393 controls for age-related macular degeneration (AMD) via whole-genome sequencing, with 46.9 million genetic variants. Our study reveals significant single-variant association signals at four loci and independent gene-based signals in CFH, C2, C3, and NRTN. Using data from the Exome Aggregation Consortium (ExAC) for a gene-based test, we demonstrate an enrichment of predicted rare loss-of-function variants in CFH, CFI, and an as-yet unreported gene in AMD, ORMDL2. Our method of using a large variant list without individual-level genotypes as an external reference provides a flexible and convenient approach to leverage the publicly available variant datasets to augment the search for rare variant associations, which can explain additional disease risk in AMD.

Internet addiction among school adolescents in Jeddah-Saudi Arabia.

BACKGROUND: Internet addiction is increasing among adolescents worldwide. There is a lack of research assessing internet addiction and factors contributing to it among adolescents in Jeddah city. The current study aimed to assess the rate of internet addiction among adolescents in Jeddah, Saudi Arabia, and the potential factors associated with it. METHODS: A cross-sectional online survey, hosted by SurveyMonkey, was used to capture data on internet use from 462 adolescents aged 12-18 years between March and May 2022. Young's Internet Addiction Scale was used to assess the degree of internet addiction as perceived by adolescents. Multiple linear regression analysis was used to identify possible predictors of internet addiction among adolescents in Jeddah. RESULTS: The mean age of the participants was 15.5 ± 1.9 years. The majority were females (75%) from public schools (63%), spent an average of six hours on the internet daily, owned smartphones (98%), accessed the internet via a smartphone (94%), and used the internet for socializing (82%). Internet addiction mean score was 39.20 ± 15.20 out of 100. More than two-thirds of the participants had mild to moderate levels of internet addiction (68%). Significant predictors contributing to internet addiction were using the internet for socialization and playing online games. The more hours spent on the internet daily, the more the internet addiction was (p ≤ 0.05). CONCLUSIONS: The internet addiction rate is high among school adolescents in Jeddah. The majority of high school adolescents had mild to moderate levels of internet addiction. Interventional multidisciplinary programs are needed to mitigate the factors that influence internet addiction.

Poly(ADP-ribose) polymerase inhibitors in the treatment landscape of triple-negative breast cancer (TNBC).

OBJECTIVE: Chemotherapy is the mainstay for triple-negative breast cancer (TNBC) patients. Over the years, the use of chemotherapy for these patients has demonstrated many adversities, including toxicity and resistance, which suggested the need to develop novel alternative therapeutic options, such as poly(ADP-ribose) polymerase inhibitors (PARPi). Herein, we provide an overview on PARPi, mechanisms of action and the role of biomarkers in PARPi sensitivity trials, clinical advances in PARPi therapy for TNBC patients based on the most recent studies and findings of clinical trials, and challenges that prevent PARP inhibitors from achieving high efficacy such as resistance and overlapping toxicities with other chemotherapies. DATA SOURCES: Searching for relevant articles was done using PubMed and Cochrane Library databases by using the keywords including TNBC; chemotherapy; PARPi; BRCA; homologous recombination repair (HRR). Studies had to be published in full-text in English in order to be considered. DATA SUMMARY: Although PARPi have been used in the treatment of local/metastatic breast malignancies that are HER2 negative and has a germline BRCA mutation, several questions are still to be answered in order to maximize the clinical benefit of PARP inhibitors in TNBC treatment, such as questions related to the optimal use in the neoadjuvant and metastatic settings as well as the best combinations with various chemotherapies. CONCLUSIONS: PARPi are emerging treatment options for patients with gBRCA1/2 mutations. Determining patients that are most likely to benefit from PARPi and identifying the optimal treatment combinations with high efficacy and fewer side effects are currently ongoing.

Family-based exome sequencing identifies rare coding variants in age-related macular degeneration.

Genome-wide association studies (GWAS) have identified 52 independent variants at 34 genetic loci that are associated with age-related macular degeneration (AMD), the most common cause of incurable vision loss in the elderly worldwide. However, causal genes at the majority of these loci remain unknown. In this study, we performed whole exome sequencing of 264 individuals from 63 multiplex families with AMD and analyzed the data for rare protein-altering variants in candidate target genes at AMD-associated loci. Rare coding variants were identified in the CFH, PUS7, RXFP2, PHF12 and TACC2 genes in three or more families. In addition, we detected rare coding variants in the C9, SPEF2 and BCAR1 genes, which were previously suggested as likely causative genes at respective AMD susceptibility loci. Identification of rare variants in the CFH and C9 genes in our study validated previous reports of rare variants in complement pathway genes in AMD. We then extended our exome-wide analysis and identified rare protein-altering variants in 13 genes outside the AMD-GWAS loci in three or more families. Two of these genes, SCN10A and KIR2DL4, are of interest because variants in these genes also showed association with AMD in case-control cohorts, albeit not at the level of genome-wide significance. Our study presents the first large-scale, exome-wide analysis of rare variants in AMD. Further independent replications and molecular investigation of candidate target genes, reported here, would assist in gaining novel insights into mechanisms underlying AMD pathogenesis.

The safety and efficacy of CAR-T cells in the treatment of prostate cancer: review.

OBJECTIVE: A new breakthrough development in cancer treatment is chimeric antigen receptor (CAR)-T cell therapy. In this review, we focussed on its efficacy & safety in prostate cancer, obstacles impeding its clinical use, and some strategies trying to overcome them. METHODS: Searching for relevant articles was done using the PubMed and Cochrane Library databases. Studies had to be published in full-text in English in order to be considered. RESULTS: Many factors can limit optimal CAR-T cell outcomes, including the hostile Prostate microenvironment, age, comorbidities, and tumour grade. The adverse effects of the therapy, particularly the cytokine release syndrome, are a major source of worry after treatment administration. Attempts to alter gamma/delta T-cells and NK cells with CAR, on the other hand, have demonstrated higher effectiveness and safety than conventional CAR-T cells. CONCLUSION: To improve the use of immunotherapies, a greater understanding of the prostate cancer microenvironment is required. Concerning toxicity, more research is needed to find the most specific and highly expressed prostate antigens. Furthermore, discovering predictive biomarkers for toxicities, as well as choosing the correct patient for therapy, might decrease immune-related side effects and achieve a greater response.

Variants in myelin regulatory factor (MYRF) cause autosomal dominant and syndromic nanophthalmos in humans and retinal degeneration in mice.

Nanophthalmos is a rare, potentially devastating eye condition characterized by small eyes with relatively normal anatomy, a high hyperopic refractive error, and frequent association with angle closure glaucoma and vision loss. The condition constitutes the extreme of hyperopia or farsightedness, a common refractive error that is associated with strabismus and amblyopia in children. NNO1 was the first mapped nanophthalmos locus. We used combined pooled exome sequencing and strong linkage data in the large family used to map this locus to identify a canonical splice site alteration upstream of the last exon of the gene encoding myelin regulatory factor (MYRF c.3376-1G>A), a membrane bound transcription factor that undergoes autoproteolytic cleavage for nuclear localization. This variant produced a stable RNA transcript, leading to a frameshift mutation p.Gly1126Valfs*31 in the C-terminus of the protein. In addition, we identified an early truncating MYRF frameshift mutation, c.769dupC (p.S264QfsX74), in a patient with extreme axial hyperopia and syndromic features. Myrf conditional knockout mice (CKO) developed depigmentation of the retinal pigment epithelium (RPE) and retinal degeneration supporting a role of this gene in retinal and RPE development. Furthermore, we demonstrated the reduced expression of Tmem98, another known nanophthalmos gene, in Myrf CKO mice, and the physical interaction of MYRF with TMEM98. Our study establishes MYRF as a nanophthalmos gene and uncovers a new pathway for eye growth and development.

Identification of Novel Deletions as the Underlying Cause of Retinal Degeneration in Two Pedigrees.

Retinal dystrophies are a phenotypically and genetically complex group of conditions. Because of this complexity, it can be challenging in many families to determine the inheritance based on pedigree analysis alone. Clinical examinations were performed and blood samples were collected from a North American (M1186) and a consanguineous Pakistani (PKRD168) pedigree affected with two different retinal dystrophies (RD). Based on the structure of the pedigrees, inheritance patterns in the families were difficult to determine. In one family, linkage analysis was performed with markers on X-chromosome. In the second family, whole-exome sequencing (WES) was performed. Subsequent Sanger sequencing of genes of interest was performed. Linkage and haplotype analysis localized the disease interval to a 70 Mb region on the X chromosome that encompassed RP2 and RPGR in M1186 . The disease haplotype segregated with RD in all individuals except for an unaffected man (IV:3) and his affected son (V:1) in this pedigree. Subsequent analysis identified a novel RPGR mutation (p. Lys857Glu fs221X) in all affected members of M1186 except V:1. This information suggests that there is an unidentified second cause of retinitis pigmentosa (RP) within the family. A novel two-base-pair deletion (p. Tyr565Ter fsX) in CHM (choroideremia) was found to segregate with RD in PKRD168. This paper highlights the challenges of interpreting family history in families with RD and reports on the identification of novel mutations in two RD families.

Hospital Magnet® Designation and Missed Nursing Care in Neonatal Intensive Care Units.

Missed nursing care is an emerging measure of front-line nursing care effectiveness in neonatal intensive care units (NICUs). Given Magnet® hospitals' reputations for nursing care quality, missed care comparisons with non-Magnet® hospitals may yield insights about how Magnet® designation influences patient outcomes. The purpose of this secondary analysis was to evaluate the relationship between hospital Magnet® designation and 1) the occurrence of nurse-reported missed care and 2) reasons for missed nursing care between NICU nurses employed in Magnet® and non-Magnet® hospitals. A random sample of certified neonatal intensive care unit nurses was invited to participate in a cross-sectional survey in 2012; data were analyzed from nurses who provided direct patient care (n=230). Logistic regression was used to model relationships between Magnet® designation and reports of the occurrence of and reasons for missed care while controlling for nurse and shift characteristics. There was no relationship between Magnet® designation and missed care occurrence for 34 of 35 types of care. Nurses in Magnet® hospitals were significantly less likely to report tensions and communication breakdowns with other staff, lack of familiarity with policies/procedures, and lack of back-up support from team members as reasons for missed care. Missed nursing care in NICUs occurs regardless of hospital Magnet® recognition. However, nurses' reasons for missed care systematically differ in Magnet® and non-Magnet® hospitals and these differences merit further exploration.

Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are associated with macular degeneration.

Neurodegenerative diseases affecting the macula constitute a major cause of incurable vision loss and exhibit considerable clinical and genetic heterogeneity, from early-onset monogenic disease to multifactorial late-onset age-related macular degeneration (AMD). As part of our continued efforts to define genetic causes of macular degeneration, we performed whole exome sequencing in four individuals of a two-generation family with autosomal dominant maculopathy and identified a rare variant p.Glu1144Lys in Fibrillin 2 (FBN2), a glycoprotein of the elastin-rich extracellular matrix (ECM). Sanger sequencing validated the segregation of this variant in the complete pedigree, including two additional affected and one unaffected individual. Sequencing of 192 maculopathy patients revealed additional rare variants, predicted to disrupt FBN2 function. We then undertook additional studies to explore the relationship of FBN2 to macular disease. We show that FBN2 localizes to Bruch's membrane and its expression appears to be reduced in aging and AMD eyes, prompting us to examine its relationship with AMD. We detect suggestive association of a common FBN2 non-synonymous variant, rs154001 (p.Val965Ile) with AMD in 10 337 cases and 11 174 controls (OR = 1.10; P-value = 3.79 × 10(-5)). Thus, it appears that rare and common variants in a single gene--FBN2--can contribute to Mendelian and complex forms of macular degeneration. Our studies provide genetic evidence for a key role of elastin microfibers and Bruch's membrane in maintaining blood-retina homeostasis and establish the importance of studying orphan diseases for understanding more common clinical phenotypes.

Comparing variant calling algorithms for target-exon sequencing in a large sample.

BACKGROUND: Sequencing studies of exonic regions aim to identify rare variants contributing to complex traits. With high coverage and large sample size, these studies tend to apply simple variant calling algorithms. However, coverage is often heterogeneous; sites with insufficient coverage may benefit from sophisticated calling algorithms used in low-coverage sequencing studies. We evaluate the potential benefits of different calling strategies by performing a comparative analysis of variant calling methods on exonic data from 202 genes sequenced at 24x in 7,842 individuals. We call variants using individual-based, population-based and linkage disequilibrium (LD)-aware methods with stringent quality control. We measure genotype accuracy by the concordance with on-target GWAS genotypes and between 80 pairs of sequencing replicates. We validate selected singleton variants using capillary sequencing. RESULTS: Using these calling methods, we detected over 27,500 variants at the targeted exons; >57% were singletons. The singletons identified by individual-based analyses were of the highest quality. However, individual-based analyses generated more missing genotypes (4.72%) than population-based (0.47%) and LD-aware (0.17%) analyses. Moreover, individual-based genotypes were the least concordant with array-based genotypes and replicates. Population-based genotypes were less concordant than genotypes from LD-aware analyses with extended haplotypes. We reanalyzed the same dataset with a second set of callers and showed again that the individual-based caller identified more high-quality singletons than the population-based caller. We also replicated this result in a second dataset of 57 genes sequenced at 127.5x in 3,124 individuals. CONCLUSIONS: We recommend population-based analyses for high quality variant calls with few missing genotypes. With extended haplotypes, LD-aware methods generate the most accurate and complete genotypes. In addition, individual-based analyses should complement the above methods to obtain the most singleton variants.

Vitamin A supplementation during pregnancy for maternal and newborn outcomes.

BACKGROUND: The World Health Organization recommends routine vitamin A supplementation during pregnancy or lactation in areas with endemic vitamin A deficiency (where night blindness occurs), based on the expectation that supplementation will improve maternal and newborn outcomes including mortality, morbidity and prevention of anaemia or infection.   OBJECTIVES: To review the effects of supplementation of vitamin A, or one of its derivatives, during pregnancy, alone or in combination with other vitamins and micronutrients, on maternal and newborn clinical outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 March 2015) and reference lists of retrieved studies. SELECTION CRITERIA: All randomised or quasi-randomised trials, including cluster-randomised trials, evaluating the effect of vitamin A supplementation in pregnant women. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We reviewed 106 reports of 35 trials, published between 1931 and 2015. We included 19 trials including over 310,000 women, excluded 15 trials and one is ongoing. Overall, seven trials were judged to be of low risk of bias, three were high risk of bias and for nine it was unclear. 1) Vitamin A alone versus placebo or no treatmentOverall, when trial results are pooled, vitamin A supplementation does not affect the risk of maternal mortality (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.65 to 1.20; four trials Ghana, Nepal, Bangladesh, UK, high quality evidence), perinatal mortality (RR 1.01, 95% CI 0.95 to 1.07; one study, high quality evidence), neonatal mortality, stillbirth, neonatal anaemia, preterm birth (RR 0.98, 95% CI 0.94 to 1.01, five studies, high quality evidence), or the risk of having a low birthweight baby.Vitamin A supplementation reduces the risk of maternal night blindness (RR 0.79, 95% CI 0.64 to 0.98; two trials). There is evidence that vitamin A supplements may reduce maternal clinical infection (RR 0.45, 95% CI 0.20 to 0.99, five trials; South Africa, Nepal, Indonesia, Tanzania, UK, low quality evidence) and maternal anaemia (RR 0.64, 95% CI 0.43 to 0.94; three studies, moderate quality evidence). 2) Vitamin A alone versus micronutrient supplements without vitamin AVitamin A alone compared to micronutrient supplements without vitamin A does not decrease maternal clinical infection (RR 0.99, 95% CI 0.83 to 1.18, two trials, 591 women). No other primary or secondary outcomes were reported 3) Vitamin A with other micronutrients versus micronutrient supplements without vitamin AVitamin A supplementation (with other micronutrients) does not decrease perinatal mortality (RR 0.51, 95% CI 0.10 to 2.69; one study, low quality evidence), maternal anaemia (RR 0.86, 95% CI 0.68 to 1.09; three studies, low quality evidence), maternal clinical infection (RR 0.95, 95% CI 0.80 to 1.13; I² = 45%, two studies, low quality evidence) or preterm birth (RR 0.39, 95% CI 0.08 to 1.93; one study, low quality evidence).In HIV-positive women vitamin A supplementation given with other micronutrients was associated with fewer low birthweight babies (< 2.5 kg) in the supplemented group in one study (RR 0.67, 95% CI 0.47 to 0.96; one study, 594 women). AUTHORS' CONCLUSIONS: The pooled results of three large trials in Nepal, Ghana and Bangladesh (with over 153,500 women) do not currently suggest a role for antenatal vitamin A supplementation to reduce maternal or perinatal mortality. However, the populations studied were probably different with regard to baseline vitamin A status and there were problems with follow-up of women. There is good evidence that antenatal vitamin A supplementation reduces maternal night blindness, maternal anaemia for women who live in areas where vitamin A deficiency is common or who are HIV-positive. In addition the available evidence suggests a reduction in maternal infection, but these data are not of a high quality.

Comparative toxicity of eight metals on freshwater fish.

Two freshwater fish, Rasbora sumatrana (Cyprinidae) and Poecilia reticulata (guppy; Poeciliidae), were exposed to a range of eight heavy metals (copper (Cu), cadmium (Cd), zinc (Zn), lead (Pb), nickel (Ni), iron (Fe), aluminium (Al), and manganese (Mn)) at varied concentrations for 96 h in the laboratory. Mortality was assessed and median lethal concentrations (LC50) were calculated. It was observed that the LC50 values increased with a decrease in mean exposure times, for all metals and for both fish types. The 96-h LC50 values for Cu, Cd, Zn, Pb, Ni, Fe, Al, and Mn were 0.006, 0.10, 0.46, 0.63, 0.83, 1.71, 1.53, and 5.71 mg/L for R. sumatrana and 0.038, 0.17, 1.06, 1.99, 15.62, 1.46, 6.76, and 23.91 mg/L for P. reticulata, respectively. The metal toxicity trend for R. sumatrana and P. reticulata from most to least toxic was Cu > Cd > Zn > Pb > Ni > Al > Fe > Mn and Cu > Cd > Zn > Fe > Pb > Al > Ni > Mn, respectively. Results indicated that Cu was the most toxic metal on both fish, and R. sumatrana was more sensitive than P. reticulata to all the eight metals.

CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration.

In developed countries, age-related macular degeneration is a common cause of blindness in the elderly. A common polymorphism, encoding the sequence variation Y402H in complement factor H (CFH), has been strongly associated with disease susceptibility. Here, we examined 84 polymorphisms in and around CFH in 726 affected individuals (including 544 unrelated individuals) and 268 unrelated controls. In this sample, 20 of these polymorphisms showed stronger association with disease susceptibility than the Y402H variant. Further, no single polymorphism could account for the contribution of the CFH locus to disease susceptibility. Instead, multiple polymorphisms defined a set of four common haplotypes (of which two were associated with disease susceptibility and two seemed to be protective) and multiple rare haplotypes (associated with increased susceptibility in aggregate). Our results suggest that there are multiple disease susceptibility alleles in the region and that noncoding CFH variants play a role in disease susceptibility.

Genome-wide association study and meta-analysis of intraocular pressure.

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is influenced by genetic and environmental factors. Recent genome-wide association studies (GWAS) reported associations with IOP at TMCO1 and GAS7, and with primary open-angle glaucoma (POAG) at CDKN2B-AS1, CAV1/CAV2, and SIX1/SIX6. To identify novel genetic variants and replicate the published findings, we performed GWAS and meta-analysis of IOP in >6,000 subjects of European ancestry collected in three datasets: the NEI Glaucoma Human genetics collaBORation, GLAUcoma Genes and ENvironment study, and a subset of the Age-related Macular Degeneration-Michigan, Mayo, AREDS and Pennsylvania study. While no signal achieved genome-wide significance in individual datasets, a meta-analysis identified significant associations with IOP at TMCO1 (rs7518099-G, p = 8.0 × 10(-8)). Focused analyses of five loci previously reported for IOP and/or POAG, i.e., TMCO1, CDKN2B-AS1, GAS7, CAV1/CAV2, and SIX1/SIX6, revealed associations with IOP that were largely consistent across our three datasets, and replicated the previously reported associations in both effect size and direction. These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk.

Solid pseudopapillary neoplasm of the pancreas with prominent atypical multinucleated giant tumour cells.

AIMS: Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare low-grade malignant neoplasm. To our knowledge, SPN with prominent atypical multinucleated giant tumour cells (MNGTCs) has not yet been reported. METHODS AND RESULTS: We identified four cases of SPN with prominent atypical MNGTCs in a cohort of 62 cases of SPN (6.5%). The MNGTCs contained multiple enlarged, hyperchromatic, irregular nuclei with ample eosinophilic cytoplasm, typically present in the solid area of the tumour. The MNGTCs had an immunohistochemical profile typical of the conventional SPN and were positive for vimentin, ß-catenin, CD10 and progesterone receptor, but negative for pan-cytokeratin, chromogranin, synaptophysin, trypsin, Ki-67 and CD68 in all four cases. Patients of SPN with prominent MNGTCs were older than those with conventional SPN (P = 0.01); tumours were discovered incidentally by imaging studies for an unrelated disease in all four cases, and with a female to male ratio of 1:1. The proliferation index (Ki-67) was <1% in all four cases. None of the three patients for whom information was available developed recurrence during follow-up of 2.7, 3.8 and 5.0 years. CONCLUSIONS: The presence of MNGTCs in SPN most probably represents degenerative change of the tumour cells and does not seem to affect the prognosis.

Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.

We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10(-75)), ARMS2 (P < 10(-59)), C2/CFB (P < 10(-20)), C3 (P < 10(-9)), and CFI (P < 10(-6)). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 x 10(-11)), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 x 10(-7); CETP, P = 7.4 x 10(-7)) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c-associated alleles near LPL (P = 3.0 x 10(-3)) and ABCA1 (P = 5.6 x 10(-4)). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.

Bilateral Pyosalpinx Due to a 16-Year-Old Intrauterine Device Presented as Appendicitis.

Pyosalpinx is the collection of pus in the fallopian tube. Pyosalpinx usually follows pelvic inflammatory disease, sexually transmitted disease, or rarely non-sexually transmitted infection. This is the first-ever report of bilateral pyosalpinx due to intrauterine device in situ for the past 16 years, which presented as appendicitis. Pyosalpinx should be considered in female patients with lower abdominal pain.

Antibacterial effect of a diet pill supplement on the human intestinal bacteria.

INTRODUCTION: Many people worldwide attempt to lose weight or adopt strategies to control it. Some have resorted to the consumption of commercialized diet pills to achieve this goal. Multiple brands exist without clearly indicating their mechanism of action or adverse effects on human health. This study aims to determine the antibacterial effect of commercial diet pills on members of the intestinal microbiota. METHODOLOGY: Commercialized diet pills were bought from a pharmacy in the North of Lebanon. Broth microdilution test was performed to determine the Minimum Inhibitory Concentrations (MICs) of the aqueous suspension against forty-two isolates distributed into four Enterobacterales species. MIC of the digested form was determined against six different strains. GC-MS analysis was performed to elucidate the components of the diet pill compared to the manufacturer's list. RESULTS: Broth microdilution results revealed that MICs of the diet pill aqueous suspension ranged from 3.9x103-9.76x102 µg/mL for Escherichia coli, Enterobacter spp., and Proteus spp. For Klebsiella species, MIC of carbapenem-resistant isolates reached 1.95x103 µg/mL. The digested form had a significantly lower antibacterial effect compared to the aqueous suspension. GC-MS analysis results corresponded with the list of ingredients provided by the manufacturer. CONCLUSIONS: The results showed significant antibacterial activity of a commercial diet pill on different members of the human intestinal microbiota regardless of their resistance profile. Further work is needed to elucidate the antibacterial effect of the digested components to accurately understand their effect on the intestinal microflora and thus on human health.

Finger-Actuated Micropump of Constant Flow Rate without Backflow.

This paper presents a finger-actuated micropump with a consistent flow rate and no backflow. The fluid dynamics in interstitial fluid (ISF) extraction microfluidics are studied through analytical, simulation, and experimental methods. Head losses, pressure drop, diodocity, hydrogel swelling, criteria for hydrogel absorption, and consistency flow rate are examined in order to access microfluidic performance. In terms of consistency, the experimental result revealed that after 20 s of duty cycles with full deformation on the flexible diaphragm, the output pressure became uniform and the flow rate remained at nearly constant levels of 2.2 µL/min. The flow rate discrepancy between the experimental and predicted flow rates is around 22%. In terms of diodicity, when the serpentine microchannel and hydrogel-assisted reservoir are added to the microfluidic system integration, the diodicity increases by 2% (Di = 1.48) and 34% (Di = 1.96), respectively, compared to when the Tesla integration (Di = 1.45) is used alone. A visual and experimentally weighted analysis finds no signs of backflow. These significant flow characteristics demonstrate their potential usage in many low-cost and portable microfluidic applications.

Understanding the Impact of Vitamin B Supplements on a Saudi Population.

Introduction B vitamins help generate energy within cells. A significant portion of populations in developed countries suffer a deficiency in one or more B vitamins. This study assesses the use of vitamin B supplements and their effects. Methodology This cross-sectional study was conducted using public participants in Saudi Arabia. Participants from all over Saudi Arabia were recruited through self-conducted surveys to study the effects of using vitamin B supplements on appetite, BMI, energy, and sleep, and to identify any side effects in participants. Inclusion criteria included age (18 years or older) and use of vitamin B supplements. Children, pregnant women, adults who had never used vitamin B, and those not willing to participate in the study were excluded. Results In total, 1,521 adults were recruited. Most of the participants were young Saudi Females. While taking vitamin B supplements, a minority of participants complained of mild gastrointestinal upset, but a significant proportion experienced no side effects. In this study, a significant proportion of participants experienced an increase in appetite, which was associated with a significant increase in BMI after taking vitamin B supplements. This study also explored increases in energy, which were significant and associated with significant increases in sleeping time. Male participants in the present study noticed a significant increase in erectile dysfunction (ED). Conclusions This study found significant effects of vitamin B supplements on BMI, appetite, energy, and sleep, as well as an increase in ED in male participants. More studies are needed to further explore these findings.