Analysis of endometrial biopsy reports from adult women with abnormal uterine bleeding, a cross-sectional descriptive study

Background: Abnormal uterine bleeding is a common complaint in most women of different ages that prompts seeking gynecologic care. This study aimed to analyze and age-classify the prevalence of endometrial pathologies in women with abnormal uterine bleeding.Methods: This is a cross-sectional and a descriptive study, conducted at the obstetrics and gynecology department of the American Mission Hospital in the Kingdom of Bahrain on 88 patients who presented with abnormal uterine bleeding between January 2019 and January 2020.Results: Eighty-eight women with abnormal uterine bleeding demonstrated a fluctuating pattern of twenty endometrial pathologies distributed among five age groups in the range of 30-71. The mean age of the study cohort was 44.9±7.65 years; 55% of which were reported in the 41-50 age group. Benign endometrial polyp was reported as the most common pathology, accounting for 47.8% of the cohort. Although benign endometrial polyp was significantly the highest overall finding in all three age groups younger than 60, disordered proliferative endometrium was the highest reported single pathology in the age group 41-50, (N=10, p≤0.0001).Conclusions: This study demonstrated that benign endometrial polyp was the most common finding in women with abnormal uterine bleeding. This information could be essential for patient guidance and awareness of the benefits of endometrial biopsy. Eventually, the prediction of the potential endometrial pathology in women with abnormal uterine bleeding is vital for early disease management

Hepatitis C treatment: where are we now?

Chronic hepatitis C infection affects millions of people worldwide and confers significant morbidity and mortality. Effective treatment is needed to prevent disease progression and associated complications. Previous treatment options were limited to interferon and ribavirin regimens, which gave low cure rates and were associated with unpleasant side effects. The era of direct acting antiviral (DAA) therapies began with the development of the first-generation of NS3/4A protease inhibitors (PI) in 2011. They vastly improved outcomes for patients, particularly those with genotype 1 infection, the most prevalent genotype globally. Since then a multitude of DAAs have been licensed for use and outcomes for patients have improved further, with fewer side effects and cure rates approaching 100%. Recent regimens are interferon-free, and in many cases, ribavirin-free and involve a combination of DAA agents. This review summarises the treatment options currently available and discusses potential barriers that may delay the global eradication of hepatitis C

Synthesis and biological evaluation of novel cYY analogues targeting Mycobacterium tuberculosis CYP121A1

The rise in multidrug resistant (MDR) cases of tuberculosis (TB) has led to the need for the development of TB drugs with different mechanisms of action. The genome sequence of Mycobacterium tuberculosis (Mtb) revealed twenty different genes coding for cytochrome P450s. CYP121A1 catalyzes a C-C crosslinking reaction of dicyclotyrosine (cYY) producing mycocyclosin and current research suggests that either mycocyclosin is essential or the overproduction of cYY is toxic to Mtb. A series of 1,4-dibenzyl-2-imidazol-1-yl-methylpiperazine derivatives were designed and synthesised as cYY mimics. The derivatives substituted in the 4-position of the phenyl rings with halides or alkyl group showed promising antimycobacterial activity (MIC 6.25 μg/mL), with the more lipophilic branched alkyl derivatives displaying optimal binding affinity with CYP121A1 (iPr KD = 1.6 μM; tBu KD = 1.2 μM). Computational studies revealed two possible binding modes within the CYP121A1 active site both of which would effectively block cYY from binding

An Investigation of the Sensing Capabilities of Magnetotactic Bacteria

We investigate the sensing capabilities of magnetotactic bacteria (Magnetospirillum gryphiswaldense strain MSR1) to MCF-7 breast cancer cells. Cancer cells are allowed to grow inside a capillary tube with depth of 200 μ m and motion of magnetotactic bacteria is investigated under the influence of oxygen gradient and geomagnetic field. The influence of cancer cells is modeled to predict the oxygen gradient within the capillary tube in three-dimensional space. Our experimental motion analysis and count of motile magnetotactic bacteria indicate that they migrate towards less-oxygenated regions within the vicinity of cancer cells. Bands of magnetotactic bacteria with average concentration of 18.8±2.0% are observed in close proximity to MCF-7 cells (h = 20~ μ m), whereas the concentration at proximity of 190~ μ m is 5.0 ± 6.8%

Novel styryl-indoles as small molecule inhibitors of 25-hydroxyvitamin D-24-hydroxylase (CYP24A1): Synthesis and biological evaluation

The synthesis of a series of imidazole styrylindoles and sulfonyl styrylindoles derivatives is described. Evaluation of binding affinity and inhibitory activity against CYP24A1 identified the imidazole styrylindoles as potent inhibitors with activity greater or comparable with the standard ketoconazole. Flexible alignment and docking studies of the inhibitors in the CYP24A1 enzyme active site confirmed that complete occupation of the vitamin D access tunnel is essential to inhibitory activity, allowing exposure to multiple hydrophobic binding interactions and optimal conformation for the interaction of the imidazole nitrogen lone pair and the active site haem

Novel 1,5-diaryl pyrazole-3-carboxamides as selective COX-2/sEH inhibitors with analgesic, anti-inflammatory, and lower cardiotoxicity effects

Funding Information: The authors extend their appreciation to the Deanship of Scientific Research at Jouf University for funding this work through research grant number (DSR2020-04-421 )Peer reviewedPostprin

Interactive Effects of Immunoglobulin Gamma and Human Leucocyte Antigen Genotypes on Response to Interferon Based Therapy of Hepatitis C Virus

AIM: We examined the role that immunoglobulin GM 23 and KM allotypes—genetic markers of γ and κ chains, respectively—play in response to treatment of hepatitis C virus (HCV) infection in Egyptian patients.MATERIAL AND METHODS: A total of 120 persons who had responded to HCV treatment and 125 with persistent HCV infection were genotyped for the presence of GM23 and KM determinants. HLA –C genotyping was also done.RESULTS: Association of GM 23+ and KM3 was significantly associated with non response to treatment (P < 0.0001). Individuals who lacked this GM genotype (but were positive for KM1,2 and 3) were likely to respond to treatment (P=0.045). Association of heterozygous GM23 (+/-) with KM 1,2 and 3 or KM3 alone was significantly associated with SVR (P = 0.001) and (P = 0.0001) respectively. Particular combinations of HLA and GM genotypes were associated significantly with the response to HCV treatment. The combination of HLAC2C2 and GM23+ was associated with persistence of infection (P = 0.027) while the association of HLAC2C2 and heterozygous GM23+/- was associated with SVR (P = 0.001).The association of HLAC1C1 and heterozygous GM23+/- was significantly associated with SVR (P = 0.001) and also subjects with HLA C1/C2 and heterozygous GM23+/- were likely to respond to treatment (P = 0.003) while subjects with HLA C1/C2 and GM23+ show tendency to resist to treatment (P = 0.0001).CONCLUSION: Our results didn’t support a role for KM allotypes, GM23 allotype plays a role in the persistence of HCV infection in the presence or absence of KM1,3. Interaction between certain GM and HLA-C genotypes may favor adequate response to interferon based therapies

Design and synthesis of imidazole and triazole pyrazoles as mycobacterium tuberculosis CYP121A1 inhibitors

The emergence of untreatable drug‐resistant strains of Mycobacterium tuberculosis is a major public health problem worldwide, and the identification of new efficient treatments is urgently needed. Mycobacterium tuberculosis cytochrome P450 CYP121A1 is a promising drug target for the treatment of tuberculosis owing to its essential role in mycobacterial growth. Using a rational approach, which includes molecular modelling studies, three series of azole pyrazole derivatives were designed through two synthetic pathways. The synthesized compounds were biologically evaluated for their inhibitory activity towards M. tuberculosis and their protein binding affinity (KD). Series 3 biarylpyrazole imidazole derivatives were the most effective with the isobutyl (10 f) and tert‐butyl (10 g) compounds displaying optimal activity (MIC 1.562 μg/mL, KD 0.22 μM (10 f) and 4.81 μM (10 g)). The spectroscopic data showed that all the synthesised compounds produced a type II red shift of the heme Soret band indicating either direct binding to heme iron or (where less extensive Soret shifts are observed) putative indirect binding via an interstitial water molecule. Evaluation of biological and physicochemical properties identified the following as requirements for activity: LogP >4, H‐bond acceptors/H‐bond donors 4/0, number of rotatable bonds 5–6, molecular volume >340 Å3, topological polar surface area <40 Å2

Expression of the retinoic acid catabolic enzyme CYP26B1 in the human brain to maintain signaling homeostasis

Date of Acceptance: 27/08/2015 Funding was provided by the Wellcome Trust grant WT081633MA-NCE and Biological Sciences Research Council Grant BB/K001043/1. Prof Fragoso is the recipient of a Post Doctoral Science without Borders grant from the Brazilian National Council for Scientific and Technological Development (CNPq, 237450/2012-7).Peer reviewedPublisher PD

Safety and efficacy of percutaneous nephrolithotripsy in comorbid patients: A 3 years prospective observational study

Purpose: To report the result of percutaneous nephrolithotripsy (PCNL) via standard nephrostomy tract in a single training institution. The perioperative complications in relation to the comorbid state are particularly assessed. Patients and methods: A prospective interventional study between January 2019 to November 2022, included 210 patients scheduled for PCNL. The average age was 40.3 ± 11.8 years (range 18- 67 years). Patients were categorized into two groups. The first group comprised 146 cases (69 .5%) with no associated co-morbidities while the second group 64 (30.5%) had co-morbidities such as obesity in 4 cases (1.9%), hypertension (HTN) in 24 cases (11.4%) cases, diabetes mellitus (DM) in 17 (8.1%) cases, history of recurrent stone surgery in 11 (5.2%) cases and more than one in 8 cases (3.8%). Co-morbidities, stone burden, location of stone, time of surgery, stay in the hospital, further operations, and negative events were among the reported data. Complications and the stone-free rate were the main outcome indicators. Results: Intraoperative complications were reported in 40 (18.8%) patients (18 group 1 and 22 group 2) during PCNL. Bleeding occurred in 22 (10.5%) patients (9 group 1 and 13 group 2), blood transfusions were needed in 4 (1.9%) (2 group 1 and 2 group 2), extravasation was observed in 11 patients (5.2%) (6 group 1 and 5 group 2) and cardiac arrhythmia in 3 (1.4%) (1 group 1 and 2 group 2) patients. Postoperative complications occurred in 61 patients (29%) (24 group 1 and 37 group 2) in the form of fever in 10 patients (4.8 %) (3 group 1 and 7 group 2) and prolonged leakage in 50 patients (23.8%) (21 group 1 and 29 group 2). One patient of group 2 died from postoperative sepsis. Extravasation and postoperative leakage were higher in diabetic patients than in non-diabetics. Stonefree rate was 60.5% (127 of 210). Clinically significant residual fragments (CSRFs) found in 70 cases (33.3%) (33 group 1 and 37 group 2). In 13 cases (6.2%) (5 group 1 and 8 group 2), clinically insignificant residual fragments (CIRFs) were found. In 8 (3 group 1 and 5 group 2) of the 13 cases, spontaneous stone passage was observed within 4-6 weeks of surgery. Residual stones in three cases (1 group 1 and 2 group 2) were asymptomatic and 4 mm or less, whereas stones increased in two cases of group 2. Among all factors studied, stone burden was significantly correlated to both intraoperative and postoperative complications. The occurrence of postoperative fever increased with large stone burden. Conclusions: PCNL is a therapeutic modality that is effective, feasible, and safe for a wide range of patients with concurrent medical issues. A steep curve is required to reduce intraoperative and postoperative complications