Prevalence of non-communicable chronic diseases in rural India amongst peri- and post-menopausal women: Can artificial intelligence help in early identification?

Aims: To identify peri- and post-menopausal women at risk of non-communicable diseases in rural India and to assess their prevalence amongst these groups via the use of artificial intelligence.

Settings And Design: An observational study conducted by the Indian Menopause Society in collaboration with the Government of Maharashtra. The study included rural women residents of three villages in the Latur district of Maharashtra, India.

Enhanced Efficacy of Carvedilol by Utilization of Solid Dispersion and Other Novel Strategies: A Review.

Carvedilol is classified as a second class drug of Biopharmaceutical classification system (BCS), and it is an excellent beta blocker and vasodilating agent. It is used in a diverse range of disease states. Despite having tremendous advantages, the drug cannot be used effectively and productively due to aquaphobicity and poor bioavailability.

A Clinical Evaluation of Difference in Shades among Maxillary Central Incisor, Canine, and First Molar in a Young Age-group Using Digital Spectrophotometer: An Study.

Aim: The aim of this study was to evaluate and compare the most common shades of maxillary central incisor, canine and first molar and to confirm the shade difference between maxillary central incisor and canine in a young population of 18-25 years.

Materials And Methods: The shade of the maxillary central incisor, canine, and first molar of 100 study participants in a young population between 18 and 25 years were measured by digital spectrophotometer (VITA Easyshade). The shade of each tooth was assessed thrice with a digital spectrophotometer at the center of the tooth.

Role of poly(ADP-ribose) polymerase-1 in regulating human islet cell differentiation.

Poly(ADP-ribose) polymerase-1 (PARP1), a fundamental DNA repair enzyme, is known to regulate β cell death, replication, and insulin secretion. PARP1 knockout (KO) mice are resistant to diabetes, while PARP1 overactivation contributes to β cell death. Additionally, PARP1 inhibition (PARPi) improves diabetes complications in patients with type-2 diabetes.

XPC-PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair.

Cells employ global genome nucleotide excision repair (GGR) to eliminate a broad spectrum of DNA lesions, including those induced by UV light. The lesion-recognition factor XPC initiates repair of helix-destabilizing DNA lesions, but binds poorly to lesions such as CPDs that do not destabilize DNA. How difficult-to-repair lesions are detected in chromatin is unknown.

Deubiquitinating enzymes and the proteasome regulate preferential sets of ubiquitin substrates.

The ubiquitin-proteasome axis has been extensively explored at a system-wide level, but the impact of deubiquitinating enzymes (DUBs) on the ubiquitinome remains largely unknown. Here, we compare the contributions of the proteasome and DUBs on the global ubiquitinome, using UbiSite technology, inhibitors and mass spectrometry. We uncover large dynamic ubiquitin signalling networks with substrates and sites preferentially regulated by DUBs or by the proteasome, highlighting the role of DUBs in degradation-independent ubiquitination.

Bilateral same session flexible ureterorenoscopy for endoscopic management of bilateral renal calculi is noninferior to unilateral flexible ureterorenoscopy for management of multiple unilateral renal calculi: outcomes of a prospective comparative study.

Purpose: The aim of the study was to prospectively evaluate safety and efficacy of bilateral same session ureterorenoscopy (BSS-FURS) for management of bilateral renal calculi.

Methods: A prospective comparative study was designed to compare the results of BSS-FURS with unilateral flexible ureterorenoscopy (U-FURS) for management of renal calculi between June 2003 and May 2016. A sample size of 55 patients in each arm was calculated considering a 20% increase in the incidence of complications with BSS-FURS over 15% complication rate in U-FURS (alpha = 0.

A prospective evaluation of high- and low-power holmium laser settings for transurethral lithotripsy in the management of adults with large bladder calculi.

Purpose: To prospectively investigate the efficacy and safety of high-power (100 W) vs low-power (20 W) laser settings for transurethral laser lithotripsy in the management large vesical calculi (> 4 cm).

Methods: All patients with vesical calculi > 4 cm in the maximum dimension and scheduled for transurethral holmium laser lithotripsy were invited to participate in the study. Every alternate patient was treated with either the low- or high-power laser settings.

Simultaneous Holmium Laser Enucleation of Prostate with Removal of the Permanent Prostatic Urethral Stent Using the High-Power Holmium Laser: Technique in Two Cases and Review of the Literature.

Although the prostatic urethral stents are no longer used in the United States for treatment of prostatomegaly, urologists will encounter patients with complications of previously placed permanent prostatic stents. We report two cases of persistent bothersome lower urinary tract symptoms (LUTS) after prostatic stent placement treated with simultaneous holmium laser enucleation of prostate (HoLEP) with endoscopic removal of the prostatic urethral stent using high-power holmium laser. We also reviewed the literature regarding the removal of prostatic stents with holmium laser combined with surgical management of benign prostatic hyperplasia.

Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells.

The peptide receptor radionuclide therapy (PRRT) with Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2.

Poly(ADP-ribosyl)ation temporally confines SUMO-dependent ataxin-3 recruitment to control DNA double-strand break repair.

DNA damage-induced SUMOylation serves as a signal for two antagonizing proteins that both stimulate repair of DNA double-strand breaks (DSBs). Here, we demonstrate that the SUMO-dependent recruitment of the deubiquitylating enzyme ataxin-3 to DSBs, unlike recruitment of the ubiquitin ligase RNF4, additionally depends on poly [ADP-ribose] polymerase 1 (PARP1)-mediated poly(ADP-ribosyl)ation (PARylation). The co-dependence of ataxin-3 recruitment on PARylation and SUMOylation temporally confines ataxin-3 to DSBs immediately after occurrence of DNA damage.

A randomized controlled trial comparing high and medium power settings for holmium laser enucleation of prostate.

Purpose: To report the results of a randomized controlled trial comparing outcomes between medium power (MP) and high power (HP) laser settings for HoLEPs.

Methods: The primary objective was to compare the enucleation efficiency (EE) of HP- HoLEP (80-100 W) with MP-HoLEP (50 - 60 W). The secondary objectives were to compare treatment efficacy and safety between both groups.

Methods to Study Intracellular Movement and Localization of the Nucleotide Excision Repair Proteins at the DNA Lesions in Mammalian Cells.

Nucleotide excision repair (NER) is the most versatile DNA repair pathway that removes a wide variety of DNA lesions caused by different types of physical and chemical agents, such as ultraviolet radiation (UV), environmental carcinogen benzo[a]pyrene and anti-cancer drug carboplatin. The mammalian NER utilizes more than 30 proteins, in a multi-step process that begins with the lesion recognition within seconds of DNA damage to completion of repair after few hours to several days. The core proteins and their biochemical reactions are known from in vitro DNA repair assays using purified proteins, but challenge was to understand the dynamics of their rapid recruitment and departure from the lesion site and their coordination with other proteins and post-translational modifications to execute the sequential steps of repair.

Holmium Laser Enucleation of Prostate Within 6 Weeks of Transrectal Ultrasound Guided Prostate Biopsy is Safe and Effective.

Objective: To evaluate the safety and efficacy of performing Holmium laser enucleation of the prostate (HoLEP) for the treatment of bladder outlet obstruction secondary to an enlarged prostate within 6-weeks of a transrectal ultrasound (TRUS) guided prostate biopsy.

Materials And Methods: We performed a retrospective review of patients who underwent a HoLEP at our institution, excluding any patients with a confounding urologic history and compared patients who underwent a TRUS-guided 6- or 12-core prostate biopsy, and then underwent a HoLEP within 6 weeks (study group) with all other patients (control group). Our primary outcomes were enucleation efficiency (EE) and perioperative complication rate.

Chloroquine and hydroxychloroquine for COVID-19: Perspectives on their failure in repurposing.

What Is Known And Objective: Non-clinical studies suggest that chloroquine (CQ) and hydroxychloroquine (HCQ) have antiviral activities. Early clinical reports of successful HCQ-associated reduction in viral load from small studies in COVID-19 patients spurred a large number of national and international clinical trials to test their therapeutic potential. The objective of this review is to summarize the current evidence on the safety and efficacy of these two agents and to provide a perspective on why their repurposing has hitherto failed.

Loss of ZBTB24 impairs nonhomologous end-joining and class-switch recombination in patients with ICF syndrome.

The autosomal recessive immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a genetically heterogeneous disorder. Despite the identification of the underlying gene defects, it is unclear how mutations in any of the four known ICF genes cause a primary immunodeficiency. Here we demonstrate that loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance.

Genotype-guided warfarin therapy: Still of only questionable value two decades on.

What Is Known And Objective: Despite an apparently sound pharmacological basis, clinical studies of genotype-guided warfarin dosing have yielded mixed and conflicting results, leading to reluctance in its clinical implementation. The objective of this critique is to re-evaluate key warfarin pharmacogenetic studies with a view to explaining why this may be so.

Methods: Major widely-cited warfarin pharmacogenetic studies as well as recent meta-analyses were identified and a critical analysis of these was undertaken to identify factors that may account for poor clinical implementation of pre-treatment genotyping.

Synthesis of thiophene derivatives and their anti-microbial, antioxidant, anticorrosion and anticancer activity.

Background: A new series of thiophene analogues was synthesized and checked for their in vitro antibacterial, antifungal, antioxidant, anticorrosion and anticancer activities.

Results: A series of ethyl-2-(substituted benzylideneamino)-4,5,6,7-tetrahydrobenzo[]thiophene-3-carboxylate derivatives were synthesized by using Gewald synthesis and their structures were confirmed by FTIR, MS and H-NMR. The synthesized compounds were further evaluated for their in vitro biological potentials i.

Safety and Tolerability of Phosphatidylinositol-3-Kinase (PI3K) Inhibitors in Oncology.

Activation of phosphatidylinositol-3-kinase (PI3K) and downstream signalling by AKT/mammalian target of rapamycin (mTOR) modulates cellular processes such as increased cell growth, cell proliferation and increased cell migration as well as deregulated apoptosis and oncogenesis. The PI3K/AKT/mTOR pathway (particularly Class I PI3K isoforms) is frequently activated in a variety of solid tumours and haematological malignancies, making PI3K an attractive therapeutic target in oncology. Inhibitors of PI3K also have the potential to restore sensitivity to other modalities of treatments when administered as part of combination regimens.

Safety and Tolerability of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors in Oncology.

Tyrosine kinase inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) have dramatically improved progression-free survival in non-small-cell lung cancer (NSCLC) patients who carry sensitizing EGFR-activating mutations and in patients with breast and pancreatic cancers. However, EGFR-TKIs are associated with significant and disabling undesirable effects that adversely impact on quality of life and compliance. These effects include dermatological reactions, diarrhoea, hepatotoxicity, stomatitis, interstitial lung disease and ocular toxicity.

Safety and Tolerability of Histone Deacetylase (HDAC) Inhibitors in Oncology.

Histone deacetylases (HDACs) are expressed at increased levels in cells of various malignancies, and the use of HDAC inhibitors has improved outcomes in patients with haematological malignancies (T-cell lymphomas and multiple myeloma). However, they are not as effective in solid tumours. Five agents are currently approved under various jurisdictions, namely belinostat, chidamide, panobinostat, romidepsin and vorinostat.