Holmium laser enucleation versus bipolar resection in the management of large-volume benign prostatic hyperplasia: A randomized controlled trial.

OBJECTIVES: To compare the mid-term safety and efficacy of holmium laser enucleation of the prostate versus bipolar transurethral resection of the prostate in the management of large-volume benign prostatic hyperplasia. METHODS: From December 2016 to March 2018, patients with benign prostatic hyperplasia (≥80 cc) were randomized (block randomization, computer-generated random list) to holmium laser enucleation of the prostate (57 patients) or bipolar transurethral resection of the prostate (55 patients). Patients were excluded if they had an International Prostate Symptom Score <13, a maximum urinary flow rate >15 mL/s or presence of prostate cancer, bladder stone, urethral stricture, neurogenic bladder, or previous prostate surgery. The primary outcome was hemoglobin loss. The analysis was intention-to-treat. Postoperative findings (36 months) were compared to baseline characteristics. Univariate and logistic regression analyses were performed for risk factors predicting hemoglobin loss or operative time in all patients. RESULTS: There was no significant difference in baseline characteristics between the two groups. Holmium laser enucleation of the prostate was associated with significantly better operative time (P = 0.019), operative efficiency (P < 0.001), hemoglobin loss (P < 0.001), catheterization duration (P < 0.001) and hospital stay (P < 0.001) compared to bipolar transurethral resection of prostate. Both procedures were safe, with no significant difference in total complications (P = 0.128). Blood transfusion (P = 0.026) and capsular perforation (P = 0.239) were reported only in the bipolar transurethral resection of the prostate group. There was no significant difference in rates of urinary tract infections (P = 0.714), urethral strictures (P = 0.359), or transient stress incontinence (P = 0.717). At the last follow-up (3 years), holmium laser enucleation of the prostate was associated with significantly better International Prostate Symptom Scores, prostate-specific antigen levels and maximum urinary flow rates compared to bipolar transurethral resection of the prostate (P < 0.05). In logistic regression analyses, prostate size and bipolar transurethral resection of the prostate were associated with significantly greater hemoglobin loss, whereas prostate size, capsular perforation, and bipolar transurethral resection of the prostate were associated with significantly longer operative time. CONCLUSION: Holmium laser enucleation of the prostate and bipolar transurethral resection of the prostate are effective and safe for the management of moderate-to-severe lower urinary tract symptoms attributable to large-volume benign prostatic hyperplasia (≥80 cc). However, if both techniques are available, holmium laser enucleation of the prostate is preferred due its better efficacy and safety profile.

Thiourea-Capped Nanoapatites Amplify Osmotic Stress Tolerance in Zea mays L. by Conserving Photosynthetic Pigments, Osmolytes Biosynthesis and Antioxidant Biosystems.

Salinity is one of the most prevalent abiotic stresses which not only limits plant growth and yield, but also limits the quality of food products. This study was conducted on the surface functionalization of phosphorus-rich mineral apatite nanoparticles (ANPs), with thiourea as a source of nitrogen (TU-ANPs) and through a co-precipitation technique for inducing osmotic stress tolerance in Zea mays. The resulting thiourea-capped apatite nanostructure (TU-ANP) was characterized using complementary analytical techniques, such as EDX, SEM, XRD and IR spectroscopy. The pre-sowing of soaked seeds of Zea mays in 1.00 µg/mL, 5.00 µg/mL and 10 µg/mL of TU-ANPs yielded growth under 0 mM, 60 mM and 100 mM osmotic stress of NaCl. The results show that Ca and P salt acted as precursors for the synthesis of ANPs at an alkaline pH of 10-11. Thiourea as a source of nitrogen stabilized the ANPs' suspension medium, leading to the synthesis of TU-ANPs. XRD diffraction analysis validated the crystalline nature of TU-ANPs with lattice dimensions of 29 nm, calculated from FWHM using the Sherrer equation. SEM revealed spherical morphology with polydispersion in size distribution. EDS confirmed the presence of Ca and P at a characteristic KeV, whereas IR spectroscopy showed certain stretches of binding functional groups associated with TU-ANPs. Seed priming with TU-ANPs standardized germination indices (T50, MGT, GI and GP) which were significantly declined by NaCl-based osmotic stress. Maximum values for biochemical parameters, such as sugar (39.8 mg/g at 10 µg/mL), protein (139.8 mg/g at 10 µg/mL) and proline (74.1 mg/g at 10 µg/mL) were recorded at different applied doses of TU-ANP. Antioxidant biosystems in the form of EC 1.11.1.6 catalase (11.34 IU/g FW at 10 µg/mL), EC 1.11.1.11 APX (0.95 IU/G FW at 10 µg/mL), EC 1.15.1.1 SOD (1.42 IU/g FW at 5 µg/mL), EC 1.11.1.7 POD (0.43 IU/g FW at 5 µg/mL) were significantly restored under osmotic stress. Moreover, photosynthetic pigments, such as chlorophyll A (2.33 mg/g at 5 µg/mL), chlorophyll B (1.99 mg/g at 5 µg/mL) and carotenoids (2.52 mg/g at 10 µg/mL), were significantly amplified under osmotic stress via the application of TU-ANPs. Hence, the application of TU-ANPs restores the growth performance of plants subjected to induced osmotic stress.

The Glycemic Control Potential of Some Amaranthaceae Plants, with Particular Reference to In Vivo Antidiabetic Potential of Agathophora alopecuroides.

Natural products continue to provide inspiring moieties for the treatment of various diseases. In this regard, investigation of wild plants, which have not been previously explored, is a promising strategy for reaching medicinally useful drugs. The present study aims to investigate the antidiabetic potential of nine Amaranthaceae plants: Agathophora alopecuroides, Anabasis lachnantha, Atriplex leucoclada, Cornulaca aucheri, Halothamnus bottae, Halothamnus iraqensis, Salicornia persia, Salsola arabica, and Salsola villosa, growing in the Qassim area, the Kingdom of Saudi Arabia. The antidiabetic activity of the hydroalcoholic extracts was assessed using in vitro testing of α-glucosidase and α-amylase inhibitory effects. Among the nine tested extracts, A. alopecuroides extract (AAE) displayed potent inhibitory activity against α-glucosidase enzyme with IC50 117.9 µg/mL noting better activity than Acarbose (IC50 191.4 µg/mL). Furthermore, AAE displayed the highest α- amylase inhibitory activity among the nine tested extracts, with IC50 90.9 µg/mL. Based upon in vitro testing results, the antidiabetic activity of the two doses (100 and 200 mg/kg) of AAE was studied in normoglycemic and streptozotocin (STZ)-induced diabetic mice. The effects of the extract on body weight, food and water intakes, random blood glucose level (RBGL), fasting blood glucose level (FBGL), insulin, total cholesterol, and triglycerides levels were investigated. Results indicated that oral administration of the two doses of AAE showed a significant dose-dependent increase (p < 0.05) in the body weight and serum insulin level, as well as a significant decrease in food and water intake, RBGL, FBGL, total cholesterol, and triglyceride levels, in STZ-induced diabetic mice, compared with the diabetic control group. Meanwhile, no significant differences of both extract doses were observed in normoglycemic mice when compared with normal control animals. This study revealed a promising antidiabetic activity of the wild plant A. alopecuroides.

Anti-HIV Ermiasolides from Croton megalocarpus.

In recent years, elucidation of novel anti-HIV bioactive compounds from natural products is gaining importance rapidly, not only from the research and publications, but also from controlled clinical studies. Here we report three new anti-HIV eudesmane-type sesquiterpenes, 5ß-Hydroxy-8α-methoxy eudesm-7(11)-en-12,8-olide (1), 5ß,8α-Dihydroxy eudesm-7(11)-en-12,8-olide (2) and 5ß-Hydroxy-8H-ß-eudesm-7(11)-en-12,8-olide (3). These are trivially named ermiasolide A-C and were isolated from the bark of Croton megalocarpus. 5ß-Hydroxy-8α-methoxy eudesm-7(11)-en-12,8-olide (1), showed the highest anti-HIV activity by inhibiting 93% of the viral replication with an IC50 = 0.002 µg/mL. On the other hand, 5ß-Hydroxy-8H-ß-eudesm-7(11)-en-12,8-olide (3) and 5ß,8α-dihydroxy eudesm-7(11)-en-12,8-olide (2), inhibited viral replication by 77.5% at IC50 = 0.04 µg/mL and 69.5% at IC50 = 0.002 µg/mL, respectively. Molecular docking studies showed that the proposed mechanism of action leading to these results is through the inhibition of HIV-protease.

A Single-Center Experience and Literature Review of Management Strategies for Clostridium difficile Infection in Hematopoietic Stem Cell Transplant Patients.

INTRODUCTION: The aim of our study is to evaluate risk factors associated with the development of C. difficile infection (CDI) in hematopoietic stem cell transplant (HSCT) patients, determine its incidence and report outcomes of CDI in our patient population. METHODS: We performed a retrospective review of medical records of adult HSCT recipients diagnosed between 2013 and 2016 at our center. Logistic regression models were used to determine the relationship between risk factors and the odds of CDI. RESULTS: The overall incidence of CDI in HSCT patients was 9.4%. The incidence of CDI was higher in allogeneic HSCT (20%) versus autologous HSCT (4.8%). No statistically significant differences in age, gender, cancer type, transplant type were found between those who developed CDI and those who did not. However, patients with CDI had a longer length of stay (25 days) and used more antibiotics (30 days prior to and during admission for HSCT) than non-CDI patients (19 days). Only two of 17 patients (11.8%) with CDI experienced recurrence among 180 patients after HSCT. No patient suffered from toxic megacolon or ileus and no patient underwent colectomy. There was no mortality associated with CDI at our center. CONCLUSION: CDI has an incidence rate of 9.4% in HSCT recipients. Established risk factors including age, gender, cancer type, and transplant type were not identified as risk factors in our population. However, longer LOS and use of greater than four lines of antibiotics were observed among those with CDI compared to those without CDI.

Nano-Antenna Coupled Infrared Detector Design.

Since the 1940s, infrared (IR) detection and imaging at wavelengths in the two atmospheric windows of 3 to 5 and 8 to 14 µm has been extensively researched. Through several generations, these detectors have undergone considerable developments and have found use in various applications in different fields including military, space science, medicine and engineering. For the most recently proposed generation, these detectors are required to achieve high-speed detection with spectral and polarization selectivity while operating at room temperature. Antenna coupled IR detectors appear to be the most promising candidate to achieve these requirements and has received substantial attention from research in recent years. This paper sets out to present a review of the antenna coupled IR detector family, to explore the main concepts behind the detectors as well as outline their critical and challenging design considerations. In this context, the design of both elements, the antenna and the sensor, will be presented individually followed by the challenging techniques in the impedance matching between both elements. Some hands-on fabrication techniques will then be explored. Finally, a discussion on the coupled IR detector is presented with the aim of providing some useful insights into promising future work.

Buprenorphine shared medical appointments for the treatment of opioid dependence in a homeless clinic.

BACKGROUND: Opioid misuse and dependence are prevalent and rising problems in the United States. Treatment with buprenorphine is a successful treatment option for individuals with opioid dependence. This study describes and preliminarily evaluates a unique delivery system that provides buprenorphine treatment via a shared medical appointment. METHODS: A retrospective medical record review on all 77 opioid-dependent patients referred for a buprenorphine shared medical appointment in a homeless clinic from 2010 to 2012. RESULTS: Most patients were currently homeless (61%), unemployed (92%), had an Axis I psychiatric diagnosis (81%), and had recent polysubstance use (53%). Of the 77 patients, 95% attended at least 1 shared medical appointment. Treatment retention at 12 and 24 weeks was 86% and 70%, respectively. CONCLUSIONS: In a patient population with complex social and mental health histories, buprenorphine treatment via a shared medical appointment had high retention rates. Findings can help guide the development of unique delivery systems to serve real-world complex patients with opioid dependence.

Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy.

Autophagy is a cell-protective and degradative process that recycles damaged and long-lived cellular components. Cancer cells are thought to take advantage of autophagy to help them to cope with the stress of tumorigenesis; thus targeting autophagy is an attractive therapeutic approach. However, there are currently no specific inhibitors of autophagy. ULK1, a serine/threonine protein kinase, is essential for the initial stages of autophagy, and here we report that two compounds, MRT67307 and MRT68921, potently inhibit ULK1 and ULK2 in vitro and block autophagy in cells. Using a drug-resistant ULK1 mutant, we show that the autophagy-inhibiting capacity of the compounds is specifically through ULK1. ULK1 inhibition results in accumulation of stalled early autophagosomal structures, indicating a role for ULK1 in the maturation of autophagosomes as well as initiation.

Prevalence of Anal Dysplasia in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Although the prevalence of anal dysplasia is higher in some immunosuppressed populations, the prevalence in patients with inflammatory bowel disease (IBD) is unknown. We examined the prevalence of abnormal anal cytology among IBD patients, and its relation to the human papilloma virus (HPV). METHODS: Adults with IBD and age-matched healthy controls (HC) were recruited. IBD patients were categorized as nonimmunosuppressed (IBD-N) or immunosuppressed (IBD-I). Anal Papanicolaou tests were performed for HPV testing and classification by a cytopathologist as follows: negative, atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, cancer, or unsatisfactory. RESULTS: A total of 270 subjects (100 IBD-I, 94 IBD-N, and 76 HC) were recruited. ASC-US were detected in 19 subjects, with a trend toward a higher prevalence among IBD subjects compared with HC (8.8% vs 2.6%; P = .10). The prevalence did not differ with respect to immunosuppression. Crohn's disease (CD) subjects had a higher prevalence of ASC-US compared with others with IBD (P = .02). Among those with CD, female sex and disease duration longer than 10 years were risk factors. There were no cases of low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, or anal cancer in the cohort. HPV was present in 5.3% and 1.5% of subjects with and without ASC-US, respectively (P = .26). CONCLUSIONS: Although there was a trend toward abnormal anal Papanicolaou tests in IBD subjects compared with HC, there was no difference based on immunosuppression. The presence of HPV did not correlate with abnormal anal cytology. Risk factors associated with this increased trend include female CD subjects and those with a longer duration of CD. ClinicalTrials.gov number: NCT01860963; https://clinicaltrials.gov/ct2/show/NCT01860963.

Ethnic disparities in the association of body mass index with the risk of hypertension and diabetes.

Despite having lower body mass index (BMI) compared to other ethnic groups, Asians continue to develop significant metabolic diseases such as hypertension and diabetes. To evaluate the disparate association of BMI and risk of hypertension and diabetes in Asians. We retrospectively studied 150,753 adults from the 1985-2011 California Behavioral Risk Factor Survey. Trends in prevalence of obesity, hypertension, and diabetes were stratified by ethnicity. Multivariate logistic regression models evaluated the incremental effect of one unit BMI increase on risk of hypertension and diabetes and the disparate risks of hypertension and diabetes at different BMI thresholds. Asians had the lowest BMI among all groups. However, the impact of increasing BMI on risk of hypertension and diabetes was significantly greater in Asians. For each one unit increase in BMI, Asians were significantly more likely to have hypertension (OR 1.15; 95% CI 1.13-1.18) compared to non-Hispanic whites, blacks, and Hispanics. Similar trends were seen for diabetes (Asians: OR 1.15; 95% CI 1.13-1.18). The risk of hypertension in Asians with BMI ≥ 22 was similar to non-Hispanic whites with BMI ≥ 27 and blacks with BMI ≥ 28. The risk of diabetes in Asians with BMI ≥ 28 was similar to non-Hispanic whites with BMI ≥ 30. Despite lower overall BMI compared to other groups, weight gain in Asians is associated with significantly higher risks of hypertension and diabetes. Compared to other ethnic groups, similar risks of hypertension and diabetes are seen in Asians at much lower BMI.

Exploring nature's hidden treasure: Unraveling the untapped phytochemical and pharmacological potentials of Clinopodium vulgare L. - A hidden gem in the Lamiaceae family.

Folk medicine, rooted in historical practice, has long been used for medicinal purposes, emphasizing the need to ensure the safety, quality, and efficacy of herbal medicines. This imperative has grown over time, prompting collaborative efforts to document historical records and preserve invaluable knowledge of medicinal plants. The Lamiaceae (Labiatae) family, renowned for its rich assortment of medicinal plants characterized by high concentrations of volatile oils, stands out in this regard. This review focuses on Clinopodium vulgare (C. vulgare) L., commonly known as wild basil or basil thyme, a significant species within the Lamiaceae family found across diverse global regions. C. vulgare boasts a storied history of application in treating various ailments, such as gastric ulcers, diabetes, and inflammation, dating back to ancient times. Rigorous research has substantiated its pharmacological properties, revealing its antioxidant, antiviral, antibacterial, anti-inflammatory, anticancer, antihypertensive, and enzyme-inhibitory effects. This comprehensive review provides an insightful overview of the Lamiaceae family, elucidates the extraction methods employed to obtain medicinal compounds, explores the phytoconstituents present in C. vulgare, and systematically details its diverse pharmacological properties. Additionally, the review delves into considerations of toxicity. By synthesizing this wealth of information, this study opens avenues for the potential therapeutic applications of C. vulgare. The practical value of this research lies in its contribution to the understanding of medicinal plants, mainly focusing on the pharmacological potential of C. vulgare. This exploration enriches our knowledge of traditional medicine and paves the way for innovative therapeutic approaches, offering promising prospects for future drug development. As the demand for natural remedies continues to increase, this work provides a valuable resource for researchers, practitioners, and stakeholders in herbal medicine and pharmacology.

Donor diabetes mellitus is an independent risk factor for graft loss in HCV positive but not HCV negative liver transplant recipients.

BACKGROUND AND AIMS: Graft survival in HCV (hepatitis C virus) infected recipients is worse than those transplanted for other liver diseases. We studied whether several donor cardiovascular risk factors (including advanced age, smoking, hypertension, and diabetes mellitus) contribute to worse outcomes for HCV positive and HCV negative liver transplant recipients. METHODS: We obtained data from the United Network for Organ Sharing on all adult liver transplants performed in the United States between January 1, 1998 and December 31, 2003. In total, 27,033 transplant cases were evaluated. Independent predictors of graft survival were determined using Cox proportional hazards regression analysis after controlling for factors previously found to be associated with differences in transplant outcomes. RESULTS: Donor diabetes was a strong independent risk factor for graft failure [hazard ratio (HR) = 1.20, p = 0.006] only in HCV positive recipients. Neither donor smoking status nor hypertension predicted graft loss in either cohort. Consistent with previous studies, advanced donor age, donation after cardiac death, height, and African American donor all predicted graft loss amongst both cohorts. CONCLUSION: Accounting for donor diabetes in relation to recipient HCV status in the selection of liver recipients may result in improved graft survival.

The association of ABO blood group distribution and clinical characteristics in patients with SARS-CoV-2.

INTRODUCTION: SARS-COV-2, the novel severe acute respiratory syndrome coronavirus, has become a life-threatening public health crisis. This kind of pandemic is frightening the world with clinical, psychological, and emotional distress and leading to an economic slowdown. To explore any association between the ABO blood type and the susceptibility to coronavirus disease 2019 (COVID-19), we compared ABO blood group distribution among 671 COVID-19 patients with the local control population. METHODOLOGY: The study was conducted in Blood Bank Hospital in Erbil, Kurdistan Region, Iraq. The ABO-typed blood samples were obtained from 671 patients infected with SARS-CoV-2 between February and June 2021. RESULTS: Our results demonstrated that the risk of SARS-COV-2 was higher for patients with blood group A than those with not-A blood type patients. Of the 671 patients with COVID-19, 301 had type A (44.86%), 232 had type B (34.58%), 53 had type AB blood (7.9%), and 85 had type O (12.67%). CONCLUSIONS: We concluded that the Rh-negative blood type has a protective effect on SARS-COV-2. Our results also indicate that the decreased susceptibility of individuals with blood group O and the increased susceptibility of individuals with blood group A to COVID-19 could be linked to the presence of natural anti-blood group antibodies, particularly anti-A antibody, in the blood. However, there might be other mechanisms that require further study.

Fungal Endophytes: Microfactories of Novel Bioactive Compounds with Therapeutic Interventions; A Comprehensive Review on the Biotechnological Developments in the Field of Fungal Endophytic Biology over the Last Decade.

The seminal discovery of paclitaxel from endophytic fungus Taxomyces andreanae was a milestone in recognizing the immense potential of endophytic fungi as prolific producers of bioactive secondary metabolites of use in medicine, agriculture, and food industries. Following the discovery of paclitaxel, the research community has intensified efforts to harness endophytic fungi as putative producers of lead molecules with anticancer, anti-inflammatory, antimicrobial, antioxidant, cardio-protective, and immunomodulatory properties. Endophytic fungi have been a valuable source of bioactive compounds over the last three decades. Compounds such as taxol, podophyllotoxin, huperzine, camptothecin, and resveratrol have been effectively isolated and characterized after extraction from endophytic fungi. These findings have expanded the applications of endophytic fungi in medicine and related fields. In the present review, we systematically compile and analyze several important compounds derived from endophytic fungi, encompassing the period from 2011 to 2022. Our systematic approach focuses on elucidating the origins of endophytic fungi, exploring the structural diversity and biological activities exhibited by these compounds, and giving special emphasis to the pharmacological activities and mechanism of action of certain compounds. We highlight the tremendous potential of endophytic fungi as alternate sources of bioactive metabolites, with implications for combating major global diseases. This underscores the significant role that fungi can play in the discovery and development of novel therapeutic agents that address the challenges posed by prevalent diseases worldwide.

Chiroptical Response Inversion and Enhancement of Room-Temperature Exciton-Polaritons Using 2D Chirality in Perovskites.

Although chiral semiconductors have shown promising progress in direct circularly polarized light (CPL) detection and emission, they still face potential challenges. A chirality-switching mechanism or approach integrating two enantiomers is needed to discriminate the handedness of a given CPL; additionally, a large material volume is required for sufficient chiroptical interaction. These two requirements pose significant obstacles to the simplification and miniaturization of the devices. Here, room-temperature chiral polaritons fulfilling dual-handedness functions and exhibiting a more-than-two-order enhancement of the chiroptical signal are demonstrated, by embedding a 40 nm-thick perovskite film with a 2D chiroptical effect into a Fabry-Pérot cavity. By mixing chiral perovskites with different crystal structures, a pronounced 2D chiroptical effect is accomplished in the perovskite film, featured by an inverted chiroptical response for counter-propagating CPL. This inversion behavior matches the photonic handedness switch during CPL circulation in the Fabry-Pérot cavity, thus harvesting giant enhancement of the chiroptical response. Furthermore, affected by the unique quarter-wave-plate effects, the polariton emission achieves a chiral dissymmetry of ±4% (for the emission from the front and the back sides). The room-temperature polaritons with the strong dissymmetric chiroptical interaction shall have implications on a fundamental level and future on-chip applications for biomolecule analysis and quantum computing.

In vitro and in silico evaluations of actinomycin X2and actinomycin D as potent anti-tuberculosis agents.

Background: Multidrug-resistant tuberculosis (MDR-TB) is one of the world's most devastating contagious diseases and is caused by the MDR-Mycobacterium tuberculosis (MDR-Mtb) bacteria. It is therefore essential to identify novel anti-TB drug candidates and target proteins to treat MDR-TB. Here, in vitro and in silico studies were used to investigate the anti-TB potential of two newly sourced actinomycins, actinomycin-X2 (act-X2) and actinomycin-D (act-D), from the Streptomyces smyrnaeus strain UKAQ_23 (isolated from the Jubail industrial city of Saudi Arabia). Methods: The anti-TB activity of the isolated actinomycins was assessed in vitro using the Mtb H37Ra, Mycobacterium bovis (BCG), and Mtb H37Rv bacterial strains, using the Microplate Alamar Blue Assay (MABA) method. In silico molecular docking studies were conducted using sixteen anti-TB drug target proteins using the AutoDock Vina 1.1.2 tool. The molecular dynamics (MD) simulations for both actinomycins were then performed with the most suitable target proteins, using the GROningen MAchine For Chemical Simulations (GROMACS) simulation software (GROMACS 2020.4), with the Chemistry at HARvard Macromolecular Mechanics 36m (CHARMM36m) forcefield for proteins and the CHARMM General Force Field (CGenFF) for ligands. Results: In vitro results for the Mtb H37Ra, BCG, and Mtb H37Rv strains showed that act-X2 had minimum inhibitory concentration (MIC) values of 1.56 ± 0.0, 1.56 ± 0.0, and 2.64 ± 0.07 µg/mL and act-D had MIC values of 1.56 ± 0.0, 1.56 ± 0.0, and 1.80 ± 0.24 µg/mL respectively. The in silico molecular docking results showed that protein kinase PknB was the preferred target for both actinomycins, while KasA and pantothenate synthetase were the least preferred targets for act-X2and act-D respectively. The molecular dynamics (MD) results demonstrated that act-X2 and act-D remained stable inside the binding region of PknB throughout the simulation period. The MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) binding energy calculations showed that act-X2 was more potent than act-D. Conclusion: In conclusion, our results suggest that both actinomycins X2 and D are highly potent anti-TB drug candidates. We show that act-X2is better able to antagonistically interact with the protein kinase PknB target than act-D, and thus has more potential as a new anti-TB drug candidate.

Synthesis and structure-activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKε kinases.

The design, synthesis and structure-activity relationships of a novel series of 2,4-diamino-5-cyclopropyl pyrimidines is described. Starting from BX795, originally reported to be a potent inhibitor of PDK1, we have developed compounds with improved selectivity and drug-like properties. These compounds have been evaluated in a range of cellular and in vivo assays, enabling us to probe the putative role of the TBK1/IKKε pathway in inflammatory diseases.

Antihypertensive medication in frail older adults: A narrative review through a deprescribing lens.

Purpose of review: The management of hypertension in frail older adults remains controversial, as these patients are underrepresented in clinical trials and practice guidelines. Overtreatment may cause harm while undertreatment may lead to greater risk of cardiovascular events. Our research aims to examine this controversy and provide guidance regarding deprescribing decisions in frail older adults. Results: Current evidence suggests that there may be minimal cardiovascular benefit and significant harm of antihypertensive medication in the frail older adult population. A minority of hypertension guidelines provide sufficient recommendations for frail older adults, and there are limited tools available to guide clinical decision-making. Conclusion: Randomized controlled trials and well-designed observational studies are needed to confirm the benefit-to-harm relationship of antihypertensive medication in frail older adults. Decision tools that comprehensively address antihypertensive deprescribing would be advantageous to help clinicians with hypertension management in this population. Clinicians should engage in shared decision-making with the patient and family to ensure that decisions regarding antihypertensive deprescribing best meet the needs of all involved.

Evaluation of Renessans (Iodine Complex Molecule) Safety in Human Beings: An Open-Labeled Clinical Study.

Extensive studies on evaluation of effectiveness/toxicity of different oral doses of iodine have not been explored yet. An open-labeled phase I clinical studies were conducted using iodine complex based research compound called Renessans. Study groups were observed for development of any adverse/serious adverse events and alteration in laboratory values of vital organs, TSH and T4 hormones before and after the administration of the products. Out of 31 consented individuals, 24 healthy individuals participated in the study. Rate of occurrence of mild Adverse Events (AEs) in group A was 8.3% while in Group B it was 33.33% but these Adverse Events were self-resolving. After completion of study treatment blood serum iodine was reported to 3522.88 µg/l while mean urine iodine concentration (MUIC) was greater than 2000 µg/l. Hormonal and vital organ's testing revealed that all parameters of TSH and T4, LFT, CBC, RFT remained unaltered except from ALT-SGPT (P-value = .006) and AST-SGOT (P-value = .02). From all of these findings, it can be inferred that the use of Renessans formulations did not pose any sort of risk to human body and can be considered safe through this pilot study.

Morpho-physiological growth performance and phytoremediation capabilities of selected xerophyte grass species toward Cr and Pb stress.

Being sessile organisms, plants cannot escape unwanted changes in the environment. The rapid human population explosion caused significant environmental problems. Heavy metals produced through various sources can cause severe damage to living organisms. The study was planned to evaluate four grass species' morpho-physiological growth characteristics and phytoremediation capabilities under chromium (Cr) and lead stress (Pb) in the arid climate. Typha angustifolia, Tragus roxburghii, Aeluropus logopoides, and Cenchrus ciliaris grass species were used for the study. One-year-old stubbles from the Cholistan desert were used for the experiment. Cr treatments in the form of K2Cr2O7 were applied at 0, 20, 40, and 80 mg L-1, whereas Pb was applied as PbCl2 at 0, 50, 200, and 500 mg L-1 as control, low, moderate and high-stress, respectively. After 6 weeks of heavy metals treatments, plants were harvested and analyzed for growth performance and phytoremediation capabilities. Results depicted that, regarding morphological attributes, T. angustifolia performed better, followed by C. ciliaris; no clear pattern was observed for T. roxburghii and A. logopoides. The CO2 assimilation rate (Co2d) and water use efficiency (WUE) increased as the heavy metal stress increased in all species under both metals. In contrast, total chlorophyll content was higher under low stress. Other physiological parameters, such as relative humidity (RHd), net photosynthetic rate (A), transpiration rate (E), stomatal conductance (Gs), leaf internal CO2 concentration (Ci) and membrane stability index (MSI) gradually decreased as the Cr, and Pb stress levels increased among all the species. Moreover, Cr and Pb absorption contents of T. angustifolia were higher than the other three species at each stress level. Overall, T. angustifolia thrived against heavy metals stress and showed higher biomass, maximum photosynthetic measurements, WUE and higher metal absorption among all the selected species. Results concluded that although all the selected species behaved fine under stress conditions, T. angustifolia performance was better; thus, it can be used to remediate the soil near industrial estates.