Antitumor activity and phenolic profile of Melissa officinalis extract against human gastric adenocarcinoma cells.

Gastric cancer remains a global health concern, driving the exploration of natural products with anticancer potential. This study investigated the antiproliferative activity and chemical composition of a 70% ethanolic extract from Melissa officinalis L. against human gastric cancer cells. The extract was prepared and evaluated for total phenolic content, antioxidant capacity and flavonoid content. The MTT test checked how well it stopped the growth of human gastric adenocarcinoma (AGS) and normal dermal fibroblast (HDF) cells. Data analysis (SPSS Statistics) determined viable cell percentages and performed regression analysis (p<0.05). The extract exhibited significant antiproliferative activity against AGS cells compared to normal cells (p<0.05), with decreasing IC50 values (564.3, 258.0 and 122.5 µg/ml) over 24, 48 and 72 hours. It also displayed antioxidant activity (IC50=16.8±1.41µg/ml) and contained substantial phenolics (225.76±4.1 mg GAE/g) and flavonoids (22.36±2.6 mg RUT/g). This study suggests the 70% ethanolic extract of M. officinalis effectively suppresses AGS cell growth and possesses promising antioxidant properties, highlighting its potential as a natural source of anticancer and antioxidant agents, deserving further investigation.

Postmicturition dribble in men with no previous urogenital surgery: Systematic review and meta-analysis of treatment modalities.

INTRODUCTION: Postmicturition dribble (PMD) is common in males. Little is known about PMD etiology, but it is either secondary to urethral/prostatic surgery or primary (no previous surgery). Despite PMD's high prevalence, the effectiveness of its treatment modalities remains lacking. OBJECTIVE: To undertake a systematic review of the available treatments for primary PMD in adult males and meta-analysis of their effectiveness. MATERIALS AND METHODS: We searched four electronic databases from inception to 2023 for original articles that evaluated PMD treatments in male adults without previous urethral/prostatic surgery (PROSPERO protocol CRD42023444591). Study quality and risk of bias were evaluated using established tools. We extracted a range of variables including treatment modality used and its effectiveness on PMD volume and patient complaint. Meta-analysis was undertaken where feasible, and where this was not feasible, narrative synthesis was conducted. RESULTS: Out of 335 studies, four were included (four clinical trials, n = 344 patients). Two trials used physical/behavioral therapy (pelvic floor muscle exercises [PFMEs], urethral milking); the other two employed phosphodiesterase (PDE5) inhibitors (tadalafil, Udenafil). All studies were of good quality, but physical/behavioral therapy studies had some risk of bias. As the two physical/behavioral therapy studies used heterogenous outcome measures, narrative synthesis showed PMD volume improvement with PFMEs more than with urethral milking, both modalities were more effective than counseling, and in one study, PFMEs were effective in reducing PMD self-reported complaint than counseling. Meta-analyses of the two PDE5 inhibitors studies showed a large effect size with high heterogeneity for decreased PMD volume favoring PDE5 inhibitors over placebo (g = -0.86, 95% confidence interval [CI] -1.75; 0.02, p = 0.05; I2 = 88%); and a significant improvement equivalent to -1.06 points on the Hallym PMD Questionnaire score with no discernable heterogeneity (95% CI -1.65; -0.47, p = 0.0004; I2 = 0%), favoring PDE5 inhibitors compared to controls. CONCLUSIONS: Physical/behavioral therapy and PDE5 inhibitors are effective primary PMD treatments. PMD management studies in males with no previous urethral/prostatic surgery are very scarce and lack the use of consistent/comparable outcome measures. Further studies addressing these deficiencies would benefit this very thin evidence base.

The bioengineered and multifunctional nanoparticles in pancreatic cancer therapy: Bioresponisive nanostructures, phototherapy and targeted drug delivery.

The multidisciplinary approaches in treatment of cancer appear to be essential in term of bringing benefits of several disciplines and their coordination in tumor elimination. Because of the biological and malignant features of cancer cells, they have ability of developing resistance to conventional therapies such as chemo- and radio-therapy. Pancreatic cancer (PC) is a malignant disease of gastrointestinal tract in which chemotherapy and radiotherapy are main tools in its treatment, and recently, nanocarriers have been emerged as promising structures in its therapy. The bioresponsive nanocarriers are able to respond to pH and redox, among others, in targeted delivery of cargo for specific treatment of PC. The loading drugs on the nanoparticles that can be synthetic or natural compounds, can help in more reduction in progression of PC through enhancing their intracellular accumulation in cancer cells. The encapsulation of genes in the nanoparticles can protect against degradation and promotes intracellular accumulation in tumor suppression. A new kind of therapy for cancer is phototherapy in which nanoparticles can stimulate both photothermal therapy and photodynamic therapy through hyperthermia and ROS overgeneration to trigger cell death in PC. Therefore, synergistic therapy of phototherapy with chemotherapy is performed in accelerating tumor suppression. One of the important functions of nanotechnology is selective targeting of PC cells in reducing side effects on normal cells. The nanostructures are capable of being surface functionalized with aptamers, proteins and antibodies to specifically target PC cells in suppressing their progression. Therefore, a specific therapy for PC is provided and future implications for diagnosis of PC is suggested.

Scoping review of sexual and reproductive healthcare for men in the MENA (Middle East and North Africa) region: a handful of paradoxes?

BACKGROUND: No study appraised the knowledge gaps and factors impacting men's sexual and reproductive health (SRH) in MENA (Middle East and North Africa). The current scoping review undertook this task. METHODS: We searched PubMed and Web of Science (WoS) electronic databases for original articles on men's SRH published from MENA. Data was extracted from the selected articles and mapped out employing the WHO framework for operationalising SRH. Analyses and data synthesis identified the factors impacting on men's experiences of and access to SRH. RESULTS: A total of 98 articles met the inclusion criteria and were included in the analysis. The majority of studies focused on HIV and other sexually transmissible infections (67%); followed by comprehensive education and information (10%); contraception counselling/provision (9%); sexual function and psychosexual counselling (5%); fertility care (8%); and gender-based violence prevention, support/care (1%). There were no studies on antenatal/intrapartum/postnatal care and on safe abortion care (0% for both). Conceptually, there was lack of knowledge of the different domains of men's SRH, with negative attitudes, and many misconceptions; as well as a deficiency of health system policies, strategies and interventions for SRH. CONCLUSION: Men's SRH is not sufficiently prioritized. We observed five 'paradoxes': strong focus on HIV/AIDS, when MENA has low prevalence of HIV; weak focus on both fertility and sexual dysfunctions, despite their high prevalence in MENA; no publications on men's involvement in sexual gender-based violence, despite its frequency across MENA; no studies of men's involvement in antenatal/intrapartum/postnatal care, despite the international literature valuing such involvement; and, many studies identifying lack of SRH knowledge, but no publications on policies and strategies addressing such shortcoming. These 'mismatches' suggest the necessity for efforts to enhance the education of the general population and healthcare workers, as well as improvements across MENA health systems, with future research examining their effects on men's SRH.

In Vitro Inhibition of Xanthine Oxidase Purified from Arthritis Serum Patients by Nanocurcumin and Artemisinin Active Compounds.

Curcumin and artemisinin are commonly used in traditional East Asian medicine. In this study, we investigated the inhibitory effects of these active compounds on xanthine oxidase (XO) using allopurinol as a control. XO was purified from the serum of arthritis patients through ammonium sulfate precipitation (65%) and ion exchange chromatography on diethylaminoethyl (DEAE)-cellulose. The specific activity of the purified enzyme was 32.5 U/mg protein, resulting in a 7-fold purification with a yield of 66.8%. Molecular docking analysis revealed that curcumin had the strongest interaction energy with XO, with a binding energy of -9.28 kcal/mol. The amino acid residues Thr1077, Gln762, Phe914, Ala1078, Val1011, Glu1194, and Ala1079 were located closer to the binding site of curcumin than artemisinin, which had a binding energy of -7.2 kcal/mol. In vitro inhibition assays were performed using nanocurcumin and artemisinin at concentrations of 5, 10, 15, 20, and 25 µg/mL. Curcumin inhibited enzyme activity by 67-91%, while artemisinin had a lower inhibition ratio, which ranged from 40-70% compared to allopurinol as a control.

Detection of Nonsynonymous Single Variants in Human HLA-DRB1 Exon 2 Associated with Renal Transplant Rejection.

Background: HLA-DRB1 is the most polymorphic gene in the human leukocyte antigen (HLA) class II, and exon 2 is critical because it encodes antigen-binding sites. This study aimed to detect functional or marker genetic variants of HLA-DRB1 exon 2 in renal transplant recipients (acceptance and rejection) using Sanger sequencing. Methods: This hospital-based case-control study collected samples from two hospitals over seven months. The 60 participants were equally divided into three groups: rejection, acceptance, and control. The target regions were amplified and sequenced by PCR and Sanger sequencing. Several bioinformatics tools have been used to assess the impact of non-synonymous single-nucleotide variants (nsSNVs) on protein function and structure. The sequences data that support the findings of this study with accession numbers (OQ747803-OQ747862) are available in National Center for Biotechnology Information (GenBank database). Results: Seven SNVs were identified, two of which were novel (chr6(GRCh38.p12): 32584356C>A (K41N) and 32584113C>A (R122R)). Three of the seven SNVs were non-synonymous and found in the rejection group (chr6(GRCh38.p12): 32584356C>A (K41N), 32584304A>G (Y59H), and 32584152T>A (R109S)). The nsSNVs had varying effects on protein function, structure, and physicochemical parameters and could play a role in renal transplant rejection. The chr6(GRCh38.p12):32584152T>A variant showed the greatest impact. This is because of its conserved nature, main domain location, and pathogenic effects on protein structure, function, and stability. Finally, no significant markers were identified in the acceptance samples. Conclusion: Pathogenic variants can affect intramolecular/intermolecular interactions of amino acid residues, protein function/structure, and disease risk. HLA typing based on functional SNVs could be a comprehensive, accurate, and low-cost method for covering all HLA genes while shedding light on previously unknown causes in many graft rejection cases.

Effectiveness and safety of Ivermectin in COVID-19 patients: A prospective study at a safety-net hospital.

Ivermectin has been found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. It is unknown whether this inhibition of SARS-CoV-2 replication correlates with improved clinical outcomes. To assess the effectiveness and safety of ivermectin in hospitalized patients with COVID-19. A total of 286 patients with COVID-19 were included in the study. Univariate analysis of the primary mortality outcome and comparisons between treatment groups were determined. Logistic regression and propensity score matching (PSM) was used to adjust for confounders. Patients in the ivermectin group received 2 doses of Ivermectin at 200 µg/kg in addition to usual clinical care on hospital Days 1 and 3. The ivermectin group had a significantly higher length of hospital stay than the control group; however, this significance did not maintain on multivariable logistic regression analysis. The length of intensive care unit (ICU) stay and duration of mechanical ventilation were longer in the control group. However, a mortality benefit was not seen with ivermectin treatment before and after PSM (p values = 0.07 and 0.11, respectively). ICU admission, and intubation rate were not significantly different between the groups (p = 0.49, and p = 1.0, respectively). No differences were found between groups regarding the length of hospital stay, ICU admission, intubation rate, and in-hospital mortality.

Implementation and evaluation of a Project ECHO telementoring program for the Namibian HIV workforce.

BACKGROUND: The Namibian Ministry of Health and Social Services (MoHSS) piloted the first HIV Project ECHO (Extension for Community Health Outcomes) in Africa at 10 clinical sites between 2015 and 2016. Goals of Project ECHO implementation included strengthening clinical capacity, improving professional satisfaction, and reducing isolation while addressing HIV service challenges during decentralization of antiretroviral therapy. METHODS: MoHSS conducted a mixed-methods evaluation to assess the pilot. Methods included pre/post program assessments of healthcare worker knowledge, self-efficacy, and professional satisfaction; assessment of continuing professional development (CPD) credit acquisition; and focus group discussions and in-depth interviews. Analysis compared the differences between pre/post scores descriptively. Qualitative transcripts were analyzed to extract themes and representative quotes. RESULTS: Knowledge of clinical HIV improved 17.8% overall (95% confidence interval 12.2-23.5%) and 22.3% (95% confidence interval 13.2-31.5%) for nurses. Professional satisfaction increased 30 percentage points. Most participants experienced reduced professional isolation (66%) and improved CPD credit access (57%). Qualitative findings reinforced quantitative results. Following the pilot, the Namibia MoHSS Project ECHO expanded to over 40 clinical sites by May 2019 serving more than 140 000 people living with HIV. CONCLUSIONS: Similar to other Project ECHO evaluation results in the United States of America, Namibia's Project ECHO led to the development of ongoing virtual communities of practice. The evaluation demonstrated the ability of the Namibia HIV Project ECHO to improve healthcare worker knowledge and satisfaction and decrease professional isolation.

Lessons learned from the PMTCT program in Swaziland: challenges with accepting lifelong ART for pregnant and lactating women - a qualitative study.

BACKGROUND: Swaziland has one of the highest HIV prevalence rates in sub-Saharan Africa, 26 % of the adult population is infected with HIV. The prevalence is highest among pregnant women, at 41.1 %. According to Swaziland's prevention of mother-to-child transmission (PMTCT) guidelines, approximately 50 % of pregnant women are eligible for antiretroviral therapy (ART) by CD4 criteria (<350 cells/ml). Studies have shown that most mother-to-child transmission and postnatal deaths occur among women who are eligible for ART. Therefore, ensuring that ART eligible women are initiated on ART is critical for PMTCT and for mother and baby survival. This study provides insight into the challenges of lifelong ART initiation among pregnant women under Option A in Swaziland. We believe that these challenges and lessons learned from initiating women on lifelong ART under Option A are relevant and important to consider during implementation of Option B+. METHODS: HIV-positive, treatment-eligible, postpartum women and nurses were recruited within maternal and child health (MCH) units using convenience and purposive sampling. Participants came from both urban and rural areas. Focus group discussions (FGDs) and structured interviews using a short answer questionnaire were conducted to gain an understanding of the challenges experienced when initiating lifelong ART. Seven FGDs (of 5-11 participants) were conducted, four FGDs with nurses, two FGDs with women who initiated ART, and one FGD with women who did not initiate ART. A total of 83 interviews were conducted; 50 with women who initiated ART and 33 with women who did not initiate. Data collection with the women was conducted in the local language of SiSwati and data collection with the nurses was done in English. FGDs were audio-recorded and simultaneously transcribed and translated into English. Analysis was conducted using thematic analysis. Transcripts were coded by two researchers in the qualitative software program MAXqda v.10. Thematic findings were illustrated using verbatim quotes which were selected on the basis of being representative of a specific theme. The short-answer interview questionnaire included specific questions about the different steps in the woman's experience initiating ART; therefore the responses for each question were analyzed separately. RESULTS: Findings from the study highlight women feeling overwhelmed by the lifetime commitment of ART, feeling "healthy" when asked to initiate ART, preference for short-course prophylaxis and fear of side effects (body changes). Also, the preference for nurses to determine on an individual basis the number of counseling appointments a woman needs before initiating ART, more information about HIV and ART needed at the community level, and the need to educate men about HIV and ART. CONCLUSION: Women face a myriad of challenges initiating lifelong ART. Understanding women's concerns will aid in developing effective counseling messages, designing appropriate counseling structures, understanding where additional support is needed in the process of initiating ART, and knowing who to target for community level messages.

A novel vaccine strategy against Brucellosis using Brucella abortus multi-epitope OMPs vaccine based on Lactococcus lactis live bacterial vectors.

Brucella infections typically occur in mucosal membranes, emphasizing the need for mucosal vaccinations. This study evaluated the effectiveness of orally administering Lactococcus lactis (L. lactis) for producing the Brucella abortus multi-epitope OMPs peptide. A multi-epitope plasmid was generated through a reverse vaccinology method, and mice were administered the genetically modified L. lactis orally as a vaccine. The plasmid underwent digestion, synthesizing a 39 kDa-sized protein known as OMPs by the target group. The sera of mice that were administered the pNZ8124-OMPs-L. lactis vaccine exhibited a notable presence of IgG1 antibodies specific to outer membrane proteins (OMPs), heightened levels of interferon (IFN-λ) and tumor necrosis factor alpha (TNF-α), and enhanced transcription rates of interleukin 4 (IL-4) and interleukin 10 (IL-10). The spleen sections from the pNZ8124-OMPs-L. lactis and IRIBA group had less morphological damage associated with inflammation, infiltration of lymphocytes, and lesions to the spleen. The findings present a novel approach to utilizing the food-grade, non-pathogenic L. lactis as a protein cell factory to synthesize innovative immunological candidate OMPs. This approach offers a distinctive way to evaluate experimental medicinal items' practicality, safety, affordability, and long-term sustainability.