Acid Etching's Effect on Hypomineralized Teeth's Bond Strength and Enamel Surface Structure.

The current study evaluated the bracket bond strength of hypomineralized teeth with and without acid etching. Twenty premolar teeth extracted for orthodontic purposes were used in this study. Hypomineralization was induced in all experimental teeth using a cariogenic solution. Then the teeth were divided into two groups. In the first group, orthodontic brackets were bonded by orthodontic adhesive (Green Gloo, Ormco, USA) without etching, while in the second group, further etching was used before bonding. All specimens were examined for morphological changes in the enamel surface after demineralization and debonding using a scanning electron microscope. The shear bond strength was also measured, and the recorded values of bond strengths were collected and statistically analyzed. All massed results were statistically evaluated via an independent t-test to equate Group 1 (G1) and Group 2 (G2). A p-value of < 0.05 is deemed to be statistically substantial. The shear bond strength of groups interacted by orthodontic adhesive with etching (Group 2) was considerably greater than that of groups bonded by orthodontic adhesive without etching. The etching indicates considerably greater tackiness rates compared to bonding without etching, although it leaves more destructed cores, which may need further treatment.

Response of Purslane Plants Grown under Salinity Stress and Biostimulant Formulations.

Purslane has been suggested as an alternative crop suitable for human consumption due to its high content of minerals, omega-3 fatty acids, and several health-beneficial compounds. In this study, we aimed to evaluate the effect of salinity stress (tap water (control), 2000, 4000, 6000, 8000, and 10,000 mg L-1), biostimulant application (putrescine and salicylic acid at 200 mg L-1), and the combination of the tested factors (i.e., salinity × biostimulant application) on the growth and chemical composition of purslane plants (Portulaca oleracea L.) over two growing seasons (2022 and 2023). Irrigation with tap water and putrescine application resulted in the highest plant height, weight of aboveground and underground parts, and number of shoots per plant. In contrast, the lowest values of growing parameters were recorded under severe saline stress (10,000 mg L-1), especially for the plants that were not treated with biostimulants. The same trends were observed for macronutrients (N, P, K), total carbohydrates, total chlorophylls, and vitamin C content in leaves. Moreover, nitrate and proline content was higher in plants grown under salinity stress, especially under severe stress (8000-10,000 mg L-1) without biostimulant application. In general, the application of biostimulants mitigated the negative impact of salinity on plant growth and leaf chemical composition, while the effect of putrescine on the tested parameters was more beneficial than that of salicylic acid. In conclusion, this study provides useful information regarding the use of putrescine and salicylic acid as biostimulatory agents with the aim of increasing purslane growth under salinity conditions.

Novel 3-substituted coumarins inspire a custom pharmacology prediction pipeline: an anticancer discovery adventure.

Aim: This research aims to expand the established pharmacological space of tumor-associated carbonic anhydrases (TACAs) by exploring the synthetically accessible chemical space of 3-substituted coumarins, with the help of in silico pharmacology prediction.Materials & methods: 52 novel 3-substituted coumarins were sketched, prioritizing synthetic feasibility. Their pharmacological potentials were estimated using a custom machine-learning approach. 17 compounds were predicted as cytotoxic against HeLa cells by interfering with TACAs. Those compounds were synthesized and biologically tested against HeLa cells. The three most potent compounds were assayed against multiple carbonic anhydrases, and their enzyme binding mechanism(s) were studied using molecular docking.Results: Experimental results exhibited pronounced consensus with in silico pharmacology predictions.Conclusion: Novel 3-substituted coumarins are herein dispatched to the cancer therapeutics space.

[Box: see text].

Breast self-examination knowledge, attitude, and practice among Jazan women, Kingdom of Saudi Arabia

Breast cancer is the most common cancer among women worldwide. It is a major cause of cancer death, and its incidence rate has been gradually increasing in the Arab world, Saudi Arabia has a higher proportion of young females getting breast cancer than other countries. This study was conducted to investigate the knowledge, attitude, and practice regarding breast self-examination among females from 20 to 60 years old in Jazan Region, Saudi Arabia. Using A Community-based descriptive cross-sectional approach, data were gathered from 567 Saudi and non-Saudi women using structured interviews and then analyzed using the Statistical Package for Social Sciences (IBM) version 21.0 software program. Where the study indicated that around half of the participants (55.7%) had good total knowledge scores regarding breast self-examination, and most had positive attitudes. However, only 205 (36.2%) respondents practice it regularly. Moreover, the study reveals a significant association between respondents' knowledge and attitudes toward breast self-examination (P = 0.05). These findings indicate moderate knowledge, poor breast self-examination practices, and a significant association between knowledge and attitudes. Therefore, conducting health education programs is necessary to raise awareness about breast self-examination (BSE) among Jazan women.

Le cancer du sein est le cancer le plus répandu chez les femmes dans le monde. Il s'agit d'une cause majeure de décès par cancer et son taux d'incidence augmente progressivement dans le monde arabe. L'Arabie saoudite compte une proportion plus élevée de jeunes femmes atteintes d'un cancer du sein que les autres pays. Cette étude a été menée pour étudier les connaissances, l'attitude et la pratique concernant l'auto-examen des seins chez les femmes de 20 à 60 ans dans la région de Jazan, en Arabie Saoudite. À l'aide d'une approche transversale descriptive communautaire, les données ont été recueillies auprès de 567 femmes saoudiennes et non saoudiennes à l'aide d'entretiens structurés, puis analysées à l'aide du logiciel Statistical Package for Social Sciences (IBM) version 21.0. L'étude a indiqué qu'environ la moitié des participantes (55,7 %) avaient de bons scores totaux de connaissances concernant l'auto-examen des seins et que la plupart avaient des attitudes positives. Cependant, seuls 205 (36,2%) répondants le pratiquent régulièrement. De plus, l'étude révèle une association significative entre les connaissances et les attitudes des répondants à l'égard de l'auto-examen des seins (P = 0,05). Ces résultats indiquent des connaissances modérées, de mauvaises pratiques d'auto-examen des seins et une association significative entre les connaissances et les attitudes. Par conséquent, il est nécessaire de mener des programmes d'éducation sanitaire pour sensibiliser les femmes de Jazan à l'auto-examen des seins (ESB).

Effect of Slow Maxillary Expansion and Alternative Rapid Maxillary Expansion Protocols on Airway Volume in Cleft Palate Cases: A Cone Beam Computed Tomography Based Study.

A total of 22 patients with cleft palate aged 8 to 12 years were selected and categorized into two groups: the first group was treated with alternate rapid maxillary expansion and constriction (Alt-RAMEC) using an expander with differential opening (EDO) and facemask, while the second group was treated using slow maxillary expansion (SME) using an EDO. Finally, the pharyngeal airway volume in the two groups was compared using cone beam computed tomography (CBCT). CBCT scans were performed before expansion and six months following the expansion. Alveolar crest level, maxillary breadth, nasal cavity width, arch width, inclination of the molar teeth, buccal and palatal alveolar bone thickness, and maxillary alveolar width were all assessed. Paired t-tests (p=0.05) were applied to compare interphase data. The two groups showed a non-significant difference in terms of nasopharyngeal volume (cm3), oropharyngeal volume (cm3), and overall pre- and post-treatment results (p>0.005). Results of comparison of pre- and post-treatment periods in the Alt-RAMEC group revealed a significantly higher cleft volume (cm3) (p=0.001). Results of comparison of pre- and post-treatment periods in the SME group revealed a substantial rise in cleft volume (cm3) (p=0.003). Results from a comparison of the cleft volume (cm3) between the two study groups pre- and post-intervention revealed a non-significant difference (p=0.200 and 0.054, respectively).

A novel approach of using Maca root as a radioprotector in a rat testicular damage model focusing on GRP78/CHOP/Caspase-3 pathway.

PURPOSE: Despite the effectiveness of ionizing radiation in treating cancer, it can damage healthy tissues in the vicinity. Due to the high radio-sensitivity of testicular tissues, radiation therapy may affect spermatogenesis, which may result in infertility. Hence, in this study testicular damage model is constructed to investigate the mitigation effect of Maca root powder and its potential radioprotective activity through both oxidative and endoplasmic reticulum (ER) stresses, besides the apoptotic pathway. METHODS: Male albino rats were exposed to 6Gy of whole-body gamma radiation single dose. Maca root powder (1 g/kg b.wt./day, by oral gavage) was administered for a week before irradiation, then d-galactose (300 mg/kg, by oral gavage) and Maca daily for another week. RESULTS: Gamma radiation and d-galactose revealed a significant decrease in serum testosterone, sperm count, and motility and higher percentage of the sperm head abnormality, while Maca root treatment maintained all sperm morphology parameters. Maca root treatment demonstrated a notable defense against radiation-induced oxidative stress and ameliorated malonaldehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), glutathione-S-transferase (GST) levels, reduced glutathione (GSH), oxidized glutathione (GSSG) and the ratio of GSH/GSSG in testis tissues. Exposure to gamma rays and d-galactose displayed a significant elevation in GRP78, CHOP, total caspase-3 as well as active (cleaved) caspase-3 levels, whereas treatment with Maca significantly reduced the ER and apoptotic markers levels. Also, Maca improved the histological changes of the disorganized seminiferous tubules induced by irradiation. CONCLUSION: Our findings show for the first time that Maca has a protective effect on male reproductive damage induced by radiotherapy. Maca root reveals anti-apoptotic effect and protection against testicular damage via GRP78/CHOP/caspase-3 pathway.

Perceived Social Stigma of Cutaneous Leishmaniasis in Hubuna, Saudi Arabia.

Background: Cutaneous Leishmaniasis (CL) is a vector-borne skin infection that remains prevalent in regions with poor socioeconomic conditions. Stigmatization occurs when individuals with physical or psychological disorders interact with societal stereotypes. The aim of this study was to explore the perceived social stigma surrounding CL among people residing in Hubuna, Saudi Arabia. Methods: This cross-sectional community-based survey recruited 618 individuals aged 18 years and above using the snowball sampling technique to reach hidden cases within the target population. Data was collected using a self-administered questionnaire and the Explanatory Model Interview Catalogue for Perceived Social Stigma (EMIC-SS-12) was used to assess the level of perceived social stigma. It includes questions on demographic variables, behaviors, and experiences. The analysis was performed using SPSS. Results: The study included 618 participants, the majority of whom were women and girls (54.2%), with a mean age of 28 ± 12.7 years. The median score for perceived social stigma was 26.0. Only 2.1% (n = 13) of participants had the highest EMIC-SS-12 score of 36, while 7.6% (n = 47) scored zero. The mean score for overall perceived social stigma was 1.89 ± 0.91, while the mean score for experienced stigma was 1.99 ± 1.02. Univariate analysis showed that sex, employment, location of lesions, and number of lesions were insignificantly associated with stigmatization (P-value < 0.05), because these associations were uncertain because the CI includes or very close to 1. Conclusion: The study reveals insights into stigmatization associated with CL in the Habuna area of Saudi Arabia. It found that the median of perceived social stigma was 26. Factors such as sex, employment status, and location of the lesion are uncertainly associated with stigma. It is crucial to explore negative behaviors and perceptions and develop suitable health education programs.

Ameliorative effect of zinc oxide-chitosan conjugates on the anticancer activity of cisplatin: Approach for breast cancer treatment.

Breast cancer is the second most prevalent cancer affecting both males and females, comprising nearly 30 % of all cancer cases. While chemotherapeutic agents, such as cisplatin (Cis), have proven successful in cancer treatment, concerns persist regarding their efficacy and the potentially dangerous side effects. Consequently, there is a crucial and ongoing need to develop approaches that minimize side effects associated with chemotherapy. In the present work, various types of nanoparticles (NPs) were synthesized and loaded with Cis. Cis was conjugated with nanocarriers such as zinc oxide (ZnO), ZnO modified with mandelic acid and graphene oxide (GO), chitosan (CS), and CS modified with ZnO and GO to enhance the selectivity of Cis towards cancer cells. Zeta potentials and particles size were assessed using electrophoretic light scattering and dynamic light scattering. NPs were characterized using transmission electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction. The impact of standalone Cis as well as its nanoconjugated form on the behavior of MCF-7 cell line was investigated using WST-1 cell proliferation and apoptosis/necrosis assays. Experimental findings revealed that among the various NPs tested, ZnO, and CS NPs exhibited the highest loading percentage of Cis, surpassing the loading percentages achieved with other NPs. Cytotoxicity assay showed the enhanced effect of Cis when conjugated with ZnO and CS NPs. Flow cytometry-based assays and confocal microscopy confirmed that ZnO/Cis and CS/Cis induced apoptosis. The cisplatin-nanocomplex exhibited a descending order of early apoptosis and late apoptosis in the following order: ZnO, Cis, CS, ZnO-M, CS-GO, ZnO-GO, CS-ZnO, and CS-ZnO, Cis, CS, CS-GO, ZnO-M, ZnO, ZnO-GO, respectively. None of the nanoparticle complexes displayed a significant percentage of necrotic cells, with the highest percentage reaching 4.65 % in the case of CS-GO/Cis.

Spermatozoa in mice lacking the nucleoporin NUP210L show defects in head shape and motility but not in nuclear compaction or histone replacement.

Biallelic loss-of-function mutation of NUP210L, encoding a testis-specific nucleoporin, has been reported in an infertile man whose spermatozoa show uncondensed heads and histone retention. Mice with a homozygous transgene intronic insertion in Nup210l were infertile but spermatozoa had condensed heads. Expression from this insertion allele is undefined, however, and residual NUP210L production could underlie the milder phenotype. To resolve this issue, we have created Nup210lem1Mjmm , a null allele of Nup210l, in the mouse. Nup210lem1Mjmm homozygotes show uniform mild anomalies of sperm head morphology and decreased motility, but nuclear compaction and histone removal appear unaffected. Thus, our mouse model does not support that NUP210L loss alone blocks spermatid nuclear compaction. Re-analyzing the patient's exome data, we identified a rare, potentially pathogenic, heterozygous variant in nucleoporin gene NUP153 (p.Pro485Leu), and showed that, in mouse and human, NUP210L and NUP153 colocalize at the caudal nuclear pole in elongating spermatids and spermatozoa. Unexpectedly, in round spermatids, NUP210L and NUP153 localisation differs between mouse (nucleoplasm) and human (nuclear periphery). Our data suggest two explanations for the increased phenotypic severity associated with NUP210L loss in human compared to mouse: a genetic variant in human NUP153 (p.Pro485Leu), and inter-species divergence in nuclear pore function in round spermatids.

Pleural effusion due to lymphangiomatosis and the role of sirolimus: A case report.

Introduction: Lymphangiomatosis is a rare abnormal proliferation of lymphatic vessels involving multiple organs like the brain, lung, heart, spleen, liver, and bones. Lymphangiomas constitute 5.6% of all benign tumors in infancy and adulthood. Case presentation: We report a case of a young lady who presented with constitutional symptoms and progressive dyspnea. Her medical history is significant for muco-cutaneous albinism, diffuse hemangiomas of the bone and viscera, and consumptive coagulopathy status post-splenectomy. After initial investigations, she was found to have right-sided pleural effusion. Pleural fluid analysis indicated chylothorax. She had multiple drainages of the pleural fluid done, and afterward, ligation of the right thoracic duct was performed with a trial of sirolimus, which improved her chylothorax. Clinical discussion: Several case reports have reported positive outcomes with sirolimus in the treatment of lymphangiomatosis. However, larger controlled studies are needed to confirm these findings. Conclusion: Sirolimus is promising as a medical treatment for diffuse pulmonary lymphangiomatosis.

Targeting of HPV E6 at the binding sites to the host-cell E6AP, p53, and the endoplasmic reticulum-resident chaperone, GRP78.

Background: Human papillomavirus (HPV) represents an etiological factor for many cancer types, especially cervical cancer. Its oncoprotein E6 sheds drug designers who aim to stop its cellular protein associations, such as p53 and E6AP. Recently, it was discovered that the host-cell chaperone glucose-regulated protein 78 (GRP78) plays a crucial function in HPV infectivity by association with the viral E6 and E7 proteins. Therefore, we aimed to test small molecules inhibitor that could contradict the association between E6 and cellular factors E6AP, GRP78, and p53. Methods: In this study, molecular docking protocol was elaborated to test 115 small molecule compounds against the three binding sites of HPV E6 to the host-cell proteins; E6AP, p53, and GRP78. After that, molecular dynamics simulation and free energy calculations were performed on the best three complexes. Results: The results reveal the potency of 18 compounds against the HPV E6 at different binding sites, which give lower free energies than paclitaxel (positive control). The best two compounds, hypericin, and anabsinthin, could bind effectively and stably during the 100 ns MD simulation period to HPV E6. The calculated average free energies for hypericin and anabsinthin are -18.76 and -14.40 kcal/mol, respectively. They formed stable complexes with the three binding sites by forming hydrophobic contacts. The key residues that stabilize the two ligands in HPV E6 binding sites are V31, Y32, V62, and Y70 (E6AP), P13, C16, T22, I23 and A46 (p53), and M1, V31, L50, L67, and Q107 (GRP78). Conclusions: The best two compounds, hypericin, and anabsinthin, are potential candidates against HPV E6 at the host-cell factors binding sites, hence could block the oncoprotein activity of E6 in infected cells. Further experimental validation is yet to be performed and suggested as future work.Communicated by Ramaswamy H. Sarma.

A systematic review and meta-analysis on the efficacy and safety of the Baska mask versus other laryngeal mask airways during general anaesthesia.

BACKGROUND: The Baska mask is a supraglottic airway device used during general anaesthesia that combines features from various other devices. This systematic review aims to compare its efficacy and safety with other laryngeal mask airways. METHODS: Randomised controlled trials were identified by searching PubMed, Scopus, Web of Science and Cochrane Library. RevMan software was used for meta-analysis, with mean difference and risk ratios calculated for continuous and dichotomous data, respectively, along with a 95% confidence interval. RESULTS: The meta-analysis found that the Baska mask provides a better oropharyngeal seal pressure (mean difference = 7.03; 95% confidence interval = [6.00, 8.07], p < 0.00001) and a higher rate of maximal seal pressure (risk ratio = 18.38; 95% confidence interval = [2.53, 133.47], p = 0.004) compared to other laryngeal mask airways. However, the Baska mask had lower success rates in first-attempt insertion (risk ratio = 0.79; 95% confidence interval = [0.72, 0.86], p < 0.00001) and higher rates of insertion manipulation (risk ratio = 16.64; 95% confidence interval = [5.86, 47.24], p < 0.00001). CONCLUSION: The Baska mask offers better oropharyngeal seal pressure, but may be more difficult to insert than other laryngeal mask airways, without causing significant delays. The Baska mask appears as safe as other laryngeal mask airways, but larger trials are needed to support these findings.

Parental health-seeking behavior on self-medication, antibiotic use, and antimicrobial resistance in children.

Aim and Objectives: The study sought to identify parental trends in children's self-medication, health-seeking behavior, knowledge of self-medication, antibiotic use, and antimicrobial resistance in Asir, Saudi Arabia. Methods: A web-based cross-sectional study was carried out by a survey questionnaire. Snow Ball sampling technique was used to select the Eight hundred and sixteen parents with children in the Asir region by WhatsApp and email, and 650 participants who met the inclusion criteria consented to participate in the study. Results: There were 1809 episodes of childhood illnesses reported during the study period. The mean scores are on knowledge at 8.11 ±â€¯2.43, favorable attitude at 17.60 ±â€¯1.17, and practice was 7.72 ±â€¯1.72, and a significant correlation was found between knowledge, attitude, and practice (KAP) at p = 0.01. Out of 624, the majority of parents showed strong knowledge and proficiency in antibiotics. However, the attitude scores of over 50% towards the usage of antibiotics were subpar. Around 54% of parents were self-medicating their children and 43% were unaware that skipping doses contributes to anti-microbial resistance (AMR). The facilitators for self-medication were male gender (aOR: 2.13; 95% CI: 1.26-3.98, p < 0.05), having more children (aOR: 2.78; 95% CI: 1.27-4.12 p < 0.01), professional qualification (aOR:3.07; 95% CI 1.57- 4.68; p < 0.01), residing in urban area (aOR: 3.17; 95% CI: 2.13-5.61, p < 0.05), working in health care (aOR: 5.99; 95% CI: 1.78-18.2, p < 0.01) and high income (aOR: 3.57; 95% CI: 2.08-6.34, p < 0.05). Conclusions: The findings indicated that the majority of parents had unfavorable views and improper practices of antibiotic usage. Strategic education programs to the targeted population, especially to the parents about side effects of antibiotics, dangerous consequences of self-medication, and crucial AMR concerns must be addressed immediately.

The Association Between Periodontal Disease and Chronic Migraine: A Systematic Review.

Migraine is a neurologic illness that produces intense throbbing pain on one side of the head and affects roughly 1 billion people worldwide. Recent research indicates a relationship between periodontitis and chronic migraines. This study aimed to review the association between chronic migraines and periodontitis through a systematic literature review. Four research databases (Google Scholar, PubMed, ProQuest, and SpringerLink) were searched according to PRISMA guidelines to retrieve the studies included in this review. A search strategy was developed to answer the study question with appropriate inclusion and exclusion criteria. Out of 34 published studies, 8 studies were included in this review. Three of the studies were cross-sectional, 3 were case-control, and 2 were clinical report and medical hypothesis papers. Seven of the 8 included studies showed that there is an association between periodontal disease and chronic migraine. The elevated blood levels of some biomarkers such as leptins, ProCalcitonin (proCT), calcitonin gene-related peptides (CGRPs), Pentraxin 3 (PTX3), and Soluble Tumor Necrosis Factor-like Weak Inducer Of Apoptosis (sTWEAK) play a significant role in this association. The limitations include a small sample size, the influence of anti-inflammatory drugs, and a self-reported headache measure that is subject to misclassification bias. This systematic review reveals a supposed correlation between periodontal disease and chronic migraine, as evidenced by various biomarkers and inflammatory mediators. This suggests that periodontal disease could potentially contribute to the development of chronic migraine. However, to further assess the potential benefits of periodontal treatment in patients with chronic migraine, additional longitudinal studies with larger sample sizes and interventional studies are needed.

Home Management and Prevention of Vaso-Occlusive Crisis of Sickle Cell Disease Knowledge among Nursing Students.

Sickle cell crisis, or vaso-occlusive crisis, is a painful complication of sickle cell disease that occurs in adolescents and adults, which is considered the most common reason these patients seek medical attention in an emergency room. Despite the high prevalence of sickle cell disease in the Jazan region, Saudi Arabia, there hasn't been a study looking at nursing students' knowledge about sickle cell disease and home management and prevention of vaso-occlusive crises associated with sickle cell disease. Most of those focused on the investigation of the public, parents of children with sickle cell disease, school students, and patients with sickle cell disease. Therefore, this study aims to assess the level of knowledge about home management and prevention of vaso-occlusive crises among Saudi nursing students at the Aldayer University College, Jazan University, Kingdom of Saudi Arabia. A descriptive cross-sectional design was used in this study that involved 167 nursing students. The study revealed that Aldayer nursing students had adequate knowledge about the home management and prevention of sickle cell disease vaso-occlusive crises.

Cross-Talk between Mucosal-Associated Invariant T, Natural Killer, and Natural Killer T Cell Populations is Implicated in the Pathogenesis of Placenta Accreta Spectrum.

The study included 32 women with PAS and 20 with normally implanted placenta as a control group. Vascular endothelial cell growth factor (VEGF), Soluble FMS Like Tyrosine Kinase (sFLT-1/sVEGFR1), and Endoglin (ENG) were measured in placenta tissue by ELISA. Granzyme B (GrzB) expression in trophoblastic and stromal mesenchymal cells was evaluated by immunohistochemistry. MAIT, NK, and NKT cells were assessed in blood and placenta by flow cytometry. Alterations were observed in levels of MAIT cells, NK cell subsets, and NKT cells in patients compared with controls. Several significant correlations were detected between these cells and GrzB scores, VEGF, ENG, and sFLT-1 levels. This is the first study analysing these cells in PAS patients and correlating their levels with changes in some angiogenic and antiangiogenic factors implicated in trophoblast invasion and with GrzB distribution in trophoblast and stroma. Interrelation between these cells probably plays an important role in pathogenesis of PAS.

Cutaneous Leishmaniasis: Associated Risk Factors and Prevention in Hubuna, Najran, Saudi Arabia.

Background: Many countries are currently affected by leishmaniasis, and cutaneous leishmaniasis is ranked among the ten most neglected diseases. The aim of this study was to determine the risk factors related to cutaneous leishmaniasis and preventive measures among people living in Hubuna, Najran, Saudi Arabia. Methods: A community-based cross-sectional survey was conducted from January to October 2022. A convenience sampling technique was used, with 396 individuals invited to participate in the current study and 391 included. A self-administered questionnaire was utilized for collecting data. Descriptive analysis was used for risk factors and preventive measures, while χ2 tests were used for determining associations with risk factors. Results: Among participants, 38.1% (n=149) reported having cutaneous leishmaniasis clinically diagnosed and under treatment. Age 0-10 years was found to be associated significantly with cutaneous leishmaniasis infection (AOR 3.08, 95% CI 1.6-6.4; P=0.002) compared to other groups. A significant association was noted too for those residing in/around planted areas versus those who were not (AOR 1.18, 95% CI 0.13-2.24; P<0.001). In terms of occupation, farming was significantly associated with cutaneous leishmaniasis (AOR 2.54, 95% CI 1.15-3.76; P=0.010). No significant associations were observed in regard to sex (AOR 1.4, 95% CI 0.7-1.6; P=0.11), education (P=0.072), or preventive measures used (P>0.05). Conclusion: The cutaneous leishmaniasis endemicity level in Hubuna was high. Several socioeconomic and environmental factors contribute enormously to the spread of the disease in the area. Further investigation of risk factors of cutaneous leishmaniasis all over the country and setting up appropriate interventions to prevent its spread are recommended.

Cardioprotective and renoprotective effects of venlafaxine on cisplatin-induced cardiotoxicity and nephrotoxicity in rats.

AIM: The current work aims to demonstrate the potential defensive function of venlafaxine (VLF) in cardiotoxicity and nephrotoxicity caused by cisplatin (CP), that could be by modulating extracellular signal-regulated kinase (ERK)1/2 and nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase NOX4 pathways. MAIN METHODS: Five groups of rats were used, as follow: three control groups (control, carboxymethyl cellulose, and VLF), CP group got CP once (7 mg/kg, intraperitoneally, i.p.), and (CP+ VLF) group got CP once then after 1 h they got VLF {50 mg/kg daily, orally for 14 days}. At the end of the study; electrocardiogram (ECG) was recorded for anaesthized rats then blood samples and tissues were taken for biochemical and histopathological investigations. Caspase 3, a marker of cellular damage and apoptosis was detected by immunohistochemistry. KEY FINDINGS: CP treatment significantly impaired cardiac functions as evidenced by changes in rats' ECG. Cardiac enzymes, renal markers and inflammatory markers were increased with decreased activities of the total antioxidant capacity, superoxide dismutase and glutathione peroxidase. Also, ERK1/2 and NOX4 were upregulated with histopathological and immunohistochemical alterations of heart and kidney. While, VLF markedly alleviated CP-induced functional cardiac abnormalities and improved ECG pattern. It reduced both cardiac and renal biomarkers, oxidative stress, proinflammatory cytokine with ERK1/2 and NOX4 downregulation, improved the histopathological and immunohistochemical changes induced by cisplatin in heart and kidney. SIGNIFICANCE: VLF treatment impedes cardiotoxicity and nephrotoxicity caused by CP. This beneficial effect was mediated through reduction of oxidative stress, inflammation, and apoptosis by targeting the ERK1/2 and NOX4.

Anti-breast cancer drugs targeting cell-surface glucose-regulated protein 78: a drug repositioning in silico study.

Breast cancer (BC) is prevalent worldwide and is a leading cause of death among women. However, cell-surface glucose-regulated protein 78 (cs-GRP78) is overexpressed in several types of cancer and during pathogen infections. This study examines two well-known BC drugs approved by the FDA as BC treatments to GRP78. The first type consists of inhibitors of cyclin-based kinases 4/6, including abemaciclib, palbociclib, ribociclib, and dinaciclib. In addition, tunicamycin, and doxorubicin, which are among the most effective anticancer drugs for early and late-stage BC, are tested against GRP78. As (-)-epiGallocatechin gallate inhibits GRP78, it is also being evaluated (used as positive control). Thus, using molecular dynamics simulation approaches, this study aims to examine the advantages of targeting GRP78, which represents a promising cancer therapy regime. In light of recent advances in computational drug response prediction models, this study aimed to examine the benefits of GRP78 targeting, which represents a promising cancer therapy regime, by utilizing combined molecular docking and molecular dynamics simulation approaches. The simulated protein (50 ns) was docked with the drugs, then a second round of dynamics simulation was performed for 100 ns. After that, the binding free energies were calculated from 30 to 100 ns for each complex during the simulation period. These findings demonstrate the efficacy of abemaciclib, ribociclib, and tunicamycin in binding to the nucleotide-binding domain of the GRP78, paving the way for elucidating the mode of interactions between these drugs and cancer (and other stressed) cells that overexpress GRP78.Communicated by Ramaswamy H. Sarma.

Acute toxic effects of new synthetic cannabinoid on brain: Neurobehavioral and Histological: Preclinical studies.

The psychoactive effects of new synthetic cannabinoids (SCs), MDMB-4en-PINACA, are being marketed as a blend of herbs and spices. This study aims to determine the behavioral, neurochemical, histopathological, and immunohistochemical alterations associated with the acute toxicity of MDMB-4en-PINACA compounds. METHODS: Adult male albino rats were administered various toxic doses of the drug (1.5, 3, and 6 mg/kg), and behavioral studies were conducted 2 and 24 h later; animals were then sacrificed. Histopathological and neurochemical examinations were performed. Two hours after intraperitoneal. RESULTS: Intraperitoneal injection of MDMB-4en-PINACA, horizontal movement, the number of stops, and mobility ratio were significantly impaired, along with coordination and balance. In addition, it led to a decline in spatial learning and memory, and neurotransmitter concentrations decreased significantly in a dose-dependent manner. Further examination of the cerebral cortex and hippocampus histopathology revealed pathological degeneration of small pyramidal cells. CONCLUSION: Thus, these findings revealed that MDMB-4en-PINACA interferes with hippocampal function and impairs cognitive performance, highlighting the cognitive risk associated with SC abuse.