Modulation of GABA by sodium butyrate ameliorates hypothalamic inflammation in experimental model of PCOS.

Polycystic ovarian syndrome (PCOS) is a known endocrine disorder that has affected many women of childbearing age, and is accompanied by various neurodegenerative conditions. Hence, this study investigates the impact of butyrate in reversing hypothalamic-related disorder, possibly through γ aminobutyric acid (GABA) in a rat model of PCOS. Eight-week-old female Wistar rats were allotted into four groups (n = 5), which include control, butyrate, letrozole, and letrozole + butyrate groups. PCOS was induced by administering 1 mg/kg of letrozole (oral gavage) for 21 days. After confirmation of PCOS, 200 mg/kg of butyrate (oral gavage) was administered for 6 weeks. Rats with PCOS were characterized by elevated levels of plasma insulin and testosterone. Increases in plasma and hypothalamic triglyceride levels, inflammatory biomarker (SDF-1), apoptotic marker (caspase-6), and decreased plasma GnRH were observed. Additionally, a decrease in hypothalamic GABA was revealed. Nevertheless, the administration of butyrate attenuated these alterations. The present study suggests that butyrate ameliorates hypothalamic inflammation in an experimental model of PCOS, a beneficial effect that is accompanied by enhanced GABA production.

Silver(I) pyridinyl complexes with benzothiazole, thiophene, and furan moieties: DNA/protein-binding, antibacterial, antioxidant, and anticancer studies.

We have synthesized and characterized nine Ag(I) complexes of Schiff bases containing thiophene, furan, and pyridine moieties for in vitro antibacterial, antioxidant, anticancer activities, and DNA/bovine serum albumin (BSA) binding studies. Based on the analytical and spectral analyses, a linear geometry was proposed for all the Ag(I) complexes, except for one (with the furan moiety), which formed a distorted T-shaped geometry. UV-vis absorption studies on the interactions of calf thymus-DNA (CT-DNA) with the nine Ag(I) complexes pointed to an intercalative binding mode. With a binding constant Kb of 3.75 × 105 M-1 , the complex bearing a benzothiazole moiety (1) interacted stronger with CT-DNA than the rest of the complexes. Fluorescence spectroscopic data revealed that the complexes had a modest binding affinity for BSA through static quenching. The complexes displayed good antioxidant properties, especially those with a benzothiazole moiety. Notable antibacterial activities against methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae were observed for complexes with the furan and thiophene moieties. The in vitro anticancer studies of selected complexes against three cancer cell lines showed that the complexes were more effective against the inhibition of the growth of cervical cancer cells relative to cisplatin.

A study of structure-activity relationship and anion-controlled quinolinyl Ag(I) complexes as antimicrobial and antioxidant agents as well as their interaction with macromolecules.

In this communication, we feature the synthesis and in-depth characterization of a series of silver(I) complexes obtained from the complexation of quinolin-4-yl Schiff base ligands ((E)-2-((quinolin-4-ylmethylene)amino)phenol La, 2-(quinolin-4-yl)benzo[d]thiazole Lb, (E)-N-(2-fluorophenyl)-1-(quinolin-4-yl)methanimine Lc, (E)-N-(4-chlorophenyl)-1-(quinolin-4-yl)methanimine Ld, (E)-1-(quinolin-4-yl)-N-(p-tolyl)methanimine Le, (E)-1-(quinolin-4-yl)-N-(thiophen-2-ylmethyl)methanimine Lf) and three different silver(I) anions (nitrate, perchlorate and triflate). Structurally, the complexes adopted different coordination geometries, which included distorted linear or distorted tetrahedral geometry. The complexes were evaluated in vitro for their potential antibacterial and antioxidant activities. In addition, their interactions with calf thymus-DNA (CT-DNA) and bovine serum albumin (BSA) were evaluated. All the complexes had a wide spectrum of effective antibacterial activity against gram-positive and gram-negative bacterial and good antioxidant properties. The interactions of the complexes with CT-DNA and BSA were observed to occur either through intercalation or through a minor groove binder, while the interaction of the complexes with BSA reveals that some of the complexes can strongly quench the fluorescence of BSA through the static mechanism. The molecular docking studies of the complexes were also done to further elucidate the modes of interaction with CT-DNA and BSA.

Low-dose spironolactone abates cardio-renal disorder by reduction of BAX/inflammasome expression in experimentally induced polycystic ovarian syndrome rat model.

The impact of low-dose spironolactone (LSPL) on polycystic ovarian syndrome (PCOS)-associated cardio-renal disorder is unknown. Therefore, the present study hypothesized that LSPL would ameliorate cardio-renal disorders in experimental PCOS animals. Eight-week-old female Wistar rats were allotted into three groups. The control group received vehicle (distilled water; per os (p.o.)), the letrozole (LET)-treated group designated as PCOS group received LET (1 mg/kg; p.o.), and PCOS+LSPL received LET and LSPL (0.25 mg/kg, p.o.). The treatment was done once daily for 21 days uninterrupted. The experimental PCOS rats were characterized with insulin resistance, as well as elevated testosterone and luteinizing hormone/follicle-stimulating hormone, with a significant increase in cardiac and renal lipid profile, oxidative stress, inflammatory biomarkers (nuclear factor-κB and tumor necrosis factor-α), lactate dehydrogenase and lactate content and decrease in cardiac and renal antioxidant system (glutathione peroxidase and reduced glutathione) compared with the control rats. In addition, immunohistochemical assessment of cardiac and renal tissue showed significant expression of inflammasome and B-cell lymphoma-2 associated X-protein (BAX) in animals with PCOS. Nevertheless, these perturbations were attenuated following the administration of LSPL. Collectively, the present results suggest that LSPL attenuates PCOS-associated cardio-renal disorders by reduction of oxidative stress and BAX/inflammasome expression.

Low dose spironolactone-mediated androgen-adiponectin modulation alleviates endocrine-metabolic disturbances in letrozole-induced PCOS.

Polycystic ovarian syndrome (PCOS), is a multifactorial endocrine disorder in women of reproductive age. It usually associates with metabolic disorders (MDs), which aggravates the risk of infertility, cardiometabolic events and associated comorbidities in women with PCOS. Adiponectin, a circulating protein produced by adipocytes, which has been suggested to inversely correlate with MDs. Spironolactone, a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. Herein, we investigated the effects of low dose spironolactone (LDS) and the role of adiponectin in endocrine-metabolic disturbances in experimentally-induced PCOS rats. Eighteen female Wistar rats (160-180 g) were randomly allotted into 3 groups and treated with vehicle (p.o.), letrozole (LET; 1 mg/kg) and LET + LDS (0.25 mg/kg), once daily for 21 days, respectively. The results showed that LET-treated animals had features of PCOS, characterized by elevated plasma testosterone and prolactin, increased body weight gain and ovarian weight as well as disrupted ovarian cytoarchitecture and degenerated follicles. Additionally, elevated fasting blood glucose, 1 h-postload glucose and plasma insulin, impaired glucose tolerance, insulin resistance, reduced insulin sensitivity, increased plasma and ovarian lipid profile, plasma lipid peroxidation, TNF-α, IL-6 and decreased plasma glutathione peroxidase and glutathione content were observed. These alterations were associated with decreased circulating adiponectin and were reversed when treated with LDS. The present results suggest that LDS ameliorates endocrine-metabolic disturbances and inflammation-related comorbidities associated with LET-induced PCOS by modulating circulating androgen-adiponectin status.

Quinoline Functionalized Schiff Base Silver (I) Complexes: Interactions with Biomolecules and In Vitro Cytotoxicity, Antioxidant and Antimicrobial Activities.

A series of fifteen silver (I) quinoline complexes Q1-Q15 have been synthesized and studied for their biological activities. Q1-Q15 were synthesized from the reactions of quinolinyl Schiff base derivatives L1-L5 (obtained by condensing 2-quinolinecarboxaldehyde with various aniline derivatives) with AgNO3, AgClO4 and AgCF3SO3. Q1-Q15 were characterized by various spectroscopic techniques and the structures of [Ag(L1)2]NO3Q1, [Ag(L1)2]ClO4Q6, [Ag(L2)2]ClO4Q7, [Ag(L2)2]CF3SO3Q12 and [Ag(L4)2]CF3SO3Q14 were unequivocally determined by single crystal X-ray diffraction analysis. In vitro antimicrobial tests against Gram-positive and Gram-negative bacteria revealed the influence of structure and anion on the complexes' moderate to excellent antibacterial activity. In vitro antioxidant activities of the complexes showed their good radical scavenging activity in ferric reducing antioxidant power (FRAP). Complexes with the fluorine substituent or the thiophene or benzothiazole moieties are more potent with IC50 between 0.95 and 2.22 mg/mL than the standard used, ascorbic acid (2.68 mg/mL). The compounds showed a strong binding affinity with calf thymus-DNA via an intercalation mode and protein through a static quenching mechanism. Cytotoxicity activity was examined against three carcinoma cell lines (HELA, MDA-MB231, and SHSY5Y). [Ag(L2)2]ClO4Q7 with a benzothiazole moiety and [Ag(L4)2]ClO4Q9 with a methyl substituent had excellent cytotoxicity against HELA cells.

The Epidemiology of Suicide and Suicidal Behaviour across the Lifespan in Nigeria: A Systematic Review of the Literature.

BACKGROUND/PURPOSE: Suicidal behaviour is a global public health issue affecting all ages, gender, and regions of the world. This systematic review sought to synthesize the available evidence on the prevalence and risk factors for suicide and suicidal behaviour across the lifespan in Nigeria. DATA SOURCE: The databases of PubMed, Embase, Medline, PsychInfo, Google Scholar and African Journals OnLine (AJOL). STUDY SELECTION: Literature on suicidal behaviour and suicide from Nigeria published between 2000 and 2019. DATA EXTRACTION: Data were extracted independently by two authors using a fixed template. RESULTS: The search identified 431 articles; 23 were eligible for inclusion. The 12-month prevalence of suicide ideation among adolescents was between 6.1-22.9% and 3-12.5% for attempts; identified risk factors were sexual abuse, family dysfunction and food insecurity. For the adult population, lifetime rates of suicidal ideation, plan and attempt were 3.2%, 1.0% and 0.7% respectively; risk factors included age (peak in the third decade of life), childhood adverse experiences and the presence of mood disorders. In the elderly the rates were 4.0% for ideation, 0.7% for plan and 0.2% for attempt. Risk factors identified in the elderly were being single (separation or widowhood) and rural residence. Suicides accounted for 0.3- 1.6% of autopsies performed by the coroners and constituted the least common cause of death. Suicides were more common in males and peaked in the third decade of life. CONCLUSION: Suicide and suicidal behaviour in the Nigerian population seem to peak in young adult life suggesting that suicide prevention initiatives should target late adolescence.

CONTEXTE/BUT: Le comportement suicidaire est un problème mondial de santé publique qui touche tous les âges, tous les sexes et toutes les régions du monde. Cet examen systématique visait à synthétiser les données probantes disponibles sur la prévalence et les facteurs de risque de suicide et de comportement suicidaire tout au long de la vie au Nigéria. SOURCE DE DONNEES: Les bases de données de PubMed, Embase, Medline, PsychInfo, Google Scholar et African Journals OnLine (AJOL). SELECTION DE L'ETUDE: Publication de la littérature sur les comportements suicidaires et le suicide au Nigéria entre 2000 et 2019. EXTRACTION DE DONNEES: Les données ont été extraites indépendamment par deux auteurs à l'aide d'un modèle fixe. RESULTATS: La recherche a permis d'identifier 431 articles; 23 étaient admissibles à l'inclusion. La prévalence sur 12 mois de l'idée de suicide chez les adolescents se situe entre 6,1 et 22,9 % et 3 à 12,5 % pour les tentatives; les facteurs de risque identifiés étaient la violence sexuelle, le dysfonctionnement familial et l'insécurité alimentaire. Pour la population adulte, les taux à vie d'idées, de planifier et de tenter suicidaires étaient de 3,2 %, 1,0 % et 0,7 % respectivement; les facteurs de risque comprenaient l'âge (sommet au cours de la troisième décennie de la vie), les expériences indésirables de l'enfance et la présence de troubles de l'humeur. Chez les personnes âgées, les taux étaient de 4,0 % pour l'idée, de 0,7 % pour le régime et de 0,2 % pour les tentatives. Les facteurs de risque identifiés chez les personnes âgées étaient état matrimonial célibataire (séparation ou veuvage) et la résidence rurale. Les suicides représentaient de 0,3 à 1,6 % des autopsies effectuées par les coroners et constituaient la cause de décès la moins fréquente. Les suicides étaient plus fréquents chez les hommes et ont atteint un sommet au cours de la troisième décennie de leur vie. CONCLUSION: Le suicide et les comportements suicidaires dans la population Nigériane semblent culminer chez les jeunes adultes, ce qui suggère que les initiatives de prévention du suicide devraient cibler la fin de l'adolescence. Mots-clés: Le suicide, comportements suicidaires, Les facteurs de risque, autopsies du coroner, la vie.

Pubertal Communication Between School Nurses and Adolescent Girls in Ile-Ife, Nigeria.

We examined information on pubertal changes provided by school nurses to adolescent girls, the methods, and media of communication. We also examined the challenges faced by the nurses in the course of communication. The study setting was five private high schools located in Ile-Ife, Nigeria. Participants were 10 school nurses and 420 school adolescent girls. Cross-sectional descriptive design was employed using quantitative and qualitative data collection methods. Results showed school nurses paid more attention to physical body changes, menarche, and menstrual hygiene as contents of pubertal communication rather than contraception, prevention of sexually transmitted infection, and teenage pregnancy prevention. Materials for communication were reportedly lacking in many of the schools while the school management censors pubertal information. Efforts should be tailored at equipping the school clinic with audiovisual aids and school nurses should be encouraged to give comprehensive pubertal education irrespective of their values and beliefs.

K-D:rib dampens Hs 578T cancer cell chemoinvasion and proliferation.

BACKGROUND: Cancer cells, even in the presence of available oxygen, have a glycolysis enhancement. The "aerobic glycolysis" is known as the Warburg effect and it is considered one of the fundamental hallmarks of metabolic alteration during malignant transformation. A feature of many tumors is also a change into ions equilibrium, with particular reference to K(+) intracellular concentration. Another hallmark in cancer is the reprogrammed chemotaxis pathways in favour of tumor cell dissemination. RESULTS: The doubling population time of 5 mM K:D-rib treated Hs 578T (HTB-126 ® ATCC) cell line is reduce by 30% respect to the control. During the chemotactic invasion assay, the relative number of motile and invasive cells, counted inside the FBS-AGAR spot, shows a decrease with the maintenance of the treatment reaching the 25% after nine days. Hs 578Bst (HTB-125 ® ATCC) non-tumor cell line treated for nineteen days with 5 mM K:D-rib was split twice as well as the control. No morphological change was visible in the treated respect to untreated cells. CONCLUSIONS: We demonstrate that the synergic action of potassium bicarbonate and D-ribose has effect on Hs 578T cancer cell line proliferation reducing the cell cycle time. At 5 mM concentration, K:D-rib is able to modify the tumorigenic potential of human breast cancer cell line Hs 578T, interfering in vitro with the capability of Hs 578 T cell line to migrate under chemotactic stimuli. Despite this, K:D-rib solution, does not exhibit any appreciable toxicity as confirmed by the proliferation assay accomplished on Hs 578Bst cell line.

In vitro studies on the sensitivity pattern of Plasmodium falciparum to anti-malarial drugs and local herbal extracts.

BACKGROUND: The resistance of human malaria parasites to anti-malarial compounds has become considerable concern, particularly in view of the shortage of novel classes of anti-malarial drugs. One way to prevent resistance is by using new compounds that are not based on existing synthetic antimicrobial agents. RESULTS: Sensitivity of 100 Plasmodium falciparum isolates to chloroquine, quinine, amodiaquine, mefloquine, sulphadoxine/pyrimethamine, artemisinin, Momordica charantia ('Ejirin') Diospyros monbuttensis ('Egun eja') and Morinda lucida ('Oruwo') was determined using the in vitro microtest (Mark III) technique to determine the IC50 of the drugs. All the isolates tested were sensitive to quinine, mefloquine and artesunate. Fifty-one percent of the isolates were resistant to chloroquine, 13% to amodiaquine and 5% to sulphadoxine/pyrimethamine. Highest resistance to chloroquine (68.9%) was recorded among isolates from Yewa zone while highest resistance to amodiaquine (30%) was observed in Ijebu zone. Highest resistance to sulphadoxine/pyrimethamine was recorded in Yewa and Egba zones, respectively. A positive correlation was observed between the responses to artemisinin and mefloquine (P<0.05), artemisinin and quinine (P<0.05) and quinine and mefloquine (P<0.05). A negative correlation was observed between the responses to chloroquine and mefloquine (P>0.05). Highest anti-plasmodial activity was obtained with the ethanolic extract of D. monbuttensis (IC50 = 3.2 nM) while the lowest was obtained from M. lucida (IC50 = 25 nM). CONCLUSIONS: Natural products isolated from plants used in traditional medicine, which have potent anti-plasmodial action in vitro, represent potential sources of new anti-malarial drugs.

Awareness of risk factors and warning signs of stroke in a Nigeria university.

BACKGROUND: Rapid access to medical services which is an important predictor of treatment and rehabilitation outcome requires that there is an understanding of stroke risk factors and early warning signs. This study assessed awareness of stroke risk factors and warning signs among students and staff of Obafemi Awolowo University, Nigeria. METHODS: This was a cross sectional survey involving 994 (500 students and 494 staff) respondents. Information on the awareness of stroke risk factors and warning signs was collected with the aid of a structured questionnaire. Descriptive and inferential statistics were used for data analysis. RESULTS: Weakness (66.2%) was the most commonly identified warning sign of stroke with more staff (69.8%) identifying correctly than students (62.6%). Hypertension (83.4%) was the most commonly identified stroke risk factor, with more staff (91.7%) identifying correctly than students (83.2%). There were significant differences (p < 0.05) in the awareness of some risk factors (age, hypertension, stress and obesity), and warning signs (dizziness, numbness, weakness, headache and vision problems) between students and staff. Predictors for adequate awareness of both stroke risk factors and warning signs were younger age, smoking history and higher educational level. CONCLUSIONS: Majority of the respondents recognized individual important stroke risk factors and warning signs, but few recognized multiple stroke risk factors and warning signs. Awareness programs on stroke should be organized, even in communities with educated people to increase public awareness on the prevention of stroke and on the reduction of morbidity in the survivors.

Antidiabetes and antioxidant potential of Schiff bases derived from 2-naphthaldehye and substituted aromatic amines: Synthesis, crystal structure, Hirshfeld surface analysis, computational, and invitro studies.

Three Schiff bases were synthesised by the condensation reaction between 2-napthaldehyde and aromatic amines to afford (E)-N-mesityl-1-(naphthalen-2-yl)methanimine (L1), (E)-N-(2,6-dimethylphenyl)-1-(naphthalen-2-yl)methanimine (L2) and (E)-N-(2,6-diisopropylphenyl)-1-(naphthalen-2-yl)methanimine (L3). The synthesised compounds were characterised using UV-visible, NMR (13C & 1H), and Fourier transform infrared spectroscopic methods while their purity was ascertained by elemental analysis. Structural analysis revealed that the naphthalene ring is almost coplanar with the imine functional group as evident by C1-C10-C11-N1 torsion angles of 176.4(2)° and 179.4(1)° in L2 and L3, respectively. Of all the various intermolecular contacts, H⋯H interactions contributed mostly towards the Hirshfeld surfaces of both L2 (58.7 %) and L3 (69.7 %). Quantum chemical descriptors of L1 - L3 were determined using Density Functional Theory (DFT) and the results obtained showed that the energy band gap (ΔE) for L1, L2 and L3 are 3.872, 4.023 and 4.004 eV respectively. The antidiabetic potential of the three compounds were studied using α-amylase and α-glucosidase assay. Compound L1 showed very promising antidiabetic activities with IC50 values of 58.85 µg/mL and 57.60 µg/mL while the reference drug (Acarbose) had 405.84 µg/mL and 35.69 µg/mL for α-amylase and α-glucosidase respectively. In-silico studies showed that L1 docking score as well as binding energies are higher than that of acarbose, which are recognized inhibitors of α-amylase together with α-glucosidase. Further insight from the RMSF, RMSD and RoG analysis predicted that, throughout the simulation L1 showcased evident influence on the structural stability of α-amylase. The antioxidant potential of the compounds was carried out using nitric oxide (NO), ferric reducing ability power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The compounds exhibited good to fairly antioxidant properties with L1 as well as L3 having IC50 values of 70.91 and 91.21 µg/mL respectively for NO scavenging activities assay, which comparatively outshined acarbose (reference drug) with IC50 value of 109.95 µg/mL. Pharmacology and pharmacokinetics approximations of L1 - L3 showed minimal violation of Lipinski's Ro5 and this projects them to be less toxic and orally bioavailable as potential templates for the design of therapeutics with antioxidant and antidiabetic activities.

The Prevalence of SARS-CoV-2 in Autopsies Surrounding the Time of Pandemic Onset: A Retrospective Review of Cases.

CONTEXT.­: The first case of COVID-19 in the United States was confirmed in January 2020. Initially, little was known about the epidemiology and clinical course of the disease, and diagnostic testing was limited in the United States until March/April 2020. Since then, many studies have speculated that SARS-CoV-2 may have preexisted undiagnosed outside China before the known outbreak. OBJECTIVE.­: To evaluate the prevalence of SARS-CoV-2 in adult autopsy cases performed just before and during the beginning of the pandemic at our institution, where autopsy was not performed on known COVID-19 cases. DESIGN.­: We included adult autopsies performed in our institution from June 1, 2019, to June 30, 2020. Cases were divided into groups based on the likelihood of cause of death being related to COVID-19, presence of a clinical respiratory illness, and histologic findings of pneumonia. Archived formalin-fixed, paraffin-embedded lung tissue of all COVID-possible cases and COVID-unlikely cases with pneumonia was tested for SARS-CoV-2 RNA, using Centers for Disease Control and Prevention 2019-nCoV quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS.­: Eighty-eight cases were identified, and among those, 42 (48%) were considered COVID-possible cause of death, with 24 of those 42 cases (57%) showing respiratory illness and/or pneumonia. COVID-19 as cause of death was considered unlikely in 46 of 88 cases (52%), with 34 of those 46 cases (74%) showing no respiratory illness or pneumonia. SARS-CoV-2 real-time reverse transcription-polymerase chain reaction was performed on a total of 49 cases, 42 COVID-possible and 7 COVID-unlikely with pneumonia, and all cases were negative (0 of 49). CONCLUSIONS.­: Our data suggest that autopsied patients in our community who died between June 1, 2019, and June 30, 2020, without known COVID-19 were unlikely to have had subclinical and/or undiagnosed COVID-19 infection.

Cardiac Angiosarcoma With Pulmonary Metastasis: A Rare and Challenging Case.

Cardiac angiosarcoma is a rare and aggressive malignant tumor arising from the endothelial cells of the heart. It accounts for only a small fraction of all cardiac neoplasms and has a poor prognosis. We present a challenging case of a 20-year-old student who presented exertional dyspnea, palpitation, and occasional chest discomfort. Her clinical picture, radiological and pathological investigations confirm the diagnosis of cardiac angiosarcoma with pulmonary metastasis. This case highlights the importance of early diagnosis and multidisciplinary management for improved patient outcomes.

Ni2+ and Cu2+ complexes of N-(2,6-dichlorophenyl)-N-mesityl formamidine dithiocarbamate structural and functional properties as CYP3A4 potential substrates.

Metal compounds continued to attract diverse applications due to their malleability in several capacities. In this study, we present our findings on the crystal structures and functional properties of Ni2+ and Cu2+ complexes of N'-(2,6-dichlorophenyl)-N-mesitylformamidine dithiocarbamate (L) comprising [Ni-(L)2] (1) and [Cu-(L)2] (2) with a four-coordinate metal center. We established the two complex structures through 1H and 13C nuclear magnetic resonance (NMR), elemental, and single-crystal X-ray analysis. The analyses showed that the two complexes are isomorphous, having P21/c as a space group and a unit-cell similarity index (π) of 0.002. The two complexes conform to a distorted square planar geometry around the metal centers. The calculated and experimental data, including bond lengths, angles, and NMR values, are similar. Hirshfeld surface analysis revealed the variational contribution of the different types of intermolecular contacts driven by the crystal lattice of the two solvated complexes. Our knowledge of the potential biological implication of these structures enabled us to probe the compounds as prospective CYP3A4 inhibitors. This approach mimics current trends in pharmaceutical design and biomedicine by incorporating potentially active molecules into various media to predict their biological efficacies. The simulations show appreciable binding of compounds 1 and 2 to CYP3A4 with average interaction energies of -97 and -87 kcal/mol, respectively. The protein attains at least five conformational states in the three studied models using a Gaussian Mixture Model-based clustering and free energy prediction. Electric field analysis shows the crucial residues to substrate binding at the active site, enabling CYP3A4 structure to function prediction. The predicted inhibition with these Ni2+ and Cu2+ complexes indicates that CYP3A4 overexpression in a diseased state like cancer would reduce, thereby increasing the chemotherapeutic compounds' shelf-lives for adsorption. This multidimensional study addresses various aspects of molecular metal electronics, including their application as substrate-mimicking inhibitors. The outcome would enable further research on bio-metal compounds of critical potential.

Type 1 Autoimmune Pancreatitis Masquerading as Pancreatic Head Carcinoma.

Obstructive jaundice is a joint clinical presentation with many etiologies, including pancreatic cancer and autoimmune pancreatitis (AIP). Differentiating between these two conditions is pivotal due to the divergent management approaches and prognoses. In this case report, we present a case of a 49-year-old female patient who presented with weight loss, intermittent chronic abdominal pain, and jaundice. She was initially suspected of having pancreatic cancer because of clinical presentation and imaging findings. However, she was ultimately diagnosed with Type 1 AIP due to histopathology findings and elevated immunoglobulin G4. This case highlights the complexities in diagnosis, the role of advanced imaging techniques and tissue sampling, and the lessons learned regarding managing this challenging clinical scenario.

Immune Thrombocytopenia and Cerebral Venous Sinus Thrombosis Following COVID-19 Vaccination: A Case Report.

Mass vaccination against coronavirus disease 2019 (COVID-19) has been safe and effective. The ongoing emergence of vaccine-induced complications has challenged the public trust in vaccination programs and, though uncommon, can lead to significant morbidity and mortality. Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare and fatal complication of the COVID-19 vaccine. We present a rare case of VITT in a young female who presented with worsening headache, body rash with deteriorating neurological deficit after 12 days of the second dose of the ChAdOx1 COVID-19 vaccine. Initial blood tests showed thrombocytopenia with deranged clotting time and D-dimer levels. Her computed tomography venogram showed thrombosis in the left transverse sinus, and she was diagnosed with a provisional diagnosis of VITT. She initially managed with dexamethasone, intravenous immunoglobulins, and apixaban to reverse the autoimmune process. Our case highlights the clinical course, diagnosis, and management of VITT, which will assist physicians in the timely recognition and adequate management of VITT.

The link between relative stability constant of DNA- and BSA-chromenopyrimidine complexes and cytotoxicity towards human breast cancer cells (MCF-7).

In this study, we synthesized and characterized ten chromenopyrimidine derivatives using analytical and spectroscopic methods. Studies on DNA and albumin binding affinity, as well as cytotoxicity tests on human breast cancer (MCF-7) cells, of the chromenopyrimidines, were conducted. The natural logarithm of the relative stability constant of DNA- and BSA-chromenopyrimidine complexes [ln(KDNA/KBSA)] was used as a criterion for selecting compounds for cytotoxicity studies. We found that ln(KDNA/KBSA) was inversely related to IC50 values of the compounds in MCF-7 cells. The antiproliferative effects of the compounds were found to induce apoptosis in MCF-7 cells, which is a desired mechanism of cell death. Correlations between the DNA and albumin binding affinities of chromenopyrimidines were established. We propose that this relationship approach can, for a given set of compounds, assist in predicting the cytotoxicity of potential drug candidates towards MCF-7 cells based on their experimentally determined CT-DNA and BSA binding affinities.

Intention for internal whistleblowing to report sexual violence in higher education institutions: a Nigerian national study.

Background: Sexual violence is prevalent in higher education institutions in Nigeria and stakeholders have encouraged staff and students to blow the whistle whenever they fall victim to or are aware of any sexual violence case. However, there is lack of data about whether the staff and students of these institutions have the intention to blow the whistle internally (within the institution) or not. There is also a lack of data on the existing reporting mechanisms or preferred whistleblowing mechanisms in these institutions. These have hindered the analysis of stakeholders' opinions on this topic. Methods: This data note presents a comprehensive quantitative and qualitative data set collected from staff and students of three categories of government owned higher education institutions (Universities, Polytechnics, Colleges of Education) in Nigeria. Data collection was between February and December, 2021, during which quantitative data were collected from 21,937 students and 3,108 staff. Qualitatively, 138 students and 111 staff participated in a total of 35 focus group discussion sessions. The study provides unique information on respondents' attitude, self-efficacy, and subjective norm to sexual violence whistleblowing. It also provides information on self-reported sexual violence experiences, whistleblowing intention, reporting systems in higher institutions and the preferred sexual violence whistleblowing mechanisms. Conclusions: In this data note, we provide a detailed account of the variables in the dataset and then highlight the potential of this study to contribute to improved sexual violence reporting in higher education institutions, thereby reducing the occurrence of the social menace.

Non-ST-Segment Elevation Myocardial Infarction As Initial Thrombotic Event of Thrombotic Thrombocytopenic Purpura: A Rare Challenging Case.

Thrombotic thrombocytopenic purpura (TTP) is a rare autoimmune and devastating blood disorder that results in micro-clots throughout the body, leading to tissue damage and organ dysfunction resulting in widespread microangiopathic hemolytic anemia, thrombocytopenia, fever, and neurological symptoms. TTP patients commonly manifest renal and neurological symptoms; however, cardiovascular involvement is not widely reported in the literature. We report a case of non-ST-segment elevation myocardial infarction (NSTEMI) as an initial manifestation of TTP. Although rare, TTP complications must be considered among other possible causes of unexpected thrombocytopenia during acute phase treatment of acute coronary syndrome because of high morbidity and mortality.