CuII-Catalyzed cis-Selective Synthesis of Ketoepoxides from Phenacyl Bromides and Water.

A verity of α,ß-ketoepoxides was synthesized using a CuII-catalyzed oxidative C-C/O-C coupled cyclization strategy with high yield and cis-selectivity. Water is used as the source of oxygen and phenacyl bromide as the carbon in the valuable epoxides. The self-coupling method was extended to cross-coupling between phenacyl bromides with benzyl bromides. A high cis-diastereoselectivity was observed in all the synthesized ketoepoxides. Control experiments and density functional theory (DFT) study were performed to understand the CuII-CuI transition mechanism.

Unveiling the Stereoselectivity and Regioselectivity of the [3+2] Cycloaddition Reaction between N-methyl-C-4-methylphenyl-nitrone and 2-Propynamide from a MEDT Perspective.

[3+2] cycloaddition reactions play a crucial role in synthesizing complex organic molecules and have significant applications in drug discovery and materials science. In this study, the [3+2] cycloaddition (32CA) reactions of N-methyl-C-4-methyl phenyl-nitrone 1 and 2-propynamide 2, which have not been extensively studied before, were investigated using molecular electron density theory (MEDT) at the B3LYP/6-311++G(d,p) level of theory. According to an electron localization function (ELF) study, N-methyl-C-4-methyl phenyl-nitrone 1 is a zwitterionic species with no pseudoradical or carbenoid centers. Conceptual density functional theory (CDFT) indices were used to predict the global electronic flux from the strong nucleophilic N-methyl-C-4-methyl phenylnitrone 1 to the electrophilic 2-propynamide 2 functions. The 32CA reactions proceeded through two pairs of stereo- and regioisomeric reaction pathways to generate four different products: 3, 4, 5, and 6. The reaction pathways were irreversible owing to their exothermic characters: -136.48, -130.08, -130.99, and -140.81 kJ mol-1, respectively. The enthalpy of the 32CA reaction leading to the formation of cycloadduct 6 was lower compared with the other path owing to a slight increase in its polar character, observed through the global electron density transfer (GEDT) during the transition states and along the reaction path. A bonding evolution theory (BET) analysis showed that these 32CA reactions proceed through the coupling of pseudoradical centers, and the formation of new C-C and C-O covalent bonds did not begin in the transition states.

Population genomic structure and adaptation in the zoonotic malaria parasite Plasmodium knowlesi.

Malaria cases caused by the zoonotic parasite Plasmodium knowlesi are being increasingly reported throughout Southeast Asia and in travelers returning from the region. To test for evidence of signatures of selection or unusual population structure in this parasite, we surveyed genome sequence diversity in 48 clinical isolates recently sampled from Malaysian Borneo and in five lines maintained in laboratory rhesus macaques after isolation in the 1960s from Peninsular Malaysia and the Philippines. Overall genomewide nucleotide diversity (π = 6.03 × 10(-3)) was much higher than has been seen in worldwide samples of either of the major endemic malaria parasite species Plasmodium falciparum and Plasmodium vivax. A remarkable substructure is revealed within P. knowlesi, consisting of two major sympatric clusters of the clinical isolates and a third cluster comprising the laboratory isolates. There was deep differentiation between the two clusters of clinical isolates [mean genomewide fixation index (FST) = 0.21, with 9,293 SNPs having fixed differences of FST = 1.0]. This differentiation showed marked heterogeneity across the genome, with mean FST values of different chromosomes ranging from 0.08 to 0.34 and with further significant variation across regions within several chromosomes. Analysis of the largest cluster (cluster 1, 38 isolates) indicated long-term population growth, with negatively skewed allele frequency distributions (genomewide average Tajima's D = -1.35). Against this background there was evidence of balancing selection on particular genes, including the circumsporozoite protein (csp) gene, which had the top Tajima's D value (1.57), and scans of haplotype homozygosity implicate several genomic regions as being under recent positive selection.

Deriving an optimal threshold of waist circumference for detecting cardiometabolic risk in sub-Saharan Africa.

BACKGROUND: Waist circumference (WC) thresholds derived from western populations continue to be used in sub-Saharan Africa (SSA) despite increasing evidence of ethnic variation in the association between adiposity and cardiometabolic disease and availability of data from African populations. We aimed to derive a SSA-specific optimal WC cut-point for identifying individuals at increased cardiometabolic risk. METHODS: We used individual level cross-sectional data on 24 181 participants aged ⩾15 years from 17 studies conducted between 1990 and 2014 in eight countries in SSA. Receiver operating characteristic curves were used to derive optimal WC cut-points for detecting the presence of at least two components of metabolic syndrome (MS), excluding WC. RESULTS: The optimal WC cut-point was 81.2 cm (95% CI 78.5-83.8 cm) and 81.0 cm (95% CI 79.2-82.8 cm) for men and women, respectively, with comparable accuracy in men and women. Sensitivity was higher in women (64%, 95% CI 63-65) than in men (53%, 95% CI 51-55), and increased with the prevalence of obesity. Having WC above the derived cut-point was associated with a twofold probability of having at least two components of MS (age-adjusted odds ratio 2.6, 95% CI 2.4-2.9, for men and 2.2, 95% CI 2.0-2.3, for women). CONCLUSION: The optimal WC cut-point for identifying men at increased cardiometabolic risk is lower (⩾81.2 cm) than current guidelines (⩾94.0 cm) recommend, and similar to that in women in SSA. Prospective studies are needed to confirm these cut-points based on cardiometabolic outcomes.International Journal of Obesity advance online publication, 31 October 2017; doi:10.1038/ijo.2017.240.

Oxidative stress among subjects with metabolic syndrome in Sokoto, North-Western Nigeria.

BACKGROUND: Oxidative stress is known to play a role in the pathophysiology of metabolic syndrome and its components. Racial differences may exist in the level of markers of oxidative stress and antioxidants in patients with metabolic syndrome. AIM: The aim of this study was to determine the oxidative stress and antioxidants status in subjects with metabolic syndrome in Sokoto, North-Western Nigeria. METHODS: A cross-sectional community-based study was carried out. Two hundred subjects (96 males and 104 females) were recruited for the study using a multi-stage sampling technique. Demographic data were obtained from the participants. Evaluation of anthropometric variables, blood pressure, blood glucose levels, lipid profiles, plasma insulin levels, total antioxidant status, and oxidative stress markers was performed. RESULTS: The subjects with metabolic syndrome had significantly higher malondialdehyde as compared to those without metabolic syndrome (236.4 [92.2] vs. 184 [63.2] nmol/l). The antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) were significantly lower in subjects with metabolic syndrome than in those without metabolic syndrome (11.3 [4.2] vs. 13.9 [4.1] U/ml, 160[42] vs. 220[32] U/ml, and 2.12 [0.2] vs. 2.42 [0.2] U/ml, respectively). Similarly, the antioxidant Vitamins (A, C, and E) levels were significantly lower in subjects with metabolic syndrome than in those without metabolic syndrome (7.1 [4.1] vs. 7.7 [4.2] µmol/L, 225 [55.3] vs. 227.6 [62.3] µmol/L, and 75.9 [13.9] vs. 82.8 [18.6] mg/dl, respectively). There was a positive correlation between components of metabolic syndrome and free radicals. CONCLUSION: Significantly increased oxidative stress and diminished antioxidant defenses were found among Nigerians with metabolic syndrome.

Genome-wide transposon mutagenesis indicates that Mycobacterium marinum customizes its virulence mechanisms for survival and replication in different hosts.

The interaction of environmental bacteria with unicellular eukaryotes is generally considered a major driving force for the evolution of intracellular pathogens, allowing them to survive and replicate in phagocytic cells of vertebrate hosts. To test this hypothesis on a genome-wide level, we determined for the intracellular pathogen Mycobacterium marinum whether it uses conserved strategies to exploit host cells from both protozoan and vertebrate origin. Using transposon-directed insertion site sequencing (TraDIS), we determined differences in genetic requirements for survival and replication in phagocytic cells of organisms from different kingdoms. In line with the general hypothesis, we identified a number of general virulence mechanisms, including the type VII protein secretion system ESX-1, biosynthesis of polyketide lipids, and utilization of sterols. However, we were also able to show that M. marinum contains an even larger set of host-specific virulence determinants, including proteins involved in the modification of surface glycolipids and, surprisingly, the auxiliary proteins of the ESX-1 system. Several of these factors were in fact counterproductive in other hosts. Therefore, M. marinum contains different sets of virulence factors that are tailored for specific hosts. Our data imply that although amoebae could function as a training ground for intracellular pathogens, they do not fully prepare pathogens for crossing species barriers.

Lipoatrophy among patients on antiretroviral therapy in Lagos, Nigeria: Prevalence, pattern and association with cardiovascular risk factors.

CONTEXT: Antiretroviral therapy (ART) is linked with morphologic abnormalities such as lipoatrophy (LA), which may accompany metabolic alterations (dysglycemias, dyslipidemia and insulin resistance) that increase cardiovascular disease risk. LA and its association with metabolic alterations have been infrequently studied amongst Nigerians on ART. AIMS: To determine the prevalence, pattern and association of LA with metabolic abnormalities and hypertension among patients on ART attending an ambulatory human immunodeficiency virus clinic in Lagos, Nigeria. SUBJECTS AND METHODS: A cross-sectional study was carried out among patients on ART using a structured interviewer administered questionnaire. Data obtained included patients and physician's assessment of body fat changes, drug history, blood pressure, body composition assessment using bioelectrical impedance analysis and biochemical evaluation (glucose, lipids). LA was defined clinically. Data were analyzed using IBM SPSS statistical software version 21. RESULTS: A total of 48 (33.1%) of the 145 patients had LA. The face was the most frequently affected body region. Patients with LA with lower body circumferences, skin-fold thickness and body fat (P < 0.05). The frequencies of lipid abnormalities were: Reduced high density lipoprotein-cholesterol (47.1%), elevated total cholesterol (35.6%), reduced low density lipoprotein-cholesterol (19.2%), elevated triglycerides (14.4%). Fasting plasma glucose (FPG)≥6.1 mmol/l and hypertension were present among 9.6% and 40.7% respectively. LA was not significantly associated with the presence of glucose intolerance, dyslipidemia or hypertension (P > 0.05). CONCLUSIONS: Lipoatrophy, though commonly encountered in patients on ART in Nigeria was not associated with the presence of dyslipidemia, abnormal FPG or hypertension. Regular monitoring by the physician and increased patients awareness are necessary to reduce its prevalence and impact.

Self-reported physical activity among health care professionals in South-West Nigeria.

INTRODUCTION: Physical activity (PA) is a key requirement for maintaining good health. There is growing evidence of declining PA worldwide. Physical inactivity is linked with the global obesity pandemic and increasing burden of noncommunicable diseases (NCDs) in developing countries. A barrier to PA counseling by health care providers (HCPs) is personal PA habits. Information regarding PA among HCPs in Nigeria is limited. We aimed to determine the adequacy and predictors of PA among HCPs of a tertiary health care facility in Lagos, Nigeria. METHODS: A cross-sectional study was carried out with the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Using the World Health Organization (WHO) guideline, PA was categorized as adequate or inadequate. Predictors of PA were explored with multivariate logistic regression. RESULTS: A total of 300 HCPs were recruited, comprising 47.7% doctors and dentists, 43.3% nurses and 9.0% other HCPs. Mean age was 39.9 (9.0 years), 79.2%, 9.7% and 11.1% of the HCPs had low, moderate or high PA levels respectively. Thus, only 20.8% had adequate PA. 71.3% had body mass index (BMI) above the recommended value. BMI of ≥25 kg/m2 was associated with inadequate PA (Adjusted Odds Ratio-2.1,P=0.018). CONCLUSION: Majority of the HCPs had inadequate PA levels according to WHO guidelines. BMI≥25 kg/m2 was associated with inadequate physical inactivity. The low level of PA implies that these HCPs are at risk for NCDs. This will have a negative impact on availability of human resource for health. There is an urgent need to establish programs to increase PA among HCPs.

Obesity, overweight, and underweight among urban Nigerians.

BACKGROUND: Disease burden from communicable and noncommunicable diseases is a significant health challenge facing many developing nations. Among the noncommunicable diseases, is obesity, which has become a global epidemic associated with urbanization. OBJECTIVE: The aim was to evaluate the prevalence of weight abnormalities, their pattern of distribution and regional differences among apparently healthy urban dwelling Nigerians. METHODS: A cross-sectional community-based descriptive survey was carried out in five urban cities, each from one geo-political zone of Nigeria. Multistage sampling procedures were used to select participants using the World Health Organization STEPS instrument. Ethical approval and consents were duly and respectively obtained from the Ethics Committee in the tertiary centers and participants in each of these cities. Analysis was performed using SPSS version 20 (IBM Corp., Amonk, NY; released 2011) with P value set at < 0.05. RESULTS: A total of 5392 participants were recruited; of which, 54.5% and 45.5% were males and females respectively. Mean (standard deviation) age and body mass index (BMI) were 40.6 (14.3) years and 25.3 (5.1) kg/m 2 . Obesity, overweight, and underweight were found in 17%, 31%, and 5% of participants respectively. Significantly, while underweight declined with increasing age, overweight, and obesity increased to peak in the middle age brackets. Age of ≥ 40 years was found to confer about twice the risk of becoming overweight. The prevalence of obesity and mean BMI were significantly higher both among the females and the participants from southern zones. CONCLUSION: Obesity and overweight are common in our urban dwellers with accompanying regional differences. Attainment of middle age increases the likelihood of urban dwelling Nigerians to become overweight/obese. There is therefore the need to institute measures that will check development of overweight/obesity early enough, while improving the nutritional status of the few who may still be undernourished.

Evaluation of ivermectin and vitamin E based combination with antiseizure rufinamide drug for mitigation of pentylenetetrazole-induced kindling, behavioral challenges and histopathological aberrations.

Pentylenetetrazole- (PTZ)-induced kindling is a broadly used experimental model to evaluate the impact of antiseizure drugs and their novel combination on seizure progression. The current study aimed to evaluate the anti-kindling effects of ivermectin (IVM) and rufinamide (RUFI) alone and their combination with vitamin E. The mice were administered 11 injections of PTZ (40 mg/kg) followed by assessment for anxiety-like behavior and cognitive abilities in a series of behavior tests with subsequent brain isolation for biochemical and histopathological evaluation. The outcomes showed a marked protection by IVM + RUFI (P<0.001) from kindling progression, anxiety-like behavior and cognitive deficit. However, additional supplementation with vitamin E worked superior to duo therapy as these mice were noted to be most fearless to visiting open, illuminated and elevated zones of open field, light/dark and elevated-plus maze (P<0.0001). Further, they showed marked remembrance of the familiar milieu in y-maze (P<0.01) and novel objection recognition (P<0.05) tests. Additionally, their recollection of aversive stimuli in passive avoidance and spatial memory in Morris water maze were evident (P<0.0001), in comparison to kindled mice. The IVM + RUFI duo therapy and its co-administration with vitamin E prevented kindling-triggered oxidative stress in brains and neuronal damage in hippocampus. We conclude that the benefits of the co-administration of vitamin E might be the results of antioxidant and anti-inflammatory effects of vitamin E which might be potentiating the antiseizure effects of RUFI and GABA-A modulating potential by ivermectin.

Artificial Extracellular Vesicles Generated from T Cells Using Different Induction Techniques.

Cell therapy is at the forefront of biomedicine in oncology and regenerative medicine. However, there are still significant challenges to their wider clinical application such as limited efficacy, side effects, and logistical difficulties. One of the potential approaches that could overcome these problems is based on extracellular vesicles (EVs) as a cell-free therapy modality. One of the major obstacles in the translation of EVs into practice is their low yield of production, which is insufficient to achieve therapeutic amounts. Here, we evaluated two primary approaches of artificial vesicle induction in primary T cells and the SupT1 cell line-cytochalasin B as a chemical inducer and ultrasonication as a physical inducer. We found that both methods are capable of producing artificial vesicles, but cytochalasin B induction leads to vesicle yield compared to natural secretion, while ultrasonication leads to a three-fold increase in particle yield. Cytochalasin B induces the formation of vesicles full of cytoplasmic compartments without nuclear fraction, while ultrasonication induces the formation of particles rich in membranes and membrane-related components such as CD3 or HLAII proteins. The most effective approach for T-cell induction in terms of the number of vesicles seems to be the combination of anti-CD3/CD28 antibody activation with ultrasonication, which leads to a seven-fold yield increase in particles with a high content of functionally important proteins (CD3, granzyme B, and HLA II).

Rural-urban difference in plasma lipid levels and prevalence of dyslipidemia in Hausa-Fulani of north-western Nigeria.

OBJECTIVES: To compare the serum lipids levels, prevalence of dyslipidaemia, and adiposity of rural versus urban dwellers in Sokoto, Nigeria. METHODS: A cross-sectional study was conducted in both rural and urban areas of Sokoto, Nigeria. One hundred participants were recruited using a multi-stage sampling method. Demographic data and anthropometric measurements were obtained. Fasting blood was drawn for assessment of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol. The classification of dyslipidemia was based on the National Cholesterol Education Program-Adult Treatment Panel guidelines. RESULTS: The (mean [SD]) waist circumference of the urban participants (83.8 [9.5] cm) was significantly higher than the rural participants (79.2 [11.2] cm) (P = .030). The mean BMI of the urban participants (23.9 [3.9] kg/m2) was higher than the rural participants (22.2 [3.7] kg/m2) (P = .09). The mean TC was significantly higher in urban (175.9 [49.6] mg/dL) than rural participants (148.3 [24.3] mg/dL) P < .001. Mean serum LDL-C, and TG concentrations were higher in the urban than rural participants but the difference was not statistically significant. Mean serum HDL-C was also insignificantly higher in the rural (51.1 [7.9] mg/dL) than in urban participants (50.2 [11.7] mg/dL) (P = .64). The most frequent dyslipidemia was abnormally low HDL-C (13%) and this was more common in the urban participants (16%) than in rural participants (10%). CONCLUSION: This study demonstrated that compared to the rural dwellers, the urban dweller were more likely to be obese and had higher frequency of adverse plasma lipid profile. This may have implications for rural-urban patterns of lipid related cardiovascular disease.

CALCINOSIS CUTIS - A SERIES OF 59 CONSECUTIVE CASES CONFINED AMONG WOMEN.

BACKGROUND: Calcinosis cutis is the cutaneous deposition of calcium salts. Tumoral Calcinosis is a condition consisting of massive subcutaneous deposits of calcium salts often overlying large joints in otherwise healthy patients. OBJECTIVE: To describe the characteristics of a series of patients with Tumoral Calcinosis in the Gurage Zone of Central Ethiopia. METHODOLOGY: Data was collected from 59 patients who presented with clinical diagnosis of calcinosis cutis around hip region between January 2005 and January 2009. RESULTS: All cases were females, with a mean (standard deviation) age at diagnosis of 50.7(10.8). The duration of illness ranged from one to eighteen years. The cases were distributed in the different villages of Gurage Zone without any sign of clustering of cases. The lesions were localized around hip region on both sides. The patients did not have any related co-morbidity or any history of similar illness among close family members. None of the patients gave history of evident trauma to the site of the lesions. Significant proportion of the patients (53.4%) confirmed to carry water container and/or other goods on their side. Serum Phosphate and Calcium levels in selected patients were with in normal limit. Histo-pathological examinations of five cases revealed Calcium deposits in collagenous connective tissue. CONCLUSION: The lesion was found to be relatively common in the study area and specifically confined to females. The probable factor associated with the cases is carrying objects on their side (hip area). Further research with in-depth clinical and laboratory evaluation is of paramount importance.

Cu(I)-catalysed cross-coupling reaction of in situ generated azomethine ylides towards easy construction of fused N-heterocycles.

In this study, we have devised a new method for synthesizing highly valuable 5,6,7,8a-tetrahydropyrrolo[2,1-b]thiazoles using a decarboxylative C-N coupling reaction between phenyl glyoxal and proline or its analogue, which is catalyzed by CuI in the presence of K2CO3. This reaction is followed by a regiospecific C-C and C-S coupling cyclization with dialkyl trithiocarbonate. Furthermore, we have demonstrated that this cross-coupling method can also be extended to imines, leading to the formation of fused symmetrical and unsymmetrical 6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles. This finding greatly expands the scope and versatility of the synthetic approach. Therefore, this work represents a significant contribution to the field of organic synthesis, providing a novel and efficient method for the preparation of fused N-heterocyclic compounds that could have useful applications in areas such as material science and pharmaceuticals.

A Rare Case of Transplanted Kidney Lymphangiectasia in a Patient With Joubert Syndrome.

Renal lymphangiectasia is one of the rarest surgical complications in post-transplant kidney patients. A few patients may clinically complain of nonspecific symptoms, and the other few might be diagnosed incidentally. We report the case of a 32-year-old female patient with a known case of Joubert syndrome who presented with nonspecific clinical manifestations. The patient underwent ultrasound, magnetic resonance imaging (MRI), and nuclear medicine (NM) imaging to confirm the diagnosis, which showed radiologic features of renal lymphangiectasia. Conservative medical management was delivered to the patient.

Outcome of Transplant Recipients Infected with Omicron BA.1 and BA.2: A Single-Center Retrospective Study in Saudi Arabia.

The outcome of transplant recipients is variable depending on the study population, vaccination status and COVID-19 variants. Our aim was to study the impact of Omicron subvariants on the mortality of transplant recipients. We reviewed the results of SARS-CoV-2 whole genome sequence of random isolates collected from 29 December 2021 until 17 May 2022 in King Faisal Specialist Hospital and Research center, Jeddah (KFSHRC-J), Saudi Arabia performed as hospital genomic surveillance program for COVID-19 variants. We included 25 transplant patients infected with confirmed Omicron variants.17 (68%) and 8 (32%) patients had Omicron BA.1 and BA.2, respectively. 12 (68%) patients had renal transplants. Only 36% of patients received three doses of COVID-19 vaccines. 23 (92%) patients required hospitalization. 20 (80%) patients survived and 6 (25%) required intensive care unit (ICU) admission. Among ICU patients, 66.7% were more than 50 years, 50% had two to three comorbidities and 5 out of 6 (83%) died. The mortality of transplant patients infected with Omicron variants in our cohort was higher than other centers as a limited number of patients received booster vaccines. Optimizing booster vaccination is the most efficient method to improve the mortality of COVID-19 in transplant recipients recognizing the inefficacy of monoclonal antibodies in the presence of SARS-CoV-2 emerging variants. We did not show a difference in mortality in transplant patients infected with Omicron BA.1 and BA.2 knowing the limitation of our sample size.

Complete genome sequence of Mycobacterium xenopi type strain RIVM700367.

Mycobacterium xenopi is a slow-growing, thermophilic, water-related Mycobacterium species. Like other nontuberculous mycobacteria, M. xenopi more commonly infects humans with altered immune function, such as chronic obstructive pulmonary disease patients. It is considered clinically relevant in a significant proportion of the patients from whom it is isolated. We report here the whole genome sequence of M. xenopi type strain RIVM700367.

Complete genome sequence of Mycobacterium phlei type strain RIVM601174.

Mycobacterium phlei is a rapidly growing nontuberculous Mycobacterium species that is typically nonpathogenic, with few reported cases of human disease. Here we report the whole genome sequence of M. phlei type strain RIVM601174.

Complete genome sequence of Mycobacterium fortuitum subsp. fortuitum type strain DSM46621.

Mycobacterium fortuitum is a member of the rapidly growing nontuberculous mycobacteria (NTM). It is ubiquitous in water and soil habitats, including hospital environments. M. fortuitum is increasingly recognized as an opportunistic nosocomial pathogen causing disseminated infection. Here we report the genome sequence of M. fortuitum subsp. fortuitum type strain DSM46621.