Breast lesions and cancer: histopathology and molecular classification in a referral hospital in Ghana

Background: Histological diagnosis is crucial to the management of breast diseases. It determines the kind of disease, the treatment modalities, and the outcome of management. Our department receives breast biopsies from the northern sector of Ghana constituting over 50% of the Ghanaian population. This study aimed at elucidating the pattern of disease and associated traditional prognostic indices of breast cases in our department over a period of 9 years.Methods: Information on the demographic characteristics and the histological diagnoses made on all breast cases received and processed in the department were accessed and entered into an Excel spreadsheet. Slides were reviewed and IHC was done on suitable cases. Descriptive statistics were generated using IMB-SPSS version 23.Results: A total of 4276 breast cases were received by the department within the study period, with 97.6% being female. Age ranged (female/male) from 10 to 98/13 to 102 years, with mean ages of 38.2 years (SD ± 16.7) and 41.15 years (SD ± 21.6), respectively. Cases were evenly distributed in both left and right breasts and 4.3% were bilateral. Inflammatory conditions were seen in 7.5% of cases. The most diagnosed benign tumor was fibroadenoma (54%), followed by fibrocystic change (8.1%). Gynecomastia was diagnosed in 66.3% of males. Malignant cases were 38.6%, with invasive carcinoma NST being the most frequent (87.5%). Histological grades were I = 9.4%, II = 41.6%, and III = 49%. Molecular subtypes were luminal A (19.8%), luminal B (9.9%), Her2 (16%), and TNBC (54.3%).Conclusion: Our findings show an increase in breast cancer cases compared to previous studies in our center, suggesting increased awareness and improved diagnosis. However, this increase is consistent with most studies in sub-Saharan Africa

The human microbiota is associated with cardiometabolic risk across the epidemiologic transition.

Oral and fecal microbial biomarkers have previously been associated with cardiometabolic (CM) risk, however, no comprehensive attempt has been made to explore this association in minority populations or across different geographic regions. We characterized gut- and oral-associated microbiota and CM risk in 655 participants of African-origin, aged 25-45, from Ghana, South Africa, Jamaica, and the United States (US). CM risk was classified using the CM risk cut-points for elevated waist circumference, elevated blood pressure and elevated fasted blood glucose, low high-density lipoprotein (HDL), and elevated triglycerides. Gut-associated bacterial alpha diversity negatively correlated with elevated blood pressure and elevated fasted blood glucose. Similarly, gut bacterial beta diversity was also significantly differentiated by waist circumference, blood pressure, triglyceridemia and HDL-cholesterolemia. Notably, differences in inter- and intra-personal gut microbial diversity were geographic-region specific. Participants meeting the cut-points for 3 out of the 5 CM risk factors were significantly more enriched with Lachnospiraceae, and were significantly depleted of Clostridiaceae, Peptostreptococcaceae, and Prevotella. The predicted relative proportions of the genes involved in the pathways for lipopolysaccharides (LPS) and butyrate synthesis were also significantly differentiated by the CM risk phenotype, whereby genes involved in the butyrate synthesis via lysine, glutarate and 4-aminobutyrate/succinate pathways and LPS synthesis pathway were enriched in participants with greater CM risk. Furthermore, inter-individual oral microbiota diversity was also significantly associated with the CM risk factors, and oral-associated Streptococcus, Prevotella, and Veillonella were enriched in participants with 3 out of the 5 CM risk factors. We demonstrate that in a diverse cohort of African-origin adults, CM risk is significantly associated with reduced microbial diversity, and the enrichment of specific bacterial taxa and predicted functional traits in both gut and oral environments. As well as providing new insights into the associations between the gut and oral microbiota and CM risk, this study also highlights the potential for novel therapeutic discoveries which target the oral and gut microbiota in CM risk

Reduced levels of intracellular calcium releasing in spermatozoa from asthenozoospermic patients

<p>Abstract</p> <p>Background</p> <p>Asthenozoospermia is one of the most common findings present in infertile males characterized by reduced or absent sperm motility, but its aetiology remains unknown in most cases. In addition, calcium is one of the most important ions regulating sperm motility. In this study we have investigated the progesterone-evoked intracellular calcium signal in ejaculated spermatozoa from men with normospermia or asthenozoospermia.</p> <p>Methods</p> <p>Human ejaculates were obtained from healthy volunteers and asthenospermic men by masturbation after 4–5 days of abstinence. For determination of cytosolic free calcium concentration, spermatozoa were loaded with the fluorescent ratiometric calcium indicator Fura-2.</p> <p>Results</p> <p>Treatment of spermatozoa from normospermic men with 20 micromolar progesterone plus 1 micromolar thapsigargin in a calcium free medium induced a typical transient increase in cytosolic free calcium concentration due to calcium release from internal stores. Similar results were obtained when spermatozoa were stimulated with progesterone alone. Subsequent addition of calcium to the external medium evoked a sustained elevation in cytosolic free calcium concentration indicative of capacitative calcium entry. However, when progesterone plus thapsigargin were administered to spermatozoa from patients with asthenozoospermia, calcium signal and subsequent calcium entry was much smaller compared to normospermic patients. As expected, pretreatment of normospermic spermatozoa with both the anti-progesterone receptor c262 antibody and with progesterone receptor antagonist RU-38486 decreased the calcium release induced by progesterone. Treatment of spermatozoa with cytochalasin D or jasplakinolide decreased the calcium entry evoked by depletion of internal calcium stores in normospermic patients, whereas these treatments proved to be ineffective at modifying the calcium entry in patients with asthenozoospermia.</p> <p>Conclusion</p> <p>Our results suggest that spermatozoa from asthenozoospermic patients present a reduced responsiveness to progesterone.</p

A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features

Item does not contain fulltextBACKGROUND: Congenital deletions affecting 3q11q23 have rarely been reported and only five cases have been molecularly characterised. Genotype-phenotype correlation has been hampered by the variable sizes and breakpoints of the deletions. In this study, 14 novel patients with deletions in 3q11q23 were investigated and compared with 13 previously reported patients. METHODS: Clinical data were collected from 14 novel patients that had been investigated by high resolution microarray techniques. Molecular investigation and updated clinical information of one cytogenetically previously reported patient were also included. RESULTS: The molecular investigation identified deletions in the region 3q12.3q21.3 with different boundaries and variable sizes. The smallest studied deletion was 580 kb, located in 3q13.31. Genotype-phenotype comparison in 24 patients sharing this shortest region of overlapping deletion revealed several common major characteristics including significant developmental delay, muscular hypotonia, a high arched palate, and recognisable facial features including a short philtrum and protruding lips. Abnormal genitalia were found in the majority of males, several having micropenis. Finally, a postnatal growth pattern above the mean was apparent. The 580 kb deleted region includes five RefSeq genes and two of them are strong candidate genes for the developmental delay: DRD3 and ZBTB20. CONCLUSION: A newly recognised 3q13.31 microdeletion syndrome is delineated which is of diagnostic and prognostic value. Furthermore, two genes are suggested to be responsible for the main phenotype.1 februari 201

Resolving the Role of Plant Glutamate Dehydrogenase. I. in vivo Real Time Nuclear Magnetic Resonance Spectroscopy Experiments

In higher plants the glutamate dehydrogenase (GDH) enzyme catalyzes the reversible amination of 2-oxoglutarate to form glutamate, using ammonium as a substrate. For a better understanding of the physiological function of GDH either in ammonium assimilation or in the supply of 2-oxoglutarate, we used transgenic tobacco (Nicotiana tabacum L.) plants overexpressing the two genes encoding the enzyme. An in vivo real time 15N-nuclear magnetic resonance (NMR) spectroscopy approach allowed the demonstration that, when the two GDH genes were overexpressed individually or simultaneously, the transgenic plant leaves did not synthesize glutamate in the presence of ammonium when glutamine synthetase (GS) was inhibited. In contrast we confirmed that the primary function of GDH is to deaminate Glu. When the two GDH unlabeled substrates ammonium and Glu were provided simultaneously with either [15N]Glu or 15NH4+ respectively, we found that the ammonium released from the deamination of Glu was reassimilated by the enzyme GS, suggesting the occurrence of a futile cycle recycling both ammonium and Glu. Taken together, these results strongly suggest that the GDH enzyme, in conjunction with NADH-GOGAT, contributes to the control of leaf Glu homeostasis, an amino acid that plays a central signaling and metabolic role at the interface of the carbon and nitrogen assimilatory pathways. Thus, in vivo NMR spectroscopy appears to be an attractive technique to follow the flux of metabolites in both normal and genetically modified plants

Adolescent health in rural Ghana: A cross-sectional study on the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors.

In sub-Saharan Africa, infectious diseases and malnutrition constitute the main health problems in children, while adolescents and adults are increasingly facing cardio-metabolic conditions. Among adolescents as the largest population group in this region, we investigated the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors (CRFs), and evaluated demographic, socio-economic and medical risk factors for these entities. In a cross-sectional study among 188 adolescents in rural Ghana, malarial infection, common infectious diseases and Body Mass Index were assessed. We measured ferritin, C-reactive protein, retinol, fasting glucose and blood pressure. Socio-demographic data were documented. We analyzed the proportions (95% confidence interval, CI) and the co-occurrence of infectious diseases (malaria, other common diseases), malnutrition (underweight, stunting, iron deficiency, vitamin A deficiency [VAD]), and CRFs (overweight, obesity, impaired fasting glucose, hypertension). In logistic regression, odds ratios (OR) and 95% CIs were calculated for the associations with socio-demographic factors. In this Ghanaian population (age range, 14.4-15.5 years; males, 50%), the proportions were for infectious diseases 45% (95% CI: 38-52%), for malnutrition 50% (43-57%) and for CRFs 16% (11-21%). Infectious diseases and malnutrition frequently co-existed (28%; 21-34%). Specifically, VAD increased the odds of non-malarial infectious diseases 3-fold (95% CI: 1.03, 10.19). Overlap of CRFs with infectious diseases (6%; 2-9%) or with malnutrition (7%; 3-11%) was also present. Male gender and low socio-economic status increased the odds of infectious diseases and malnutrition, respectively. Malarial infection, chronic malnutrition and VAD remain the predominant health problems among these Ghanaian adolescents. Investigating the relationships with evolving CRFs is warranted

Evaluation of a learner-designed course for teaching health research skills in Ghana

<p>Abstract</p> <p>Background</p> <p>In developing countries the ability to conduct locally-relevant health research and high quality education are key tools in the fight against poverty. The objective of our study was to evaluate the effectiveness of a novel UK accredited, learner-designed research skills course delivered in a teaching hospital in Ghana.</p> <p>Methods</p> <p>Study participants were 15 mixed speciality health professionals from Komfo Anokye Teaching Hospital, Kumasi, Ghana. Effectiveness measures included process, content and outcome indicators to evaluate changes in learners' confidence and competence in research, and assessment of the impact of the course on changing research-related thinking and behaviour. Results were verified using two independent methods.</p> <p>Results</p> <p>14/15 learners gained research competence assessed against UK Quality Assurance Agency criteria. After the course there was a 36% increase in the groups' positive responses to statements concerning confidence in research-related attitudes, intentions and actions. The greatest improvement (45% increase) was in learners' actions, which focused on strengthening institutional research capacity. 79% of paired before/after responses indicated positive changes in individual learners' research-related attitudes (n = 53), 81% in intention (n = 52) and 85% in action (n = 52). The course had increased learners' confidence to start and manage research, and enhanced life-long skills such as reflective practice and self-confidence. Doing their own research within the work environment, reflecting on personal research experiences and utilising peer support and pooled knowledge were critical elements that promoted learning.</p> <p>Conclusion</p> <p>Learners in Ghana were able to design and undertake a novel course that developed individual and institutional research capacity and met international standards. Learning by doing and a supportive peer community at work were critical elements in promoting learning in this environment where tutors were scarce. Our study provides a model for delivering and evaluating innovative educational interventions in developing countries to assess whether they meet external quality criteria and achieve their objectives.</p

MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus

Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.3 contains PXDN and MYT1L. MYT1L is expressed only within the brain in humans. We hypothesized that single nucleotide variants (SNVs) in MYT1L would cause a phenotype resembling deletion at 2p25.3. To examine this we sought MYT1L SNVs in exome sequencing data from 4, 296 parent-child trios. Further variants were identified through a genematcher-facilitated collaboration. We report 9 patients with MYT1L SNVs (4 loss of function and 5 missense). The phenotype of SNV carriers overlapped with that of 2p25.3 deletion carriers. To identify the transcriptomic consequences of MYT1L loss of function we used CRISPR-Cas9 to create a knockout cell line. Gene Ontology analysis in knockout cells demonstrated altered expression of genes that regulate gene expression and that are localized to the nucleus. These differentially expressed genes were enriched for OMIM disease ontology terms “mental retardation”. To study the developmental effects of MYT1L loss of function we created a zebrafish knockdown using morpholinos. Knockdown zebrafish manifested loss of oxytocin expression in the preoptic neuroendocrine area. This study demonstrates that MYT1L variants are associated with syndromic obesity in humans. The mechanism is related to dysregulated expression of neurodevelopmental genes and altered development of the neuroendocrine hypothalamus

Physical activity and fat-free mass during growth and in later life

Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass.A study is presented of the association between FFM and physical activity in relation to age.In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3–96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical activity level (PAL = TEE/REE), and calculation of FFM from isotope dilution.PAL was a main determinant of body composition at all ages. Models with age, fat mass (FM), and PAL explained 76\% and 85\% of the variation in FFM in females and males &lt; 18 y old, and 32\% and 47\% of the variation in FFM in females and males ≥ 18 y old, respectively. In participants &lt; 18 y old, mean FM-adjusted FFM was 1.7 kg (95\% CI: 0.1, 3.2 kg) and 3.4 kg (95\% CI: 1.0, 5.6 kg) higher in a very active participant with PAL = 2.0 than in a sedentary participant with PAL = 1.5, for females and males, respectively. At age 18 y, height and FM–adjusted FFM was 3.6 kg (95\% CI: 2.8, 4.4 kg) and 4.4 kg (95\% CI: 3.2, 5.7 kg) higher, and at age 80 y 0.7 kg (95\% CI: −0.2, 1.7 kg) and 1.0 kg (95\% CI: −0.1, 2.1 kg) higher, in a participant with PAL = 2.0 than in a participant with PAL = 1.5, for females and males, respectively.If these associations are causal, they suggest physical activity is a major determinant of body composition as reflected in peak FFM, and that a physically active lifestyle can only partly protect against loss of FFM in aging adults