Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression.

Prostate cancer (PCa) development and progression relies on the programming of glucose and lipid metabolism, and this involves alterations in androgen receptor expression and signalling. Defining the molecular mechanism that underpins this metabolic programming will have direct significance for patients with PCa who have a poor prognosis. Here we show that there is a dynamic balance between sortilin and syndecan-1, that reports on different metabolic phenotypes. Using tissue microarrays, we demonstrated by immunohistochemistry that sortilin was highly expressed in low-grade cancer, while syndecan-1 was upregulated in high-grade disease. Mechanistic studies in prostate cell lines revealed that in androgen-sensitive LNCaP cells, sortilin enhanced glucose metabolism by regulating GLUT1 and GLUT4, while binding progranulin and lipoprotein lipase (LPL) to limit lipid metabolism. In contrast, in androgen-insensitive PC3 cells, syndecan-1 was upregulated, interacted with LPL and colocalised with ß3 integrin to promote lipid metabolism. In addition, androgen-deprived LNCaP cells had decreased expression of sortilin and reduced glucose-metabolism, but increased syndecan-1 expression, facilitating interactions with LPL and possibly ß3 integrin. We report a hitherto unappreciated molecular mechanism for PCa, which may have significance for disease progression and how androgen-deprivation therapy might promote castration-resistant PCa.

Implementation of community-based management of severe acute malnutrition in conflict affected regions: a case of South Kordofan, Sudan.

Malnutrition is the major cause of mortality and morbidity globally with undernutrition contributing about 45% of all deaths of under five children. Besides the direct effects of protracted conflicts, the macroeconomic crisis that has greatly increased the national inflation rate hence devastating the purchasing power, the COVID-19 outbreak, flooding, and the Desert Locusts have contributed to a food security emergency. Besides being among the most under resourced states, South Kordofan has experienced years of conflict resulting in displacement of people and extensive infrastructure destruction with high rates of malnutrition. The state currently has 230 health facilities and out of these, only 140 are providing outpatient therapeutic programme centres with 28.6% (40) of these being operated by the state ministry of health and the rest by the international non-governmental organizations. Limited resources leading to donor dependence, limited accessibility due to insecurity and floods, poor referral system and gaps in continuity of care, lack of operational and implementation research data and limited integration of management of malnutrition in other health services have negatively affected effective implementation. Ensuring effective and efficient community based management of acute malnutrition, implementation needs action beyond the health sector with a multi-sectoral and integration approach. Federal and state development frameworks should ensure a comprehensive multi-sectoral nutrition policy with strong political commitment and allocation of adequate resources to ensure integrated and quality implementation.

Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer.

Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occurring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop biomarkers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients. Online gene expression databases were interrogated and a pathogenic pathway for prostate cancer was identified. The protein expression of key genes in the pathway, including adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (Appl1), Sortilin and Syndecan-1, was examined by immunohistochemistry (IHC) in a pilot study of 29 patients with prostate cancer, using monoclonal antibodies designed against unique epitopes. Appl1, Sortilin, and Syndecan-1 expression was first assessed in a tissue microarray cohort of 112 patient samples, demonstrating that the monoclonal antibodies clearly illustrate gland morphologies. To determine the impact of a novel IHC-assisted interpretation (the utility of Appl1, Sortilin, and Syndecan-1 labelling as a panel) of Gleason grading, versus standard haematoxylin and eosin (H&E) Gleason grade assignment, a radical prostatectomy sample cohort comprising 114 patients was assessed. In comparison to H&E, the utility of the biomarker panel reduced subjectivity in interpretation of prostate cancer tissue morphology and improved the reliability of pathology assessment, resulting in Gleason grade redistribution for 41% of patient samples. Importantly, for equivocal IHC-assisted labelling and H&E staining results, the cancer morphology interpretation could be more accurately applied upon re-review of the H&E tissue sections. This study addresses a key issue in the field of prostate cancer pathology by presenting a novel combination of three biomarkers and has the potential to transform clinical pathology practice by standardising the interpretation of the tissue morphology.

A survey of contagious ecthyma and molecular characterization of Orf virus in sheep and goats in Nigeria (2014-2016).

Background: Outbreaks of contagious ecthyma (CE) are frequently reported in sheep and goat flocks in Nigeria with severe clinical outcomes. CE is a debilitating and economically important disease primarily affecting sheep and goats caused by the Orf virus (ORFV). Despite field reports of CE in the country, there is no concise country-wide epidemiological data on the disease and limited genetic data of circulating Nigerian ORFV are available in the public domain. Aim: An epidemiological survey of CE and molecular characterization of ORFV circulating in Nigeria from 2014 to 2016. Method: Data were collected using designed questionnaires, administered to veterinarians and farmers in selected States of Nigeria. Samples were collected during passive surveillance for CE from 2014 to 2016 which were analyzed by polymerase chain reaction (PCR). The A32L and B2L genes of circulating ORFV were also characterized. Results: Analysis of the questionnaire showed that 69.54% (n = 82/118) of the farmers claimed to have experienced CE in their flocks with average morbidity and mortality rates of 25% and 15%, respectively. A total of 113 veterinarians participated in the study, with 69.9% (n = 79) familiar with CE and claimed CE causes morbidity rates of 25%-37% and mortality rates of 10%-15% in sheep and goats. Laboratory results revealed that ORFV was detected in 72% (18/25) of outbreak samples analyzed by real-time PCR. Phylogenetic analysis of A32L and B2L genes revealed that Nigerian ORFV sequences belong to clusters I and II and are similar to viruses from India, Ethiopia, and China. Conclusions: This study is the first nationwide epidemiological data on the status of CE in sheep and goats in Nigeria. It is also the first report of molecular characterization of two genes of ORFV circulating and causing outbreaks in small ruminants in the country. This study showed that CE is under-reported, widespread and of economic importance to sheep and goat farmers in Nigeria.

Experimental beam combining stabilization using machine learning trained while phases drift.

An 8-beam, diffractive coherent beam combiner is phase controlled by a learning algorithm trained while optical phases drift, using a differential mapping technique. Combined output power is stable to 0.4% with 95% of theoretical maximum efficiency, limited by the diffractive element.

Flavonoid fractions of diosmin and hesperidin mitigate lead acetate-induced biochemical, oxidative stress, and histopathological alterations in Wistar rats.

This study aims at investigating the protective effects of flavonoid fractions of diosmin and hesperidin in mitigating sub-chronic lead acetate-induced biochemical, oxidative stress, and histopathological alterations in adult male Wistar rats. Forty animals were randomly assigned into five groups, each consisting of eight animals. Group I animals was treated with deionised water only, group II, IV, and V were administered lead acetate 90 mg/Kg body weight (1/20th of the LD50), groups III, and IV was administered Daflon (100 mg/Kg), while group V was administered Daflon (200 mg/Kg), 30 min prior treatment with lead acetate. All treatments lasted for 42 days. Blood lead levels, electrolyte parameters, zinc protoporphyrin (ZPP) levels, activities of antioxidant enzymes, and histopathology of vital organs, were evaluated following standard practice. Sub-chronic lead acetate exposure induced a decrease in levels of serum electrolytes, and activities of antioxidant enzymes, while blood lead levels, ZPP, and malondialdehyde levels were increased. Lead exposure also instigated marked variation in histopathology of vital organs. Conversely, co-treatment with graded doses of daflon improved the levels of blood lead, electrolytes, ZPP, activities of antioxidant enzymes, and histopathology of vital organs. Data obtained from the current study indicate that rats exposed to sub-chronic doses of lead acetate show increased blood lead levels, electrolyte imbalance, alongside impairment in ZPP levels, activities of antioxidant enzymes, and histopathology, while pretreatment using daflon mitigated the ensued perturbations. This, therefore, suggests that consumption of foods enriched with flavonoid fractions of diosmin and hesperidin may be beneficial for individuals inhabiting lead-polluted environments.

Alpha 2-antiplasmin deficiency in a Sudanese child: a case report.

BACKGROUND: The plasma serine protease inhibitor alpha 2-antiplasmin (α2-AP, otherwise known as α2-plasmin inhibitor) is a rapid-acting plasmin inhibitor recently found in human plasma, which seems to have a significant role in the regulation of in vivo fibrinolysis. Congenital deficiency of α2-AP is extremely uncommon. CASE PRESENTATION: We report here a case of absolute deficiency of α2-AP in an 11-year-old Sudanese boy, who had a lifelong intermittent hemorrhagic tendency (gum bleeding, epistaxis, and exaggerated bleeding after trauma). Coagulation tests including prothrombin time, partial thromboplastin time, thrombin time, bleeding time, platelet count, clot retraction test, antithrombin, and factor VIII levels were within normal limits. Hepatic function tests and complete blood count were also normal. The main interesting finding in this patient was that the whole blood clot lysis was extremely fast, completed within 5-8 hours. The second abnormal finding is that the euglobulin clot lysis time was short. Nevertheless, the concentration of α2-AP in the patient's plasma was 0.2 IU/ml (reference range is 0.80-1.20 IU/ml). The addition of pooled plasma (with normal α2-AP) to the patient's whole blood corrected the accelerated fibrinolysis. CONCLUSION: The study showed that α2-AP deficiency resulted in uninhibited fibrinolysis that caused the hemorrhagic tendency in this patient. Thus, this report demonstrates the significant role of α2-AP in coagulation.

COVID-19 in conflict border regions: a case of South Kordofan, Sudan.

The novel coronavirus disease (COVID-19) was first reported in Sudan on 13 March 2020. Since then, Sudan has experienced one of the highest rates of COVID-19 spread and fatalities in Africa. One year later, as per 22 March 2021, Sudan had registered 29,661 confirmed cases and 2,028 deaths with a case fatality rate (CFR) of 6.8 %. By 12 December 2020, of the 18 states in Sudan, South Kordofan had the fifth highest CFR of 17.4 %, only surpassed by the other conflict affected North (57.5 %), Central (50.0 %) and East (31.8 %) Darfur States. By late March 2021, just three months from December 2020, the number of cases in South Kordofan increased by 100 %, but with a significant decline in the CFR from 17.4 to 8.5 %. South Kordofan is home to over 200,000 poor and displaced people from years of destructive civil unrests. To date, several localities such as the Nubba mountains region remain under rebel control and are not accessible. South Kordofan State Ministry of Health in collaboration with the federal government and non-governmental organizations set up four isolation centres with 40 total bed capacity, but with only two mechanical ventilators and no testing centre. There is still need for further multi-sectoral coalition and equitable allocation of resources to strengthen the health systems of rural and conflict affected regions. This article aims at providing insight into the current state of COVID-19 in South Kordofan amidst the second wave to address the dearth of COVID-19 information in rural and conflict affected regions.

Co-infection of peste des petits ruminants and goatpox in a mixed flock of sheep and goats in Kanam, North Central Nigeria.

Peste-des-petits-ruminants (PPR) and Goat pox (GTP) are two devastating and economically important transboundary animal diseases of small ruminants in Africa and Asia that have been difficult to control. This study however, investigated an outbreak of PPR and GTP in a mixed flock of indigenous sheep and goats in Kanam, North Central Nigeria. A total of nine sera and seven tissues (lungs, spleen, scab and skin) samples were collected and analysed in the laboratory using competitive enzyme linked immunosorbent assay (cELISA) for PPR antibodies and polymerase chain reaction (PCR) for detection of PPR virus (PPRV) and GTP virus (GTPV). Gene fragments of the nucleoprotein of PPRV and the G-protein-coupled chemokine receptor (GPCR) of GTPV were amplified and sequenced to confirm the presence of the causative viruses. Serologically, antibodies to PPRV were detected in all (9/9) sera collected. GTPV and PPRV was detected in corresponding samples (42.8% n = 3/7) of the scab/skin samples collected by both PCR and RT-PCR technique. The phylogenetic analysis of PPRV revealed that the virus belongs to lineage IV and clustered with viruses from Gabon and Cameroon. Similarly, the GTPV also clustered with other sequences from Burkina Faso and Yemen. The positive cELISA, RT-PCR and PCR results from samples collected from the same animals confirmed co-infection of PPR and GTP in this mixed flock of sheep and goats. This is the first report of concurrent infection of PPR and GTP in mixed flock of sheep and goats in Nigeria. Our findings underscore the need for farmers to vaccinate their flock to control spread and economic losses as result of these diseases.

Assessment of source of information for polio supplementary immunization activities in 2014 and 2015, Somali, Ethiopia.

INTRODUCTION: Communication is key for the successful implementation of polio vaccination campaigns. The purpose of this study is to review and analyse the sources of information utilized by caregivers during polio supplementary immunization activities (SIAs) in Somali, Ethiopia in 2014 and 2015. METHODS: Data on sources of information about the polio campaign were collected post campaign from caregivers by trained data collectors as part of house to house independent monitoring. The sources of information analysed in this paper include town criers (via megaphones), health workers, religious leaders, kebele leaders (Kebele is the lowest administrative structure in Ethiopia), radio, television, text message and others. The repetition of these sources of information was analysed across years and zones for trends. Polio vaccination campaign coverage was also reviewed by year and zones within the Somali region in parallel with the major sources of information used in the respective year and zones. 57,745 responses were used for this analysis but the responses were received from < or = 57,745 individuals since some of them may provide more than one response. Moreover, because sampling of households is conducted independently during each round of independent monitoring, the same household may have been included more than once in our analysis. The methodology used for independent monitoring does not allow for the calculation of response rates. Monitors go from house to house until information from 20 households is received. RESULTS: From the total 57,745 responses reviewed, over 37% of respondents reported that town criers were their source for information about the 2014 and 2015 polio SIAs. Zonal trends in using town criers as a major source of information in both study years remained consistent except in two zones. 87.5% of zones that reported at least 90% coverage during both study years had utilized town criers as a major source of information while the rest (12.5%) used health workers. CONCLUSION: We found that town criers were consistently the major source of information about the polio campaigns for Somali region parents and caregivers during polio immunization days held in 2014 and 2015. Health workers and kebele leaders were also important sources of information about the polio campaign for parents.

Urbanization and carbon dioxide emissions in Singapore: evidence from the ARDL approach.

The main aim of this article is to examine empirically the impact of urbanization on carbon dioxide emissions in Singapore from 1970 to 2015. The autoregressive distributed lags (ARDL) approach is applied within the analysis. The main finding reveals a negative and significant impact of urbanization on carbon emissions in Singapore, which means that urban development in Singapore is not a barrier to the improvement of environmental quality. Thus, urbanization enhances environmental quality by reducing carbon emissions in the sample country. The result also highlighted that economic growth has a positive and significant impact on carbon emissions, which suggests that economic growth reduces environmental quality through its direct effect of increasing carbon emissions in the country. Despite the high level of urbanization in Singapore, which shows that 100 % of the populace is living in the urban center, it does not lead to more environmental degradation. Hence, urbanization will not be considered an obstacle when initiating policies that will be used to reduce environmental degradation in the country. Policy makers should consider the country's level of economic growth instead of urbanization when formulating policies to reduce environmental degradation, due to its direct impact on increasing carbon dioxide emissions.

Psychosocial Predictors of Breast Self-Examination among Female Students in Malaysia: A Study to Assess the Roles of Body Image, Self-efficacy and Perceived Barriers.

BACKGROUND: Early detection is a critical part of reducing the burden of breast cancer and breast selfexamination (BSE) has been found to be an especially important early detection strategy in low and middle income countries such as Malaysia. Although reports indicate that Malaysian women report an increase in BSE activity in recent years, additional research is needed to explore factors that may help to increase this behavior among Southeastern Asian women. OBJECTIVE: This study is the first of its kind to explore how the predicting variables of self-efficacy, perceived barriers, and body image factors correlate with self-reports of past BSE, and intention to conduct future breast self-exams among female students in Malaysia. MATERIALS AND METHODS: Through the analysis of data collected from a prior study of female students from nine Malaysian universities (n=842), this study found that self-efficacy, perceived barriers and specific body image sub-constructs (MBSRQ-Appearance Scales) were correlated with, and at times predicted, both the likelihood of past BSE and the intention to conduct breast self-exams in the future. RESULTS: Self-efficacy (SE) positively predicted the likelihood of past self-exam behavior, and intention to conduct future breast self-exams. Perceived barriers (BR) negatively predicted past behavior and future intention of breast self-exams. The body image sub-constructs of appearance evaluation (AE) and overweight preoccupation (OWP) predicted the likelihood of past behavior but did not predict intention for future behavior. Appearance orientation (AO) had a somewhat opposite effect: AO did not correlate with or predict past behavior but did correlate with intention to conduct breast self-exams in the future. The body image sub-constructs of body area satisfaction (BASS) and self-classified weight (SCW) showed no correlation with the subjects' past breast self-exam behavior nor with their intention to conduct breast self-exams in the future. CONCLUSIONS: Findings from this study indicate that both self-efficacy and perceived barriers to BSE are significant psychosocial factors that influence BSE behavior. These results suggest that health promotion interventions that help enhance self-efficacy and reduce perceived barriers have the potential to increase the intentions of Malaysian women to perform breast self-exams, which can promote early detection of breast cancers. Future research should evaluate targeted communication interventions for addressing self-efficacy and perceived barriers to breast self-exams with at-risk Malaysian women. and further explore the relationship between BSE and body image.

Risk factors for suicidal attempts among lower socioeconomic rural population of telangana region.

BACKGROUND: Suicide is an act of intentionally causing one's own death. Number of suicidal incidences is proportional to attempted suicide cases hence if attempt cases are reduced, number of suicidal death can also be decreased and for that purpose risk factors should be identified and reduced. Therefore, this study is planned to identify risk factors among lower socioeconomic rural population of surrounding areas of Hyderabad in India. MATERIALS AND METHODS: This was a prospective study in which all the suicide attempt cases reported at Bhaskar Medical College and General Hospital were included. The study period was from January 2013 to July 2013. They were undergone a detailed psychiatric interview, including their demographic details, and complete suicide risk assessment was done using Beck's suicide intent scale. RESULTS: It was found that females in the age group of 20-30 years, uneducated, married and daily laborers by occupation had higher incidence of suicidal attempts. Depressive disorder is the most common associated psychiatric disorder in both the genders, followed by alcohol use related problems. Family disputes are the other major risk factors. Most common mode for attempt was organophosphorous poisoning followed by ingestion of calotropis. CONCLUSION: Risk of suicide attempt is almost equal in terms of medium and high category of suicide assessment scale in both genders. We suggest that all individuals with alcohol related disorders must be screened for suicidal ideation so that appropriate methods can be adopted to reduce the risk.

An outline of the need for psychology knowledge in health professionals: implications for community development and breast cancer prevention.

Knowledge of health and community psychology in health professionals influences psychosocial and community determinants of health and promoting participation in disease prevention at the community level. This paper appraises the potential of knowledge on psychology in health care professionals and its contribution to community empowerment through individual behavior change and health practice. The authors proposed a schematic model for the use of psychological knowledge in health professionals to promote participation in health interventions/disease prevention programs in developing countries. By implication, the paper provides a vision on policies towards supporting breast cancer secondary prevention efforts for community health development in Asian countries.

Changes in Lipid Profiles and Other Biochemical Parameters in HIV-1 Infected Patients Newly Commenced on HAART Regimen.

Abnormalities of lipid metabolism are common in human immunodeficiency virus (HIV)-infected patients and tend to be accentuated in those receiving antiretroviral therapy, particularly with protease inhibitors (PIs). However, there is a dearth of information on serum lipid profiles and biochemical parameters among treatment-naive HIV-positive patients in our environment. We found that after 24 months of highly active antiretroviral therapy (HAART), there was a significant increase in serum lipids. After 24 months of HAART, renal impairment was associated with a low increase in mean HDL and a high increase in triglycerides (TG). In conclusion, abnormality of serum lipid is common and showed female preponderance among treatment-naive HIV patients in our environment. Patients with HIV infection on HAART should be screened for lipid disorders given their high prevalence as observed in this study, because of its potential for morbidity and mortality in patients on HAART.

Peak expiratory flow in normal medical students in Maiduguri, Borno state, Nigeria.

BACKGROUND: The assessment of lung function is of considerable importance in the diagnosis of respiratory diseases, normal reference values need to be determined. The peak expiratory flow (PEF) is a simple, reproducible and easily affordable test of lung function which has been used in resource poor countries like Nigeria. A study PEF was carried out in medical students of the University of Maiduguri and the result was compared with various prediction equations calculated in other parts of Nigeria. METHODS: It was a cross-sectional study involving 255 medical students. Data was collected between March and June 2010 using MicroPeak™ peak flow meter (Micromedical MEI 2A2 Kent) as the instrument. RESULTS: There was a statistically significant difference between the measured PEF and the predicted values based on different formulae derived from the different parts of Nigeria. However, the values in females in this study was consistent with the one obtained by one investigator in the north western part of the country. PEF positively correlated with the measured anthropometric parameters and age. CONCLUSION: The result of the study showed that the prediction formulae of Njoku et al and Salisu et al may be used in the assessment of PEF of individuals in this environment; however, further studies with larger sample size may be needed.

Streptococcus pneumoniae-induced inhibition of rat ependymal cilia is attenuated by antipneumolysin antibody.

Ciliated ependymal cells line the ventricular surfaces and aqueducts of the brain. In ex vivo experiments, pneumolysin caused rapid inhibition of the ependymal ciliary beat frequency and caused ependymal cell disruption. Wild-type pneumococci and pneumococci deficient in pneumolysin caused ciliary slowing, but penicillin lysis of wild-type, not pneumolysin-deficient, pneumococci increased the extent of ciliary inhibition. This effect was abolished by antipneumolysin antibody. Ependymal ciliary stasis by purified pneumolysin was also blocked by the addition of antipneumolysin monoclonal antibodies. These data show that antibiotic lysis of Streptococcus pneumoniae can be detrimental to the ciliated ependyma and that antipneumolysin antibody may have a therapeutic potential.