Association between proNGF receptors and apoptotic factors in human placentae.

INTRODUCTION: Earlier studies have shown higher apoptosis in the pre-term placenta as compared to term. However, the exact mechanisms triggering these are not completely understood. Studies in neuronal and non-neuronal tissues have shown that the precursor form of NGF (proNGF) triggers apoptosis through preferential activation of p75NTR and sortilin receptors. We therefore, investigated placental expression of proNGF, mature NGF, p75NTR, co-receptor sortilin and their association with apoptosis. We further compared the levels of pro-protein convertase, furin between samples having high and low proNGF: mature NGF ratio. METHODS: Placenta samples were collected from women delivering at term (≥37 weeks; n = 41) and preterm (<37 weeks; n = 44). The protein levels of NGF, proNGF, p75NTR, Bax, Bcl-2 and furin were estimated by ELISA. Mean values of variables between different groups were compared using the independent sample t-test and associations were studied by Pearson correlation analysis. RESULTS: The placental mature NGF, proNGF and p75NTR protein levels were comparable between groups. Bax: Bcl-2 ratio was higher in preterm (p < 0.05) compared to term placenta. p75NTR was positively associated with Bax levels and sortilin levels were positively associated with p75NTR in whole cohort as well as individual groups. DISCUSSION: The higher Bax: Bcl-2 ratio in preterm placenta suggests the sensitivity to apoptosis. There were no differences in levels of NGF, proNGF, p75NTR, sortilin, and furin between groups. The observed associations between p75NTR, sortilin and Bax suggest that p75NTR and sortilin mediated signalling may be involved in the mechanisms leading to higher apoptosis in preterm placentae.

Determinants of early initiation of breastfeeding in The Gambia: a population-based study using the 2019-2020 demographic and health survey data.

BACKGROUND: Early initiation of breastfeeding within the first hour of life prevents neonatal and infant mortality. Sustainable Development Goals (SDGs) Target 3.2 aims to reduce neonatal mortality and under 5 mortality globally. The decline in the early initiation of breastfeeding in The Gambia coincides with deviations from the SDGs, due to poor indicators of child survival. Our work studied the determinants of early initiation of breastfeeding in The Gambia. METHODS: We used the 2019-2020 Gambia Demographic Health Survey (GDHS) conducted across all regions of the country. Since our population of interest was children born two years preceding the study, we only included children less than 24 months of age, living with an eligible respondent. Thus, a weighted sample of 5691 mother-child pairs was applied in the analysis. We reported summary statistics of individuals' sociodemographic, obstetrics and antenatal, household, and community-level factors. A logistic regression model was used to determine associations between early initiation of breastfeeding and covariates. RESULTS: The prevalence of early initiation of breastfeeding was 64.3% (n = 3659). Mothers who had secondary education or higher educational level had higher odds of early initiation of breastfeeding (AOR 1.22; 95% CI 1.07, 1.40). Regions with rural population notably Lower and Central and Upper River Region had lower odds of early initiation of breastfeeding [Mansakonko (AOR 0.37; 95% CI 0.26, 0.15), Kerewan (AOR 0.26; 95% CI 0.19, 0.36), Kuntaur (AOR 0.39; 95% CI 0.28, 0.54), Janjanbureh (AOR 0.48; 95% CI 0.35, 0.66) and Basse (AOR 0.64; 95%CI 0.49, 0.85)]. Also, women in the high quintile of the wealth index were more likely to initiate breastfeeding early (AOR 1.29; 95% CI 1.06, 1.57). Four or more antenatal care visits did not increase early initiation of breastfeeding. CONCLUSIONS: The results of the analyses demand affirmative action to improve maternal education, reduce poverty and inequality and empower rural communities in The Gambia. The IYCF component in antenatal care needs to be strengthened. Programs and policies on IYCF must resonate to address determinants of timely breastfeeding initiation to chart progress towards the SDG.

Highlighting an Advanced Practice Fellowship for Leadership Transition.

As the advanced practice provider (APP) workforce continues to rapidly grow in healthcare, there is a greater need for APP leadership positions. Often, these positions are organically designated to the best clinicians on the team, who may not have leadership experience. Stanford Health Care Center for Advanced Practice embarked on formalized leadership training using a newly developed administration specialty within the APP Fellowship Program to support new leader transition.

Analysis of Serum Immune Markers in Seropositive and Seronegative Rheumatoid Arthritis Among Sudanese Patients and the Relation Between the Serotype and Joint Involvement: A Cohort Study.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the synovial membrane. RA is classified as seropositive or seronegative, according to the absence or presence of primarily IgM RF, RF, and/or ACPA. The aim of this study is to identify the relationship between the serotype of rheumatoid arthritis and the level of ESR. METHODS AND MATERIALS: This is a descriptive, cross-sectional study done in Omdurman military hospital, Khartoum, Sudan. Conducted with 60 patients with RA, data were collected through a designated questionnaire which included demographic, age, gender, duration of the disease, laboratory finding. All the patients in the study were treated with conventional DMARDs and diagnosed according to the 2010 ACR/EULAR criteria; their disease activity status was assessed by DAS28/ESR. Data were analyzed using SPSS version 23. RESULTS: The study found that 91.7% of the patients were females, patients of age group between 36 and 50 years had the highest percentage at 38.3% followed by those between 51 and 70 years and the least age group between 20 and 35 years, 36.7% and 15%, respectively. Of all the patients 61.7% were found to be SPRA, while the remaining 38.3% were seronegative (SNRA). Altogether 55% of the patients had moderate disease activity, followed by 16.7% who had a remission, 15% had high disease activity and the remaining 13.3% had low disease activity. The metacarpophalangeal (MCP) joint was found to be the only joint that was significantly associated with DAS28 and its involvement was greater among seropositive patients. The most affected joints were found to be shoulders, knees, wrist, MCP, PIP and elbow, in that order. CONCLUSION: Females, middle-age group and shoulder joint were the most affected. Most RA was found to be SPRA, and the seropositive group was found to be more associated with high disease activity, while the seronegative group was associated with remission and low disease activity.

Targeting NUPR1 for Cancer Treatment: A Risky Endeavor.

NUPR1 is a transcription factor that has attracted great attention because of its various roles in cancer. Several studies were carried out to determine its molecular targets and mechanism of action to develop novel therapies against cancer. Here, we shed light on the role of NUPR1 in different types of cancer. NUPR1 regulates a complex network of pathways that may be affected by its silencing, which can cause varying effects. Its role in some types of cancer has been reported but remains incompletely understood, whereas its roles in other types of cancers have not been reported yet. Therefore, targeting NUPR1 for cancer treatment remains challenging and risky.

Silymarin and silymarin nanoparticles guard against chronic unpredictable mild stress induced depressive-like behavior in mice: involvement of neurogenesis and NLRP3 inflammasome.

BACKGROUND: The neuropathology of depression is quite complex. Thus, treatment failures are frequent with current antidepressants, raising the need for more effective ones. AIMS: This study aimed to investigate the influence of silymarin on depressive-like behavior induced by chronic unpredictable mild stress (CUMS) and explore the underlying mechanisms. METHODS: Silymarin was formulated as nanostructured lipid carriers (a lipid-based type of nanoparticle with the advantages of physical stability, good release profile, and targeted delivery). Mice were subjected to CUMS paradigm during 14 days. During this period, mice received silymarin (200 mg/kg, p.o.) per se or in its nanoparticle form or fluoxetine (10 mg/kg, p.o.). On the 15th day behavioral and biochemical parameters were analyzed. RESULTS: Oral administration of silymarin (200 mg/kg), particularly in its nanoparticulate form, exerted an antidepressant-like effect, comparable with fluoxetine in mice, as demonstrated in the behavioral despair tests. Silymarin also reversed prefrontal cortical and hippocampal CUMS-induced oxidative stress and neuroinflammation. Furthermore, silymarin augmented neurotransmitter levels, enhanced neurogenesis and inhibited nod-like receptor protein 3 inflammasome activation. Silymarin nanoparticles were superior to silymarin in certain parameters probably due to significantly higher brain silybinin (the major active component of silymarin) concentration by 12.46 fold in the group administered silymarin nanoparticles compared with the mice which were administered silymarin per se. CONCLUSIONS: The antidepressant-like effect of silymarin can be attributed to its antioxidant and anti-inflammatory effects as well as increased neurogenesis in the prefrontal cortex and hippocampus, which delineates silymarin, especially in nanoparticle form, as a promising strategy for treatment of depression.

Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors.

BACKGROUND: Stereotactic radiosurgery (SRS) for benign intracranial tumors is an established standard of care. The widespread implementation of SRS for benign spinal tumors has been limited by lack of long-term data. OBJECTIVE: To update our institutional experience of safety and efficacy outcomes after SRS for benign spinal tumors. METHODS: We performed a retrospective cohort study of 120 patients with 149 benign spinal tumors (39 meningiomas, 26 neurofibromas, and 84 schwannomas) treated with SRS between 1999 and 2016, with follow-up magnetic resonance imaging available for review. The primary endpoint was the cumulative incidence of local failure (LF), with death as a competing risk. Secondary endpoints included tumor shrinkage, symptom response, toxicity, and secondary malignancy. RESULTS: Median follow-up was 49 mo (interquartile range: 25-103 mo, range: 3-216 mo), including 61 courses with >5 yr and 24 courses with >10 yr of follow-up. We observed 9 LF for a cumulative incidence of LF of 2%, 5%, and 12% at 3, 5, and 10 yr, respectively. Excluding 10 tumors that were previously irradiated or that arose within a previously irradiated field, the 3-, 5-, and 10-yr cumulative incidence rates of LF were 1%, 2%, and 8%, respectively. At last follow-up, 35% of all lesions had decreased in size. With a total of 776 patient-years of follow-up, no SRS-related secondary malignancies were observed. CONCLUSION: Comparable to SRS for benign intracranial tumors, SRS provides longer term local control of benign spinal tumors and is a standard-of-care alternative to surgical resection.

Emotions mediate the relationship between autistic traits and disordered eating: A new autistic-emotional model for eating pathology.

The aim of the study was to assess the extent of overlap between autistic traits, body dissatisfaction and disordered eating and to explore the mediating effects of negative attitudes towards emotional expression and emotion dysregulation. The sample comprised 416 university students (82% females, 17-48 years [M=19.76, SD=3.85]), who completed an online questionnaire assessing eating attitudes and behaviours (including dieting, bulimia and oral control), body dissatisfaction, and autistic traits (including the Autism Quotient [AQ] and its related subscales as well as the Empathising Quotient). Attitudes towards emotional expression and emotion regulation were also assessed. Results revealed that eating pathology correlated highly with all AQ subscales, with the exception of the attention to detail subscale. However, there was no significant relationship between empathising and eating pathology. Path-analyses indicated that emotion dysregulation, but not negative attitudes towards emotional expression, was a significant mediator of the relationship between AQ, body dissatisfaction and eating pathology. Direct relationships were also obtained for the AQ-bulimia and the AQ-oral control paths. Prevention and early intervention programs for eating pathology would likely benefit from addressing abnormalities in emotion processes in individuals who score highly on measures of autistic traits.