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1.
Afr J Disabil ; 13: 1326, 2024.
Article in English | MEDLINE | ID: mdl-38840718

ABSTRACT

Background: The immediate implementation of early childhood education (ECE) for children with disabilities in South Africa and Kenya has been impeded by obstacles. Major gaps in implementation remain. We investigate, firstly, the widely held, but in our view fallacious, belief that the implementation of inclusive ECE can be progressively realised only when there are available resources. Secondly, we examine the other fallacious belief that children with severe and profound intellectual disabilities are ineducable, and thirdly, the belief that the provision of inclusive ECE is merely a regulatory governmental function, implying that accessibility and reasonable accommodation requirements for children with disabilities do not rest primarily on the state. Objectives: This study aimed to investigate the gaps in both countries between the policies and legislation and effective implementation, to show that these gaps are exacerbated by the perpetuation of these fallacious beliefs and by information vacuums at governmental level. Method: A critical analysis of inclusive ECE was undertaken on relevant law and policy processes in both countries to expose both governments' reasons for their lack of effective implementation of inclusive ECE. Results: The factors contributing to the lack of immediate and significant implementation of inclusive ECE for children with disabilities in both countries have been investigated. Conclusion: Accountability and transparency need to be implemented at the governance level to ensure that both governments fully implement and prioritise inclusive ECE. Contribution: This article establishes that mistaken premises and information vacuums may be used by governments in an attempt to renege on their international and constitutional obligations to implement inclusive ECE.

2.
Proc Natl Acad Sci U S A ; 121(9): e2320129121, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38377195

ABSTRACT

Despite numerous female contraceptive options, nearly half of all pregnancies are unintended. Family planning choices for men are currently limited to unreliable condoms and invasive vasectomies with questionable reversibility. Here, we report the development of an oral contraceptive approach based on transcriptional disruption of cyclical gene expression patterns during spermatogenesis. Spermatogenesis involves a continuous series of self-renewal and differentiation programs of spermatogonial stem cells (SSCs) that is regulated by retinoic acid (RA)-dependent activation of receptors (RARs), which control target gene expression through association with corepressor proteins. We have found that the interaction between RAR and the corepressor silencing mediator of retinoid and thyroid hormone receptors (SMRT) is essential for spermatogenesis. In a genetically engineered mouse model that negates SMRT-RAR binding (SMRTmRID mice), the synchronized, cyclic expression of RAR-dependent genes along the seminiferous tubules is disrupted. Notably, the presence of an RA-resistant SSC population that survives RAR de-repression suggests that the infertility attributed to the loss of SMRT-mediated repression is reversible. Supporting this notion, we show that inhibiting the action of the SMRT complex with chronic, low-dose oral administration of a histone deacetylase inhibitor reversibly blocks spermatogenesis and fertility without affecting libido. This demonstration validates pharmacologic targeting of the SMRT repressor complex for non-hormonal male contraception.


Subject(s)
DNA-Binding Proteins , Repressor Proteins , Humans , Female , Male , Animals , Mice , DNA-Binding Proteins/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism , Co-Repressor Proteins/genetics , Nuclear Receptor Co-Repressor 2/genetics , Tretinoin/pharmacology , Contraception , Nuclear Receptor Co-Repressor 1
3.
Nat Metab ; 6(2): 273-289, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38286821

ABSTRACT

Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance and fatty liver disease. Here we show that high-fat diet (HFD) feeding causes mitochondrial fragmentation in inguinal white adipocytes from male mice, leading to reduced oxidative capacity by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes after HFD. Targeted deletion of RalA in white adipocytes prevents fragmentation of mitochondria and diminishes HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, RalA increases fission in adipocytes by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1, leading to more mitochondrial fragmentation. Adipose tissue expression of the human homolog of Drp1, DNM1L, is positively correlated with obesity and insulin resistance. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics toward excessive fission, contributing to weight gain and metabolic dysfunction.


Subject(s)
Insulin Resistance , ral GTP-Binding Proteins , Animals , Humans , Male , Mice , Adipocytes, White/metabolism , Adipose Tissue/metabolism , Obesity/etiology , Obesity/metabolism , Weight Gain , ral GTP-Binding Proteins/metabolism
4.
Aging Ment Health ; 28(3): 551-556, 2024.
Article in English | MEDLINE | ID: mdl-37545400

ABSTRACT

OBJECTIVES: Suicide in late life is a public health concern. Determining profiles of psychiatric/medical comorbidity in those who attempt while engaged in mental health services may assist with prevention. We identified comorbidity profiles and their association with utilization, means, and fatality in a national sample who attempted suicide. METHODS: Using latent class analysis, all patients aged ≥ 65 from the Department of Veterans Affairs (VA) healthcare services (2012-2018) last seen in mental health prior to suicide attempt were included. Diagnoses and attempt data were obtained from VA and Center for Medicare & Medicaid Services, VA Suicide Prevention Applications Network, and VA National Mortality Data Repository. RESULTS: 2,269 patients were clustered into three profiles, all with high probability of depression. Profiles included minimal comorbidity (50.4%), high medical comorbidity (28.6%), and high (psychiatric/medical) comorbidity (21.0%). Over half (61.7%) attempted suicide within one week of their visit. The class with highest comorbidity had lowest proportion of fatal attempts, while minimal comorbidity class had highest proportion. CONCLUSIONS: Older patients last seen in mental health prior to suicide attempt were characterized by depression and varying additional comorbidity and attempt-related factors. Findings have implications for risk assessment and intervention in mental health settings, beyond depression.


Subject(s)
Suicide, Attempted , Veterans , Humans , Aged , United States/epidemiology , Suicide, Attempted/psychology , Mental Health , Medicare , Comorbidity , Suicide Prevention , Veterans/psychology
5.
Nat Rev Endocrinol ; 20(3): 168-184, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38097671

ABSTRACT

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.


Subject(s)
Adrenal Gland Neoplasms , Paraganglioma , Pheochromocytoma , Adult , Humans , Child , Pheochromocytoma/genetics , Pheochromocytoma/therapy , Pheochromocytoma/diagnosis , Paraganglioma/genetics , Paraganglioma/therapy , Germ-Line Mutation/genetics , Adrenal Gland Neoplasms/genetics , Adrenal Gland Neoplasms/therapy , Adrenal Gland Neoplasms/diagnosis , Succinate Dehydrogenase/genetics
6.
Nat Commun ; 14(1): 7791, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38057326

ABSTRACT

Oncogenic lesions in pancreatic ductal adenocarcinoma (PDAC) hijack the epigenetic machinery in stromal components to establish a desmoplastic and therapeutic resistant tumor microenvironment (TME). Here we identify Class I histone deacetylases (HDACs) as key epigenetic factors facilitating the induction of pro-desmoplastic and pro-tumorigenic transcriptional programs in pancreatic stromal fibroblasts. Mechanistically, HDAC-mediated changes in chromatin architecture enable the activation of pro-desmoplastic programs directed by serum response factor (SRF) and forkhead box M1 (FOXM1). HDACs also coordinate fibroblast pro-inflammatory programs inducing leukemia inhibitory factor (LIF) expression, supporting paracrine pro-tumorigenic crosstalk. HDAC depletion in cancer-associated fibroblasts (CAFs) and treatment with the HDAC inhibitor entinostat (Ent) in PDAC mouse models reduce stromal activation and curb tumor progression. Notably, HDAC inhibition (HDACi) enriches a lipogenic fibroblast subpopulation, a potential precursor for myofibroblasts in the PDAC stroma. Overall, our study reveals the stromal targeting potential of HDACi, highlighting the utility of this epigenetic modulating approach in PDAC therapeutics.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Animals , Mice , Cell Line, Tumor , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreas/metabolism , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Fibroblasts/metabolism , Carcinogenesis/pathology , Tumor Microenvironment
7.
Police Pract Res ; 24(6): 728-734, 2023.
Article in English | MEDLINE | ID: mdl-37981953

ABSTRACT

Cities have been experimenting with less police-centered models for responding to people experiencing mental health crises. Ten focus groups were conducted with Philadelphia police officers to understand their experiences encountering mental health distress in the community and their perspectives on a new co-deployment initiative. There was general consensus that conventional police-centered responses to mental health concerns are often problematic. However, perspectives varied on the value of co-deployment and the general feasibility of reducing police involvement. This variation is traced to different notions of what constitutes a mental health crisis, whether crises are prospectively identifiable, how dangerousness is assessed, and whether civilian co-response partners will effectively complete key response activities. Bringing greater understanding and consensus to these issues is essential to healthier and more effective responses to mental health crises.

8.
Food Funct ; 14(20): 9194-9203, 2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37779469

ABSTRACT

Blended complementary foods from cereals and high-protein sources are used worldwide to cope with infants' malnutrition. However, the usefulness of the food matrix during traditional processes reaches suboptimal effectiveness due to cereal gelatinization and viscosity, which reduce consumption. The interplay between nutritional and physical qualities needed for weaning children presents further significant constraints. A combination of processing methods can improve and optimize the overall product quality. This paper investigated the nutritional, functional, and anti-nutritional factors of a complementary infant porridge made by combining fermented sorghum flour with germinated bottle gourd seed flour. Overall, the combination improved the functional and physical properties of the porridge suitable for children of 10 months and over. A serving of 100 g would contribute 115-145% and 23-31% of the recommended nutritional intake of protein and energy, respectively, for low breast milk energy between 6-24 months. The results demonstrate that a combination of strategies and technologies are needed to balance nutritional and physical quality.


Subject(s)
Developing Countries , Eating , Infant , Female , Child , Humans , Weaning , Milk, Human , Nutrients
9.
Drug Alcohol Depend ; 251: 110949, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37699288

ABSTRACT

PURPOSE: Exclusionary school discipline is an initiating component of the school-to-prison pipeline that is racialized and may lead to short- and long-term negative substance use and criminal legal outcomes. However, these impacts, and racial disparities therein, have not been well explored empirically at the individual-level. PROCEDURES: We analyzed data from the National Longitudinal Study of Adolescent to Adult Health (1995-2009). We fit survey-weighted multivariable logistic regression models to estimate reciprocal relationships between exclusionary discipline and adolescent substance use, between these factors and subsequent exposure to the adult criminal legal system, and whether these relationships were modified by race or ethnicity. RESULTS: We found that students reporting substance use had 2.07 (95% CI 1.57, 2.75) times greater odds of reporting subsequent school discipline, and students exposed to school discipline had 1.59 (95% CI 1.26, 2.02) times greater odds of reporting subsequent substance use. Substance use and school discipline were associated with 2.69 (95% CI 2.25, 3.22) and 2.98 (95% CI 2.46, 3.60) times the odds of reporting subsequent adult criminal legal system exposure, respectively. There was little evidence of effect modification by race/ethnicity. CONCLUSIONS: Findings indicate that school discipline and substance use are reciprocally associated and have direct implications for adolescent health and future criminal legal system exposure.


Subject(s)
Prisons , Substance-Related Disorders , Humans , Adult , Adolescent , Longitudinal Studies , Public Health , Substance-Related Disorders/epidemiology , Schools
10.
Nat Commun ; 14(1): 5195, 2023 09 06.
Article in English | MEDLINE | ID: mdl-37673892

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy in need of new therapeutic options. Using unbiased analyses of super-enhancers (SEs) as sentinels of core genes involved in cell-specific function, here we uncover a druggable SE-mediated RNA-binding protein (RBP) cascade that supports PDAC growth through enhanced mRNA translation. This cascade is driven by a SE associated with the RBP heterogeneous nuclear ribonucleoprotein F, which stabilizes protein arginine methyltransferase 1 (PRMT1) to, in turn, control the translational mediator ubiquitin-associated protein 2-like. All three of these genes and the regulatory SE are essential for PDAC growth and coordinately regulated by the Myc oncogene. In line with this, modulation of the RBP network by PRMT1 inhibition reveals a unique vulnerability in Myc-high PDAC patient organoids and markedly reduces tumor growth in male mice. Our study highlights a functional link between epigenetic regulation and mRNA translation and identifies components that comprise unexpected therapeutic targets for PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Male , Animals , Mice , RNA , Epigenesis, Genetic , Regulatory Sequences, Nucleic Acid , Pancreatic Neoplasms/genetics , Carcinoma, Pancreatic Ductal/genetics , Methyltransferases , RNA-Binding Proteins/genetics
11.
bioRxiv ; 2023 Sep 14.
Article in English | MEDLINE | ID: mdl-37745372

ABSTRACT

Oncogenic lesions in pancreatic ductal adenocarcinoma (PDAC) hijack the epigenetic machinery in stromal components to establish a desmoplastic and therapeutic resistant tumor microenvironment (TME). Here we identify Class I histone deacetylases (HDACs) as key epigenetic factors facilitating the induction of pro-desmoplastic and pro-tumorigenic transcriptional programs in pancreatic stromal fibroblasts. Mechanistically, HDAC-mediated changes in chromatin architecture enable the activation of pro-desmoplastic programs directed by serum response factor (SRF) and forkhead box M1 (FOXM1). HDACs also coordinate fibroblast pro-inflammatory programs inducing leukemia inhibitory factor (LIF) expression, supporting paracrine pro-tumorigenic crosstalk. HDAC depletion in cancer-associated fibroblasts (CAFs) and treatment with the HDAC inhibitor entinostat (Ent) in PDAC mouse models reduce stromal activation and curb tumor progression. Notably, HDAC inhibition (HDACi) enriches a lipogenic fibroblast subpopulation, a potential precursor for myofibroblasts in the PDAC stroma. Overall, our study reveals the stromal targeting potential of HDACi, highlighting the utility of this epigenetic modulating approach in PDAC therapeutics.

12.
Cell Rep ; 42(8): 112997, 2023 08 29.
Article in English | MEDLINE | ID: mdl-37611587

ABSTRACT

Colorectal cancer (CRC) is driven by genomic alterations in concert with dietary influences, with the gut microbiome implicated as an effector in disease development and progression. While meta-analyses have provided mechanistic insight into patients with CRC, study heterogeneity has limited causal associations. Using multi-omics studies on genetically controlled cohorts of mice, we identify diet as the major driver of microbial and metabolomic differences, with reductions in α diversity and widespread changes in cecal metabolites seen in high-fat diet (HFD)-fed mice. In addition, non-classic amino acid conjugation of the bile acid cholic acid (AA-CA) increased with HFD. We show that AA-CAs impact intestinal stem cell growth and demonstrate that Ileibacterium valens and Ruminococcus gnavus are able to synthesize these AA-CAs. This multi-omics dataset implicates diet-induced shifts in the microbiome and the metabolome in disease progression and has potential utility in future diagnostic and therapeutic developments.


Subject(s)
Colorectal Neoplasms , Gastrointestinal Microbiome , Microbiota , Animals , Mice , Bile Acids and Salts , Metabolome
13.
Heliyon ; 9(8): e18642, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37576258

ABSTRACT

Entomophagy has recently gained attention as a potential solution to the problems of food and nutritional security. One example is the consumption of edible stinkbug. Different drying techniques may affect the nutritional, microbiological and sensory properties of the edible stinkbugs. Thus, the study assessed the effects of toasting, microwave, oven and sun drying on the nutritional composition, microbiological quality and sensory attributes of processed edible stinkbugs. Drying significantly (p < 0.05) increased the crude protein and fat content of the edible stink bugs with the highest values being recorded for the toasted samples (66.65 & 37.17% respectively). Highest Ca, K, Zn, Mg, Fe and P values were recorded after microwave drying. Reduction of 2.94 and 2.99 log cycles of the total viable count (TVC) was observed in oven and microwave dried edible stinkbugs. Toasting and microwave drying eliminated the yeasts and moulds, Enterobacteriaceae and lactic acid bacteria (LAB) in edible stinkbugs. The appearance, aroma, taste, texture and overall acceptability scores were in the same order for toasted > oven dried > microwave dried > sun dried edible stinkbugs. Toasting, oven and microwave drying can be used for processing of edible stinkbugs.

14.
Clin Endocrinol (Oxf) ; 99(3): 233-245, 2023 09.
Article in English | MEDLINE | ID: mdl-37272391

ABSTRACT

OBJECTIVE: Primary hyperparathyroidism is a common endocrine disorder, with 80% of all cases usually caused by one single hyperfunctioning parathyroid adenoma. Conventional imaging modalities for the diagnostic work-up of primary hyperparathyroidism (PHPT) include ultrasound of the neck, 99mTc-sestamibi scintigraphy, and four-dimensional computed tomography (4D-CT). However, the role of other imaging modalities, such as 11C-methionine PET/CT, in the care pathway for PHPT is currently unclear. Here, we report our experience of the diagnostic utility of 11C-methionine PET/CT in a single-center patient cohort (n = 45). DESIGN: Retrospective single-center cohort study. PATIENTS AND MEASUREMENTS: The data of eligible patients that underwent 11C-methionine PET/CT between 2014 and 2022 at Addenbrooke's Hospital (Cambridge, UK) were collected and analyzed. The clinical utility of imaging modalities was determined by comparing the imaging result with histopathological and biochemical outcomes following surgery. RESULTS: In patients with persistent primary hyperparathyroidism following previous surgery, 11C-methionine PET/CT identified a candidate lesion in 6 of 10 patients (60.0%), and histologically confirmed in 5 (50.0%). 11C-methionine PET/CT also correctly identified a parathyroid adenoma in 9 out of 12 patients (75.0%) that failed to be localized on other imaging modalities. 11C-methionine PET/CT had a sensitivity of 70.0% (95% CI 55.8 - 84.2%) for the detection of parathyroid adenomas. CONCLUSIONS: This study highlights a diagnostic role for 11C-methionine PET/CT in patients that have undergone unsuccessful prior surgery or have equivocal or negative prior imaging results, aiding localization and a targeted surgical approach.


Subject(s)
Adenoma , Hyperparathyroidism, Primary , Parathyroid Neoplasms , Humans , Positron Emission Tomography Computed Tomography , Hyperparathyroidism, Primary/diagnostic imaging , Hyperparathyroidism, Primary/etiology , Parathyroid Neoplasms/diagnostic imaging , Parathyroid Neoplasms/complications , Retrospective Studies , Cohort Studies , Adenoma/diagnosis , Adenoma/diagnostic imaging , Methionine , Technetium Tc 99m Sestamibi , Racemethionine , United Kingdom , Parathyroid Glands
15.
Proc Natl Acad Sci U S A ; 120(21): e2217826120, 2023 05 23.
Article in English | MEDLINE | ID: mdl-37192160

ABSTRACT

Molecular classification of gastric cancer (GC) identified a subgroup of patients showing chemoresistance and poor prognosis, termed SEM (Stem-like/Epithelial-to-mesenchymal transition/Mesenchymal) type in this study. Here, we show that SEM-type GC exhibits a distinct metabolic profile characterized by high glutaminase (GLS) levels. Unexpectedly, SEM-type GC cells are resistant to glutaminolysis inhibition. We show that under glutamine starvation, SEM-type GC cells up-regulate the 3 phosphoglycerate dehydrogenase (PHGDH)-mediated mitochondrial folate cycle pathway to produce NADPH as a reactive oxygen species scavenger for survival. This metabolic plasticity is associated with globally open chromatin structure in SEM-type GC cells, with ATF4/CEBPB identified as transcriptional drivers of the PHGDH-driven salvage pathway. Single-nucleus transcriptome analysis of patient-derived SEM-type GC organoids revealed intratumoral heterogeneity, with stemness-high subpopulations displaying high GLS expression, a resistance to GLS inhibition, and ATF4/CEBPB activation. Notably, coinhibition of GLS and PHGDH successfully eliminated stemness-high cancer cells. Together, these results provide insight into the metabolic plasticity of aggressive GC cells and suggest a treatment strategy for chemoresistant GC patients.


Subject(s)
Phosphoglycerate Dehydrogenase , Stomach Neoplasms , Humans , Phosphoglycerate Dehydrogenase/genetics , Phosphoglycerate Dehydrogenase/metabolism , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Cell Line, Tumor , Glutamine/metabolism , Nutrients
16.
Lancet Diabetes Endocrinol ; 11(5): 345-361, 2023 05.
Article in English | MEDLINE | ID: mdl-37011647

ABSTRACT

Patients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in almost 20% of patients, might coexist with paragangliomas arising from other locations (eg, adrenal medulla, para-aortic, cardiac or thoracic, and pelvic). Given the higher risk of tumour multifocality and bilaterality for phaeochromocytomas and paragangliomas (PPGLs) because of SDHD pathogenic variants than for their sporadic and other genotypic counterparts, the management of patients with SDHD PPGLs is clinically complex in terms of imaging, treatment, and management options. Furthermore, locally aggressive disease can be discovered at a young age or late in the disease course, which presents challenges in balancing surgical intervention with various medical and radiotherapeutic approaches. The axiom-first, do no harm-should always be considered and an initial period of observation (ie, watchful waiting) is often appropriate to characterise tumour behaviour in patients with these pathogenic variants. These patients should be referred to specialised high-volume medical centres. This consensus guideline aims to help physicians with the clinical decision-making process when caring for patients with SDHD PPGLs.


Subject(s)
Adrenal Gland Neoplasms , Paraganglioma , Pheochromocytoma , Humans , Adrenal Gland Neoplasms/diagnosis , Adrenal Gland Neoplasms/genetics , Adrenal Gland Neoplasms/therapy , Germ-Line Mutation/genetics , Paraganglioma/diagnosis , Paraganglioma/genetics , Paraganglioma/therapy , Pheochromocytoma/diagnosis , Pheochromocytoma/genetics , Pheochromocytoma/therapy , Succinate Dehydrogenase/genetics , Practice Guidelines as Topic
17.
Cureus ; 15(3): e36546, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37095796

ABSTRACT

Keto diet is defined as a high-fat, adequate-protein, and low-carbohydrate nutrition which forces the body to burn fats and use an alternative metabolic fuel resource by stimulating endogenous ketone production. The standard range of ketones in ketosis is up to 3.00mmol/L, and anything beyond this level can result in serious medical conditions. This diet's most common and easily reversible consequences are constipation, low-grade acidosis, hypoglycemia, kidney stones, and increased lipid in the blood. We present a case of a 36-year-old female who presented with pre-renal azotemia after starting a keto diet regimen.

18.
Foods ; 12(4)2023 Feb 05.
Article in English | MEDLINE | ID: mdl-36832764

ABSTRACT

With food insecurity rising dramatically in Sub-Saharan Africa, promoting the use of sorghum, cowpea and cassava flours in staple food such as bread may reduce wheat imports and stimulate the local economy through new value chains. However, studies addressing the technological functionality of blends of these crops and the sensory properties of the obtained breads are scarce. In this study, cowpea varieties (i.e., Glenda and Bechuana), dry-heating of cowpea flour and cowpea to sorghum ratio were studied for their effects on the physical and sensory properties of breads made from flour blends. Increasing cowpea Glenda flour addition from 9 to 27% (in place of sorghum) significantly improved bread specific volume and crumb texture in terms of instrumental hardness and cohesiveness. These improvements were explained by higher water binding, starch gelatinization temperatures and starch granule integrity during pasting of cowpea compared to sorghum and cassava. Differences in physicochemical properties among cowpea flours did not significantly affect bread properties and texture sensory attributes. However, cowpea variety and dry-heating significantly affected flavour attributes (i.e., beany, yeasty and ryebread). Consumer tests indicated that composite breads could be significantly distinguished for most of the sensory attributes compared to commercial wholemeal wheat bread. Nevertheless, the majority of consumers scored the composite breads from neutral to positive with regard to liking. Using these composite doughs, chapati were produced in Uganda by street vendors and tin breads by local bakeries, demonstrating the practical relevance of the study and the potential impact for the local situation. Overall, this study shows that sorghum, cowpea and cassava flour blends can be used for commercial bread-type applications instead of wheat in Sub-Saharan Africa.

19.
JAMA Psychiatry ; 80(4): 287-295, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36811913

ABSTRACT

Importance: Frailty is associated with reduced physiological reserve, lack of independence, and depression and may be salient for identifying older adults at increased risk of suicide attempt. Objectives: To examine the association between frailty and risk of suicide attempt and how risk differs based on components of frailty. Design, Setting, and Participants: This nationwide cohort study integrated databases from the US Department of Veterans Affairs (VA) inpatient and outpatient health care services, Centers for Medicare & Medicaid Services data, and national suicide data. Participants included all US veterans aged 65 years or older who received care at VA medical centers from October 1, 2011, to September 30, 2013. Data were analyzed from April 20, 2021, to May 31, 2022. Exposures: Frailty, defined based on a validated cumulative-deficit frailty index measured using electronic health data and categorized into 5 levels: nonfrailty, prefrailty, mild frailty, moderate frailty, and severe frailty. Main Outcomes and Measures: The main outcome was suicide attempts through December 31, 2017, provided by the national Suicide Prevention Applications Network (nonfatal attempts) and Mortality Data Repository (fatal attempts). Frailty level and components of the frailty index (morbidity, function, sensory loss, cognition and mood, and other) were assessed as potential factors associated with suicide attempt. Results: The study population of 2 858 876 participants included 8955 (0.3%) who attempted suicide over 6 years. Among all participants, the mean (SD) age was 75.4 (8.1) years; 97.7% were men, 2.3% were women, 0.6% were Hispanic, 9.0% were non-Hispanic Black, 87.8% were non-Hispanic White, and 2.6% had other or unknown race and ethnicity. Compared with patients without frailty, risk of suicide attempt was uniformly higher among patients with prefrailty to severe frailty, with adjusted hazard ratios (aHRs) of 1.34 (95% CI, 1.27-1.42; P < .001) for prefrailty, 1.44 (95% CI, 1.35-1.54; P < .001) for mild frailty, 1.48 (95% CI, 1.36-1.60; P < .001) for moderate frailty, and 1.42 (95% CI, 1.29-1.56; P < .001) for severe frailty. Lower levels of frailty were associated with greater risk of lethal suicide attempt (aHR, 1.20 [95% CI, 1.12-1.28] for prefrail veterans). Bipolar disorder (aHR, 2.69; 95% CI, 2.54-2.86), depression (aHR, 1.78; 95% CI, 1.67-1.87), anxiety (aHR, 1.36; 95% CI, 1.28-1.45), chronic pain (aHR, 1.22; 95% CI, 1.15-1.29), use of durable medical equipment (aHR, 1.14; 95% CI, 1.03-1.25), and lung disease (aHR, 1.11; 95% CI, 1.06-1.17) were independently associated with increased risk of suicide attempt. Conclusions and Relevance: This cohort study found that among US veterans aged 65 years or older, frailty was associated with increased risk of suicide attempts and lower levels of frailty were associated with greater risk of suicide death. Screening and involvement of supportive services across the spectrum of frailty appear to be needed to help reduce risk of suicide attempts.


Subject(s)
Frailty , Veterans , Male , Humans , Aged , Female , United States , Suicide, Attempted/prevention & control , Cohort Studies , Medicare
20.
Am J Geriatr Psychiatry ; 31(7): 525-539, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36494291

ABSTRACT

Older veterans are vastly underrepresented in studies that shape national suicide prevention strategies. This is of great concern because factors that impact younger veterans may not be as robust in later life. Although younger veterans have higher rate of suicide, the highest counts of death by suicide are in older veterans. However, it remains unclear from the extant literature what factors may influence increased or decreased risk of late-life suicide in veterans. The objective of this systematic review was to identify risk and protective factors related to suicide outcomes (i.e., ideation, attempt, death, or suicide-related behavior [SRB]) among older veterans. Furthermore, it offers data regarding future study directions and hypothesis generation for late-life suicide research and for informing potential intervention and prevention efforts in this area. We searched 4 databases from inception up to May 5, 2022. We screened 2,388 abstracts for inclusion and 508 articles required full text review. The final sample included 19 studies published between 2006 and 2022. We found five domains of factors studied (i.e., neuropsychiatric, social determinants of health, aging stereotypes, residential and supportive housing settings, and multifactorial-neuropsychiatric/mental health and physical health) with more risk factors than protective factors reported. Across the three suicide outcomes only neuropsychiatric factors were consistently identified as risk factors. Neuropsychiatric factors also comprised the largest group of risk factors studied. More innovative targets to consider for intervention and more innovative methods to predict suicide in late-life are needed. There is also continued necessity to design suicide prevention interventions for older veterans given lethality trends.


Subject(s)
Suicide , Veterans , Humans , Aged , Veterans/psychology , Suicidal Ideation , Suicide Prevention , Risk Factors
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