Health-seeking behaviors and self-care practices of Dominican women with lymphoedema of the leg: implications for lymphoedema management programs

BACKGROUND: In the Dominican Republic, a Latin American country with filariasis-endemic areas, more than 63,000 people have lymphatic filariasis and more than 400,000 people are at risk of future infection. In this paper, we explore the health beliefs, health-seeking behaviors and self-care practices of women with lymphoedema in filariasis-endemic areas to better understand the needs of women when developing lymphoedema morbidity control programs. METHODS: Qualitative data were collected through semi-structured interviews of 28 women, 3 focus group discussions with 28 women, field notes and photographs. RESULTS: Women described exhaustive and expensive attempts at seeking a cure for their lymphoedema. Family members were influential in providing women with initial care seeking referrals to indigenous healers credited with influence over physical, mental, spiritual and supernatural properties of illness. When indigenous treatments proved to be ineffectual, the women sought care from trained healthcare providers. Most healthcare providers incorrectly diagnosed the edema, failed to adequately treat and meet the needs of women and were viewed as expensive. Most women resorted to self-prescribing injectable, oral, or topical antibiotics along with oral analgesics as a standard practice of self-care. CONCLUSION: Healthcare providers must understand a woman's cultural perspectives of illness, her natural networks of support and referral, her behavioural practices of care-seeking and self-care and the financial burden of seeking care. In the culture of the Dominican Republic family members and traditional healthcare providers are influential advisors on initial health-seeking behaviors and self-care practices. For this reason family-oriented interventions, support groups for women and their families, community education and training on simple, low cost lymphoedema management techniques for indigenous healers are viable ways to influence the early detection, diagnosis and treatment of women with lymphoedema. The extensive use of injectable, oral and topical antibiotics by indigenous healers and women without medical supervision suggests a need for health education messages related to the risks of such practices

The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer

The natural history of cancers associated with virus exposure is intriguing, since only a minority of human tissues infected with these viruses inevitably progress to cancer. However, the molecular reasons why the infection is controlled or instead progresses to subsequent stages of tumorigenesis are largely unknown. In this article, we provide the first complete DNA methylomes of double-stranded DNA viruses associated with human cancer that might provide important clues to help us understand the described process. Using bisulfite genomic sequencing of multiple clones, we have obtained the DNA methylation status of every CpG dinucleotide in the genome of the Human Papilloma Viruses 16 and 18 and Human Hepatitis B Virus, and in all the transcription start sites of the Epstein-Barr Virus. These viruses are associated with infectious diseases (such as hepatitis B and infectious mononucleosis) and the development of human tumors (cervical, hepatic, and nasopharyngeal cancers, and lymphoma), and are responsible for 1 million deaths worldwide every year. The DNA methylomes presented provide evidence of the dynamic nature of the epigenome in contrast to the genome. We observed that the DNA methylome of these viruses evolves from an unmethylated to a highly methylated genome in association with the progression of the disease, from asymptomatic healthy carriers, through chronically infected tissues and pre-malignant lesions, to the full-blown invasive tumor. The observed DNA methylation changes have a major functional impact on the biological behavior of the viruses

HIV-1 Inhibits Autophagy in Bystander Macrophage/Monocytic Cells through Src-Akt and STAT3

Autophagy is a homeostatic mechanism of lysosomal degradation. Defective autophagy has been linked to various disorders such as impaired control of pathogens and neurodegeneration. Autophagy is regulated by a complex array of signaling pathways that act upstream of autophagy proteins. Little is known about the role of altered regulatory signaling in disorders associated with defective autophagy. In particular, it is not known if pathogens inhibit autophagy by modulation of upstream regulatory pathways. Cells infected with HIV-1 blocked rapamycin-induced autophagy and CD40-induced autophagic killing of Toxoplasma gondii in bystander (non-HIV-1 infected) macrophage/monocytic cells. Blockade of autophagy was dependent on Src-Akt and STAT3 triggered by HIV-1 Tat and IL-10. Neutralization of the upstream receptors VEGFR, β-integrin or CXCR4, as well as of HIV-1 Tat or IL-10 restored autophagy in macrophage/monocytic cells exposed to HIV-1-infected cells. Defective autophagic killing of T. gondii was detected in monocyte-derived macrophages from a subset of HIV-1+ patients. This defect was also reverted by neutralization of Tat or IL-10. These studies revealed that a pathogen can impair autophagy in non-infected cells by activating counter-regulatory pathways. The fact that pharmacologic manipulation of cell signaling restored autophagy in cells exposed to HIV-1-infected cells raises the possibility of therapeutic manipulation of cell signaling to restore autophagy in HIV-1 infection

Comprehensive dissection of prevalence rates, sex differences, and blood level-dependencies of clozapine-associated adverse drug reactions

Clozapine is often underused due to concerns about adverse drug reactions (ADRs) but studies into their prevalences are inconclusive. We therefore comprehensively examined prevalences of clozapineassociated ADRs in individuals with schizophrenia and demographic and clinical factors associated with their occurrence. Data from a multi-center study (n=698 participants) were collected. The mean number of ADRs during clozapine treatment was 4.8, with 2.4% of participants reporting no ADRs. The most common ADRs were hypersalivation (74.6%), weight gain (69.3%), and increased sleep necessity (65.9%), all of which were more common in younger participants. Participants with lower BMI prior to treatment were more likely to experience significant weight gain (>10%). Constipation occurred more frequently with higher clozapine blood levels and doses. There were no differences in ADR prevalence rates between participants receiving clozapine monotherapy and polytherapy. These findings emphasize the high prevalence of clozapine-associated ADRs and highlight several demographic and clinical factors contributing to their occurrence. By understanding these factors, clinicians can better anticipate and manage clozapine-associated ADRs, leading to improved treatment outcomes and patient well-being

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Elevers upplevelse av talsyntes som digitalt hjälpmedel i kemiundervisningen

Den här induktiva kvalitativa intervjustudien syftar till att undersöka hur elever med läs- och skrivsvårigheter upplever digitala talsynteser som redskap i kemiundervisningen och hur de upplever att skolan har hanterat deras behov av stöd. I studien genomfördes semistrukturerade intervjuer där högstadie- och gymnasieelever fick beskriva sina upplevelser att använda talsynteser i kemiundervisningen samt det stöd som skolan gett eleverna. Intervjuerna transkriberades och analyserades utifrån ett fenomenologiskt perspektiv. Det identifierades fyra kategorier: Elever upplever den digitala talsyntesen som ett stöd i lärandet, Elever upplever svårigheter med användandet av den digitala talsyntesen, Elever upplever brister i skolans resurstillsättning och Elever upplever svårigheter i kommunikationen med skolan.Resultaten visade på vikten av lärarens engagemang och elevernas behov av stöttning av läraren vid introduktion och användning av talsynteser. Då de uttalade kemins komplexa termer och begrepp inkorrekt, vilket enligt eleverna kräver ett engagemang hos kemiläraren för att talsynteserna ska fylla sin tänkta funktion. Fick eleven stöd av läraren så upplevde flertalet av eleverna att talsynteser var ett hjälpmedel för dem i kemiundervisningen. Alla eleverna upplevde att skolans resurser sattes in för sent och att de själva och deras föräldrar fått kämpaför att få stöd och digitala hjälpmedel. Alla eleverna upplevde att skolan borde varitmer förberedd för att kunna identifiera elever med läs- och skrivsvårigheter och introducera digitala hjälpmedel tidigare. Studiens slutsats är att talsynteser upplevs som ett fungerande digitalt hjälpmedel för elever med läs- och skrivsvårigheter i kemiundervisningen om eleven har stöd av läraren.

Elevers upplevelse av talsyntes som digitalt hjälpmedel i kemiundervisningen

Den här induktiva kvalitativa intervjustudien syftar till att undersöka hur elever med läs- och skrivsvårigheter upplever digitala talsynteser som redskap i kemiundervisningen och hur de upplever att skolan har hanterat deras behov av stöd. I studien genomfördes semistrukturerade intervjuer där högstadie- och gymnasieelever fick beskriva sina upplevelser att använda talsynteser i kemiundervisningen samt det stöd som skolan gett eleverna. Intervjuerna transkriberades och analyserades utifrån ett fenomenologiskt perspektiv. Det identifierades fyra kategorier: Elever upplever den digitala talsyntesen som ett stöd i lärandet, Elever upplever svårigheter med användandet av den digitala talsyntesen, Elever upplever brister i skolans resurstillsättning och Elever upplever svårigheter i kommunikationen med skolan.Resultaten visade på vikten av lärarens engagemang och elevernas behov av stöttning av läraren vid introduktion och användning av talsynteser. Då de uttalade kemins komplexa termer och begrepp inkorrekt, vilket enligt eleverna kräver ett engagemang hos kemiläraren för att talsynteserna ska fylla sin tänkta funktion. Fick eleven stöd av läraren så upplevde flertalet av eleverna att talsynteser var ett hjälpmedel för dem i kemiundervisningen. Alla eleverna upplevde att skolans resurser sattes in för sent och att de själva och deras föräldrar fått kämpaför att få stöd och digitala hjälpmedel. Alla eleverna upplevde att skolan borde varitmer förberedd för att kunna identifiera elever med läs- och skrivsvårigheter och introducera digitala hjälpmedel tidigare. Studiens slutsats är att talsynteser upplevs som ett fungerande digitalt hjälpmedel för elever med läs- och skrivsvårigheter i kemiundervisningen om eleven har stöd av läraren.

Generation of regionally specified neurons in expanded glial cultures derived from the mouse and human lateral ganglionic eminence

The specific identity of neuronal precursors within the embryonic brain is, at present, not clear. Here we show that cultures with glial characteristics derived from the embryonic mouse or human lateral ganglionic eminence (LGE) can be expanded over many passages and maintain their glial identity. Interestingly, removal of serum and EGF from the culture medium results in the generation of large numbers of neurons. The neurons derived from these cultures display many characteristic features of striatal neurons, which normally derive from the LGE, even after extensive expansion in vitro. Furthermore, a portion of the neurons generated in these cultures were shown to arise from glial fibrillary acidic protein (GFAP)-expressing cells. These results demonstrate that at least a subpopulation of neurogenic LGE precursors exhibit glial characteristics