In utero exposure to maternal diabetes exacerbates dietary sodium intake-induced endothelial dysfunction by activating cyclooxygenase 2-derived prostanoids.

Prenatal exposure to maternal diabetes has been recognized as a significant cardiovascular risk factor, increasing the susceptibility to the emergence of conditions such as high blood pressure, atherosclerosis, and heart disease in later stages of life. However, it is unclear if offspring exposed to diabetes in utero have worse vascular outcomes on a high-salt (HS) diet. To test the hypothesis that in utero exposure to maternal diabetes predisposes to HS-induced vascular dysfunction, we treated adult male wild-type offspring (DM_Exp, 6 mo old) of diabetic Ins2+/C96Y mice (Akita mice) with HS (8% sodium chloride, 10 days) and analyzed endothelial function via wire myograph and cyclooxygenase (COX)-derived prostanoids pathway by ELISA, quantitative PCR, and immunochemistry. On a regular diet, DM_Exp mice did not manifest any vascular dysfunction, remodeling, or inflammation. However, HS increased aortic contractility to phenylephrine and induced endothelial dysfunction (analyzed by acetylcholine-induced endothelium-dependent relaxation), vascular hydrogen peroxide production, COX2 expression, and prostaglandin E2 (PGE2) overproduction. Interestingly, ex vivo antioxidant treatment (tempol) or COX1/2 (indomethacin) or COX2 (NS398) inhibitors improved or reverted the endothelial dysfunction in DM_Exp mice fed a HS diet. Finally, DM_Exp mice fed with HS exhibited greater circulating cytokines and chemokines accompanied by vascular inflammation. In summary, our findings indicate that prenatal exposure to maternal diabetes predisposes to HS-induced vascular dysfunction, primarily through the induction of oxidative stress and the generation of COX2-derived PGE2. This supports the concept that in utero exposure to maternal diabetes is a cardiovascular risk factor in adulthood.NEW & NOTEWORTHY Using a unique mouse model of prenatal exposure to maternal type 1 diabetes, our study demonstrates the novel observation that prenatal exposure to maternal diabetes results in a predisposition to high-salt (HS) dietary-induced vascular dysfunction and inflammation in adulthood. Mechanistically, we demonstrated that in utero exposure to maternal diabetes and HS intake induces vascular oxidative stress, cyclooxygenase-derived prostaglandin E2, and inflammation.

Spiritual Interventions Among Pediatric Patients With Cancer: A Systematic Review And Meta-Analysis.

CONTEXT: Although spiritual intervention is crucial in the care of childhood cancer patients (CCPs), its effectiveness has not yet been systematically evaluated. OBJECTIVES: To determine the effectiveness of existing spiritual interventions on psychological, spiritual outcomes, and quality of life (QoL) in CCPs. METHODS: We searched eight databases to identify relevant randomized controlled trials and quasi-experimental studies. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials. Results were either synthesized in a systematic narrative synthesis or a meta-analysis using a random effects model, where appropriate. The pooled treatment effect was estimated using the standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: Twelve studies with 576 CCPs were included. Eight studies showed a high risk of bias. The overall effect of existing spiritual interventions on QoL (Z = 1.05, SMD = 0.64, 95%CI = -0.15 to 1.83, P = 0.29), anxiety (Z = 1.11, SMD = -0.83, 95%CI = -2.30 to 0.64, P = 0.28) and depressive symptoms (Z = 1.06, SMD = -0.49, 95%CI = -1.40 to 0.42, P = 0.12) were statistically nonsignificant. The nonsignificant findings could be attributed to the high heterogeneity among the included studies (QoL: I2 = 85%; anxiety: I2 = 90%; depressive symptoms: I2 = 58%). CONCLUSION: Evidence to support the positive effects of existing spiritual interventions on psychological and spiritual outcomes and QoL in CCPs is insufficient. Future studies should adopt a more rigorous design and unify the outcome measures to reduce the risk of bias and heterogeneity, respectively.

Role of the CCL5 and Its Receptor, CCR5, in the Genesis of Aldosterone-Induced Hypertension, Vascular Dysfunction, and End-Organ Damage.

BACKGROUND: Aldosterone has been described to initiate cardiovascular diseases by triggering exacerbated sterile vascular inflammation. The functions of CCL5 (C-C motif chemokine ligand 5) and its receptor CCR5 (C-C motif chemokine receptor 5) are well known in infectious diseases, their contributions to aldosterone-induced vascular injury and hypertension remain unknown. METHODS: We analyzed the vascular profile, blood pressure, and renal damage in wild-type (CCR5+/+) and CCR5 knockout (CCR5-/-) mice treated with aldosterone (600 µg/kg per day for 14 days) while receiving 1% saline to drink. Vascular function was analyzed in aorta and mesenteric arteries, blood pressure was measured by telemetry and renal injury and inflammation were analyzed via histology and flow cytometry. Endothelial cells were used to study the molecular signaling whereby CCL5 induces endothelial dysfunction. RESULTS: Aldosterone treatment resulted in exaggerated CCL5 circulating levels and vascular CCR5 expression in CCR5+/+ mice accompanied by endothelial dysfunction, hypertension, and renal inflammation and damage. CCR5-/- mice were protected from these aldosterone-induced effects. Mechanistically, we demonstrated that CCL5 increased NOX1 (NADPH oxidase 1) expression, reactive oxygen species formation, NFκB (nuclear factor kappa B) activation, and inflammation and reduced NO production in isolated endothelial cells. These effects were abolished by antagonizing CCR5 with Maraviroc. Finally, aorta incubated with CCL5 displayed severe endothelial dysfunction, which is prevented by blocking NOX1, NFκB, or CCR5. CONCLUSIONS: Our data demonstrate that CCL5/CCR5, through activation of NFκB and NOX1, is critically involved in aldosterone-induced vascular and renal damage and hypertension placing CCL5 and CCR5 as potential therapeutic targets for conditions characterized by aldosterone excess.

MicroRNA-19 is regulated by aldosterone in a sex-specific manner to alter kidney sodium transport.

A key regulator of blood pressure homeostasis is the steroid hormone aldosterone, which is released as the final signaling hormone of the renin-angiotensin-aldosterone-signaling (RAAS) system. Aldosterone increases sodium (Na+) reabsorption in the kidney distal nephron to regulate blood volume. Unregulated RAAS signaling can lead to hypertension and cardiovascular disease. The serum and glucocorticoid kinase (SGK1) coordinates much of the Na+ reabsorption in the cortical collecting duct (CCD) tubular epithelial cells. We previously demonstrated that aldosterone alters the expression of microRNAs (miRs) in CCD principal cells. The aldosterone-regulated miRs can modulate Na+ transport and the cellular response to aldosterone signaling. However, the sex-specific regulation of miRs by aldosterone in the kidney distal nephron has not been explored. In this study, we report that miR-19, part of the miR-17-92 cluster, is upregulated in female mouse CCD cells in response to aldosterone activation. Mir-19 binding to the 3'-untranslated region of SGK1 was confirmed using a dual-luciferase reporter assay. Increasing miR-19 expression in CCD cells decreased SGK1 message and protein expression. Removal of this cluster using a nephron-specific, inducible knockout mouse model increased SGK1 expression in female mouse CCD cells. The miR-19-induced decrease in SGK1 protein expression reduced the response to aldosterone stimulation and may account for sex-specific differences in aldosterone signaling. By examining evolution of the miR-17-92 cluster, phylogenetic sequence analysis indicated that this cluster arose at the same time that other Na+-sparing and salt regulatory proteins, specifically SGK1, first emerged, indicating a conserved role for these miRs in kidney function of salt and water homeostasis.NEW & NOTEWORTHY Expression of the microRNA-17-92 cluster is upregulated by aldosterone in mouse cortical collecting duct principal cells, exclusively in female mice. MiR-19 in this cluster targets the serum and glucocorticoid kinase (SGK1) to downregulate both mRNA and protein expression, resulting in a decrease in sodium transport across epithelial cells of the collecting duct. The miR-17-92 cluster is evolutionarily conserved and may act as a novel feedback regulator for aldosterone signaling in females.

Importance of parental involvement in paediatric palliative care in Hong Kong: qualitative case study.

OBJECTIVE: To compare and contrast the perceived care needs of children with life-limiting conditions (CLLC) from the perspectives of the children, parents and healthcare providers. DESIGN: A qualitative case study method using semistructured interviews was employed with a within-case and across-case analysis. Themes and subthemes emerging from the cases were compared and contrasted in the across-case analysis to explore the similarities and variations in participant perceptions. SETTING/PARTICIPANTS: The setting was the paediatric departments of five regional hospitals in Hong Kong. Twenty-five sets of informants (CLLC-parent-healthcare provider) were recruited, with 65 individual interviews conducted. RESULTS: A total of 3784 units of analysis were identified, resulting in three themes with subthemes. 'Living with the disease' (55.8%) occupied the largest proportion, followed by 'information and understanding about the disease' (27.4%), and 'care support and palliative care' (16.8%). Healthcare provider support mainly focused on physical concerns. Family and social support were present, but carer stress created tension between couples. Doctors were the primary source of medical information, but the parents had to seek further information via the internet and support from patient groups. There was a perceived need for better coordination and collaboration of care. The palliative care approach coordinated by nurses was seen as helpful in addressing the care needs of the CLLC. CONCLUSIONS: This original study identified the importance of palliative care with active engagement of parents which can address the service gap for CLLC.

What makes a city 'breastfeeding-friendly'? A scoping review of indicators of a breastfeeding-friendly city.

A breastfeeding-friendly city is one where there is an enabling environment to support breastfeeding throughout the first 2 years or more of a child's life. Indicators of a breastfeeding-friendly city have yet to be identified. What are the indicators or criteria used to define breastfeeding friendliness in a geographic area such as a city and the settings within, which we have classified as community, healthcare and workplace? Three major databases and grey literature were searched. Records were screened to identify publications describing criteria such as indicators or descriptions of a breastfeeding-friendly setting, defined as 'criteria-sets'. These criteria-sets were then categorized and summarized by settings. The search up to 2 September 2021 found 119 criteria-sets from a range of settings: geographic locations (n = 33), community entities (n = 24), healthcare facilities (n = 28), workplaces (n = 28) and others (n = 6). Overall, 15 community, 22 healthcare and 9 workplace related criteria were extracted from the criteria-sets. Criteria that were consistently present in all settings were policy, training & education, skilled breastfeeding support and physical infrastructure. Some criteria-sets of geographic locations contained criteria only from a single setting (e.g., the presence of breastfeeding-friendly cafes). Criteria-sets were present for all settings as defined in this review, but few were actual indicators. Specifically, there were no existing indicators of a breastfeeding-friendly city. Several common components of the criteria-sets were identified, and these could be used in developing indicators of a breastfeeding-friendly city. Future studies should determine which of these are important and how each can be measured.

Mitigating Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: Ameliorating Sexual Function and Psychological Well-Being in Older Men.

This study aimed to investigate the prevalence of lower urinary tract symptoms (LUTS) in older men (N= 3056) with benign prostatic hyperplasia (BPH) and its effects on their sexual function and mental health. Descriptive, correlation, and regression analyses were used to explore the relationships between prostate and lower urinary tract health and psychological well-being. Better prostate and lower urinary tract health positively affected psychological well-being, and sexual function also had a positive influence. LUTS have an adverse impact on sexual function and mental health. Early intervention is crucial for mitigating the negative impact of LUTS on the quality of life in older men. Addressing prostate and lower urinary tract health issues through appropriate interventions may improve psychological well-being. Health care professionals must consider the adverse effects of BPH and LUTS on sexual function and mental health, and implement interventions to enhance the overall quality of life in older men.

Exploring factors influencing the uptake of kangaroo mother care: key informant interviews with parents.

BACKGROUND: The updated World Health Organization (WHO) guideline recommends immediate kangaroo mother care (KMC) for all infants, particularly those born preterm. However, its uptake and sustainability have been unsatisfactory. Therefore, we aimed to gain deeper insight into factors influencing the uptake of KMC practice in our setting, and thereby identify possible solutions for the development of relevant interventions to improve its adoption and make KMC a routine practice for all infants. METHODS: Using the Triandis model of social behaviour as our framework, we conducted key informant interviews with parents and healthcare providers. Trained interviewers conducted interviews with nine parents, recruited via purposive sampling. These parents were parents of preterm infants who had been introduced to KMC. Data was transcribed and analysed based on Triandis' Theory of Interpersonal Behaviour. This paper only reports the results of the parent interviews. RESULTS: Major findings were how positive feelings like warmth and contentment, the sense of parenthood with KMC, the benefits of KMC for their infant and parents being enablers for KMC uptake. Conversely, the lack of KMC awareness, the initial negative feelings such as fear, uncertainty and embarrassment, the prioritization of time for milk expression, overcrowding in the ward, lack of space and privacy, limited visiting hours, lack of support and poor communication resulting in misapprehension about KMC were major barriers. CONCLUSION: A deeper understanding of the factors influencing the uptake of KMC using the Triandis behavioural model provided a way forward to help improve its uptake and sustainability in our settings. TRIAL REGISTRATION: This study was registered with the National Medical Research Registry (NMRR-17-2984-39191).

Role Of The C-C Motif Chemokine Ligand 5 (CCL5) And Its Receptor, C-C Motif Chemokine Receptor 5 (CCR5) In The Genesis Of Aldosterone-induced Hypertension, Vascular Dysfunction, And End-organ Damage.

Background: Aldosterone, a mineralocorticoid steroid hormone, has been described to initiate cardiovascular diseases by triggering exacerbated sterile vascular inflammation. The functions of C-C Motif Chemokine Ligand 5 (CCL5) and its receptor, C-C Motif Chemokine Receptor 5 (CCR5), are well known in infectious diseases, but their roles in the genesis of aldosterone-induced vascular injury and hypertension are unknown. Methods: We analyzed the vascular profile, blood pressure, and renal damage in wild-type (CCR5+/+) and CCR5 knockout (CCR5-/-) mice treated with aldosterone (600 µg/kg/day for 14 days) while receiving 1% saline to drink. Results: Here, we show that CCR5 plays a central role in aldosterone-induced vascular injury, hypertension, and renal damage. Long-term infusion of aldosterone in CCR5+/+ mice resulted in exaggerated CCL5 circulating levels and vascular CCR5 expression. Aldosterone treatment also triggered vascular injury, characterized by endothelial dysfunction and inflammation, hypertension, and renal damage. Mice lacking CCR5 were protected from aldosterone-induced vascular damage, hypertension, and renal injury. Mechanistically, we demonstrated that CCL5 increased NADPH oxidase 1 (Nox1) expression, reactive oxygen species (ROS) formation, NFκB activation, and inflammation and reduced nitric oxide production in isolated endothelial cells. These effects were abolished by antagonizing CCR5 with Maraviroc. Finally, aortae incubated with CCL5 displayed severe endothelial dysfunction, which is prevented by blocking Nox1, NFκB, or with Maraviroc treatment. Conclusions: Our data demonstrate that CCL5/CCR5, through activation of NFkB and Nox1, is critically involved in aldosterone-induced vascular and renal damage and hypertension. Our data place CCL5 and CCR5 as potential targets for therapeutic interventions in conditions with aldosterone excess.

Continuous positive airway pressure (CPAP) for apnoea of prematurity.

BACKGROUND: Apnoea of prematurity (AoP) is defined as a pause in breathing for 20 seconds or longer, or for less than 20 seconds when accompanied by bradycardia and hypoxaemia, in a preterm infant. An association between the severity of apnoea and neurodevelopmental delay has been reported. Continuous positive airway pressure (CPAP) is a form of non-invasive ventilatory assistance that has been shown to be relatively safe and effective in preventing and treating respiratory distress among preterm infants. It is less clear whether CPAP treatment is safe and effective in the prevention and treatment of AoP. OBJECTIVES: 1. To assess the effects of CPAP on AoP in preterm infants (this may be compared to supportive care or mechanical ventilation). 2. To assess the effects of different CPAP delivery systems on AoP in preterm infants. SEARCH METHODS: Searches were conducted in September 2022 in the following databases: Cochrane Library, MEDLINE, Embase, and CINAHL. We also searched clinical trial registries and the reference lists of studies selected for inclusion. SELECTION CRITERIA: We included all randomised and quasi-randomised controlled trials (RCTs) in which researchers determined that CPAP was necessary for AoP in preterm infants (born before 37 weeks). Cross-over studies were also included, provided sufficient data were available for analysis. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane and Cochrane Neonatal, including independent assessment of risk of bias and extraction of data by at least two review authors. Discrepancies were resolved by involvement of a third author. We used the GRADE approach to assess the certainty of evidence for the following outcomes: 1) failed CPAP; 2) apnoea; 3) adverse effects of CPAP. MAIN RESULTS: We included four single-centre trials conducted in Malaysia, Spain, Germany, and North America, involving 138 infants with a mean/median gestation of 26 to 28 weeks. Two studies were parallel-group RCTs and two were cross-over trials. None of the studies compared CPAP with supportive care. All trials compared one form of CPAP with another. Two compared a variable flow device with ventilator CPAP, one compared two different variable flow devices, and one compared a variable flow device with bubble CPAP. Interventions were administered for periods ranging between six and 48 hours, with pressures between 4 and 6 cm H2O. We assessed all trials as having a high risk of bias for blinding of participants and personnel, and two studies for blinding of outcome assessors. We found a high risk of a carry-over effect in two studies where the washout period was not adequately described, and a high risk of bias in a study that appeared to use an analysis method not generally accepted for cross-over studies. Comparison 1. CPAP and supportive care compared to supportive care alone We did not identify any study for inclusion in this comparison. Comparison 2. CPAP delivered by different types of devices 2a. Variable flow compared to ventilator CPAP Two studies were included in this comparison. We are very uncertain whether there is any difference in the incidence of failed CPAP, defined as the need for mechanical ventilation (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.01 to 2.90; 1 study, 26 participants; very low-certainty). We are very uncertain whether there is any difference in the frequency of apnoea events (mean difference (MD) per four-hour interval -0.10, 95% CI -1.30 to 1.10; 1 study, 26 participants; very low-certainty). We are uncertain whether there is any difference in adverse events. Neurodevelopmental outcomes were not reported. 2b. Variable flow compared to bubble CPAP We included one study in this comparison, but it did not report our pre-specified outcomes. 2c. Infant Flow variable flow CPAP compared to Medijet variable flow CPAP We are very uncertain whether there is any difference in the incidence of failed CPAP (RR 2.62, 95% CI 0.91 to 7.53; 1 study, 80 participants; very low-certainty). The frequency of apnoea was not reported, and we do not know whether there is any difference in adverse events. Neurodevelopmental outcomes were not reported. Comparison 3. CPAP compared to mechanical ventilation We did not identify any studies for inclusion in this comparison. AUTHORS' CONCLUSIONS: Due to the limited available evidence, we are very uncertain whether any CPAP device is more effective than other forms of supportive care, other CPAP devices, or mechanical ventilation for the prevention and treatment of AoP. The devices used in these studies included two types of variable flow CPAP device: bubble CPAP and ventilator CPAP. For each comparison, data were only available from a single study. There are theoretical reasons why these devices might have different effects on AoP, therefore further trials are indicated.

Needs and experiences of cancer care in patients' perspectives among the lesbian, gay, bisexual, transgender and queer community: a systematic review.

Individuals within the Lesbian, Gay, Bisexual, Transgender and Queer (LGBTQ) community who are diagnosed with cancer experience inequitable treatment in healthcare systems worldwide, resulting in dissatisfaction, communication challenges with healthcare providers, and a deep sense of disappointment. Stigma, discrimination, and perceived homophobia further heighten the risk of psychological and attitudinal disorders, including depression and suicidal tendencies, among LGBTQ cancer patients. To comprehensively assess the discrimination faced by LGBTQ cancer patients and gain deeper insights into their needs and experiences, we conducted a systematic review following PRISMA guidelines. We searched for relevant articles using specific keywords in reputable databases such as PubMed, Google Scholar, and PsycINFO. We rigorously evaluated article quality using the CASP (Critical Appraisal Skills Programme) checklist. From a total of 75 eligible studies, we carefully selected 14 studies, specifically examining LGBTQ cancer patients who were currently undergoing or had previously undergone cancer treatment. The studies revealed various factors, including unmet needs related to anxiety and depression, instances of discrimination, disparities in care, and inadequate support systems. A majority of patients expressed dissatisfaction with their cancer care and continued to encounter discrimination and disparities throughout their treatment journeys. Consequently, this led to heightened levels of anxiety, stress, depression, and negative perceptions of healthcare providers. Based on these findings, we recommend providing specialized training to social workers and healthcare providers. This training will equip them with the necessary skills and knowledge to deliver culturally sensitive care tailored to the unique needs of LGBTQ cancer patients. By addressing discrimination, reducing disparities, and fostering an inclusive environment, healthcare professionals can strive to ensure that LGBTQ cancer patients receive the care they deserve.

Effectiveness of spiritual interventions on psychological outcomes and quality of life among paediatric patients with cancer: a study protocol for a systematic review.

INTRODUCTION: Cancer and its treatment affect children's physical, psychological and social well-being throughout the disease trajectory. Spiritual well-being is a fundamental dimension of people's overall health and is considered a source of strength to motivate patients to cope with and adapt to their disease. Appropriate spiritual interventions are important to mitigate the psychological impact of cancer on children, with an ultimate goal of improving their quality of life (QoL) throughout the treatment course. However, the overall effectiveness of spiritual interventions for paediatric patients with cancer remains unclear. This paper describes a protocol to systematically summarise the characteristics of studies related to existing spiritual interventions and synthesise their effectiveness on psychological outcomes and QoL among children with cancer. METHODS AND ANALYSIS: Ten databases will be searched to identify appropriate literature: MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, PsycINFO, LILACS, OpenSIGLE, the Chinese Biomedical Literature Database, the Chinese Medical Current Contents and the Chinese National Knowledge Infrastructure. All randomised controlled trials that meet our inclusion criteria will be included. The primary outcome will be QoL as evaluated by self-reported measures. The secondary outcomes will be self-reported or objectively measured psychological outcomes, including anxiety and depression. Review Manager V.5.3 will be used to synthesise the data, calculate treatment effects, perform any subgroup analyses and assess the risk of bias in included studies. ETHICAL AND DISSEMINATION: The results will be presented at international conferences and published in peer-reviewed journals. As no individual data will be involved in this review, ethical approval is not required.

Effects of parity on preterm delivery in twin gestations conceived with in vitro fertilization.

Objective: To determine the relationship between prior obstetrical history and gestational age at delivery in a twin pregnancy. Design: Retrospective cohort study using the United States Society for Assisted Reproductive Technology Clinic Outcomes Reporting System database. Setting: Clinic-based data. Patients: Patients undergoing in vitro fertilization (IVF) in the United States with live delivery of twins. Interventions: None. Main outcome measures: The main outcome measures are median gestational age at delivery and rate of preterm delivery (before 37 weeks). Results: The median gestational age at delivery of IVF-conceived twins was 36.3 (interquartile rate 34.4, 37.6) weeks for nulliparous women, 35.9 (34.0, 37.1) weeks for parous women with a prior preterm birth, and 36.7 (35.1, 37.7) weeks for parous women without a prior preterm birth. The rate of preterm delivery was 61% for nulliparous women, 70% for parous women with a prior preterm birth, and 55% for parous women without a prior preterm birth. Conclusions: Parous women without a history of preterm delivery had lower rates of preterm delivery in a subsequent twin pregnancy than nulliparous women. Nulliparous women had lower rates of preterm delivery compared with parous women with a history of preterm delivery.

Foetal haemoglobin inducers for reducing blood transfusion in non-transfusion-dependent beta-thalassaemias.

BACKGROUND: Non-transfusion-dependent ß-thalassaemia (NTDßT) is a subset of inherited haemoglobin disorders characterised by reduced production of the ß-globin chain of haemoglobin leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it may be required to prevent complications of chronic anaemia, such as impaired growth and hypercoagulability. People with NTDßT also experience iron overload due to increased iron absorption from food sources which becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin (HbF) level have been found to require fewer blood transfusions, thus leading to the emergence of treatments that could increase its level. HbF inducers stimulate HbF production without altering any gene structures. Evidence for the possible benefits and harms of these inducers is important for making an informed decision on their use. OBJECTIVES: To compare the effectiveness and safety of the following for reducing blood transfusion for people with NTDßT: 1. HbF inducers versus usual care or placebo; 2. single HbF inducer with another HbF inducer, and single dose with another dose; and 3. combination of HbF inducers versus usual care or placebo, or single HbF inducer. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 21 August 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs comparing single HbF inducer with placebo or usual care, with another single HbF inducer or with a combination of HbF inducers; or comparing different doses of the same HbF inducer. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were blood transfusion and haemoglobin levels. Our secondary outcomes were HbF levels, the long-term sequelae of NTDßT, quality of life and adverse events. MAIN RESULTS: We included seven RCTs involving 291 people with NTDßT, aged two to 49 years, from five countries. We reported 10 comparisons using eight different HbF inducers (four pharmacological and four natural): three RCTs compared a single HbF inducer to placebo and seven to another HbF inducer. The duration of the intervention lasted from 56 days to six months. Most studies did not adequately report the randomisation procedures or whether and how blinding was achieved. HbF inducer against placebo or usual care Three HbF inducers, HQK-1001, Radix Astragali or a 3-in-1 combined natural preparation (CNP), were compared with a placebo. None of the comparisons reported the frequency of blood transfusion. We are uncertain whether Radix Astragali and CNP increase haemoglobin at three months (mean difference (MD) 1.33 g/dL, 95% confidence interval (CI) 0.54 to 2.11; 1 study, 2 interventions, 35 participants; very low-certainty evidence). We are uncertain whether Radix Astragali and CNP have any effect on HbF (MD 12%, 95% CI -0.74% to 24.75%; 1 study, 2 interventions, 35 participants; very low-certainty evidence). Only medians on haemoglobin and HbF levels were reported for HQK-1001. Adverse effects reported for HQK-1001 were nausea, vomiting, dizziness and suprapubic pain. There were no prespecified adverse effects for Radix Astragali and CNP. HbF inducer versus another HbF inducer Four studies compared a single inducer with another over three to six months. Comparisons included hydroxyurea versus resveratrol, hydroxyurea versus thalidomide, hydroxyurea versus decitabine and Radix Astragali versus CNP. No study reported our prespecified outcomes on blood transfusion. Haemoglobin and HbF were reported for the comparison Radix Astragali versus CNP, but we are uncertain whether there were any differences (1 study, 24 participants; low-certainty evidence). Different doses of the same HbF inducer Two studies compared two different types of HbF inducers at different doses over two to six months. Comparisons included hydroxyurea 20 mg/kg/day versus 10 mg/kg/day and HQK-1001 10 mg/kg/day, 20 mg/kg/day, 30 mg/kg/day and 40 mg/kg/day. Blood transfusion, as prespecified, was not reported. In one study (61 participants) we are uncertain whether the lower levels of both haemoglobin and HbF at 24 weeks were due to the higher dose of hydroxyurea (haemoglobin: MD -2.39 g/dL, 95% CI -2.80 to -1.98; very low-certainty evidence; HbF: MD -10.20%, 95% CI -16.28% to -4.12%; very low-certainty evidence). The study of the four different doses of HQK-1001 did not report results for either haemoglobin or HbF. We are not certain if major adverse effects may be more common with higher hydroxyurea doses (neutropenia: risk ratio (RR) 9.93, 95% CI 1.34 to 73.97; thrombocytopenia: RR 3.68, 95% CI 1.12 to 12.07; very low-certainty evidence). Taking HQK-1001 20 mg/kg/day may result in the fewest adverse effects. A combination of HbF inducers versus a single HbF inducer Two studies compared three combinations of two inducers with a single inducer over six months: hydroxyurea plus resveratrol versus resveratrol or hydroxyurea alone, and hydroxyurea plus l-carnitine versus hydroxyurea alone. Blood transfusion was not reported. Hydroxyurea plus resveratrol may reduce haemoglobin compared with either resveratrol or hydroxyurea alone (MD -0.74 g/dL, 95% CI -1.45 to -0.03; 1 study, 54 participants; low-certainty evidence). We are not certain whether the gastrointestinal disturbances, headache and malaise more commonly reported with hydroxyurea plus resveratrol than resveratrol alone were due to the interventions. We are uncertain whether hydroxyurea plus l-carnitine compared with hydroxyurea alone may increase mean haemoglobin, and reduce pulmonary hypertension (1 study, 60 participants; very low-certainty evidence). Adverse events were reported but not in the intervention group. None of the comparisons reported the outcome of HbF. AUTHORS' CONCLUSIONS: We are uncertain whether any of the eight HbF inducers in this review have a beneficial effect on people with NTDßT. For each of these HbF inducers, we found only one or at the most two small studies. There is no information on whether any of these HbF inducers have an effect on our primary outcome, blood transfusion. For the second primary outcome, haemoglobin, there may be small differences between intervention groups, but these may not be clinically meaningful and are of low- to very low-certainty evidence. Data on adverse effects and optimal doses are limited. Five studies are awaiting classification, but none are ongoing.

Exploring the Use of Virtual Funerals during the COVID-19 Pandemic: A Scoping Review.

The COVID-19 pandemic and physical distancing limitations have had a profound impact on funeral practices and associated grieving processes. The purpose of the present scoping review is to summarize the existing literature on the emerging use of virtual funerals. Five medical databases, five social science databases, and five grey literature databases were searched, identifying 1,351 titles and abstracts, of which 62 met inclusion criteria. Four themes, each with various subthemes emerged: (a) Impact of virtual funerals on coping with death; (b) Impact of the COVID-19 pandemic on the funeral industry; (c) Benefits and disadvantages of virtual funerals; and (d) Future implications for health and social work practitioners. Virtual funerals are an evolving resource for individuals, families, and communities to mourn in response to the interruptions to traditional grieving practices due to the COVID-19 pandemic.

Impacts of psychological wellbeing with HIV/AIDS and cancer among sexual and gender minorities: A systematic review and meta-analysis.

Background: The agony and economic strain of cancer and HIV/AIDS therapies severely impact patients' psychological wellbeing. Meanwhile, sexual minorities experience discrimination and mental illness. LGBT individuals with cancer and HIV/AIDS play two roles. It is important to understand and examine this groups mental wellbeing. Objective: The purpose of this study is to synthesize current studies on the impact of HIV/AIDS and cancer on LGBT patients' psychological wellbeing. Methods: This research uses a systematic literature review at first and later stage a meta-analysis was run on the same review. In this study, data from Google academic and Web of Science has been used to filter literature. PRISMA 2020 Flow Diagram seeks research on LGBT cancer and HIV/AIDS patients. The above sites yielded 370 related papers, some of which were removed due to age or inaccuracy. Finally, meta-analyses was done on 27 HIV/AIDS and 33 cancer patients's analyse. Results: The research included 9,898 LGBT cancer sufferers with AIDS and 14,465 cancer sufferers with HIV/AIDS. Using meta-analysis, we discovered the gap in psychological wellbeing scores between HIV/AIDS LGBT and non-LGBT groups ranged from -10.86 to 15.63. The overall score disparity between the HIV/AIDS LGBT and non-LGBT groups was 1.270 (95% CI = 0.990-1.560, Z = 86.58, P < 0.1). The disparity in psychological wellbeing scores between cancer LGBT group and general group varies from -8.77 to 20.94 in the 34 papers examined in this study. Overall, the psychological wellbeing score disparity between the cancer LGBT subset and the general group was 12.48 (95% CI was 10.05-14.92, Test Z-value was 268.40, P-value was <0.1). Conclusion: Inflammation and fibrosis in HIV/AIDS and cancer sufferers adversely affect their psychological wellbeing.

A Participatory, Needs-Based Approach to Breastfeeding Training for Confinement Centres.

With a focus on traditional practices rather than evidence-based practices, breastfeeding support is sub-optimal in confinement centres (CCs). We used a participatory, needs-based approach to develop a training module for CC staff adopting Kern's six-step approach as our conceptual framework. Of 46 identified CCs, 25 accepted our invitation to a dialogue aimed at establishing relationships and understanding their needs. An interactive training workshop was developed from the dialogue's findings. The workshop, attended by 32 CCs (101 participants), was conducted four times over a four-month period. Questions raised by the participants reflected deficits in understanding breastfeeding concepts and erroneous cultural beliefs. Correct answers rose from 20% pre-test to 51% post-test. Post-workshop feedback showed that participants appreciated the safe environment to ask questions, raise concerns and correct misconceptions. An interview conducted 14 months later showed that while some CCs improved breastfeeding support, others made no change due to conflict between breastfeeding and traditional postnatal practices, which was aggravated by a lack of support due to the COVID-19 pandemic. A participatory approach established a trustful learning environment, helping CCs appreciate the value of learning and adopting new concepts. However, cultural perceptions take time to change, hence continuous training and support are vital for sustained changes.

Use of Galactagogues in a Multi-Ethnic Community in Southeast Asia: A Descriptive Study.

Purpose: Galactagogues are substances that increase breast-milk production. They can be medication, herbs or food. Use of galactagogues may be different among the major ethnic groups in Malaysia. The primary objective of this cross-sectional study is to determine the prevalence of galactagogues use among breastfeeding mothers in a multi-ethnic community. Patients and Methods: Self-administered questionnaires were distributed between November 2016 and January 2017 to mothers attending the health clinics and private hospital paediatric clinics in Penang, Malaysia, whose infants were below 6 months of age. The questionnaire enquired about use of galactagogues, types of galactagogue used, perceived effectiveness and sources of information. It also asked mothers about what they would do to increase milk supply. Results: We analyzed 322 out of 530 questionnaires distributed where 76% of mothers reported use of galactagogues; most of which were food-based: dates (66%), oats (58%) and soya bean (56%). Each major ethnic group had a different preference for galactagogues: Malays (dates), Chinese (soya bean) and Indians (oats). Only one mother used pharmacological galactagogues alone. Galactagogues were perceived to be effective by 65% of mothers who used them. Multivariate analysis showed that use of galactagogues was not related to ethnicity, education, work, perception of milk supply or use of formula milk. The most common source of information on galactagogues came from family and friends. Conclusion: Use of galactagogues is common in our population, especially food-based ones, and the choice of galactagogues differs by ethnicity. Future studies on efficacy and safety galactagogues should be focused these commonly used ones. There is also a need for qualitative studies to improve our understanding of why they are widely used in this region.

Public attitudes in the United States toward insurance coverage for in vitro fertilization and the provision of infertility services to lower income patients.

Objective: To assess attitudes and factors that influence public opinion in the general US population toward insurance coverage and provision of infertility care to lower income patients. Design: Cross-sectional survey. Setting: Online. Patients: A nationally representative sample of US residents. Interventions: Questionnaire with multiple choice and open response questions. Main Outcome Measures: Public attitudes toward in vitro fertilization and infertility care coverage for lower income patients. Results: A total of 1,027 (90.2%) participants completed the survey, among whom 620 (60.4%) had private insurance, 275 (26.8%) had Medicare/Medicaid, and 56 (5.5%) were uninsured. The majority (916, 89.2%) did not consider infertility a disease. Over half of the respondents (568, 55.3%) supported private insurance coverage of infertility services, including for in vitro fertilization. Most respondents, 735 (71.6%) believed that the prevalence and psychosocial impact of infertility were equal among the lower and higher income people. The majority of respondents with an opinion (512, 67.6%) believed that doctors should provide infertility treatments regardless of the income level of the patients. Of supporters, 40.1% believed in the right to have a family regardless of income, and 38.2% believed that doctors had a social responsibility to provide infertility services. After adjusting for covariates, age <45 years, noncollege graduates, desiring more children, believing that infertility was a disease, and residence in the Northeast region remained significant predictors for support of private insurance coverage. Conclusions: Public perception of infertility as a disease is one of the strongest predictors of support for insurance coverage for infertility services, underscoring the need for enhanced advocacy and education in the general public.