Need For Treatment Research Articles

Comparison of Different Doses of Oral and Ocular Propranolol for Retinopathy of Prematurity: A Network Meta-Analysis.

The efficacy and safety of propranolol for retinopathy of prematurity (ROP) remain under debate. This network meta-analysis (NMA) focuses on whether a ranking may be established for different dose levels of propranolol as treatment of ROP in terms of stage progression as the primary outcome, with appearance of plus disease and need for anti-vascular endothelial growth factors (anti-VEGFs) or laser therapy as secondary endpoints. Fourteen studies (10 randomised controlled trials, three single-arm trials and one retrospective observational study) of 474 patients treated with oral or ocular propranolol were retrieved from databases up to April 2024. Meta-insight and model-based NMA were undertaken to evaluate the propranolol dose-response relationship. Studies were evaluated for model fit, risk of bias and Confidence of evidence In Network Meta-Analysis (CINeMA). Effect sizes were determined as odds ratio (OR) with 95% credible interval (CrI). Bayesian analysis showed a trend towards improved effects for propranolol given at late stages (stages 2-3; S23) of ROP progression compared with its administration at earlier stages (stages 0-1; S01). OR values for oral propranolol 1.5 and 2mg/kg/day given at S23 were 0.13 (95% CrI 0.04-0.37) and 0.16 (95% CrI 0.04-0.61), respectively, while given at S01 were 0.28 (95% CrI 0.02-2.96) and 0.78 (95% CrI 0.14-4.43), respectively. Similarly, OR of eye propranolol 0.2% at S23 was 0.37 (95% CrI 0.09-1.00) versus an S01 OR of 0.64 (95% CrI 0.21-2.04). Surface under the cumulative ranking curve (SUCRA) analyses confirmed best probability values for oral propranolol 1.5-2mg/kg followed by eye propranolol 0.2%, all at S23. Model-based NMA showed nonlinearity in the dose-response for oral propranolol with a trend to greater maximal effect for its administration at late versus early stages. For secondary endpoints, lower risk values were found with oral propranolol 1.5mg/kg/day at S23 for progression to plus disease (OR 0.14; 95% CrI 0.02-0.84) and need for anti-VEGFs (OR 0.23; 95% CrI 0.05-0.93) and laser (OR 0.16; 95% CrI 0.02-1.10) therapies also followed by eye propranolol 0.2%, and a similar profile was obtained with SUCRA analysis. Lower doses (0.5-1.0mg/kg/day) of oral propranolol retained efficacy. Threat of adverse events was estimated as risk difference versus control with no difference for eye propranolol 0.2% and oral propranolol 0.5mg/kg/day, modest increases of risk for oral propranolol 1.0 and 1.5mg/kg/day and the highest risk difference for oral propranolol 2.0mg/kg/day (0.06; 95% CI -0.01 to 0.13). A diminished risk of disease progression and need for additional treatment was obtained with propranolol in ROP, but safety is a potential concern. Propranolol eye micro-drops (0.2%) can be as efficacious as oral propranolol. Nonetheless, the evidence is limited due to the paucity and quality of the available studies.

Cryopreserved apoptotic mesenchymal stromal cells retain functional efficacy in suppressing an allergic inflammation in a murine model.

Mesenchymal stromal cell (MSC) apoptosis is required for in vivo immunosuppression. However, the induction of apoptosis is heavily dependent on the recipient's immune system. In graft-versus-host disease (GvHD), patients who fail to respond to MSCs are in fact those whose immune cells are unable to induce MSC apoptosis ex vivo. The information is critical to explain why responses in clinical trials vary even though the same sources of MSC products are infused. More importantly, it highlights the need for an alternative MSC treatment for the nonresponders. By using a mouse model of ovalbumin (OVA)-induced allergic inflammation, we demonstrated that we could generate apoptotic MSCs (ApoMSCs) in vitro and use them to successfully reduce allergic airway inflammation. In order to address the logistics of their potential future clinical application, we have shown that ApoMSCs could be cryopreserved without impairing efficacy compared to freshly generated ApoMSCs. We have also highlighted that MSCs need to undergo complete apoptosis before cryopreservation to retain their immunosuppressive activity. The cryopreserved ApoMSCs could serve as a potential future off-the-shelf cellular product, in particular for patients who suffer from inflammatory conditions yet do not harbor the immune capacity to induce MSC apoptosis in vivo. Our data provide proof-of-concept that under laboratory conditions, ApoMSCs can be successfully frozen and thawed without affecting their anti-inflammatory activity, as tested in a murine model of allergic inflammation.

A cross-sectional study to correlate oral hygiene habit among orthodontic patients with their clinical findings and periodontal treatment need

BackgroundOrthodontic treatment requires good oral hygiene for successful completion of treatment. As protocol, patients are usually given instructions for oral hygiene and diet at the start of treatment, however, they are not fully followed. Different methods are employed in order to increase patient compliance including digital means, however, these are not possible in teaching hospitals with high burden of patient care and limited resources. The present study aims to correlate the patient reported behavior with their clinical findings and treatment need. This will enable us to identify potential sources of motivation which will be incorporated in daily practice and enable us to improve methods to enhance patient’s behavior.MethodA cross-sectional study was conducted in the orthodontic department of a semi-government teaching hospital from August to October 2023 using a modified questionnaire. The clinical examination was done using a Community Periodontal Index for Treatment Need-C (CPITN-C) probe. The diagnosis of presenting clinical conditions and treatment need was done using Community Periodontal Index for Treatment Need (CPITN) and Gingival Bleeding Index (BI). Data collected was analyzed for frequencies and correlation was done using Spearman Correlation Coefficient. P- value ≤ 0.05 was taken as statistically significant.ResultThe sample size consisted of 110 patients of which 60% were entitled to receive treatment. The predominant age group was 15–20 years (39.1%). Approximately 70% patients were in code 1 for CPITN and GI and in need of oral hygiene instructions. Overall patients’ showed good level of awareness, however, they were not compliant in behavior.ConclusionAlthough patients showed a good level of awareness towards oral hygiene practices, there was a lack of compliance in following them. Patients were more concerned for being affected by dental caries due to poor oral hygiene than its effect on overall treatment outcome.

The severity level of malocclusion and orthodonthic treatment needs based on the index of orthodonthic treatment need (IOTN) on students aged 9-12 years old at candijati jember 1 state elementary school

Malocclusion is a condition of dental occlusion that is not suitable from normal conditions that affect oral function and facial aesthetics and has now become a great concern in the health sector. Malocclusion occurs mostly in children aged 9-12 years which is the second phase of the mixed teeth period. The severity’s level of malocclusion and orthodontic treatment needs can be measured using the malocclusion index, one of which is the Index of Orthodontic Treatment Need (IOTN). Dental Health Component (DHC) is one component of IOTN that is effective in overcoming malocclusion and has good potential for orthodontic treatment because it assesses objectively by examining and measuring the circumstances of the teeth. The purpose of this study was to determine the severity of malocclusion and orthodontic treatment needs based on the Index of Orthodontic Treatment Need (IOTN) in students aged 9-12 years at SDN 01 Candijati Jember. Sampling was determined using the total sampling method on subjects encountered inclusion criteria; 96 samples were obtained. This study was conducted by measuring the study model of the patient's dental printing results based on DHC from IOTN and analyzed descriptively. The results of the study found the severity of malocclusion and the need for orthodontic treatment based on the Index of Orthodontic Treatment Need (IOTN) in students aged 9-12 years SDN 01 Candijati Jember is most commonly found in grade 2, namely mild malocclusion with little need for treatment. Then the severity’s level of malocclusion and the need for orthodontic treatment is greater in women than men and great-est in students aged 12 years.

Psychogastroenterology of cyclic vomiting syndrome: A crucial need to build evidence.

Cyclic vomiting is a disorder of gut brain interaction (DGBI) emphasizing the need for treatment of both the brain and the gut. Despite clinical success of psychological therapies for CVS, also called brain-gut treatments, an evidence-base is lacking and these treatments are available in few GI practices. This has resulted in an "all guts no brain" approach to CVS. The current paper is a call to action to develop more evidence and use of brain-gut therapies in CVS.

Patients with Thyroid Dyshormonogenesis and DUOX2 Variants: Molecular and Clinical Description and Genotype–Phenotype Correlation

Thyroid dyshormonogenesis (THD) is a heterogeneous group of genetic diseases caused by the total or partial defect in the synthesis or secretion of thyroid hormones. Genetic variants in DUOX2 can cause partial to total iodination organification defects and clinical heterogeneity, from transient to permanent congenital hypothyroidism. The aim of this study was to undertake a molecular characterization and genotype–phenotype correlation in patients with THD and candidate variants in DUOX2. A total of 31 (19.38%) patients from the Catalan Neonatal Screening Program presented with variants in DUOX2 that could explain their phenotype. Fifteen (48.39%) patients were compound heterozygous, 10 (32.26%) heterozygous, and 4 (12.90%) homozygous. In addition, 8 (26.67%) of these patients presented variants in other genes. A total of 35 variants were described, 10 (28.57%) of these variants have not been previously reported in literature. The most frequent variant in our cohort was c.2895_2898del/p.(Phe966SerfsTer29), classified as pathogenic according to reported functional studies. The final diagnosis of this cohort was permanent THD in 21 patients and transient THD in 10, according to reevaluation and/or need for treatment with levothyroxine. A clear genotype–phenotype correlation could not be identified; therefore, functional studies are necessary to confirm the pathogenicity of the variants.

Predictors of improvement in disease activity in childhood and adolescent Crohn's disease: an analysis of age, localization, initial severity and drug therapy - data from the Saxon Registry for Inflammatory Bowel Disease in Children in Germany (2000-2014).

The escalating worldwide prevalence of Crohn's disease (CD) among children and adolescents, coupled with a trend toward earlier onset, presents significant challenges for healthcare systems. Moreover, the chronicity of this condition imposes substantial individual burdens. Consequently, the principal objective of CD treatment revolves around rapid inducing remission. This study scrutinizes the impact of age, gender, initial disease localization, and therapy on the duration to achieve disease activity amelioration. Data from the Saxon Pediatric IBD Registry in Germany were analyzed over a period of 15 years. In addition to descriptive methods, logistic and linear regression analyses were conducted to identify correlations. Furthermore, survival analyses and Cox regressions were utilized to identify factors influencing the time to improvement in disease activity. These effects were expressed as Hazard Ratios (HR) with 95% confidence intervals. Data on the clinical course of 338 children and adolescents with CD were available in the registry. The analyses showed a significant correlation between a young age of onset and the severity of disease activity. It was evident that treatment with anti-TNF (Infliximab) was associated with a more favorable prognosis in terms of the time required for improvement in disease activity. Similarly, favorable outcomes were observed with the combination therapies of infliximab with enteral nutrition therapy and Infliximab with immunosuppressants.Conclusion: Our analysis of data from the Saxon Pediatric IBD Registry revealed that the timeframe for improvement of disease activity in pediatric Crohn's disease is influenced by several factors. Specifically, patient age, treatment modality, and initial site of inflammation were found to be significant factors. The study provides important findings that underline the need for individualized treatment.

The politics of belonging in Arunachal Pradesh: rules of exclusion and differentiated citizenship

ABSTRACT This paper unravels the politics of belonging, the legal-political regime of exclusion, and differentiated citizenship in the multi-layered social and political context of Arunachal Pradesh, India. This paper aims to engage with the institutional arrangements of the Indian state that accommodate the ethno-cultural differences in a multi-ethnic society. Set amidst the changing social and economic realities of Arunachal Pradesh, this study relates to the emerging contestations around the protection of Indigenous identity and the need for differential treatment of people in multiethnic societies by embedding these discussions within policy debates on Inner Line Regulation and land legislations in the state. This paper adopts an incisive approach to understand the implications of such protective measures on the conceptualization of citizenship in states with a significant Indigenous population. It argues for examining the implications of ethnicised forms of governance in favour of democratic power sharing structures and representative institutions of the economy.

Assessment of treatment needs, barriers, and self-perception regarding oral health among female university students: a cross-sectional study

BackgroundThe study aimed to compare the self-perceived oral health status measured through a self-administered questionnaire with clinically determined oral health status measured by decayed-missing-filled teeth (DMFT) and community periodontal index of treatment need (CPITN) indices in university going females. In addition, access barriers to treatment related to oral healthcare were also determined.MethodsA 3-month analytical cross-sectional study was designed for consenting university going females (aged 18–22 years) in Islamabad, Pakistan. The self-perceived oral health was recorded through a questionnaire requesting information regarding socio-demographics, self-perception of oral health, frequency of dental visits and barriers to seeking oral health. Seven independent examiners performed intraoral clinical examination and assessed the oral health status using globally standardized oral health assessment indices (DMFT and CPITN).ResultsA total of 400 students were included in the final sample. The study revealed a significant disparity between self-perceived oral health and clinical assessment. Although perceived oral health was considered “good” by 80.0% of the respondents, clinical examination revealed moderate DMFT scores (mean 2.95 ± 1.41) and periodontal disease requiring treatment in 89.5% of the individuals. The most common barriers in seeking dental care were lack of knowledge, dental phobia, affordability issue and false self-perception.ConclusionThe present study demonstrated a notable discrepancy between self-perception of oral health and clinically assessed oral health. These results emphasize the importance of focused educational programs and community outreach programs, especially directed towards this demographic. Prioritizing such initiatives will help individuals to recognize their actual oral health condition thus encouraging positive oral health behaviors and outcomes.

Post hoc analysis of the characteristics and treatment needs of patients with dementia with Lewy bodies (DLB) and their caregivers and their physicians' awareness of those treatment needs according to the duration after diagnosis of DLB.

To investigate the differences in patient/caregiver characteristics, their treatment needs, and the attending physician's understanding of those treatment needs according to the duration after diagnosis of dementia with Lewy bodies (DLB). This was a post hoc analysis of a multicenter, cross-sectional, questionnaire survey study. A total of 263 patient-caregiver pairs were reclassified into two groups according to the median duration after diagnosis of DLB as follows: short (<24months; S-group) and long (≥24months; L-group) post-DLB diagnosis duration. Treatment need was defined as the symptom domain that caused the patient or caregiver the most distress. Concordance rates between patient-physician and caregiver-physician were calculated for physicians' understanding of treatment needs. In this analysis, 126 pairs (32 physicians) and 137 pairs (34 physicians) were classified as the S- and L-groups, respectively. Patient and caregiver characteristics were broadly similar between groups (mean age for patients 78.7±6.6 vs. 79.8±6.7, for caregivers 64.7±12.9 vs. 64.9±12.8; number of male/female for patients 61/65 vs. 67/70, for caregivers 34/92 vs. 38/99), but the prevalence of parkinsonism (82.5% vs. 66.7%) and autonomic dysfunction (49.6% vs. 33.3%), severity of parkinsonism (MDS-UPDRS Part III total scores, 29.2±22.6 vs. 18.0±16.4; Part II total score, 14.6±12.0 vs. 7.6±7.9), and caregiver burden (J-ZBI_8 score, 9.1±6.7 vs. 7.5±5.8) were higher in the L-group than the S-group. Regarding treatment needs, the invalid answer rates for patients were 34.9% and 46.8%, and those for caregivers were 28.6% and 34.9% in the S- and L groups, respectively. Patients' treatment needs did not significantly differ (p=0.056), but S-group patients were more likely to select cognitive impairment (p=0.045) as their treatment need, whereas L-group patients were more likely to select parkinsonism (p=0.003). Caregivers' treatment needs significantly differed (p=0.032) between groups. S-group caregivers were more likely to select cognitive impairment (p=0.001), whereas L-group caregivers were more likely to select other symptom domains such as parkinsonism (S-group vs. L-group: 10.3% vs. 16.7%), psychiatric symptoms (20.6% vs. 24.6%), sleep-related disorder (4.0% vs. 7.1%), and autonomic dysfunction (4.8% vs. 9.5%). Concordance rates between patient-physician and caregiver-physician were low in both groups. There were some differences in characteristics according to the duration after diagnosis of DLB. Cognitive dysfunction may be a particular concern for patients and caregivers soon after diagnosis of DLB. Treatment needs of patients and caregivers for parkinsonism, psychiatric symptoms, sleep-related disorder, or autonomic dysfunction were different according to the duration after diagnosis of DLB. Physicians' perception of patients'/caregivers' treatment needs was poor regardless of the duration after diagnosis of DLB. UMIN Clinical Trials Registry (UMIN000041844).

Efficacy of antihypertensive treatment for target organ protection in patients with masked hypertension (ANTI-MASK): a multicentre, double-blind, placebo-controlled trial

Masked hypertension is associated with target organ damage (TOD) and adverse health outcomes, but whether antihypertensive treatment improves TOD in patients with masked hypertension is unproven. In this multicentre, randomised, double-blind, placebo-controlled trial at 15 Chinese hospitals, untreated outpatients aged 30-70 years with an office blood pressure (BP) of <140/<90mm Hg and 24-h, daytime or nighttime ambulatory BP of ≥130/≥80, ≥135/≥85, or ≥120/≥70mm Hg were enrolled. Patients had ≥1 sign of TOD: electrocardiographic left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (baPWV) ≥1400cm/s, or urinary albumin-to-creatinine ratio (ACR) ≥3.5mg/mmol in women and ≥2.5mg/mmol in men. Exclusion criteria included secondary hypertension, diabetic nephropathy, serum creatinine ≥176.8μmol/L, and cardiovascular disease within 6 months of screening. After stratification for centre, sex and the presence of nighttime hypertension, eligible patients were randomly assigned (1:1) to receive antihypertensive treatment or placebo. Patients and investigators were masked to group assignment. Active treatment consisted of allisartan starting at 80mg/day, to be increased to 160mg/day at month 2, and to be combined with amlodipine 2.5mg/day at month 4, if the ambulatory BP remained uncontrolled. Matching placebos were used likewise in the control group. The primary endpoint was the improvement of TOD, defined as normalisation of baPWV, ACR or LVH or a ≥20% reduction in baPWV or ACR over the 48-week follow-up. The intention-to-treat analysis included all randomised patients, the per-protocol analysis patients who fully adhered to the protocol, and the safety analysis all patients who received at least one dose of the study medication. This study is registered with ClinicalTrials.gov, NCT02893358. Between February 14, 2017, and October 31, 2020, 320 patients (43.1% women; mean age±SD 53.7±9.7 years) were enrolled. Baseline office and 24-h BP averaged 130±6.0/81±5.9mm Hg and 136±8.6/84±6.1mm Hg, and the prevalence of elevated baPWV, ACR and LVH were 97.5%, 12.5%, and 7.8%, respectively. The 24-h BP decreased on average (±SE) by 10.1±0.9/6.4±0.5mm Hg in 153 patients on active treatment and by 1.3±0.9/1.0±0.5mm Hg in 167 patients on placebo. Improvement of TOD occurred in 79 patients randomised to active treatment and in 49 patients on placebo: 51.6% (95% CI 43.7%, 59.5%) versus 29.3% (22.1, 36.5%; p<0.0001). Per-protocol and subgroup analyses were confirmatory. Adverse events were generally mild and occurred in 38 (25.3%) and 43 (26.4%) patients randomised to active treatment and placebo, respectively (p=0.83). Our results suggest that antihypertensive treatment improves TOD in patients with masked hypertension, highlighting the need of treatment. However, the long-term benefit in preventing cardiovascular complications still needs to be established. Salubris China.

Association of hepatitis B virus treatment with all-cause and liver-related mortality among individuals with HBV and cirrhosis: a population-based cohort study

We evaluated the association of hepatitis B virus (HBV) treatment with all-cause, and liver-related mortality among individuals with HBV and cirrhosis in British Columbia (BC), Canada. This analysis included people diagnosed with HBV and had cirrhosis in the BC Hepatitis Testers Cohort, including data on all individuals diagnosed with HBV from 1990 to 2015 in BC and integrated with healthcare administrative data. We followed people with cirrhosis from the first cirrhosis diagnosis date until death or December 31, 2020. We compared all-cause and liver related mortality between those who received treatment and those who did not. HBV treatment was considered a time-varying variable. We performed multivariable Cox proportional hazards model and competing risk regression models to assess the association of HBV treatment with all causes, and liver-related mortality respectively using inverse probability of treatment weighted population. Among 4962 individuals with HBV and cirrhosis, 48.1% received HBV treatment. Treated individuals had a median follow-up of 2.97 years, compared to 2.87 years for untreated individuals. The treated group was older (median age 57 vs 54 years), had higher proportion of treated of males [1802 (75.50%) vs 1766 (68.8%)], from urban area [2318 (97.2%) vs 2355 (91.8%)], and from East and South Asian ethnicity [1506 (63.1%) vs 709 (27.5%)] compared to untreated group. Untreated people experienced higher all-cause mortality (115.47 vs. 35.72 per 1000 person-years) and liver-related mortality (49.86 vs. 11.39 per 1000 person-years). Multivariable models showed that HBV treatment significantly lowered the risk of all-cause mortality (adjusted hazard ratio (aHR) 0.74; 95% CI: 0.65, 0.84) and liver-related mortality (adjusted subdistribution hazard ratio (asHR) 0.72; 95% CI: 0.58, 0.89) compared to untreated individuals. Among untreated individuals with HBV, those with HCV coinfection had a higher risk of both all-cause and liver-related mortality (aHR 1.57; 95% CI: 1.22, 2.04, and asHR 1.60; 95% CI: 1.25, 2.05, respectively). HBV treatment was associated with a significant reduction in all-cause and liver-related mortality among individuals with cirrhosis. The findings highlight the need for treatment among individuals with HBV related cirrhosis especially those with coinfection with hepatitis C virus. This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-142832, PJT-156066, and SC1 -178736]. JDM has received doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and doctoral fellowship from the CanHepC. CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

Small Bowel Crohn's Disease: Proximal Lesions Linked to Increased Inflammation and Biologic Treatment Needs

Objective: Crohn's disease (CD) is heterogeneous, and proximal involvement in the small bowel (SB) is associated with worse outcomes. Nonetheless, studies on the impact of duodenal and jejunal lesions in SB CD are limited. This study aimed to investigate the clinical characteristics and outcomes of individuals diagnosed with SB CD, comparing those with and without proximal inflammation.Methods: A cohort of 53 treatment-naive SB CD patients that underwent Capsule Endoscopy at diagnosis were retrospectively selected. The inflammatory activity was quantified using the Lewis Score for each SB tertile.Results: Thirty-seven (69.8%) patients displayed inflammatory activity in the first and/or second tertile together with third tertile involvement (Proximal+T3 group). Sixteen (30.2%) had inflammation in the third tertile only (T3 group). Individuals in the Proximal+T3 group had a higher risk for moderate-to-severe inflammation (OR 4.93, 95% CI: 1.3-18.3, p=0.013). A subgroup analysis for those with mild inflammatory activity showed that individuals in the Proximal+T3 group initiated biologic drugs more often (OR 11, 95% CI: 1.1-109.7, p=0.036).Conclusion: Proximal SB lesions are associated with increased inflammatory activity, necessitating more frequent use of biologics in patients with mild disease. Early detection of proximal SB CD with Capsule Endoscopy may contribute to timely treatment.

Understanding and treating diabetic foot ulcers: Insights into the role of cutaneous microbiota and innovative therapies.

Notoriously known as the silent pandemic, chronic, non-healing diabetic foot ulcers (DFUs), pose a significant rate of incidence for amputation and are a major cause of morbidity. Alarmingly, the treatment and management strategies of chronic wounds represent a significant economic and health burden as well as a momentous drain on resources with billions per annum being spent in the US and UK alone. Defective wound healing is a major pathophysiological condition which propagates an acute wound to a chronic wound, further propelled by underlying conditions such as diabetes and vascular complications which are more prevalent amongst the elderly. Chronic wounds are prone to infection, which can exacerbate the condition, occasionally resulting in amputation for the patient, despite the intervention of modern therapies. However, amputation can only yield a 5-year survival rate for 50% of patients, highlighting the need for new treatments for chronic wounds. The dynamic cutaneous microbiota is comprised of diverse microorganisms that often aid wound healing. Conversely, the chronic wound microbiome consists of a combination of common skin commensals such as Staphylococcus aureus and Staphylococcus epidermidis, as well as the opportunistic pathogen Pseudomonas aeruginosa. These bacteria have been identified as the most prevalent bacterial pathogens isolated from chronic wounds and contribute to prolific biofilm formation decreasing the efficiency of antimicrobials and further perpetuating a hyper-inflammatory state. Here, we review recent advances and provide a new perspective on alternative treatments including phage and microbiome transplant therapies and how the definitive role of the cutaneous microbiota impacts the aetiology of DFUs.

Integrative Modeling of Signaling Network Dynamics Identifies Cell Type-selective Therapeutic Strategies for FGFR4-driven Cancers.

Oncogenic FGFR4 signaling represents a potential therapeutic target in various cancer types, including triple negative breast cancer (TNBC) and hepatocellular carcinoma (HCC). However, resistance to FGFR4 single-agent therapy remains a major challenge, emphasizing the need for effective combinatorial treatments. Our study sought to develop a comprehensive computational model of FGFR4 signaling and provide network-level insights into resistance mechanisms driven by signaling dynamics. An integrated approach, combining computational network modeling with experimental validation, uncovered potent AKT reactivation following FGFR4 targeting in TNBC cells. Analyzing the effects of co-targeting specific network nodes by systematically simulating the model predicted synergy of co-targeting FGFR4 and AKT or specific ErbB kinases, which was subsequently confirmed through experimental validation; however, co-targeting FGFR4 and PI3K was not synergistic. Protein expression data from hundreds of cancer cell lines was incorporated to adapt the model to diverse cellular contexts. This revealed that while AKT rebound was common, it was not a general phenomenon. For example, ERK reactivation occurred in certain cell types, including an FGFR4-driven HCC cell line, where there is a synergistic effect of co-targeting FGFR4 and MEK but not AKT. In summary, this study offers key insights into drug-induced network remodeling and the role of protein expression heterogeneity in targeted therapy responses. These findings underscore the utility of computational network modeling for designing cell type-selective combination therapies and enhancing precision cancer treatment.

A cellular reporter system to evaluate endogenous fetal hemoglobin induction and screen for therapeutic compounds.

Reactivation of fetal hemoglobin expression alleviates the symptoms associated with β-globinopathies, severe hereditary diseases with significant global health implications due to their high morbidity and mortality rates. The symptoms emerge following the postnatal transition from fetal-to-adult hemoglobin expression. Extensive research has focused on inducing the expression of the fetal γ-globin subunit to reverse this switch and ameliorate these symptoms. Despite decades of research, only one compound, hydroxyurea, found its way to the clinic as an inducer of fetal hemoglobin. Unfortunately, its efficacy varies among patients, highlighting the need for more effective treatments. Erythroid cell lines have been instrumental in the pursuit of both pharmacological and genetic ways to reverse the postnatal hemoglobin switch. Here, we describe the first endogenously tagged fetal hemoglobin reporter cell line based on the adult erythroid progenitor cell line HUDEP2. Utilizing CRISPR-Cas9-mediated knock-in, a bioluminescent tag was integrated at the HBG1 gene. Subsequent extensive characterization confirmed that the resulting reporter cell line closely mirrors the HUDEP2 characteristics and that the cells report fetal hemoglobin induction with high sensitivity and specificity. This novel reporter cell line is therefore highly suitable for evaluating genetic and pharmacologic strategies to induce fetal hemoglobin. Furthermore, it provides an assay compatible with high-throughput drug screening, exemplified by the identification of a cluster of known fetal hemoglobin inducers in a pilot study. This new tool is made available to the research community, with the aspiration that it will accelerate the search for safer and more effective strategies to reverse the hemoglobin switch.

Introduction to the special issue on the consequences of immigration policies on children, youth, and families who experience migration-related trauma.

We are excited to introduce this special issue on the consequences of immigration policies on children, youth, and families who experience migration-related trauma. International migration has increased over the last 5 decades. Recent estimates suggest that 281 million people live in a country other than the one in which they were born (McAuliffe & Triandafyllidou, 2021). These migratory patterns are complex and present both challenges and opportunities for trauma psychologists and professionals from diverse disciplines who approach their work with immigrants from a trauma-informed perspective. In this 21st century, a variety of stressors and crises continue to propel the movement of children, youth, and families across the globe. Trauma often pervades the experiences that cause people to leave their homes. They may need to escape oppressive political systems; criminal gangs, war, or disasters; or simply to survive. Migration itself can lead to exposure to additional traumatic events, such as physical and sexual violence, kidnapping, and trafficking. Finally, upon arrival in a host country, individuals may experience further stressors as they struggle to navigate immigration systems with discriminatory processes and inadequate resources. In this special issue, 14 articles illustrate various ways by which migration-related traumatic experiences can inform assessment and treatment, public health policy, and human rights advocacy. Focusing primarily on children and families, unaccompanied youth, and adult migrants from Latin America and other regions, the authors explore premigration, migration itself, and postmigration issues that arise when individuals migrate to survive. The articles highlight how the resiliency and strength of individuals and families can be called upon to empower them in their journey toward healing and the critical need for cross-disciplinary treatment and advocacy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Psychoeducation group facilitation training for nurses: A quality improvement project.

According to the 2020-2021 National Survey of Children's Health, 23.3% of children and adolescents met criteria for one or more mental, emotional, developmental, or behavioral problems. However, the prevalence of depression, anxiety, and post traumatic stress disorder have risen dramatically since the COVID-19 pandemic, leading to an increase in suicidal ideations, completed suicides, and pediatric psychiatric hospitalizations. There is a critical need for high quality mental healthcare treatments, including psychoeducation. Inpatient psychiatric nurses are well positioned to lead psychoeducation groups, but few receive training. Nurses at a designated inpatient pediatric psychiatric unit expressed discomfort in facilitating psychoeducation groups. This is a one-group prepost and follow-up quality improvement study designed to improve the quality of psychoeducation group facilitation skills provided by nurses at a child and adolescent inpatient psychiatric unit. A convenience sample of nurses (N = 16) participated. Baseline (T1), post-test (T2), and follow-up (T3) data were collected regarding nurses' self-efficacy, evidence based-practice attitudes, and knowledge of psychoeducation group facilitation. Nurses received 45 min of psychoeducation group facilitation education and 15 min of skills simulation. The nurses' knowledge, self-efficacy, and attitudes toward evidence-based practice when facilitating psychoeducation groups increased significantly from the baseline to the post-test, which was sustained from the post-test to the follow-up period. Study findings indicate the importance of supporting nurses in their role of psychoeducation group facilitation through education and program structure. Further research is needed to assess longer term sustainability and efficacy in leading psychoeducation groups.

The Tax Landscape of Split Contracts in Engineering, Procurement, and Construction (EPC) Investments: An In-Depth Study

The study examines tax complexities in Engineering, Procurement, and Construction (EPC) contracts, focusing on Indonesia's regulations. It stresses the importance of segregating contracts to simplify taxation, with Final Income Tax applying mainly to construction services. Challenges arise from offshore and onshore components, like equipment supplies and services, leading to disputes over Permanent Establishment (PE) presence and income attribution. Case studies from Indonesia and India demonstrate different tax interpretations. Indonesia typically taxes EPC contracts as unified, while India focuses on profit attribution within its jurisdiction. The paper highlights the role of Tax Treaties, like the Indonesia-Germany protocol, in determining tax treatment based on activities within each country. It underscores the need for consistent tax treatment through contract segregation, considering jurisdictional activities and relevant Tax Treaties.

Assessing breast cancer-related lymphedema screening and treatment gaps in a safety-net hospital.

We evaluated the unmet breast cancer-related lymphedema(BCRL) treatment and education needs at New England's largest safety-net hospital serving a diverse population by assessing prevalence, risk factors, and treatment. This was a retrospective cohort study examining breast cancer surgery patients from September 2016 to September 2021. The primary outcome was BCRL diagnosis. Secondary outcomes included BCRL risk factors, and physical and occupational therapy (PT/OT)referral frequency and completion. Of 639 patients, 17% of patients had documented BCRL, which was significantly associated with axillary lymph node dissection (ALND).There were no racial, insurance, breast radiation, or BMI category differences between patients with and without a BCRL diagnosis. Of those with BCRL, 58% received a PT/OTreferral, and 56% completed their referral. There were no racial, insurance, or BMI category differences between those who received a PT/OTreferral and those who did not. In our high-risk population, rates of documented BCRL were higher than expected, approaching rates of ALND, despite the majority undergoing sentinel lymph node biopsy (SLNB).PT/OTreferral and completion rates were low, concerning for an unmet BCRL treatment and education need. No disparities in care delivery were seen, but a program that addresses treatment gaps and ensures accessible and patient-centered BCRL care is urgently needed.