Non-muscle-invasive bladder cancer (NMIBC) accounts for the majority of bladder cancers. Its follow-up entails high costs and significant impact on quality of life. Cystoscopy is the standard method, although uncertainties remain regarding the optimal frequency and duration. The aim was to review the available evidence on surveillance schedules and their impact on recurrence and progression. A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta- Analyses). Searches in PubMed, Web of Science and Scopus included clinical and observational studies published between 2004 and 2024. After applying inclusion criteria and assessment with QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies), 8 articles were selected out of a total of 3679. The studies included a total of 30,600 patients. With regard to the first cystoscopy, performing it within 3-4 months after transurethral resection of the bladder showed better outcomes, whereas excessively early or delayed procedures increased the risk of recurrence and progression. In low-risk patients, some studies support discontinuing surveillance after 5 years without recurrence, while others recommend prolonging it in patients with risk factors such as smoking or multiple tumours. In high-risk patients, across the different surveillance schedules analysed, no differences were found in terms of mortality or progression. No conclusive studies were identified for the intermediate-risk group. The first cystoscopy should be performed within 3-4 months after the initial surgery. Although risk-stratified recommendations exist, current evidence is limited and sometimes contradictory. Prospective and long-term studies are required to define optimal surveillance schedules, with the aim of optimising resources and reducing the burden on patients.
Hippocampal sclerosis (HS) represents a higher proportion of surgical pathology in adult epilepsy patients compared to pediatric surgical cohorts. We hypothesized that while HS may serve as an initial pathological substrate, hippocampal abnormalities in epilepsy may also represent a duration-related structural change process that evolves with disease progression. To test this duration-dependent hypothesis, we investigated associations between disease duration and hippocampal morphological features using advanced neuroimaging in a large multicenter cohort. This study included 705 patients with unilateral focal epilepsy (age 25.4 ± 14.9 years, disease duration 14.8 ± 13.6 years) and 424 healthy controls from three centers in China. Global hippocampal features (volume, thickness, gyrification, mean curvature, intrinsic curvature) and subfield volumes were extracted using HippUnfold and AID-HS. Z-scores were calculated using normative models controlling for age, sex, total intracranial volume, and site. Associations between disease duration and hippocampal features were assessed using Spearman correlations and duration-stratified group comparisons. Longitudinal changes were evaluated in 80 patients with serial MRI scans using linear mixed-effects models. Patients with epilepsy showed significant bilateral hippocampal abnormalities compared to controls, with more severe changes ipsilateral to the seizure focus. Disease duration significantly correlated with all ipsilateral hippocampal metrics: negatively with volume (ρ = -0.181, p < 0.001), thickness (ρ = -0.135, p < 0.001), and gyrification (ρ = -0.141, p < 0.001), and positively with mean curvature (ρ = 0.121, p = 0.003) and intrinsic curvature (ρ = 0.171, p < 0.001). Contralateral associations were observed for volume (ρ = -0.085, p = 0.044), thickness (ρ = -0.082, p = 0.049), and intrinsic curvature (ρ = 0.080, p = 0.049). Longitudinal analysis revealed significant annual decline in ipsilateral hippocampal volume (β = -0.21 Z-score units/year, p = 0.042). We provide novel neuroimaging evidence supporting the duration-related structural alteration hypothesis of hippocampal structural changes in focal epilepsy. These findings may help explain the higher proportion of HS observed in adult surgical cohorts compared to pediatric surgical cohorts and enhance understanding of epilepsy pathophysiology, suggesting that disease duration is significantly associated with hippocampal structural abnormalities, indicating that it may serve as an important reference indicator for clinical monitoring and therapeutic decision-making.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by debilitating pain and progressive joint destruction. Tumor necrosis factor-alpha (TNF-α), a key pro-inflammatory cytokine, has been implicated in modulating both peripheral and central pain pathways. TNF-α inhibitors, initially developed to halt structural damage in RA, have demonstrated substantial efficacy in pain relief, independent of their anti-inflammatory properties. This narrative review explores the mechanistic pathways through which TNF-α contributes to pain sensitization and highlights the role of TNF-α inhibitors in disrupting these pathways. Evidence suggests that these biologics not only reduce synovial inflammation but also modulate neuroinflammatory circuits, altering pain perception at the spinal and supraspinal levels. Despite their clinical success, variability in patient response and concerns regarding long-term safety necessitate further research into personalized therapeutic strategies. Identifying biomarkers predictive of pain relief could enhance treatment precision. Ultimately, the integration of TNF-α inhibitors into multidisciplinary pain management approaches holds promise for improving clinical outcomes and quality of life in RA.
Although laparoscopy continues to be the predominant minimally invasive approach in most emergency settings, the advantages of robotics, well established in elective surgery, are currently being explored in selected scenarios and specialized centres. A systematic review was conducted using PubMed, Cochrane Library and Scopus databases until January 2025. Primary outcome was safety and feasibility of robotics in emergency colorectal surgery. Secondary endpoints included perioperative and postoperative outcomes. Fifteen articles were included with a total of 46 robotic emergency colorectal surgical procedures. Most were performed in a tertiary centre with a da Vinci system. Most common procedures were robotic right hemicolectomy for colon cancer and sigmoid colectomy for acute diverticulitis. Mean operating time for robotic right hemicolectomy was 134 min for benign cases and 241 ± 7 min for malignant cases; robotic sigmoid colectomy showed a mean operating time of 171 ± 3 min. No intraoperative complications were recorded. One case required conversion. Intracorporeal anastomosis was performed in most cases (n = 13). Mean length of stay was 5 days. No Clavien-Dindo grade ≥ 3 complications, reoperation or readmission were reported. Five complete mesocolic excisions (CMEs) were performed. Pathology outcomes were available for four CMEs: showing R0 resection with a mean lymph node harvest of 54 ± 13. In four CMEs, the involved team included an on-call robotic colorectal surgeon and an experience theatre team including experienced anaesthetist in robotic procedures. Robotics in emergency settings is feasible and safe but requires additional training and dedicated teams for optimal outcomes.
To examine the extent of polysubstance use in the general population of Croatia, determine trends in polysubstance use between 2011 and 2023, and identify distinct subgroups based on the patterns of polysubstance use and compare these subgroups across survey years. Four studies were conducted between 2011 and 2023 on nationally representative samples of Croatian residents aged 15 to 64, with a total of 19 730 respondents, through face-to-face surveys in private households. Last-year substance use (tobacco, alcohol, cannabis, ecstasy, amphetamines, cocaine, and LSD) was assessed using the Croatian translation of the European Model Questionnaire. Across all four survey years, alcohol (71.8%-83.3%), tobacco (39.4%-43.7%), and cannabis (5.1%-10.2%) were the most commonly used substances in the Croatian general population. Last-year abstinence showed a declining trend between 2011 and 2023, single-substance use remained stable, and polysubstance use increased over this period. Latent class analysis identified three distinct subgroups: alcohol-only use, alcohol and tobacco use, and polysubstance use. Alcohol and tobacco use and polysubstance use classes increased in size from 2011 to 2023, with the polysubstance use class increasing from 0.9% in 2011 to 2.8% in 2023, alongside higher probabilities of cocaine and ecstasy use over time. Polysubstance use is a growing public health concern in Croatia. The trends of co-use of alcohol and tobacco and stimulants use with polysubstance use patterns were rising. These trends emphasize the need for further research and the development of targeted prevention and intervention efforts, accounting for distinct effects of polysubstance use and cultural specificities of Croatian society.
This study seeks to investigate the relationship between pericardial fat volume and the risk of developing type 2 diabetes mellitus (T2DM) and major adverse cardiovascular events (MACE). The analysis included a cohort of 39, 125 participants from the UK Biobank. The associations between the mean estimate pericardial fat area (MEPFA), as measured by cardiac magnetic resonance imaging, and the incidence of T2DM and MACE were evaluated using multivariable Cox proportional hazards regression models and Kaplan-Meier survival curves. There were 343 occurrences of new-onset T2DM and 1, 894 occurrences of new-onset MACE over a median follow-up period of 55 months. Compared with patients with MEPFA ≤ 13.80 cm2, there was a significantly higher risk of new-onset T2DM (adjusted-HR: 2.09, 95% CI 1.38 to 3.18, P < 0.001) and MACE (adjusted-HR: 1.19, 95% CI 1.02 to 1.39, P = 0.027) in the highest MEPFA quartiles. The survival analysis further substantiated this discrepancy, with a log-rank test yielding P < 0.001. Participants exhibiting higher levels of MEPFA demonstrated poorer left ventricular morphology, systolic function, and global strain. The findings indicated that elevated MEPFA levels were significantly and independently associated with the onset of T2DM and MACE. Preliminary results suggested that increased levels of pericardial fat might enhance the predictive capability for cardio-metabolic risk.
Altered brain activity preceding behavior may reflect a reduced ability to suppress the sensory consequences of self-generated actions in schizophrenia. The corollary discharge (CD) mechanism has been proposed to underlie this process. In the present study, we investigated CD by analyzing the readiness potential (RP) and its relationship to auditory N1 suppression in patients with schizophrenia compared to healthy controls (HCs). We also examined the association between RP activity and anomalous self-experiences (ASEs). Event-related potentials were recorded from 48 patients with schizophrenia and 55 HCs during a vocalization paradigm including talk and listen conditions. RP amplitude and N1 suppression were quantified as the amplitude difference between listen and talk conditions. Regression analyses assessed the relationship between these components within each group and examined associations between RP and N1 amplitudes and ASEs, measured using the Inventory of Psychotic-Like Anomalous Self-Experiences (IPASE) scale, in the schizophrenia group. In the talk condition, HCs showed greater RP amplitude compared with the listen condition, a difference that was absent in the schizophrenia group. In HCs, this RP increase was followed by suppression of the N1 component. A significant correlation between RP amplitude and N1 suppression was observed in HCs but not in patients. Importantly, reduced N1 suppression in patients with schizophrenia was associated with higher IPASE scores. These findings suggest that schizophrenia involves impairments in early cortical processes related to efference copy and corollary discharge mechanisms, reflected in reduced RP amplitude and the lack of coupling with N1 suppression. Such alterations may contribute to deficits in sensory prediction and to anomalous self-experiences in schizophrenia.
IntroductionTrastuzumab deruxtecan (T-DXd)-induced interstitial lung disease/pneumonitis (ILD) represents a clinically significant and potentially fatal toxicity. Discrepancies exist regarding its reported frequency and severity between clinical trials (CTs) and real-world data (RWD). This meta-analysis aims to evaluate the incidence of T-DXd-related ILD and investigate its differences between CTs and RWD.MethodsA systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Databases were searched from their inception through January 2026. CTs and real-world studies reporting T-DXd-related ILD were included in the analysis. Pooled incidences for all-grade, grade ≥3, and fatal ILD were calculated using random-effects models. Subgroup analyses comparing CTs and RWD, and meta-regression analyses for relevant outcomes were performed.ResultsThirty-five studies (19 CTs, 16 RWD) including 6840 patients were analyzed. The pooled incidence was 8.8% for all-grade ILD, 1.6% for grade ≥3 ILD, and 0.26% for fatal ILD. RWD was independently associated with lower reported rates of all-grade and fatal ILD, while prior lines of therapy were the main predictor of grade ≥3 ILD.ConclusionILD risk with T-DXd differs by severity and data source. Vigilant monitoring is essential, particularly in heavily pretreated patients.
Hepatocellular carcinoma (HCC) faces a critical shortage of prognostic biomarkers and therapeutic targets. While solute carrier family 26 member 2 (SLC26A2) is known to be involved in skeletal disorders and even tumors, its specific role in HCC pathogenesis remains undefined. We utilized public databases to conduct a comprehensive analysis of SLC26A2 across 33 different cancer types. Additionally, we performed in vitro and in vivo experiments to investigate the functional role of SLC26A2 in the biological behavior of HCC and to explore its mechanistic pathways. A pan‑cancer analysis revealed significant variability in SLC26A2 mRNA and protein levels, with prognostic implications across cancers. In HCC, SLC26A2 was identified as an independent risk factor for poor overall survival (HR = 1.539, 95% CI 1.084-2.186, p = 0.016) and correlated with higher pathological grade. Functional assays showed that silencing SLC26A2 inhibited HCC cell proliferation, migration, and invasion, while promoting apoptosis; conversely, overexpression led to opposite outcomes. Notably, silencing SLC26A2 significantly increased intracellular ROS, which was linked to subsequent modulation of the JNK/ERK/p38 MAPK signaling pathway-an effect suggested to be reversible by the antioxidant N‑acetylcysteine. In vivo studies demonstrated that silencing SLC26A2 suppressed subcutaneous tumor growth in an HCC xenograft model. Additionally, bioinformatics analysis predicted a competing endogenous RNA regulatory axis comprising the SNHG3/LINC00662-hsa-miR‑122‑5p-SLC26A2. Our study identifies SLC26A2 as a clinically relevant biomarker and candidate therapeutic target in HCC. Mechanistically, SLC26A2 modulates JNK/ERK/p38 MAPK activity in a manner involving ROS signaling. While its biological roles extend beyond HCC, the clinical implications are most pronounced in this malignancy.
Alcohol consumption profiles among the Orang Asli (OA) remain tribe specific. This study presents the first nationwide analysis of consumption patterns among 9225 OA adults across various tribes, based on the 2022 Orang Asli Health Survey. Alcohol consumption was assessed using the validated Alcohol Use Disorder Identification Test (AUDIT-M) questionnaire; subsequently, multinomial logistic regression was performed using Stata 16 to identify sociodemographic factors associated with non-drinkers, low-risk drinkers, and risky drinkers. Current drinker prevalence was 9.1% (95% confidence interval [6.4, 12.8]), and 88.1% preferred beer. Among drinkers, 59.5% were risky drinkers, 36.3% were binge drinkers, and 8.0% were heavy episodic drinkers. Risky drinking was significantly associated with males (P < .001), younger adults (P = .001), smokers (P < .001), the Senoi (P < .001) and Proto-Malay tribes (P = .014), and those residing in fringe (P < .001) or urban (P = .009) areas. Integrating targeted alcohol screening into community health campaigns is essential to mitigate risky drinking behaviors within these vulnerable populations.
This study examines the association between PR and the progression of cognitive frailty among older adults in China. Data were obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) conducted from 2002 to 2018. Cognitive frailty is defined as the presence of both physical frailty and cognitive impairment in older adults without a dementia diagnosis. Fixed-effect models analyzed the relationship between PR and cognitive frailty over time. Latent Class Growth Models were used to study the trajectories of PR and cognitive frailty, and multinomial logistic regression and Cox proportional hazards regression were applied to examine the links between PR trajectories and cognitive frailty progression. An increase of 1 point in the PR score is associated with an 9% reduction in the risk of cognitive frailty (RRR = 0.91, 95% CI: 0.90, 0.93). Compared to participants in the high-level stable PR group, those in the moderate-level declining and low-level rising PR groups faced a greater risk of experiencing a subsequent trajectory of low probability mild cognitive impairment (MCI) along with accelerated frailty, or a higher likelihood of both conditions. These findings emphasize the role of promoting psychological resilience in achieving the broader goals of healthy aging.
Somalia has one of the lowest childhood immunization coverage rates globally, with only 34.8% of children aged 0-59 months having received at least one vaccine and a high burden of zero-dose children. Immunization uptake is influenced by socioeconomic, maternal, healthcare access, and geographic factors. This study examined determinants of childhood immunization coverage in Somalia to inform equity-focused strategies. A cross-sectional analysis was conducted using nationally representative data from the 2020 Somalia Demographic and Health Survey (SDHS), including 7,373 mother-child pairs. bivariate and multivariable logistic regression models assessed associations between sociodemographic, economic, maternal, healthcare access, and geographic characteristics and child vaccination status, accounting for survey design and confounders. Overall vaccination coverage was 34.8%. Health facility delivery was the strongest independent predictor (AOR = 1.93; 95% CI:1.68-2.22; p < 0.001). Children from the highest household wealth quintile had higher odds than the poorest (AOR = 2.45; 95% CI:2.00-3.00; p < 0.001). Maternal primary and secondary education were positively associated with vaccination (AOR = 1.58; 95% CI:1.34-1.87 and AOR = 1.94; 95% CI:1.40-2.67; respectively; p < 0.001). Nomadic residence was associated with higher odds compared with rural residence (AOR = 1.69; 95% CI:1.46-1.96; p < 0.001). Compared with infants aged 0-11 months, children aged 12-23 months (AOR = 1.36; 95% CI:1.10-1.69; p = 0.005) and 24-59 months (AOR = 1.33; 95% CI:1.12-1.59; p = 0.001) were more likely to be vaccinated. Lack of radio exposure was associated with lower vaccination odds (AOR = 0.64; 95% CI:0.50-0.82; p < 0.001). Children living in Gedo region had markedly lower odds of vaccination than those in Awdal region (AOR = 0.26; 95% CI:0.17-0.39; p < 0.001). Childhood immunization coverage in Somalia remains critically low, reflecting socioeconomic, maternal, healthcare access, and geographic inequalities that require strategies targeting disadvantaged populations and regions.
Surgical wounds healing by secondary intention occur if a surgical wound is not closed or dehisces following primary closure. Surgical wounds healing by secondary intention are common and adversely affect patients' quality of life. Treatment is often prolonged, complex and expensive. Negative pressure wound therapy applies a controlled vacuum to the wound and is increasingly used to promote surgical wound healing by secondary intention despite limited rigorous evidence for the clinical and cost-effectiveness of negative pressure wound therapy to augment surgical wound healing by secondary intention. Assess the clinical and cost-effectiveness of negative pressure wound therapy versus usual care (no negative pressure wound therapy) in treating surgical wounds healing by secondary intention. A pragmatic, two-arm, parallel-group, randomised controlled superiority trial. Twenty-eight UK NHS Trusts randomised adult patients with a surgical wounds healing by secondary intention to receive negative pressure wound therapy or usual care (no negative pressure wound therapy). The planned sample size was 696 participants. Participants were followed up for 12 months via weekly telephone contact to collect the primary outcome (time to healing: full cover with no scab in days since randomisation) and clinical secondary outcomes: wound healing, surgical site infection, pain, hospital re-admission, current treatment and reasons for treatment change (if applicable), reoperation, amputation, antibiotic use, death. Patient-reported outcomes (pain, health-related quality of life and resource use) were collected by postal questionnaire at 3, 6 and 12 months. Validation of the Bluebelle Wound Healing Questionnaire, a patient-reported measure of surgical site infection, was also undertaken. A cost-effectiveness decision model considering all available evidence, and a within-trial cost-utility analysis, was also undertaken to evaluate the cost-effectiveness of negative pressure wound therapy against usual care. Neither participants nor the investigators were blind to treatment allocation. Between 15 May 2019 and 13 January 2023, 686 participants were recruited, randomised and included in the analysis (negative pressure wound therapy n = 349; usual care n = 337). Most participants had a single surgical wound healing by secondary intention (n = 622, 90.7%), located on the foot (n = 551, 80.3%) or leg (n = 69, 10.1%) arising following vascular surgery (n = 619, 90.2%). Most participants had comorbidities; diabetes (n = 549, 80.0%), cardiovascular disease (n = 446, 65.0%) and/or peripheral vascular disease (n = 349, 50.9%). Median time to healing was 187 days (negative pressure wound therapy) versus 195 days (usual care), with no evidence that negative pressure wound therapy reduced the time to wound healing compared to usual care (hazard ratio 1.08, 95% CI 0.88 to 1.32; p = 0.47). Odds of re-admission, reoperation, surgical site infection and antibiotic use were slightly higher, and odds of amputation or death slightly lower for negative pressure wound therapy participants. These results were not clinically or statistically significant. Bluebelle Wound Healing Questionnaire, quality of life and wound pain scores were not statistically significantly different at any time point. Serious adverse events were rare (nine negative pressure wound therapy vs. five usual-care participants). Both cost-effectiveness analyses concluded that negative pressure wound therapy generates higher costs and marginally higher quality-adjusted life-years than usual care, although findings were statistically insignificant. The probability of negative pressure wound therapy being cost-effective was under the recommended National Institute for Health and Care Excellence cost-effectiveness thresholds. The Bluebelle Wound Healing Questionnaire was acceptable to participants, had low levels of missing data and demonstrated good levels of sensitivity and specificity in the detection of surgical site infection in surgical wounds healing by secondary intention. The trial included a high proportion of diabetic participants with foot wounds, which may affect study generalisability. Negative pressure wound therapy use for 'wound management', common in certain surgical specialties, was not assessed in this study. Negative pressure wound therapy is not clinically or cost-effective in augmenting healing in patients with surgical wounds healing by secondary intention, particularly those with comorbidities. Evaluation of methods to treat or prevent infection of surgical wounds healing by secondary intention and evaluation of negative pressure wound therapy for 'wound management' are recommended. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/42/94. After an operation, most wounds are closed using stitches or staples. Some wounds cannot be closed and are left open. Some closed wounds may reopen. These ‘open’ wounds are usually left to heal slowly from the bottom up. Negative pressure wound therapy is commonly used to treat ‘open’ wounds. Negative pressure wound therapy uses a machine to apply gentle suction to a wound, which removes wound fluid, and may help keep the wound clean and perhaps aid healing. We do not know if negative pressure wound therapy is as good as, better than or worse than standard wound dressings that are also used for healing ‘open’ surgical wounds. We also do not know if negative pressure wound therapy is good value for money. There has not been enough, high quality, independent research to enable doctors and nurses to decide on the best treatment. Between May 2019 and January 2023, 686 patients with an open wound agreed to take part and were equally randomly assigned to standard dressings or negative pressure wound therapy. Most of the wounds were on patient’s feet. Most patients had diabetes, and many patients also had conditions affecting their heart and/or blood vessels. We collected wound healing data, treatment information and health outcomes for each participant for a year. We found no clear evidence that negative pressure wound therapy provided any significant benefits for patients and specifically that negative pressure wound therapy did not reduce the time it took for wounds to heal compared to standard wound care. Negative pressure wound therapy was also more expensive than standard dressings and so was not likely to be a good use of healthcare resources. Patients and doctors will be able to make more informed decisions about which dressing to use to help wounds heal. The National Health Service can save money by recommending the use of standard dressings for open wounds instead of using the more expensive negative pressure wound therapy.
The number of older people in Germany has risen steadily in recent decades. One in four people is now aged 65 or over. As people age, their health problems tend to increase, as do their fundamental care needs. Nurses play a key role in addressing these needs through a holistic approach. To fulfil this responsibility effectively, it is necessary to examine existing nursing research on the fundamentals of care for older people and to identify gaps in the current evidence base. Therefore, we plan to conduct a mapping review with the aim of mapping the extent, range and nature of nursing research activities on the fundamentals of care, as defined in the physical, psychosocial and relational components of the Integration of Care dimension of the Fundamentals of Care Framework for older people in Germany. We will search the electronic databases PubMed/MEDLINE, CINAHL, CareLit and GeroLit, the catalogue of the German Federal Ministry of Research, Technology and Space and the German National Library for publications on nursing research based on the Integration of Care dimension of the Fundamentals of Care Framework among older people (≥ 65 years). There will be no time limit. We will include studies published in English and German. Initial screening of the first ten per cent of titles and abstracts and other stages will be carried out by two independent researchers. This process will be repeated until full agreement between the researchers. Any discrepancies will be resolved with consultation of a third reviewer. Results will be reported in a narrative synthesis and complemented by tabular and numerical presentations. To the best of our knowledge, this mapping review will be the first to provide an overview of current nursing research on the fundamentals of care for older people in Germany. The inclusion of German-language texts and the absence of time limits in this review are intended to complement previous reviews. The planned mapping review will also identify the evidence gap in research in this area and contribute to the determination of future scientific research in Germany. Consequently, the findings of the mapping review could be of great interest to nurses and other health professionals for evidence-based practice, research and educational programmes. In addition, the data can be used to develop a programme for the provision of age-friendly and caring living conditions for older people in the future. The protocol was registered with Open Science Framework (osf.io/9e3uv).
The purpose of this systematic review was to analyze whether breathing therapy is effective in reducing pain, improving health-related quality of life, improving physical functioning/activity, and improving sleep quality in patients suffering from complex chronic non-cancer pain conditions (CNCP). An electronic literature search was conducted in MEDLINE, CINAHL, EMBASE, Cochrane Library, PEDro, and PsycINFO from inception to October 2024. The inclusion criteria were randomized clinical trials (RCT) examining breathing therapy as a sole or central intervention component in adult patients with CNCP. From 2,369 abstracts, a total of 10 RCTs (n=638) met the inclusion criteria. The population in the selected studies were patients with chronic neck pain, chronic low back pain, fibromyalgia, or tension-typed headache. Breathing therapy significantly improved pain and/or health-related quality of life in six studies. However, the quality of the included RCTs ranged from high to critically low, and substantial heterogeneity in participants, intervention, and methods prevented synthesis of results across studies. This systematic review highlights breathing therapy as a promising pain management strategy in patients suffering from CNCP. We evaluated two RCTs examining similar daily slow diaphragmatic breathing for 15 min to have a low risk of bias; both demonstrating statistically significant relevant pain reduction up to 37 %. However, the strength of recommendations for clinical practice depends on the level of evidence as indicated by a risk of bias assessment (internal validity), consistency of results between studies, and generalizability (external validity). Based on the findings of this systematic review evidence of breathing therapy invention in patients suffering from CNCP conditions remains sparse. Striving to eliminate or minimize opioid management for complex CNCP, high-quality research is needed to reinforce the evidence base for non-pharmacological interventions such as breathing therapy to support modern pain management rather than former traditional pharmacological treatment. Trial registry number: PROSPERO #CRD42023460181.
In Mexico, tobacco use represents one of the leading threats to public health, being associated with thousands of preventable deaths and diseases. Social factors, such as peer pressure, play a significant role in the initiation of tobacco use among young people, who seek acceptance and identity. Although intervention studies exist, few address peer pressure comprehensively and from a theoretical framework. Therefore, a psychoeducational intervention is proposed for university students, with the aim of assessing its acceptability and feasibility, as well as exploring changes in self-esteem, emotional dependence, and social skills. Its contribution lies in providing preliminary evidence for future large-scale clinical trials. The study was designed as a prospective, single-arm pilot. Nursing students from a faculty in Veracruz will participate, with a recruitment target of 30 students aged 18 years or older. The group intervention consists of four 50-min sessions, in addition to pre- and post-test evaluations, addressing peer pressure, self-esteem, social skills, and emotional dependence. Tobacco use among young people is a multifactorial problem in which peer pressure constitutes a central factor. The proposed psychoeducational intervention seeks to strengthen resistance, promote self-esteem, enhance social skills, and address emotional dependence. Its implementation entails practical challenges, including student participation, retention, logistical organization, and resource availability. This study will allow for the evaluation of the intervention's acceptability and feasibility, generating preliminary evidence for future trials. The findings will contribute to the design of evidence-based preventive strategies relevant to the university setting and adolescent public health. UMIN000059102.
Sperm DNA fragmentation (SDF) has emerged as a clinically important biomarker in male infertility evaluation, offering diagnostic information beyond conventional semen analysis. The inclusion of SDF testing into the World Health Organization 6th edition laboratory manual underscores its growing relevance in reproductive medicine. Elevated SDF levels have been associated with reduced fertilization rates, impaired embryo quality, decreased pregnancy rates, and increased miscarriage risk, particularly in couples with otherwise normal semen parameters. This narrative review examines current SDF testing methodologies, focusing on clinical applicability and diagnostic thresholds. We compared four principal testing modalities-terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), sperm chromatin structure assay (SCSA), sperm chromatin dispersion (SCD) test, and Comet assay, by evaluating their technical characteristics, reproducibility, and predictive value for assisted reproductive technology (ART) outcomes. The evidence demonstrates that, although universal thresholds remain elusive, methodology-specific cut-off values provide meaningful clinical guidance: TUNEL (>16.8-20%), SCSA DNA fragmentation index (>25%), SCD (15-25%), and alkaline Comet assay (>26%). Clinical indications for SDF testing include recurrent pregnancy loss, unexplained infertility, and recurrent ART failure. Evidence-based management strategies encompass varicocelectomy, short ejaculatory abstinence protocols, antioxidant therapy, and testicular sperm extraction for refractory cases. Interpretation should be contextualised by female partner age, oocyte quality, and planned ART modality, as these factors substantially influence the clinical impact of elevated SDF. By integrating findings of recent literature, this review provides a practical, evidence-based framework for the judicious application of SDF testing, including patient selection criteria, methodological considerations, and stepwise therapeutic interventions.
To review the literature on psychosocial care and experiences of young adults with early-onset type 2 diabetes (EOT2D), to identify what is known, current gaps and to develop recommendations to help advance psychosocial care and support for the population. We searched Medline (Ovid), Google Scholar and diabetes-specific journals for English-language articles focused on psychosocial aspects in young adults (aged 18-45 years) with EOT2D. Two people with lived experience reviewed and commented on the review findings. Growing evidence indicates that a diagnosis of EOT2D is associated with an increased risk of developing diabetes-related psychological comorbidities. Experiences of diabetes-related stigma, compounded by age-related negative preconceptions, contribute to heightening the psychosocial impact of EOT2D. Some population sub-groups appear to be more likely to experience adverse psychological effects. However, the evidence base is limited by a dearth of diverse research specifically focused on the psychosocial experiences and needs of this population (e.g., longitudinal and qualitative studies). Adults with EOT2D also experience unmet education, care and support needs relevant to optimising their psychosocial well-being and diabetes management. Overall, they require enhanced, tailored care and support that is age-appropriate, person-centred and responsive to their psychosocial needs. Digital technology and support-based strategies may help to address current gaps and improve the psychological well-being of this group, but these require further exploration. Despite the importance of psychosocial factors in young adults' diabetes management and outcomes, there remain gaps in research and practice and the need for further research, alongside changes in practice.
Autophagy is a central cellular quality-control pathway that maintains metabolic and proteostatic homeostasis by degrading damaged organelles and proteins. In the lung, autophagy contributes to normal development, epithelial integrity, mitochondrial quality control, and immune regulation. Emerging evidence indicates that environmental exposures such as cigarette smoke (CS), electronic cigarette (EC) aerosols, and nicotine profoundly disrupt these processes, contributing to both chronic lung disease and developmental programming of respiratory pathology. In this review, we propose a unifying framework in which autophagy functions as a redox-modulated rheostat that integrates oxidative, metabolic, and epigenetic stress signals triggered by smoke and nicotine exposure. Under physiological conditions, autophagy mitigates oxidative stress by removing dysfunctional mitochondria and maintaining proteostasis. However, chronic exposure to CS or EC aerosols generates excessive reactive oxygen species, impairs lysosomal degradation, and disrupts mitochondrial quality control, shifting autophagy from an adaptive protective response to a maladaptive driver of epithelial injury, inflammation, and tissue remodeling. Integrating experimental and clinical evidence, we identify four mechanistic axes underlying smoke-induced autophagy dysregulation: lysosomal dysfunction with TFEB suppression, mitochondrial redox amplification, disruption of selective autophagy pathways (including mitophagy, ER-phagy, xenophagy, and lipophagy), and immune polarization associated with inflammasome activation and cellular senescence. Importantly, maternal smoke and EC exposure similarly perturb autophagy in the placenta and fetal lung, altering developmental trajectories and increasing susceptibility to asthma and chronic lung disease. Viewing autophagy as a dynamic, redox-sensitive rheostat highlights new therapeutic opportunities to restore autophagic flux, lysosomal competence, and mitochondrial quality control in smoke- and nicotine-related lung disease.
Parkinsonian disorders, including Parkinson's disease, Lewy body dementia, multiple system atrophy, and progressive supranuclear palsy, are progressive neurodegenerative conditions with no treatment options to slow disease progression. This systematic review provides an overview of evidence of disease-modifying therapies that have been evaluated in clinical studies across these disorders, based on a comprehensive literature search up to May 2025. Eligible studies included clinical trials investigating pharmacological interventions aimed at slowing disease progression. Most clinical development has focused on Parkinson's disease, with limited progress in other Parkinsonian disorders. Therapies targeting alpha-synuclein, such as monoclonal antibodies and small molecules, have shown target engagement but limited clinical efficacy. Glucocerebrosidase-enhancing agents, particularly ambroxol, demonstrated promising biomarker and clinical signals in early-phase trials. Glucagon-like peptide-1 receptor agonists and kinase inhibitors have yielded mixed results, with some agents progressing to phase 3 trials. Neurotrophic factors, cell survival and neuroprotective therapies, stem cell therapies, and anti-inflammatory agents remain largely investigational, with limited evidence of efficacy. Repurposed drugs, including memantine and riluzole, have shown preliminary signals of benefit, though confirmatory trials are lacking. Despite substantial research efforts, no disease-modifying therapy has been approved for any Parkinsonian disorder. The heterogeneity of disease mechanisms and the limitations of current clinical endpoints, such as the Unified Parkinson's Disease Rating Scale, underscore the need for biomarker-driven approaches and stratified trial designs. Future success will likely depend on improved patient selection, mechanistic targeting, and the integration of fluid and imaging biomarkers to demonstrate disease modification.