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PubMed2026

Precision Optimization of Behavioral Activation for Major and Subthreshold Depression: A Meta-Analysis of Exploring Dose-Response Relationships and Moderating Factors.

OBJECTIVE: This meta-analysis evaluated the efficacy of behavioral activation (BA) in adolescents with subthreshold depression (SD) or major depressive disorder (MDD), exploring dose-response relationships and moderating factors. METHOD: We searched PubMed, EMBASE, Web of Science, EBSCO, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) through December 31, 2024. Risk of bias was assessed using RoB-2, and evidence quality with Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Analyses were performed with R, using standardized mean difference (SMD) for continuous variables and meta-regression for dose-response relationships. Subgroup analyses included symptom severity, intervention setting, delivery format, and parental involvement. The primary outcome was the reduction in depressive symptoms (PROSPERO: CRD42023444273). RESULTS: A total of 14 studies were included (11 RCTs meta-analyzed, comprising 572 participants). BA demonstrated a moderate effect size compared to treatment-as-usual (SMD = -0.42) and a large effect size compared to no-treatment controls (SMD = -0.87). BA was more effective for mild depressive symptoms (SMD = -0.93) than severe symptoms (SMD = -0.43), with significant efficacy in university settings (SMD = -0.94). Intervention without parental involvement exhibited significantly larger effects than those with parental participation (SMD = -0.94 vs -0.38; p < .0001), although this finding was likely confounded by age, symptom severity, and intervention setting. BA moderately improved both behavioral activation levels and functioning (SMD = 0.49). CONCLUSION: Short-term, school-based BA is significantly beneficial for older adolescents with mild depressive symptoms. Findings provide practical guidance for optimizing BA implementation and highlight directions for future research, including the need for larger sample sizes, standardized follow-up assessments, and more representative samples. PLAIN LANGUAGE SUMMARY: This meta-analysis evaluated the effectiveness of behavioral activation (BA), a therapeutic approach focused on improving positive activities, in adolescents with subthreshold depression or major depressive disorder. Based on 14 included studies and 572 participants, BA was found to be more effective for subthreshold compared to major depression. These findings suggest a promising role for BA as an early intervention tool in adolescent depression. STUDY REGISTRATION INFORMATION: Precision Optimization of Behavioral Activation for Major and Subthreshold Depression: A Meta-Analysis of Exploring Dose-response Relationships and Moderating Factors; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023444273. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. Diverse cell lines and/or genomic datasets were not available. We actively worked to promote sex and gender balance in our author group.

Humans↗

PubMed2006

An exploration of the patient's experience of electro-convulsive therapy in mid-twentieth century creative literature: a historical study with implications for practice today.

BACKGROUND: Understanding a patient's subjective experience of electro-convulsive therapy (ECT) is important. Creative literature may both express such experiences and influence how ECT is perceived since scenarios and characters in literature become incorporated into cultural stereotypes and mythologies. Clinical discussions with patients and their families suggest that One Flew over the Cuckoo's Nest still has an impact on their perceptions of ECT, and therefore still has clinical relevance today. This study aims to explore experiences of ECT through creative literature focussing on novels from the 1960s. METHOD: Study of three novels depicting ECT in their historical context. RESULTS: Various factors identified in the books studied may be associated with reluctance to accept ECT as a treatment, in particular images related to electricity. LIMITATIONS: Since this is a historical survey rather than a clinical research project, and is based on creative literature, it may not reflect 21st century reality. CONCLUSIONS: Fear of electricity and other factors in the practice of ECT in the past may still be important in the acceptance of ECT as a clinical treatment. This warrants further qualitative exploration.

Creativity↗

PubMed2005

Technical complications are rising as common duct exploration is becoming rare.

BACKGROUND: Both hospital and surgeon volume influence outcomes. With introduction of new technologies, some procedures are now performed less frequently. ERCP has replaced the need for common duct exploration (CDE) in most cases of choledocholithiasis. We explored the secular trends and outcomes of CDE and how they have changed relative to introduction of ERCP. STUDY DESIGN: The National Hospital Discharge Survey database was analyzed for the years 1979 to 2001. Procedural frequency of ERCP and CDE was determined. Charlson and Elixhauser comorbidity indices were used to characterize patients' disease burden for the years 1993 to 2001. Length of stay, mortality, and complication rates for each procedure were determined. RESULTS: At the beginning of the study period, an estimated 47,000 CDEs were performed annually. These declined to 7,700 per year as ERCP increased to 42,500 procedures per year at the end of the study period. CDE complication rates increased from 3.4% to 17.4% over the same period. Comorbidity analysis for the years 1993 to 2001 revealed that ERCP and CDE patients had equivalent disease burdens. Technical complication rates rose in parallel to the increased overall CDE complication rate. CONCLUSIONS: ERCP has replaced the need for most but not all CDE. With diminished CDE experience at a national level, the complication rate has markedly increased, at least in part from technical complications. Both choledocholithiasis treatment algorithms and clinical training paradigms need to account for the rarity of CDE and high complication rates associated with it, by incorporation of training modules in surgical residencies and advocating referral to centers having expertise in biliary tract operations from surgeons with little CDE experience.

Age Factors↗

PubMed2006

Exploring design-related bias in clinical studies on receptor genetic polymorphism of hypertension.

BACKGROUND AND OBJECTIVES: Although several candidate genes of Renin-Angiotensin-Aldosterone System (RAAS) have been investigated, the gene-drug relationship remains unclear. The objective was to appraise the elements of research methodology and explore potential biases, which may be contributing to discordant results in the gene-drug interaction assessment for RAAS. METHODS: Systematic review of studies involving candidate polymorphisms, searching PubMed, and EMBASE. RESULTS: Sixteen studies were identified. Nine studies had a genomic evaluation as the primary question. Six studies investigated more than one gene. A gene-drug interaction was evaluated in two studies and only one of the studies had a placebo arm for accurately exploring the interaction. Almost, 90% of the studies had sample sizes of less than 500 patients. Four studies combined the allele frequencies of the heterozygotes group with one of the homozygotes groups. Almost one quarter of the studies combined different therapeutics in one group. Five studies included patients in one group from previous studies in which selection criteria were not quite similar. CONCLUSION: Most studies contain several methodological limitations. Also biases driven from patient selection, combining different alleles, combining different therapeutics, and combining end points may have occurred in these studies. These limitations and biases may contribute to inconsistency of the results of these studies.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2004

Quantifying structure-function uncertainty: a graph theoretical exploration into the origins and limitations of protein annotation.

Since the advent of investigations into structural genomics, research has focused on correctly identifying domain boundaries, as well as domain similarities and differences in the context of their evolutionary relationships. As the science of structural genomics ramps up adding more and more information into the databanks, questions about the accuracy and completeness of our classification and annotation systems appear on the forefront of this research. A central question of paramount importance is how structural similarity relates to functional similarity. Here, we begin to rigorously and quantitatively answer these questions by first exploring the consensus between the most common protein domain structure annotation databases CATH, SCOP and FSSP. Each of these databases explores the evolutionary relationships between protein domains using a combination of automatic and manual, structural and functional, continuous and discrete similarity measures. In order to examine the issue of consensus thoroughly, we build a generalized graph out of each of these databases and hierarchically cluster these graphs at interval thresholds. We then employ a distance measure to find regions of greatest overlap. Using this procedure we were able not only to enumerate the level of consensus between the different annotation systems, but also to define the graph-theoretical origins behind the annotation schema of class, family and superfamily by observing that the same thresholds that define the best consensus regions between FSSP, SCOP and CATH correspond to distinct, non-random phase-transitions in the structure comparison graph itself. To investigate the correspondence in divergence between structure and function further, we introduce a measure of functional entropy that calculates divergence in function space. First, we use this measure to calculate the general correlation between structural homology and functional proximity. We extend this analysis further by quantitatively calculating the average amount of functional information gained from our understanding of structural distance and the corollary inherent uncertainty that represents the theoretical limit of our ability to infer function from structural similarity. Finally we show how our measure of functional "entropy" translates into a more intuitive concept of functional annotation into similarity EC classes.

Biochemical Phenomena↗

PubMed2005

Spin relaxation measurements of electrostatic bias in intermolecular exploration.

We utilize the paramagnetic contribution to proton spin-lattice relaxation rate constants induced by freely diffusing charged paramagnetic centers to investigate the effect of charge on the intermolecular exploration of a protein by the small molecule. The proton NMR spectrum provided 255 resolved resonances that report how the explorer molecule local concentration varies with position on the surface. The measurements integrate over local dielectric constant variations, and, in principle, provide an experimental characterization of the surface free energy sampling biases introduced by the charge distribution on the protein. The experimental results for ribonuclease A obtained using positive, neutral, and negatively charged small nitroxide radicals are qualitatively similar to those expected from electrostatic calculations. However, while systematic electrostatic trends are apparent, the three different combinations of the data sets do not yield internally consistent values for the electrostatic contribution to the intermolecular free energy. We attribute this failure to the weakness of the electrostatic sampling bias for charged nitroxides in water and local variations in effective translational diffusion constant at the water-protein interface, which enters the nuclear spin relaxation equations for the nitroxide-proton dipolar coupling.

Journal Article↗

PubMed2006

Is contralateral exploration necessary in preterm infants with unilateral inguinal hernia?

PURPOSE: Contralateral inguinal exploration has been the preferred approach to preterm infants with unilateral inguinal hernia. There is no literature evidence to justify this. The aim of this prospective study is to analyze the incidence and to determine any risk factors for the development of contralateral metachronous hernia (MH) in the preterm when compared with term infants. METHODS: Preterm and term infants with unilateral inguinal hernia younger than 6 months who underwent surgery were included. Those infants who subsequently developed MH were analyzed. RESULTS: Two hundred sixty-six patients met the inclusion criteria. One hundred five were preterm and 161 were term. Ten preterm (10.31%) and 9 term infants (5.92%) presented subsequently with MH (P =.18). All but 1 were male. There was no relation between the side of hernia, presentation with incarceration, age at surgery, sex of the patient, and the development of MH. However, a trend toward a higher incidence of MH in very low birth weight and early gestational age preterms was noted. CONCLUSION: There is no significant difference between the occurrence of MH in preterm when compared with term infants. Routine contralateral exploration in preterm infants with its associated risks is therefore not justified in unilateral hernia.

Female↗

PubMed2004

The Swedish driver licensure examination: exploration of a two-stage model.

INTRODUCTION: Sweden, together with several countries in the world, has no compulsory educational requirement prior to the drivers license examination. Having a valid license examination (i.e., a knowledge test and a driving test) is therefore important in order to ensure competent drivers. METHOD: The aim of this paper is to explore the possibility of a two stage testing approach for the Swedish licensure examination. In order to explore the relationship between the knowledge test and the road test, a descriptive and a logistic regression approach were carried out. RESULTS: The result indicates that how the driving candidates perform on the road test depends on their performance on the knowledge test. Therefore, the Swedish drivers licensing examination is suitable for a two-stage testing model.

Adolescent↗

PubMed2005

An exploration of student midwives' language to describe non-formal learning in professional practice.

The essence of non-formal learning in midwifery practice has not been previously explored. This paper provides an in-depth analysis of the language of a sample of student midwives' descriptions of their practice learning in a range of clinical settings. The students submitted audio-diaries as part of a national study (Pope, R., Graham. L., Finnerty. G., Magnusson, C. 2003. An investigation of the preparation and assessment for midwifery practice within a range of settings. Project Report. University of Surrey). Participants detailed their learning activities and support obtained whilst working with their named mentors for approximately 10 days or shifts. The rich audio-diary data have been analysed using Discourse Analysis. A typology of non-formal learning (Eraut, M. 2000. Non-formal learning and implicit knowledge in professional work. British Journal of Educational Psychology 70, 113-136) has been used to provide a framework for the analysis. Non-formal learning is defined as any learning which does not take place within a formally organised learning programme (Eraut, M. 2000. Non-formal learning and implicit knowledge in professional work. British Journal of Educational Psychology 70, 113-136). Findings indicate that fear and ambiguity hindered students' learning. Recommendations include the protection of time by mentors within the clinical curriculum to guide and supervise students in both formal and non-formal elements of midwifery practice. This paper will explore the implications of the findings for practice-based education.

Attitude of Health Personnel↗

PubMed2006

The influence of familiarity on brain activation during haptic exploration of 3-D facemasks.

Little is known about the neural substrates that underlie difficult haptic discrimination of 3-D within-class object stimuli. Recent work [A.R. Kilgour, R. Kitada, P. Servos, T.W. James, S.J. Lederman, Haptic face identification activates ventral occipital and temporal areas: an fMRI study, Brain Cogn. (in press)] suggests that the left fusiform gyrus may contribute to the identification of facemasks that are haptically explored in the absence of vision. Here, we extend this line of research to investigate the influence of familiarity. Subjects were trained extensively to individuate a set of facemasks in the absence of vision using only haptic exploration. Brain activation was then measured using fMRI while subjects performed a haptic face recognition task on familiar and unfamiliar facemasks. A group analysis contrasting familiar and unfamiliar facemasks found that the left fusiform gyrus produced greater activation with familiar facemasks.

Adult↗

PubMed2005

Time to imagine space: a chronometric exploration of representational neglect.

When describing known places from memory, patients with left spatial neglect may mention more right- than left-sided items, thus showing representational, or imaginal, neglect. This suggests that these patients cannot either build or explore left locations in visual mental imagery. However, in place description there is no guarantee that patients are really employing visual mental imagery abilities, rather than verbal-propositional knowledge. Thus, patients providing symmetrical descriptions might be using other strategies than visual mental imagery. To address this issue, we devised a new test which strongly encourages the use of visual mental imagery. Twelve participants without brain damage and 12 right brain-damaged patients, of whom 7 had visual neglect, were invited to conjure up a visual mental image of the map of France. They subsequently had to state by pressing a left- or a right-sided key whether auditorily presented towns or regions were situated to the left or right of Paris on the imagined map. This provided measures of response time and accuracy for imagined locations. A further task, devised to assess response bias, used the words "left" or "right" as stimuli and the same keypress responses. Controls and non-neglect patients performed symmetrically. Neglect patients were slower for left than for right imagined locations. On single-case analysis, two patients with visual neglect had a greater response time asymmetry on the geographical task than predicted by the response bias task, but with symmetrical accuracy. The dissociation between response times and accuracy suggests that, in these patients, the left side of the mental map of space was not lost, but only "explored" less efficiently.

Adult↗

PubMed2026

An acute dose of glyphosate alters novel object exploration and hippocampal cFos expression in a sex-dependent manner in wildtype mice.

Glyphosate (GLY) is the active ingredient in most herbicides, including off-the-shelf weed killers such as Roundup®. GLY crosses the blood-brain barrier, increases oxidative stress and genotoxicity, and impacts reproduction, but the extent of its effects remains unclear. Previous research reports conflicting evidence on sex-specific susceptibility to GLY's effects, and very few investigate the effects of a single, acute dose on learning, memory, and neuronal activation. In vitro studies have found GLY interferes with gene expression and is uniquely capable of inducing DNA double strand breaks (DSBs) compared to other herbicides. DSBs can induce expression of immediate early genes (IEGs), which are important for synaptic plasticity, learning, and memory. However, a clear connection between GLY, IEGs, and learning and memory has yet to be made. To explore this, we tested male and female wildtype mice in novel object recognition after they received an acute, oral dose of 0, 250, or 500 mg/kg of GLY and assessed hippocampal DSB and IEG levels. We hypothesized that a single dose of GLY would impair memory by disrupting IEG expression and would affect males more than females. We did not find robust evidence that GLY impaired memory, though females that received 500 mg/kg did not explore the novel object more than the familiar. Hippocampal DSBs were decreased following 500 mg/kg in both sexes, yet hippocampal IEG immunoreactivity was decreased in GLY-exposed males only, revealing a complex sex-dependent relationship. These data add to the literature that GLY is potentially detrimental, highlighting the need for further investigations.

Animals↗

PubMed2004

Comparison of the effects of entorhinal and retrosplenial cortical lesions on habituation, reaction to spatial and non-spatial changes during object exploration in the rat.

This study was aimed at comparing the effects of damage to the entorhinal cortex and retrosplenial cortex on exploration and reaction-to-change in rats. Following habituation to a configuration of objects, a familiar object was displaced therefore producing a spatial change. A non-spatial change was made by substituting a familiar object by a novel object. Both entorhinal cortex lesions and retrosplenial cortex lesions elicited a deficit in the rat's reaction to a spatial change. In addition, rats with entorhinal lesions showed hypoactive object exploration and exhibited a mild deficit in reaction to a non-spatial change. This may reflect the importance of temporal cortical input in object recognition. Overall, these results suggest that the entorhinal cortex and the retrosplenial cortex contribute to the processing of the geometric properties of the environment and have thus close functional links.

Animals↗

PubMed2026

Exploring Primary Care Clinicians' Sexual and Reproductive Health Care Delivery to Male Adolescents and Young Adults.

INTRODUCTION: Despite existing guidance for adolescent sexual and reproductive health (SRH) care, male adolescent SRH care receipt is inadequate. Limited research has explored factors affecting clinicians' provision of SRH care to male adolescents, specifically. METHODS: This mixed-method study with 12 primary care clinicians included a brief survey assessing care delivery practices and confidence, followed by an in-depth interview to explore factors affecting SRH care delivery. RESULTS: Clinicians reported high confidence delivering male adolescent SRH care (mean ± SD: 8.31 ± 1.71 out of 10), but delivered only about half the recommended services (20 items out of 38). Factors influencing care delivery included gaps in education/training, assumptions about male SRH care, and behavioral constraints at various levels. DISCUSSION: Findings underscore the need to strengthen male adolescent SRH care by enhancing provider training, increasing clinic-level supports, and addressing structural barriers. CONCLUSIONS: Findings can inform strategies to improve the quality and comprehensiveness of SRH services for male adolescents in primary care settings.

Humans↗

PubMed2006

Exploring differences in caseloads of rural and urban healthcare providers in Alaska and New Mexico.

OBJECTIVES: Although it is commonly accepted that rural healthcare providers face demands that are both qualitatively and quantitatively different from those faced by urban providers, this conclusion is based largely on data from healthcare consumers and relies on qualitative work with small sample sizes, surveys with small sample sizes, theoretical reviews and anecdotal reports. To enhance our knowledge of the demands faced by rural healthcare providers and to gain the perspectives of healthcare providers themselves, this study explored the caseloads of rural providers compared with those of urban providers. METHOD: An extensive survey of over 1500 licensed clinicians across eight physical and behavioural healthcare provider groups in Alaska and New Mexico was undertaken to explore differences in caseloads based on community size (small rural, rural, small urban, urban), state (Alaska, New Mexico) and discipline (health, behavioural). RESULTS: Findings indicated numerous caseload differences between community sizes that were consistent across both states, with complex case presentations being described most commonly by small rural and rural providers. Substance abuse, alcohol use, cultural diversity, economic disadvantage and age diversity were issues faced more often by providers in rural and small rural communities than by providers in small urban and urban communities. Rural, but not small rural, providers faced challenges around work with prisoners and individuals needing involuntary hospitalization. Although some state and discipline differences were noted, the most important findings were based on community size. CONCLUSIONS: The findings of this study have important implications for provider preparation and training, future research, tailored resource allocation, public health policy, and efforts to prevent 'burnout' of rural providers.

Adolescent↗

PubMed2005

Microbial ecology of the closed artificial ecosystem MELiSSA (Micro-Ecological Life Support System Alternative): reinventing and compartmentalizing the Earth's food and oxygen regeneration system for long-haul space exploration missions.

MELiSSA is a bioregenerative life support system designed by the European Space Agency (ESA) for the complete recycling of gas, liquid and solid wastes during long distance space exploration. The system uses the combined activity of different living organisms: microbial cultures in bioreactors, a plant compartment and a human crew. In this minireview, the development of a short-cut ecological system for the biotransformation of organic waste is discussed from a microorganism's perspective. The artificial ecological model--still in full development--that is inspired by Earth's own geomicrobiological ecosystem serves as an ideal study object on microbial ecology and will become an indispensable travel companion in manned space exploration.

Bacteria↗

PubMed2006

Access point analysis on the state of health care services in South African prisons: a qualitative exploration of correctional health care workers' and inmates' perspectives in Kwazulu-Natal and Mpumalanga.

This paper explores inmates and prison health care workers perceptions of the state of health care services in four correctional facilities in South Africa. Structural and organisational issues are explored in terms of how they impact the delivery and provision of health care to inmates within correctional facilities. Additionally, the study forms an access point analysis of prisons as a health care setting as part of the development and testing of a STI/HIV health education intervention for soon to be released inmates. Focus group discussions (6-8 participants per group) were conducted with male inmates in four facilities in KwaZulu-Natal and Mpumalanga provinces. Individual face-to-face interviews were conducted with eight health personnel to get a view from both providers and end users of health care in correctional settings. Data were analysed thematically. We found strong evidence of prison being a strategic point to increase access to health services for offenders. Curative services within prisons were well established and running despite the presence of certain challenges varying across institutions. Prevention programmes emerged as an area that requires stronger emphasis to facilitate imparting skills and promoting safer practices for inmates upon release. Peer-led education programmes emerged as a key aspect of preparation for release and community reintegration amongst inmates.

Adolescent↗

PubMed2004

Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen.

OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth.

Biopsy↗