Miracle-dz/UniFAR-FTUs huggingface dataset:
Self-reported overdose among injecting drug users in London: extent and nature of the problem.

AIMS To estimate the extent and nature of overdose and factors associated with overdose among injecting drug users in London. DESIGN Three hundred and twelve current injecting drug users were recruited and interviewed in community settings by a team of "privileged access interviewers". MEASUREMENTS A structured questionnaire was used that covered the following areas: demographic characteristics, drug use, injecting behaviour, sharing practices, severity of drug dependence, experience of overdose, injecting-related health problems and treatment history. FINDINGS The results showed that experience of overdose was common (38%). A majority (54%) had witnessed someone else overdose. Overdosing was not a solitary experience; over 80% of subjects who had overdosed had done so in the presence of someone else, but only 27% reported ambulances having been called. Factors found to be associated with overdose were: age at which injecting began; gender (women being more likely to experience overdose); use of alcohol; and polydrug injection. The overall rate of overdosing was one per 6 years of injecting; however, once an individual had an overdose the chance of having another increased. The risk of experiencing a first overdose fell with years of injecting. CONCLUSIONS Harm-reduction interventions with drug injectors should educate users on the risk factors associated with overdose and actions that should be taken when someone has overdosed. Interventions designed to reduce the risk of overdose may be more effective if they are differentially targeted on drug injectors who have already experienced an overdose.
Effect of Superficial Cervical Plexus Block on Baroreceptor Sensitivity in Patients Undergoing Carotid Endarterectomy.

OBJECTIVES Regional anesthesia for patients undergoing carotid endarterectomy is associated with improved intraoperative hemodynamic stability compared with general anesthesia. The authors hypothesized that the reported advantages might be related to attenuated ipsilateral baroreflex control of blood pressure, caused by chemical denervation of the carotid bulb baroreceptor nerve fibers. DESIGN A prospective cohort study. SETTING Single-center university hospital. PARTICIPANTS The study included 46 patients undergoing carotid endarterectomy using superficial cervical block. INTERVENTIONS A noninvasive computational periprocedural measurement of baroreceptor sensitivity was performed in all patients. Two groups were formed, depending on the patients' subjective response to surgical stimulation regarding the necessity of additional intraoperative local anesthesia (LA) administration on the carotid bulb. Group A (block alone) included 23 patients who required no additional anesthesia, and group B (block + LA) consisted of 23 patients who required additional anesthesia. MEASUREMENTS AND MAIN RESULTS Baroreceptor sensitivity showed no significant change after application of the block in both groups (group A: median [IQR], 5.19 [3.07-8.54] v 4.96 [3.1-9.07]; p = 0.20) (group B: median [IQR], 4.47 [3.36-8.09] v 4.53 [3.29-8.01]; p = 0.55). There was a significant decrease in baroreceptor sensitivity in group B after intraoperative LA administration (median [IQR], 4.53 [3.29-8.01] v 3.31 [2.26-7.31]; p = 0.04). CONCLUSIONS Standard superficial cervical plexus block did not impair local baroreceptor function, and, therefore, it was not related to improved cerebral perfusion in awake patients undergoing carotid endarterectomy. However, direct infiltration of the carotid bulb was associated with the expected attenuation of baroreflex sensitivity.
Survival in second primary malignancies of patients with head and neck cancer

Second primary tumours occur frequently in patients with a history of head and neck malignancies. Delays in making an early and correct diagnosis can seriously affect the therapy management and survival. This was a retrospective study of 120 patients with a history of head and neck cancer, presenting with a second primary tumour. Current follow-up strategies and the use of routine sonographic imaging of the head and neck regions were evaluated, and the impact that tumour chronology, the tumour site and the various treatment modalities have on the survival were assessed. Forty-two per cent of patients developed a metachronous second malignancy more than five years after diagnosis of the index tumour. The accuracy of colour-duplex sonography in detection of second primaries in the head and neck was 82.3 per cent. First and second primary tumours located in the larynx were observed to have the highest five-year survival rate. Patients who developed metachronous tumours had a five-year survival rate of 68.9 per cent for the index tumours, and a 26 per cent five-year survival rate with the occurrence of a second neoplasm. With synchronous tumours a mean survival time of 18 months and a five-year survival rate of 11.9 per cent was found (p < 0.0001). Where clinically appropriate an aggressive treatment strategy was employed and yielded the most favourable results with a five-year survival rate of 66.8 per cent and 35.9 per cent for index tumours and second primary malignancies, respectively. Since more than 40 per cent of the metachronous second primaries in patients with a history of head and neck malignancy occur beyond the five-year follow-up period, an extended protocol with individually adjusted close monitoring of high-risk patients seems appropriate. Colour-duplex sonography is a valuable screening investigation for the early detection of second primary tumours. The treatment of a second primary is often less successful than for the same malignancy occurring primarily. The prognosis of synchronous tumours is significantly lower when compared to malignancies of a metachronous nature, despite some encouraging individual results. Only the early implementation of aggressive treatment methods for second primaries is successful in terms of survival.
Outcome of first-episode schizophrenia in India: longitudinal study of effect of insight and psychopathology

Background Transcultural studies have found lack of insight to be an almost invariable feature of acute and chronic schizophrenia, but its influence on prognosis is unclear. Aims To investigate the relationship between insight, psychopathology and outcome of first-episode schizophrenia in Vellore, India. Method Patients with a DSM–IV diagnosis of schizophrenia (η = 131) were assessed prospectively at baseline and at 6-month and 12-month follow-up. Demographic and clinical measures included insight, psychopathology, duration of untreated psychosis (DUP) and social functioning. Linear and logistic regression was used to measure predictors of outcome. Results Follow-up data were available for 115 patients at 1 year. All achieved remission, half of them with and half without residual symptoms. Changes in psychopathology and insight during the first 6 months and DUP strongly predicted outcome (relapse or functional impairment), controlling for baseline measures. Conclusions Outcome of schizophrenia in this setting is driven by early symptomatic improvement and is relatively favourable, in line with other studies from low- and middle-income countries. Early improvement in insight might be a useful clinical guide to future outcome. Reduction of DUP should be a target for intervention.
A Transport Metabolon

The cytoplasmic carboxyl-terminal domain of AE1, the plasma membrane chloride/bicarbonate exchanger of erythrocytes, contains a binding site for carbonic anhydrase II (CAII). To examine the physiological role of the AE1/CAII interaction, anion exchange activity of transfected HEK293 cells was monitored by following the changes in intracellular pH associated with AE1-mediated bicarbonate transport. AE1-mediated chloride/bicarbonate exchange was reduced 50–60% by inhibition of endogenous carbonic anhydrase with acetazolamide, which indicates that CAII activity is required for full anion transport activity. AE1 mutants, unable to bind CAII, had significantly lower transport activity than wild-type AE1 (10% of wild-type activity), suggesting that a direct interaction was required. To determine the effect of displacement of endogenous wild-type CAII from its binding site on AE1, AE1-transfected HEK293 cells were co-transfected with cDNA for a functionally inactive CAII mutant, V143Y. AE1 activity was maximally inhibited 61 ± 4% in the presence of V143Y CAII. A similar effect of V143Y CAII was found for AE2 and AE3cardiac anion exchanger isoforms. We conclude that the binding of CAII to the AE1 carboxyl-terminus potentiates anion transport activity and allows for maximal transport. The interaction of CAII with AE1 forms a transport metabolon, a membrane protein complex involved in regulation of bicarbonate metabolism and transport.
Empowerment of Cancer Survivors Through Information Technology: An Integrative Review

Background Patient empowerment may be an effective approach to strengthen the role of cancer survivors and to reduce the burden on health care. However, it is not well conceptualized, notably in oncology. Furthermore, it is unclear to what extent information technology (IT) services can contribute to empowerment of cancer survivors. Objective We aim to define the conceptual components of patient empowerment of chronic disease patients, especially cancer survivors, and to explore the contribution of existing and new IT services to promote empowerment. Methods Electronic databases were searched to identify theoretical and empirical articles regarding empowerment. We extracted and synthesized conceptual components of patient empowerment (ie, attributes, antecedents, and consequences) according to the integrated review methodology. We identified recent IT services for cancer survivors by examining systematic reviews and a proposed inventory of new services, and we related their features and effects to the identified components of empowerment. Results Based on 26 articles, we identified five main attributes of patient empowerment: (1) being autonomous and respected, (2) having knowledge, (3) having psychosocial and behavioral skills, (4) perceiving support from community, family, and friends, and (5) perceiving oneself to be useful. The latter two were specific for the cancer setting. Systematic reviews of IT services and our additional inventory helped us identify five main categories: (1) educational services, including electronic survivorship care plan services, (2) patient-to-patient services, (3) electronic patient-reported outcome (ePRO) services, (4) multicomponent services, and (5) portal services. Potential impact on empowerment included knowledge enhancement and, to a lesser extent, enhancing autonomy and skills. Newly developed services offer promising and exciting opportunities to empower cancer survivors, for instance, by providing tailored advice for supportive or follow-up care based on patients' input. Conclusions We identified five main components of empowerment and showed that IT services may especially contribute to empowerment by providing knowledge. The components of empowerment could be used to develop IT services for cancer survivors. It is important to take into account patients’ needs, follow up on these needs, and create a service that is attractive and easy to use.
Respiratory Syncytial Virus G and/or SH Protein Alters Th1 Cytokines, Natural Killer Cells, and Neutrophils Responding to Pulmonary Infection in BALB/c Mice

ABSTRACT BALB/c mice sensitized to vaccinia virus expressed G protein of respiratory syncytial virus (RSV) develop a Th2-type cytokine response and pulmonary eosinophilia when challenged with live RSV. In this study, BALB/c mice were immunized or challenged with an RSV mutant lacking the G and SH proteins or with DNA vaccines coding for RSV G or F protein. F or G protein DNA vaccines were capable of sensitizing for pulmonary eosinophilia. The absence of the G and/or SH protein in the infecting virus resulted in a consistent increase both in pulmonary natural killer cells and in gamma interferon and tumor necrosis factor expression, as well as, with primary infection, a variable increase in neutrophils and CD11b+ cells. The development of pulmonary eosinophilia in formalin-inactivated RSV-vaccinated mice required the presence of the G and/or SH protein in the challenge virus. These data show that G and/or SH protein has a marked impact on the inflammatory and innate immune response to RSV infection.
Effects of Depolarization and NMDA Antagonists on the Survival of Cerebellar Granule Cells: A Pivotal Role for Protein Kinase C Isoforms

Abstract: Primary cultures of cerebellar granule cells (CGCs) grown in high‐K+ (25 mM; K25) medium progressively differentiate in vitro. Differentiation is noticeable after 3–4 days in vitro (DIV) and reach a mature stage after 8 DIV. Longer cultivation of CGCs (>13 DIV) triggers the processes of spontaneous cell death. However, if cultured in normal physiological K+ concentration (5 mM; K5), a significant proportion of the cells dies by the end of the first week in culture. To address the role of protein kinase C (PKC) in the development of CGCs, we measured the kinase activity as well as the protein level of the kinase isoforms. As the K25 CGC culture proceeded, the PKC activity time‐dependently increased by 3.2‐fold, reaching a steady state at 8 DIV. Western blot analysis using PKC isoform‐specific antibodies revealed an increase in levels of PKC α, γ, μ, λ, and ι from 2 to 8 DIV. A slight increase or decrease at 4 DIV was observed for PKC ε and βII, respectively, whereas no significant change was observed for βI. The isoforms of δ, θ, η, and ζ were not detected. Comparing the 14 DIV cultures with the 10 DIV cultures, the immunoreactivities of PKC ι and ε were decreased, those of PKC α, βI, βII, γ, and λ were unchanged, whereas that of PKC μ was still increased. In K5 cultures, the immunoreactivity of each PKC isoform at 2–4 DIV was similar to that observed in K25 cells, although no remarkable differentiation features were observed. Coordinated with the appearance of cell death at 8 DIV in low‐K+ cultures, levels of PKC α, μ, λ, and ι, but not the others, were markedly decreased. The NMDA receptor antagonists MK‐801 and 2‐amino‐5‐phosphopentanoic acid markedly prevented the age‐induced apoptosis of CGCs, and the cells survived >18 DIV under these conditions. The cytoprotective effect of MK‐801 was concomitant with the increases in levels of PKC γ, λ, ι, and μ at 10 and 14 DIV. In addition, the PKC ε level was increased at 14 DIV but decreased at early stages, whereas PKC α, βI, and βII levels were unchanged, as compared with K25 culture alone. Taken together, induction and up‐regulation of PKC isoforms may play an important role in the maintenance of CGC survival by depolarization and MK‐801.
Time-restricted feeding in young men performing resistance training: A randomized controlled trial†

Abstract A randomized controlled trial was conducted to examine eight weeks of resistance training (RT) with and without time-restricted feeding (TRF) in order to assess nutrient intake and changes in body composition and muscular strength in young recreationally active males. The TRF programme consisted of consuming all calories within a four-hour period of time for four days per week, but included no limitations on quantities or types of foods consumed. The RT programme was performed three days per week and consisted of alternating upper and lower body workouts. For each exercise, four sets leading to muscular failure between 8 and 12 repetitions were employed. Research visits were conducted at baseline, four, and eight weeks after study commencement. Measurements of total body composition by dual-energy X-ray absorptiometry and muscle cross-sectional area by ultrasound were obtained. Upper and lower body strength and endurance were assessed, and four-day dietary records were collected. TRF reduced energy intake by ∼650 kcal per day of TRF, but did not affect total body composition within the duration of the study. Cross-sectional area of the biceps brachii and rectus femoris increased in both groups. Effect size data indicate a gain in lean soft tissue in the group that performed RT without TRF (+2.3 kg, d = 0.25). Upper and lower body strength and lower body muscular endurance increased in both groups, but effect sizes demonstrate greater improvements in the TRF group. Overall, TRF reduced energy intake and did not adversely affect lean mass retention or muscular improvements with short-term RT in young males.
Penicillin-resistant Streptococcus mitis as a cause of septicemia with meningitis in febrile neutropenic children.

PURPOSE The purpose of this report is to emphasize the importance of occurrence of Streptococcus mitis meningitis in febrile neutropenic children with hematopoietic malignancy. PATIENTS AND METHODS Symptoms of meningitis and sepsis (fever, headache, changes in mental status) were seen in three patients who were severely neutropenic and undergoing cytotoxic chemotherapy for CNS relapse of their underlying malignancy (acute lymphoblastic leukemia (ALL), n = 2; Burkitt's lymphoma, n = 1). Chemotherapy had included cytosine arabinoside administered 7-14 days prior to presenting with sepsis and meningitis. All three patients had buccal mucositis or sinusitis. Blood cultures and CSF cultures showed S. mitis resistant to penicillin but sensitive to vancomycin. Vancomycin, at a dosage of 60 mg/kg/day to maximize CNS levels of antibiotic, was administered to all three children. RESULTS Two of the patients recovered from S. mitis meningitis; recovery was associated with an improvement in their peripheral granulocyte counts. One patient, who remained neutropenic, died despite being treated with both intravenous and intraventricular vancomycin. CONCLUSION Physicians caring for patients who are neutropenic and febrile need to be aware of the risk of meningitis occurring with S. mitis sepsis. Early treatment with high dosages of vancomycin (60 mg/kg/day) and an attempt to limit the duration of neutropenia are important factors in the outcome of such patients.
Angiotensin-converting enzyme 2 attenuates atherosclerotic lesions by targeting vascular cells

Angiotensin-converting enzyme 2 (ACE2) is a newly discovered homolog of ACE whose actions oppose those of angiotensin II (AngII). However, the underlying mechanisms by which ACE2 effectively suppresses early atherosclerotic lesions remain poorly understood. Here, we show, both in vitro and in vivo, that ACE2 inhibited the development of early atherosclerotic lesions by suppressing the growth of vascular smooth muscle cells (VSMCs) and improving endothelial function. In a relatively large cohort animal study (66 rabbits), aortic segments transfected by Ad-ACE2 showed significantly attenuated fatty streak formation, neointimal macrophage infiltration, and alleviation of impaired endothelial function. Segments also showed decreased expression of monocyte chemoattractant protein 1, lectin-like oxidized low-density lipoprotein receptor 1, and proliferating cell nuclear antigen, which led to the delayed onset of atherosclerotic lesions. At the cellular level, ACE2 significantly modulated AngII-induced growth and migration in human umbilical vein endothelial cells and VSMCs. The antiatherosclerotic effect of ACE2 involved down-regulation of the ERK-p38, JAK-STAT, and AngII-ROS-NF-κB signaling pathways and up-regulation of the PI3K-Akt pathway. These findings revealed the molecular mechanisms of the antiatherosclerotic activity of ACE2 and suggested that modulation of ACE2 could offer a therapeutic option for treating atherosclerosis.
Investigation of the utility of colorectal function tests and Rome II criteria in dyssynergic defecation (Anismus)

Although 30–50% of constipated patients exhibit dyssynergia, an optimal method of diagnosis is unclear. Recently, consensus criteria have been proposed but their utility is unknown. To examine the diagnostic yield of colorectal tests, reproducibility of manometry and utility of Rome II criteria. A total of 100 patients with difficult defecation were prospectively evaluated with anorectal manometry, balloon expulsion, colonic transit and defecography. Fifty‐three patients had repeat manometry. During attempted defecation, 30 showed normal and 70 one of three abnormal manometric patterns. Forty‐six patients fulfilled Rome criteria and showed paradoxical anal contraction (type I) or impaired anal relaxation (type III) with adequate propulsion. However, 24 (34%) showed impaired propulsion (type II). Forty‐five (64%) had slow transit, 42 (60%) impaired balloon expulsion and 26 (37%) abnormal defecography. Defecography provided no additional discriminant utility. Evidence of dyssynergia was reproducible in 51 of 53 patients. Symptoms alone could not differentiate dyssynergic subtypes or patients. Dyssynergic patients exhibited three patterns that were reproducible: paradoxical contraction, impaired propulsion and impaired relaxation. Although useful, Rome II criteria may be insufficient to identify or subclassify dyssynergic defecation. Symptoms together with abnormal manometry, abnormal balloon expulsion or colonic marker retention are necessary to optimally identify patients with difficult defecation.
A novel rhodopsin-like gene expressed in zebrafish retina

Abstract The visual pigment rhodopsin (rh1) constitutes the first step in the sensory transduction cascade in the rod photoreceptors of the vertebrate eye, forming the basis of vision at low light levels. In most vertebrates, rhodopsin is a single-copy gene whose function in rod photoreceptors is highly conserved. We found evidence for a second rhodopsin-like gene (rh1-2) in the zebrafish genome. This novel gene was not the product of a zebrafish-specific gene duplication event and contains a number of unique amino acid substitutions. Despite these differences, expression of rh1-2 in vitro yielded a protein that not only bound chromophore, producing an absorption spectrum in the visible range (λmax ≈ 500 nm), but also activated in response to light. Unlike rh1, rh1-2 is not expressed during the first 4 days of embryonic development; it is expressed in the retina of adult fish but not the brain or muscle. Similar rh1-2 sequences were found in two other Danio species, as well as a more distantly related cyprinid, Epalzeorhynchos bicolor. While sequences were only identified in cyprinid fish, phylogenetic analyses suggest an older origin for this gene family. Our study suggests that rh1-2 is a functional opsin gene that is expressed in the retina later in development. The discovery of a new previously uncharacterized opsin gene in zebrafish retina is surprising given its status as a model system for studies of vertebrate vision and visual development.