Temperature during the free-living phase of an ectoparasite influences the emergence pattern of the infective phase.
Understanding the population dynamics and co-evolution of host–parasite systems requires detailed knowledge of their phenology which, in turn, requires a deep knowledge of the effect of abiotic factors on the life cycles of organisms. Temperature is known to be a key environmental influence that participates in the regulation of diapause. Yet, not much is known about the effect of temperature on the free-living stages of true parasites and how it may influence host–parasite interactions. Here we experimentally study the effect of ambient temperature on overwintering pupae of Carnus hemapterus (Diptera, Carnidae), an ectoparasitic fly of various bird species. We also test whether chilling is a prerequisite for completion of diapause in this species. In the course of three winter seasons we experimentally exposed carnid pupae from nests of various host species to spring temperatures with and without chilling and recorded the emergence patterns in experimental and control groups. Experimental groups showed an advanced emergence date, a lower emergence rate and, consequently, a protracted emergence period. Chilling had no obvious effect on the start of emergence but it did advance the mean emergence date, shortened the length of the emergence period when compared with the control treatment and increased the emergence rate when compared with the spring treatment. This study identifies an environmental cue, namely temperature during the free-living stage, affecting the emergence of a widespread parasite and demonstrates the plasticity of diapause in this parasite. Our findings are of potential significance in understanding host–parasite interactions.


COPD risk among older construction workers-Updated analyses 2020.
A 2010 study of construction workers participating in medical screening programs at the Department of Energy (DOE) nuclear facilities demonstrated increased chronic obstructive pulmonary disease (COPD) risk. The current study of a larger worker cohort allowed for a more nuanced analysis of COPD risk, including for employment beginning after the mid-1990s. Study participants included 17,941 workers with demographic and smoking data and spirometry with a minimum of three recorded expiratory efforts and reproducibility of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1 ) of 0.2 L or less. COPD was defined as a FEV1 /FVC ratio below the lower limit of normal using established prediction equations without use of bronchodilation. Stratified analyses explored COPD prevalence by demographic variables and trade. Logistic regression analyses assessed risks by trade and time periods of trade and DOE site work, controlling for age, gender, race/ethnicity, body mass index, and smoking. Overall COPD prevalence was 13.4% and 67.4% of cases were classified as moderate to severe. Compared to nonconstruction workers, construction trade workers were at significantly increased risk of all COPD (OR = 1.34, 95% CI = 1.29-1.79) and even more so for severe COPD (OR = 1.61, 95% CI = 1.32-1.96). The highest risk trades were cement masons/bricklayers (OR = 2.36; 95% CI = 1.71-3.26) and roofers (OR = 2.22; 95% CI = 1.48-3.32). Risk among workers employed after 1995 was elevated but not statistically significant. Construction workers are at increased COPD risk. Results support the prevention of both smoking and occupational exposures to reduce these risks. While the number of participants employed after 1995 was small, patterns of risk were consistent with findings in the overall cohort.


Recent CR1 non-LTR retrotransposon activity in coscoroba reveals an insertion site preference.
Chicken repeat 1 (CR1) is a taxonomically widespread non-LTR retrotransposon. Insertion site bias, or lack thereof, has not been demonstrated for CR1. Recent CR1 retrotranspositions were used to examine flanking regions for GC content and nucleotide bias at the insertion site. Elucidation of the exact octomer repeat sequence (TTCTGTGA) allowed for the identification of younger insertion events. The number of octomer repeats associated with a CR1 element increases after insertion with CR1s having one octomer being youngest. These young CR1s are flanked by regions of low GC content (38%). Furthermore, a bias for specific bases within the first four positions at the site of insertion was revealed. This study focused on those loci where the insertion event has been most recent, as this would tend to minimize noise introduced by post-integration mutational events. Our data suggest that CR1 is not inserting into regions of higher GC content within the coscoroba genome; but rather, preferentially inserting into regions of lower GC content. Furthermore, there appears to be a base preference (TTCT) for the insertion site. The results of this study increase the current level of understanding regarding the elusive CR1 non-LTR retrotransposon.


Accurate diagnosis of sarcopenia without using a body composition analyzer in a convalescent rehabilitation ward.
Hishikawa N, Sawada K, Shono S, Sakurai M, Yokozeki M, Maeda H, Ohashi S, Ueshima K, Mikami Y. Accurate diagnosis of sarcopenia without using a body composition analyzer in a convalescent rehabilitation ward. Jpn J Compr Rehabil Sci 2023; 14: 26-32. The Asian Working Group for Sarcopenia 2019 recommends diagnosing sarcopenia without using a body composition analyzer and initiating treatment early. The present study aimed to investigate the accuracy of diagnosing sarcopenia without a body composition analyzer in a convalescent rehabilitation ward. Eighty-five patients admitted to a convalescent rehabilitation ward were included, and sarcopenia diagnoses were performed with and without a body composition analyzer. To assess the accuracy of diagnosing sarcopenia without using a body composition analyzer, sensitivity, specificity, positive predictive value, and negative predictive value were calculated relative to sarcopenia diagnoses made using a body composition analyzer. The sensitivity of the technique for diagnosing sarcopenia was 0.94, specificity was 0.77, positive predictive value was 0.86, and negative predictive value was 0.90. The accuracy of diagnosing sarcopenia without using a body composition analyzer was high. However, this technique may miss sarcopenia cases in patients with increased calf circumference due to adipose tissue and/or edema.


The ileocaecal knot.
Variations in intestinal knot syndromes have been described in the past, including ileoileal knots, ileosigmoid knots and appendico-ileal knots. We report a new type of intestinal knot syndrome, an ileocaecal knot, which, to our knowledge, has not been reported before in the world literature. Features on CT that may raise suspicion of an ileal knot syndrome are described.


Study on the ability of 1,2,3,4-tetrahydropapaveroline to cause oxidative stress: Mechanisms and potential implications in relation to parkinson's disease.
Tetrahydropapaveroline (THP) is a compound derived from dopamine monoamine oxidase-mediated metabolism, particularly present in the brain of parkinsonian patients receiving L-dopa therapy, and is capable of causing dopaminergic neurodegeneration. The aim of this work was to evaluate the potential of THP to cause oxidative stress on mitochondrial preparations and to gain insight into the molecular mechanisms responsible for its neurotoxicity. Our data show that THP autoxidation occurs with a continuous generation of hydroxyl radicals (*OH) and without the involvement of the Fenton reaction. The presence of ascorbate enhances this process by establishing a redox cycle, which regenerates THP from its quinolic forms. It has been shown that the production of *OH is not affected by the presence of either ferrous or ferric iron. Although THP does not affect lipid peroxidation, it is capable of reducing the high levels of thiobarbituric acid-reactive substances obtained in the presence of ascorbate and/or iron. However, THP autoxidation in the presence of ascorbate causes both an increase in protein carbonyl content and a reduction in protein-free thiol content. THP also increases protein carbonyl content when the autoxidation occurs in the presence of iron. The remarkable role played by ascorbate in the production of oxidative stress by THP autoxidation is of particular interest.


Redox-dependent niche differentiation provides evidence for multiple bacterial sources of glycerol tetraether lipids in lakes.
Terrestrial paleoclimate archives such as lake sediments are essential for our understanding of the continental climate system and for the modeling of future climate scenarios. However, quantitative proxies for the determination of paleotemperatures are sparse. The relative abundances of certain bacterial lipids, i.e., branched glycerol dialkyl glycerol tetraethers (brGDGTs), respond to changes in environmental temperature, and thus have great potential for climate reconstruction. Their application to lake deposits, however, is hampered by the lack of fundamental knowledge on the ecology of brGDGT-producing microbes in lakes. Here, we show that brGDGTs are synthesized by multiple groups of bacteria thriving under contrasting redox regimes in a deep meromictic Swiss lake (Lake Lugano). This niche partitioning is evidenced by highly distinct brGDGT inventories in oxic vs. anoxic water masses, and corresponding vertical patterns in bacterial 16S rRNA gene abundances, implying that sedimentary brGDGT records are affected by temperature-independent changes in the community composition of their microbial producers. Furthermore, the stable carbon isotope composition (δ13C) of brGDGTs in Lake Lugano and 34 other (peri-)Alpine lakes attests to the widespread heterotrophic incorporation of 13C-depleted, methane-derived biomass at the redox transition zone of mesotrophic to eutrophic lake systems. The brGDGTs produced under such hypoxic/methanotrophic conditions reflect near-bottom water temperatures, and are characterized by comparatively low δ13C values. Depending on climate zone and water depth, lake sediment archives predominated by deeper water/low-13C brGDGTs may provide more reliable records of climate variability than those where brGDGTs derive from terrestrial and/or aquatic sources with distinct temperature imprints.


Emerging drugs for diabetic retinopathy.
Diabetic retinopathy (DR) is prevalent even among "well controlled" diabetics, and remains the commonest cause of visual loss in working age adults. Current evidence based treatments, including intensive glycemic and hypertensive control and laser photocoagulation, rarely improves visual outcomes in those with established DR. There has been an increasing focus on the underlying molecular mechanisms involved in DR, and targeted therapeutic interventions to temper their damaging effects. We review potential targets and emerging therapies for DR, including treatments currently in clinical trials. Emerging therapies including inhibition of aldose reductase/polyol pathway, non-enzymatic glycation/advanced glycated end products inhibitors, protein kinase C inhibitors, and reduction of oxidative stress/superoxide induced damage. Newer drugs modulating growth factor and cytokine production (including VEGF, TNF and cytokines such as NF-kB) and newer targeted therapeutics utilising antisense oligonucleotides, and small interfering RNAs are also currently in clinical trials. Emerging treatments, possibly used in combination with standard therapy, offer the hope of effective and safe treatment that may allow us to improve visual outcomes and prevent the damaging consequences of DR.


Solid-phase synthesis of 1,2-diheterocyclic-substituted (E)-olefins from a supported selenium resin.
A library of 1,2,3-triazoles, isoxazoles, 1,2,4-oxadiazoles, and isoxazoline-containing 1,2-di-heterocyclic-substituted compounds with three points of diversity linked by an E double bond were prepared. Key steps include a 1,3-dipolar cycloaddition and Porco's two-step, one-pot condensation and alpha-alkylation reaction of selenium resins.


High frequency oscillatory ventilation.
We at Virginia Baptist Hospital feel that the Sensor Medics 3100A high frequency oscillatory ventilator to be an effective and safe ventilator for the treatment of RDS and PIE. This ventilator appears to offer a gentler form of mechanical ventilation which is potentially of greatest value to the smallest premature infants.


Carbapenem-resistant Enterobacteriaceae and the correlation between carbapenem and fluoroquinolone usage and resistance in the US military health system.
Whether carbapenem or fluoroquinolone usage is correlated with carbapenem-resistant Enterobacteriaceae (CRE) has not been investigated at the level of an entire US nationwide managed health care system. We analyzed 75 million person-years of surveillance and 1,969,315 cultures from all 266 hospitals in the geographically dispersed US military health system. Incidences of CRE remained under 1 case per 100,000 person-years. Incidences of CRE increased relative to 2005 baseline levels in 3 of 7 subsequent years, then decreased in 2012 (P<0.05). Incident proportions of carbapenem resistance (CR) differed significantly among years, geographical regions, and bacterial species. Although use and resistance strongly correlated (R>0.80) for several "drug-bug" combinations, none were significant at the national or facility level. One exception was that inpatient consumption of fluoroquinolones was significantly correlated (P=0.0007) with CR in Escherichia coli when data from the major referral centers of the Southern and Northern regions were combined.


The practice doctorate: perspectives of early adopters.
The emergence of the Doctor of Nursing Practice (DNP) degree is being described as a disruptive innovation that is altering the landscape of nursing and health care and creating a great deal of controversy within and beyond the profession of nursing. This article proposes that the DNP is actually the natural evolution of a larger disruptive innovation begun in the late 1960s with the advent of nurse practitioner programs. As expected with disruptive innovations, many challenges face those who are early adopters and who forge ahead during the early phase of innovation and later during the upmarketing phase. As faculty and administrators of one of the early, second-generation DNP programs, the authors are fully aware of ongoing discussion and issues related to the practice doctorate. This article shares the experiences of this group of early adopters and their insights into controversies surrounding the DNP movement.


Melanoma patients' disease-specific knowledge, information preference, and appreciation of educational YouTube videos for self-inspection.
Informing and educating melanoma patients is important for early detection of a recurrence or second primary. This study aimed to investigate Dutch melanoma patients' disease-specific knowledge, and their opinions on information provision and the value of e-Health videos. All AJCC stage I-II melanoma patients in follow-up between March 2015 and March 2016 at a single melanoma center were invited to complete 19 online questions, addressing respondents' characteristics, knowledge on melanoma, and opinions on melanoma-specific information received and the educational YouTube videos. In total, 100 patients completed the survey (response = 52%); median age was 60 years and 51% were female. Breslow tumor thickness was unknown by 34% and incorrectly indicated by 19%, for presence of ulceration this was 33% and 11%, for mitosis 65% and 14%, and for AJCC stage 52% and 23%, respectively. Only 5% correctly reproduced all four tumor characteristics. Orally delivered information regarding warning signs, severity, treatment possibilities, and importance of self-inspection was clearest for patients, compared to information in the melanoma brochure. According to 77% of patients, YouTube videos regarding self-inspection of the skin and regional lymph nodes had additional value. Altogether, 63% preferred receiving information in multiple ways; 92% orally by their physician, 62% through videos, and 43% through brochures. Patients' melanoma-specific knowledge appears to be limited. There is an urgent need for further improvement of providing information and patient education. In addition to oral and written information, e-Health videos seem to be a convenient supplemental and easy accessible method for patient education.


Forensic authentication method for audio recordings generated by Voice Recorder application on Samsung Galaxy Watch4 series.
The number of smartwatch users has been rapidly increasing in recent years. A smartwatch is a wearable device that collects various types of data using sensors and provides basic functions, such as healthcare-related measurements and audio recording. In this study, we proposed the forensic authentication method for audio recordings from the Voice Recording application in the Samsung Galaxy Watch4 series. First, a total of 240 audio recordings from each of the four different models, paired with four different smartphones for synchronization via Bluetooth, were collected and verified. To analyze the characteristics of smartwatch audio recordings, we examined the transition of the audio latency, writable audio bandwidth, timestamps, and file structure between those generated in the smartwatches and those edited using the Voice Recording application of the paired smartphones. In addition, the devices with the audio recordings were examined via the Android Debug Bridge (ADB) tool and compared with the timestamps stored in the file system. The experimental results showed that the audio latency, writable audio bandwidth, and file structure of audio recordings generated by smartwatches differed from those generated by smartphones. Additionally, by analyzing the file structure, audio recordings can be classified as unmanipulated, manipulation has been attempted, or manipulated. Finally, we can forensically authenticate the audio recordings generated by the Voice Recorder application in the Samsung Galaxy Watch4 series by accessing the smartwatches and analyzing the timestamps related to the audio recordings in the file system.


[Epidemiology of hepatitis A in Sardinia: mathematical model].
The prevalence of antibodies to hepatitis A in South-Sardinia was determined in samples of students and workers. In 1987 sera were collected from the children who attended kindergarten and elementary schools, in 1988 from students 13-20 years old (high schools) and from a group of workers who went to the public health office to ask for a certificate of good health. As far as the workers are concerned, the force of infection can be taken as a constant. In childhood, on the contrary, our findings are suggestive for a different immunization model. In this research work the prevalence observed in the population is analyzed using a mathematical model. Our model is based on the assumption that the force of infection increases linearly with age. The estimated fraction of susceptibles to hepatitis A is denoted by Y (X). The parameter h (X) represents the force of infection, the per capita rate at which susceptible population acquires infection. We assume that susceptibility may be lost only by natural infection and that permanent immunity results from first infection. So the fraction of susceptible population is gamma = exp (- x o integral of h (chi) d chi) if the force of infection increases linearly with age h (X) = ax + b then Y = exp (aX2 + bX + c) We can write In Y = y We obtain y = aX2 + bX + c Goodness of fit has been tested using the coefficient of determination R2. The number of cases in the group of age X - X + 1 can be estimated, for 10000 inhabitants, as (Y (X) - Y(X + 1) * 10000) Our findings are suggestive for a linear increasing of the force of infection with the group of age (R2 = 0.974). This could result from an age-dependent force of infection presumably as a consequence of age-related changes in behavioural patterns. Another explication could be a time-dependent force of infection according to improvements in socioeconomic and hygienic conditions. There is clear need for further research to separate the variations attributable to age from those attributable to time. Case notifications records could be very useful, but these data are notoriously unreliable.


Genetic diversity and interrelationship among Indian and exotic melons based on fruit morphology, quality components and microsatellite markers.
Seventy melon (Cucumis melo L.) accessions comprising of landraces, inbred lines, cultivars, wild relatives and exotic populations were characterized using fifteen fruit traits and 30 SSR markers. Overall, aim of this study was to investigate the genetic relatedness across origins, horticultural groups and accession categories. Significant differences were observed for days to first fruit maturity, fruit weight, fruits per vine, yield per plant, flesh thickness, fruit shape index, total soluble solids, β-carotene, ascorbic acid and titrable acidity. Twenty-four polymorphic SSRs detected 67 distinct alleles with moderate polymorphic information content (0.43) and genetic diversity (0.44). Observed heterozygosity (0.53) was higher than expected heterozygosity (0.48) which can be attributed to out-cross nature of melons. Neighbor joining tree based on SSRs diverged 70 accessions into six clusters independent of geographic sites of collections. Momordica and inodorus accessions formed distinct clusters, with some exceptions. Intermixing of landraces, modern cultivars and exotic accessions belonging to different taxa and geographic regions indicated genetic resemblance with each other. Hybridization among exotic and indigenous genetic resources can be utilized for genetic enhancement and introgression of new traits in modern melon cultivars.


Recent reconfiguration of an ancient developmental gene regulatory network in Heliocidaris sea urchins.
Changes in developmental gene regulatory networks (dGRNs) underlie much of the diversity of life, but the evolutionary mechanisms that operate on regulatory interactions remain poorly understood. Closely related species with extreme phenotypic divergence provide a valuable window into the genetic and molecular basis for changes in dGRNs and their relationship to adaptive changes in organismal traits. Here we analyse genomes, epigenomes and transcriptomes during early development in two Heliocidaris sea urchin species that exhibit highly divergent life histories and in an outgroup species. Positive selection and chromatin accessibility modifications within putative regulatory elements are enriched on the branch leading to the derived life history, particularly near dGRN genes. Single-cell transcriptomes reveal a dramatic delay in cell fate specification in the derived state, which also has far fewer open chromatin regions, especially near conserved cell fate specification genes. Experimentally perturbing key transcription factors reveals profound evolutionary changes to early embryonic patterning events, disrupting regulatory interactions previously conserved for ~225 million years. These results demonstrate that natural selection can rapidly reshape developmental gene expression on a broad scale when selective regimes abruptly change. More broadly, even highly conserved dGRNs and patterning mechanisms in the early embryo remain evolvable under appropriate ecological circumstances.


Inhibitory effects of acupuncture manipulation and focal electrical stimulation of the nucleus submedius on a viscerosomatic reflex in anesthetized rats.
To examine the participation of nucleus submedius (Sm) in the medial thalamus of pain inhibitory systems, we investigated the effects of acupuncture and focal electrical stimulation of the Sm and adjacent brain sites (0.3 ms, 50 Hz, 50-100 microA, 10 s) on the EMG activity of the external oblique muscle evoked by colorectal distension in urethane-anesthetized Wistar rats. The viscerosomatic reflex (VSR) activity was suppressed after the administration of morphine (1.0 mg/kg, i.v.) and the effect was reversed by naloxone (0.5 mg/kg, i.v.). Transection of the spinal cord at the Th2 level also eliminated the VSR. Acupuncture manipulation applied to the cheek (manual rotation at 1 Hz) suppressed the VSR, and this inhibition was eliminated by microinjections of lidocaine into the bilateral Sm nuclei (0.5 microliter of 1.0% solution). Electrical stimulation in the ventral part but not the dorsal part of the Sm suppressed the VSR. The inhibition of the VSR induced by electrical stimulation of the Sm was not reversed by the administration of naloxone (1.0 mg/kg, i.v.). Electrical stimulation of the adjacent medial thalamic nuclei (mediodorsal nucleus (MD) or centromedial nucleus (CM)) and ventrobasal complex (VB) of the thalamus had very little effect on the VSR. These results suggests that the Sm is not only involved in the relay of nociceptive information to the cortex, but may also be involved in a non-opioid mediated pain inhibitory system and may participate, at least in part, in the suppressive effects of intense acupuncture manipulation on VSR activity.


[Production of monoclonal antibody that recognizes glycogen and its application for immunohistochemistry].
In this study, I made a monoclonal antibody, using the mandibular condylar cartilage as antigen. By light microscopic immunocytochemical observations, this antibody reacted with the chondrocytes both in the mandibular condyle and the costal cartilage, hepatocytes and skeletal muscle cells. By electron microscopic immunocytochemical observations, reaction products (gold particles) were seen on the glycogen particles in the chondrocytes. Further, by dot blotting assay, this antibody was found to react directly with the purified glycogen. Meanwhile, all these reactions disappeared after alpha-amylase digestion. These results indicate that this antibody specifically recognizes glycogen or glycogen-related sugar chains. Therefore, I think that this antibody is very much useful for detecting the glycogen instead of the PAS reaction, since PAS reaction is not a specific method to detect the glycogen.


Bilateral Basal cell adenocarcinoma of the parotid gland: in a recipient of kidney transplant.
We report a rare case of bilateral basal cell adenocarcinoma (BcAC) of the parotid gland in a male patient 30 years after kidney transplantation and continuous administration of immunosuppressive therapy. BcAC is a salivary gland malignancy first recognized as a distinct neoplastic entity in WHO classification of salivary gland tumours in 1991. Over 90% of BcACs are detected in the parotid gland. The most important differential diagnosis is basal cell adenoma. Infiltrative growth is the distinguishing feature of BcAC. Administration of immunosuppressive medication to this patient for three decades may have contributed to development of this rare neoplasia. To our knowledge, similar cases of BcAC have not been reported previously.


MicroRNA-100 Enhances Autophagy and Suppresses Migration and Invasion of Renal Cell Carcinoma Cells via Disruption of NOX4-Dependent mTOR Pathway.
Renal cell carcinoma (RCC) is the most common kidney malignancy and has a poor prognosis owing to its resistance to chemotherapy. Recently, microRNAs (miRNAs or miRs) have been shown to have a role in cancer metastasis and potential as prognostic biomarkers in cancer. In the present study, we aim to explore the potential role of miR-100 in RCC by targeting nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) through the mammalian target of rapamycin (mTOR) pathway. Initially, microarray-based gene expression profiling of RCC was used to identify differentially expressed genes. Next, the expression of miR-100 and NOX4 was examined in RCC tissues and cell lines. Then, the interaction between miR-100 and NOX4 was identified using bioinformatics analysis and dual-luciferase reporter assay. Gain-of-function or loss-of-function approaches were adopted to manipulate miR-100 and NOX4 in order to explore the functional roles in RCC. The results revealed the presence of an upregulated NOX4 and a downregulated miR-100 in both RCC tissues and cell lines. NOX4 was verified as a target of miR-100 in cells. In addition, overexpression of miR-100 or NOX4 silencing could increase autophagy while decreasing the expression of mTOR pathway-related genes and migration and invasion. Conjointly, upregulated miR-100 can potentially increase the autophagy and inhibit the invasion and migration of RCC cells by targeting NOX4 and inactivating the mTOR pathway, which contributes to an extensive understanding of RCC and may provide novel therapeutic options for this disease.


Fluorescence detected circular dichroism study of the anticodon loop of yeast tRNAPhe.
Fluorescence detected circular dichroism (FDCD) measurements have been used to study the conformations of the anticodon loop of yeast phenylalanine tRNA. To our knowledge this is the first application of fluorescence detected circular dichroism. Much smaller amounts of tRNA are needed for the measurement of FDCD than for the conventionally measured circular dichroism. Furthermore, FDCD is specific for conformational changes near the anticodon loop. The FDCD measurements suggest a transition in the anticodon loop near 20 degrees in 0.01 M MgCl2-0.1 M NaCl (pH 7). This is followed by a broad transition from 30 to 60 degrees and finally a sharp melting at 75 degrees consistent with the absorbance detected melting of the entire tRNA. Removal of Mg2+ from the tRNA at 1 degrees causes nearly a factor of two decrease in the FDCD near 230 nm. This indicates a decrease in conformational rigidity in the anticodon loop on removal of Mg2+.


Long-term results in hairy cell leukemia treated by splenectomy.
Splenectomy as a therapeutic modality has been evaluated in a group of 24 consecutive patients. Before and after splenectomy only supportive therapy was applied with the exception of two patients in whom corticosteroids were administered because of vasculitis. Radiation therapy was applied in one patient because of massive retroperitoneal lymphadenopathy. One patient received Leukeran shortly before the fatal outcome because his response to splenectomy was poor. Out of 24 patients 14 patients died. The median survival for the partial responders and non-responders was 6 months only. Patients with a complete response did not reach median survival yet and 8 of them (33% of the whole group) have been alive for more than 9 years, one patient for more than 20 years. Two distinct groups of patients with respect to the outcome of splenectomy can be distinguished: The first group is characterized by a rapid fatal outcome mostly within two years after splenectomy, the second group has a more favorable course with a plateau and only occasional deaths after the fourth year.


Influence of eating with distractors on caloric intake of children and adolescents: a systematic review and meta-analysis of interventional controlled studies.
Eating habits developed during childhood can be perpetuated along life and contribute to the emergence of disorders. We aimed to investigate the influence of distractors during experimental meals on the energy intake of children and adolescents. We followed the PRISMA guidelines and the study was registered in PROSPERO (CRD42021259946). The PICOS strategy consisted of children and adolescents (P), exposed to distractors during meals (I), compared with no distraction (C) and the outcome was energy intake (Kcal) (O) evaluated in crossover and parallel randomized clinical trials (RCTs) (S). Searches were conducted in PubMed, Scopus, Web of Science, Cochrane, Proquest, Embase, and LILACs databases. We employed RoB 2 tool and NutriGrade. Databases searches returned 9,576 references. Thirteen articles were selected (five crossover and eight parallel RCTs). Volunteers aged 3 to 17 years-old. All studies evaluated TV as distractor. Most studies presented high/moderate risk of bias. Meta-analysis of parallel RCT indicated no significant difference in energy intake while eating with TV (MD = 0.05; 95% CI -0.13 - 0.23, P = 0.57), with moderate certainty level. In conclusion, under laboratory conditions, eating with distractors seems to barely alter energy intake for children and adolescents.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2055525 .


Prediction of intraoperative bleeding and blood transfusion in patients with recurrent retroperitoneal liposarcoma: a retrospective study.
Surgery is the main treatment for recurrent retroperitoneal liposarcoma (RPLS). The aim of the present study was to explore the factors associated with blood loss during surgery for recurrent RPLS. This retrospective study included patients with first recurrence of RPLS who were treated at our hospital between January 2015 and December 2019. Factors associated with intraoperative blood loss were identified by univariate and multivariate logistic regression analyses. Receiver-operating characteristic (ROC) curve analyses were conducted to evaluate whether tumor size and number of tumor-containing abdominal/pelvic zones were predictive of the need for blood transfusion. The study included 67 cases. The number of zones containing tumors was 1 in 4 cases (6%), 2 in 36 cases (53.7%), 3 in 14 cases (20.9%), and 4 in 13 cases (19.4%). Tumor size was associated with blood loss >500 mL [odds ratio (OR): 1.153, 95% confidence interval (CI): 1.051-1.266, P=0.003]. The number of tumor-containing zones was associated with blood loss >1,000 mL (OR: 3.161, 95% CI: 1.248-8.003, P=0.015) and >1,500 mL (OR: 2.674, 95% CI: 1.061-6.739, P=0.037). Multiple tumors were associated with blood loss >2,000 mL (OR: 3.161, 95% CI: 1.092-13.133, P=0.036) and >2,500 mL (OR: 2.674, 95% CI: 1.243-16.299, P=0.022). Tumor dedifferentiation was associated with blood loss >1,000 mL (OR: 4.802, 95% CI: 1.287-17.916, P=0.019) and >1,500 mL (OR: 9.249, 95% CI: 1.927-44.39, P=0.005). ROC curve analysis showed that tumor size >15.25 cm [area under the ROC curve (AUC): 0.772, P<0.001] and the number of tumor-containing zones >2.5 (AUC: 0.670; P=0.023) were predictive of the need for blood transfusion. The main finding of the present study was that a larger tumor size, a larger number of tumor-containing zones, multiple tumors, and dedifferentiation were independently associated with a larger volume of intraoperative blood loss in patients with recurrent RPLS. The tumor size >15.25 cm and the tumor area >2.5 areas predicted the need for blood transfusion. Formulating the intraoperative blood transfusion plan for recurrent RPLS, it is necessary to pay attention to two spatial factors, tumor size and affected area, rather than one of them.


Evaluation of the effects of time, temperature, and specimen storage on in vitro lactate concentrations in healthy dogs.
Lactate concentrations increase significantly under certain storage conditions, except for when glycolysis-arresting agents are used. Evaluation of time and storage conditions on heparinized whole blood lactate concentrations without glycolysis-arresting agents have not been evaluated in dogs. The purpose of the study was to determine the effects of preanalytic storage conditions on the in vitro concentration of lactate in heparinized canine venous blood specimens. In this prospective study, blood collected from 30 healthy dogs was aliquoted and stored under different conditions: anaerobic refrigerated (3°C), aerobic refrigerated, anaerobic room temperature (RT), and aerobic RT. Whole blood lactate was analyzed at 15-25, 30-40, 60-70, and 120-130 minutes from time 0 (T0) under all storage conditions. Percent increases from the T0 specimen were calculated. There were significantly increased lactate concentrations at all time points within the anaerobic refrigerated specimens compared to T0, and in the anaerobic RT specimens after 15-25 minutes. The aerobic refrigerated specimens did not have significant changes in lactate when compared to anaerobic refrigerated specimens, while the aerobic RT specimens had significant increases at all time points. Anaerobically refrigerated specimens stored < 40 minutes and aerobically refrigerated specimens stored < 25 minutes had in vitro lactate increases of < 20%. Results support analyzing lactate specimens immediately. If lactate analysis is delayed, anaerobic refrigerated specimens should be analyzed within 40 minutes, and aerobic refrigerated specimens should be analyzed within 25 minutes. Room temperature specimens stored either aerobically or anaerobically should be avoided as lactate concentrations may be falsely increased.


Image review on mobile devices for suspected stroke patients: Evaluation of the mRay software solution.
Software solutions such as mRay allow review of radiological images on handheld devices. We investigated if the quality is adequate for evaluating CT scans of patients with suspected stroke. 50 patients (Median age 80 years, 28 females) were retrospectively selected. All patients had undergone multidetector CT angiography ± perfusion and presented with clinical signs of acute stroke. Out of the 50 patients, 19 had large-vessel occlusion (LVO), 5 had intracranial hemorrhage (ICH), 10 had severe intracranial stenosis of at least one major vessel, 2 had intracranial tumor and 15 had no or an unrelated pathology. One experienced neuroradiologist and one resident scored the anonymized pictures separately on two handheld devices (iPhone 7 Plus, MED-TAB) equipped with mRay Software and on a PACS workstation. Each case was reviewed on all three devices with a break in-between of at least 12 weeks. The scoring on the traditional workstation was compared with the two handheld devices, regarding detection of early ischemic signs, LVOs, CBV/CBF-mismatch, ICHs and severe stenosis. Both raters were asked to rate the diagnostic quality of both handheld devices regarding detection of LVOs, ICHs, early ischemic signs and overall. All LVOs, intracranial tumors and ICHs were detected on both mobile devices. There was no significant difference in the rating of CCT and CBF ASPECTS between all three devices, while the sensitivity for detecting a CBF/CBV-mismatch was above 80% on both devices. Both raters assessed the diagnostic quality to be sufficient on both mobile devices to base treatment decisions on. Software solutions such as mRay for handheld devices provide adequate diagnostic quality for the review of CT scans of suspected stroke patients.


Comparing Off-clamp and On-clamp Robot-assisted Partial Nephrectomy: A Prospective Randomized Trial.
To determine whether performing robot-assisted partial nephrectomy without warm ischemia "off-clamp" results in favorable postoperative renal functional outcomes compared with the on-clamp method. We conducted a prospective trial of 80 patients who underwent robot-assisted partial nephrectomy. They were randomized in a 1:1 ratio to undergo the procedure with renal artery clamping or without clamping. The groups were compared across demographics, operative information, perioperative outcomes, and postoperative renal function. We assessed renal function by estimated glomerular filtration rate and renal scintigraphy both preoperatively and at 3 months postoperatively. Patients in the on-clamp and off-clamp groups were similar in age, gender, body mass index, comorbidities, clinical tumor size, nephrometry score, and laterality. Off-clamp procedures were lengthier at an average 178.0 minutes vs 156.0 minutes for on-clamp (P = .011). Estimated blood loss, rates of pelvicalyceal repair, postoperative complications, and positive margins were not different. At a median 3-month follow-up, no significant differences were seen in change in postoperative estimated glomerular filtration rate or percent split renal function between both groups. In this prospective study, off-clamp robot-assisted partial nephrectomy resulted in similar perioperative outcomes compared with the on-clamp technique. No benefit was demonstrated in the preservation of renal function. Urologists may safely employ either an on-clamp or off-clamp strategy depending on surgeon preference and patient-specific factors including baseline renal insufficiency, multiple masses, or solitary kidney.


The University Integrated Automated Information System at the Uniformed Services University of the Health Sciences.
The Integrated Automation System put into place at the University Services University of the Health Sciences has been said to be 5 years ahead of those employing the most advanced comparable configurations. This automated data processing creation was accomplished without augmentation of manpower or funding. A brief history of this development and some of its features are presented.


How Much Do Strategy Reports Tell About the Outcomes of Neurofeedback Training? A Study on the Voluntary Up-Regulation of the Sensorimotor Rhythm.
The core learning mechanisms of neurofeedback (NF) training are associative, implicit, and, consequently, largely impervious to consciousness. Many other aspects of training that determine training outcomes, however, are accessible to conscious processing. The outcomes of sensorimotor rhythm (SMR) up-regulation training are related to the strategies reported by participants. The classification methods of individual strategies employed hitherto were possibly under influence of the idiosyncratic interpretation of the rater. To measure and possibly overcome this limitation, we employed independent raters to analyze strategies reported during SMR up-regulation training. Sixty-two healthy young participants took part in a single session of SMR up-regulation training. After completing six blocks of training, in which they received either simple visual feedback or a gamified version thereof, participants were required to report the strategies employed. Their individual learning outcomes were computed as well. Results point out that individual strategies as well as NF learning outcomes were not particularly sensitive to the presence of gamified elements in training the SMR up-regulation. A high degree of consistency across independent raters classifying strategy reports was observed. Some strategies were more typical of responders while other ones were more common among non-responders. In summary, we demonstrate a more objective and transparent way to analyze individual mental strategies to shed more light on the differences between NF responders and non-responders.


Identifying N-nitrosofenfluramine in a nutrition supplement.
The analytical data for identifying an unknown substance that was found in a nutrition supplement is presented. The unknown substance is purified using thin-layer chromatography and then measured using high-resolution mass spectrometry (HRMS) giving the exact mass from which the structure of the unknown substance was proposed. The procedure for synthesizing N-nitrosofenfluramine from fenfluramine is described. The extracted, synthesized, and standard N-nitrosofenfluramine are compared using HRMS, high-performance liquid chromatography (HPLC)-MS, HPLC-UV, Fourier transform IR spectroscopy, gas chromatography-MS, TLC, and NMR (1H NMR and 13C NMR). All analytical data obtained confirm that the unknown peak in the nutrition supplement is N-nitrosofenfluramine and that the synthetic procedure described can easily provide the N-nitrosofenfluramine reference substance for identification.


Are physical symptoms among survivors of a disaster presented to the general practitioner? A comparison between self-reports and GP data.
Most studies examining medically unexplained symptoms (MUS) have been performed in primary or secondary care and have examined symptoms for which patients sought medical attention. Disasters are often described as precipitating factors for MUS. However, health consequences of disasters are typically measured by means of questionnaires, and it is not known whether these self-reported physical symptoms are presented to the GP. It is also not known if the self-reported symptoms are related to a medical disorder or if they remain medically unexplained. In the present study, three research questions were addressed. Firstly, were self-reported symptoms among survivors presented to the GP? Secondly, were the symptoms presented to the GP associated with a high level of functional impairment and distress? Thirdly, what was the GP's clinical judgment of the presented symptoms, i.e. were the symptoms related to a medical diagnosis or could they be labeled MUS? Survivors of a man-made disaster (N = 887) completed a questionnaire 3 weeks (T1) and 18 months (T2) post-disaster. This longitudinal health survey was combined with an ongoing surveillance program of health problems registered by GPs. The majority of self-reported symptoms was not presented to the GP and survivors were most likely to present persistent symptoms to the GP. For example, survivors with stomachache at both T1 and T2 were more likely to report stomachache to their GP (28%) than survivors with stomachache at only T1 (6%) or only T2 (13%). Presentation of individual symptoms to the GP was not consistently associated with functional impairment and distress. 56 - 91% of symptoms were labeled as MUS after clinical examination. These results indicate that the majority of self-reported symptoms among survivors of a disaster are not presented to the GP and that the decision to consult with a GP for an individual symptom is not dependent on the level of impairment and distress. Also, self-reported physical symptoms such as headache, back pain and shortness of breath are likely to remain medically unexplained after the clinical judgment of a GP.


The effects of long-term administration of methyltestosterone on the development of liver lesions in BALB/c mice.
Male and female BALB/c mice were treated orally with 5 mg/kg body weight of methyltestosterone for 10 months. Age-matched control animals received no steroid treatment. The livers of all animals were examined by standard histopathological methods. Hepatocellular dysplasia was found in livers of all treated mice, but not in control animals. The extent and severity of this dysplasia showed a sex difference. Most of the male mice (55/78) developed severe dysplasia and in 23/78 the dysplasia was only moderate; the corresponding numbers for female mice were: mild, 15/71; moderate, 48/71 and severe dysplasia, 8/71. Microscopic hepatocytic nodules were found in 6/78 males and 7/71 females. Hepatocellular carcinoma was seen in one male mouse. These findings indicate that methyltestosterone appears to act as a weak total hepatocarcinogen under the experimental conditions used.


Carney complex and teratoma maturum ovarii--a case report.
This is a case report of an extremely rare Carney complex (CNC) syndrome in a 17-year-old patient. After the decision made by a team of cancer specialists, the patient was admitted to the hospital for surgery because of adnexal tumor associated with ascites and increased Ca 125 tumor marker level. The patient underwent cardiac surgery twice. Adnexal mass and ascites, revealed by transvaginal ultrasound (TVUS) and confirmed by magnetic resonance imagings (MRI), indicated the malignant alteration. Surgery was performed and surgical pathological staging was refined according to the FIGO guideline and included a staging laparotomy. After surgery, general condition of the patient was good, without ascites and pain, with Ca 125 marker levels within reference ranges.


Second generation of cryoballoons can improve efficiency of cryoablation for atrial fibrillation.
We investigated whether the new second generation of cryoballoons can improve the efficiency and safety of cryoablation for atrial fibrillation (AF) during ablation and in terms of outcome. Data of AF patients consecutively treated with a single 28-mm cryoballoon were analyzed. Patients were divided into two groups: the G1 group was treated with the first-generation cryoballoons (ArcticFront) and G2 with the second generation (ArcticFront Advance). Failure of cryoablation treatment was defined as detection of an episode of AF, atrial flutter, or atrial tachycardia lasting ≥ 30 seconds during 3-month follow-up. Left atrial diameter (LAD) was measured by transthoracic echocardiography before cryoablation. One hundred twenty-five patients (group G1/G2: 57/68) were enrolled. Mean total time of the whole procedure, cryomapping, and cryoablation was shorter with G2 than with G1 (P < 0.05). No complication occurred with G1 whereas with G2 the complication rate was 8.8%. During mean 12 ± 4 months follow-up, the overall success rate of cryoablation was 76.0% (95/125); it was higher with G2 (89.7% [61/68] vs 59.7% [34/57], P < 0.001). Patients in whom treatment failed had larger LAD (48 ± 8 mm vs 44 ± 6 mm, P = 0.002) than those in whom it succeeded. Type of cryoballoon (relative risk [RR] = 5.75 [2.16, 15.27], P < 0.0001) and LAD (RR = 0.90 [0.83, 0.97], P = 0.0043) were shown in multivariable analysis to be individually related to the difference in success rate. Ablation for AF with the new generation of cryoballoons is associated with higher success rate of pulmonary vein isolation and better outcome. However, more complications occurred during the early stage of application of the G2 cryoballoon.


Fractional dynamics of globally slow transcription and its impact on deterministic genetic oscillation.
In dynamical systems theory, a system which can be described by differential equations is called a continuous dynamical system. In studies on genetic oscillation, most deterministic models at early stage are usually built on ordinary differential equations (ODE). Therefore, gene transcription which is a vital part in genetic oscillation is presupposed to be a continuous dynamical system by default. However, recent studies argued that discontinuous transcription might be more common than continuous transcription. In this paper, by appending the inserted silent interval lying between two neighboring transcriptional events to the end of the preceding event, we established that the running time for an intact transcriptional event increases and gene transcription thus shows slow dynamics. By globally replacing the original time increment for each state increment by a larger one, we introduced fractional differential equations (FDE) to describe such globally slow transcription. The impact of fractionization on genetic oscillation was then studied in two early stage models--the Goodwin oscillator and the Rössler oscillator. By constructing a "dual memory" oscillator--the fractional delay Goodwin oscillator, we suggested that four general requirements for generating genetic oscillation should be revised to be negative feedback, sufficient nonlinearity, sufficient memory and proper balancing of timescale. The numerical study of the fractional Rössler oscillator implied that the globally slow transcription tends to lower the chance of a coupled or more complex nonlinear genetic oscillatory system behaving chaotically.


Relation of Vitamin D levels with positive and negative symptoms of schizophrenia - A hospital based cross-sectional comparative study.
The association between altered serum Vitamin D levels and schizophrenia has been an area that has evoked a recent fervor. The neurohumoral and neuro immunomodulatory functions of Vitamin D might have a role to play in understanding the causation of the disease and thus appear promising in the diagnostic and therapeutic frontiers of the disease. We aimed to estimate and compare serum Vitamin D levels in drug-free cases of schizophrenia and in healthy control groups. The comparison was also made among the subgroups of positive and negative schizophrenia. The study, a hospital-based cross-sectional comparative study was carried out in the Department of Psychiatry, in a hospital in Assam over a period of 1 year. Fifty drug-free subjects of schizophrenia (Group A) diagnosed and confirmed according to International Classification of Diseases 10 were selected by consecutive sampling and 50 age and sex frequency-matched subjects (Group B) were selected from the healthy population. The cases (Group A) were divided into positive and negative groups (Group A1 and A2) based on the composite scoring of the Positive and Negative Syndrome Scale. After approval from the institutional ethics committee and obtaining written informed consent, Vitamin D levels were assessed in both groups of cases and controls and comparison was made. After statistical analysis, it was seen that males were more in proportion and mostly in the age group of 20-39 years. The median Vitamin D level among the cases was 12.45 ng/mL and that among controls was 20.03 ng/mL which was statistically significant (P value .00932). Among the positive and negative schizophrenia subgroup, there was no statistically significant difference in Vitamin D levels at means of 16.54 ng/mL and 16.25 ng/Ml, respectively. The variation in Vitamin D levels in schizophrenics and the healthy population is thus discernible. It can be said that serum Vitamin D levels were significantly low in people with schizophrenia compared to the general population. Furthermore, it is seen that mean Vitamin D status is similar in both the groups of positive and negative schizophrenia negating the possibility of alteration of Vitamin D levels depending on the differences in symptomatology or in pathophysiology of the two groups.


Neurotoxicity from Old and New Radiation Treatments for Brain Tumors.
Research regarding the mechanisms of brain damage following radiation treatments for brain tumors has increased over the years, thus providing a deeper insight into the pathobiological mechanisms and suggesting new approaches to minimize this damage. This review has discussed the different factors that are known to influence the risk of damage to the brain (mainly cognitive disturbances) from radiation. These include patient and tumor characteristics, the use of whole-brain radiotherapy versus particle therapy (protons, carbon ions), and stereotactic radiotherapy in various modalities. Additionally, biological mechanisms behind neuroprotection have been elucidated.


Frequency of generalised anxiety disorder and associated factors in an urban settlement of Karachi.
The study was undertaken to find the frequency of Generalised Anxiety Disorder (GAD) along with associated factors in an urban settlement of Karachi. A cross-sectional study was conducted at Defence Housing Authority (DHA), a posh area of Karachi. The sample population consisted of residents of ages between 18 and 65. The sample of 420 was completed by randomly going to residences in the DHA area. Self-administered questionnaires were handed out after taking informed consent. General Anxiety Disorder (GAD) 7 scale was used to estimate the anxiety level. The data was entered and analysed using SPSS version 16.0. Pearson's chi-square was used as the primary statistical test. The mean anxiety score of the total individuals selected was 5.1 +/- 3.79. Males reported a mean score of 4.99 +/- 4.01 while females reported a mean score of 5.25 +/- 3.42. A score of 5 is considered as the threshold for anxiety and anything below 5 is considered as normal. Based on this benchmark, out of the total sample size of 420, 211 (50.2%) individuals reported some degree of anxiety. Employment and education status were found to be significantly associated (p = 0.01) with anxiety among the participants. Based on the results, the high prevalence of anxiety in one of the most developed areas of Karachi is alarming. For 50.2% of the respondents to have anxiety is high considering the sample chosen represented individuals that were educated and had a high standard of living. The major factors responsible for anxiety cited by respondents were chronic diseases and emotional harm.


A cross-sectional analysis of the relationship between tobacco and alcohol outlet density and neighbourhood deprivation.
There is a strong socio-economic gradient in both tobacco-and alcohol-related harm. One possible factor contributing to this social gradient may be greater availability of tobacco and alcohol in more socially-deprived areas. A higher density of tobacco and alcohol outlets is not only likely to increase supply but also to raise awareness of tobacco/alcohol brands, create a competitive local market that reduces product costs, and influence local social norms relating to tobacco and alcohol consumption. This paper examines the association between the density of alcohol and tobacco outlets and neighbourhood-level income deprivation. Using a national tobacco retailer register and alcohol licensing data this paper calculates the density of alcohol and tobacco retail outlets per 10,000 population for small neighbourhoods across the whole of Scotland. Average outlet density was calculated for neighbourhoods grouped by their level of income deprivation. Associations between outlet density and deprivation were analysed using one way analysis of variance. There was a positive linear relationship between neighbourhood deprivation and outlets for both tobacco (p <0.001) and off-sales alcohol (p <0.001); the most deprived quintile of neighbourhoods had the highest densities of both. In contrast, the least deprived quintile had the lowest density of tobacco and both off-sales and on-sales alcohol outlets. The social gradient evident in alcohol and tobacco supply may be a contributing factor to the social gradient in alcohol- and tobacco-related disease. Policymakers should consider such gradients when creating tobacco and alcohol control policies. The potential contribution to public health, and health inequalities, of reducing the physical availability of both alcohol and tobacco products should be examined in developing broader supply-side interventions.


Distributed Acoustic Sensing Using Chirped-Pulse Phase-Sensitive OTDR Technology.
In 2016, a novel interrogation technique for phase-sensitive (Φ)OTDR was mathematically formalized and experimentally demonstrated, based on the use of a chirped-pulse as a probe, in an otherwise direct-detection-based standard setup: chirped-pulse (CP-)ΦOTDR. Despite its short lifetime, this methodology has now become a reference for distributed acoustic sensing (DAS) due to its valuable advantages with respect to conventional (i.e., coherent-detection or frequency sweeping-based) interrogation strategies. Presenting intrinsic immunity to fading points and using direct detection, CP-ΦOTDR presents reliable high sensitivity measurements while keeping the cost and complexity of the setup bounded. Numerous technique analyses and contributions to study/improve its performance have been recently published, leading to a solid, highly competitive and extraordinarily simple method for distributed fibre sensing. The interesting sensing features achieved in these last years CP-ΦOTDR have motivated the use of this technology in diverse applications, such as seismology or civil engineering (monitoring of pipelines, train rails, etc.). Besides, new areas of application of this distributed sensor have been explored, based on distributed chemical (refractive index) and temperature-based transducer sensors. In this review, the principle of operation of CP-ΦOTDR is revisited, highlighting the particular performance characteristics of the technique and offering a comparison with alternative distributed sensing methods (with focus on coherent-detection-based ΦOTDR). The sensor is also characterized for operation in up to 100 km with a low cost-setup, showing performances close to the attainable limits for a given set of signal parameters [≈tens-hundreds of pe/sqrt(Hz)]. The areas of application of this sensing technology employed so far are briefly outlined in order to frame the technology.


The effects of national and international HIV/AIDS funding and governance mechanisms on the development of civil-society responses to HIV/AIDS in East and Southern Africa.
The study takes stock of the exponential growth in the number of new civil-society organisations (CSOs) working in the HIV/AIDS field in East and Southern Africa during the period 1996-2004. We researched this development through a survey of 439 CSOs in six countries and case studies focused on the evolution of community responses to HIV/AIDS in specific communities in eight countries. We describe the types of CSOs that emerged, their relationships with governments and donors, and their activities, organisational characteristics and funding requirements. The data presented show that the vision of social mobilisation of HIV/AIDS responses through community-level organisations has faced strong external challenges. Evidence from survey data, national HIV/AIDS spending assessments and case studies shows that in some respects the changing international aid environment undermines the prospects for development of the civil-society sector's contributions in HIV/AIDS responses. Of particular interest is to understand how the "Three Ones" and the Paris Declaration on Aid Effectiveness have reshaped international funding for HIV/AIDS responses. There has been relatively little attention paid to the impact of the new management and funding modalities--including national performance frameworks, general budget support, joint funding arrangements and basket funds--on civil-society agencies at the forefront of community HIV/AIDS responses. Evidence is presented to show that in important respects the new modalities limit the unique contribution that CSOs can make to national HIV/AIDS responses. It is also shown that the drive to rapidly intensify the scale of HIV/AIDS responses has involved using community organisations as service providers for externally formulated programmes. We discuss this as a strong threat to the development of sustainable civil-society economies as well as to CSOs' diversity and responsiveness. The ways in which CSOs are responding to these challenges are discussed, pointing to possibilities for a new phase of development of the civil-society sector.


Does a Vacation Break Impact the Outcomes of Required Clinical Clerkships?
Our objective was to assess the impact of disruption by a new 2-week vacation break on outcomes of required third-year clerkships. Mean scores on National Board of Medical Examiners (NBME) clerkship specific clinical science subject ("subject") examinations and overall student evaluations were compared for clerkships with the break and those over the previous 3 years without the break. Students were surveyed about the impact of the break on learning and the time spent studying during the break. No significant differences were found in examination scores between clerkships with the break and those without. Overall student clerkship evaluations were significantly different only for the surgery clerkship. The break was regarded more favorably by students on the 8-week than the 6-week clerkships, but student perspectives varied significantly by specialty. The time reported studying varied significantly by specialty and campus. Student comments were predominantly supportive of the break and focused on the advantages of opportunity to relax, spend time with family, and to study. Concerns included forgetting content knowledge, losing skills, and having difficulty regaining momentum on return to the clerkship. Interruption of clerkships by a 2-week break was not associated with any significant change in subject examination scores or overall student evaluation of the clerkship, despite predominantly positive comments. Significant differences were reported by specialty in student perception of benefit and reported time studying during the break.


Maternal anxiety versus depressive disorders: specific relations to infants' crying, feeding and sleeping problems.
Maternal depression has been associated with excessive infant crying, feeding and sleeping problems, but the specificity of maternal depression, as compared with maternal anxiety remains unclear and manifest disorders prior to pregnancy have been widely neglected. In this prospective longitudinal study, the specific associations of maternal anxiety and depressive disorders prior to, during and after pregnancy and infants' crying, feeding and sleeping problems were investigated in the context of maternal parity. In the Maternal Anxiety in Relation to Infant Development (MARI) Study, n = 306 primiparous and multiparous women were repeatedly interviewed from early pregnancy until 16 months post partum with the Composite International Diagnostic Interview for Women (CIDI-V) to assess DSM-IV anxiety and depressive disorders. Information on excessive infant crying, feeding and sleeping problems was obtained from n = 286 mothers during postpartum period via questionnaire and interview (Baby-DIPS). Findings from this study revealed syndrome-specific risk constellations for maternal anxiety and depressive disorders as early as prior to pregnancy: Excessive infant crying (10.1%) was specifically associated with maternal anxiety disorders, especially in infants of younger and lower educated first-time mothers. Feeding problems (36.4%) were predicted by maternal anxiety (and comorbid depressive) disorders in primiparous mothers and infants with lower birth weight. Infant sleeping problems (12.2%) were related to maternal depressive (and comorbid anxiety) disorders irrespective of maternal parity. Primiparous mothers with anxiety disorders may be more prone to anxious misinterpretations of crying and feeding situations leading to an escalation of mother-infant interactions. The relation between maternal depressive and infant sleeping problems may be better explained by a transmission of unsettled maternal sleep to the fetus during pregnancy or a lack of daily structure and bedtime routine with the infant. Maternal disorders prior to pregnancy require more attention in research and clinical practice.


Organic nanoparticle systems for spatiotemporal control of multimodal chemotherapy.
Chemotherapeutic drugs are used in combination to target multiple mechanisms involved in cancer cell survival and proliferation. Carriers are developed to deliver drug combinations to common target tissues in optimal ratios and desirable sequences. Nanoparticles (NP) have been a popular choice for this purpose due to their ability to increase the circulation half-life and tumor accumulation of a drug. Areas covered: We review organic NP carriers based on polymers, proteins, peptides, and lipids for simultaneous delivery of multiple anticancer drugs, drug/sensitizer combinations, drug/photodynamic therapy or drug/photothermal therapy combinations, and drug/gene therapeutics with examples in the past three years. Sequential delivery of drug combinations, based on either sequential administration or built-in release control, is introduced with an emphasis on the mechanistic understanding of such control. Expert opinion: Recent studies demonstrate how a drug carrier can contribute to co-localizing drug combinations in optimal ratios and dosing sequences to maximize the synergistic effects. We identify several areas for improvement in future research, including the choice of drug combinations, circulation stability of carriers, spatiotemporal control of drug release, and the evaluation and clinical translation of combination delivery.


The secret language of destiny: stress imprinting and transgenerational origins of disease.
Epigenetic regulation modulates gene expression without altering the DNA sequence to facilitate rapid adjustments to dynamically changing environmental conditions. The formation of an epigenetic memory allows passing on this information to subsequent generations. Here we propose that epigenetic memories formed by adverse environmental conditions and stress represent a critical determinant of health and disease in the F3 generation and beyond. Transgenerational programming of epigenetic regulation may represent a key to understand adult-onset complex disease pathogenesis and cumulative effects of life span and familial disease etiology. Ultimately, the mechanisms of generating an epigenetic memory may become of potentially promising diagnostic and therapeutic relevance due to their reversible nature. Exploring the role of environmental factors, such as stress, in causing variations in epigenetic profiles may lead to new avenues of personalized, preventive medicine based on epigenetic signatures and interventions.


Factors influencing uptake of measles, mumps and rubella (MMR) immunization in site-dwelling Gypsy, Roma and Traveller (G&T) communities: a qualitative study of G&T parents' beliefs and experiences.
Increasing immunization in the Gypsy, Roma and Traveller (G&T) community is a key priority for improving health outcomes in this community. This study aimed to explore G&T parents: (1) beliefs about childhood immunization; (2) beliefs about the risks of immunization and non-immunization; (3) perceived obstacles to, and facilitators of, immunization and (4) views on increasing immunization levels. A cross-sectional, qualitative study was conducted comprising of five focus groups with 16 site-dwelling G&T women with pre-school aged children. Data were transcribed verbatim and analysed thematically. Five main themes were identified: Lay understandings of causation and risk; Timing of immunization; Children being perceived as vulnerable; The fit between lifestyle and healthcare provision; The impact of living with a high burden of disease. Understanding of the risks and benefits of measles, mumps and rubella immunization did not differ significantly from the wider population or those promoted by the health service. The majority of barriers stemmed from living with the effects of long-standing health inequalities, which posed further barriers to accessing immunization, and shaped beliefs about immunization. Factors facilitating uptake occurred where access to immunization services was made flexible, e.g. immunization on traveller sites.


Lung cancer prognostic index: a risk score to predict overall survival after the diagnosis of non-small-cell lung cancer.
Non-small-cell lung cancer outcomes are poor but heterogeneous, even within stage groups. To improve prognostic precision we aimed to develop and validate a simple prognostic model using patient and disease variables. Prospective registry and study data were analysed using Cox proportional hazards regression to derive a prognostic model (hospital 1, n=695), which was subsequently tested (Harrell's c-statistic for discrimination and Cox-Snell residuals for calibration) in two independent validation cohorts (hospital 2, n=479 and hospital 3, n=284). The derived Lung Cancer Prognostic Index (LCPI) included stage, histology, mutation status, performance status, weight loss, smoking history, respiratory comorbidity, sex, and age. Two-year overall survival rates according to LCPI in the derivation and two validation cohorts, respectively, were 84, 77, and 68% (LCPI 1: score⩽9); 61, 61, and 42% (LCPI 2: score 10-13); 33, 32, and 14% (LCPI 3: score 14-16); 7, 16, and 5% (LCPI 4: score ⩾15). Discrimination (c-statistic) was 0.74 for the derivation cohort, 0.72 and 0.71 for the two validation cohorts. The LCPI contributes additional prognostic information, which may be used to counsel patients, guide trial eligibility or design, or standardise mortality risk for epidemiological analyses.


Differentially expressed genes in the liver of lean and fat chickens.
This study aimed to investigate gene expression in the chicken liver for lean and fat broiler lines. Birds used in this study were 2 and 4 weeks of age; they were derived from the 14th generation of Northeast Agricultural University broiler lines, which were divergently selected based on abdominal fat content. Chicken Genome Arrays were used to screen differentially expressed genes in the liver tissue from lean and fat birds. At 2 and 4 weeks of age, 770 and 452 genes were differentially expressed between the 2 lines, respectively. The differentially expressed genes were involved in Wnt, insulin signaling, and cell cycle pathways. At 2 and 4 weeks, 42 shared, differentially expressed genes were revealed by the analysis. We speculate that these genes might regulate chicken lipid metabolism.


Synthesis and Evaluation of Galloyl Conjugates of Flavanones as BMP-2 Upregulators with Promising Bone Anabolic and Fracture Healing Properties.
The molecular hybridization concept led us to design a series of galloyl conjugates of flavanones that have potent osteoblast differentiation ability in vitro and promote bone formation in vivo. An array of in vitro studies, especially gene expression of osteogenic markers, evinced compound 5e as the most potent bone anabolic agent, found to be active at 1 pM, which was then further assessed for its osteogenic potential in vivo. From in vivo studies on rat calvaria and a fracture defect model, we inferred that compound 5e, at an oral dose of 5 mg/(kg day), increased the expression of osteogenic genes (RUNX2, BMP-2, Col1, and OCN) and the bone formation rate and significantly promoted bone regeneration at the fracture site, as evidenced by the increased bone volume/tissue fraction compared with vehicle-treated rats. Furthermore, structure-activity relationship studies and pharmacokinetic studies suggest 5e as a potential bone anabolic lead for future osteoporosis drug development.


Three-dimensional, tomographic super-resolution fluorescence imaging of serially sectioned thick samples.
Three-dimensional fluorescence imaging of thick tissue samples with near-molecular resolution remains a fundamental challenge in the life sciences. To tackle this, we developed tomoSTORM, an approach combining single-molecule localization-based super-resolution microscopy with array tomography of structurally intact brain tissue. Consecutive sections organized in a ribbon were serially imaged with a lateral resolution of 28 nm and an axial resolution of 40 nm in tissue volumes of up to 50 µm×50 µm×2.5 µm. Using targeted expression of membrane bound (m)GFP and immunohistochemistry at the calyx of Held, a model synapse for central glutamatergic neurotransmission, we delineated the course of the membrane and fine-structure of mitochondria. This method allows multiplexed super-resolution imaging in large tissue volumes with a resolution three orders of magnitude better than confocal microscopy.


Expression of cAMP-responsive element modulator (CREM) in rat testes following chronic cocaine administration.
c-AMP-responsive element modulator (CREM), one of the nuclear factors involved in the regulation of gene expression by cAMP, has an important role in spermatogenesis. Our recent study has shown that chronic administration of cocaine to male rats results in disruption of spermatogenesis, including reduction of germ cells. As a further step toward understanding this process, we have studied the role of CREM in cocaine-induced testicular damage. Sprague-Dawley rats were administered cocaine hydrochloride subcutaneously daily for 90 days. Control animals received equal volumes of normal saline daily for 90 days. Testes were removed after 15, 30, 90 days of cocaine administration. Total RNA was extracted from the testes and subjected to RT-PCR. Testicular tissue was also homogenized in a lysis buffer, and Western blotting was performed using anti-CREM antibody. RT-PCR analysis detected a single fragment of approximately 520 base pairs (bp) in control testes at all time points. The cocaine-treated testes showed reduced expression of CREM fragment. Western blot analysis using CREM antibodies confirmed the RNA data. There were reduced CREM proteins in the cocaine-treated testes compared with controls. The CREM gene is essential for spermatogenesis. Our results indicate that the reduction in testicular CREM expression may be one of the mechanisms responsible for disruption or impairment of spermatogenesis in the testes following chronic cocaine administration.


Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus.
Gene-set analysis (GSA) is an approach using the results of single-marker genome-wide association studies when investigating pathways as a whole with respect to the genetic basis of a disease. We performed a meta-analysis of seven GSAs for lung cancer, applying the method META-GSA. Overall, the information taken from 11,365 cases and 22,505 controls from within the TRICL/ILCCO consortia was used to investigate a total of 234 pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. META-GSA reveals the systemic lupus erythematosus KEGG pathway hsa05322, driven by the gene region 6p21-22, as also implicated in lung cancer (p = 0.0306). This gene region is known to be associated with squamous cell lung carcinoma. The most important genes driving the significance of this pathway belong to the genomic areas HIST1-H4L, -1BN, -2BN, -H2AK, -H4K and C2/C4A/C4B. Within these areas, the markers most significantly associated with LC are rs13194781 (located within HIST12BN) and rs1270942 (located between C2 and C4A). We have discovered a pathway currently marked as specific to systemic lupus erythematosus as being significantly implicated in lung cancer. The gene region 6p21-22 in this pathway appears to be more extensively associated with lung cancer than previously assumed. Given wide-stretched linkage disequilibrium to the area APOM/BAG6/MSH5, there is currently simply not enough information or evidence to conclude whether the potential pleiotropy of lung cancer and systemic lupus erythematosus is spurious, biological, or mediated. Further research into this pathway and gene region will be necessary.


Blood donor incentives: A step forward or backward.
Dramatic increase in blood usage and critical seasonal blood shortages are faced by various countries. Countries which previously reached 100% voluntary nonremunerated donation have been led to offer different kinds of incentives to recruit blood donors and meet their blood demands. In some cases, these incentives are considered monetary and are in complete contrast with International standards like World Health Organization (WHO). It seems that attitudes toward sole dependency on nonremunerated voluntary blood donation have been changed in recent years and experts in some developed countries are reevaluating partial reliance on paid donation. On the other hand, besides the effects of such incentives on blood safety, several economic and psychological studies have shown that incentives have discouraging effects on pro-social behaviors like blood donation and will reduce the number of blood donors in long term. With regard to the results of such studies, it seems that implementing incentive-based blood donor recruitment programs to meet blood requirements by some countries is becoming a challenge for blood banks.


Pediatric Nasoorbitoethmoid Fractures: A Single Institution's 15-Year Experience.
Nasoorbitoethmoid (NOE) fractures impact growth of the craniofacial skeleton in children, which may necessitate differentiated management from adult injuries. This study describes characteristics, management, and outcomes of NOE fractures in children seen at a single institution. A retrospective review of patients under 18 years who presented to our institution from 2006 to 2021 with facial fractures was conducted; patients with NOE fractures were included. Data collected included demographics, mechanism of injury, fracture type, management, and outcomes. Fifty-eight patients met inclusion criteria; 77.6% presented with Manson-Marcowitz Type I fractures, 17.2% with Type II, and 5.2% with Type III. The most common cause of injury was motor vehicle accidents (MVAs, 39.7%) and sports (31%). Glasgow Coma Scale and injury mechanism were not predictive of injury severity in the pediatric population ( P =0.353, P =0.493). Orbital fractures were the most common associated fractures (n=55, 94.8%); parietal bone fractures were more likely in Type III fractures ( P =0.047). LeFort III fractures were more likely in type II fractures ( P =0.011). Soft tissue and neurological injuries were the most common associated injuries regardless of NOE fracture type (81% and 58.6%, respectively). There was no significant difference in type of operative management or in the rates of adverse outcomes between types of NOE fractures. These findings suggest that pediatric NOE fractures, although rare, present differently from adult NOE fractures and that revisiting predictive heuristics and treatment strategies is warranted in this population.


Metrondazole-induced neurotoxicity.
A 50 year old male with history of prolonged intake of metronidazole for treatment of liver abscess developed acute ataxia, disorientation, distal symmetrical sensory and proximal motor neuropathy. Patients being treated with metronidazole particularly those on high doses for prolonged period should be monitored for neurotoxicity.


On Racial Disparities in Child Abuse Reports: Exploratory Mapping the 2018 NCANDS.
Research suggests children from non-White and Hispanic/Latinx communities are at higher risk for child maltreatment. This study identified in which states children from specific non-White communities were overrepresented in child protective services reports for child physical, sexual, and emotional/psychological abuse through exploratory mapping. Reports on child maltreatment originated from the 2018 National Child Abuse and Neglect Data System and state-level population estimates from the U.S. Census Bureau. Racial disparities were identified in states with unequal proportions of reported child maltreatment among a non-White child population compared to the proportion among the White child population. We found disparities for children from non-White communities in many states, especially for Black communities (Disparity Ratio [DR]: 15.10 for child physical abuse, DR: 12.77 for child sexual abuse in Washington DC, and DR: 5.25 for child emotional/psychological abuse in California). The ability to identify high disparities among Pacific Islanders highlights one of the study's strengths, given we separately examined Asian Americans, Pacific Islanders and multiracial communities. Results from our exploratory mapping provide insight into how preventive resources might be differentially allocated to non-White communities with higher child protective services reporting compared with White communities, and manifest states with multiple non-White communities overrepresented across maltreatment types.


A Gene-Based Analysis of Acoustic Startle Latency.
Latency of the acoustic startle response is the time required from the presentation of startling auditory stimulus until the startle response is elicited and provides an index of neural processing speed. Latency is prolonged in subjects with schizophrenia compared to controls in some but not all studies and is 68-90% heritable in baseline startle trials. In order to determine the genetic association with latency as a potential inroad into genetically based vulnerability to psychosis, we conducted a gene-based study of latency followed by an independent replication study of significant gene findings with a single-nucleotide polymorphism (SNP)-based analysis of schizophrenia and control subjects. 313 subjects from an urban population of low socioeconomic status with mixed psychiatric diagnoses were included in the gene-based study. Startle testing was conducted using a Biopac M150 system according to our published methods. Genotyping was performed with the Omni-Quad 1M or the Omni Express BeadChip. The replication study was conducted on 154 schizophrenia subjects and 123 psychiatric controls. Genetic analyses were conducted with Illumina Human Omni1-Quad and OmniExpress BeadChips. Twenty-nine SNPs were selected from four genes that were significant in the gene-based analysis and also associated with startle and/or schizophrenia in the literature. Linear regressions on latency were conducted, controlling for age, race, and diagnosis as a dichotomous variable. In the gene-based study, 2,870 genes demonstrated the evidence of association after correction for multiple comparisons (false discovery rate < 0.05). Pathway analysis of these genes revealed enrichment for relevant biological processes including neural transmission (p = 0.0029), synaptic transmission (p = 0.0032), and neuronal development (p = 0.024). The subsequent SNP-based replication analysis revealed a strong association of onset latency with the SNP rs901561 on the neuregulin gene (NRG1) in an additive model (beta = 0.21, p = 0.001), indicating that subjects with the AA and AG genotypes had slower mean latency than subjects with GG genotype. In conclusion, startle latency, a highly heritable measure that is slowed in schizophrenia, may be a useful biological probe for genetic contributions to psychotic disorders. Our analyses in two independent populations point to a significant prediction of startle latency by genetic variation in NRG1.


Kitamura Electrophilic Fluorination Using HF as a Source of Fluorine.
This review article focused on the innovative procedure for electrophilic fluorination using HF and in situ generation of the required electrophilic species derived from hypervalent iodine compounds. The areas of synthetic application of this approach include fluorination of 1,3-dicarbonyl compounds, aryl-alkyl ketones, styrene derivatives, α,β-unsaturated ketones and alcohols, homoallyl amine and homoallyl alcohol derivatives, 3-butenoic acids and alkynes.


Gas-Phase and Computational Study of Identical Nickel- and Palladium-Mediated Organic Transformations Where Mechanisms Proceeding via M(II) or M(IV) Oxidation States Are Determined by Ancillary Ligands.
Gas-phase studies utilizing ion-molecule reactions, supported by computational chemistry, demonstrate that the reaction of the enolate complexes [(CH2CO2-C,O)M(CH3)](-) (M = Ni (5a), Pd (5b)) with allyl acetate proceed via oxidative addition to give M(IV) species [(CH2CO2-C,O)M(CH3)(η(1)-CH2-CH═CH2)(O2CCH3-O,O')](-) (6) that reductively eliminate 1-butene, to form [(CH2CO2-C,O)M(O2CCH3-O,O')](-) (4). The mechanism contrasts with the M(II)-mediated pathway for the analogous reaction of [(phen)M(CH3)](+) (1a,b) (phen = 1,10-phenanthroline). The different pathways demonstrate the marked effect of electron-rich metal centers in enabling higher oxidation state pathways. Due to the presence of two alkyl groups, the metal-occupied d orbitals (particularly dz(2)) in 5 are considerably destabilized, resulting in more facile oxidative addition; the electron transfer from dz(2) to the C═C π* orbital is the key interaction leading to oxidative addition of allyl acetate to M(II). Upon collision-induced dissociation, 4 undergoes decarboxylation to form 5. These results provide support for the current exploration of roles for Ni(IV) and Pd(IV) in organic synthesis.


Chaperonin-mediated folding of green fluorescent protein.
Chaperonin-mediated folding of green fluorescent protein (GFP) was examined by real-time monitoring of recovery of fluorescence and by gel filtration high-performance liquid chromatography. Acid-denatured GFP can fold spontaneously upon dilution into the neutral buffer. When Escherichia coli GroEL/ES was present, folding of GFP was arrested. Folding was resumed by subsequent addition of 100 microM or 1 mM ATP, and native GFP was regenerated to 100% yield. When folding was resumed by 10 microM ATP (1.4 mol/mol GroEL subunit), about 60% of GFP recovered native structure, and one-half of them (30%) was found to be still bound to GroEL/ES, indicating the occurrence of folding in the central cavity of the GroEL ring underneath GroES (cis-folding). Because the overall rates of GroEL/ES-, ATP-mediated GFP folding were all similar to that of spontaneous folding, it was concluded that cis-folding proceeded as fast as spontaneous folding. The GroEL/ES-bound native GFP was observed only when both GroES and ATP (but not ADP) were present in the folding mixture. Holo-chaperonin from Thermus thermophilus, which was purified as a cpn60/10 complex, exhibited the similar cis-folding. Consistently, ATP-dependent exchange of cpn10 in the holo-chaperonin with free cpn10 was observed.


Invasive assessment of mitral regurgitation: comparison of hemodynamic parameters.
We sought to analyze several new hemodynamic characteristics which address the interplay of left atrial (LA) and left ventricular (LV) pressures, as well as to re-analyze several other V wave characteristics employed in the determination of mitral regurgitation (MR) severity in order to determine which, if any, had adequate correlation with grade of MR for clinical utility. Invasive assessment of mitral regurgitation includes analysis of intracardiac pressures and LV angiography. The V wave, when obtained from the pulmonary capillary wedge position (PCWP), and its various characteristics are believed to be of limited value for prediction of MR severity. We analyzed the transeptal pressure tracings of patients with various degrees of MR. Several relationships from the simultaneous pressure-time curves of the LA and LV were defined. Biplane left ventricular angiography was used to grade MR. Correlation between each parameter and MR grade was determined by calculating a Pearson correlation coefficient. The ratio of the area under the V wave to the LV systolic area (V(a)/LV(a)) best correlates with the degree of MR with a Pearson correlation coefficient of 0.60. The V(a)/LV(a) was significantly lower in patients with 0-1+ MR compared to > or =2+ MR (0.14 vs. 0.23 p = 0.002). Invasive hemodynamic assessment of MR severity could be enhanced by calculating our new ratio, V(a)/LV(a), due to its ability to account for LV work that is lost to the LA with a proportional decrease in forward or useful LV work with progressively increasing severity of MR.


Risk-taking behaviors among injecting drug users who obtain syringes from pharmacies, fixed sites, and mobile van needle exchanges.
Needle-exchange programs (NEPs) have been shown to be effective in reducing harm related to injection drug use and to act as an important link between the injection drug using community and preventive/treatment services. Different needle-exchange distribution methods may reach different subpopulations of injecting drug users (IDUs). We undertook this study to characterize risk behaviors by primary source of clean needles accessed by IDUs in a city with pharmacy access and fixed and mobile exchange programs. We hypothesized there would be a gradient of risk across the three types of distribution. Data were collected from within the Vancouver Injection Drug Users Study (VIDUS), a prospective cohort study. Participants who primarily obtained clean needles from pharmacies, fixed sites, or mobile exchange vans were compared using the Cochran-Armitage trend test to test for trends in increasing risk behaviors across the three types of distribution. Ordinal multivariate regression was used to adjust the associations for potential confounders. Results illustrate clear trends for increasing risk profiles from pharmacy to fixed site to mobile exchange vans. Van users were generally at higher risk than fixed-site and pharmacy users. Independent predictors of van use were fewer years injecting, difficulty finding needles, Aboriginal ethnicity, incarceration in the previous 6 months, and injecting cocaine daily. An important component of needle-exchange programs is outreach to access those who are at highest risk. Use of distribution beyond fixed sites will improve such outreach, thereby increasing program effectiveness and further preventing the transmission of blood-borne infections.


Characteristics of available studies and dissemination of research using major clinical data sharing platforms.
Over the past decade, numerous data sharing platforms have been launched, providing access to de-identified individual patient-level data and supporting documentation. We evaluated the characteristics of prominent clinical data sharing platforms, including types of studies listed as available for request, data requests received, and rates of dissemination of research findings from data requests. We reviewed publicly available information listed on the websites of six prominent clinical data sharing platforms: Biological Specimen and Data Repository Information Coordinating Center, ClinicalStudyDataRequest.com, Project Data Sphere, Supporting Open Access to Researchers-Bristol Myers Squibb, Vivli, and the Yale Open Data Access Project. We recorded key platform characteristics, including listed studies and available supporting documentation, information on the number and status of data requests, and rates of dissemination of research findings from data requests (i.e. publications in a peer-reviewed journals, preprints, conference abstracts, or results reported on the platform's website). The number of clinical studies listed as available for request varied among five data sharing platforms: Biological Specimen and Data Repository Information Coordinating Center (n = 219), ClinicalStudyDataRequest.com (n = 2,897), Project Data Sphere (n = 154), Vivli (n = 5426), and the Yale Open Data Access Project (n = 395); Supporting Open Access to Researchers did not provide a list of Bristol Myers Squibb studies available for request. Individual patient-level data were nearly always reported as being available for request, as opposed to only Clinical Study Reports (Biological Specimen and Data Repository Information Coordinating Center = 211/219 (96.3%); ClinicalStudyDataRequest.com = 2884/2897 (99.6%); Project Data Sphere = 154/154 (100.0%); and the Yale Open Data Access Project = 355/395 (89.9%)); Vivli did not provide downloadable study metadata. Of 1201 data requests listed on ClinicalStudyDataRequest.com, Supporting Open Access to Researchers-Bristol Myers Squibb, Vivli, and the Yale Open Data Access Project platforms, 586 requests (48.8%) were approved (i.e. data access granted). The majority were for secondary analyses and/or developing/validating methods (ClinicalStudyDataRequest.com = 262/313 (83.7%); Supporting Open Access to Researchers-Bristol Myers Squibb = 22/30 (73.3%); Vivli = 63/84 (75.0%); the Yale Open Data Access Project = 111/159 (69.8%)); four were for re-analyses or corroborations of previous research findings (ClinicalStudyDataRequest.com = 3/313 (1.0%) and the Yale Open Data Access Project = 1/159 (0.6%)). Ninety-five (16.1%) approved data requests had results disseminated via peer-reviewed publications (ClinicalStudyDataRequest.com = 61/313 (19.5%); Supporting Open Access to Researchers-Bristol Myers Squibb = 3/30 (10.0%); Vivli = 4/84 (4.8%); the Yale Open Data Access Project = 27/159 (17.0%)). Forty-two (6.8%) additional requests reported results through preprints, conference abstracts, or on the platform's website (ClinicalStudyDataRequest.com = 12/313 (3.8%); Supporting Open Access to Researchers-Bristol Myers Squibb = 3/30 (10.0%); Vivli = 2/84 (2.4%); Yale Open Data Access Project = 25/159 (15.7%)). Across six prominent clinical data sharing platforms, information on studies and request metrics varied in availability and format. Most data requests focused on secondary analyses and approximately one-quarter of all approved requests publicly disseminated their results. To further promote the use of shared clinical data, platforms should increase transparency, consistently clarify the availability of the listed studies and supporting documentation, and ensure that research findings from data requests are disseminated.


Heart transplantation in patients with diuretic resistant heart failure.
Advanced heart failure is becoming an increasing cause of mortality and morbidity in a large number of patients. Heart transplantation is the treatment of choice for many selected patients in this group. According to the clinical status at the time of transplant, patients may have a different outcome related to the early survival, while the late results are similar and not affected by the patient's initial clinical status. All surviving patients showed recovery of kidney function as soon the cardiac output was restored to normal values. High urine output was present in a large number of patients in the early postoperative period. However, in severely ill patients with cardiac index <2.5 l/min/m2, diuretic resistance and mortality were higher.


Multiple Machine Learning Approaches Based on Postoperative Prediction of Pulmonary Complications in Patients With Emergency Cerebral Hemorrhage Surgery.
This study aimed to create a prediction model of postoperative pulmonary complications for the patients with emergency cerebral hemorrhage surgery. Patients with hemorrhage surgery who underwent cerebral hemorrhage surgery were included and divided into two groups: patients with or without pulmonary complications. Patient characteristics, previous history, laboratory tests, and interventions were collected. Univariate and multivariate logistic regressions were used to predict postoperative pulmonary infection. Multiple machine learning approaches have been used to compare their importance in predicting factors, namely K-nearest neighbor (KNN), stochastic gradient descent (SGD), support vector classification (SVC), random forest (RF), and logistics regression (LR), as they are the most successful and widely used models for clinical data. Three hundred and fifty four patients with emergency cerebral hemorrhage surgery between January 1, 2017 and December 31, 2020 were included in the study. 53.7% (190/354) of the patients developed postoperative pulmonary complications (PPC). Stepwise logistic regression analysis revealed four independent predictive factors associated with pulmonary complications, including current smoker, lymphocyte count, clotting time, and ASA score. In addition, the RF model had an ideal predictive performance. According to our result, current smoker, lymphocyte count, clotting time, and ASA score were independent risks of pulmonary complications. Machine learning approaches can also provide more evidence in the prediction of pulmonary complications.


Patch grafts or tubular grafts in the repair of coarctation of the aorta. A follow-up study.
The occurrence of aneurysms after repair of aortic coarctation with patch graft and tubular graft techniques was studied. In the patch graft group, 3 out of 6 re-investigated patients developed aneurysms; 2 of them after several years. It is suggested that the causes of aneurysms originate from mechanical factors. In the tubular graft group, 2 out of 18 patients developed aneurysms. In this group, the aneurysms seemed to be due to infection.