Increased Rate of Complications following Trigger Finger Release in Diabetic Patients.
The purpose of this study was to investigate the impact of diabetes on complications after open trigger finger release compared with a cohort matched for age, sex, race, and body mass index class. A retrospective chart review was performed of diabetic patients who underwent trigger finger release at an academic institution within the past 10 years. Exclusion criteria included rheumatoid arthritis, malignancy, human immunodeficiency virus/acquired immunodeficiency syndrome, connective tissue disorders, or systemic steroid use. These patients were then matched by age, sex, race, and body mass index class to nondiabetic patients who underwent trigger finger release during the same period. One hundred thirty-seven patients met inclusion criteria and were matched with controls. Complications included superficial or deep infection, delayed wound healing, limited range of motion at 6 weeks, pain requiring medication at 6 weeks, and return to the operating room. In adjusted analyses, diabetic patients had a significantly higher rate of all-cause complication following trigger finger release compared with matched nondiabetic controls at an odds ratio of 2.1. Diabetic patients also had a significantly higher rate of limitation in postoperative range of motion compared to the controls with an odds ratio of 2.4. This retrospective case-control study identified that diabetic patients undergoing trigger finger release are at increased risk of all-cause postoperative complications and, specifically, range of motion limitation when compared with similar patients without diabetes. Risk, II.


A theranostic agent for in vivo near-infrared imaging of β-amyloid species and inhibition of β-amyloid aggregation.
Amyloid-β (Aβ) peptide as one of the main components of senile plaques is closely related to the onset and progression of incurable Alzheimer's disease (AD). Numerous efforts have been devoted to develop probes for Aβ species/plaque imaging for AD diagnostics and to develop aggregation inhibitors preventing formation of toxic soluble oligomeric Aβ for therapeutics. Herein, for the first time, a series of novel charged molecules, which can simultaneously perform near infra-red in vivo imaging of Aβ species/plaques in animal model and inhibition of self-aggregation of Aβ monomer from forming toxic oligomers, are reported. Among them, DBA-SLOH showed excellent blood-brain barrier (BBB) permeability and biocompatibility due to the incorporation of lipophilic alkyl chains with moderate length into the charged skeleton. Importantly, DBA-SLOH was found to have a high binding affinity toward Aβ species exhibiting a dramatic fluorescence enhancement upon interacting with Aβ species. Despite a weaker binding with Aβ monomers as compared to Aβ aggregates, DBA-SLOH could effectively prevent the Aβ1-40 and Aβ1-42 peptides from self-aggregation and forming toxic oligomers. This multifunctional fluorescent molecule shows promising potential as a theranostic agent for the diagnosis and therapy of AD.


Everyday life for the spouses of patients with untreated OSA syndrome.
The aim of this study was to generate a theoretical model describing concerns for spouses of patients with untreated obstructive sleep apnoea syndrome (OSAS) and how they manage these concerns in their everyday life. Twelve spouses were interviewed about their experiences and how they manage everyday life. The interviews were analysed according to the Grounded Theory method as described by Strauss and Corbin. Two main categories emerged from the data: 'Social adjustment' and 'New feelings'. 'Social adjustment' reveals how the spouses made adjustments in their daily lives, both according to their partners' tiredness and owing to their own fatigue. 'New feelings' reveals emotional reactions related to the effects of their partner's illness and the impact it had on the spouse's everyday life. These two main categories could be seen in relation to four dimensions describing how the spouses manage their everyday life: 'Sacrificing', 'Controlling', 'Changing' and 'Understanding'. The results show how the spouses made adjustments in everyday life and how their feelings were affected by their partner's OSAS. Healthcare personnel could use information from this study to gain a deeper understanding and knowledge of what spouses of untreated patients with OSAS experience as their main concerns and how they manage their everyday life. This knowledge can be used to improve the support to the spouses, as well as in the educational situation concerning the illness, as well as the treatment.


Mortality Risk Assessment in COVID-19 Venovenous Extracorporeal Membrane Oxygenation.
A life-threatening complication of coronavirus disease 2019 (COVID-19) is acute respiratory distress syndrome (ARDS) refractory to conventional management. Venovenous (VV) extracorporeal membrane oxygenation (ECMO) (VV-ECMO) is used to support patients with ARDS in whom conventional management fails. Scoring systems to predict mortality in VV-ECMO remain unvalidated in COVID-19 ARDS. This report describes a large single-center experience with VV-ECMO in COVID-19 and assesses the utility of standard risk calculators. A retrospective review of a prospective database of all patients with COVID-19 who underwent VV-ECMO cannulation between March 15 and June 27, 2020 at a single academic center was performed. Demographic, clinical, and ECMO characteristics were collected. The primary outcome was in-hospital mortality; survivor and nonsurvivor cohorts were compared by using univariate and bivariate analyses. Forty patients who had COVID-19 and underwent ECMO were identified. Of the 33 patients (82.5%) in whom ECMO had been discontinued at the time of analysis, 18 patients (54.5%) survived to hospital discharge, and 15 (45.5%) died during ECMO. Nonsurvivors presented with a statistically significant higher Prediction of Survival on ECMO Therapy (PRESET)-Score (mean ± SD, 8.33 ± 0.8 vs 6.17 ± 1.8; P = .001). The PRESET score demonstrated accurate mortality prediction. All patients with a PRESET-Score of 6 or lowers survived, and a score of 7 or higher was associated with a dramatic increase in mortality. These results suggest that favorable outcomes are possible in patients with COVID-19 who undergo ECMO at high-volume centers. This study demonstrated an association between the PRESET-Score and survival in patients with COVID-19 who underwent VV-ECMO. Standard risk calculators may aid in appropriate selection of patients with COVID-19 ARDS for ECMO.


Detection and identification of Bartonella sp. in fleas from carnivorous mammals in Andalusia, Spain.
A total of 559 fleas representing four species (Pulex irritans, Ctenocephalides felis, Ctenocephalides canis and Spilopsyllus cuniculi) collected on carnivores (five Iberian lynx Lynx pardinus, six European wildcat Felis silvestris, 10 common genet Genetta genetta, three Eurasian badger Meles meles, 22 red fox Vulpes vulpes, 87 dogs and 23 cats) in Andalusia, southern Spain, were distributed in 156 pools of monospecific flea from each carnivore, and tested for Bartonella infection in an assay based on polymerase chain reaction (PCR) amplification of the 16 S-23 S rRNA intergenic spacer region. Twenty-one samples (13.5%) were positive and the sequence data showed the presence of four different Bartonella species. Bartonella henselae was detected in nine pools of Ctenocephalides felis from cats and dogs and in three pools of Ctenocephalides canis from cats; Bartonella clarridgeiae in Ctenocephalides felis from a cat, and Bartonella alsatica in Spilopsyllus cuniculi from a wildcat. DNA of Bartonella sp., closely related to Bartonella rochalimae, was found in seven pools of Pulex irritans from foxes. This is the first detection of B. alsatica and Bartonella sp. in the Iberian Peninsula. All of these Bartonella species have been implicated as agents of human diseases. The present survey confirms that carnivores are major reservoirs for Bartonella spp.


A modelling framework to assess the likely effectiveness of facemasks in combination with 'lock-down' in managing the COVID-19 pandemic.
COVID-19 is characterized by an infectious pre-symptomatic period, when newly infected individuals can unwittingly infect others. We are interested in what benefits facemasks could offer as a non-pharmaceutical intervention, especially in the settings where high-technology interventions, such as contact tracing using mobile apps or rapid case detection via molecular tests, are not sustainable. Here, we report the results of two mathematical models and show that facemask use by the public could make a major contribution to reducing the impact of the COVID-19 pandemic. Our intention is to provide a simple modelling framework to examine the dynamics of COVID-19 epidemics when facemasks are worn by the public, with or without imposed 'lock-down' periods. Our results are illustrated for a number of plausible values for parameter ranges describing epidemiological processes and mechanistic properties of facemasks, in the absence of current measurements for these values. We show that, when facemasks are used by the public all the time (not just from when symptoms first appear), the effective reproduction number, Re , can be decreased below 1, leading to the mitigation of epidemic spread. Under certain conditions, when lock-down periods are implemented in combination with 100% facemask use, there is vastly less disease spread, secondary and tertiary waves are flattened and the epidemic is brought under control. The effect occurs even when it is assumed that facemasks are only 50% effective at capturing exhaled virus inoculum with an equal or lower efficiency on inhalation. Facemask use by the public has been suggested to be ineffective because wearers may touch their faces more often, thus increasing the probability of contracting COVID-19. For completeness, our models show that facemask adoption provides population-level benefits, even in circumstances where wearers are placed at increased risk. At the time of writing, facemask use by the public has not been recommended in many countries, but a recommendation for wearing face-coverings has just been announced for Scotland. Even if facemask use began after the start of the first lock-down period, our results show that benefits could still accrue by reducing the risk of the occurrence of further COVID-19 waves. We examine the effects of different rates of facemask adoption without lock-down periods and show that, even at lower levels of adoption, benefits accrue to the facemask wearers. These analyses may explain why some countries, where adoption of facemask use by the public is around 100%, have experienced significantly lower rates of COVID-19 spread and associated deaths. We conclude that facemask use by the public, when used in combination with physical distancing or periods of lock-down, may provide an acceptable way of managing the COVID-19 pandemic and re-opening economic activity. These results are relevant to the developed as well as the developing world, where large numbers of people are resource poor, but fabrication of home-made, effective facemasks is possible. A key message from our analyses to aid the widespread adoption of facemasks would be: 'my mask protects you, your mask protects me'.


Postconvulsive central apnea as a biomarker for sudden unexpected death in epilepsy (SUDEP).
To characterize peri-ictal apnea and postictal asystole in generalized convulsive seizures (GCS) of intractable epilepsy. This was a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of sudden unexpected death in epilepsy (SUDEP) in patients ≥18 years old with intractable epilepsy and monitored GCS. Video-EEG, thoracoabdominal excursions, nasal airflow, capillary oxygen saturation, and ECG were analyzed. We studied 148 GCS in 87 patients. Nineteen patients had generalized epilepsy; 65 had focal epilepsy; 1 had both; and the epileptogenic zone was unknown in 2. Ictal central apnea (ICA) preceded GCS in 49 of 121 (40.4%) seizures in 23 patients, all with focal epilepsy. Postconvulsive central apnea (PCCA) occurred in 31 of 140 (22.1%) seizures in 22 patients, with generalized, focal, or unknown epileptogenic zones. In 2 patients, PCCA occurred concurrently with asystole (near-SUDEP), with an incidence rate of 10.2 per 1,000 patient-years. One patient with PCCA died of probable SUDEP during follow-up, suggesting a SUDEP incidence rate 5.1 per 1,000 patient-years. No cases of laryngospasm were detected. Rhythmic muscle artifact synchronous with breathing was present in 75 of 147 seizures and related to stertorous breathing (odds ratio 3.856, 95% confidence interval 1.395-10.663, p = 0.009). PCCA occurred in both focal and generalized epilepsies, suggesting a different pathophysiology from ICA, which occurred only in focal epilepsy. PCCA was seen in 2 near-SUDEP cases and 1 probable SUDEP case, suggesting that this phenomenon may serve as a clinical biomarker of SUDEP. Larger studies are needed to validate this observation. Rhythmic postictal muscle artifact is suggestive of post-GCS breathing effort rather than a specific biomarker of laryngospasm.


Optic ataxia revisited: visually guided action versus immediate visuomotor control.
Optic ataxia and visual agnosia have been proposed to constitute a double dissociation which provides the main argument for the assimilation of the anatomical distinction between a dorsal and a ventral visual stream to the functional distinction between perception and action. In the present review, we argue that insufficient evidence has been collected to argue for this double dissociation. Several criteria are reviewed: (1) exploration of the visuomotor behavior in central versus peripheral vision has not been matched for the two types of patients; (2) the temporal constraints of visual processes that are impaired in the two neurological conditions appear to play a crucial role in the apparent dissociation; (3) the necessary reductionism of experimental conditions used to study action has led to an overconsideration of optic ataxia as a global deficit for action. Altogether optic ataxia appears to result from a specific impairment of immediate visuomotor control rather than of visually guided action as a whole. These results are discussed in the light of recent research on optic ataxia and on motor control, and directions for future research are proposed.


Melatonin attenuates ifosfamide-induced Fanconi syndrome in rats.
Regarding the mechanisms of ifosfamide (IFO)-induced nephrotoxicity and hemorrhagic cystitis, several hypotheses have been put forward, among which oxidative stress and depletion of glutathione (GSH) are suggested. This investigation elucidates the role of free radicals in IFO-induced toxicity and the protection by melatonin. Wistar albino rats were injected intraperitoneally with saline (0.9% NaCl; control-C group), melatonin (Mel group; 10 mg/kg daily for 5 days) or ifosfamide (50 mg/kg daily for 5 days; IFO group) or IFO + Mel. On the 5th day (120 hr) after the first IFO dose, animals were killed by decapitation and trunk blood was collected. Kidney and bladder tissues were obtained for biochemical and histological analysis. Urine was collected 24 hr before the rats were killed. The results demonstrated that IFO induced a Fanconi syndrome (FS) characterized by wasting of sodium, phosphate, and glucose, along with increased serum creatinine and urea. Melatonin markedly ameliorated the severity of renal dysfunction induced by IFO with a significant decrease in urinary sodium, phosphate, and glucose and increased creatinine excretion. Moreover, melatonin significantly improved the IFO-induced GSH depletion, malondialdehyde accumulation and neutrophil infiltration in both renal and bladder tissues. In the kidney, Na+,K+ -ATPase activity which was significantly reduced by IFO, was increased with melatonin treatment. Increased collagen contents of the kidney and bladder tissues by IFO treatment were reversed back to the control levels with melatonin. Our results suggest that IFO causes oxidative damage in renal and bladder tissues and melatonin, via its antioxidant effects, protects these tissues. These data suggest that melatonin may be of therapeutic use in preventing acquired FS due to IFO toxicity.


Thoracic positron emission tomography: 18F-fluorodeoxyglucose and beyond.
Ongoing technologic and therapeutic advancements in medicine are now testing the limits of conventional anatomic imaging techniques. The ability to image physiology, rather than simply anatomy, is critical in the management of multiple disease processes, especially in oncology. Nuclear medicine has assumed a leading role in detecting, diagnosing, staging and assessing treatment response of various pathologic entities, and appears well positioned to do so into the future. When combined with computed tomography (CT) or magnetic resonance imaging (MRI), positron emission tomography (PET) has become the sine quo non technique of evaluating most solid tumors especially in the thorax. PET/CT serves as a key imaging modality in the initial evaluation of pulmonary nodules, often obviating the need for more invasive testing. PET/CT is essential to staging and restaging in bronchogenic carcinoma and offers key physiologic information with regard to treatment response. A more recent development, PET/MRI, shows promise in several specific lung cancer applications as well. Additional recent advancements in the field have allowed PET to expand beyond imaging with 18F-flurodeoxyglucose (FDG) alone, now with the ability to specifically image certain types of cell surface receptors. In the thorax this predominantly includes 68Ga-DOTATATE which targets the somatostatin receptors abundantly expressed in neuroendocrine tumors, including bronchial carcinoid. This receptor targeted imaging technique permits targeting these tumors with therapeutic analogues such as 177Lu labeled DOTATATE. Overall, the proper utilization of PET in the thorax has the ability to directly impact and improve patient care.


Guanine nucleotide-independent inhibition of adenylate cyclase by a stimulatory hormone.
Stimulation of basal adenylate cyclase activity in membranes of neuroblastoma x glioma hybrid cells by prostaglandin E1 (PGE1) is half-maximal and maximal (about 8-fold) at 0.1 and 10 microM respectively. This hormonal effect requires GTP, being maximally effective at 10 microM. However, at the same concentrations that stimulate adenylate cyclase in the presence of GTP, PGE1 inhibited basal adenylate cyclase activity when studied in the absence of GTP, by maximally 60%. A similar dual action of PGE1 was observed with the forskolin-stimulated adenylate cyclase, although the potency of PGE1 in both stimulating and inhibiting adenylate cyclase was increased and the extent of stimulation and inhibition of the enzyme by PGE1 was decreased by the presence of forskolin. The inhibition of forskolin-stimulated adenylate cyclase by PGE1 occurred without apparent lag phase and was reversed by GTP and its analogue guanosine 5'-[gamma-thio]triphosphate at low concentrations. Treatment of neuroblastoma x glioma hybrid cells or membranes with agents known to eliminate the function of the inhibitory GTP-binding protein were without effect on PGE1-induced inhibition of adenylate cyclase. The data suggest that stimulatory hormone agonist, apparently by activating one receptor type, can cause both stimulation and inhibition of adenylate cyclase, and that the final result depends only on the activity state of the stimulatory GTP-binding protein, Gs. Possible mechanisms responsible for the observed adenylate cyclase inhibition by the stimulatory hormone PGE1 are discussed.


Human CYP2D6 and mouse CYP2Ds: organ distribution in a humanized mouse model.
Polymorphic cytochrome P450 (P450) 2D6 (CYP2D6) metabolizes several classes of therapeutic drugs, endogenous neurochemicals, and toxins. A CYP2D6-humanized transgenic mouse line was previously developed to model CYP2D6-poor and -extensive metabolizer phenotypes. Human CYP2D6 was detected in the liver, kidney, and intestine of these animals. In this study, we investigated further the cellular expression and relative tissue levels of human CYP2D6 in these transgenic mice in liver, intestine, kidney, and brain. In addition, we compared this with the expression of mouse CYP2D enzymes in these organs. In humans, these organs are of interest with respect to P450-mediated drug metabolism, toxicity, and disease. The expression of human CYP2D6 and mouse CYP2D enzymes in humanized and wild-type mice was quantified by immunoblotting and detected at the cellular level by immunocytochemistry. The cell-specific expression of human CYP2D6 in liver, kidney, and intestine in humanized mice was similar to that reported in humans. The expression patterns of mouse CYP2D proteins were similar to those in humans in liver and kidney but substantially different in intestine. Human CYP2D6 was not detected in brain of transgenic mice. Mouse CYP2D proteins were detected in brain, allowing, for the first time, a direct comparison of CYP2D expression among mouse, rat, and human brain. This transgenic mouse model is useful for investigating CYP2D6-mediated metabolism in liver, kidney, and especially the intestine, where expression patterns demonstrated substantial species differences.


Thyroid-like metastases to the scalp from a papillary renal cell carcinoma: a case report.
The skin can host metastatic tumors originating from different organs. We report a case of metastatic renal cell carcinoma to the scalp in a 73-year-old man with features very similar to those of thyroid papillary carcinoma. The histogenesis in relation to its structure is discussed.


Strategies to optimize aged care volunteer recruitment and retention: A systematic review.
Population aging and resource constraints in aged care indicate an ever increasing need for volunteers in this growing sector. Volunteers in aged care have different expectations and experiences, as they typically form longer and closer relationships with residents, and perform important social support functions that may otherwise not be delivered. Tailored strategies to recruit and retain these volunteers are needed. The aims of this review were to identify the motivations and expectations of aged care volunteers, and to examine strategies that foster their recruitment, retention and role satisfaction. A systematic review of MEDLINE, PsycINFO, CINAHL, Embase and Cochrane Library was conducted. Selection criteria included qualitative and quantitative studies published in English, with no date restrictions. Volunteering roles were restricted to residential aged care services. The 18 studies eligible for review presented consistently strong themes across volunteer motivation, recruitment/retention, and satisfaction/involvement. Implications for policy and practice relate to the importance of setting clear role expectations, matching volunteers' skills with roles, ongoing training and support, and the need for operational frameworks that support volunteers with administrative processes, communication and complaint resolution. Improved volunteer management that enables the consistent provision of social support in this setting stands to improve residents' quality of life.


Nutritional assessment of residents in long-term care facilities (LTCFs): recommendations of the task force on nutrition and ageing of the IAGG European region and the IANA.
Unintentional weight loss and Undernutrition are major problems among older people living in Long-Term Care Facilities (LTCF). Undernutrition manifests in LTCF particularly as weight loss and low Body Mass Index (BMI) and is associated with increased morbidity and mortality as well as with functional decline. There are many factors associated with poor nutritional status and affecting protein-energy intake and/or energy expenditure. These include age of 85 years or older, low nutrient intake, loss of ability to eat independently, swallowing and chewing difficulties, becoming bed-ridden, pressure ulcers, history of hip fracture, dementia, depressive symptoms and suffering from two or more chronic illnesses. Nutritional evaluation is an essential part of the Comprehensive Geriatric Assessment (CGA). This evaluation ranges from methods such as BMI to several validated tools such as Mini-Nutritional Assessment (MNA). After diagnosis, the management of undernutrition in LTCF requires a multidisciplinary approach which may involve dietary and environmental improvements and managing multiple co-morbidities, while avoiding polypharmacy as far as possible. Finally, the need for supplementation or artificial (tube) feeding may be considered taking into account the CGA and individual needs. This document presents a succinct review and recommendations of evaluation and treatment of undernutrition.


Altered GH-IGF-1 Axis in Severe Obese Subjects is Reversed after Bariatric Surgery-Induced Weight Loss and Related with Low-Grade Chronic Inflammation.
Endocrine disorders are common in obesity, including altered somatotropic axis. Obesity is characterized by reduced growth hormone (GH) secretion, although the insulin-like growth factor-1 (IGF-1) values are controversial. The aim of this study was to evaluate the effect of weight loss after bariatric surgery in the GH-IGF-1 axis in extreme obesity, in order to investigate IGF-1 values and the mechanism responsible for the alteration of the GH-IGF-1 axis in obesity. We performed an interventional trial in morbidly obese patients who underwent bariatric surgery. We included 116 patients (97 women) and 41 controls (30 women). The primary endpoint was circulating GH and IGF-1 values. Circulating IGF-1 values were lower in the obese patients than in the controls. Circulating GH and IGF-1 values increased significantly over time after surgery. Post-surgery changes in IGF-1 and GH values were significantly negatively correlated with changes in C-reactive protein (CRP) and free T4 values. After adjusting for preoperative body mass index (BMI), free T4 and CRP in a multivariate model, only CRP was independently associated with IGF-1 values in the follow-up. In summary, severe obesity is characterized by a functional hyposomatotropism at central and peripheral level that is progressively reversible with weight loss, and low-grade chronic inflammation could be the principal mediator.


Treatment of acute herpes zoster with amantadine hydrochloride (Symmetrel).
A double-blind, placebo-controlled trial of amantadine hydrochloride (Symmetrel) in acute herpes zoster (shingles) was carried out in 100 patients in general practice. The cases were serologically proved. There was no difference in duration of pain between the drug and placebo groups when pain disappeared during the 28 days' observation period. However, pain lasted more than 28 days in a significantly greater proportion of patients receiving placebo than of those on amantadine. Patients with pain after the 28-day observation period were significantly older than those whose pain disappeared during the study. The drug had no effect on rate of healing or appearance of new lesions.


AnSBBR applied to a personal care industry wastewater treatment: effects of fill time, volume treated per cycle, and organic load.
A study was performed regarding the effect of the relation between fill time, volume treated per cycle, and influent concentration at different applied organic loadings on the stability and efficiency of an anaerobic sequencing batch reactor containing immobilized biomass on polyurethane foam with recirculation of the liquid phase (AnSBBR) applied to the treatment of wastewater from a personal care industry. Total cycle length of the reactor was 8 h (480 min). Fill times were 10 min in the batch operation, 4 h in the fed-batch operation, and a 10-min batch followed by a 4-h fed batch in the mixed operation. Settling time was not necessary since the biomass was immobilized and decant time was 10 min. Volume of liquid medium in the reactor was 2.5 L, whereas volume treated per cycle ranged from 0.88 to 2.5 L in accordance with fill time. Influent concentration varied from 300 to 1,425 mg COD/L, resulting in an applied volumetric organic load of 0.9 and 1.5 g COD/L.d. Recirculation flow rate was 20 L/h, and the reactor was maintained at 30 °C. Values of organic matter removal efficiency of filtered effluent samples were below 71% in the batch operations and above 74% in the operations of fed batch followed by batch. Feeding wastewater during part of the operational cycle was beneficial to the system, as it resulted in indirect control over the conversion of substrate into intermediates that would negatively interfere with the biochemical reactions regarding the degradation of organic matter. As a result, the average substrate consumption increased, leading to higher organic removal efficiencies in the fed-batch operations.


Traumatic joint luxations in cats: Reduce, repair, replace, remove.
Traumatic joint luxations are usually associated with significant trauma and there may be concomitant systemic injury. Joints are unstable as a result of injury to one or more supporting structures and the clinician should aim to determine which structures are damaged with physical examination, diagnostic imaging and careful assessment under sedation/anaesthesia. The aim is to reduce the joint back to its anatomical position, and then to maintain this through repair of damaged structures. However, where this is not possible, replacement or removal (arthrodesis/excision arthroplasty) of the joint remain viable options. Owing to the small size of feline joints and the severity of damage often seen, surgical management of these cases can be challenging. The first priority is to ensure the patient is systemically well before embarking on any specific surgical treatment of a luxated joint. Cats also present challenges in the postoperative period and a lack of patient and owner compliance can be detrimental to postoperative outcomes. This article aims to help the reader diagnose joint luxations and to assist decision-making with an overview of the management and treatment options available. There are a number of original articles and textbook chapters in the literature covering aspects of different joint luxations, particularly for the more common luxations. This article draws on information from key feline research and, where necessary, extrapolates from relevant canine research. The authors also offer practical guidance based on their own clinical experience.


Gene expression variation between mouse inbred strains.
In this study, we investigated the effect of genetic background on expression profiles. We analysed the transcriptome of mouse hindlimb muscle of five frequently used mouse inbred strains using spotted oligonucleotide microarrays. Through ANOVA analysis with a false discovery rate of 10%, we show that 1.4% of the analysed genes is significantly differentially expressed between these mouse strains. Differential expression of several of these genes has been confirmed by quantitative RT-PCR. The number of genes affected by genetic background is approximately ten-fold lower than the number of differentially expressed genes caused by a dystrophic genetic defect. We conclude that evaluation of the effect of background on gene expression profiles in the tissue under study is an effective and sensible approach when comparing expression patterns in animal models with heterogeneous genetic backgrounds. Genes affected by the genetic background can be excluded in subsequent analyses of the disease-related changes in expression profiles. This is often a more effective strategy than backcrossing and inbreeding to obtain isogenic backgrounds.


Resolving the backbone tilt of crystalline poly(3-hexylthiophene) with resonant tender X-ray diffraction.
The way in which conjugated polymers pack in the solid state strongly affects the performance of polymer-based optoelectronic devices. However, even for the most crystalline conjugated polymers the precise packing of chains within the unit cell is not well established. Here we show that by performing resonant X-ray diffraction experiments at the sulfur K-edge we are able to resolve the tilting of the planar backbones of crystalline poly(3-hexylthiophene) (P3HT) within the unit cell. This approach exploits the anisotropic nature of the X-ray optical properties of conjugated polymers, enabling us to discern between different proposed crystal structures. By comparing our data with simulations based on different orientations, a tilting of the planar conjugated backbone with respect to the side chain stacking direction of 30 ± 5° is determined.


Analysis of the Functioning of Families of Children with Autism Spectrum Disorder: A Psychometric Study of the Family APGAR Scale.
Normalised family functioning is a predictor of individual well-being. The diagnosis of a family member with autism spectrum disorder (ASD) can alter the ordinary dynamics of family systems, having a variable impact on family functioning. This research employed a non-probability convenience sampling method to gather a sample of 327 families with and without children diagnosed with ASD. This study has dual objectives: to analyse the psychometric properties of the Spanish version of the Family APGAR Scale and to compare family functioning in families with and without a child with ASD. The results reveal several favourable psychometric properties in the application of the APGAR scale within families of children with ASD. The use of the Family APGAR Scale in the selected sample confirms that the functioning of families with children with ASD can be categorized as mildly dysfunctional, attributed to the inherent challenges in caring for and raising a child with ASD. The presence of ASD within family systems presents a challenge to typical family functioning, with significant differences observed between families with and without children with ASD. This underscores the necessity of implementing effective intervention programs based on empirical evidence to improve the quality of life for individuals with ASD and their families.


Overproduction and elimination of retinal axons in the fetal rhesus monkey.
Quantitative electron microscopic analysis reveals 2.85 million retinal axons in fetal rhesus monkeys--a number that is more than twice the 1.2 million present in the adult. More than 1 million supernumerary optic axons are eliminated before birth, simultaneously with the segregation of inputs from the two eyes into separate layers of the lateral geniculate nucleus. Selective elimination of optic axons may not only play a role in the segregation of binocular visual connections but, secondarily, may establish the ratio of crossed and uncrossed retinogeniculate projections.


Visual acuity and contrast sensitivity in patients with cerebral lesions.
Spatial contrast sensitivity as a function of spatial frequency was measured in patients with cerebral lesions. In most of these patients visual acuity, as measured by the Snellen chart, was 20/30 or better, yet marked departures from normal contrast sensitivity were found. The greatest loss in contrast sensitivity occurred at high frequencies, but in one patient the loss was greatest in the midfrequency range. This finding lends support to the channel hypothesis of spatial contrast discrimination.


Prenatal assessment of ventriculocoronary connections and ventricular endocardial fibroelastosis in hypoplastic left heart.
The outlook for newborns with hypoplastic left heart (HLH) has substantially improved over the last decade. However, differences in outcome among various anatomical subgroups have been described. We aimed to describe the incidence of ventriculocoronary communications and endocardial fibroelastosis in HLH and the possible implication on hospital survival (30 d). We retrospectively reviewed our medical records, still frames and video loops of 72 fetuses with HLH and critical aortic valve stenosis and evolving HLH from 2008 - 2013. The presence of VCAC and EFE were systematically assessed. Outcome parameters were incidence of VCAC and EFE among different anatomical subgroups of HLH and hospital survival (30 d). 72 fetuses were included in this series. The incidence of VCAC was 11.1 % (8 cases) and EFE occurred in 33.3 % (24 cases). 5 fetuses with VCAC occurred in the subgroup of mitral valve stenosis/aortic valve atresia (MS/AA, 62.5 %) and 2 fetuses with VCAC occurred in the group of mitral atresia/aortic valve atresia (MA/AA, 25 %). Further classification was not possible in one case with VCAC (12.5 %). EFE predominantly occurred in the subgroup of MS/AA, MA/AA and in those cases with aortic valve stenosis and evolving HLH. The overall hospital survival on an intention-to-treat basis was 91.2 % (52/57 newborns). Hospital survival was 91 % for the subgroup of cases with MS/AA and for all other anatomical subgroups. The presence of VCAC in HLH can be diagnosed by fetal echocardiography predominantly occurring in cases with obstructed outflow and to some extent patent mitral valve. EFE is a frequent coexisting finding. Hospital survival was comparable among different anatomical subgroups and in cases with VCAC. The presence of VCAC in HLH did not limit the results of surgical palliation within the observation period of 30 days.


A systematic review of food deserts, 1966-2007.
"Food deserts," areas characterized by poor access to healthy and affordable food, may contribute to social and spatial disparities in diet and diet-related health outcomes. However, the extent to which food deserts exist is debated. We review the evidence for the existence of food deserts in socioeconomically disadvantaged areas. We conducted a systematic review of primary, quantitative, observational studies, published in English or French, that used geographic or market-basket approaches in high-income countries. The literature search included electronic and hand searches and peer-reviewed and grey literature from 1966 through 2007. We also contacted key researchers to identify other studies. We analyzed the findings and quality of the studies qualitatively. Forty-nine studies in 5 countries met inclusion criteria; the amount and consistency of the evidence varied by country. These studies were a mix of geographic and market-basket approaches, but the methodologic quality of studies and completeness of reported findings were mixed. We found clear evidence for disparities in food access in the United States by income and race. Findings from other high-income countries were sparse and equivocal. This review suggests that food deserts exist in the United States, where area-level deprivation compounds individual disadvantage. Evidence for the existence of food deserts in other high-income nations is weak.


BMP-2/-4 and Wnt-8 cooperatively pattern the Xenopus mesoderm.
Establishment of the dorsoventral axis is central to animal embryonic organization. In Xenopus two different classes of signaling molecules function in the dorsoventral patterning of the mesoderm. Both the TGF-beta-related products of the BMP-2 and BMP-4 genes and the Wnt molecule encoded by Xenopus Wnt-8 specify ventral fate and appear to inhibit dorsal mesodermal development. The similar functions of these molecularly very different classes of signaling molecules prompted us to study their mutual regulation and to closely compare their roles in mesoderm patterning. We find that Wnt-8 and BMP-4 are indistinguishable in their abilities to induce expression of ventral genes. Although BMP-2/-4 signaling regulates Wnt-8 expression, these genes do not function in a linear pathway because Wnt-8 overexpression cannot compensate for an inhibition of BMP-2/-4 function, but rather BMP-4 overexpression rescues ventral gene expression in embryos with inhibited Wnt-8 function. We further find that Wnt-8 and BMP-2/-4 differ in their abilities to regulate dorsal gene expression. While BMP-4 appears to generally inhibit the expression of dorsal genes, XenopusWnt-8 only inhibits the expression of the notochord marker Xnot. Whereas the inhibitory effect of BMP-2/-4 localizes dorsal mesodermal fate, our results suggest that Xenopus Wnt-8 functions in the further patterning of the dorsal mesoderm into the most dorsal sector from which the notochord develops and the dorsolateral sector from where the somites differentiate.


Delayed Effect of Blood Flow-restricted Resistance Training on Rapid Force Capacity.
The aim of the present study was to investigate the effect and time course of high-frequent low-load blood flow-restricted (BFR) resistance training on rapid force capacity (i.e., rate of torque development [RTD]). Ten male subjects (22.8 ± 2.3 yr) performed four sets of knee extensor exercise (20% one-repetition maximum) to concentric failure during concurrent BFR of the thigh (100 mm Hg), and eight work-matched controls (21.9 ± 3.0 yr) trained without BFR (CON). Twenty-three training sessions were performed within 19 d. Maximal slow and fast knee joint velocity muscle strength and rapid force capacity (e.g., RTD) and evoked twitch contractile parameters were assessed before (Pre) and 5 and 12 d after (Post5 and Post12) training. Muscle biopsies were obtained Pre, after 8 d (Mid8), and 3 and 10 d after (Post3 and Post10) training to examine changes in myofiber area and expression of myocellular proteins known to be modified by cellular stress (CaMKII, annexin A6, SNO-CYS). RTD remained unchanged after BFR training at Post5, while increasing 15%-20% Post12 (P < 0.01). Evoked muscle twitch parameters showed a general decline Post5 (P < 0.01) while returning to baseline levels at Post12. All contractile parameters essentially remained unchanged in CON. Elevated CaMKII was observed with BFR training at Post3 (57%) and Post10 (71%) (P < 0.05), whereas SNO-CYS increased in CON at Mid8 (P < 0.05). This study is the first to show that low-load resistance exercise performed with BFR leads to marked increases in rapid force capacity (RTD). However, a general delayed adaptive response was observed for voluntary contractile parameters (including RTD) in parallel with a decline and subsequent recovery in evoked contractile properties, suggesting the delayed gain in rapid force capacity mainly have a peripheral origin.


The corepressor CTBP2 is a coactivator of retinoic acid receptor/retinoid X receptor in retinoic acid signaling.
Retinoids play key roles in development, differentiation, and homeostasis through regulation of specific target genes by the retinoic acid receptor/retinoid X receptor (RAR/RXR) nuclear receptor complex. Corepressors and coactivators contribute to its transcriptional control by creating the appropriate chromatin environment, but the precise composition of these nuclear receptor complexes remains to be elucidated. Using an RNA interference-based genetic screen in mouse F9 cells, we identified the transcriptional corepressor CTBP2 (C-terminal binding protein 2) as a coactivator critically required for retinoic acid (RA)-induced transcription. CTBP2 suppression by RNA interference confers resistance to RA-induced differentiation in diverse murine and human cells. Mechanistically, we find that CTBP2 associates with RAR/RXR at RA target gene promoters and is essential for their transactivation in response to RA. We show that CTBP2 is indispensable to create a chromatin environment conducive for RAR/RXR-mediated transcription by recruiting the histone acetyltransferase p300. Our data reveal an unexpected function of the corepressor CTBP2 as a coactivator for RAR/RXR in RA signaling.


Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis.
Canine degenerative myelopathy (DM) is a fatal neurodegenerative disease prevalent in several dog breeds. Typically, the initial progressive upper motor neuron spastic and general proprioceptive ataxia in the pelvic limbs occurs at 8 years of age or older. If euthanasia is delayed, the clinical signs will ascend, causing flaccid tetraparesis and other lower motor neuron signs. DNA samples from 38 DM-affected Pembroke Welsh corgi cases and 17 related clinically normal controls were used for genome-wide association mapping, which produced the strongest associations with markers on CFA31 in a region containing the canine SOD1 gene. SOD1 was considered a regional candidate gene because mutations in human SOD1 can cause amyotrophic lateral sclerosis (ALS), an adult-onset fatal paralytic neurodegenerative disease with both upper and lower motor neuron involvement. The resequencing of SOD1 in normal and affected dogs revealed a G to A transition, resulting in an E40K missense mutation. Homozygosity for the A allele was associated with DM in 5 dog breeds: Pembroke Welsh corgi, Boxer, Rhodesian ridgeback, German Shepherd dog, and Chesapeake Bay retriever. Microscopic examination of spinal cords from affected dogs revealed myelin and axon loss affecting the lateral white matter and neuronal cytoplasmic inclusions that bind anti-superoxide dismutase 1 antibodies. These inclusions are similar to those seen in spinal cord sections from ALS patients with SOD1 mutations. Our findings identify canine DM to be the first recognized spontaneously occurring animal model for ALS.


The association of iron and manganese with bacteria on marine macroparticulate material.
Evidence of in situ metal (iron and manganese) deposition onto bacteria associated with rapidly sinking particles in the open ocean is reported. Below 100 meters, bacteria are found with extracellular capsules containing metal precipitates; the frequency of these capsules increases with depth. The capsular metal deposits appear to contribute a major portion of the weakly bound fraction of the particulate iron flux.


Selectively desulfated heparin inhibits fibroblast growth factor-induced mitogenicity and angiogenesis.
Fibroblast growth factors (FGFs) are known to induce formation of new blood vessels, angiogenesis. We show that FGF-induced angiogenesis can be modulated using selectively desulfated heparin. Chinese hamster ovary cells (CHO677) deficient in heparan sulfate biosynthesis were employed to assess the function of heparin/heparan sulfate in FGF receptor-1 (FGFR-1) signal transduction and biological responses. In the presence of FGF-2, FGFR-1 kinase and subsequent mitogen-activated protein kinase Erk2 activities were augmented in a dose-dependent manner, whereas high concentrations of heparin resulted in decreased activity. The length of the heparin oligomer, minimally an 8/10-mer, was critical for the ability to enhance FGFR-1 kinase activity. The N- and 2-O-sulfate groups of heparin were essential for binding to FGF-2, whereas stimulation of FGFR-1 and Erk2 kinases by FGF-2 also required the presence of 6-O-sulfate groups. Sulfation at 2-O- and 6-O-positions was moreover a prerequisite for binding of heparin to a lysine-rich peptide corresponding to amino acids 160-177 in the extracellular domain of FGFR-1. Selectively 6-O-desulfated heparin, which binds to FGF-2 but fails to bind the receptor, decreased FGF-2-induced proliferation of CHO677 cells, presumably by displacing intact heparin. Furthermore, FGF-2-induced angiogenesis in chick embryos was inhibited by 6-O-desulfated heparin. Thus, formation of a ternary complex of FGF-2, heparin, and FGFR-1 appears critical for the activation of FGFR-1 kinase and downstream signal transduction. Preventing complex formation by modified heparin preparations may allow regulation of FGF-2 functions, such as induction of angiogenesis.


A molecular-based estimation of the prevalence of hypophosphatasia in the European population.
The prevalence of hypophosphatasia (HP), a rare metabolic disorder due to loss-of-function mutations in the ALPL gene, has never been estimated in the European population. Only one published study evaluated the incidence of severe HP at 1/100,000 in Canada 53 years ago. Moderate forms of hypophosphatasia (mHP), including HP with moderate bone features and the mildest form odontohypophosphatasia, reflect both recessive and dominant inheritance, and are therefore expected to be more frequent than severe forms of HP. Here we estimated both the prevalences of severe and mHP in European populations. The prevalence of severe HP was estimated at 1/300,000 on the basis of the number of cases tested in our laboratory and originating from France during the period 2000-2009. The prevalence of mHP was then estimated by using the proportion of dominant mutations among severe alleles and by estimating the penetrance of the disease in heterozygotes for dominant mutations. According to a genetic model with four alleles resulting in 10 distinct genotypes, the prevalence of dominant mHP in the European population was estimated to be 1/6370, pointing out that mHP is much more frequent than severe HP.


Role of collagen-binding heat shock protein 47 and transforming growth factor-beta1 in conjunctival scarring in ocular cicatricial pemphigoid.
Submucosal fibrosis due to excessive accumulation of collagens is an important histologic feature in the pathogenesis of ocular cicatricial pemphigoid (OCP). Heat shock protein 47 (HSP47), a collagen-binding protein, plays an important role in the biosynthesis of procollagens. In the present study, we examined the role of HSP47 in conjunctival scarring in patients with OCP. Biopsy specimens of the conjunctiva of 15 patients with OCP and 5 normal subjects were studied for the expression of HSP47, transforming growth factor (TGF)-beta1, type I collagen, and type III collagen. The role of TGF-beta1 on the induction of HSP47 and type I collagen by conjunctival fibroblasts was studied by immunostaining, Western blot analysis, and quantitative real-time PCR. Compared with the control, increased accumulations of type I and type III collagens were detected by immunohistochemistry in fibrotic conjunctiva of patients with OCP. Weak and sparse expression of HSP47 was detected in the epithelial cells and stromal fibroblasts in control conjunctival tissues. In contrast to the control, the expression of HSP47 was markedly increased in the stromal fibroblasts in conjunctival tissues obtained from patients with OCP, as detected by immunohistochemistry. By quantitative real-time PCR, compared with control conjunctival tissues, a 3.4-fold increase in the expression of HSP47 was noted in the conjunctival tissues obtained from patients with OCP. Similar to conjunctival tissues, fibroblasts isolated from conjunctiva of patients with OCP exhibited 4.8-fold increase in the expression of HSP47, compared with control fibroblasts. When conjunctival fibroblasts were treated with various concentration of TGF-beta1, upregulation in the expression of HSP47 and type I collagen was detected. This study demonstrated increased expression of HSP47 and TGF-beta1 by conjunctival fibroblasts in biopsy specimens obtained from patients with OCP. TGF-beta1 induced the expression of HSP47 and type I collagen by conjunctival fibroblasts. Increased levels of TGF-beta1 and HSP47 may regulate increased synthesis, assembly, and production of collagens and thereby could significantly contribute to the process of conjunctival scarring in patients with OCP.


Likelihood-based clustering (LiBaC) for codon models, a method for grouping sites according to similarities in the underlying process of evolution.
Models of codon evolution are useful for investigating the strength and direction of natural selection via a parameter for the nonsynonymous/synonymous rate ratio (omega = d(N)/d(S)). Different codon models are available to account for diversity of the evolutionary patterns among sites. Codon models that specify data partitions as fixed effects allow the most evolutionary diversity among sites but require that site partitions are a priori identifiable. Models that use a parametric distribution to express the variability in the omega ratio across site do not require a priori partitioning of sites, but they permit less among-site diversity in the evolutionary process. Simulation studies presented in this paper indicate that differences among sites in estimates of omega under an overly simplistic analytical model can reflect more than just natural selection pressure. We also find that the classic likelihood ratio tests for positive selection have a high false-positive rate in some situations. In this paper, we developed a new method for assigning codon sites into groups where each group has a different model, and the likelihood over all sites is maximized. The method, called likelihood-based clustering (LiBaC), can be viewed as a generalization of the family of model-based clustering approaches to models of codon evolution. We report the performance of several LiBaC-based methods, and selected alternative methods, over a wide variety of scenarios. We find that LiBaC, under an appropriate model, can provide reliable parameter estimates when the process of evolution is very heterogeneous among groups of sites. Certain types of proteins, such as transmembrane proteins, are expected to exhibit such heterogeneity. A survey of genes encoding transmembrane proteins suggests that overly simplistic models could be leading to false signal for positive selection among such genes. In these cases, LiBaC-based methods offer an important addition to a "toolbox" of methods thereby helping to uncover robust evidence for the action of positive selection.


Professional abuse of children: Responsibility for the delivery of services.
Determination of which children will receive or be excluded from services, as well as the nature and extent of those services is largely the province of professionals. This paper examines the responsibility of professionals and social service agencies for the delivery - and denial-of services to children,discusses children's rights, and examines the role and oligation of professionals in the resolution of larger social issues.


Percutaneous Electrical Neurostimulation of Dermatome T6 for Short-term Weight Loss in Overweight and Obese Patients: Effect on Ghrelin Levels, Glucose, Lipid, and Hormonal Profile.
Percutaneous electrical neurostimulation of dermatome T6 (PENS T6), associated with a low-caloric diet, has previously demonstrated to achieve a reduction in the appetite perception, inducing a better compliance of the prescribed diet and finally leading to a greater weight loss. Ghrelin has been hypothesized to be implicated in the effect of PENS T6. The aim of this study was to evaluate the effect of PENS T6 with hypocaloric diet on appetite, weight loss and dietary compliance, and its association with plasma ghrelin levels, in comparison with PENS T6 associated with normocaloric diet, transcutaneous electrical neurostimulation of T11-T12 (placebo) with hypocaloric diet, and only hypocaloric diet. A prospective, randomized study was performed. Patients with body mass index >25 kg/m were included. The subjects were randomized into 4 groups: patients undergoing PENS T6 in conjunction with a 1200 kcal/d diet (group 1). Patients undergoing PENS T6 and following a normocaloric diet (group 2), patients undergoing transcutaneous electrical neurostimulation of dermatomes in right iliac fossa (T11-T12) and following a 1200 kcal/d diet(group 3) and those patients following only a 1200 kcal/d diet (group 4). A total of 200 patients were included, 50 in each group. A significantly greater weight loss was obtained in patients following PENS T6 combined with diet, when compared with the other groups. Patients undergoing PENS T6, associated or not to hypocaloric diet, experienced appetite reduction and lower ghrelin levels, when compared with the other groups. The greater weight loss experienced in the patients undergoing PENS T6 is associated with appetite reduction and greater diet compliance. Appetite reduction is associated with ghrelin decrease.


The mitochondrial 12S gene is a suitable marker of populations of Sarcoptes scabiei from wombats, dogs and humans in Australia.
We sequenced part of the mitochondrial 12S ribosomal RNA gene of 23 specimens of Sarcoptes scabiei from eight wombats, one dog and three humans. Twelve of the 326 nucleotide positions varied among these mites and there were nine haplotypes (sequences) that differed by 1-8 nucleotides. Phylogenetic analyses indicated that these mites were from two lineages: (1) mites from wombats from Victoria, Australia, and mites from the humans and dog from the Northern Territory, Australia (haplotypes 1-4, 9); and (2) mites from the humans and dog from the Northern Territory (haplotypes 5-8). Mites from the three different hosts (wombats, a dog and humans) had not diverged phylogenetically; rather, these mites had similar 12S sequences. Thus, we conclude that these mites from wombats, humans and a dog are closely related, and that they diverged from a common ancestor relatively recently. This conclusion is consistent with the argument that people and/or their dogs introduced to Australia the S. scabiei mites that infect wombats in Australia . So, S. scabiei, which has been blamed for the extinction of populations of wombats in Australia, may be a parasitic mite that was introduced to Australia with people and/or their dogs. These data show that the mitochondrial 12S rRNA gene may be a suitable population marker of S. scabiei from wombats, dogs and humans in Australia.


Glomerular structure in lithium-induced chronic renal failure in rats.
The effects of long-term lithium administration on glomerular structure and intervention with angiotensin converting enzyme inhibitor (ACEI) were studied in rats. Male Wistar rats were fed a lithium-containing diet (Li) or control diet (C) for 16 weeks postnatally. Li-treated rats developed renal failure, hypertension and proteinuria. During the subsequent 24 weeks, subgroups were treated with ACEI. The kidneys were fixed by perfusion, and tissue blocks were serially cut for estimation of glomerular volume and glomerular characteristics by light microscopy. Mesangial and mesangial matrix volume fractions, surface density of capillary walls, basement membrane thickness and foot process width (FPW) were measured by electron microscopy. Glomerular volume was decreased in Li-rats, with increased intra-individual variation. In all Li-rats, some glomeruli (mean 27%) were abnormal, with severe changes in only three rats. Ultrastructural parameters obtained by systematic sampling of three glomeruli in each rat showed no differences among groups. Among Li-treated animals there was a significant correlation between FPW and albumin excretion per unit filtration surface, and between filtration surface per glomerulus and inulin clearance. In conclusion, long-term lithium administration to newborn rats caused marked changes in glomerular volume which were not associated with measurable changes in structural parameters. No effect of ACEI-treatment was detectable.


In Vitro and In Vivo Antioxidant Properties of Taraxacum officinale in Nω-Nitro-l-Arginine Methyl Ester (L-NAME)-Induced Hypertensive Rats.
Oxidative stress has gained attention as one of the fundamental mechanisms responsible for the development of hypertension. The present study investigated in vitro and in vivo antioxidant effects of 70% ethanol-water (v/v) leaf and root extracts of T. officinale (TOL and TOR, respectively). Total phenolic and flavonoid content of plant extracts were assessed using Folin Ciocalteau and aluminium chloride colorimetric methods; while, 2,2-diphenyl-1-picrlhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) protocols were used to determine the free radical scavenging and total antioxidant capacities (TAC), respectively. The in vivo total antioxidant capacity and malondialdehyde acid (MDA) levels for lipid peroxidation tests were performed on organ homogenate samples from Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats treated with leaf extract, TOL (500 mg/kg/day) and TOR (500 mg/kg/day) for 21 days. Results showed that compared to TOR, TOL possessed significantly higher (p < 0.01) polyphenol (4.35 ± 0.15 compared to 1.14 ± 0.01) and flavonoid (23.17 ± 0.14 compared to 3 ± 0.05) content; free radical scavenging activity (EC50 0.37 compared to 1.34 mg/mL) and total antioxidant capacities (82.56% compared to 61.54% ABTS, and 156 ± 5.28 compared to 40 ± 0.31 FRAP) and both extracts showed no toxicity (LD50 > 5000 mg/kg). TOL and TOR significantly (p < 0.01) elevated TAC and reduced MDA levels in targets organs. In conclusion, T. officinale leaf extract possesses significant anti-oxidant effects which conferred significant in vivo antioxidant protection against free radical-mediated oxidative stress in L-NAME-induced hypertensive rats.


[Anatomical description of the anterior hip approach: safety and effect for total arthroplasty].
The anterior hip approach was described since 1881, since then several studies have been conducted that have shown significant advantages over the posterior and lateral direct approaches of the hip. We conducted a descriptive study with continuous non-probabilistic cases at the Institute of Forensic Sciences from October 2015 to July 2017. Anatomy and distances were described to the neurovascular bundles. Correlation of Spearmans Pearson and Rho was performed. 22 dissections were made, the Femorocutaneous Nerve was identified in 9 specimens, the average lateral Femorocutaneous Nerve distance at Smith-Petersen interval was 11.4 mm, We identified the Ascending Lateral Circumflex artery under the femoral rectum towards the central region of the approach, the separators could be placed around the coxofemoral joint without injuring vital structures, the riskier separator we place it in the anterior wall of the acetabulum, below the Psoasyland with an average distance 28.25 mm to the femoral package. The older you go, the longer the neurovascular bundles were located p 0.05. High level of safety of the previous approach for hip replacement, distances to vital structures have a reasonable margin, hip replacement offers adequate joint exposure, direct acetabulum vision and atraumatic surgical dissection.


Acrylamide inhibits autophagy, induces apoptosis and alters cellular metabolic profiles.
Acrylamide (ACR) is generated during thermal processing of carbohydrate-rich foods at high temperature and can directly enter the body through ingestion, inhalation and skin contact. The toxicity of ACR has been widely studied. The main results of these studies show that exposure to ACR can cause neurotoxicity in both animals and humans, and show reproductive toxicity and carcinogenicity in rodent animal models. However, the mechanism of toxicity of ACR has not been studied by metabolomics approaches, and the effect of ACR on autophagy remains unknown. Here, U2OS cell were treated with ACR 6 and 24 h and collected for further study. We have demonstrated that ACR inhibited autophagic flux, and increased ROS content. Accumulation of ROS resulted in increase of apoptosis rates and secretion of inflammatory factors. In addition, significant differences in metabolic profiles were observed between ACR treated and control cells according to multiple analysis models. A total of 73 key differential metabolites were identified. They were involved in multiple metabolic pathways. Among them, exposure to ACR caused glycolysis/gluconeogenesis attenuation by decreasing levels of glycolytic intermediates, reduced the rate of the TCA cycle, while elevating levels of several amino acid metabolites and lipid metabolites. In summary, our study provides useful evidence of cytotoxicity caused by ACR via metabolomics and multiple bioanalytic methods.


Cobalt Ferrite Nanoparticles for Tumor Therapy: Effective Heating versus Possible Toxicity.
Magnetic nanoparticles (MNPs) are widely considered for cancer treatment, in particular for magnetic hyperthermia (MHT). Thereby, MNPs are still being optimized for lowest possible toxicity on organisms while the magnetic properties are matched for best heating capabilities. In this study, the biocompatibility of 12 nm cobalt ferrite MNPs, functionalized with citrate ions, in different dosages on mice and rats of both sexes was investigated for 30 days after intraperitoneal injection. The animals' weight, behavior, and blood cells changes, as well as blood biochemical parameters are correlated to histological examination of organs revealing that cobalt ferrite MNPs do not have toxic effects at concentrations close to those used previously for efficient MHT. Moreover, these MNPs demonstrated high specific loss power (SLP) of about 400 W g-1. Importantly the MNPs retained their magnetic properties inside tumor tissue after intratumoral administration for several MHT cycles within three days. Thus, cobalt ferrite MNPs represent a perspective platform for tumor therapy by MHT due to their ability to provide effective heating without exerting a toxic effect on the organism. This opens up new avenues for smaller MNPs sizes while their heating efficiency is maintained.


Mutagenicity studies with urine concentrates from coke plant workers.
Urine from coke plant workers, collected before and after work, were tested for the content of mutagenic substances in the Salmonella test system. Urine extracts from exposed smokers showed mutagenic activity, whereas urine from exposed nonsmokers did not. The mutagenicity of exposed smoker's urine was not significantly different from that of urine from nonexposed smokers. Mutagenicity of smokers' urine was only evident in the presence of a rat liver metabolic activation system. The addition of beta-glucuronidase did not enhance the mutagenic effect. The facts that coke plant workers are exposed to very high levels of polycyclic aromatic hydrocarbons (PAH) and that there is no observed enhanced mutagenicity of their urine indicate that the mutagenicity observed with urine from smokers is not due to conventional PAH.


Prediction of DNA-binding residues from sequence.
Thousands of proteins are known to bind to DNA; for most of them the mechanism of action and the residues that bind to DNA, i.e. the binding sites, are yet unknown. Experimental identification of binding sites requires expensive and laborious methods such as mutagenesis and binding essays. Hence, such studies are not applicable on a large scale. If the 3D structure of a protein is known, it is often possible to predict DNA-binding sites in silico. However, for most proteins, such knowledge is not available. It has been shown that DNA-binding residues have distinct biophysical characteristics. Here we demonstrate that these characteristics are so distinct that they enable accurate prediction of the residues that bind DNA directly from amino acid sequence, without requiring any additional experimental or structural information. In a cross-validation based on the largest non-redundant dataset of high-resolution protein-DNA complexes available today, we found that 89% of our predictions are confirmed by experimental data. Thus, it is now possible to identify DNA-binding sites on a proteomic scale even in the absence of any experimental data or 3D-structural information. http://cubic.bioc.columbia.edu/services/disis.


Microinjection of Antibodies Targeting the Lamin A/C Histone-Binding Site Blocks Mitotic Entry and Reveals Separate Chromatin Interactions with HP1, CenpB and PML.
Lamins form a scaffold lining the nucleus that binds chromatin and contributes to spatial genome organization; however, due to the many other functions of lamins, studies knocking out or altering the lamin polymer cannot clearly distinguish between direct and indirect effects. To overcome this obstacle, we specifically targeted the mapped histone-binding site of A/C lamins by microinjecting antibodies specific to this region predicting that this would make the genome more mobile. No increase in chromatin mobility was observed; however, interestingly, injected cells failed to go through mitosis, while control antibody-injected cells did. This effect was not due to crosslinking of the lamin polymer, as Fab fragments also blocked mitosis. The lack of genome mobility suggested other lamin-chromatin interactions. To determine what these might be, mini-lamin A constructs were expressed with or without the histone-binding site that assembled into independent intranuclear structures. HP1, CenpB and PML proteins accumulated at these structures for both constructs, indicating that other sites supporting chromatin interactions exist on lamin A. Together, these results indicate that lamin A-chromatin interactions are highly redundant and more diverse than generally acknowledged and highlight the importance of trying to experimentally separate their individual functions.


Applied strategy in the Iowa Gambling Task: Comparison of individuals with Parkinson's disease to healthy controls.
Decision-making impairments in Parkinson's disease (PD) have frequently been measured using the Iowa Gambling Task (IGT), though results have been inconsistent. At present, task performance has primarily been evaluated based on the total IGT score, and there is a need for further analysis of the strategy of older individuals with PD and healthy control (HC) participants in IGT. The present study aims to explore possible impairments in IGT performance in individuals with PD compared to healthy controls using strategy analysis, extending previous results on this subject, and to discuss potential effects of medication on task performance. 67 individuals with PD and 29 HC participants completed the IGT. Results were analyzed to evaluate impairments, applied strategies, presence of subgroups, and potential effects of medication on performance. Both groups obtained a low overall IGT score and individuals with PD had significantly lower total IGT scores compared to HC participants. Regression analysis showed a small, but significant relationship between levodopa and dopamine agonist dosage and total IGT score, indicating that medication level could be a marker of level of executive functions. Subgroups of advantageous and disadvantageous choosers differed significantly in deck preferences for both groups. Individuals with PD were significantly impaired in IGT performance, both in overall scores and in detailed analyses, and they utilized an inefficient strategy during task performance. However, HC participants also presented with a suboptimal strategy and results suggest the presence of subgroups in both individuals with PD and HC participants, which may reflect age-related changes. These results are in line with previous research on performance of older individuals and alternative deck preferences in the IGT and underline the importance of considering the applied strategy in the evaluation of IGT performance.


Mothers' Personal and Interpersonal Function as Potential Mediators Between Maternal Maltreatment History and Child Behavior Problems.
This study examined maternal depressive symptoms, social support, parenting, and adult attachment as mediators explaining the relation between maternal childhood maltreatment and child behavior in offspring. We assessed a community sample of 96 mother-child dyads. At child age 16 months, mothers self-reported maltreatment history, adult attachment, depressive symptoms, and social support, and maternal sensitivity was assessed via 2 hr of direct behavioral observation. Maternal reports of child behavior were collected at 5 years. Single and parallel mediation models were constructed. Only maternal depressive symptoms mediated the relation between maternal maltreatment history and children's internalizing problems. Maternal sensitivity emerged as a suppressor variable. With respect to the relation between maternal maltreatment history and children's externalizing problems, when entered singly, maternal depressive symptoms, social support, and avoidant attachment emerged as mediators. When examined in parallel, only maternal depressive symptoms and avoidant attachment accounted for unique mediating variance. Findings have implications with respect to important maternal factors that might be targeted to reduce the probability of maladaptive child behavior.


A robust Zn(ii)/Na(i)-MOF decorated with [(OAc)2(H2O)2]n2n- anions for the luminescence sensing of copper ions based on the inner filter effect.
Based on the inner filter effect, a luminescent Zn(ii)/Na(i) metal-organic framework (MOF) {[Zn2Na(L)(HL)2(H2O)2][OAc]·2H2O}n (1, H2L = 5-methyl-1,3-benzenedicarboxylic acid) with excellent stability was constructed for the fluorescence detection of Cu2+ ions. MOF 1 holds a 3D cationic framework in which [(OAc)2(H2O)2]n2n- anions are embedded into its 1D channels. Abundant hydrogen-bonding and π-π interactions in the MOF facilitate electron transfer from ligand-to-metal, resulting in a good luminescence peak at 412 nm and an efficient fluorescence quenching of MOF 1 in the presence of Cu2+ ions, due to the inner filter effect. The interactions between the Cu2+ ions and the OAc- anion in the channel endowed the Cu2+ ions with facile access to be adsorbed, and afforded the selective quenching of fluorescence. The MOF particles are well dispersed in water and the Cu2+ ions are pre-concentrated by adsorption, thus facilitating the determination of Cu2+ ions with a detection limit down to 0.65 μM. Our work thus paves a way for developing MOFs as an appealing platform to construct materials for environmental applications.


Cost-effectiveness of procalcitonin for detection of serious bacterial infections in children presenting with fever without source.
Procalcitonin (PCT) offers better specificity than C-reactive protein (CRP) to detect SBI. However, their cost limited their use and routine application. The objective of this work is to determine the cost-effectiveness of PCT against CPR or Rochester scale in infants between 1 and 3 months from the perspective of the third payer in Colombia. A Monte Carlo simulation was performed with a hypothetical cohort of 10,000 patients with fever without focus (FWS) between 1 to 3 months, to estimate the number of cases correctly diagnosed for each test and the associated costs with each test. The test with the highest number of correctly diagnosed cases was PCT 79%, followed by C-reactive protein 75%, and the Rochester scale 68%. The test with the lowest cost per patient was PCT $645 (95% CI US$646-US$645) followed by C-reactive protein U$ 653 (95% CI US$655-$645) and Rochester scale US$804 (95% CI US$807-US$804). This position of dominance of PCT eliminated the need to calculate an incremental cost effectiveness ratio. PCT is the most cost-effective strategy for the detection of IBS in infants with FWS. These results should be interpreted within the clinical context of the patient and not as a single method for therapeutic decision-making.


Saccharomyces boulardii CNCM I-745: A Non-bacterial Microorganism Used as Probiotic Agent in Supporting Treatment of Selected Diseases.
The yeast Saccharomyces boulardii CNCM I-745 is a unique, non-bacterial microorganism classified as a probiotic agent. In this review article, at first, we briefly summarized the mechanisms responsible for its probiotic properties, e.g. adhesion to and elimination of enteropathogenic microorganisms and their toxins; extracellular cleavage of pathogens' virulent factors; trophic and anti-inflammatory effects on the intestinal mucosa. The efficacy of S. boulardii administration was tested in variety of human diseases. We discussed the results of S. boulardii CNCM I-745 use in the treatment or prevention of Helicobacter pylori infections, diarrhoea (Clostridium difficile infections, antibiotic-associated diarrhoea, and traveller's diarrhoea), inflammatory bowel diseases, irritable bowel syndrome, candidiasis, dyslipidemia, and small intestine bacterial overgrowth in patients with multiple sclerosis. In case of limited number of studies regarding this strain, we also presented studies demonstrating properties and efficacy of other strains of S. boulardii. Administration of S. boulardii CNCMI I-745 during antibiotic therapy has certain advantage over bacterial probiotics, because-due to its fungal natural properties-it is intrinsically resistant to the antibiotics and cannot promote the spread of antimicrobial resistance. Even though cases of fungemia following S. boulardii CNCM I-745 administration were reported, it should be treated as a widely available and safe probiotic strain.


New targets for PPARgamma in the vessel wall: implications for restenosis.
Peroxisome proliferator-activated receptor {gamma} (PPARgamma), the nuclear receptor that binds the insulin-sensitizing thiazolidinediones (TZDs), is prominently upregulated in intimal vascular smooth muscle cells (VSMC) after mechanical injury to the vessel wall. Several TZD PPARgamma ligands have been shown to inhibit neointima formation in both normal and insulin-resistant vasculature. The suppression of intimal hyperplasia by TZD PPARgamma ligands probably results from their activity to inhibit VSMC growth and promote apoptosis. TZDs prevent VSMC proliferation by blocking the activity of regulatory proteins, such as phosphorylation of the retinoblastoma protein (Rb). Rb functions as a G(1) gatekeeper by controlling S phase gene expression mediated by the E2F transcription factor. Consistent with their effect on Rb phosphorylation, PPARgamma ligands inhibit the mitogenic induction of minichromosome maintenance (MCM) proteins 6 and 7, two E2F-regulated S phase genes essential for DNA replication. PPARgamma ligands also induced apoptosis in VSMC, which correlated with a potent induction of GADD45, a gene implicated in controlling cell growth and survival. A constitutively active form of PPARgamma targeted the same cell cycle regulators as did PPARgamma ligands, consistent with a nuclear-receptor-dependent mechanism of action. This review will summarize mechanisms through which PPARgamma modulates VSMC proliferation and apoptosis suggesting that PPARgamma itself is a novel important regulator of cell cycle and apoptosis and may provide a new therapeutic approach to prevent restenosis.


Finasteride treatment of female pattern hair loss.
To evaluate the efficacy of oral finasteride therapy associated with an oral contraceptive containing drospirenone and ethinyl estradiol in premenopausal women with female pattern hair loss. Outpatient consultation for hair disorders at the Department of Dermatology, University of Bologna. Thirty-seven women with female pattern hair loss were treated with oral finasteride, 2.5 mg/d, while taking an oral contraceptive containing drospirenone and ethinyl estradiol. Treatment efficacy was evaluated using global photography and the hair density score from videodermoscopy. A self-administered questionnaire was used to assess patient evaluation of treatment effectiveness. At 12-month follow-up, 23 of the 37 patients were rated as improved using global photography (12 were slightly improved, 8 were moderately improved, and 3 were greatly improved). No improvement was recorded in 13 patients. One patient experienced worsening of the condition. There was a statistically significant (P = .002) increase in the hair density score in 12 patients. No adverse reactions to the drug were reported. Sixty-two percent of the patients demonstrated some improvement of their hair loss with the use of finasteride, 2.5 mg/d, while taking the oral contraceptive. It is unclear whether the success was due to a higher dosage of finasteride (2.5 mg instead of 1 mg) or to its association with the oral contraceptive containing drospirenone, which has an antiandrogenic effect. Further studies are necessary to understand which patterns of female pattern hair loss respond better to this treatment.


DisP+V: A Unified Framework for Disentangling Prototype and Variation From Single Sample per Person.
Single sample per person face recognition (SSPP FR) is one of the most challenging problems in FR due to the extreme lack of enrolment data. To date, the most popular SSPP FR methods are the generic learning methods, which recognize query face images based on the so-called prototype plus variation (i.e., P+V) model. However, the classic P+V model suffers from two major limitations: 1) it linearly combines the prototype and variation images in the observational pixel-spatial space and cannot generalize to multiple nonlinear variations, e.g., poses, which are common in face images and 2) it would be severely impaired once the enrolment face images are contaminated by nuisance variations. To address the two limitations, it is desirable to disentangle the prototype and variation in a latent feature space and to manipulate the images in a semantic manner. To this end, we propose a novel disentangled prototype plus variation model, dubbed DisP+V, which consists of an encoder-decoder generator and two discriminators. The generator and discriminators play two adversarial games such that the generator nonlinearly encodes the images into a latent semantic space, where the more discriminative prototype feature and the less discriminative variation feature are disentangled. Meanwhile, the prototype and variation features can guide the generator to generate an identity-preserved prototype and the corresponding variation, respectively. Experiments on various real-world face datasets demonstrate the superiority of our DisP+V model over the classic P+V model for SSPP FR. Furthermore, DisP+V demonstrates its unique characteristics in both prototype recovery and face editing/interpolation.


Three-dimensional ultrasound matrix imaging.
Matrix imaging paves the way towards a next revolution in wave physics. Based on the response matrix recorded between a set of sensors, it enables an optimized compensation of aberration phenomena and multiple scattering events that usually drastically hinder the focusing process in heterogeneous media. Although it gave rise to spectacular results in optical microscopy or seismic imaging, the success of matrix imaging has been so far relatively limited with ultrasonic waves because wave control is generally only performed with a linear array of transducers. In this paper, we extend ultrasound matrix imaging to a 3D geometry. Switching from a 1D to a 2D probe enables a much sharper estimation of the transmission matrix that links each transducer and each medium voxel. Here, we first present an experimental proof of concept on a tissue-mimicking phantom through ex-vivo tissues and then, show the potential of 3D matrix imaging for transcranial applications.


Phagocytosis of dying tumor cells by human peritoneal mesothelial cells.
Peritoneal carcinomatosis is an advanced form of metastatic disease characterized by cancer cell dissemination onto the peritoneum. It is commonly observed in ovarian and colorectal cancers and is associated with poor patient survival. Novel therapies consist of cytoreductive surgery in combination with intraperitoneal chemotherapy, aiming at tumor cell death induction. The resulting dying tumor cells are considered to be eliminated by professional as well as semi-professional phagocytes. In the present study, we have identified a hitherto unknown type of 'amateur' phagocyte in this environment: human peritoneal mesothelial cells (HMCs). We demonstrate that HMCs engulf corpses of dying ovarian and colorectal cancer cells, as well as other types of apoptotic cells. Flow cytometric, confocal and electron microscopical analyses revealed that HMCs ingest dying cell fragments in a dose- and time-dependent manner and the internalized material subsequently traffics into late phagolysosomes. Regarding the mechanisms of prey cell recognition, our results show that HMCs engulf apoptotic corpses in a serum-dependent and -independent fashion and quantitative real-time PCR (qRT-PCR) analyses revealed that diverse opsonin receptor systems orchestrating dying cell clearance are expressed in HMCs at high levels. Our data strongly suggest that HMCs contribute to dying cell removal in the peritoneum, and future studies will elucidate in what manner this influences tumor cell dissemination and the antitumor immune response.


The regional distribution of fibroblastoid progenitors in murine femoral marrow revisited.
The distribution of fibroblastoid colony-forming units (CFU-F) in mouse femoral marrow was investigated. Mechanically dispersed marginal and axial marrow fractions had the same CFU-F frequency. Metaphyseal marrow had a high CFU-F frequency in young (6 week) mice. Trypsinization of bone marrow fractions before mechanical dispersion resulted in an increased CFU-F plating efficiency and a higher incidence of CFU-F in marginal marrow (156 +/- 41%) than in axial marrow. The femoral marrow CFU-F distribution correlates with that expected on the basis of their role in both bone and marrow stroma formation.


Evaluation of an immunofluorescent test for the rapid diagnosis of field infections of infectious bovine rhinotracheitis.
An indirect immunofluorescent test for the rapid detection of infectious bovine rhinotracheitis (IBR) virus in smears of nasal and ocular secretions from infected cattle, was compared with conventional virus isolation procedures using 200 swabs from 107 field outbreaks of suspected IBR. Virus was isolated from 38 per cent of the swabs and the indirect immunofluorescent test detected virus in 14.5 per cent of the positive swabs. Examination of samples from more than one animal increased the confirmation rates of infection during outbreaks to 39 per cent by virus isolation and 21.5 per cent by the immunofluorescent test. Ocular swabs were better than nasal swabs for confirming infection both by virus isolation and immunofluorescence, and agreement between the two tests increased with the number of samples collected during an outbreak.


Feasibility Randomized Controlled Trial of ImpulsePal: Smartphone App-Based Weight Management Intervention to Reduce Impulsive Eating in Overweight Adults.
ImpulsePal is a theory-driven (dual-process), evidence-informed, and person-centered smartphone app intervention designed to help people manage impulsive processes that prompt unhealthy eating to facilitate dietary change and weight loss. The aims of this study were to (1) assess the feasibility of trial procedures for evaluation of the ImpulsePal intervention, (2) estimate standard deviations of outcomes, and (3) assess usability of, and satisfaction with, ImpulsePal. We conducted an individually randomized parallel two-arm nonblinded feasibility trial. The eligibility criteria included being aged ≥16 years, having a body mass index of ≥25 kg/m2, and having access to an Android-based device. Weight was measured (as the proposed primary outcome for a full-scale trial) at baseline, 1 month, and 3 months of follow-up. Participants were randomized in a 2:1 allocation ratio to the ImpulsePal intervention or a waiting list control group. A nested action-research study allowed for data-driven refinement of the intervention across 2 cycles of feedback. We screened 179 participants for eligibility, and 58 were randomized to the intervention group and 30 to the control group. Data were available for 74 (84%, 74/88) participants at 1 month and 67 (76%, 67/88) participants at 3 months. The intervention group (n=43) lost 1.03 kg (95% CI 0.33 to 1.74) more than controls (n=26) at 1 month and 1.01 kg (95% CI -0.45 to 2.47) more than controls (n=43 and n=24, respectively) at 3 months. Feedback suggested changes to intervention design were required to (1) improve receipt and understanding of instructions and (2) facilitate further engagement with the app and its strategies. The evaluation methods and delivery of the ImpulsePal app intervention are feasible, and the trial procedures, measures, and intervention are acceptable and satisfactory to the participants. International Standard Randomized Controlled Trial Number (ISRCTN): 14886370; http://www.isrctn.com/ISRCTN14886370 (Archived by WebCite at http://www.webcitation.org/76WcEpZ51).


Designing a Clinician-Centered Wearable Data Dashboard (CarePortal): Participatory Design Study.
The recent growth of eHealth is unprecedented, especially after the COVID-19 pandemic. Within eHealth, wearable technology is increasingly being adopted because it can offer the remote monitoring of chronic and acute conditions in daily life environments. Wearable technology may be used to monitor and track key indicators of physical and psychological stress in daily life settings, providing helpful information for clinicians. One of the key challenges is to present extensive wearable data to clinicians in an easily interpretable manner to make informed decisions. The purpose of this research was to design a wearable data dashboard, named CarePortal, to present analytic visualizations of wearable data that are meaningful to clinicians. The study was divided into 2 main research objectives: to understand the needs of clinicians regarding wearable data interpretation and visualization and to develop a system architecture for a web application to visualize wearable data and related analytics. We used a wearable data set collected from 116 adolescent participants who experienced trauma. For 2 weeks, participants wore a Microsoft Band that logged physiological sensor data such as heart rate (HR). A total of 834 days of HR data were collected. To design the CarePortal dashboard, we used a participatory design approach that interacted directly with clinicians (stakeholders) with backgrounds in clinical psychology and neuropsychology. A total of 8 clinicians were recruited from the Rhode Island Hospital and the University of Massachusetts Memorial Health. The study involved 5 stages of participatory workshops and began with an understanding of the needs of clinicians. A User Experience Questionnaire was used at the end of the study to quantitatively evaluate user experience. Physiological metrics such as daily and hourly maximum, minimum, average, and SD of HR and HR variability, along with HR-based activity levels, were identified. This study investigated various data visualization graphing methods for wearable data, including radar charts, stacked bar plots, scatter plots combined with line plots, simple bar plots, and box plots. We created a CarePortal dashboard after understanding the clinicians' needs. Results from our workshops indicate that overall clinicians preferred aggregate information such as daily HR instead of continuous HR and want to see trends in wearable sensor data over a period (eg, days). In the User Experience Questionnaire, a score of 1.4 was received, which indicated that CarePortal was exciting to use (question 5), and a similar score was received, indicating that CarePortal was the leading edge (question 8). On average, clinicians reported that CarePortal was supportive and can be useful in making informed decisions. We concluded that the CarePortal dashboard integrated with wearable sensor data visualization techniques would be an acceptable tool for clinicians to use in the future.


Pregnancy and birth outcomes after SARS-CoV-2 vaccination in pregnancy.
SARS-CoV-2 infection during pregnancy is associated with significant maternal morbidity and increased rates of preterm birth. For this reason, COVID-19 vaccination in pregnancy has been endorsed by multiple professional societies, including the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, despite the exclusion of pregnant women from initial clinical trials of vaccine safety and efficacy. However, to date, little data exist regarding the outcomes of pregnant patients after COVID-19 vaccination. To assess the safety and efficacy of COVID-19 vaccines in pregnant patients. A comprehensive vaccine registry was combined with a delivery database for an integrated healthcare system to create a delivery cohort that included vaccinated patients. Maternal sociodemographic data were examined to identify factors associated with COVID-19 vaccination. Pregnancy and birth outcomes were analyzed, including a composite measure of maternal and neonatal pregnancy complications, the Adverse Outcome Index. Of 2002 patients in the delivery cohort, 140 (7.0%) received a COVID-19 vaccine during pregnancy, and 212 (10.6%) experienced a COVID-19 infection during pregnancy. The median gestational age at first vaccination was 32 weeks (range, 13 6/7-40 4/7 weeks), and patients vaccinated during pregnancy were less likely than unvaccinated patients to experience COVID-19 infection before delivery (2/140 [1.4%] vs 210/1862 [11.3%]; P<.001). No maternal COVID-19 infection occurred after the vaccination of pregnant patients. Factors significantly associated with increased likelihood of vaccination in a multivariable logistic regression model included older age, higher level of maternal education, being a nonsmoker, use of infertility treatment for the current pregnancy, and lower gravidity. Compared with unvaccinated patients, no significant difference in the composite adverse outcome (7/140 [5.0%] vs 91/1862 [4.9%]; P=.95) or other maternal or neonatal complications, including thromboembolic events and preterm birth, was observed in vaccinated patients. In this birth cohort, vaccinated pregnant women were less likely than unvaccinated pregnant patients to experience COVID-19 infection, and COVID-19 vaccination during pregnancy was not associated with increased pregnancy or delivery complications. The cohort was skewed toward late pregnancy vaccination, and thus, findings may not be generalizable to vaccination during early pregnancy.


Protective effects of Gynostemma pentaphyllum polysaccharides on PC12 cells impaired by MPP(+).
The aim of the present study was to explore the neuroprotective effects of Gynostemma pentaphyllum polysaccharides (GP) in a 1-methyl-4-phenylpyridiniumion (MPP(+))-induced cellular model of Parkinson's disease (PD) and the underlying mechanisms. Our results indicated that exposure of PC12 cells to 1mM MPP(+) significantly decreased the cell viability when examined by MTT assay, LDH assay, and annexin-V-FITC and propidium iodide (PI) apoptosis detection assays. MPP(+)-induced apoptosis in PC12 cells was accompanied by an increased Bax/Bcl-2 ratio, release of mitochondrial cytochrome c into the cytosol, activation of caspase-3/9 and cleavage of poly (ADP-ribose) polymerase (PARP). However, pretreatment of PC12 cells with 50μg/ml GP prior to MPP(+) exposure effectively attenuated the cytotoxicity and improved cell viability via inhibiting elevated Bax/Bcl-2 ratio, as well as the release of cytosolic cytochrome c. Furthermore, GP was effective in attenuating caspase-3/9 activation and cleavage of PARP in MPP(+)-exposed PC12 cells. These results suggest that the GP has protective effects against MPP(+)-induced neuronal apoptosis in PC12 cells by suppressing apoptosis-related protein, and therefore, might likely be a promising candidate for the treatment of Parkinson's disease (PD).


GB virus B and hepatitis C virus NS3 serine proteases share substrate specificity.
GB virus B (GBV-B) is a recently discovered virus responsible for hepatitis in tamarins (Saguinus species). GBV-B belongs to the Flaviviridae family and is closely related to the human pathogen hepatitis C virus (HCV). Nonstructural protein 3 (NS3) of HCV has been shown to encompass a serine protease domain required for viral maturation. GBV-B and HCV share only about 30% of the amino acid sequence within the NS3 protease domain. The catalytic triad is conserved, and the residue Phe-154, presumed to be a crucial amino acid for determining the S1 specificity pocket of the HCV NS3 protease, is also conserved. We have expressed a synthetic gene encoding the GBV-B NS3 protease domain in Escherichia coli and have characterized the purified recombinant protein for its activity on HCV substrates. We have shown that the NS3 region of the GBV-B genome actually encodes a serine protease that, despite the low sequence homology, shares substrate specificity with the HCV NS3 protease.


Bacillus pycnus sp. nov. and Bacillus neidei sp. nov., round-spored bacteria from soil.
Bacillus sphaericus sensu lato currently consists of seven or more groups of unrelated taxa, one of which is B. sphaericus sensu stricto and another of which is Bacillus fusiformis. Members of two groups (groups 6 and 7), in common with all other B. sphaericus-like organisms, are unable to grow anaerobically or to use common hexoses, pentoses and hexitols as sources of carbon, have G+C contents of 34-36 mol % and form round spores. Groups 6 and 7 can be differentiated from other B. sphaericus-like organisms by low DNA relatedness and by variations in whole-cell fatty acid composition. Unique characteristics of group 6 include the ability to oxidize beta-hydroxybutyrate, the non-requirement for biotin and thiamin and failure to grow in 5% NaCl. Distinctive traits of group 7 include the inability to oxidize pyruvate and a requirement for biotin, thiamin and cystine for growth. These data show that groups 6 and 7 represent two novel species, for which the names Bacillus pycnus sp. nov. and Bacillus neidei sp. nov., respectively, are proposed; the corresponding type strains are NRRL NRS-1691T (= JCM 11075T) and NRRL BD-87T (= JCM 11077T).