Vascularized bone grafts for the treatment of carpal bone pathology.
Primary bone healing fails to occur in 5-15 % of scaphoid bones that undergo fracture fixation. Untreated, occult fractures result in nonunion up to 12 % of the time. Conventional bone grafting is the accepted management in the treatment algorithm of scaphoid nonunion if the proximal pole is vascularized. Osteonecrosis of the proximal scaphoid pole intuitively suggests a need for transfer of the vascularized bone to the nonunion site. Scaphoid nonunion treatment aims to prevent biological and mechanical subsidence of the involved bone, destabilization of the carpus, and early degenerative changes associated with scaphoid nonunion advanced collapse. Pedicled distal radius and free vascularized bone grafts (VBGs) offer hand surgeons an alternative treatment option in the management of carpal bone nonunion. VBGs are also indicated in the treatment of avascular necrosis of the scaphoid (Preiser's disease), lunate (Kienböck's disease), and capitate. Relative contraindications to pedicled dorsal radius vascularized bone grafting include humpback deformity, carpal instability, or collapse. The free medial femoral condyle bone graft has offered a novel treatment option for the humpback deformity to restore geometry of the carpus, otherwise not provided by pedicled grafts. In general, VBGs are contraindicated in the setting of a carpal bone without an intact cartilaginous shell, in advanced carpal collapse with degenerative changes, and in attempts to salvage small or collapsed bone fragments. Wrist salvage procedures are generally accepted as the more definitive treatment option under such circumstances. This manuscript offers a current review of the techniques and outcomes of VBGs to the carpal bones.


Development and validation of perceived sexual resentment scale for women (PSRS-W).
To develop a valid and reliable scale to asses perceived sexual resentment among married women. The cross-sectional validation study was conducted from September 2018 to July 2019 at the International Islamic University, Islamabad, Pakistan, and had three phases. Phase I comprised initial generation/selection of items regarding sexual resentment among married women. Phase II comprised pilot testing of the perceived sexual resentment scale for women items before applying the scale on the actual sample. Phase III determined convergent validity by estimating correlation of the newly developed scale with the Sexual Coercion in Intimate Relationship Scale, and its divergent validity by finding correlation with the Satisfaction with Life Scale. Data was analysed using SPSS 23. The pilot study, done on 20 married women, established the internal consistency of the newly developed scale (α=0.82). Overall, three factors emerged following factor analysis. The scale had 29 items and reliability analysis of the entire scale indicated adequate internal consistency (α=0.93). The convergent validity of the scale and the Sexual Coercion in Intimate Relationship Scale was positive (p<0.001), and the correlation with the Satisfaction with Life Scale was negative (p<0.01), indicating that the newly-developed instrument had a good convergent and divergent validity. The Perceived Sexual Resentment Scale for Women was found to be a precise and concise 29-item self-reporting tool developed to assess sexual dislikes and displeasures among married women.


Utility of esophageal mucosal impedance as a diagnostic test for esophageal disease.
The aim of this review is to summarize the use of direct mucosal impedance (MI) for the evaluation and management of esophageal diseases. Esophageal multichannel intraluminal impedance with pH (MII-pH) monitoring has been considered the most sensitive test for gastroesophageal reflux disease (GERD), but recent studies have failed to establish impedance parameters that reliably predict treatment response to medical and surgical GERD therapies. MII-pH uses a catheter passed through the nose, which is uncomfortable for patients, and the test is compromised by the day-to-day variability of reflux patterns. Recently, an MI device has been developed that can be passed through the working channel of an endoscope to measure esophageal epithelial conductivity as a marker of chronic GERD. The MI values so obtained are available within seconds, correlate with histological findings of epithelial barrier dysfunction, normalize with effective treatment, and show promise for diagnosing eosinophilic esophagitis and for distinguishing it from GERD. MI can differentiate esophageal disorders instantly during endoscopy, and can monitor treatment responses in GERD and eosinophilic esophagitis.


Peripheral polyneuropathy complicating conditions of sepsis and multi-organ failure.
We studied five patients who developed evidence of acute mainly motor peripheral polyneuropathy complicating a condition of prolonged sepsis associated with multi-organ failure. In the electrophysiological studies we observed normal motor and sensory nerve conduction velocities but there were drops in the amplitudes of the compound action potentials in the muscles and sensory peripheral nerves as well as high denervation activity on electromyography. Analytical studies of cerebrospinal fluid and blood did not show any findings of interest except for a deterioration in the nutritional parameters without specific deficiencies. The immunological and microbiological studies failed to determine factors related to the development of polyneuropathies. Nerve and muscle biopsies showed axonal neuropathy with some demyelination changes and reinnervation. Three patients survived the critical state and were re-examined presenting a moderate improvement in the neurological condition accompanied with signs of reinnervation in the electromyographic study. Given the absence of known factors implicated in the development of acute polyneuropathies in our patients, we suggest that the relevant disorders of the cellular metabolism observed in patients with prolonged sepsis aggravated by the defective nutritional condition, may be factors related to the development of these polyneuropathies.


Herbivory meets fungivory: insect herbivores feed on plant pathogenic fungi for their own benefit.
Plants are regularly colonised by fungi and bacteria, but plant-inhabiting microbes are rarely considered in studies on plant-herbivore interactions. Here we show that young gypsy moth (Lymantria dispar) caterpillars prefer to feed on black poplar (Populus nigra) foliage infected by the rust fungus Melampsora larici-populina instead of uninfected control foliage, and selectively consume fungal spores. This consumption, also observed in a related lepidopteran species, is stimulated by the sugar alcohol mannitol, found in much higher concentration in fungal tissue and infected leaves than uninfected plant foliage. Gypsy moth larvae developed more rapidly on rust-infected leaves, which cannot be attributed to mannitol but rather to greater levels of total nitrogen, essential amino acids and B vitamins in fungal tissue and fungus-infected leaves. Herbivore consumption of fungi and other microbes may be much more widespread than commonly believed with important consequences for the ecology and evolution of plant-herbivore interactions.


Capture Sequencing to Explore and Map Rare Casein Variants in Goats.
Genetic variations in the four casein genes CSN1S1, CSN2, CSN1S2, and CSN3 have obtained substantial attention since they affect the milk protein yield, milk composition, cheese processing properties, and digestibility as well as tolerance in human nutrition. Furthermore, milk protein variants are used for breed characterization, biodiversity, and phylogenetic studies. The current study aimed at the identification of casein protein variants in five domestic goat breeds from Sudan (Nubian, Desert, Nilotic, Taggar, and Saanen) and three wild goat species [Capra aegagrus aegagrus (Bezoar ibex), Capra nubiana (Nubian ibex), and Capra ibex (Alpine ibex)]. High-density capture sequencing of 33 goats identified in total 22 non-synonymous and 13 synonymous single nucleotide polymorphisms (SNPs), of which nine non-synonymous and seven synonymous SNPs are new. In the CSN1S1 gene, the new non-synonymous SNP ss7213522403 segregated in Alpine ibex. In the CSN2 gene, the new non-synonymous SNPs ss7213522526, ss7213522558, and ss7213522487 were found exclusively in Nubian and Alpine ibex. In the CSN1S2 gene, the new non-synonymous SNPs ss7213522477, ss7213522549, and ss7213522575 were found in Nubian ibex only. In the CSN3 gene, the non-synonymous SNPs ss7213522604 and ss7213522610 were found in Alpine ibex. The identified DNA sequence variants led to the detection of nine new casein protein variants. New variants were detected for alpha S1 casein in Saanen goats (CSN1S1 ∗C1), Bezoar ibex (CSN1S1 ∗J), and Alpine ibex (CSN1S1 ∗K), for beta and kappa caseins in Alpine ibex (CSN2 ∗F and CSN3 ∗X), and for alpha S2 casein in all domesticated and wild goats (CSN1S2 ∗H), in Nubian and Desert goats (CSN1S2 ∗I), or in Nubian ibex only (CSN1S2 ∗J and CSN1S2 ∗K). The results show that most novel SNPs and protein variants occur in the critically endangered Nubian ibex. This highlights the importance of the preservation of this endangered breed. Furthermore, we suggest validating and further characterizing the new casein protein variants.


Variations in the anatomy of ansa cervicalis.
With the emerging utilisation of ansa cervicalis in nerve reconstructive surgery, it is important for surgeons to be conversant with the anatomy of these nerves. This descriptive cross sectional study aimed at describing the morphology and topographic anatomy of ansa cervicalis. We examined 38 adult human formalin-fixed cadavers. The superior root was present in 38 (100%) cases and 37 (97%) cases, on the right and left sides, respectively. More than half (56%) of these roots were located superior to the posterior belly of the digastric muscle. The inferior root, on the other hand, was present in 34 (89.5%) cases on the right side and 31 (81.6%) cases on the left side. Of all the inferior roots, 81.5% were located lateral to the internal jugular vein. The loop was seen in all the cases that had the inferior root, and was mostly (64.6%) located above the superior belly of the omohyoid muscle. Knowledge of the anatomy of ansa cervicalis is not only important for nerve reconstruction surgeries, but also for operations in the neck, so as to avoid injuring the great vessels that are closely related to it.


Selection on vocal output affects laryngeal morphology in rats.
Although laryngeal morphology often reflects adaptations for vocalization, the structural consequences of selection for particular aspects of vocal behavior remain poorly understood. In this study, we investigated the effects of increased ultrasonic calling in pups on the adult larynx morphology in selectively bred rat lines. Laryngeal morphology was assessed using multiple techniques: mineralized cartilage volumes were compared in 3D-models derived from microCT scans, internal structure was compared using clearing and staining procedures combined with microscopy, cellular structure was compared using histology and microscopy, and element composition was assessed with scanning energy dispersive X-ray spectroscopy. Our results show that adult rats from lines bred to produce ultrasonic calls at higher rates as pups have shorter vocal folds and a more mineralized thyroid cartilage compared to rats bred to produce ultrasonic calls at lower rates. The change in vocal fold length appears to account for differences in low-frequency calls in these two rat lines. We suggest that the observed increases in mineralization of the thyroid cartilage in the high-ultrasound lineage provide increased reinforcement of the laryngeal structure during ultrasonic call production. Our findings therefore demonstrate an effect of selection for vocal behavior on laryngeal morphology, with acoustic consequences.


AN ADAPTIVE TRACKING ALGORITHM OF LUNG TUMORS IN FLUOROSCOPY USING ONLINE LEARNED COLLABORATIVE TRACKERS.
Accurate tracking of tumor movement in fluoroscopic video sequences is a clinically significant and challenging problem. This is due to blurred appearance, unclear deforming shape, complicate intra- and inter- fractional motion, and other facts. Current offline tracking approaches are not adequate because they lack adaptivity and often require a large amount of manual labeling. In this paper, we present a collaborative tracking algorithm using asymmetric online boosting and adaptive appearance model. The method was applied to track the motion of lung tumors in fluoroscopic sequences provided by radiation oncologists. Our experimental results demonstrate the advantages of the method.


Essentials of Proteolytic Machineries in Chloroplasts.
Plastids are unique organelles that can alter their structure and function in response to environmental and developmental stimuli. Chloroplasts are one type of plastid and are the sites for various metabolic processes, including photosynthesis. For optimal photosynthetic activity, the chloroplast proteome must be properly shaped and maintained through regulated proteolysis and protein quality control mechanisms. Enzymatic functions and activities are conferred by protein maturation processes involving consecutive proteolytic reactions. Protein abundances are optimized by the balanced protein synthesis and degradation, which is depending on the metabolic status. Malfunctioning proteins are promptly degraded. Twenty chloroplast proteolytic machineries have been characterized to date. Specifically, processing peptidases and energy-driven processive proteases are the major players in chloroplast proteome biogenesis, remodeling, and maintenance. Recently identified putative proteases are potential regulators of photosynthetic functions. Here we provide an updated, comprehensive overview of chloroplast protein degradation machineries and discuss their importance for photosynthesis. Wherever possible, we also provide structural insights into chloroplast proteases that implement regulated proteolysis of substrate proteins/peptides.


Downregulation of TAP1 and TAP2 in early stage breast cancer.
TAP1-TAP2 heterodimeric complexes are recognized as the transporter associated with antigen processing of major histocompatibility complex class I peptides for recognition by tumor-specific cytotoxic T lymphocytes. In this study, we investigated the immunohistochemical expression of TAP1 and TAP2 in 160 patients with breast cancer and correlated their expression levels with clinicopathologic parameters. The median age of the patient cohort was 52.5 years (range, 30-86 years). Both TAP1 and TAP2 immunohistochemical expression levels correlated significantly with breast cancer characteristics (P < .001). TAP1 expression levels were low to negative in stage I breast tumors. TAP1 and TAP2 levels were significantly higher in grade 3 tumors than low-grade (grade 1 and 2) tumors. TAP1 and TAP2 expression levels were not significantly different among different levels of HER2-expressing tumors and did not vary by estrogen and progesterone receptor status or patient age. Both TAP1 and TAP2 overexpression in breast cancer might be an indicator of an aggressive breast tumor.


Escherichia coli hemolysin is a potent inductor of phosphoinositide hydrolysis and related metabolic responses in human neutrophils.
Escherichia coli hemolysin (Hly) is a proteinaceous pore-forming exotoxin that probably represents a significant virulence factor in E. coli infections. We investigated its influence on human polymorphonuclear neutrophils (PMN), previously identified as highly susceptible targets. Hly provoked rapid secretion of elastase and myeloperoxidase, generation of superoxide, and synthesis of platelet-activating factor (PAF) and lyso-PAF. Concomitantly, marked phosphatidylinositol (PtdIns) hydrolysis with sequential appearance of the inositol-phosphates, inositol-phosphates, inositol triphosphate, diphosphate, and monophosphate, respectively, and formation of diacylglycerol, occurred. The metabolic responses displayed distinct bell-shaped dose dependencies, with maximum events noted at low toxin concentrations of 0.1-0.5 hemolytic units per milliliter. PtdIns hydrolysis and metabolic responses elicited by Hly exceeded those evoked by optimal concentrations of formylmethionyl-leucyl phenylalanine, PAF, leukotriene B4, A23187, or staphylococcal alpha-toxin. The toxin-induced effects were sensitive toward modulators of PMN stimulus transmission pathways (pertussis toxin, the kinase C inhibitor H7, and phorbol myristate acetate "priming"). We conclude that the marked capacity of low doses of Hly to elicit degranulation, respiratory burst, and lipid mediator generation in human PMN probably envolves signal transduction via PtdIns hydrolysis.


CUSTOM-SEQ: a prototype for oncology rapid learning in a comprehensive EHR environment.
As targeted cancer therapies and molecular profiling become widespread, the era of "precision oncology" is at hand. However, cancer genomes are complex, making mutation-specific outcomes difficult to track. We created a proof-of-principle, CUSTOM-SEQ: Continuously Updating System for Tracking Outcome by Mutation, to Support Evidence-based Querying, to automatically calculate and display mutation-specific survival statistics from electronic health record data. Patients with cancer genotyping were included, and clinical data was extracted through a variety of algorithms. Results were refreshed regularly and injected into a standard reporting platform. Significant results were highlighted for visual cueing. A subset was additionally stratified by stage, smoking status, and treatment exposure. By August 2015, 4310 patients with a median follow-up of 17 months had sufficient data for survival calculation. As expected, epidermal growth factor receptor (EGFR) mutations in lung cancer were associated with superior overall survival, hazard ratio (HR) = 0.53 (P < .001), validating the approach. Guanine nucleotide binding protein (G protein), q polypeptide (GNAQ) mutations in melanoma were associated with inferior overall survival, a novel finding (HR = 3.42, P < .001). Smoking status was not prognostic for epidermal growth factor receptor-mutated lung cancer patients, who also lived significantly longer than their counterparts, even with advanced disease (HR = 0.54, P = .001). CUSTOM-SEQ represents a novel rapid learning system for a precision oncology environment. Retrospective studies are often limited by study of specific time periods and can lead to incomplete conclusions. Because data is continuously updated in CUSTOM-SEQ, the evidence base is constantly growing. Future work will allow users to interactively explore populations by demographics and treatment exposure, in order to further investigate significant mutation-specific signals.


Titrametric characterization of pH-induced phase transitions in functionalized microgels.
The chain and radial functional group distributions in carboxylic acid-functionalized poly(N-isopropylacrylamide)-based microgels have significant impacts on the types of swelling responses exhibited by the microgels upon the application of a temperature and/or pH stimulus. Potentiometric, conductometric, and calorimetric titration approaches are used in this work to characterize the chain distributions of -COOH groups in five microgels prepared using different -COOH-functionalized monomers. A direct correlation is observed between the kinetically predicted formation of functional monomer blocks within the microgel, the excess Gibbs free energy of ionization, and the apparent pK(a) versus degree of ionization profiles generated from potentiometric titration. Isothermal titration calorimetry (ITC) can be used to quantify the relative number of functional groups present in microgels prepared with the same functional monomer and/or identify differences between microgels with the same bulk -COOH content but different chain distributions. In particular, microgels prepared with diacid-functionalized monomers exhibit a characteristic two-step ITC profile. For microgels with the same bulk -COOH content, the heat of ionization measured via ITC increases systematically with the overall change in both the pK(a) and the excess Gibbs free energy for microgels prepared with monoacid-functionalized monomers. Diacid monomer-functionalized microgels have lower ionization enthalpies attributable to the break-up of hydrogen-bonded intramolecular ring complexes upon carboxylic acid ionization. The inferred chain functional group distributions can be used to understand differences in microgel swelling across the pH-induced phase transition.


To reuse or not to reuse? An economic evaluation of hemodialyzer reuse versus conventional single-use hemodialysis for chronic hemodialysis patients.
To evaluate the cost-effectiveness of reusing hemodialyzers for patients with kidney failure on dialysis employing either a heated citric acid or formaldehyde sterilization method, in comparison to the standard practice of single-use dialysis. A meta-analysis of all relevant studies was performed to determine whether hemodialyzer reuse was associated with an increased relative risk of mortality or hospitalization. A decision tree was constructed to model the effect of three different dialysis strategies (single-use dialysis, heated citric acid, and formaldehyde dialyzer reuse) on the costs and quality-adjusted life expectancy of "typical" hemodialysis patients. The cost of heated citric acid reuse was estimated from a center experienced with the technique. The cost of end-stage renal disease (ESRD) care, survival data, and patient utilities were estimated from published sources. There was evidence of a higher relative risk of hospitalization (but not mortality) for hemodialyzer reuse compared with single-use dialysis. Depending on the assumptions used, the cost savings that could be expected by switching from single-use dialysis to heated citric acid reuse were small, ranging from CAN $0-739 per patient per year. ESRD programs can incorporate the results of this study based on their individual situations to determine whether hemodialyzer reuse is appropriate in their setting.


Identification of a novel, tissue-specific calpain htra-3; a human homologue of the Caenorhabditis elegans sex determination gene.
We cloned a novel human gene encoding a tissue-specific calpain, termed htra-3, which is highly homologous to the tra-3 sex determination gene of Caenorhabditis elegans. The predicted htra-3 polypeptide had similarity to the calpain large subunits in domain organization throughout domains I to III, but the sequences of domain IV lacked calcium-binding motifs. Northern blot analysis revealed high expression in the colon, small intestine and testis. Radiation hybrid mapping localized the htra-3 gene to chromosome 11q14 (2.53cR apart from WI-3895). Western blot analysis demonstrated that the approximately 73-kDa htra-3 protein was transiently expressed in COS-7 cells. These observations, together with the genetic information in C.elegans, suggest a unique function for htra-3 protein.


Sexual selection on female ornaments in the sex-role-reversed Gulf pipefish (Syngnathus scovelli).
Understanding how selection acts on traits individually and in combination is an important step in deciphering the mechanisms driving evolutionary change, but for most species, and especially those in which sexual selection acts more strongly on females than on males, we have no estimates of selection coefficients pertaining to the multivariate sexually selected phenotype. Here, we use a laboratory-based mesocosm experiment to quantify pre- and post-mating selection on female secondary sexual traits in the Gulf pipefish (Syngnathus scovelli), a sexually dimorphic, sex-role-reversed species in which ornamented females compete for access to choosy males. We calculate selection differentials and gradients on female traits, including ornament area, ornament number and body size for three episodes of selection related to female reproductive success (number of mates, number of eggs transferred and number of surviving embryos). Selection is strong on both ornament area and ornament size, and the majority of selection occurs during the premating episode of selection. Interestingly, selection on female body size, which has been detected in previous studies of Gulf pipefish, appears to be indirect, as evidenced by a multivariate analysis of selection gradients. Our results show that sexual selection favours either many bands or larger bands in female Gulf pipefish.


Does parental substance use always engender risk for children? Comparing incidence rate ratios of abusive and neglectful behaviors across substance use behavior patterns.
Parental substance use disorder (SUD) is associated with an added risk for child abuse and neglect, but less is understood about how a range of parental use behaviors is associated with differential maltreatment frequencies. This study used the National Survey of Child and Adolescent Well-Being (NSCAW I) to create categories for parental substance use behaviors that are conceptually associated with varying levels of substance-related impairments. The study sample was composed of 2100 parents of children ages 2-17 years from Wave 4 data collection. Weighted negative binomial regression models assessed the relationship between substance use behavior patterns and maltreatment frequencies by type. Behavior patterns defined by some form of past year substance use were associated with a higher frequency of physical or emotional abuse compared to non-users. In contrast, only past year SUD was associated with a higher frequency of neglect compared to other categories. In sum, the relationship between substance use and maltreatment frequencies differed for abuse and neglect, suggesting different pathways may be underlying these observed relationships.


Horticultural activity predicts later localized limb status in a contemporary pre-industrial population.
Modern humans may have gracile skeletons due to low physical activity levels and mechanical loading. Tests using pre-historic skeletons are limited by the inability to assess behavior directly, while modern industrialized societies possess few socio-ecological features typical of human evolutionary history. Among Tsimane forager-horticulturalists, we test whether greater activity levels and, thus, increased loading earlier in life are associated with greater later-life bone status and diminished age-related bone loss. We used quantitative ultrasonography to assess radial and tibial status among adults aged 20+ years (mean ± SD age = 49 ± 15; 52% female). We conducted systematic behavioral observations to assess earlier-life activity patterns (mean time lag between behavioural observation and ultrasound = 12 years). For a subset of participants, physical activity was again measured later in life, via accelerometry, to determine whether earlier-life time use is associated with later-life activity levels. Anthropometric and demographic data were collected during medical exams. Structural decline with age is reduced for the tibia (female: -0.25 SDs/decade; male: 0.05 SDs/decade) versus radius (female: -0.56 SDs/decade; male: -0.20 SDs/decade), which is expected if greater loading mitigates bone loss. Time allocation to horticulture, but not hunting, positively predicts later-life radial status (βHorticulture = 0.48, p = 0.01), whereas tibial status is not significantly predicted by subsistence or sedentary leisure participation. Patterns of activity- and age-related change in bone status indicate localized osteogenic responses to loading, and are generally consistent with the logic of bone functional adaptation. Nonmechanical factors related to subsistence lifestyle moderate the association between activity patterns and bone structure.


Critical care nurses' perception of nursing error and its causes: a qualitative study.
Abstract Nurses' perceptions of nursing error could affect their professional practice. The aim of the study was to explore critical care nurses' perceptions of nursing error and its causes. This was a qualitative study in which 12 critical care nurses were recruited through purposive sampling. The data were collected via in-depth interviews and analyzed through qualitative content analysis method (Elo & Kyngas, 2008). Nursing error was deemed as an unavoidable issue which consisted of the lack of congruence with standards, doing extra-nursing tasks and giving care against the agreed-upon routines. Five categories emerged as the causes of error: individual reasons, work pressure, caring blindly, the uniqueness of caring environment and the lack of coordination among health care team members. The perception of nursing error is sort of unique; hence, managers should provide support for critical care nurses and pave the way for the prevention of errors.


The role of phytosterols in the pathogenesis of liver complications of pediatric parenteral nutrition.
Long-term parenteral nutrition of infants who have had major gut resections is associated with a high incidence of cholestatic liver disease. Affected infants have high plasma concentrations of phytosterols--compounds that resemble cholesterol but have an alkylated side chain. The phytosterols that accumulate in patients receiving parenteral nutrition are derived from the soya oil and/or soya lecithin used to make the intravenous lipid emulsion. There is a striking association between phytosterolemia and cholestatic liver disease. This has led us to put forward the hypothesis that phytosterols can cause cholestasis in susceptible infants. Experiments using neonatal piglets indicate that phytosterols (given without any of the other components of parenteral nutrition) can indeed reduce bile flow. We suggest that increasing the content of phytosterols in cell membranes may interfere with the function of important transport proteins involved in the secretion of bile. Other factors that might contribute to cholestasis (such as inhibition of cholesterol 7 alpha-hydroxylase) are discussed.


Psychosocial interventions as part of breast cancer rehabilitation programs? Results from a systematic review.
This systematic review aimed to determine the effectiveness of psychoeducation, cognitive behavioural therapy (CBT) and social support interventions used in the rehabilitation of breast cancer (BC) patients. We conducted a systematic literature search to identify randomised controlled trials of female BC patients who underwent different psychosocial interventions during or after primary cancer treatment. The methodological quality of all studies was independently assessed by two reviewers. Studies with low quality, less than 20 participants in each group, patients with metastatic cancer, data not presented separately for BC and studies that included other cancer types were excluded. Among 9617 identified studies, only 18 RCTs published between 1999 and 2008, including 3272 patients were finally included in this systematic evaluation. Outcome measures were categorised into quality of life (QoL), fatigue, mood, health behaviour and social function. Six trials examined psychoeducation had inconsistent results, both during and after the primary treatment. Seven trials examined the effect of CBT, four of which given after primary treatment (range 6-12 weeks) demonstrated improvements in QoL; the other three CBT studies given during primary treatment (range 9-20 weeks) had inconsistencies. Five studies addressed social support and showed no conclusive impacts of this intervention. Limited documentation exists on the efficacy of psychosocial rehabilitation interventions among BC patients. However, we found that patients might have QoL benefits from CBT given after primary BC treatment. More documentation is needed regarding the effects of CBT during primary treatment and the effects of psychoeducation and social support.


Peripheral and central immune system crosstalk in Alzheimer disease - a research prospectus.
Dysregulation of the immune system is a cardinal feature of Alzheimer disease (AD), and a considerable body of evidence indicates pathological alterations in central and peripheral immune responses that change over time. Considering AD as a systemic immune process raises important questions about how communication between the peripheral and central compartments occurs and whether this crosstalk represents a therapeutic target. We established a whitepaper workgroup to delineate the current status of the field and to outline a research prospectus for advancing our understanding of peripheral-central immune crosstalk in AD. To guide the prospectus, we begin with an overview of seminal clinical observations that suggest a role for peripheral immune dysregulation and peripheral-central immune communication in AD, followed by formative animal data that provide insights into possible mechanisms for these clinical findings. We then present a roadmap that defines important next steps needed to overcome conceptual and methodological challenges, opportunities for future interdisciplinary research, and suggestions for translating promising mechanistic studies into therapeutic interventions.


Sent to destroy: the ubiquitin proteasome system regulates cell signaling and protein quality control in cardiovascular development and disease.
The ubiquitin proteasome system (UPS) plays a crucial role in biological processes integral to the development of the cardiovascular system and cardiovascular diseases. The UPS prototypically recognizes specific protein substrates and places polyubiquitin chains on them for subsequent destruction by the proteasome. This system is in place to degrade not only misfolded and damaged proteins, but is essential also in regulating a host of cell signaling pathways involved in proliferation, adaptation to stress, regulation of cell size, and cell death. During the development of the cardiovascular system, the UPS regulates cell signaling by modifying transcription factors, receptors, and structural proteins. Later, in the event of cardiovascular diseases as diverse as atherosclerosis, cardiac hypertrophy, and ischemia/reperfusion injury, ubiquitin ligases and the proteasome are implicated in protecting and exacerbating clinical outcomes. However, when misfolded and damaged proteins are ubiquitinated by the UPS, their destruction by the proteasome is not always possible because of their aggregated confirmations. Recent studies have discovered how these ubiquitinated misfolded proteins can be destroyed by alternative "specific" mechanisms. The cytosolic receptors p62, NBR, and histone deacetylase 6 recognize aggregated ubiquitinated proteins and target them for autophagy in the process of "selective autophagy." Even the ubiquitination of multiple proteins within whole organelles that drive the more general macro-autophagy may be due, in part, to similar ubiquitin-driven mechanisms. In summary, the crosstalk between the UPS and autophagy highlight the pivotal and diverse roles the UPS plays in maintaining protein quality control and regulating cardiovascular development and disease.


The effects of childlessness on the care and psychological well-being of older adults with disabilities.
Adult children are a primary focus of family and caregiver research. In contrast, relatively little is known about childless elders with a disability, including their care needs and the state of their overall well-being compared to elderly parents. We addressed this gap by examining the relationship between childlessness and the care and well-being of adults aged 75 and older with a disability. Parents and childless persons aged 75 and older were compared using data from the 1998 to 2004 waves of the Health and Retirement Study (HRS). We used logistic regression to examine the relationship between childlessness and care provision (personal care and assistive devise use) and ordinal regression to examine the relationships of parental status, personal care, and use of assistive devices with well-being. The analysis was based on 2048 observations from 1456 community-dwelling respondents who had difficulty walking across a room or getting into or out of bed. Compared to parents, childless elders with a disability generally do not receive less care or have worse psychological well-being. However, being unmarried reduces the likelihood of having personal care and is associated with depressive affect. Use of assistive devices is associated with less depressive affect. Childless older adults are similar to parents on measures of psychological well-being and care provision. This finding has important implications, as it is projected that 30% of baby boomers who will need assistance will lack care from spouses or adult children. Further exploration of compensatory resources is suggested.


Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea.
BACKGROUND. The pathogenesis of Ebola virus (EBOV) disease (EVD) is poorly characterized. The establishment of well-equipped diagnostic laboratories close to Ebola treatment centers (ETCs) has made it possible to obtain relevant virological and biological data during the course of EVD and to assess their association with the clinical course and different outcomes of the disease. METHODS. We were responsible for diagnosing EBOV infection in patients admitted to two ETCs in forested areas of Guinea. The pattern of clinical signs was recorded, and an etiological diagnosis was established by RT-PCR for EBOV infection or a rapid test for malaria and typhoid fever. Biochemical analyses were also performed. RESULTS. We handled samples from 168 patients between November 29, 2014, and January 31, 2015; 97 patients were found to be infected with EBOV, with Plasmodium falciparum coinfection in 18%. Overall mortality for EVD cases was 58%, rising to 86% if P. falciparum was also present. Viral load was higher in fatal cases of EVD than in survivors, and fatal cases were associated with higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT), C-reactive protein (CRP), and IL-6 levels. Furthermore, regardless of outcome, EVD was characterized by higher creatine kinase (CPK), amylase, and creatinine levels than in febrile patients without EVD, with higher blood urea nitrogen (BUN) levels in fatal cases of EVD only. CONCLUSION. These findings suggest that a high viral load at admission is a marker of poor EVD prognosis. In addition, high AST, ALT, CRP, and IL-6 levels are associated with a fatal outcome of EVD. Damage to the liver and other tissues, with massive rhabdomyolysis and, probably, acute pancreatitis, is associated with EVD and correlated with disease severity. Finally, biochemical analyses provide substantial added value at ETCs, making it possible to improve supportive rehydration and symptomatic care for patients. FUNDING. The French Ministry of Foreign Affairs, the Agence Française de Développement, and Institut Pasteur.


Access related complications during anterior exposure of the lumbar spine.
The new millennium has witnessed the emergence of minimally invasive, non-posterior based surgery of the lumbar spine, in particular via lateral based methodologies to discectomy and fusion. In contrast, and perhaps for a variety of reasons, anterior motion preservation (non-fusion) technologies are playing a comparatively lesser, though incompletely defined, role at present. Lateral based motion preservation technologies await definition of their eventual role in the armamentarium of minimally invasive surgical therapies of the lumbar spine. While injury to the major vascular structures remains the most serious and feared complication of the anterior approach, this occurrence has been nearly eliminated by the use of lateral based approaches for discectomy and fusion cephalad to L5-S1. Whether anterior or lateral based, non-posterior approaches to the lumbar spine share certain access related pitfalls and complications, including damage to the urologic and neurologic structures, as well as gastrointestinal and abdominal wall issues. This review will focus on the recognition, management and prevention of these anterior and lateral access related complications.


β-Caryophyllene oxide inhibits constitutive and inducible STAT3 signaling pathway through induction of the SHP-1 protein tyrosine phosphatase.
Constitutive activation of STAT3 is frequently observed and closely linked with proliferation, survival, invasion, metastasis and angiogenesis in tumor cells. In the present study, we investigated whether β-caryophyllene oxide (CPO), a sesquiterpene isolated primarily from the essential oils of medicinal plants such as guava (Psidium guajava), and oregano (Origanum vulgare L.), can mediate its effect through interference with the STAT3 activation pathway in cancer cells. The effect of CPO on STAT3 activation, associated protein kinases and phosphatase, STAT3-regulated gene products and apoptosis was investigated using both functional proteomics tumor pathway technology platform and different tumor cell lines. We found that CPO suppressed constitutive STAT3 activation in multiple myeloma (MM), breast and prostate cancer cell lines, with a significant dose- and time-dependent effects observed in MM cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src and JAK1/2. Also, vanadate treatment reversed CPO-induced down-regulation of STAT3, suggesting the involvement of a tyrosine phosphatase. Indeed, we found that CPO induced the expression of tyrosine phosphatase SHP-1 that correlated with the down-regulation of constitutive STAT3 activation. Interestingly, deletion of SHP-1 gene by siRNA abolished the ability of CPO to inhibit STAT3 activation. The inhibition of STAT3 activation by CPO inhibited proliferation, induced apoptosis and abrogated the invasive potential of tumor cells. Our results suggest for the first time that CPO is a novel blocker of STAT3 signaling cascade and thus has an enormous potential for the treatment of various cancers harboring constitutively activated STAT3.


A new score predicting survival prognosis after whole-brain radiotherapy alone for brain metastases in elderly patients.
Elderly patients represent an important subgroup of patients with brain metastases. A survival score has been developed specifically for these patients. A total of 544 elderly patients (aged ≥65 years) receiving whole-brain radiotherapy alone were divided into a test (n=272) and a validation group (n=272). In the multivariate analysis of the test group, survival was significantly associated with gender, performance status, and number of organs involved by extracranial metastases. These factors were included in the score. Total scores representing the sum of the three factor scores were 3-13 points. Four prognostic groups were formed. The 6-month survival rates were 2% for those with 3-6 points, 17% for those with 7-9 points, 56% for those with 10-12 points and 90% for those with 13 points in the test group (p<0.001), and 4%, 21%, 50% and 86%, respectively, in the validation group (p<0.001). This score is reproducible and helps estimate the survival prognosis of elderly patients with brain metastasis.


Sex-Specific Versus Overall Clinical Decision Limits for Cardiac Troponin I and T for the Diagnosis of Acute Myocardial Infarction: A Systematic Review.
The overall clinical decision limits of high-sensitivity cardiac troponin I (hs-cTnI; 26 ng/L) and T (hs-cTnT; 14 ng/L) may contribute to underdiagnosis of acute myocardial infarction in women. We performed a systematic review to investigate sex-specific and overall 99th percentiles of hs-cTnI and hs-cTnT derived from healthy reference populations. We searched in PubMed and EMBASE for original studies, and by screening reference lists. Reference populations designed to establish 99th percentiles of hs-cTnI (Abbott) and/or hs-cTnT (Roche), published between January 2009 and October 2017, were included. Sex-specific and overall 99th percentile values of hs-cTnI and hs-cTnT were compared with overall clinical decision ranges (hs-cTnI, 23-30 ng/L; hs-cTnT, 13-25 ng/L). Twenty-eight studies were included in the systematic review. Of 16 hs-cTnI and 18 hs-cTnT studies, 14 (87.5%) and 11 (61.1%) studies reported lower female-specific hs-cTn cutoffs than overall clinical decision ranges, respectively. Conversely, male-specific thresholds of both hs-cTnI and hs-cTnT were in line with currently used overall thresholds, particularly hs-cTnT (90% concordance). The variation of estimated overall 99th percentiles was much higher for hs-cTnI than hs-cTnT (29.4% vs 80.0% of hs-cTnI and hs-cTnT studies reported values within the current overall clinical decision range, respectively). Our data show substantially lower female-specific upper reference limits of hs-cTnI and hs-cTnT than overall clinical decision limits of 26 ng/L and 14 ng/L, respectively. The statistical approach strongly affects the hs-cTnI threshold. Downward adjustment of hs-cTn thresholds in women may be warranted to reduce underdiagnosis of acute myocardial infarction in women.


Hormonal regulation of dipeptide transporter (PepT1) in Caco-2 cells with normal and anoxia/reoxygenation management.
To determine the regulation effects of recombinant human growth hormone (rhGH) on dipeptide transporter(PepT1) in Caco-2 cells with normal culture and anoxia/reoxygenation injury. A human intestinal cell monolayer (Caco-2) was used as the in vitro model of human small intestine and cephalexin as the model substrate for dipeptide transporter (PepT1). Caco-2 cells grown on Transwell membrane filters were preincubated in the presence of rhGH in the culture medium for 4 d, serum was withdrawn from monolayers for 24 h before each experiment. The transport experiments of cephalexin across apical membromes were then conducted; Caco-2 cells grown on multiple well dishes (24 pore) with normal culture or anoxia/reoxygenation injury were preincubated with rhGH as above and uptake of cephalexin was then measured. The transport and uptake of cephelaxin across apical membranes of Caco-2 cells after preincubation with rhGH were significantly increased compared with controls (P=0.045, 0.0223). Also, addition of rhGH at physiological concentration (34 nM) to incubation medium greatly stimulates cephalexin uptake by anoxia/reoxygenation injuried Caco-2 cells (P=0.0116), while the biological functions of PepT1 in injured Caco-2 cells without rhGH were markedly downregulated. Northern blot analysis showed that the level of PepT1 mRNA of rhGH-treated injured Caco-2 cells was greatly increased compared to controls. The present results of rhGH stimulating the uptake and transport of cephalexin indicated that rhGH greatly upregulates the physiological effects of dipeptide transporters of Caco-2 cells. The alteration in the gene expression may be a mechanism of regulation of PepT1. In addition, Caco-2 cells take up cephalexin by the Proton-dependent dipeptide transporters that closely resembles the transporters present in the intestine. Caco-2 cells represent an ideal cellular model for future studies of the dipeptide transporter.


The value of physical tests for subacromial impingement syndrome: a study of diagnostic accuracy.
To determine the diagnostic accuracy of commonly used physical tests for subacromial impingement syndrome, using ultrasound as the reference standard. A cross-sectional study of 59 participants with chronic shoulder pain of more than four months duration with a referral for diagnostic ultrasound scanning were invited to participate in the study. Thirty-four participants met the inclusion criteria and had an ultrasound scan followed immediately by application of the following tests: Neer's sign, Hawkins and Kennedy test, painful arc of abduction, empty and full can tests, resisted isometric shoulder abduction and resisted isometric shoulder external rotation. Using the two-way contingency table method sensitivity, specificity, likelihood ratios and overall accuracy were calculated for each physical test. Diagnostic values for each test varied considerably. The Hawkins and Kennedy test was the most accurate test for diagnosing any degree of subacromial impingement syndrome (71.0%). The most accurate tests for diagnosing subcategories of impingement were pain on resisted external rotation and weakness during the full can test (63.6%) for presence of subdeltoid fluid, pain on resisted external rotation (58.8%) for partial thickness tears and the painful arc test (62.1%) for full thickness tears. As the predictive values of these tests are shown to be variable in this study it indicates that the clinical tests identified have limited use in informing diagnosis. Emphasis on the management of dysfunction may be more appropriate rather than reliance on clinical tests with inconclusive sensitivity and specificity if ultrasound scanning is not available.


Tunable optical metamaterial-based sensors enabled by closed bipolar electrochemistry.
Enabled by the proliferation of nanoscale fabrication techniques required to create spatially-repeating, sub-wavelength structures to manipulate the behavior of visible-wavelength radiation, optical metamaterials are of increasing interest. Here we develop and characterize a chemical sensing approach based on electrochemical tuning of the optical response function of large-area, inexpensive nanoaperture metamaterials at visible and near-IR wavelengths. Nanosphere lithography is used to create an ordered array of sub-wavelength apertures in a Au film. The spacing of these apertures is established during fabrication, based on the size of the polystyrene nanospheres. Tunable shifts in the transmission spectrum can be produced post-fabrication by electrodeposition of a dissimilar metal, Ag, using the nanoaperture film as one electrode in a 2-electrode closed bipolar electrochemical (CBE) cell, altering hole size, film thickness, and film composition while maintaining hole spacing dictated by the original pattern. Optical transmission spectra acquired under galvanostatic conditions can be expressed as a linear combination of the initial and final (saturated) spectra, and the resulting response function exhibits a sigmoidal response with respect to the amount of charge (or metal) deposited. This architecture is then used to perform optical coulometry of model analytes in a CBE-based analyte-reporter dual cell device, thus expanding the capability of CBE-based sensors. Increasing the exposed electrode area of the analyte cell increases the response of the device, while modifying the circuit resistance alters the balance between sensitivity and dynamic range. These tunable nanoaperture metamaterials exhibit enhanced sensitivity compared to CBE electrochromic reporter cells to the μM to nM concentration range, suggesting further avenues for development of CBE-based chemical sensors as well as application to inexpensive, point-of-care diagnostic devices.


Facial Cutaneous Rosai-Dorfman Disease: Dermoscopic Findings with Successful Surgical Treatment.
Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by an accumulation of activated histiocytes within the affected tissues. It is a heterogeneous disease that includes the classical (nodal) and extra-nodal variants. The cutaneous form of the disease without the characteristic lymphadenopathy is rare and is often misdiagnosed as other dermatologic diseases. Misdiagnosis as lymphoproliferative and infectious diseases such as lymphoma and tuberculosis have been reported in the literature. Herein, we report a case of facial cutaneous RDD with successful surgical treatment. In addition, we provide dermoscopic findings and literature review as dermoscopy can be a useful adjuvant tool in the diagnosis of cutaneous RDD.


The immune response against the ASV-coded src-gene product in syngeneic mice.
The antigenicity of the avian sarcoma virus (ASV)-coded src-gene product pp60src, which is responsible for fibroblast transformation after ASV infection, has been investigated in STU mouse fibrosarcoma cell lines and the corresponding immune response in syngeneic mice has been determined. The development of effective anti-pp60src antibody titres depends on the mode and stie of injection of tumour cells and parallels tumour growth. It was found that mouse immunoglobulin heavy chains are unable to serve as substrate for the protein kinase activity of pp60src. Therefore, an indirect protein kinase absorption (PKA) test was initiated to demonstrate recognition of the protein kinase activity associated with the src-gene product. The availability of syngeneic mice and the corresponding ASV-transformed tumour cells should facilitate studies designed to elucidate the possible relationship between the cytoplasmic pp60src and ASV-induced tumour-specific surface antigens (TSSA), for example, by allowing the production of stable mouse hybridomas synthesizing antibodies specific for pp60src and TSSA.


Two determinants in the capsid of a persistent type 3 poliovirus exert different effects on mutant virus uncoating.
Mutant polioviruses (PV) have been previously found to be capable of establishing persistent infections in HEp-2c cells. Together, two amino acid substitutions in the viral capsid of a type 3 poliovirus (PV-3), at positions VP213 and VP1(290), are sufficient to confer the persistent phenotype to a normally lytic virus. When susceptible cells are infected, the double mutant T7L+2L(13)1N(290) undergoes unique conformational changes in the capsid, modifying its sedimentation coefficient from 160S to 147S. In the present study, we have further investigated mutant PV decapsidation and, in particular, the effect of each determinant independently. Our results indicate that the novel 147S form was also generated by a mutant carrying only the determinant 1N290. This form was not produced as a result of inherent capsid instability and it was generated only upon specific PV-host cell interactions. The second viral determinant, 2L13, also modified receptor-induced conformational changes, although differently from 1N290.


Enhanced recovery of spermatozoa and comprehensive lysis of epithelial cells from sexual assault samples having a low cell counts or aged up to one year.
Differential extraction (DE) is the most common method for processing sexual assault samples, allowing for the simultaneous recovery of sperm and epithelial cells from the swab with the separation of sperm cells from epithelial cell DNA by exploiting the differences in the cell membrane susceptibility to detergents. However, sperm cell recovery when using DE is generally 40-50% [1], which can reduce the probability of obtaining a STR profile of the semen contributor, especially if the sample is aged or has a low number of sperm cells. Here, we present a novel buffer, containing SDS and ProK that, when used as an initial incubation buffer, enhances sperm cell recovery to as high as 90%, representing a 200-300% increase over conventional DE buffer. Adjusting the incubation time and temperature provided high, reproducible sperm cell yields. Sample vortexing and replacement of SDS with sodium octyl sulfate (SOS), another sulfate-based anionic detergent, did not provide any further enhancement of the sperm cell recoveries. Furthermore, the one-step buffer provided up to a 300% increase in recovery over the conventional DE buffer when used on samples aged up to one year. STR analysis of samples containing 500 or more sperm cells treated with this buffer showed comparable results (i.e., full STR profiles; 16 of 16 loci) to those obtained using a conventional DE buffer. Finally, when the sample contained only 400 sperm cells (recovered in 100μL volume, then extracted), substantially more STR loci (14 of 16) were generated using the novel buffer in comparison to the conventional DE buffer (4 of 16 loci). This work demonstrates that this buffer may be useful as an alternative for the initial sample incubation step in differential extraction, particularly for aged or samples known to have a low number of sperm cells.


Directing surgical quality improvement initiatives: comparison of perioperative mortality and long-term survival for cancer surgery.
Quality-improvement initiatives are being developed to decrease volume-based variability in surgical outcomes. Resources for national and hospital quality-improvement initiatives are limited. It is unclear whether quality initiatives in surgical oncology should focus on factors affecting perioperative mortality or long-term survival. Our objective was to determine whether differences in hospital surgical volume have a larger effect on perioperative mortality or long-term survival using two methods. From the National Cancer Data Base, 243,103 patients who underwent surgery for nonmetastatic colon, esophageal, gastric, liver, lung, pancreatic, or rectal cancer were identified. Multivariable modeling was used to evaluate 60-day mortality and 5-year conditional survival (excluding perioperative deaths) across hospital volume strata. The number of potentially avoidable perioperative and long-term deaths were calculated if outcomes at low-volume hospitals were improved to those of the highest-volume hospitals. Risk-adjusted perioperative mortality and long-term conditional survival worsened as hospital surgical volume decreased for all cancer sites, except for liver resections where there was no difference in survival. When comparing low- with high-volume hospitals, the hazard ratios for perioperative mortality were substantially larger than for long-term survival. However, the number of potentially avoidable deaths each year in the United States, if outcomes at low-volume hospitals were improved to the level of highest-volume centers, was significantly larger for long-term survival. Although the magnitude of the hazard ratios implies that quality-improvement efforts should focus on perioperative mortality, a larger number of deaths could be avoided by focusing quality initiatives on factors associated with long-term survival.


Techno-functional characterization of salad dressing emulsions supplemented with pea, lentil and chickpea flours.
Salad dressings supplemented with pulse flours are novel products. A three-factor face-centered central composite design (CCD) was used to determine the effect of pulse flour concentration (3.5%, 7%, 10.5% w/w), egg yolk concentration (3%, 5%, 7% w/w) and oil concentration (20%, 35%, 50% w/w) on the rheological and color characteristics of salad dressings supplemented with pulse flours. The consistency coefficient m, plateau modulus G(N)(0), recoverable strain Q(t) and color values were all affected by the concentrations of pulse flours used. Scanning electron microscopy showed that dressings with lower oil and egg yolk contents had a less densely packed network compared with dressings with higher oil and egg yolk contents. Sensory results were most promising for salad dressings supplemented with the whole green lentil, yellow pea with low flour content, and chickpea with high oil content. This study should be useful for designing novel types of salad dressings to meet market requirements as well as helping to increase pulse consumption.


[Autonomic reactions in rabbits exposed to a constant magnetic field].
Chronic experiments on rabbits have shown that their exposure to a constant magnetic field of 4500 oersted for 3 hours causes a transient hypotension, a decrease in the respiratory rate and a trend for bradycardia. Immediately after the exposure the pressor reaction and bradycardia level decrease and by the end of the first day they increase. At this time the respiratory rate increases in response to the administration of epinephrine, acethylcholine or stimulation of the midbrain reticular formation. The exposure does not decrease the compensatory possibilities of the cardiovascular and respiratory systems. This follows from their reactions to accelerations of 6 and 10 g.


Using real-time polymerase chain reaction as an alternative rapid method for enumeration of colony count in live Brucella vaccines.
Brucellosis is a major bacterial zoonosis of global importance affecting a range of animal species and man worldwide. It has economic, public health, and bio-risk importance. Control and prevention of animal brucellosis mainly depend on accurate diagnostic tools and implementation of effective and safe animal vaccination program. There are three types of animal Brucella live vaccines - Brucella melitensis Rev-1 vaccine, Brucella abortus S19, and B. abortus RB51. Evaluation of these vaccines depends mainly on enumeration of Brucella viable count. At present, used colony count method is time consuming, costly and requires especial skills. Hence, the aim of this study is to use and standardize real-time polymerase chain reaction (RT-PCR) as an alternative, quantitative, sensitive, and rapid method to detect the colony count of Brucella in live Brucella vaccine. Four batches of different live Brucella vaccines were evaluated using of conventional bacterial count and RT-quantitative PCR (RT-qPCR) using BSCP31 gene specific primers and probe. Standard curve was generated from DNA template extracted from 10-fold serial dilution of living B. abortus RB51 vaccine to evaluate the sensitivity of RT-qPCR. Results revealed that three batches of living Brucella vaccines were acceptable for Brucella colony count when traditional bacterial enumeration method was used. Results of RT-qPCR were identical to that of conventional bacterial count. Results concluded that RT-qPCR was relatively sensitive compared to traditional bacterial colony count of these vaccines.


Pacing and Performance Analysis of the World's Fastest Female Ultra-Triathlete in 5x and 10x Ironman.
The aim of the present case study was to analyse the performance data of the world's best female ultra-triathlete setting a new world record in a Quintuple (5xIronman) and Deca Iron (10xIronman) ultra-triathlon, within and between race days, and between disciplines (cycling and running) and races (Quintuple and Deca Iron ultra-triathlon). The subject was an elite female triathlete (52 kg, 169 cm) born in 1983. At the time of her world record in Quintuple Iron ultra-triathlon she had an age of 35 years and at the time of the world record in Deca Iron ultra-triathlon 36 years old. The distribution of time spent in each discipline and transitions was 8.48% in swimming, 51.67% cycling, 37.91% running, and 1.94% transitions. There was no difference between the race days of the average speed neither in cycling nor running. The running pace had a within-day variation larger than the cycling pace, and also varied more between race days. In conclusion, the world's best female ultra-triathlete adopted a steady (even) pacing strategy for both cycling and running, without substantial variations within- or between race days, for both the world record in a Quintuple and a Deca Iron ultra-triathlon.


Recurrent aphthous stomatitis vs. recurrent herpes: do you know the difference?
Herpetic and aphthous ulcers can be easily separated from each other on a clinical basis. Most patients who suffer from recurrent oral ulcers, suffer from one of the three forms of aphthous stomatitis that can be effectively treated. Unfortunately, the dental and medical professions are uninformed about recurrent oral ulcer etiology and proper therapies. The result is that large numbers of patients are repeatedly told there is no adequate treatment or control for their condition when in most cases that is not true. We should not permit that trend to continue. Our patients deserve better treatment from a more informed profession.


Domestic water carrying and its implications for health: a review and mixed methods pilot study in Limpopo Province, South Africa.
Lack of access to safe water remains a significant risk factor for poor health in developing countries. There has been little research into the health effects of frequently carrying containers of water. The aims of this study were to better understand how domestic water carrying is performed, identify potential health risk factors and gain insight into the possible health effects of the task. Mixed methods of data collection from six were used to explore water carrying performed by people in six rural villages of Limpopo Province, South Africa. Data was collected through semi-structured interviews and through observation and measurement. Linear regression modelling were used to identify significant correlations between potential risk factors and rating of perceived exertion (RPE) or self reported pain. Independent t-tests were used to compare the mean values of potential risk factors and RPE between sub-groups reporting pain and those not reporting pain. Water carrying was mainly performed by women or children carrying containers on their head (mean container weight 19.5 kg) over a mean distance of 337 m. The prevalence of spinal (neck or back) pain was 69% and back pain was 38%. Of participants who carried water by head loading, the distance walked by those who reported spinal pain was significantly less than those who did not (173 m 95%CI 2-343; p = 0.048). For head loaders reporting head or neck pain compared to those who did not, the differences in weight of water carried (4.6 kg 95%CI -9.7-0.5; p = 0.069) and RPE (2.5 95%CI -5.1-0.1; p = 0.051) were borderline statistically significant. For head loaders, RPE was significantly correlated with container weight (r = 0.52; p = 0.011) and incline (r = 0.459; p = 0.018) Typical water carrying methods impose physical loading with potential to produce musculoskeletal disorders and related disability. This exploratory study is limited by a small sample size and future research should aim to better understand the type and strength of association between water carrying and health, particularly musculoskeletal disorders. However, these preliminary findings suggest that efforts should be directed toward eliminating the need for water carrying, or where it must continue, identifying and reducing risk factors for musculoskeletal disorders and physical injury.


Local and Systemic Changes Associated with Long-term, Percutaneous, Static Implantation of Titanium Alloys in Rhesus Macaques (Macaca mulatta).
Metal alloys are frequently used as implant materials in veterinary medicine. Recent studies suggest that many alloys induce both local and systemic inflammatory responses. In this study, 37 rhesus macaques with long-term skull-anchored percutaneous titanium alloy implants (duration, 0 to 14 y) were evaluated for changes in their hematology, coagulation, and serum chemistry profiles. Negative controls (n = 28) did not have implants. Macaques with implants had higher plasma D-dimer and lower antithrombin III concentrations than nonimplanted animals. In addition, animals with implants had higher globulin and lower albumin and calcium concentrations compared with nonimplanted macaques. Many of these changes were positively correlated with duration of implantation and the number of implants. Chronic bacterial infection of the skin was present around many of the implant sites and within deeper tissues. Representative histopathology around the implant site of 2 macaques revealed chronic suppurative to pyogranulomatous inflammation extending from the skin to the dura mater. X-ray fluorescence microscopy of tissue biopsies from the implant site of the same 2 animals revealed significantly higher levels of free metal ions in the tissue, including titanium and iron. The higher levels of free metal ions persisted in the tissues for as long as 6 mo after explantation. These results suggest that long-term skull-anchored percutaneous titanium alloy implants can be associated with localized inflammation, chronic infection, and leaching of metal ions into local tissues.


Building health care system capacity to respond to disasters: successes and challenges of disaster preparedness health care coalitions.
This research aimed to learn from the experiences of leaders of well-developed, disaster preparedness-focused health care coalitions (HCCs), both the challenges and the successes, for the purposes of identifying common areas for improvement and sharing "promising practices." Little data have been collected regarding the successes and challenges of disaster preparedness-focused HCCs in augmenting health care system preparedness for disasters. Semi-structured interviews were conducted with a sample of nine HCC leaders. Transcripts were analyzed qualitatively. The commonly noted benefits of HCCs were: community-wide and regional partnership building, providing an impartial forum for capacity building, sharing of education and training opportunities, staff- and resource-sharing, incentivizing the participation of clinical partners in preparedness activities, better communication with the public, and the ability to surge. Frequently noted challenges included: stakeholder engagement, staffing, funding, rural needs, cross-border partnerships, education and training, and grant requirements. Promising practices addressed: stakeholder engagement, communicating value and purpose, simplifying processes, formalizing connections, and incentivizing participation. Strengthening HCCs and their underlying systems could lead to improved national resilience to disasters. However, despite many successes, coalition leaders are faced with obstacles that may preclude optimal system functioning. Additional research could: provide further insight regarding the benefit of HCCs to local communities, uncover obstacles that prohibit local disaster-response capacity building, and identify opportunities for an improved system capacity to respond to, and recover from, disasters.


Family Communication and Cascade Testing for Fragile X Syndrome.
A total of 679 families who had at least one child with fragile X syndrome (FXS) were recruited from a research registry to participate in a survey examining cascade testing and communication about FXS. Families had a total of 1117 children (804 males, 313 females). Most families (84 %) had tested all of their children. The main reason for not testing, which did not differ by gender or age of the child, was that the child did not show signs of FXS (68 %). Families talked with their children about FXS occasionally (47 %) although 16 % said they do not talk about it. Most families (66 %) had told their children their FXS status, with males and those with the premutation being less likely to be told test results. Of those that did not, 46 % said that they would tell their child when they were old enough to understand, whereas 34 % had either decided they would not tell or were not sure if or when they were going to tell. About a quarter of respondents (28 %) indicated that no extended family members had been tested, with income and communication about FXS being the strongest predictors. Results from this large scale survey provide important data on how families communicate about FXS and reasons testing is or is not sought. This information can be used by genetic counsellors in providing follow-up to families after a FXS diagnosis.


The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Indications for intracranial pressure monitoring.
ICP monitoring per se has never been subjected to a prospective randomized clinical trial (PRCT) to establish its efficacy (or lack thereof) in improving outcome from severe head injury. Hence, there are insufficient data to support its use as a standard. However, there is a large body of published clinical experience that indicates that ICP monitoring (1) helps in the earlier detection of intracranial mass lesions, (2) can limit the indiscriminate use of therapies to control ICP which themselves can be potentially harmful, (3) can reduce ICP by CSF drainage and thus improve cerebral perfusion, (4) helps in determining prognosis, and (5) may improve outcome. ICP monitoring is therefore used by most head injury experts in the United States and is accepted as a relatively low-risk high-yield, modest cost intervention. Comatose head injury patients (GCS 3-8) with abnormal CT scans should undergo ICP monitoring. Comatose patients with normal CT scans have a much lower incidence of intracranial hypertension unless they have two or more of the following features at admission: age over 40, unilateral or bilateral motor posturing, or a systolic blood pressure of less than 90 mm Hg. ICP monitoring in patients with a normal CT scan with two or more of these risk factors is suggested as a guideline. Routine ICP monitoring is not indicated in patients with mild or moderate head injury. However, it may be undertaken in certain conscious patients with traumatic mass lesions at the discretion of the treating physician.


Homeless Shelter Characteristics and Prevalence of SARS-CoV-2.
The unfolding COVID-19 pandemic has predictably followed the familiar contours of well established socioeconomic health inequities, exposing and often amplifying preexisting disparities. People living in homeless shelters are at higher risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared to the general population. The purpose of this study was to identify shelter characteristics that may be associated with higher transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a cross-sectional assessment of five congregate shelters in Rhode Island. Shelter residents 18 years old and older were tested for SARS-CoV-2 from April 19-April 24, 2020. At time of testing, we collected participant characteristics, symptomatology, and vital signs. Shelter characteristics and infection control strategies were collected through a structured phone questionnaire with shelter administrators. A total of 299 shelter residents (99%, 299/302) participated. Thirty-five (11.7%) tested positive for SARS-CoV-2. Shelter-level prevalence ranged from zero to 35%. Symptom prevalence did not vary by test result. Shelters with positive cases of SARS-CoV-2 were in more densely populated areas, had more transient resident populations, and instituted fewer physical distancing practices compared to shelters with no cases. SARS-CoV-2 prevalence varies with shelter characteristics but not individual symptoms. Policies that promote resident stability and physical distancing may help reduce SARS-CoV-2 transmission. Symptom screening alone is insufficient to prevent SARS-CoV-2 transmission. Frequent universal testing and congregate housing alternatives that promote stability may help reduce spread of infection.


Thymic carcinoma. A clinicopathologic study of 13 cases.
Thymic carcinoma (TCA) is a thymic epithelial neoplasm with obvious cytologic atypia. We studied 13 cases of TCA by light microscopy, immunohistochemistry, and electron microscopy and correlated the findings with clinical features. The patients' mean age was 54.2 years (range 30-74); the male/female ratio was 7/6. Twelve of the 13 patients presented with signs and symptoms caused by compression of mediastinal organs; the other patient was asymptomatic. Paraneoplastic syndromes were never seen. At thoracotomy, 11 tumors invaded or adhered to surrounding structures; the other two were encapsulated. The histologic types include squamous carcinoma including the lymphoepithelioma-like subtype (seven cases), small cell carcinoma (four cases), clear cell carcinoma (one case), and adenosquamous carcinoma (one case). Positive immunoperoxidase studies were as follows: keratin (13 cases), epithelial membrane antigen (EMA) (13 cases), leukocyte common antigen (none), carcinoembryonic antigen (CEA) (five cases), B72.3 (seven cases), Leu 7 (two cases), human placental alkaline phosphatase (none), vimentin (none), and chromogranin (one case). This profile is similar to those of normal thymus and thymoma except for the absence of CEA, B72.3, EMA in normal thymus, and the absence of CEA and B72.3 in thymoma. Electron-microscopic studies performed on eight cases showed glandular and squamous differentiation in one adenosquamous carcinoma, squamous differentiation in five squamous carcinomas, and neuroendocrine differentiation in one small-cell carcinoma. Nine patients died (three due to postoperative complications and six due to recurrences or metastasis at 3-36 months). Four patients (all with squamous carcinoma) were alive without disease at 2-60 months. The clinical and pathologic features were comparable with those of approximately 62 other cases of TCA previously reported. There are a number of well-defined histologic types of TCA that allow the pathologist to make a differential diagnosis of TCA from tumors extending or metastatic to thymus or other primary mediastinal tumors. Although neither asymptomatic presentation nor encapsulation improves the poor prognosis of TCA, the squamous carcinoma subtype is associated with a better outcome than the other subtypes. Based on the electronmicroscopic and immunohistochemical findings, the presence of normal thymic tissue at the periphery of several tumors, and the observation that several TCA arose from preexisting thymomas or thymic cysts, we conclude that TCA is derived from thymic epithelium.


Impact of von Willebrand disease on health-related quality of life in a pediatric population.
Von Willebrand disease (VWD) is the most frequent inherited bleeding disorder. Whether VWD is associated with health-related quality of life (HR-QoL) in children is unknown. This nationwide cross-sectional study measured HR-QoL in children with moderate or severe VWD. Our primary aim was to compare HR-QoL of VWD patients with that of reference populations. Additionally, we studied the impact of bleeding phenotype and VWD type on HR-QoL. HR-QoL was assessed with the Infant/Toddler QoL Questionnaire (0-5 years) and Child Health Questionnaire (6-15 years), and compared with reference population scores. Multivariate analysis was used to evaluate the influence of type of VWD and bleeding phenotype on HR-QoL scores. Preschool children (0-5 years, n = 46) with VWD had lower HR-QoL scores for general health perceptions and parental time than reference populations. School children (6-15 years, n = 87) with VWD had lower scores for physical functioning, role functioning - emotional/behavioral, general health perceptions, and physical summary. Type of VWD was associated with HR-QoL in school children for bodily pain, general health perceptions, parental emotion, family activities, and physical summary. Scores of children with type 3 VWD were, on average, 15 points lower than those of the reference population on the above-mentioned scales. A more severe bleeding phenotype was associated with a lower score on 11/15 physical, emotional and social scales. HR-QoL is lower in VWD children than in reference populations, in particular in school children. The negative impact of VWD is sensitive to type of VWD and bleeding phenotype; as well as physical scales, emotional and social scales are affected.


Volume-Outcome Relationship in Surgical Interventions for Spinal Metastases.
Surgery for spinal metastases is challenging and carries a high risk of perioperative morbidity and mortality. Procedures with such characteristics often exhibit a volume-outcome relationship. This has not been previously characterized for spinal metastasis surgery to our knowledge. The Florida State Inpatient Database (2011 through 2014) was queried to identify patients who had undergone surgery for spinal metastases. Surgeon and hospital surgical volumes were compared with 90-day complication and readmission rates to develop procedural cut-points used to define high and low-volume providers. These were included in a multivariable logistic regression analysis that was adjusted for confounders. A separate analysis was performed to evaluate the effect of race/ethnicity and insurance status on the likelihood of receiving care from a high-volume surgeon or hospital. This study included 3,135 patients treated by 1,488 surgeons at 162 hospitals. Patients treated at low-volume hospitals had significantly higher odds of having postoperative complications (odds ratio [OR] = 1.47; 95% confidence interval [CI] = 1.13, 1.91) and readmissions (OR = 1.36; 95% CI = 1.06, 1.75). Those treated by low-volume surgeons also demonstrated a higher likelihood of complications (OR = 1.40; 95% CI = 1.16, 1.69) and readmissions (OR = 1.38; 95% CI = 1.17, 1.62). The likelihood of receiving intervention from a high-volume surgeon was significantly lower for African Americans (OR = 0.55; 95% CI = 0.41, 0.75) and Hispanics (OR = 0.60; 95% CI = 0.44, 0.83). The odds of being treated at a high-volume hospital were also significantly lower for African Americans (OR = 0.58; 95% CI = 0.40, 0.84) and Hispanics (OR = 0.28; 95% CI = 0.20, 0.38). There is a clear relationship between the volume and outcomes of surgical treatment of spinal metastases, with high-volume providers demonstrating reduced complication and readmission rates. Racial and ethnic minorities appear to experience health-care segregation when it comes to surgical care for spinal metastases. Regionalization of care for these conditions may help improve access to high-volume providers and mitigate disparities in care. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Growth-dependent and growth-independent translation of messengers for heterogeneous nuclear ribonucleoproteins.
The hnRNP A1 transcript has a relatively short 5'- untranslated region (UTR) starting with a pyrimidine tract similar to that of mRNAs encoded by the TOP [terminal oligo(pyrimidine)] genes in vertebrates. Such genes code for ribosomal proteins and for other proteins directly or indirectly involved in the production and function of the translation apparatus. As expected from the role of the pyrimidine tract in the translational regulation of TOP mRNAs, the A1 mRNA is more efficiently loaded onto polysomes in growing than in resting cells. On the other hand, a less stringent regulation with respect to that of other TOP mRNAs is observed, partially due to the presence of multiple transcription start sites within the pyrimidine tract, where transcripts with shorter TOP sequences are less sensitive to regulation. Thus, from the point of view of structural features and translation behaviour the A1 mRNA can be included in the class of TOP genes, suggesting a possible role of A1 in translation. Interestingly, a TOP-like behaviour was observed for hnRNP I mRNA but not for hnRNP C1/C2 and A2/B1 mRNAs, indicating the existence of two classes of hnRNPs with different translational regulation.


Biomarkers of Broccoli Consumption: Implications for Glutathione Metabolism and Liver Health.
Diet and lifestyle choices contribute to obesity and liver disease. Broccoli, a brassica vegetable, may mitigate negative effects of both diet and lifestyle. Currently, there are no clinically relevant, established molecular biomarkers that reflect variability in human absorption of brassica bioactives, which may be the cause of variability/inconsistencies in health benefits in the human population. Here, we focused on the plasma metabolite profile and composition of the gut microbiome in rats, a relatively homogenous population in terms of gut microbiota, genetics, sex and diet, to determine if changes in the plasma metabolite profiles caused by dietary broccoli relate to molecular changes in liver. Our aim was to identify plasma indicators that reflect how liver health is impacted by dietary broccoli. Rats were fed a 10% broccoli diet for 14 days. We examined the plasma metabolite composition by metabolomics analysis using GC-MS and gut microbiota using 16S sequencing after 0, 1, 2, 4, 7, 14 days of broccoli feeding. We identified 25 plasma metabolites that changed with broccoli consumption, including metabolites associated with hepatic glutathione synthesis, and with de novo fatty acid synthesis. Glutamine, stearic acid, and S-methyl-L-cysteine (SMC) relative abundance changes correlated with changes in gut bacteria previously implicated in metabolic disease and with validated increases in expression of hepatic NAD(P)H dehydrogenase [quinone] 1 (NQO1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), associated with elevated hepatic glutathione synthesis. Circulating biomarkers following broccoli consumption reflect gut-liver axis health.


Possible Internalization of an Enterovirus in Hydroponically Grown Lettuce.
Several studies have shown that enteric viruses can be transferred onto the surface of vegetables and fruits through spray irrigation, but, recently, reports have suggested viral contamination of vegetables sub-irrigated with reused wastewater. Hydroponic cultures, used to grow ready to eat fresh lettuce, have also been used to study the possibility of viral absorption through roots. This study was conducted to assess a possible risk of viral contamination in lettuce from contaminated water. The leaves of lettuce plants grown in hydroponic cultures where the roots were exposed to water containing Coxsakievirus B2, were analysed for evidence of the virus. The plants and water were sampled at different times and virus was measured using quantitative RT-PCR and infectivity assay. In leaf samples, the lowest observed infective data were lower than the qRT-PCR detection limits, suggesting that free viral RNA or damaged viruses are eliminated rapidly while infectious particles remain stable for a longer time. The obtained data revealed that the leaves were contaminated at a water concentration of 4.11 ± 1 Log Most Probable Number/L (8.03 ± 1 Log GC/L) a concentration observed in contaminated untreated water of wastewater treatment plants. However, the absorption dynamics and whether the virus is inactive in the leaves still remains to be clarified. Nevertheless, this work has practical implications for risk management in using reclaimed water for agricultural use; when irrigated vegetables are destined for raw consumption, virological contamination in water sources should be evaluated.


Biased and constitutive signaling in the CC-chemokine receptor CCR5 by manipulating the interface between transmembrane helices 6 and 7.
The equilibrium state of CCR5 is manipulated here toward either activation or inactivation by introduction of single amino acid substitutions in the transmembrane domains (TMs) 6 and 7. Insertion of a steric hindrance mutation in the center of TM7 (G286F in position VII:09/7.42) resulted in biased signaling. Thus, β-arrestin recruitment was eliminated, whereas constitutive activity was observed in Gαi-mediated signaling. Furthermore, the CCR5 antagonist aplaviroc was converted to a full agonist (a so-called efficacy switch). Computational modeling revealed that the position of the 7TM receptor-conserved Trp in TM6 (Trp-248 in position VI:13/6.48, part of the CWXP motif) was influenced by the G286F mutation, causing Trp-248 to change orientation away from TM7. The essential role of Trp-248 in CCR5 activation was supported by complete inactivity of W248A-CCR5 despite maintaining chemokine binding. Furthermore, replacing Trp-248 with a smaller aromatic amino acid (Tyr/Phe) impaired the β-arrestin recruitment, yet with maintained G protein activity (biased signaling); also, here aplaviroc switched to a full agonist. Thus, the altered positioning of Trp-248, induced by G286F, led to a constraint of G protein active, but β-arrestin inactive and thus biased, CCR5 conformation. These results provide important information on the molecular interplay and impact of TM6 and TM7 for CCR5 activity, which may be extrapolated to other chemokine receptors and possibly to other 7TM receptors.


Sphingomyelin and cholesterol promote HIV-1 gp41 pretransmembrane sequence surface aggregation and membrane restructuring.
The interfacial sequence DKWASLWNWFNITNWLWYIK, preceding the transmembrane anchor of gp41 glycoprotein subunit, has been shown to be essential for fusion activity and incorporation into virions. HIV(c), a peptide representing this region, formed lytic pores in liposomes composed of the main lipids occurring in the human immunodeficiency virus, type 1 (HIV-1), envelope, i.e. 1-palmitoyl-2-oleoylphosphatidylcholine (POPC):sphingomyelin (SPM):cholesterol (Chol) (1:1:1 mole ratio), at low (>1:10,000) peptide-to-lipid mole ratio, and promoted the mixing of vesicular lipids at >1:1000 peptide-to-lipid mole ratios. Inclusion of SPM or Chol in POPC membranes had different effects. Whereas SPM sustained pore formation, Chol promoted fusion activity. Even if partitioning into membranes was not affected in the absence of both SPM and Chol, HIV(c) had virtually no effect on POPC vesicles. Conditions described to disturb occurrence of lateral separation of phases in these systems reproduced the high peptide-dose requirements for leakage as found in pure POPC vesicles and inhibited fusion. Surface aggregation assays using rhodamine-labeled peptides demonstrated that SPM and Chol promoted HIV(c) self-aggregation in membranes. Employing head-group fluorescent phospholipid analogs in planar supported lipid layers, we were able to discern HIV(c) clusters associated to ordered domains. Our results support the notion that the pretransmembrane sequence may participate in the clustering of gp41 monomers within the HIV-1 envelope, and in bilayer architecture destabilization at the loci of fusion.


Triple-Negative Essential Thrombocythemia Complicated by Thrombosis and Acquired von Willebrand Disease in a Young Man.
BACKGROUND Essential thrombocythemia (ET) is a type of myeloproliferative neoplasm (MPN) characterized by sustained thrombocytosis in peripheral blood. Patients typically have gene mutations like JAK2V617F, CALR, and MPLW515L/K. This report describes a young man with ET without any of the above mutations who had paradoxical bleeding due to acquired Von-Willebrand disease. CASE REPORT A young man with a medical history of thrombocytosis on aspirin presented with acute chest pain and was found to have had a myocardial infarction. Emergency cardiac catheterization revealed a thrombotic occlusion of the left anterior descending (LAD) artery and the right posteriolateral system, with an ejection fraction of 25%. He underwent thrombectomy and balloon angioplasty with LAD stenting, and an Impella 2.5 was inserted due to severe left ventricular dysfunction with akinesia. Aspirin and ticagrelor were administered, but the patient later experienced postoperative bleeding from the site of the Impella device. The bleeding was attributed to acquired Von-Willebrand disease secondary to ET. Emergency plateletpheresis was recommended. Further workup demonstrated that he was triple-negative for JAK2, MPL, and CALR gene mutations. CONCLUSIONS The paradoxical bleeding resulting from acquired Von-Willebrand disease was likely an entirely separate entity from the hyper-thrombotic state expected from ET. Careful assessment of clinical symptoms and laboratory markers, in addition to a high degree of suspicion, are needed to diagnose acquired Von-Willebrand disease as a complication of ET.


Intermittent hypoxia-induced sensitization of central chemoreceptors contributes to sympathetic nerve activity during late expiration in rats.
Hypertension elicited by chronic intermittent hypoxia (CIH) is associated with elevated activity of the thoracic sympathetic nerve (tSN) that exhibits an enhanced respiratory modulation reflecting a strengthened interaction between respiratory and sympathetic networks within the brain stem. Expiration is a passive process except for special metabolic conditions such as hypercapnia, when it becomes active through phasic excitation of abdominal motor nerves (AbN) in late expiration. An increase in CO(2) evokes late-expiratory (late-E) discharges phase-locked to phrenic bursts with the frequency increasing quantally as hypercapnia increases. In rats exposed to CIH, the late-E discharges synchronized in AbN and tSN emerge in normocapnia. To elucidate the possible neural mechanisms underlying these phenomena, we extended our computational model of the brain stem respiratory network by incorporating a population of presympathetic neurons in the rostral ventrolateral medulla that received inputs from the pons, medullary respiratory compartments, and retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). Our simulations proposed that CIH conditioning increases the CO(2) sensitivity of RTN/pFRG neurons, causing a reduction in both the CO(2) threshold for emerging the late-E activity in AbN and tSN and the hypocapnic threshold for apnea. Using the in situ rat preparation, we have confirmed that CIH-conditioned rats under normal conditions exhibit synchronized late-E discharges in AbN and tSN similar to those observed in control rats during hypercapnia. Moreover, the hypocapnic threshold for apnea was significantly lowered in CIH-conditioned rats relative to that in control rats. We conclude that CIH may sensitize central chemoreception and that this significantly contributes to the neural impetus for generation of sympathetic activity and hypertension.


Effects of alkali and transition metal-doped TiO2 hole blocking layers on the perovskite solar cells obtained by a two-step sequential deposition method in air and under vacuum.
Planar perovskite solar cells (PPSCs) have received great attention in recent years due to their intriguing properties, which make them a good choice for photovoltaic applications. In this work, the effect of alkali and transition metal-doped TiO2 (cesium-doped TiO2 (Cs-TiO2) and yttrium-doped TiO2 (Y-TiO2)) compact layers on the optical, structural and the photovoltaic performance of the PPSCs have been investigated. The perovskite layer syntheses were carried out by depositing a lead iodide (PbI2) layer via spin-coating; converting PbI2 into methyl ammonium iodide (CH3NH3PbI3) by chemical vapor deposition (CVD) and spin-coating at 60 min and 60 s conversion times respectively. The as-deposited PPSCs were studied layer-by-layer using an X-ray diffractometer, scanning electron microscope, and UV-vis diffuse reflectance, transmittance and absorbance. The power conversion efficiency for stable processed perovskite solar cells were 3.61% and 12.89% for air and vacuum processed, respectively.


The impact of mitochondrial DNA on human lifespan: a view from studies on centenarians.
The role of inherited and somatic mutations of mitochondrial DNA (mtDNA) in aging and longevity is complex and highly controversial, owing to its peculiar genetics, including the phenomenon of heteroplasmy. Most of the data on mtDNA and longevity have been obtained on humans and particularly on centenarians, i. e., people who escaped or delayed the major age-related pathologies and reached the extreme limit of human lifespan. In this review we summarize the most recent advances in this field that suggest a consistent role in human longevity of both germ-line inherited and somatically acquired mutations. The particular case of the association with longevity of the somatic C150T mutation is extensively discussed, challenging the tenet that mtDNA mutations are basically detrimental. We also stress several limitations of our present knowledge, regarding the difficulty in extrapolating to humans the results obtained in animal models, owing to a variety of biological differences, including the very limited genetic variability of mtDNA in the strains used in laboratory experiments. The use of high-throughput technologies and the extensive analysis, possibly at the single cell level, of different tissues and cell types derived from the same individual will help in disentangling the complexity of mtDNA in aging and longevity.


Evolutionary Image Transition and Painting Using Random Walks.
We present a study demonstrating how random walk algorithms can be used for evolutionary image transition. We design different mutation operators based on uniform and biased random walks and study how their combination with a baseline mutation operator can lead to interesting image transition processes in terms of visual effects and artistic features. Using feature-based analysis we investigate the evolutionary image transition behaviour with respect to different features and evaluate the images constructed during the image transition process. Afterwards, we investigate how modifications of our biased random walk approaches can be used for evolutionary image painting. We introduce an evolutionary image painting approach whose underlying biased random walk can be controlled by a parameter influencing the bias of the random walk and thereby creating different artistic painting effects.


Microscopic colitis with granulomatous inflammation.
To present four cases in which the clinical and endoscopic findings were consistent with microscopic colitis, but the inflammatory infiltrate included a conspicuous granulomatous reaction. Microscopic colitis is defined as a syndrome of chronic watery diarrhoea with a chronic inflammatory cell infiltrate in the colonic mucosa and without significant abnormalities at colonoscopy. It encompasses both collagenous and lymphocytic colitis. In all cases the clinical course and endoscopic findings were unlike Crohn's disease and no infectious agents were identified. In all cases the main symptom was frequent watery diarrhoea, all were female and there were no endoscopic findings apart from mild mucosal erythema. Histologically, an active chronic inflammatory infiltrate was accompanied by scattered non-necrotizing granulomas, often closely associated with crypt epithelium (cryptolytic or pericryptal granulomas). In three of the patients the symptoms began after antibiotic use or had worsened with antibiotic use. Two of the patients were on allopurinol at the time of the onset of symptoms. In two of the patients symptoms have continued for more than 10 years. One patient died as a result of medical complications relating to severe diarrhoea and dehydration. Microscopic colitis rarely may be characterized by granulomatous inflammation. Such patients should not be regarded as having Crohn's disease.