Atypical antipsychotic medications and hyponatremia in older adults: a population-based cohort study.
A number of case reports have suggested a possible association between atypical antipsychotic medications and hyponatremia. Currently, there are no reliable estimates of hyponatremia risk from atypical antipsychotic drugs. The objective of this study was to examine the 30-day risk of hospitalization with hyponatremia in older adults dispensed an atypical antipsychotic drug relative to no antipsychotic use. The design of this study was a retrospective, population-based cohort study. The setting of this study was in Ontario, Canada, from 2003 to 2012. Adults 65 years or older with an identified psychiatric condition who were newly dispensed risperidone, olanzapine, or quetiapine in the community setting compared to adults with similar indicators of baseline health who were not dispensed such a prescription. The primary outcome was the 30-day risk of hospitalization with hyponatremia. The tracer outcome (an outcome that is not expected to be influenced by the study drugs) was the 30-day risk of hospitalization with bowel obstruction. These outcomes were assessed using hospital diagnosis codes. Using health administrative data, we applied a propensity score technique to match antipsychotic users 1:1 to non-users of antipsychotic drugs (58,008 patients in each group). We used conditional logistic regression to compare outcomes among the matched users and non-users. A total of 104 baseline characteristics were well-balanced between the two matched groups. Atypical antipsychotic use compared to non-use was associated with an increased risk of hospitalization with hyponatremia within 30 days (86/58,008 (0.15 %) versus 53/58,008 (0.09 %); relative risk 1.62 (95 % confidence interval (CI) 1.15 to 2.29); absolute risk increase 0.06 % (95 % CI 0.02 to 0.10)). The limited number of events precluded some additional analyses to confirm if the association was robust. Atypical antipsychotic use compared to non-use was not associated with hospitalization with bowel obstruction within 30 days (55/58,008 (0.09 %) versus 44/58,008 (0.08 %); relative risk 1.25 (95 % CI 0.84 to 1.86)). We could only study older adults within our data sources. In this study, the use of an atypical antipsychotic was associated with a modest but statistically significant increase in the 30-day risk of a hospitalization with hyponatremia. The association was less pronounced than that described with other psychotropic drugs.


Laparoscopic adjustable gastric banding, the past, the present and the future.
The laparoscopic implantation of an adjustable gastric banding (LAGB) was first described in 1993. Thereafter, the LAGB underwent to a lot of modifications, revision and refinements to become as it is currently defined. This procedure quickly became one of the most common bariatric surgical operations in the world in the first decade of the 2000s but, over the last few years, it has turned into the fourth more common procedure. A series of more or less clear reasons, led to this decrease of LAGB. The knowledge of the history of the LAGB, of its evolution over the years and its limitations can be the key-point to recognize the reasons that are leading to its decline. The adjustability and the absolute reversibility characteristic of LAGB, make this surgical procedure a "bridge treatment" to allow the specific goal of eradicating obesity.


A benzodiazepine receptor antagonist decreases sleep and reverses the hypnotic actions of flurazepam.
The benzodiazepine receptor antagonist 3-hydroxymethyl-beta-carboline, which blocks several of the pharmacological actions of benzodiazepines, induces a dose-dependent increase in sleep latency in the rat. Furthermore, at a low dose that by itself does not affect sleep, 3-hydroxymethyl-beta-carboline blocks sleep induction by a large dose of flurazepam. The benzodiazepine receptor may play a role in both the physiological regulation and pharmacological induction of sleep.


Covalent Enzyme Inhibition through Fluorosulfate Modification of a Noncatalytic Serine Residue.
Irreversible enzyme inhibitors and covalent chemical biology probes often utilize the reaction of a protein cysteine residue with an appropriately positioned electrophile (e.g., acrylamide) on the ligand template. However, cysteine residues are not always available for site-specific protein labeling, and therefore new approaches are needed to expand the toolkit of appropriate electrophiles ("warheads") that target alternative amino acids. We previously described the rational targeting of tyrosine residues in the active site of a protein (the mRNA decapping scavenger enzyme, DcpS) using inhibitors armed with a sulfonyl fluoride electrophile. These inhibitors subsequently enabled the development of clickable probe technology to measure drug-target occupancy in live cells. Here we describe a fluorosulfate-containing inhibitor (aryl fluorosulfate probe (FS-p1)) with excellent chemical and metabolic stability that reacts selectively with a noncatalytic serine residue in the same active site of DcpS as confirmed by peptide mapping experiments. Our results suggest that noncatalytic serine targeting using fluorosulfate electrophilic warheads could be a suitable strategy for the development of covalent inhibitor drugs and chemical probes.


The enhancement of biofilm formation in Group B streptococcal isolates at vaginal pH.
Group B streptococcus (GBS) is a common asymptomatic colonizer in acidic vagina of pregnant women and can transmit to newborns, causing neonatal pneumonia and meningitis. Biofilm formation is often associated with bacterial colonization and pathogenesis. Little is known about GBS biofilm and the effect of environmental stimuli on their growth along with biofilm formation. The objective of this study was to investigate the survival and biofilm formation of GBS, isolated from pregnant women, in nutrient-limited medium under various pH conditions. Growth and survival experiments were determined by optical density and viable counts. Crystal violet staining, scanning electron microscopy, and atomic force microscopy (AFM) were used to analyze the capacity of biofilm production. Our results showed that GBS isolates proliferated with increasing pH with highest maximum specific growth rate (μmax) at pH 6.5, but survived at pH 4.5 for longer than 48 h. Biofilm formation of the 80 GBS isolates at pH 4.5 was significantly higher than at pH 7.0. This difference was confirmed by two other methods. The low elastic modulus obtained from samples at pH 4.5 by AFM revealed the softness of biofilm; in contrast, little or no biofilm was measured at pH 7.0. Under acidic pH, the capability of biofilm formation of serotypes III and V showed statistically significant difference from serotypes Ia and Ib. Our finding suggested that survival and enhanced biofilm formation at vaginal pH are potentially advantageous for GBS in colonizing vagina and increase the risk of vaginosis and neonatal infection.


Global transcriptome analysis of salt acclimated Prochlorococcus AS9601.
Molecular processes leading to salt stress acclimation in the model cyanobacterium Prochlorococcus are not known. To address this, we used RNA sequencing (RNAseq) to compare the global transcriptome of two exponential-phase populations of Prochlorococcus AS9601 cells - acclimated to high salt (5%, w/v) and normal seawater salt (3.8%, w/v). Experiments showed that salt acclimated cells exhibit slower growth rates with a doubling time almost twice as controls. Approximately 1/3 of the genome was found to be differentially expressed (p-value <0.05), but a considerably large number of these genes are "hypothetical proteins" with unknown function. Transcript abundance were higher for genes involved in respiratory electron flow, carbon fixation, osmolyte/compatible solute biosynthesis and inorganic ion transport. Many of the highly expressed genes are 'high light inducible proteins' believed to be part of the general Prochlorococcus stress response. Transcript abundance were lower for genes involved in photosynthetic electron transport and cell division. The relative reduction in transcript abundance for genes encoding proteins containing heme groups and iron transporters suggests cellular iron requirements in salt acclimated cells maybe lower. The results presented here provide the first glimpse into global gene expression changes in Prochlorococcus cells due to salt stress.


Lower cognitive control network connectivity in stroke participants with depressive features.
Around one-third of people develop depression following ischaemic stroke, yet the underlying mechanisms are poorly understood. Post-stroke depression has been linked to frontal infarcts, mainly lesions in the left dorsolateral prefrontal cortex (DLPFC). But depression is a network disorder that cannot be fully characterised through lesion-symptom mapping. Researchers of depression in non-stroke populations have successfully tapped into the cognitive control network (CCN) using the bilateral DLPFC as a seed, and found that CCN resting-state connectivity is reduced in even mildly depressed subjects, compared to healthy controls. Hence, we aimed to investigate the association between post-stroke depressive features and the CCN resting-state connectivity in a stroke population. We analysed DLPFC resting-state connectivity in 64 stroke participants, 20 of whom showed depressive features assessed with the Patient Health Questionnaire (PHQ-9) at 3 months after stroke. We directly compared groups showing symptoms of depression with those who did not, and performed a regression with PHQ-9 scores in all participants, controlling for age, gender, lesion volume and stroke severity. Post-stroke depression was associated with lower connectivity between the left DLPFC and the right supramarginal gyrus (SMG) in both group and regression analyses. Neither the seed nor the results overlapped with stroke lesions. These findings confirm an important role of the left DLPFC in post-stroke depression, but now show that large-scale network disruptions following stroke associated with depressive features occur without lesions in the DLPFC.


Acute cardiovascular effects of ethanol A controlled non-invasive study.
The acute cardiac effects of ethanol (1 g/kg orally within 60 minutes) were examined in 22 healthy volunteers (11 men and 11 women) by M-mode echocardiography and systolic time intervals for three hours after beginning ingestion. Each subject also took part in a control study, in which the same volume of juice was substituted for ethanol. Heart rate increased by 15% and cardiac output by 17% during ethanol intake, while total peripheral resistance decreased by 15%. Left ventricular end-diastolic diameter was shortened by 2% during the declining phase of blood ethanol concentration; stroke volume and circumferential wall stress were simultaneously decreased by 7% and 5%, respectively. No ethanol-related changes were noted in echocardiographic indices of left ventricular function, neither were any sex differences observed in the cardiovascular changes after ethanol ingestion. Each of the systolic time intervals was significantly altered even during the control experiment. The responses of each of these intervals to ethanol differed significantly from those in the control test as well. Notably, the pre-ejection period/ejection time ratio rose after ethanol, this change, according to simultaneous echocardiographic data, resulting from reduced preload instead of impaired contractility, as maintained in previous investigations. It is concluded that alcohol in modest doses is capable of altering each of the extramyocardial influences on left ventricular function--heart rate, preload, and afterload--but does not impair myocardial performance, at least in normal subjects.


Epidemiology of Depression and Anxiety in Gout: A Systematic Review and Metaanalysis.
To conduct a systematic review of depression and anxiety among patients with gout that specifically evaluates the prevalence, incidence, determinants, and effects of these mental health comorbidities. We conducted a literature search in Medline, Embase, Cochrane Database of Systematic Reviews, CINAHL, and PsycINFO using indexed terms and key words to identify studies reporting on depression/anxiety in patients with gout. This review included full-text articles published in English that reported on patients with gout, evaluated depression/anxiety using a routinely reported measure, and provided estimates or sufficient data on the prevalence, incidence, determinants, or effects of depression/anxiety. Metaanalyses were conducted using random effects models. Twenty of 901 articles identified through the search strategy met our inclusion criteria. All 20 studies evaluated depression, while only 10 assessed anxiety (50%). Metaanalyses suggest a positive association between mental health disorders and gout, as resultant pooled OR were 1.29 (95% CI 1.07-1.56) for depression and 1.29 (95% CI 0.96-1.73) for anxiety. Findings from four studies reporting on the incidence of depression in patients with gout resulted in a pooled HR of 1.17 (95% CI 1.01-1.36). Significant determinants of depression included number of tophi, frequency of flares, and oligo/polyarticular gout. Our systematic review suggests that depression and anxiety are significantly associated with gout, highlighting the need for future research to focus on the onset of mental disorders after gout diagnosis. We also identify potential targets for intervention.


An FMRI auditory oddball study of combined-subtype attention deficit hyperactivity disorder.
Studies of attention deficit hyperactivity disorder (ADHD) have reliably found reduced amplitude event-related potentials (ERPs) measuring attention-related brain function, indicating impairment in the brain's ability to automatically orient attention to odd or novel environmental stimuli and to represent that information in working memory. However, the relationship between abnormal neurocognition and dysfunction in specific brain regions in ADHD remains unclear. The authors used functional magnetic resonance imaging (fMRI) to identify brain regions with abnormal hemodynamic activity during processing of target and novelty oddball stimuli that engage attention. Forty-six boys 11-18 years of age participated in the study, including 23 diagnosed as having ADHD with hyperactivity and impulsivity (combined type) and 23 demographically matched control subjects. Event-related fMRI data were collected while participants performed a three-stimulus auditory oddball task. Hemodynamic activity was compared between ADHD participants and control subjects in brain regions previously linked to P3 ERPs. Participants with ADHD showed deficits in brain activity elicited by infrequent attentionally engaging stimuli in regions associated with attentional orienting and working-memory cognitive processes. These deficits co-occurred with highly variable and slow task performance. This study links ADHD attentional orienting and working-memory deficits to dysfunction in specific cortical brain regions. The results indicate that ADHD pathophysiology impairs brain systems that are important for allocating attention and using cognitive representations to guide cognition and behavior. Attention-related neural dysfunction is thus an important factor to consider in neurobiological theories of ADHD.


Factors influencing surgical treatment decisions for breast cancer: a qualitative exploration of surgeon and patient perspectives.
The rate of mastectomy is much higher in Newfoundland and Labrador than in any other province in Canada, even for women diagnosed at an early stage. In this paper, we present qualitative data from women who have made a decision for surgical treatment and from breast surgeons in an effort to better explicate factors influencing breast cancer (bca) surgical decision-making. The study's descriptive, qualitative design involved holding interviews with breast surgeons and holding focus groups and interviews with women who were offered the choice of breast-conserving surgery (bcs) or mastectomy (mt). Participants included 35 women and 13 surgeons. High interest in mt and increasing requests for prophylactic contralateral mt were evident. A host of factors-clinical, demographic, psychosocial, education-related, and cultural-influenced the decisions. A key factor for women was fear of recurrence and a need to "just get rid of it," but the experiences of others also influenced the decisions. Life stage and family considerations also factored prominently into women's decisions. Women with early-stage bca more often chose mt and often demanded prophylactic removal of the healthy breast. Findings highlight the importance of ensuring that women at average risk are appropriately counselled about the low likelihood of a subsequent contralateral bca and the lack of survival benefit associated with prophylactic contralateral mt. Findings also revealed other areas of presurgical discussion that might help women think through their personal circumstances and values so as to encourage informed surgical decisions.


Effect of familiarity on the processing of human faces.
Most brain imaging studies on face perception have investigated the processing of unknown faces and addressed mainly the question of specific face processing in the human brain. The goal of this study was to highlight the effects of familiarity on the visual processing of faces. Using [15O]water 3D Positron Emission Tomography, regional cerebral blood flow distribution was measured in 11 human subjects performing an identical task (gender categorization) on both unknown and known faces. Subjects also performed two control tasks (a face recognition task and a visual pattern discrimination task). They were scanned after a training phase using videotapes during which they had been familiarized with and learned to recognize a set of faces. Two major results were obtained. On the one hand, we found bilateral activations of the fusiform gyri in the three face conditions, including the so-called fusiform-face area, a region in the right fusiform gyrus specifically devoted to face processing. This common activation suggests that different cognitive tasks performed on known and unknown faces require the involvement of this fusiform region. On the other hand, specific regional cerebral blood flow changes were related to the processing of known and unknown faces. The left amygdala, a structure involved in implicit learning of visual representations, was activated by the categorization task on unknown faces. The same task on known faces induced a relative decrease of activity in early visual areas. These differences between the two categorization tasks reveal that the human brain processes known and unknown faces differently.


Executive functioning in children with an Autism Spectrum Disorder: can we differentiate within the spectrum?
The aim of this study was to investigate whether children with high-functioning autism (HFA), Asperger's syndrome (AS), and pervasive developmental disorder not otherwise specified (PDDNOS) can be differentiated from each other and from normal controls on their neurocognitive executive functioning (EF) profile. Children with HFA and AS showed the most EF deficits. The EF profile of the PDDNOS group was more disturbed that the normal control group, but was less disturbed than the profile of the HFA and AS groups. Little difference was found between the three PDD subtypes with respect to EF. This study supports the view that executive dysfunctioning plays an important role in autism. The usefulness of a distinction between different PDD subtypes was not demonstrated.


Bronchial hyperresponsiveness in women with chronic obstructive pulmonary disease related to wood smoke.
Chronic obstructive pulmonary disease (COPD) related to wood smoke exposure is characterized by important inflammation of the central and peripheral airways without significant emphysema. The objective of this study is to describe the bronchial hyperresponsiveness (BHR) level in women with COPD related to wood smoke exposure and to compare it with the BHR in women with COPD related to tobacco smoking. TWO GROUPS OF WOMEN WITH STABLE COPD WERE STUDIED: (1) wood smoke exposed (WS-COPD); and (2) tobacco smoke exposed (TS-COPD). A methacholine challenge test (MCT) was performed in all patients according to American Thoracic Society criteria. BHR levels were compared using the methacholine concentration, which caused a 20% fall in the FEV1 (PC20). Thirty-one patients, 19 with WS-COPD and 12 with TS-COPD, were included. There were no significant differences between the groups in baseline FVC, FEV1, IC, FEF25-75, and FEF25-75/FVC. All 31 patients had a positive MCT (PC20<16 mg/mL) and the fall in the FEV1 and IC was similar in both groups. The severity of BHR was significantly higher in the WS-COPD patients (PC20: 0.39 mg/mL) than in the TS-COPD patients (PC20: 1.24 mg/mL) (P=0.028). The presence of cough, phlegm, and dyspnea during the test were similar in both groups. We found moderate to severe BHR in women with WS-COPD, which was more severe than in the TS-COPD women with similar age and airflow obstruction. This paper suggests that the structural and inflammatory changes induced by the chronic exposure to wood smoke, described in other studies, can explain the differences with TS-COPD patients. Future studies may clarify our understanding of the impact of BHR on COPD physiopathology, phenotypes, and treatment strategies.


Die-off of plant pathogenic bacteria in tile drainage and anoxic water from a managed aquifer recharge site.
Managed aquifer recharge (MAR) can provide irrigation water and overcome water scarcity in agriculture. Removal of potentially present plant pathogens during MAR is essential to prevent crop diseases. We studied the die-off of three plant pathogenic bacteria in water microcosms with natural or filtered tile drainage water (TDW) at 10 and 25°C and with natural anoxic aquifer water (AW) at 10°C from a MAR site. These bacteria were: Ralstonia solanacearum (bacterial wilt), and the soft rot Pectobacteriaceae (SRP) Dickeya solani and Pectobacterium carotovorum sp. carotovorum (soft rot, blackleg). They are present in surface waters and cause destructive crop diseases worldwide which have been linked to contaminated irrigation water. Nevertheless, little is known about the survival of the SRP in aqueous environments and no study has investigated the persistence of R. solanacearum under natural anoxic conditions. We found that all bacteria were undetectable in 0.1 mL samples within 19 days under oxic conditions in natural TDW at 10°C, using viable cell counting, corresponding to 3-log10 reduction by die-off. The SRP were no longer detected within 6 days at 25°C, whereas R. solanacearum was detectable for 25 days. Whereas in anoxic natural aquifer water at 10°C, the bacterial concentrations declined slower and the detection limit was reached within 56 days. Finally, we modelled the inactivation curves with a modified Weibull model that can simulate different curve shapes such as shoulder phenomena in the beginning and long tails reflecting persistent bacterial populations. The non-linear model was shown to be a reliable tool to predict the die-off of the analysed plant pathogenic bacteria, suggesting its further application to other pathogenic microorganisms in the context of microbial risk assessment.


Japanese version of the Family Dermatology Life Quality Index: Translation and validation.
Skin conditions affect the quality of life (QoL) of patients and their family. To assess family members' QoL, a questionnaire uniquely designed for family members is necessary. We translated the Family Dermatology Life Quality Index (FDLQI), originally created and validated by Basra et al., into Japanese, and evaluated its reliability and validity. For psychometric evaluations, 150 dermatology patients and their family members were included. The Japanese version of the FDLQI showed high test-retest reliability (intraclass correlation coefficient = 0.95) and internal consistency reliability (Cronbach's alpha = 0.86). FDLQI scores significantly correlated with DLQI scores (r = 0.58, P < 0.01, Spearman's rho) and global question (GQ) which measured the patient's skin condition on a visual analog scale (r = 0.36, P < 0.01). Family members of patients with inflammatory skin diseases showed higher FDLQI scores than those with isolated lesions, but the difference was not statistically significant (P = 0.062, Mann-Whitney U-test). Responsiveness to change was demonstrated in a group in which the patient's skin condition was assessed as improved (n = 37, r = 0.46, P < 0.01) but not in that in which it became worse. The difference of the change between the two groups was statistically significant (P < 0.01). Additionally, the change in FDLQI scores and GQ were significantly correlated (r = 0.40, P < 0.01). Exploratory factor analysis suggested essential unidimensionality of the instrument. We showed acceptable validity and responsiveness of this Japanese version of FDLQI. Further clinical epidemiological studies are required to confirm this.


Subclavian artery laceration due to migration of a Hagie pin.
Injuries to subclavian artery are infrequent and usually occur due to gunshot or stab wounds and occasionally by blunt trauma to the chest. An early diagnosis and control of hemorrhage is essential to prevent death which may occur due to exsanguinating hemorrhage. A case of injury to the subclavian artery due to migration of a Hagie pin, which was used to treat the acromioclavicular separation, is reported. The subclavian artery was ligated initially, which produced an ischemic and functionless upper extremity. Revascularization of the arm was successfully accomplished by an axilloaxillary bypass grafting procedure. This simple procedure is advocated in situations requiring ligation of the subclavian artery following trauma, when direct reconstruction is not feasible.


[Hypertext and expertext: how to navigate on an ocean of information].
Computers have made possible an explosive increase of information flow. In this ocean of information it becomes more and more easy to get lost. Computers again may provide answers to this problem. This article describes principles of small-volume hypertext, large-volume hypertext and expertext as up-to-date navigation tools for the beginning as well as the advanced skipper. In addition, it is argued that the orthodontist should take responsibility in guiding these developments on his or her domain. He can do this by getting acquainted with the possibilities and choosing the right software. Ultimately, technology should not be developed for its own sake, but for the benefit of orthodontists and their patients.


Uneven balance of power between hypothalamic peptidergic neurons in the control of feeding.
Two classes of peptide-producing neurons in the arcuate nucleus (Arc) of the hypothalamus are known to exert opposing actions on feeding: the anorexigenic neurons that express proopiomelanocortin (POMC) and the orexigenic neurons that express agouti-related protein (AgRP) and neuropeptide Y (NPY). These neurons are thought to arise from a common embryonic progenitor, but our anatomical and functional understanding of the interplay of these two peptidergic systems that contribute to the control of feeding remains incomplete. The present study uses a combination of optogenetic stimulation with viral and transgenic approaches, coupled with neural activity mapping and brain transparency visualization to demonstrate the following: (i) selective activation of Arc POMC neurons inhibits food consumption rapidly in unsated animals; (ii) activation of Arc neurons arising from POMC-expressing progenitors, including POMC and a subset of AgRP neurons, triggers robust feeding behavior, even in the face of satiety signals from POMC neurons; (iii) the opposing effects on food intake are associated with distinct neuronal projection and activation patterns of adult hypothalamic POMC neurons versus Arc neurons derived from POMC-expressing lineages; and (iv) the increased food intake following the activation of orexigenic neurons derived from POMC-expressing progenitors engages an extensive neural network that involves the endogenous opioid system. Together, these findings shed further light on the dynamic balance between two peptidergic systems in the moment-to-moment regulation of feeding behavior.


[Lung dysfunction in patients with mild chronic obstructive bronchitis].
VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TCL, TGV, RV, Ravt, Riin, Rex, DLCO-SS, PaO2, and PaO2 were determined in 33 patients with mild chronic obstructive lung disease (FEV1 > 70% of the normal value). All the patients were found to have impaired bronchial patency; most (63.6%) patients had lung volume and capacity changes, almost half (45.5%) the patients had pulmonary gas exchange dysfunction. Impaired bronchial patency mainly appeared as decreased MEF50, MEF15, and FEV1/VC%; altered lung volumes and capacities manifested chiefly by increased RV and decreased VC; pulmonary gas exchange dysfunction showed up primarily as lowered PaO2. The magnitude of the observed functional changes was generally slight. MEF50, MEF75, FEV1/VC%, and VC dropped to 59-20 and 79-70% of the normal value, respectively. RV increased up to 142-196% of the normal value; PaO2 reduced up to 79-60% mm Hg.


Evaluation of drug-resistant Enterobacteriaceae in retail poultry and beef.
There has been increasing concern on the emergence of multidrug-resistant foodborne pathogens from foods of animal origin, including poultry. The current study aimed to evaluate antibiotic-resistant Enterobacteriaceae from raw retail chicken/turkey parts (thigh, wings, breast, and ground) and beef meat (ground and chunks) in Middle Tennessee. Resistance of the collected Enterobacteriaceae to a panel of antibiotics was determined by the Kirby-Bauer disk diffusion test. Retail meats were also assayed for the presence of Salmonella spp. and Escherichia coli O157:H7. Two hundred thirty-seven samples representing 95.2% of the total of 249 samples tested were positive for Enterobacteriaceae. The level of contamination with Enterobacteriaceae in raw meats ranged from 3.26 log10 cfu/g to 4.94 log10 cfu/g with significant differences in counts among meat types (P < 0.05). Contamination was significantly greater (P < 0.05) in ground beef, beef chucks, ground chicken, chicken breast, and turkey wings (4.92, 4.58, 4.94, 4.75, 4.13 log10 cfu/g, respectively) than ground turkey and chicken wings (3.26 and 3.26 log10 cfu/g, respectively). Klebsiella oxytoca, Serratia spp., E. coli, and Haffnia alvei were most prevalent contaminants at 27.4, 14.3, 12.1, and 11.4%, respectively. Resistance of the Enterobacteriaceae to antimicrobials was most frequent with erythromycin, penicillin, and ampicillin at 100, 89, and 65.8%, respectively. Few (2.7%) of the Enterobacteriaceae were resistant to chloramphenicol. Salmonella spp., E. coli O157:H7, Morganella morganii, Yersinia enterocolitica, and Vibrio parahemolyticus exhibited multiple drug resistance. This investigation demonstrates that raw poultry and beef are potential reservoirs of antibiotic-resistant Enterobacteriaceae.


Bayesian regression versus machine learning for rapid age estimation of archaeological features identified with lidar at Angkor.
Lidar (light-detection and ranging) has revolutionized archaeology. We are now able to produce high-resolution maps of archaeological surface features over vast areas, allowing us to see ancient land-use and anthropogenic landscape modification at previously un-imagined scales. In the tropics, this has enabled documentation of previously archaeologically unrecorded cities in various tropical regions, igniting scientific and popular interest in ancient tropical urbanism. An emerging challenge, however, is to add temporal depth to this torrent of new spatial data because traditional archaeological investigations are time consuming and inherently destructive. So far, we are aware of only one attempt to apply statistics and machine learning to remotely-sensed data in order to add time-depth to spatial data. Using temples at the well-known massive urban complex of Angkor in Cambodia as a case study, a predictive model was developed combining standard regression with novel machine learning methods to estimate temple foundation dates for undated Angkorian temples identified with remote sensing, including lidar. The model's predictions were used to produce an historical population curve for Angkor and study urban expansion at this important ancient tropical urban centre. The approach, however, has certain limitations. Importantly, its handling of uncertainties leaves room for improvement, and like many machine learning approaches it is opaque regarding which predictor variables are most relevant. Here we describe a new study in which we investigated an alternative Bayesian regression approach applied to the same case study. We compare the two models in terms of their inner workings, results, and interpretive utility. We also use an updated database of Angkorian temples as the training dataset, allowing us to produce the most current estimate for temple foundations and historic spatiotemporal urban growth patterns at Angkor. Our results demonstrate that, in principle, predictive statistical and machine learning methods could be used to rapidly add chronological information to large lidar datasets and a Bayesian paradigm makes it possible to incorporate important uncertainties-especially chronological-into modelled temporal estimates.


Tri-Layered Nanocomposite Hydrogel Scaffold for the Concurrent Regeneration of Cementum, Periodontal Ligament, and Alveolar Bone.
A tri-layered scaffolding approach is adopted for the complete and concurrent regeneration of hard tissues-cementum and alveolar bone-and soft tissue-the periodontal ligament (PDL)-at a periodontal defect site. The porous tri-layered nanocomposite hydrogel scaffold is composed of chitin-poly(lactic-co-glycolic acid) (PLGA)/nanobioactive glass ceramic (nBGC)/cementum protein 1 as the cementum layer, chitin-PLGA/fibroblast growth factor 2 as the PDL layer, and chitin-PLGA/nBGC/platelet-rich plasma derived growth factors as the alveolar bone layer. The tri-layered nanocomposite hydrogel scaffold is cytocompatible and favored cementogenic, fibrogenic, and osteogenic differentiation of human dental follicle stem cells. In vivo, tri-layered nanocomposite hydrogel scaffold with/without growth factors is implanted into rabbit maxillary periodontal defects and compared with the controls at 1 and 3 months postoperatively. The tri-layered nanocomposite hydrogel scaffold with growth factors demonstrates complete defect closure and healing with new cancellous-like tissue formation on microcomputed tomography analysis. Histological and immunohistochemical analyses further confirm the formation of new cementum, fibrous PDL, and alveolar bone with well-defined bony trabeculae in comparison to the other three groups. In conclusion, the tri-layered nanocomposite hydrogel scaffold with growth factors can serve as an alternative regenerative approach to achieve simultaneous and complete periodontal regeneration.


Improvement in Tubulointerstitial Nephritis With Glucocorticoid Therapy in an Anorexia Nervosa Patient.
Anorexia nervosa is a psychiatric disorder that is often diagnosed in adolescents and young adults. Renal-related complications of anorexia nervosa include abnormal water metabolism, electrolyte abnormalities, and nephrocalcinosis, which may lead to irreversible renal damage. Furthermore, tubulointerstitial nephritis has been reported as a renal pathological feature of anorexia nervosa. Immunosuppressive therapy, such as with glucocorticoids, has been recommended for idiopathic interstitial nephritis treatment; however, the effectiveness of immunosuppressive therapy for interstitial nephritis in patients with anorexia nervosa remains unestablished. Here, we report a case of interstitial nephritis in a patient with anorexia nervosa whose renal function was successfully improved with glucocorticoid therapy. The patient was a 38-year-old woman who was referred for renal dysfunction (estimated glomerular filtration rate: 7.6 mL/min/1.73 m2). She had anorexia nervosa and repeated episodes of vomiting. Hypokalemia (K: 2.1 mEq/L) and metabolic alkalosis (HCO3-: 54.2 mEq/L) were observed. Fluid therapy and potassium supplementation did not improve renal function; therefore, a percutaneous renal biopsy was performed. The renal pathology results revealed interstitial fibrosis, inflammatory cell infiltration in the interstitium, and tubulitis, suggesting a diagnosis of tubulointerstitial nephritis. Glucocorticoid therapy improved the patient's renal function to an estimated glomerular filtration rate of 19.91 mL/min/1.73 m2, and the renal function remained stable thereafter. This case suggests that glucocorticoid therapy may be considered for the treatment of interstitial nephritis in patients with anorexia.


Transjugular intrahepatic portosystemic shunt after adult liver transplantation: experience in eight patients.
Transjugular intrahepatic portosystemic shunting (TIPS) has become an effective treatment for the complications of portal hypertension. We assessed the feasibility and outcome of TIPS in liver transplant recipients. During the period from December 1992 to January 1998, eight adults presenting recurrent hepatitis C virus (five patients) and hepatitis B virus (one patient) infection, veno-occlusive disease (one patient), and secondary biliary cirrhosis (one patient) had TIPS because of refractory ascites (five patients), bleeding esophageal varices (one patient), refractory hepatic hydrothorax (one patient), retransplantation (two patients), and redo-biliary surgery (one patient). In two patients, the procedure was difficult due to cavo-caval implantation. Ascites, hydrothorax, and variceal bleeding were controlled in all patients. Moderate to severe encephalopathy developed in four patients; two patients had worsening of their existing encephalopathy. Three of five patients treated with cyclosporine needed a drastic dose reduction due to the development of severe side effects. No long-term survivor developed shunt stenosis or occlusion. Two patients did moderately well at 6 and 14 months, respectively; the former died due to chronic rejection while waiting for a retransplantation. Three did well at 14, 36, and 28 months, respectively; the latter patient died of liver failure 32 months after TIPS. One jaundiced patient died after 1.5 months due to necrotic pancreatitis. Two patients died after 4 and 8.5 months, respectively, due to liver failure; the latter was doing well until 7 months after TIPS. TIPS is feasible in transplant recipients in cases of decompensated allograft cirrhosis, of allograft veno-occlusive disease or when retransplantation or redo-biliary surgery are scheduled in the presence of portal hypertension. At transplantation, the surgeon should keep in mind the eventuality of a later TIPS procedure. Close immunosuppression monitoring is warranted because modified metabolization of cyclosporine (and probably tacrolimus) may cause serious side effects.


Lestaurtinib potentiates TRAIL-induced apoptosis in glioma via CHOP-dependent DR5 induction.
Yingxiao Cao, Shiqi Kong, Yuling Xin, Yan Meng, Shuling Shang, Yanhui Qi. Lestaurtinib potentiates TRAIL-induced apoptosis in glioma via CHOP-dependent DR5 induction. J Cell Mol Med. 2020; 24: 7829-7840. https://doi.org/10.1111/jcmm.15415. The above article, published online on 22 May 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor-in-Chief, Stefan Constantinescu, The Foundation for Cellular and Molecular Medicine, and John Wiley and Sons Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate duplications of images between this and other articles that were either previously published or published later in the same year in a different scientific context. Thus, the editors consider the conclusions of this manuscript substantially compromised.


Methods to locate center of gravity in scoliosis.
Prospective evaluation of the location of the center of gravity during supine, standing, and gait. Develop methods to quantify center of gravity locations in patients with scoliosis and controls and to evaluate the merit of the quantitative assumptions relative to spinal fusion surgery. The center of gravity, or balance point of the body, is generally considered to be the single best estimate of the body's location. To date, investigators have not examined the body's center of gravity location to assist surgical planning to maintain and/or restore coronal and sagittal plane balance, nor have they used center of gravity location to help assess surgical outcomes. The whole-body center of gravity (MR-COG) was determined for three subjects from magnetic resonance imaging data obtained supine. The whole-body center of gravity was also determined using subject specific (SS-COG) and literature-based (STD-COG) segment center of gravity locations in conjunction with a video motion capture system obtained supine, standing and during gait. Differences existed among the three methods of determining COG locations in supine, with the SS-COG and MR-COG being most closely aligned. Results from gait data indicated typical anterior/superior and right/left COG shifts during the gait cycle. The SS-COG method consistently determined a COG location inferior to the STD-COG method; however, variation within the gait cycle was similar. Shifts in COG locations relative to a coordinate system fixed in the pelvis were more than 5 cm in the superior/inferior direction, approximately 4 cm in the anterior/posterior direction, and minimal in the left/right direction. Methods have been developed to determine locations of the whole body COG in both preoperative and postoperative subjects undergoing spinal fusion surgery and controls. The methods are robust to include men and women, subjects with and without instrumentation, and subjects in various positions including gait.


Critical role of the virus-encoded microRNA-155 ortholog in the induction of Marek's disease lymphomas.
Notwithstanding the well-characterised roles of a number of oncogenes in neoplastic transformation, microRNAs (miRNAs) are increasingly implicated in several human cancers. Discovery of miRNAs in several oncogenic herpesviruses such as KSHV has further highlighted the potential of virus-encoded miRNAs to contribute to their oncogenic capabilities. Nevertheless, despite the identification of several possible cancer-related genes as their targets, the direct in vivo role of virus-encoded miRNAs in neoplastic diseases such as those induced by KSHV is difficult to demonstrate in the absence of suitable models. However, excellent natural disease models of rapid-onset Marek's disease (MD) lymphomas in chickens allow examination of the oncogenic potential of virus-encoded miRNAs. Using viruses modified by reverse genetics of the infectious BAC clone of the oncogenic RB-1B strain of MDV, we show that the deletion of the six-miRNA cluster 1 from the viral genome abolished the oncogenicity of the virus. This loss of oncogenicity appeared to be primarily due to the single miRNA within the cluster, miR-M4, the ortholog of cellular miR-155, since its deletion or a 2-nucleotide mutation within its seed region was sufficient to inhibit the induction of lymphomas. The definitive role of this miR-155 ortholog in oncogenicity was further confirmed by the rescue of oncogenic phenotype by revertant viruses that expressed either the miR-M4 or the cellular homolog gga-miR-155. This is the first demonstration of the direct in vivo role of a virus-encoded miRNA in inducing tumors in a natural infection model. Furthermore, the use of viruses deleted in miRNAs as effective vaccines against virulent MDV challenge, enables the prospects of generating genetically defined attenuated vaccines.


MR imaging of pituitary adenoma: CT, clinical, and surgical correlation.
Twenty-five patients with suspected pituitary adenoma were evaluated prospectively with CT and MR. Nine patients underwent transsphenoidal surgery, and three of these showed a documented decrease in size of mass on bromocriptine therapy. CT was more sensitive than MR for detecting focal lesions (seven vs three) and sellar-floor erosion (12 vs six). MR was superior to CT in identifying infundibular abnormalities (seven vs six), focal abnormalities of the diaphragma sellae (10 vs seven), cavernous sinus invasion (four vs two), and optic chiasm compression (six vs zero). Thus, MR may be the procedure of choice for optimal identification and localization of macroadenoma. For patients with suspected microadenoma, however, this preliminary series indicates that CT remains the radiographic procedure of choice.


Affinity as a tool in life science.
The use of affinity-based tools has become invaluable as a platform for basic research and in the development of drugs and diagnostics. Applications include affinity chromatography and affinity tag fusions for efficient purification of proteins as well as methods to probe the protein network interactions on a whole-proteome level. A variety of selection systems has been described for in vitro evolution of affinity reagents using combinatorial libraries, which make it possible to create high-affinity reagents to virtually all biomolecules, as exemplified by generation of therapeutic antibodies and new protein scaffold binders. The strategies for high-throughput generation of affinity reagents have also opened up the possibility of generating specific protein probes on a whole-proteome level. Recently, such affinity proteomics have allowed the detailed analysis of human protein expression in a comprehensive manner both in normal and disease tissue using tissue microarrays and confocal microscopy.


Time courses of cell electroporation as revealed by submicrosecond imaging of transmembrane potential.
Changes in the membrane conductance of sea urchin eggs, during the course of electroporation, were investigated over the time range of 0.5 microsecond to 1 ms by imaging the transmembrane potential at a submicrosecond resolution with the voltage-sensitive fluorescent dye RH292. When a rectangular electric pulse of moderate intensity was applied across an egg, a position-dependent potential developed synchronously with the pulse, as theory predicts for a cell with an insulating membrane. From the rise and fall times, the membrane capacitance of unfertilized eggs was estimated to be 0.95 microF/cm2 and the intracellular conductance 220 omega.cm. Under an electric pulse of much higher intensity, the rise of the induced potential stopped at a certain level and then slowly decreased on the microsecond time scale. This saturation and subsequent reversal of the potential development was ascribed to the introduction of finite membrane conductance, or permeabilization of the membrane, by the action of the intense pulse (electroporation). Detailed analysis indicated the following: already at 0.5 microsecond in the rectangular electric pulse, the two sides of the egg facing the positive and negative electrodes were porated and gave a high membrane conductance in the order of 1 S/cm2; the conductance on the positive side appeared higher. Thereafter, the conductance increased steadily, reaching the order of 10 S/cm2 by 1 ms. This increase was faster on the negative-electrode side; by 1 ms the conductance on the negative side was more than twice that on the positive side. The recovery of the porated membrane after the pulse treatment was assessed from the membrane conductance estimated in a second electric pulse of a small amplitude. At least two recovery processes were distinguished, one with a time constant of 7 microseconds and the other 0.5 ms, at the end of which the membrane conductance was already < 0.1 S/cm2.


Minor head injury: predicting follow-up after discharge from the Emergency Department.
Up to 50% of ED patients discharged within a minor head injury (MHI) will develop postconcussive syndrome (PCS) within 1 month of injury. The follow-up visit is an important opportunity to identify and treat PCS before it becomes persistent. To identify factors predictive of follow-up (FU) after ED discharge in patients presenting with MHI. Prospective, observational study of a convenience sample of 71 MHI presenting within 24 hours of injury to the ED of a university teaching hospital between February 1996 and October 1997. MHI defined as loss of consciousness not greater than 10 minutes or amnesia, GCS 15, no skull fracture on PE, no new focality to neurologic exam and no brain injury on CT if one was done. Neurobehavioural test scores, clinical information and demographic data collected via use of standardized patient encounter form. All patients were discharged with written instructions to FU with their private physician within 1-2 weeks. Patients without a follow-up physician were assigned one. At 1 month post-injury, all patients were telephoned to determine if they had followed-up. Stepwise, multivariate, logistic regression. Thirty one out of 71 (43.7%) reported FU with a physician within 1 month. Factors associated with FU were performance of a head CT in the ED (OR = 3.58, 95% CI = 1.12-11.37), associated laceration (OR = 8.84, 95% CI = 1.69-42.55), female gender (OR = 3.19, 95% CI = 1.04-9.82), and African-American race (OR = 0.36, 95% CI = 0.13-0.99). Several factors predict FU after ED discharge for MHI. Patients unlikely to FU may benefit from an assessment of PCS risk before they leave the ED.


Increased skills usage statistically mediates symptom reduction in self-guided internet-delivered cognitive-behavioural therapy for depression and anxiety: a randomised controlled trial.
Cognitive-behavioural therapy (CBT) is an effective treatment for clinical and subclinical symptoms of depression and general anxiety, and increases life satisfaction. Patients' usage of CBT skills is a core aspect of treatment but there is insufficient empirical evidence suggesting that skills usage behaviours are a mechanism of clinical change. This study investigated if an internet-delivered CBT (iCBT) intervention increased the frequency of CBT skills usage behaviours and if this statistically mediated reductions in symptoms and increased life satisfaction. A two-group randomised controlled trial was conducted comparing internet-delivered CBT (n = 65) with a waitlist control group (n = 75). Participants were individuals experiencing clinically significant symptoms of depression or general anxiety. Mixed-linear models analyses revealed that the treatment group reported a significantly higher frequency of skills usage, lower symptoms, and higher life satisfaction by the end of treatment compared with the control group. Results from bootstrapping mediation analyses revealed that the increased skills usage behaviours statistically mediated symptom reductions and increased life satisfaction. Although skills usage and symptom outcomes were assessed concurrently, these findings support the notion that iCBT increases the frequency of skills usage behaviours and suggest that this may be an important mechanism of change.


Shooting control by brassinosteroids: metabolomic analysis and effect of brassinazole on Malus prunifolia, the Marubakaido apple rootstock.
To help unravel the role of brassinosteroids (BRs) in the control of shooting, we treated the shoots of Marubakaido apple rootstock (Malus prunifolia (Willd.) Borkh cv. Marubakaido) with brassinolide and Brz 220, an inhibitor of BR biosynthesis. Brassinolide differentially affected elongation and formation of main and primary lateral shoots, which resulted in reduced apical dominance. Treatment of shoots with increasing doses of Brz 220 led to a progressive inhibition of main shoot elongation. Eight different BRs were also identified in the shoots of M. prunifolia. Progressive decline in 6-deoxocathasterone, 6-deoxotyphasterol and castasterone was related to increased doses of Brz 220. Analysis of the metabolic profiles between a fluoro-containing derivative of 28-homocastasterone (5F-HCS) using treated and untreated shoots demonstrated that no 5F-HCS-specific metabolite was identified. However, 4 weeks after the treatment, fructose, glucose and the putatively identified gulonic acid were higher in 5F-HCS-treated shoots, compared to untreated shoots. These results indicate that the previously reported 5F-HCS-induced stimulation of shoot elongation and formation of new shoots in the Marubakaido shoots is under the control of changes in the endogenous BR pool. In addition, the results presented in this report also indicate that the 5F-HCS-induced shooting likely involves a variety of different mechanisms and consequently does not result from changes in the endogenous levels of any single metabolite.


Capillary haemangiomas of the scrotum and testicle in boars.
In boars, scrotal haemangiomas have been described frequently, but intratesticular haemangiomas are rare. Of 12 boars with scrotal haemangiomas, three animals also had testicular tumours, as follow: testicular haemangioma (TH) (n=1); TH with intratubular germ cell tumour (ITGT) (n=1); TH with intratubular germ cell-like tumour (ITGLT) and Sertoli cell tumour (n=1). In the nine remaining boars, no testicular tumours were found. Immunohistochemical examination of scrotal and testicular haemangiomas revealed labelling of endothelial cells for vimentin and factor VIII-related antigen. Labelling of smooth muscle actin was occasionally observed in the walls of neoplastic vessels. In the ITGT, no labelling was produced by any of the antibodies used. The Sertoli cell tumour was strongly positive for S-100. Sperm granulomas and degeneration of seminiferous tubules were also observed.


Evaluation of 18F-UCB-H as a novel PET tracer for synaptic vesicle protein 2A in the brain.
Synaptic vesicle protein 2 isoforms are critical for proper nervous system function and are involved in vesicle trafficking. The synaptic vesicle protein 2A (SV2A) isoform has been identified as the binding site of the antiepileptic levetiracetam (LEV), making it an interesting therapeutic target for epilepsy. (18)F-UCB-H is a novel PET imaging agent with a nanomolar affinity for human SV2A. Preclinical PET studies were performed with isoflurane-anesthetized rats. The arterial input function was measured with an arteriovenous shunt and a β-microprobe system. (18)F-UCB-H was injected intravenously (bolus of 140 ± 20 MBq). Brain uptake of (18)F-UCB-H was high, matching the expected homogeneous distribution of SV2A. The distribution volume (Vt) for (18)F-UCB-H was calculated with Logan graphic analysis, and the effect of LEV pretreatment on Vt was measured. In control animals the whole-brain Vt was 9.76 ± 0.52 mL/cm(3) (mean ± SD; n = 4; test-retest), and the reproducibility in test-retest studies was 10.4% ± 6.5% (mean ± SD). The uptake of (18)F-UCB-H was dose dependently blocked by pretreatment with LEV (0.1-100 mg/kg intravenously). Our results indicated that (18)F-UCB-H is a suitable radiotracer for the imaging of SV2A in vivo. To our knowledge, this is the first PET tracer for the in vivo quantification of SV2A. The necessary steps for the implementation of (18)F-UCB-H production under good manufacturing practice conditions and the first human studies are being planned.


Lgr4 and Lgr5 drive the formation of long actin-rich cytoneme-like membrane protrusions.
Embryonic development and adult tissue homeostasis require precise information exchange between cells and their microenvironment to coordinate cell behavior. A specialized class of ultra-long actin-rich filopodia, termed cytonemes, provides one mechanism for this spatiotemporal regulation of extracellular cues. We provide here a mechanism whereby the stem-cell marker Lgr5, and its family member Lgr4, promote the formation of cytonemes. Lgr4- and Lgr5-induced cytonemes exceed lengths of 80 µm, are generated through stabilization of nascent filopodia from an underlying lamellipodial-like network and functionally provide a pipeline for the transit of signaling effectors. As proof-of-principle, we demonstrate that Lgr5-induced cytonemes act as conduits for cell signaling by demonstrating that the actin motor and filopodial cargo carrier protein myosin X (Myo10) and the G-protein-coupled receptor (GPCR) signaling effector β-arrestin-2 (Arrb2) transit into cytonemes. This work delineates a biological function for Lgr4 and Lgr5 and provides the rationale to fully investigate Lgr4 and Lgr5 function and cytonemes in mammalian stem cell and cancer stem cell behavior.


European experience with cementless total hip replacements.
The differences between prostheses fixed with and without cement consist mainly of the design and the nature of the surface of the implant. The shapes of the sockets to be implanted without cement show a wide variety--cylinder, square, conus, ellipsoid with and without threads. The hemispherical shape, which was chosen for the acetabular component of the isoelastic hip joint, does not disturb the natural form and function of the hip joint since the outer surface is closely adapted to the original subchondral bone layer. Undesired stress concentrations therefore are eliminated. The fixation of the noncemented cup is secured by threads, pegs, screws, etc. and by ingrowth of bony tissue in the grooves of the surfaces. Except for some special forms, most of the stems are based on the self-locking principle. All prosthesis models show preparations that increase the surface area (ribs, wings, corrugations, or rims).


Cognitive impairment in COPD: a systematic review.
The objectives of this study were to characterize and clarify the relationships between the various cognitive domains affected in COPD patients and the disease itself, as well as to determine the prevalence of impairment in the various cognitive domains in such patients. To that end, we performed a systematic review using the following databases: PubMed, Scopus, and ScienceDirect. We included articles that provided information on cognitive impairment in COPD patients. The review of the findings of the articles showed a significant relationship between COPD and cognitive impairment. The most widely studied cognitive domains are memory and attention. Verbal memory and learning constitute the second most commonly impaired cognitive domain in patients with COPD. The prevalence of impairment in visuospatial memory and intermediate visual memory is 26.9% and 19.2%, respectively. We found that cognitive impairment is associated with the profile of COPD severity and its comorbidities. The articles reviewed demonstrated that there is considerable impairment of the cognitive domains memory and attention in patients with COPD. Future studies should address impairments in different cognitive domains according to the disease stage in patients with COPD.


Re-Irradiation for Recurrent Glioblastoma Multiforme.
Patients requiring re-irradiation for recurrent glioblastoma multiforme (GBM) may benefit from individualized therapy. This study aimed to identify predictors of survival and contribute to treatment personalization. In 28 patients with recurrent GBM, nine factors were analyzed for associations with survival: Main location and type of recurrence, Karnofsky performance score (KPS), age, gender, interval between primary radiotherapy and recurrence, gross total resection (GTR), equivalent dose in 2-Gy fractions (EQD2) of re-irradiation and cumulative EQD2 of primary and re-irradiation. On univariate analyses, GTR (p=0.047), EQD2 ≥30 Gy (p=0.029) and cumulative EQD2 ≥90 Gy (p=0.023) were significantly associated with better survival; frontal location (p=0.119) and KPS 80-100% (p=0.067) showed trends. In multivariate analyses, frontal location (p=0.032) and cumulative EQD2 ≥90 Gy (p=0.038) were significant; KPS 80-100% (p=0.110) and EQD2 ≥30 Gy (p=0.083) showed trends. Predictors of survival after re-irradiation for recurrent GBM were identified that can help when designing personalized treatments. Use of irradiation with EQD2 ≥30 Gy appeared superior to lower doses.


Whom do physicians work for? An analysis of dual practice in the health sector.
This article presents a thorough analysis of dual practice among physicians who work in both the public and private sectors. A conceptual framework is presented to help the reader understand dual practice and the contexts where it takes place. The article reviews the existing theoretical and empirical literature on this form of dual practice among physicians. It analyzes the extent of this phenomenon, the underlying factors that motivate physicians to engage in dual practice, and the main implications of their decision to do so. It also examines and discusses current policies that address dual practice. In this regard, the article provides some qualified support for the use of "rewarding" policies to retain physicians in the public sectors of more developed countries, while "limiting" policies are recommended for developing countries - with the caveat that the policies should be accompanied by the strengthening of institutional and contracting environments. The article highlights the lack of quality evaluative evidence regarding the consequences of dual practice on the delivery of health care services. It concludes that the overall impact of dual practice remains an open question that warrants more attention from researchers and policy makers alike.


Translation Synchronization via Truncated Least Squares.
In this paper, we introduce a robust algorithm, TranSync, for the 1D translation synchronization problem, in which the aim is to recover the global coordinates of a set of nodes from noisy measurements of relative coordinates along an observation graph. The basic idea of TranSync is to apply truncated least squares, where the solution at each step is used to gradually prune out noisy measurements. We analyze TranSync under both deterministic and randomized noisy models, demonstrating its robustness and stability. Experimental results on synthetic and real datasets show that TranSync is superior to state-of-the-art convex formulations in terms of both efficiency and accuracy.


Identification of the direct regulon of NtcA during early acclimation to nitrogen starvation in the cyanobacterium Synechocystis sp. PCC 6803.
In cyanobacteria, nitrogen homeostasis is maintained by an intricate regulatory network around transcription factor NtcA. Although mechanisms controlling NtcA activity appear to be well understood, its regulon remains poorly defined. To determine the NtcA regulon during the early stages of nitrogen starvation for the model cyanobacterium Synechocystis sp. PCC 6803, we performed chromatin immunoprecipitation, followed by sequencing (ChIP-seq), in parallel with transcriptome analysis (RNA-seq). Through combining these methods, we determined 51 genes activated and 28 repressed directly by NtcA. In addition to genes associated with nitrogen and carbon metabolism, a considerable number of genes without current functional annotation were among direct targets providing a rich reservoir for further studies. The NtcA regulon also included eight non-coding RNAs, of which Ncr1071, Syr6 and NsiR7 were experimentally validated, and their putative targets were computationally predicted. Surprisingly, we found substantial NtcA binding associated with delayed expression changes indicating that NtcA can reside in a poised state controlled by other factors. Indeed, a role of PipX as modulating factor in nitrogen regulation was confirmed for selected NtcA-targets. We suggest that the indicated poised state of NtcA enables a more differentiated response to nitrogen limitation and can be advantageous in native habitats of Synechocystis.


Hepaticoduodenal fistula: an unusual complication of cholecystectomy.
This report appears to be the first documented post-cholecystectomy hepaticoduodenal fistula successfully corrected. This complication may be prevented by interposing the omentum between the liver and the duodenum at the time of any operation on the biliary system and the duodenum.


Chitosan nanoparticle encapsulation increased the prophylactic efficacy of Lactobacillus plantarum RM1 against AFM1-induced hepatorenal toxicity in rats.
Aflatoxin M1 (AFM1) is a significant contaminant of food, particularly dairy products and can resist various industrial processes. Several probiotic strains like Lactobacillus plantarum are known to reduce aflatoxin availability in synthetic media and some food products. The current work investigated the possible chitosan coating prophylactic efficacy of Lactobacillus plantarum RM1 nanoemulsion (CS-RM1) against AFM1-induced hepatorenal toxicity in rats. Twenty-eight male Wistar rats were divided into four groups (n = 7) as follows: group 1 received normal saline, group 2 received CS-RM1 (1mL contains 6.7 × 1010 CFU), group 3 received AFM1 (60 µg/kg bwt), and group 4 received both CS-RM1(1 mL contains 6.7 × 1010 CFU) and AFM1 (60 µg/kg bwt). All receiving materials were given to rats daily via oral gavage for 28 days. AFM1 caused a significant elevation in serum levels of ALT, AST, ALP, uric acid, urea, and creatinine with marked alterations in protein and lipid profiles. Additionally, AFM1 caused marked pathological changes in the liver and kidneys, such as cellular necrosis, vascular congestion, and interstitial inflammation. AFM1 also increased the MDA levels and decreased several enzymatic and non-enzymatic antioxidants. Liver and kidney sections of the AFM1 group displayed strong caspase-3, TNF-α, and iNOS immunopositivity. Co-treatment of CS-RM1 with AFM1 significantly lowered the investigated toxicological parameter changes and markedly improved the microscopic appearance of liver and kidneys. In conclusion, AFM1 induces hepatorenal oxidative stress damage via ROS overgeneration, which induces mitochondrial caspase-3-dependent apoptosis and inflammation. Furthermore, CS-RM1 can reduce AFM1 toxicity in both the liver and kidneys. The study recommends adding CS-RM1 to milk and milk products for AFM1-elimination.


Foreign-language experience in infancy: effects of short-term exposure and social interaction on phonetic learning.
Infants acquire language with remarkable speed, although little is known about the mechanisms that underlie the acquisition process. Studies of the phonetic units of language have shown that early in life, infants are capable of discerning differences among the phonetic units of all languages, including native- and foreign-language sounds. Between 6 and 12 mo of age, the ability to discriminate foreign-language phonetic units sharply declines. In two studies, we investigate the necessary and sufficient conditions for reversing this decline in foreign-language phonetic perception. In Experiment 1, 9-mo-old American infants were exposed to native Mandarin Chinese speakers in 12 laboratory sessions. A control group also participated in 12 language sessions but heard only English. Subsequent tests of Mandarin speech perception demonstrated that exposure to Mandarin reversed the decline seen in the English control group. In Experiment 2, infants were exposed to the same foreign-language speakers and materials via audiovisual or audio-only recordings. The results demonstrated that exposure to recorded Mandarin, without interpersonal interaction, had no effect. Between 9 and 10 mo of age, infants show phonetic learning from live, but not prerecorded, exposure to a foreign language, suggesting a learning process that does not require long-term listening and is enhanced by social interaction.


The branched chain amino acids (BCAAs) modulate the development of the intra-cellular stages of Trypanosoma cruzi.
The life cycle of Trypanosoma cruzi, the etiological agent of Chagas disease, involves different forms of the parasite, which alternates between insect and vertebrate hosts. One critical process in the parasite's life cycle is metacyclogenesis, in which the replicative non-infective forms present in the insect midgut differentiate into non-dividing vertebrate-infective forms. It is known that proline (Pro) is important for this process and that leucine (Leu) and isoleucine (Ile) can act as inhibitors of metacyclogenesis. In this study, we investigated further the role of branched-chain amino acids (BCAAs) as negative modulators of parasite differentiation and infection capability in vitro. We found that BCAAs can down-regulate metacyclogenesis, inhibiting Pro-dependent differentiation. Furthermore, we evaluated the ability of all three BCAAs to influence the differentiation of intracellular stages and found that they could modulate the release of trypomastigotes from infected host cells. These findings suggest that BCAAs may have an important role in the complex life cycle of T. cruzi. Thus, enzymes of their metabolism and other interacting proteins could be potential targets for the development of new therapeutic strategies for Chagas disease.


Patient-doctor communication: use of complementary and alternative medicine by adult patients with cancer.
The purpose of this survey was to examine patient-doctor communication about the use of complementary and alternative medicine (CAM) by adult patients with cancer and compare patients' satisfaction with the consultation between patients who had and those who had not discussed the use of CAM with their doctors. Oncologists from three hospitals screened patients for eligibility. Eligible patients were mailed a letter of invitation with a questionnaire (N = 1,323). Three hundred eighty-one questionnaires were returned. Sixty-five percent of cancer patients used at least one form of CAM. Use of CAM was not discussed with the oncologist by 55% of respondents using biologically based CAM and by 80% of those using non-biologically based CAM since the diagnosis of cancer. Patients who discussed the use of biologic CAM with their oncologists were more satisfied with the consultation than those who had not (p = .027), whereas there were no significant differences between patients who discussed or did not discuss use of non-biologically based CAM (p = .102). A substantial proportion of cancer patients do not discuss the use of CAM with their oncologists. It is important to improve patient-doctor communication about the use of CAM to increase patients' satisfaction with the oncology consultation.


Secreted bacterial effectors that inhibit host protein synthesis are critical for induction of the innate immune response to virulent Legionella pneumophila.
The intracellular bacterial pathogen Legionella pneumophila causes an inflammatory pneumonia called Legionnaires' Disease. For virulence, L. pneumophila requires a Dot/Icm type IV secretion system that translocates bacterial effectors to the host cytosol. L. pneumophila lacking the Dot/Icm system is recognized by Toll-like receptors (TLRs), leading to a canonical NF-κB-dependent transcriptional response. In addition, L. pneumophila expressing a functional Dot/Icm system potently induces unique transcriptional targets, including proinflammatory genes such as Il23a and Csf2. Here we demonstrate that this Dot/Icm-dependent response, which we term the effector-triggered response (ETR), requires five translocated bacterial effectors that inhibit host protein synthesis. Upon infection of macrophages with virulent L. pneumophila, these five effectors caused a global decrease in host translation, thereby preventing synthesis of IκB, an inhibitor of the NF-κB transcription factor. Thus, macrophages infected with wildtype L. pneumophila exhibited prolonged activation of NF-κB, which was associated with transcription of ETR target genes such as Il23a and Csf2. L. pneumophila mutants lacking the five effectors still activated TLRs and NF-κB, but because the mutants permitted normal IκB synthesis, NF-κB activation was more transient and was not sufficient to fully induce the ETR. L. pneumophila mutants expressing enzymatically inactive effectors were also unable to fully induce the ETR, whereas multiple compounds or bacterial toxins that inhibit host protein synthesis via distinct mechanisms recapitulated the ETR when administered with TLR ligands. Previous studies have demonstrated that the host response to bacterial infection is induced primarily by specific microbial molecules that activate TLRs or cytosolic pattern recognition receptors. Our results add to this model by providing a striking illustration of how the host immune response to a virulent pathogen can also be shaped by pathogen-encoded activities, such as inhibition of host protein synthesis.


Engineering Enzymes for Environmental Sustainability.
The development and implementation of sustainable catalytic technologies is key to delivering our net-zero targets. Here we review how engineered enzymes, with a focus on those developed using directed evolution, can be deployed to improve the sustainability of numerous processes and help to conserve our environment. Efficient and robust biocatalysts have been engineered to capture carbon dioxide (CO2 ) and have been embedded into new efficient metabolic CO2 fixation pathways. Enzymes have been refined for bioremediation, enhancing their ability to degrade toxic and harmful pollutants. Biocatalytic recycling is gaining momentum, with engineered cutinases and PETases developed for the depolymerization of the abundant plastic, polyethylene terephthalate (PET). Finally, biocatalytic approaches for accessing petroleum-based feedstocks and chemicals are expanding, using optimized enzymes to convert plant biomass into biofuels or other high value products. Through these examples, we hope to illustrate how enzyme engineering and biocatalysis can contribute to the development of cleaner and more efficient chemical industry.


Continuous-discontinuous Galerkin time domain (CDGTD) method with generalized dispersive material (GDM) model for computational photonics.
The discontinuous Galerkin time domain (DGTD) method and its recent flavor, the continuous-discontinuous Galerkin time domain (CDGTD) method, have been extensively applied to simulations in the radio frequency (RF) and microwave (MW) regimes due to their inherent ability to efficiently model multiscale problems. We propose to extend the CDGTD method to nanophotonics while exploiting its advantages which have already been established in the RF and MW regimes, such as domain decomposition, non-conformal meshing, high-order elements, and hp-refinement. However, at optical frequencies many materials are highly dispersive, so the modeling of nanophotonic devices requires accurate handling of different dielectric functions, including those of plasmonic elements, dielectrics, and tunable materials. In this paper, we propose a CDGTD method that incorporates a generalized dispersive material (GDM) model which is an efficient way to implement a wide range of optical dispersion models with a universal analytic function. Physics-based dispersion models, such as the Drude, Debye, Lorentz, and critical points as well as more complicated behavior founded on ab-initio principles can all be obtained as special cases of the universal GDM approach. The accuracy and convergence of this GDM-incorporated CDGTD are verified by numerical examples. The CDGTD method, equipped with the GDM model, paves the way to the efficient design and optimization of large scale photonic devices with a diverse range of optical dispersive materials.


Effects of the dimeric PSD-95 inhibitor UCCB01-144 on functional recovery after fimbria-fornix transection in rats.
Pharmacological inhibition of PSD-95 is a promising therapeutic strategy in the treatment of stroke, and positive effects of monomeric and dimeric PSD-95 inhibitors have been reported in numerous studies. However, whether therapeutic effects will generalize to other types of acute brain injury such as traumatic brain injury (TBI), which has pathophysiological mechanisms in common with stroke, is currently uncertain. We have previously found a lack of neuroprotective effects of dimeric PSD-95 inhibitors in the controlled cortical impact model of TBI in rats. However, as no single animal model is currently able to mimic the complex and heterogeneous pathophysiology of TBI, it is necessary to assess treatment effects across a range of models. In this preliminary study we investigated the neuroprotective abilities of the dimeric PSD-95 inhibitor UCCB01-144 after fimbria-fornix (FF) transection in rats. UCCB01-144 or saline was injected into the lateral tail vein of rats immediately after sham surgery or FF-transection, and effects on spatial delayed alternation in a T-maze were assessed over a 28-day period. Task acquisition was significantly impaired in FF-transected animals, but there were no significant effects of UCCB01-144 on spatial delayed alternation after FF-transection or sham surgery, although decelerated learning curves were seen after treatment with UCCB01-144 in FF-transected animals. The results of the present study are consistent with previous research showing a lack of neuroprotective effects of PSD-95 inhibition in experimental models of TBI.


Examining the barriers, facilitators and attitudes towards COVID-19 vaccine and public health measures for black communities in Canada: a qualitative study protocol.
Black communities claim the highest number of cases and deaths due to COVID-19 in Canada. Generating culturally/contextually appropriate public health measures and strategies for vaccine uptake in black communities within Canada can better support the disproportionate impact of this pandemic. This study explores the barriers and enablers to public health measures limited to mask-wearing, disinfection, sanitation, social distancing and handwashing, as well as the barriers and attitudes towards COVID-19 vaccines among the black community. We will use qualitative approaches informed by the widely accepted Consolidated Framework for Implementation Research (CFIR) to aid our investigation. We will conduct 120 semistructured interviews and five focus groups with black populations across the major provinces of Canada to understand the barriers and facilitators to public health measures, including barriers and attitudes towards COVID-19 vaccines. Data will be organised and analysed based on the CFIR. Facilitators and barriers to COVID-19 preventative measures and the barriers, facilitators and attitudes towards COVID-19 vaccines will be organised to explore relationships across the data. This study was approved by the Social Sciences, Humanities and Education Research Ethics Board at the University of Toronto (41585). All participants are given information about the study and will sign a consent form in order to be included; participants are informed of their right to withdraw from the study. Research material will be accessible to all researchers involved in this study as no personal identifiable information will be collected during the key informant semistructured interviews and focus groups. The study results will be provided to participants and published in peer-reviewed journals.


Differentiable Graph Module (DGM) for Graph Convolutional Networks.
Graph deep learning has recently emerged as a powerful ML concept allowing to generalize successful deep neural architectures to non-euclidean structured data. Such methods have shown promising results on a broad spectrum of applications ranging from social science, biomedicine, and particle physics to computer vision, graphics, and chemistry. One of the limitations of the majority of current graph neural network architectures is that they are often restricted to the transductive setting and rely on the assumption that the underlying graph is known and fixed. Often, this assumption is not true since the graph may be noisy, or partially and even completely unknown. In such cases, it would be helpful to infer the graph directly from the data, especially in inductive settings where some nodes were not present in the graph at training time. Furthermore, learning a graph may become an end in itself, as the inferred structure may provide complementary insights next to the downstream task. In this paper, we introduce Differentiable Graph Module (DGM), a learnable function that predicts edge probabilities in the graph which are optimal for the downstream task. DGM can be combined with convolutional graph neural network layers and trained in an end-to-end fashion. We provide an extensive evaluation of applications from the domains of healthcare (disease prediction), brain imaging (age prediction), computer graphics (3D point cloud segmentation), and computer vision (zero-shot learning). We show that our model provides a significant improvement over baselines both in transductive and inductive settings and achieves state-of-the-art results.


Coronavirus Stress, Optimism-Pessimism, Psychological Inflexibility, and Psychological Health: Psychometric Properties of the Coronavirus Stress Measure.
The coronavirus (COVID-19) pandemic is currently a global health threat attributed to negatively affecting the mental health and well-being of people globally. The purpose of the present study is to examine the mediating role of optimism-pessimism and psychological inflexibility in the relationship of coronavirus stress with psychological problems among Turkish adults. The sample of the study included 451 adults (55% women). Participants mainly consisted of young adults with a mean age of 23.30 years, ranging from 18 to 65 years (SD = 6.97). A mediation model indicated that coronavirus stress had a significant predictive effect on optimism-pessimism, psychological inflexibility, and psychological problems. Further, optimism-pessimism and psychological inflexibility mediated the effect of coronavirus stress on psychological problems in adults. Lastly, optimism-pessimism predicted the psychological problems of adults through psychological inflexibility. These results elucidate our understanding of the role of mediators in coronavirus stress and psychological health problems. The findings are useful in terms of providing evidence for tailoring interventions and implementing preventative approaches to mitigate the psychopathological consequences of COVID-19. Based on the present findings, the potential utility of acceptance and commitment therapy is discussed within the context of COVID-19.


Tetanus, diphtheria, acellular pertussis vaccine during pregnancy: pregnancy and infant health outcomes.
To assess pregnancy and birth outcomes in infants born to women who did or did not receive tetanus, diphtheria, acellular pertussis (Tdap) vaccine during pregnancy. Retrospective cohort. Pregnant women 12-45 years of age who received Tdap at Intermountain Healthcare facilities and their infants were identified and compared with mother-infant pairs without documented Tdap from May 2005 through August 2009. Primary measures included pregnancy outcomes and infant health outcomes at birth through 12 months. From 162,448 pregnancies we identified 138 women (0.08%) with documented Tdap administration during pregnancy (cases); 552 pregnant women without documented Tdap were randomly selected as controls. Of 138 immunized women, 63% received Tdap in the first trimester and 37% after. Tdap was given most commonly as wound prophylaxis. The incidence of spontaneous or elective abortion was no greater in Tdap cases than in controls. There were no significant differences in preterm delivery, gestational age, or birth weight between groups. One or more congenital anomaly was identified in 3.7% (95% CI 1.2%-8.5%) of case infants and 4.4% (95% CI 2.7%-6.5%) of control infants (P = .749). In infants born to women receiving Tdap during pregnancy, 3.6% (0.8%-10.2%) had International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses consistent with complex chronic conditions within 12 months compared with 10.4% (95% CI 7.2%-14.4%) of infants of controls (P = .054). Documented Tdap administration during pregnancy was uncommon and occurred most often in the first trimester as prophylaxis following trauma. No increase in adverse outcomes was identified in infants born to women receiving Tdap compared with infants of controls.


Serum prostate specific antigen is a good indicator of prostatic volume in men with benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) is the most common cause of bladder outlet obstruction in men over the age of 50 years. An association between the prostate specific antigen (PSA), International Prostate Symptoms Score (IPSS) and prostate volume (PV) may be instrumental in determining patients who may benefit from treatment. Targeted therapy will reduce the cost of care because it is unwise to treat all men with prostate enlargement to prevent complications when the risk of occurrence is negligible. To determine the correlation between the PSA, IPSS and PV in men of African descent. This was a cross sectional analysis involving 92 patients diagnosed as having symptomatic BPH at the Ho Teaching Hospital. The data were collected using standardised questionnaires. The IPSS determined urinary symptom severity. The PV was determined using a transabdominal ultrasound machine. Serum PSA was retrieved from the electronic medical records. The mean PV was 61.04 cm3 ± 21.95 cm3, the mean PSA was 4.21 ng/mL ± 3.85 ng/mL, and mean IPSS of 21.59 ± 3.78. The Pearson's correlation between PV and PSA was 0.283 (p = 0.01), between PV and IPSS was 0.108 (p = 0.30), and finally, between Serum PSA and IPSS Score was -0.086 (p = 0.42). This study showed that serum PSA has a positive correlation with PV. However, IPSS had no significant association with PSA or PV in patients with BPH.Contribution: This study provides insights into the implications of clinical parameters on the management of prostate enlargement.


Effect of mutation mechanisms on variant composition and distribution in Caenorhabditis elegans.
Genetic diversity is maintained by continuing generation and removal of variants. While examining over 800,000 DNA variants in wild isolates of Caenorhabditis elegans, we made a discovery that the proportions of variant types are not constant across the C. elegans genome. The variant proportion is defined as the fraction of a specific variant type (e.g. single nucleotide polymorphism (SNP) or indel) within a broader set of variants (e.g. all variants or all non-SNPs). The proportions of most variant types show a correlation with the recombination rate. These correlations can be explained as a result of a concerted action of two mutation mechanisms, which we named Morgan and Sanger mechanisms. The two proposed mechanisms act according to the distinct components of the recombination rate, specifically the genetic and physical distance. Regression analysis was used to explore the characteristics and contributions of the two mutation mechanisms. According to our model, ~20-40% of all mutations in C. elegans wild populations are derived from programmed meiotic double strand breaks, which precede chromosomal crossovers and thus may be the point of origin for the Morgan mechanism. A substantial part of the known correlation between the recombination rate and variant distribution appears to be caused by the mutations generated by the Morgan mechanism. Mathematically integrating the mutation model with background selection model gives a more complete depiction of how the variant landscape is shaped in C. elegans. Similar analysis should be possible in other species by examining the correlation between the recombination rate and variant landscape within the context of our mutation model.


[New aspects in the biological preparation of tissues for plastic repair using V.P. Filatov's pedicle flap].
In the paper, the author's experience and literature data on studies of the role of biological processes developing in the host wound and grafted tissues in formation of the pedicled graft are reported. Considering these processes in the modern aspect in due account of general state of the organism, the status of local tissues, causes conditioning the defects formation and other factors, the author suggests new grounds for his concepts concerning the rational of active biological preparation of tissues in creating the pedicled graft. The technic of the preparation in question and results of its successful utilization in 25 patients are described, the conditions for wound and tissue healing being unfavourable due to different reasons, and in case of need of large quantities of plastic material the former also may be used.


The developmental, molecular, and transport biology of Malpighian tubules.
Molecular biology is reaching new depths in our understanding of the development and physiology of Malpighian tubules. In Diptera, Malpighian tubules derive from ectodermal cells that evaginate from the primitive hindgut and subsequently undergo a sequence of orderly events that culminates in an active excretory organ by the time the larva takes its first meal. Thereafter, the tubules enlarge by cell growth. Just as modern experimental strategies have illuminated the development of tubules, genomic, transcriptomic, and proteomic studies have uncovered new tubule functions that serve immune defenses and the breakdown and renal clearance of toxic substances. Moreover, genes associated with specific diseases in humans are also found in flies, some of which, astonishingly, express similar pathophenotypes. However, classical experimental approaches continue to show their worth by distinguishing between -omic possibilities and physiological reality while providing further detail about the rapid regulation of the transport pathway through septate junctions and the reversible assembly of proton pumps.


Familial hyperaldosteronism type III.
Primary aldosteronism is the most common form of endocrine hypertension. This disorder comprises both sporadic and familial forms. Four familial forms of primary aldosteronism (FH-I to FH-IV) have been described. FH-III is caused by germline mutations in KCNJ5, encoding the potassium channel Kir3.4 (also called GIRK4). These mutations alter the selectivity filter of the channel and lead to abnormal ion currents with loss of potassium selectivity, sodium influx and consequent increased intracellular calcium that causes excessive aldosterone biosynthesis. To date, eleven families have been reported, carrying six different mutations. Although the clinical features are variable, FH-III patients often display severe hyperaldosteronism with an early onset, associated with hypokalemia and diabetes insipidus-like symptoms. In most cases FH-III patients are resistant to pharmacological therapy and require bilateral adrenalectomy to control symptoms. In the present manuscript, we review the genetics and pathological basis of FH-III, the diagnostic work-up, clinical features and therapeutic management. Finally, we will describe a new case of FH-III of an Italian patient carrying a Gly151Arg mutation.


Changes in serum concentrations of markers of myocardial injury following treadmill exercise testing in patients with suspected ischaemic heart disease.
The treadmill exercise test (TEST) is frequently used in patients with suspected ischaemic heart disease to establish a diagnosis and estimate future risk. However, its predictive value is poor. We aimed to investigate whether measurement of biochemical markers of myocardial injury could improve the diagnostic value of the procedure. Twenty-four subjects with suspected acute coronary syndrome underwent a treadmill exercise stress test. Of these 13 had had a previous myocardial infarction and two had a past history of coronary artery bypass grafting. Nine subjects were found to be positive for coronary ischaemia during the treadmill test. Serum cardiac markers (total creatine kinase [CK], CK-MB, Troponin I and Troponin T) were measured pre-TEST, and 0, 1, 2, 4, 8 and 24 hours following the treadmill test. Total CK remained within the reference range for all subjects and showed no significant rise. However, mean serum concentrations of CK-MB were significantly higher than pre-test values at 2 hours (p < 0.03) following treadmill exercise testing in subjects who had a positive exercise stress test, but not in those with a negative test. In the subjects with a positive stress test, CK-MB levels returned to pre-Test value by 24 hours. Levels of neither serum troponin I, nor troponin T altered significantly at any point. The measurement of CK-MB, but not cardiac troponins may add to the diagnostic utility of the TEST.


Multimodal investigation of triple network connectivity in patients with 22q11DS and association with executive functions.
Large-scale brain networks play a prominent role in cognitive abilities and their activity is impaired in psychiatric disorders, such as schizophrenia. Patients with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing schizophrenia and present similar cognitive impairments, including executive functions deficits. Thus, 22q11DS represents a model for the study of neural biomarkers associated with schizophrenia. In this study, we investigated structural and functional connectivity within and between the Default Mode (DMN), the Central Executive (CEN), and the Saliency network (SN) in 22q11DS using resting-state fMRI and DTI. Furthermore, we investigated if triple network impairments were related to executive dysfunctions or the presence of psychotic symptoms. Sixty-three patients with 22q11DS and sixty-eighty controls (age 6-33 years) were included in the study. Structural connectivity between main nodes of DMN, CEN, and SN was computed using probabilistic tractography. Functional connectivity was computed as the partial correlation between the time courses extracted from each node. Structural and functional connectivity measures were then correlated to executive functions and psychotic symptom scores. Our results showed mainly reduced structural connectivity within the CEN, DMN, and SN, in patients with 22q11DS compared with controls as well as reduced between-network connectivity. Functional connectivity appeared to be more preserved, with impairments being evident only within the DMN. Structural connectivity impairments were also related to executive dysfunctions. These findings show an association between triple network structural alterations and executive deficits in patients with the microdeletion, suggesting that 22q11DS and schizophrenia share common psychopathological mechanisms. Hum Brain Mapp 38:2177-2189, 2017. © 2017 Wiley Periodicals, Inc.


Risk of death and readmission among individuals with heart failure and HIV: A systematic review and meta-analysis.
The association between human immunodeficiency virus (HIV) status and readmissions and death outcomes in patients with established heart failure (HF) remains unclear. We conducted a systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science up to March 1st, 2023, for cohort studies of adult patients (≥18 years) diagnosed with HF and recorded HIV status at baseline. Our analysis included 7 studies with 10,328 HF patients living with HIV and 48,757 HF patients without HIV. Compared to HF patients without HIV, those with HIV had a higher risk of all-cause deaths (HR: 1.20, 95% CI: 1.15-1.25). HIV infection was also associated with increased risks of HF-associated readmission (HR: 1.34, 95% CI: 1.03-1.75) and all-cause readmission (HR: 1.27, 95% CI: 1.10-1.46). Our study highlights the independent association between HIV and poor HF outcomes, emphasizing the need for improved management in individuals living with HIV.


Comparing two neurocognitive models of self-control during dietary decisions.
Self-control is the process of favoring abstract, distal goals over concrete, proximal goals during decision-making and is an important factor in health and well-being. We directly compare two prominent neurocognitive models of human self-control with the goal of identifying which, if either, best describes behavioral and neural data of dietary decisions in a large sample of overweight and obese adults motivated to eat more healthfully. We extracted trial-by-trial estimates of neural activity during incentive-compatible choice from three brain regions implicated in self-control, dorsolateral prefrontal cortex, ventral striatum and ventromedial prefrontal cortex and assessed evidence for the dual-process and value-based choice models of self-control using multilevel modeling. Model comparison tests revealed that the value-based choice model outperformed the dual-process model and best fit the observed data. These results advance scientific knowledge of the neurobiological mechanisms underlying self-control-relevant decision-making and are consistent with a value-based choice model of self-control.


High-resistance training and muscle metabolism during prolonged exercise.
To investigate the hypothesis that changes in muscle submaximal exercise metabolism would occur as a result of fiber hypertrophy, induced by high-resistance training (HRT), active but untrained males (age 20 +/- 0.7 yr; mean +/- SE) performed lower-limb weight training 3 days/wk for 12 wk using three sets of 6-8 repetitions maximal (RM)/day. Muscle metabolism was examined at different stages of training (4, 7, and 12 wk) using a two-stage continuous cycle test performed at the same absolute power output and duration (56.4 +/- 2.9 min) and representing 57 and 72% of pretraining peak aerobic power (VO2 peak). Compared with pretraining, at the end of exercise, HRT resulted in a higher (P < 0.05) phosphocreatine (PCr; 27.4 +/- 6. 7 vs. 38.0 +/- 1.9 mmol/kg dry wt), a lower lactate (38.9 +/- 8.5 vs. 24.4 +/- 6.1 mmol/kg dry wt), and a higher (P < 0.05) glycogen content (132 +/- 11 vs. 181 +/- 7.5 mmol glucosyl units/kg dry wt). The percent change from rest before and after training was 63 and 50% for PCr, 676 and 410% for lactate, and 60 and 43% for glycogen, respectively. These adaptations, which were observed only at 72% VO2 peak, occurred by 4 wk of training in the case of PCr and glycogen and before any changes in fiber cross-sectional area, capillarization, or oxidative potential. Fiber hypertrophy, observed at 7 and 12 wk of training, failed to potentiate the metabolic response. No effect of HRT was found on VO2 peak with training (41.2 +/- 2.9 vs. 41.0 +/- 2.1 ml. kg-1. min-1) or on the steady-state, submaximal exercise rate of oxygen consumption. It is concluded that the HRT results in muscle metabolic adaptations that occur independently of fiber hypertrophy.