Intracellular catalysis of disulfide bond formation by the human sulfhydryl oxidase, QSOX1.
The discovery that the flavoprotein oxidase, Erv2p, provides oxidizing potential for disulfide bond formation in yeast, has led to investigations into the roles of the mammalian homologues of this protein. Mammalian homologues of Erv2p include QSOX (sulfhydryl oxidases) from human lung fibroblasts, guinea-pig endometrial cells and rat seminal vesicles. In the present study we show that, when expressed in mammalian cells, the longer version of human QSOX1 protein (hQSOX1a) is a transmembrane protein localized primarily to the Golgi apparatus. We also present the first evidence showing that hQSOX1a can act in vivo as an oxidase. Overexpression of hQSOX1a suppresses the lethality of a complete deletion of ERO1 (endoplasmic reticulum oxidase 1) in yeast and restores disulfide bond formation, as assayed by the folding of the secretory protein carboxypeptidase Y.


Video-assisted hepatic abscess debridement.
Pyogenic liver abscesses are currently treated by either percutaneous computer tomography (CT)-guided drainage or by laparoscopic and a conventional liver resection when conservative treatment fails but may be associated with substantial morbidity and mortality. A minimally invasive technique involving debridement of right liver abscesses was employed using a minimally invasive video-assisted hepatic abscess debridement (VAHD) after unsuccessful percutaneous CT-guided drainage. Clinical data, complication rates and outcomes of patients were recorded retrospectively. Between 2011 and 2014, VAHD was performed on 10 patients at two centres with no observed recurrence of a liver abscess. The median age of the patients was 57 years (range 42-78) with a median pre-operative size of a liver abscess of 78 mm (range 40-115). The median operation time was 47 min (range 23-75), and the median postoperative hospital stay was 9 days (range 7-69). One patient developed a subcutaneous abscess that required further surgery. No patient died, and there were no major complications related to the VAHD. Video-assisted hepatic abscess debridement is a feasible technique that shows promising results for the treatment of a recurrent right liver abscess.


Separation in flowering time contributes to the maintenance of sympatric cryptic plant lineages.
Sympatric cryptic lineages are a challenge for the understanding of species coexistence and lineage diversification as well as for management, conservation, and utilization of plant genetic resources. In higher plants studies providing insights into the mechanisms creating and maintaining sympatric cryptic lineages are rare. Here, using microsatellites and chloroplast sequence data, morphometric analyses, and phenological observations, we ask whether sympatrically coexisting lineages in the common wetland plant Juncus effusus are ecologically differentiated and reproductively isolated. Our results show two genetically highly differentiated, homoploid lineages within J. effusus that are morphologically cryptic and have similar preference for soil moisture content. However, flowering time differed significantly between the lineages contributing to reproductive isolation and the maintenance of these lineages. Furthermore, the later flowering lineage suffered less from predispersal seed predation by a Coleophora moth species. Still, we detected viable and reproducing hybrids between both lineages and the earlier flowering lineage and J. conglomeratus, a coexisting close relative. Flowering time differentiation between the lineages can be explained by neutral divergence alone and together with a lack of postzygotic isolation mechanisms; the sympatric coexistence of these lineages is most likely the result of an allopatric origin with secondary contact.


Doppler studies comparing the effects of cervical rotation and lateral flexion on vertebral artery blood flow.
To determine the effects of cervical contralateral rotation and cervical contralateral lateral flexion on vertebral artery blood flow velocity. A prospective study was performed at a private chiropractic clinic. One hundred forty-eight patients had their vertebral arteries insonated as part of the premanipulative screening procedure. The vertebral arteries were insonated using a Doppler ultrasound velocimeter in the neutral position, during cervical contralateral rotation to the end range and during contralateral lateral flexion to the end range. Persistence or loss of Doppler signals from the vertebral arteries during neck movement was recorded. Of 280 vertebral arteries able to be insonated, 5% (0 < 5% < 9% at p = .99 confidence interval) had Doppler signals that stopped during contralateral rotation. Doppler signals from all 187 vertebral arteries tested during lateral flexion persisted, whereas 6 (3.2%) of this group of arteries had signals that ceased during contralateral rotation. Vertebral artery Doppler signals from patients can be greatly reduced or extinguished during contralateral cervical rotation. However, this is an unusual finding. The same phenomenon was not observed during contralateral cervical lateral flexion, which suggests that there may be less mechanical stress placed on the vertebral artery during lateral flexion.


Effects of nitric oxide on slow waves and spontaneous contraction of guinea pig gastric antral circular muscle.
We examined the effects of nitric oxide (NO) donors, S-nitroso-L-cysteine (Cys-NO) and 3-morpholinosydnonimine hydrochloride (SIN-1), on slow waves and contractile activity in the circular muscle of guinea pig gastric antrum. In the presence of atropine and guanethidine, electrical field stimulation (EFS) reduced the amplitude of phasic contraction. The effect of EFS was significantly inhibited by both the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester and a soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Cys-NO and SIN-1 mimicked the effect of EFS on phasic contraction and reduced the amplitude of slow waves in a concentration-dependent manner, with no effect on frequency and resting membrane potential. Phasic contraction was more sensitive to NO donors than slow waves. The inhibitory effects of NO donors were antagonized by ODQ and mimicked by a membrane permeable cGMP analogue 8-bromo-cGMP. Several K(+) channel blockers such as apamin, iberiotoxin, and glibenclamide had no effect on the inhibitory action of SIN-1. These results suggest that NO inhibits the phasic contraction and slow waves through cGMP-dependent mechanisms in guinea pig gastric antrum. The effect of NO is unlikely to be mediated by the activation of Ca(2+)-activated or ATP-sensitive K(+) channels.


Testing the effectiveness of the Amputee Mobility Protocol: a pilot study.
We studied prolonged length of stay (LOS) in the acute care setting on a medical-surgical vascular unit, related to loss of functional mobility status after lower extremity amputation, and implementation of the Amputee Mobility Protocol (AMP) as a standard of care for all patients pre- and post-lower extremity amputation who were admitted to the medical-surgical vascular unit. A comparative pre-post observational study evaluated the effect of AMP on level of functional mobility and LOS after lower extremity amputation in the patient population on the medical-surgical vascular unit. Data was collected retrospectively from patient chart reviews from November of 2004 to March of 2005 for the pre-AMP group and through concurrent patient chart reviews from November of 2005 to March of 2006 for the post-AMP group. Dependent variables included functional mobility and LOS, which were evaluated by a modified Functional Independence Measure (FIM) score and the hospital LOS. Forty-four eligible patients were enrolled in the AMP pilot study during a 5-month period. The sample population consisted of 30 patients pre-AMP and 14 patients post-AMP. LOS for transmetatarsal amputations decreased by 0.7 days, whereas functional mobility increased by a minimum of one level in the modified FIM score. Functional mobility increased for transtibial amputations by one level and transfemoral amputations by 2 levels using the modified FIM score. LOS increased for patients undergoing transtibial (7.1 days) and transfemoral (2.7 days) amputations. This quality improvement project heightened staff awareness regarding ambulation and its impact on functional mobility and early discharge. Vascular nurses were able to affect patients' functional mobility and LOS by implementing a standardized AMP. Data showed that using the standardized AMP increased patients' functional mobility but did not significantly decrease acute care setting LOS. The AMP continues to be used for this patient population because of its impact on functional mobility and independence. This pilot study relates to 3 of the top 20 vascular research priorities: 1) an interdisciplinary strategy to improve the patient's level of functional independence and thereby decrease LOS and cost; 2) the nursing intervention of early, predetermined ambulation schedules will increase the nursing knowledge of strategies that facilitate recovery after vascular surgery in this population; and 3) factors that affect patient outcomes after these three major vascular procedures will be addressed in pilot outcomes. Limitations of the AMP pilot study included the small sample size, staff turnover, and lack of a concurrent control group. The next phase of this project will create and implement a similar activity protocol for patients after abdominal aortic aneurysm repair and various types of lower extremity bypass procedures.


Electrospun fibrous scaffolds promote breast cancer cell alignment and epithelial-mesenchymal transition.
In this work we created electrospun fibrous scaffolds with random and aligned fiber orientations in order to mimic the three-dimensional structure of the natural extracellular matrix (ECM). The rigidity and topography of the ECM environment have been reported to alter cancer cell behavior. However, the complexity of the in vivo system makes it difficult to isolate and study such extracellular topographical cues that trigger cancer cells' response. Breast cancer cells were cultured on these fibrous scaffolds for 3-5 days. The cells showed elongated spindle-like morphology in the aligned fibers, whereas they maintained a mostly flat stellar shape in the random fibers. Gene expression profiling of these cells post seeding showed up-regulation of transforming growth factor β-1 (TGFβ-1) along with other mesenchymal biomarkers, suggesting that these cells undergo epithelial-mesenchymal transitions in response to the polymer scaffold. The results of this study indicate that the topographical cue may play a significant role in tumor progression.


ILOOP--a web application for two-channel microarray interwoven loop design.
Microarray technology is widely applied to address complex scientific questions. However, there remain fundamental issues on how to design experiments to ensure that the resulting data enables robust statistical analysis. Interwoven loop design has several advantages over other designs. However it suffers in the complexity of design. We have implemented an online web application which allows users to find optimal loop designs for two-color microarray experiments. Given a number of conditions (such as treatments or time points) and replicates, the application will find the best possible design of the experiment and output experimental parameters. It is freely available from http://mcbc.usm.edu/iloop.


CO2-activation for γ-butyrolactones and its application in the total synthesis of (±)-heteroplexisolide E.
An efficient nickel(0)-catalyzed highly regio- and stereoselective hydrocarboxylation of homopropargylic alcohols with ZnEt(2) in the presence of CO(2) (1 atm, balloon) to synthesize α-alkylidene-γ-butyrolactones is described. The catalyst is highly active and can be applied for the synthesis of (optically active) mono- or bicyclic α-alkylidene-γ-butyrolactones with excellent regio- and stereoselectivity and good functional group tolerance. The potential of the reaction has been demonstrated in the first synthesis of (±)-heteroplexisolide E.


Changes in spinal cord excitability in a patient with rhythmic segmental myoclonus.
Paired stimulation of the common peroneal and posterior tibial nerve was used to study the recovery cycle of lumbosacral somatosensory evoked potentials in 10 control subjects and in one patient with rhythmic segmental myoclonus of the leg involving the L2-L4 myotomes. In normal subjects the peripheral nerve volley in the cauda equina had recovered at an interstimulus interval of 3 ms whereas the postsynaptic dorsal horn potential was reduced to about 60% of its control size. Similar results were found in the patient after posterior tibial nerve but not common peroneal nerve stimulation. The second, which evokes afferent input to the affected lumbar segments, produced facilitation of the postsynaptic response at 3 ms. This finding suggests that the physiological suppression of dorsal horn interneurons which usually takes place after paired stimulation fails to occur in segmental myoclonus. This may indicate that dorsal horn interneurons are abnormally hyperactive and are involved in the pathophysiology of spinal myoclonus.


Symbolic representation of numerosity by honeybees ( Apis mellifera): matching characters to small quantities.
The assignment of a symbolic representation to a specific numerosity is a fundamental requirement for humans solving complex mathematical calculations used in diverse applications such as algebra, accounting, physics and everyday commerce. Here we show that honeybees are able to learn to match a sign to a numerosity, or a numerosity to a sign, and subsequently transfer this knowledge to novel numerosity stimuli changed in colour properties, shape and configuration. While honeybees learned the associations between two quantities (two; three) and two signs (N-shape; inverted T-shape), they failed at reversing their specific task of sign-to-numerosity matching to numerosity-to-sign matching and vice versa (i.e. a honeybee that learned to match a sign to a number of elements was not able to invert this learning to match the numerosity of elements to a sign). Thus, while bees could learn the association between a symbol and numerosity, it was linked to the specific task and bees could not spontaneously extrapolate the association to a novel, reversed task. Our study therefore reveals that the basic requirement for numerical symbolic representation can be fulfilled by an insect brain, suggesting that the absence of its spontaneous emergence in animals is not due to cognitive limitation.


Expanding the role of community mobilization to accelerate progress towards ending vertical transmission of HIV in Uganda: the Networks model.
Efforts to prevent vertical transmission of HIV have gained momentum globally since the launch of the "Global plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive", reflecting the growing consensus that we now have low-cost, efficacious interventions that promise to end vertical transmission of HIV. Uganda is one of the 22 focus countries in the global plan and one of the 10 countries with the highest need for prevention of vertical transmission globally. In the context of current shortfalls in the prevention of vertical HIV transmission, this paper presents the results of the Networks project, a community mobilisation model implemented by the International HIV/AIDS Alliance in Uganda, and draws out the theoretical foundations and promising community mobilization practices relevant to prevention of vertical transmission. A retrospective review of the Network project's activities, documentation and evaluation was performed. The Networks project, through community mobilisation and greater involvement of people living with HIV, reached an estimated 1.3 million people with at least one health service. By clustering 750 groups of people living with HIV into larger coalitions, the project supported existing groups to amalgamate their collective strengths and skills in outreach, referral and literacy activities; and improved reach and coverage of HIV services through strengthened linkages with healthcare facilities. Our analysis of the Networks model shows that it could contribute to the prevention of vertical transmission of HIV as a replicable and sustainable community mobilisation approach. In particular, the Networks model increased the uptake of decentralized interventions for preventing vertical transmission through community referrals; promoted male involvement through peer sensitisation; and linked communities to advocacy channels for advancing maternal health and prevention of vertical HIV transmission. BY placing persons living with HIV at the centre, the Networks model offers a mechanism for strengthening community and male involvement in preventing vertical transmission of HIV. The role of communities and networks of people living with HIV in planning, service delivery and monitoring of national targets for prevention of vertical transmission should be further strengthened through greater community engagement in service delivery and advocacy and through the regular sharing of data between communities and health facilities.


Improving outcomes in chronic obstructive pulmonary disease: the role of the interprofessional approach.
Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, places substantial time and cost burden on the health care system, and is now the third leading cause of death in the US. Many interventions are available to appropriately manage patients with COPD; however, fully implementing these strategies to help improve outcomes may be difficult. Collaboration between an interprofessional team of health care professionals (which includes physicians, nurses, respiratory therapists, physical therapists, dietitians, pharmacists, and many others) and COPD patients and caregivers is necessary to optimally manage these patients and to truly impact outcomes in this devastating disease. Prescribing evidence-based non-pharmacological and pharmacological therapies is an important start, but a true team-based approach is critical to successfully implement comprehensive care in patients with COPD. The goal of this review is to employ a case-based approach to provide practical information regarding the roles of the interprofessional team in implementing strategies to optimally manage COPD patients.


CXCR2-Blocking Has Context-Sensitive Effects on Rat Glioblastoma Cell Line Outgrowth (S635) in an Organotypic Rat Brain Slice Culture Depending on Microglia-Depletion (PLX5622) and Dexamethasone Treatment.
In glioblastoma (GBM), the interplay of different immune cell subtypes, cytokines, and/or drugs shows high context-dependencies. Interrelations between the routinely applied dexamethasone (Dex) and microglia remain elusive. Here, we exploited rat organotypic brain slice co-cultures (OBSC) to examine the effects on a rat GBM cell line (S635) outgrowth resulting from the presence of Dex and pretreatment with the colony-stimulating factor receptor 1 (CSF1-R) inhibitor PLX5622: in native OBSC (without PLX5622-pretreatment), a diminished S635 spheroid outgrowth was observable, whereas Dex-treatment enhanced outgrowth in this condition compared to PLX5622-pretreated OBSC. Screening the supernatants of our model with a proteome profiler, we found that CXCL2 was differentially secreted in a Dex- and PLX5622-dependent fashion. To analyze causal interrelations, we interrupted the CXCL2/CXCR2-axis: in the native OBSC condition, CXCR2-blocking resulted in increased outgrowth, in combination with Dex, we found potentiated outgrowth. No effect was found in the PLX5622-pretreated. Our method allowed us to study the influence of three different factors-dexamethasone, PLX5622, and CXCL2-in a well-controlled, simplified, and straight-forward mechanistic manner, and at the same time in a more realistic ex vivo scenario compared to in vitro studies. In our model, we showed a GBM outgrowth enhancing synergism between CXCR2-blocking and Dex-treatment in the native condition, which was levelled by PLX5622-pretreatment.


A Simple Microfluidic Chip for Long-Term Growth and Imaging of Caenorhabditis elegans.
Caenorhabditis elegans (C. elegans) have proved to be a valuable model system for studying developmental and cell biological processes. Understanding these biological processes often requires long-term and repeated imaging of the same animal. Long recovery times associated with conventional immobilization methods done on agar pads have detrimental effects on animal health making it inappropriate to repeatedly image the same animal over long periods of time. This paper describes a microfluidic chip design, fabrication method, on-chip C. elegans culturing protocol, and three examples of long-term imaging to study developmental processes in individual animals. The chip, fabricated with polydimethylsiloxane and bonded on a cover glass, immobilizes animals on a glass substrate using an elastomeric membrane that is deflected using nitrogen gas. Complete immobilization of C. elegans enables robust time-lapse imaging of cellular and sub-cellular events in an anesthetic-free manner. A channel geometry with a large cross-section allows the animal to move freely within two partially sealed isolation membranes permitting growth in the channel with a continuous food supply. Using this simple chip, imaging of developmental phenomena such as neuronal process growth, vulval development, and dendritic arborization in the PVD sensory neurons, as the animal grows inside the channel, can be performed. The long-term growth and imaging chip operates with a single pressure line, no external valves, inexpensive fluidic consumables, and utilizes standard worm handling protocols that can easily be adapted by other laboratories using C. elegans.


Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen.
Some encephalitides or seizure disorders once thought idiopathic now seem to be immune mediated. We aimed to describe the clinical features of one such disorder and to identify the autoantigen involved. 15 patients who were suspected to have paraneoplastic or immune-mediated limbic encephalitis were clinically assessed. Confocal microscopy, immunoprecipitation, and mass spectrometry were used to characterise the autoantigen. An assay of HEK293 cells transfected with rodent GABA(B1) or GABA(B2) receptor subunits was used as a serological test. 91 patients with encephalitis suspected to be paraneoplastic or immune mediated and 13 individuals with syndromes associated with antibodies to glutamic acid decarboxylase 65 were used as controls. All patients presented with early or prominent seizures; other symptoms, MRI, and electroencephalography findings were consistent with predominant limbic dysfunction. All patients had antibodies (mainly IgG1) against a neuronal cell-surface antigen; in three patients antibodies were detected only in CSF. Immunoprecipitation and mass spectrometry showed that the antibodies recognise the B1 subunit of the GABA(B) receptor, an inhibitory receptor that has been associated with seizures and memory dysfunction when disrupted. Confocal microscopy showed colocalisation of the antibody with GABA(B) receptors. Seven of 15 patients had tumours, five of which were small-cell lung cancer, and seven patients had non-neuronal autoantibodies. Although nine of ten patients who received immunotherapy and cancer treatment (when a tumour was found) showed neurological improvement, none of the four patients who were not similarly treated improved (p=0.005). Low levels of GABA(B1) receptor antibodies were identified in two of 104 controls (p<0.0001). GABA(B) receptor autoimmune encephalitis is a potentially treatable disorder characterised by seizures and, in some patients, associated with small-cell lung cancer and with other autoantibodies. National Institutes of Health.


Dancers' perceptions of pain and injury: positive and negative effects.
Two hundred and four dance students, professionals, and former dancers in the UK completed questionnaires, semi-structured interviews, and a body scanning and mapping process aimed at gaining an increased understanding of how dancers interpret pain and its relationship to injury in the context of their careers. The research was targeted at modern and contemporary dancers, as they are an underrepresented group in the dance-injury literature. Results from the questionnaires were compared with other studies of dance injury, drawing on qualitative data where relevant. Findings indicated that 90% of the sample had experienced an injury (now or in the past), and that the lower back and knee were among the most common sites of current pain and injury. Qualitative descriptions of pain and injury indicated that dancers tend to define injury as something that stops them from dancing or from moving normally. Dance injury rates do not appear to be decreasing significantly, despite greater awareness and the promotion of the "healthier dancer" in dance training schools, universities and among professionals in the UK. There is evidence to show that as dancers age they are likely to be more aware of the warning signs of injury and to take steps to prevent it. Data indicated that dancers may under report injuries on surveys, suggesting that such self-reported survey data should be treated with caution. Further qualitative research on dance injuries may provide more useful understanding of dancers' interpretations and treatment of pain and injury.


A Fall Risk mHealth App for Older Adults: Development and Usability Study.
Falls are the leading cause of injury-related death in older adults. Due to various constraints, objective fall risk screening is seldom performed in clinical settings. Smartphones offer a high potential to provide fall risk screening for older adults in home settings. However, there is limited understanding of whether smartphone technology for falls screening is usable by older adults who present age-related changes in perceptual, cognitive, and motor capabilities. The aims of this study were to develop a fall risk mobile health (mHealth) app and to determine the usability of the fall risk app in healthy, older adults. A fall risk app was developed that consists of a health history questionnaire and 5 progressively challenging mobility tasks to measure individual fall risk. An iterative design-evaluation process of semistructured interviews was performed to determine the usability of the app on a smartphone and tablet. Participants also completed a Systematic Usability Scale (SUS). In the first round of interviews, 6 older adults participated, and in the second round, 5 older adults participated. Interviews were videotaped and transcribed, and the data were coded to create themes. Average SUS scores were calculated for the smartphone and tablet. There were 2 themes identified from the first round of interviews, related to perceived ease of use and perceived usefulness. While instructions for the balance tasks were difficult to understand, participants found it beneficial to learn about their risk for falls, found the app easy to follow, and reported confidence in using the app on their own. Modifications were made to the app, and following the second round of interviews, participants reported high ease of use and usefulness in learning about their risk of falling. Few differences were reported between using a smartphone or tablet. Average SUS scores ranged from 79 to 84. Our fall risk app was found to be highly usable by older adults as reported from interviews and high scores on the SUS. When designing a mHealth app for older adults, developers should include clear and simple instructions and preventative strategies to improve health. Furthermore, if the design accommodates for age-related sensory changes, smartphones can be as effective as tablets. A mobile app to assess fall risk has the potential to be used in home settings by older adults.


Reproductive efficiency of three estrus synchronization schemes comprising fixed-time insemination in dairy cows.
The objective of this field trial was to compare the odds of pregnancy at 25 days (P25) and at 60 days (P60), of embryonic death (ED) between 25 and 60 days, and of non-pregnant cows returning to heat 20-25 days after artificial insemination (AI). Three fixed-time insemination protocols involving combined administration of either double gonadotrophin-releasing hormone (GnRH) and prostaglandins (A) or GnRH, human chorionic gonadotrophin (hCG) and prostaglandins (B), or double treatment with prostaglandins (C) were used. Cows included in the trial were selected from five herds, comprising a total of 735 (herd size range 85-250, median 120) Holstein dairy cows. Animals used for the study were multiparous, 4-7 years of age, had expressed at least one overt postpartum heat, were between 60 and 120 days of lactation and had at least one palpable corpus luteum and no gross morphological anomalies of their reproductive tracts. They were randomly allocated to receive treatment A (n = 89), B (n = 93), or C (n = 65). Pregnancy of cows not observed in heat 18-24 days post AI was diagnosed by transrectal ultrasonography at 25-30 days and confirmed by rectal palpation at 60-75 days post AI. Those that were detected in heat in the normal period post AI were re-inseminated. No differences were detected among the three treatment groups concerning the odds of P25 (P = 0.5), P60 (P = 0.2) and ED (P = 0.13). In contrast, non-pregnant cows that were administered treatment A were less likely to exhibit estrous signs in the normal period post AI than those administered treatments B (P = 0.02) or C (P = 0.005).


Under the Surface of Subcutaneous Adipose Tissue Biology.
The global obesity epidemic enhanced contemporary interest in adipose tissue biology. Two structurally and functionally distinct depots, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), are spread throughout the body. Their distribution was recognized to be a major determinant of metabolic risk. Unlike VAT, SAT showed some protective endocrine and inflammatory features that might explain the occurrence of obese but metabolically healthy persons. The unique developmental gene expression signature, angiogenesis, and adipogenic potential of SAT determines its growth ability under the positive energy balance. The overflow hypothesis suggested that when SAT is unable to expand sufficiently, fat overflows towards metabolically adverse ectopic depots. Besides white adipose tissue, recent studies found important brown adipose tissue activity responsible for thermogenesis and energy dissipation in adults as well. SAT is prone to "browning" - the appearance of particular beige adipocytes that contribute to its favorable metabolic effects. Morbid obesity, aging, hormonal status, nutrition, low physical activity, and other environmental factors impair SAT relative resistance to dysfunctional changes and promote development of metabolic disorders. The popular approach considering SAT mainly as the subject of cosmetic procedures for improving the appearance of body contours should be avoided. Complex heterogeneity of obesity revealed that a tissue of an extreme plasticity and rich interactions with vital functions of the body lies under the surface. Therapeutic manipulations to preserve and enhance healthier fat in order to correct obesity-related metabolic disorders seem to be a relevant but still unexplored opportunity.


Pharmacokinetics of intravenously administered pefloxacin in the prostate; perspectives for its application in surgical prophylaxis.
In an attempt to define whether intravenously administered pefloxacin might be appropriate for surgical prophylaxis in prostatectomy, 50 patients undergoing transvesical prostatectomy for benign prostate hyperplasia were given a single intravenous dose of 800 mg; surgery was then performed after 2, 4, 6, 8 or 10 h. Concentrations of pefloxacin were determined in serum and in both the centre and periphery of the prostate adenoma using a microbiological plate assay. Elevated concentrations of pefloxacin were found in the adenoma from 2 h onwards. The central and peripheral concentrations were similar and had a mean value of 4.39 microg/g of tissue. These concentrations were similar to those achieved in serum. Although concentrations of pefloxacin were not determined separately in the intercellular, interstitial or excreted fluid, the tissue levels found were well above the MICs of pefloxacin for the bacteria commonly causing acute and chronic prostatitis. These data suggest the intravenous administration of pefloxacin to be a satisfactory alternative for the surgical prophylaxis before prostatectomy as well as in the therapy of acute prostatitis.


Alexithymia and cancer pain: the effect of psychological intervention.
Alexithymia is likely to be involved in the pain experience of cancer patients, but the extent to which psychological interventions may modify both pain and alexithymia is unclear. A group of 52 consecutive cancer patients were enrolled in a 6-month multicomponent psychological intervention trial, and compared to 52 control patients who received standard medical care. Validated scales for pain, alexithymia, coping with disease, illness behavior, psychological distress, and psychosocial functioning were administered at baseline and 6 months later. Pain was strongly associated with alexithymia and several psychological dimensions. Although at baseline patients in the intervention group had worse psychological and somatic health, at follow-up their level of pain intensity, alexithymia, and somatic concerns had significantly improved compared to control patients. Patients in the intervention group showed dramatic improvements in pain perception, alexithymia, and other psychological variables, while control patients showed an unexpected significant worsening of alexithymia, depression, and adjustment to disease. Multiple regression showed that psychological intervention and alexithymia were both independently associated with the reduction in pain perception. These findings confirm the close association between alexithymia and pain, and show that multicomponent psychological intervention may significantly reduce both alexithymia and cancer pain. Although the present findings need replication, they should strongly encourage clinicians to provide patients with psychological interventions targeting alexithymic difficulties and helping patients to cope better with both feelings and somatic perception.


Harms and Benefits of Subcutaneous Hydration in Older Patients: Systematic Review and Meta-Analysis.
To review all available original publications on the harms and benefits of subcutaneous (SC) hydration in older patients. Systematic review and meta-analysis. All studies on SC hydration in older patients without restrictions on design or language. The Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and Web of Science databases and trial registries were searched from inception to November 5, 2019, and two reviewers independently extracted the data and assessed the risk of bias of individual outcomes. Thirty-one publications from 29 studies met the eligibility criteria. The data from six randomized controlled trials were used for the meta-analyses. The subgroup analysis including only the studies with the lowest risk of bias showed that SC hydration was associated with fewer adverse effects than intravenous (IV) hydration (risk ratio (RR) = 0.69; 95% confidence interval (CI) = 0.53-0.88; P = .003; n = 4; I2 = 0.0%; 545 infusions in each group). In absolute numbers, patients treated with SC hydration had an incidence rate of 90 adverse effects per 1,000 infusions versus 130 adverse effects per 1,000 infusions (95% CI = 102-169) with IV hydration. Secondary outcomes comparing IV with SC hydration showed that SC was 3.2 minutes faster to set up and markedly reduced the risk of agitation (RR = 0.42; 95% CI = 0.22-0.79; P = .007; I2 = 65%; n = 3); however, SC hydration delivered a lower volume of fluid and was less efficient at reducing serum osmolality (s-osmolality). SC hydration is safer than IV hydration and potentially reduces the risk of agitation, but it is less effective. SC hydration should be available as an alternative to IV hydration when treating older patients for mild-to-moderate dehydration. More high-quality studies are needed in the field to increase the confidence in the estimates.


Effects of dihydropyridines on stress, myosin phosphorylation, and V0 in smooth muscle.
Contraction of swine carotid medial fibers with KCl results in stress development associated with high levels of myosin light chain (MLC) phosphorylation and maximum shortening velocity (V0) indicative of rapidly cycling phosphorylated cross bridges. The period of stress maintenance is characterized by low levels of MLC phosphorylation and V0; the maintained stress is postulated to be supported by dephosphorylated, slowly cycling cross bridges (latch bridges). This study was designed to examine the roles of calcium in both stress development and stress maintenance. Medial strips were contracted with 110 mM KCl in the presence of varying concentrations of the calcium channel blocker nifedipine (1-100 nM) or were contracted with varying concentrations of the calcium channel activator BAY-K 8644 (0.3-3 microM). Nifedipine significantly depressed stress maintenance and V0, but had little effect on either stress development or MLC phosphorylation. Conversely, BAY-K 8644 produced contractions that were equal to those elicited with 110 mM KCl but that were characterized by low levels of V0 and basal or low levels of MLC phosphorylation. These data suggest that the mechanisms by which the cellular calcium concentration increases and the limitations on this increase may impact differently on different regulatory processes of contraction and, thereby, on cross bridge behavior.


[Mitral valve prolapse and parasystolic ventricular tachycardia: an unusual association].
Ventricular arrhythmias are common in patients with mitral valve prolapse. Conversely, parasystolic ventricular tachycardia is an uncommon arrhythmia that can be observed independent of preexisting heart disease. We report the case of an otherwise healthy 42-year-old woman with both mitral valve prolapse and parasystolic ventricular tachycardia.


Neural Networks: Making Connections about the Brain and about College while Monitoring Student Engagement in Second Graders.
This article describes a neuroscience outreach program developed by college undergraduates and aimed at second graders. Over a period of four weeks, twenty-five Denison students enrolled in a non-majors course on gender and the brain visited twenty-four second grade classrooms to engage a total of 464 students. We had a mission to both promote college awareness and to specifically bring some brain science into the classroom. The desire to engage students with the brain was in part a wish to celebrate brain awareness week and in part a wish to follow a feminist tenet of bridging theory and practice via activism. The college students chose six activities: a brain puzzle, a sock content guessing game, a jelly bean olfaction and taste test, mystery noises, a message transmission game, and a version of tag. During our outreach with the second graders, my students monitored student engagement and compared engagement between male and female second graders. Engagement was high for nearly all activities but girls were more engaged than boys during the brain puzzle and jelly bean activities. Effect sizes measured as Cohen's "d" statistics were small to large (0.2 to 0.93). The other four activities (mystery socks, mystery noises, message transmission and neuron chain tag) showed no difference in engagement between male and female second graders. Our program benefited the Denison students as well, introducing many to community involvement and awakening in them an interest in teaching or working with kids.


Gestational Estimated Glomerular Filtration Rate and Adverse Maternofetal Outcomes.
The association between gestational estimated glomerular filtration rate (eGFR) and adverse pregnancy outcomes has not been fully investigated. This observational cohort study included pregnancy cases of singleton mothers whose serum creatinine levels were measured during pregnancy at two tertiary hospitals in Korea from 2000 to 2015. Those with identified substantial renal function impairment (eGFR < 60 mL/min/1.73 m2 at baseline, during, or after pregnancy) were excluded. The Chronic Kidney Disease Epidemiology Collaboration equation was used for the eGFR calculation. We computed the time-averaged eGFR during gestation to determine representative values when there were multiple measurements. We studied the following three gestational complications: preterm birth (< 37 weeks' gestational age), low birth weight (< 2.5 kg), and preeclampsia. Among the 12,899 studied pregnancies, 4,360 cases experienced one or more gestational complications. The adjusted odds ratio (aOR) and 95% confidence interval of composite gestational complications for eGFR ranges other than the reference range of 120-150 mL/ min/1.73m2 were: ≥150 mL/min/1.73m2, aOR 1.64 (1.38-1.95), P< 0.001; 90-120 mL/min/1.73m2, aOR 1.41 (1.28-1.56), P< 0.001; and 60-90 mL/min/1.73m2, aOR 2.56 (1.70-3.84), P< 0.001. Incidence of preterm birth or low birth weight showed similar U-shaped association with eGFR values; otherwise, preeclampsia or small for gestational age occurred more often in mothers with a lower gestational eGFR than in those with a higher value. Considering the unique association between gestational eGFR and pregnancy outcomes, carefully interpreting these results may help predict obstetric complications.


Temporal changes in characteristics of injection-site sarcomas in cats: 392 cases (1990-2006).
To evaluate changes in characteristics of feline injection-site sarcomas (ISSs) from 1990 through 2006. Retrospective case series. 392 cats with a histologic diagnosis of soft tissue sarcoma, osteosarcoma, or chondrosarcoma at potential injection sites. Classification and anatomic location of tumors and signalment of affected cats were compared between ISSs diagnosed before and after publication of the Vaccine Associated Feline Sarcoma Task Force vaccination recommendations in 1996. From before to after publication of the vaccination recommendations, proportions of ISSs significantly decreased in the interscapular (53.4% to 39.5%) and right and left thoracic (10.2% to 3.6% and 9.1% to 1.3%, respectively) regions. On the other hand, proportions of ISSs significantly increased in the right thoracic limb (1.1% to 9.5%) and the combined regions of the right pelvic limb with right lateral aspect of the abdomen (12.5% to 25.0%) and the left pelvic limb with left lateral aspect of the abdomen (11.4% to 13.8%). Patterns of tumor classification and signalment did not change. Despite publication of the vaccination recommendations, a high proportion of tumors still developed in the interscapular region. There was also an increase in lateral abdominal ISSs, which are more difficult to treat and are likely attributable to aberrant placement of injections intended for the pelvic limbs. Veterinarians are complying with vaccination recommendations to some extent, but they need to focus on administering vaccines as distally as possible on a limb to allow for complete surgical margins if amputation of a limb is required.


Direct optogenetic activation of upper airway muscles in an acute model of upper airway hypotonia mimicking sleep onset.
Obstructive sleep apnea (OSA), where the upper airway collapses repeatedly during sleep due to inadequate dilator muscle tone, is challenging to treat as current therapies are poorly tolerated or have variable and unpredictable efficacy. We propose a novel, optogenetics-based therapy, that stimulates upper airway dilator muscle contractions in response to light. To determine the feasibility of a novel optogenetics-based OSA therapy, we developed a rodent model of human sleep-related upper airway muscle atonia. Using this model, we evaluated intralingual delivery of candidate optogenetic constructs, notably a muscle-targeted approach that will likely have a favorable safety profile. rAAV serotype 9 viral vectors expressing a channelrhodopsin-2 variant, driven by a muscle-specific or nonspecific promoter were injected into rat tongues to compare strength and specificity of opsin expression. Light-evoked electromyographic responses were recorded in an acute, rodent model of OSA. Airway dilation was captured with ultrasound. The muscle-specific promoter produced sufficient opsin expression for light stimulation to restore and/or enhance electromyographic signals (linear mixed model, F = 140.0, p < 0.001) and induce visible tongue contraction and airway dilation. The muscle-specific promoter induced stronger (RM-ANOVA, F(1,8) = 10.0, p = 0.013) and more specific opsin expression than the nonspecific promoter in an otherwise equivalent construct. Viral DNA and RNA were robust in the tongue, but low or absent in all other tissues. Significant functional responses to direct optogenetic muscle activation were achieved following muscle-specific promoter-driven rAAV-mediated transduction, providing proof-of-concept for an optogenetic therapy for patients with inadequate dilator muscle activity during sleep.


PLK1 targets NOTCH1 during DNA damage and mitotic progression.
Notch signaling plays a complex role in carcinogenesis, and its signaling pathway has both tumor suppressor and oncogenic components. To identify regulators that might control this dual activity of NOTCH1, we screened a chemical library targeting kinases and identified Polo-like kinase 1 (PLK1) as one of the kinases involved in arsenite-induced NOTCH1 down-modulation. As PLK1 activity drives mitotic entry but also is inhibited after DNA damage, we investigated the PLK1-NOTCH1 interplay in the G2 phase of the cell cycle and in response to DNA damage. Here, we found that PLK1 regulates NOTCH1 expression at G2/M transition. However, when cells in G2 phase are challenged with DNA damage, PLK1 is inhibited to prevent entry into mitosis. Interestingly, we found that the interaction between NOTCH1 and PLK1 is functionally important during the DNA damage response, as we found that whereas PLK1 activity is inhibited, NOTCH1 expression is maintained during DNA damage response. During genotoxic stress, cellular transformation requires that promitotic activity must override DNA damage checkpoint signaling to drive proliferation. Interestingly, we found that arsenite-induced genotoxic stress causes a PLK1-dependent signaling response that antagonizes the involvement of NOTCH1 in the DNA damage checkpoint. Taken together, our data provide evidence that Notch signaling is altered but not abolished in SCC cells. Thus, it is also important to recognize that Notch plasticity might be modulated and could represent a key determinant to switch on/off either the oncogenic or tumor suppressor function of Notch signaling in a single type of tumor.


The immediate effect of bilateral superior obliuqe tenotomy on primary position horizontal binocular alignment.
To evaluate the effect on primary position horizontal binocular alignment of superior oblique tenotomy for A-pattern exotropia with bilateral superior oblique overaction using new surgical and anesthesia techniques. We performed intraoperatively adjustable horizontal strabismus surgery under topical anesthesia in 6 cases of A-pattern exotropia. After adjusting the horizontal deviation nearly to orthotropia in primary position, we measured the angle of horizontal deviation in up-, primary, and downgaze positions. This was followed by bilateral superior oblique tenotomy and remeasurement of the horizontal deviation in the same 3 positions. Postoperatively we remeasured the deviation at one day, one month and three months. There was no immediate change in the horizontal deviation in primary position in 2 of the 6 patients, and 3-8 delta of immediate esotropic shift in 4 of the 6 patients (average 3.3 delta) after bilateral superior oblique tenotomy. At 3 months postop' the small esotropia noted at the immediate postop' measurement became orthotropic. There was a tendency of increased exotropic shift or becoming exotropic in those patients with slight exotropia or orthotropia at the immediate postop' measurement. But these shifts were minimal. When combined surgery of superior oblique and horizontal muscle is planned for A-pattern exotropia, the effect of bilateral superior oblique tenotomy on the primary position horizontal binocular alignment can be disregarded.


Febrile Neutropenia: Decreasing Time to Antibiotic Administration in a Community Hospital Emergency Department.
Febrile neutropenia, a serious complication of cytotoxic chemotherapy, is an oncologic emergency associated with high rates of morbidity and mortality. Fever is often the only clinical sign of an underlying infection in neutropenic patients with cancer. Prompt treatment with empiric broad-spectrum antibiotics is crucial to ensuring best outcomes for patients; practice guidelines recommend antibiotic administration within one hour of fever onset. A quality improvement initiative to improve time to antibiotic administration among patients with febrile neutropenia presenting to a community hospital emergency department is described in this article.


Two chromosomal genes required for killing expression in killer strains of Saccharomyces cerevisiae.
The killer character of yeast is determined by a 1.4 X 10(6) molecular weight double-stranded RNA plasmid and at least 12 chromosomal genes. Wild-type strains of yeast that carry this plasmid (killers) secret a toxin which is lethal only to strains not carrying this plasmid (sensitives).--We have isolated 28 independent recessive chromosomal mutants of a killer strain that have lost the ability to secrete an active toxin but remain resistant to the effects of the toxin and continue to carry the complete cytoplasmic killer genome. These mutants define two complementation groups, kex1 and kex2. Kex1 is located on chromosome VII between ade5 and lys5. Kex2 is located on chromosome XIV, but it does not show meiotic linkage to any gene previously located on this chromosome.--When the killer plasmid of kex1 or kex2 strains is eliminated by curing with heat or cycloheximide, the strains become sensitive to killing. The mutant phenotype reappears among the meiotic segregants in a cross with a normal killer. Thus, the kex phenotype does not require an alteration of the killer plasmid.--Kex1 and kex2 strains each contain near-normal levels of the 1.4 x 10(6) molecular weight double-stranded RNA, whose presence is correlated with the presence of the killer genome.


Disruption of fibronectin fibrillogenesis affects intraocular pressure (IOP) in BALB/cJ mice.
Increased deposition of fibronectin fibrils containing EDA+fibronectin by TGFβ2 is thought to be involved in the reduction of aqueous humor outflow across the trabecular meshwork (TM) of the eye and the elevation in intraocular pressure (IOP) observed in primary open angle glaucoma (POAG). Using a fibronectin-binding peptide called FUD that can disrupt fibronectin fibrillogenesis, we examined if disrupting fibronectin fibrillogenesis would affect IOP in the TGFβ2 BALB/cJ mouse model of ocular hypertension. BALB/cJ mice that had been intravitreally injected with an adenovirus (Ad5) expressing a bioactive TGFβ2226/228 showed a significant increase in IOP after 2 weeks. When 1μM FUD was injected intracamerally into mice 2 weeks post Ad5-TGFβ2 injection, FUD significantly reduced IOP after 2 days. Neither mutated FUD (mFUD) nor PBS had any effect on IOP. Four days after FUD was injected, IOP returned to pre-FUD injection levels. In the absence of TGFβ2, intracameral injection of FUD had no effect on IOP. Western blotting of mouse anterior segments expressing TGFβ2 showed that FUD decreased fibronectin levels 2 days after intracameral injection (p<0.05) but not 7 days compared to eyes injected with PBS. mFUD injection had no significant effect on fibronectin levels at any time point. Immunofluorescence microscopy studies in human TM (HTM) cells showed that treatment with 2ng/ml TGFβ2 increased the amount of EDA+ and EDB+ fibronectin incorporated into fibrils and 2μM FUD decreased both EDA+ and EDB+ fibronectin in fibrils. An on-cell western assay validated this and showed that FUD caused a 67% reduction in deoxycholate insoluble fibronectin fibrils in the presence of TGFβ2. FUD also caused a 43% reduction in fibronectin fibrillogenesis in the absence of TGFβ2 while mFUD had no effect. These studies suggest that targeting the assembly of fibronectin fibrillogenesis may represent a way to control IOP.


Mesoscale fronts as foraging habitats: composite front mapping reveals oceanographic drivers of habitat use for a pelagic seabird.
The oceanographic drivers of marine vertebrate habitat use are poorly understood yet fundamental to our knowledge of marine ecosystem functioning. Here, we use composite front mapping and high-resolution GPS tracking to determine the significance of mesoscale oceanographic fronts as physical drivers of foraging habitat selection in northern gannets Morus bassanus. We tracked 66 breeding gannets from a Celtic Sea colony over 2 years and used residence time to identify area-restricted search (ARS) behaviour. Composite front maps identified thermal and chlorophyll-a mesoscale fronts at two different temporal scales-(i) contemporaneous fronts and (ii) seasonally persistent frontal zones. Using generalized additive models (GAMs), with generalized estimating equations (GEE-GAMs) to account for serial autocorrelation in tracking data, we found that gannets do not adjust their behaviour in response to contemporaneous fronts. However, ARS was more likely to occur within spatially predictable, seasonally persistent frontal zones (GAMs). Our results provide proof of concept that composite front mapping is a useful tool for studying the influence of oceanographic features on animal movements. Moreover, we highlight that frontal persistence is a crucial element of the formation of pelagic foraging hotspots for mobile marine vertebrates.


[Heterozygous familial hypercholesterolemia].
Heterozygous familial hypercholesterolemia (HeFH) is an autosomal co-dominant inherited disease associated with increased risk of early cardiovascular disease. Plasma low-density lipoprotein concentrations of the affected individuals are 2 to 3 times higher than the normal population. The prevalence of the HeFH is 1/500 and only 20% of the cases are diagnosed. A minority of the diagnosed patients (16%) are able to reach treatment. Early identification of the patients with HeFH enables exact treatment and prevention of the premature coronary artery disease. So, screening of the relatives of the index cases is essential. HeFH is diagnosed by the use of clinical criteria like family history, physical examination, and cholesterol levels. Mutation analysis may provide an accurate diagnosis in suspicious cases. Treatment strategies mostly aim to provide a reduction of low-density cholesterol levels of >50% from baseline. First-line treatment is statins. However, most of the patients with HeFH do not achieve target cholesterol levels with maximum tolerated doses of statins. Combinations of statins with ezetimibe, niacin or bile acid sequestrants have limited value. New classes of drugs for the treatment of hypercholesterolemia include microsomal triglyceride transfer protein inhibitors, apolipoprotein B synthesis inhibitors, and pro-protein convertase subtilisin/kexin 9 inhibitors. This review aims to discuss the updated information regarding the diagnosis and treatment of HeFH.


Wildlife Consumption, Health, and Zoonotic Disease in China After the Emergence of COVID-19.
There has been much discussion in the conservation and policy realms of COVID-19 as a zoonotic disease, or a disease transmitted from wildlife to humans. However, wildlife consumption in China is not only a potential source of disease but also a practice embedded in complex beliefs about health. This paper used survey data (N = 974) collected in China in June 2021 to examine attitudes and behaviors related to (a) wildlife consumption, (b) Traditional Chinese Medicine (TCM) and (c) zoonotic risk after the emergence of the COVID-19 pandemic. 40.1% of respondents self-reported that they are less likely to consume wild animals since the outbreak of COVID-19. Respondents who used wildlife supplements for TCM, who believed in the benefits of wild animal consumption and fresh slaughter of wildlife, and who had higher levels of agreement with the zoonotic origin of COVID-19 were more likely to report that they had decreased their wildlife consumption after the outbreak of COVID-19. Use of wildlife in TCM significantly increased the odds that a respondent believed that COVID-19 was very likely zoonotic. We discuss how situating wildlife consumption within complex beliefs about health and disease can assist with protecting wildlife and public health in the wake of COVID-19.


Are current labeling terms suitable for people who are at risk of psychosis?
Inclusion of 'attenuated psychosis syndrome (APS)' in the DSM-5 has been hotly debated because of the concern about stigmatising young patients with a 'psychosis risk' label. This study aimed to investigate whether current labeling terms such as 'at risk mental state', 'ultra-high risk' (UHR) and 'APS' are suitable for people who are at risk of psychosis. This study included 105 subjects (55 patients aged 15-25years who used an early interventional service to prevent psychosis and 50 professionals who worked with them). A questionnaire regarding their opinions about the stigma associated with the above labels and the Mental Health Consumers' Experience of Stigma scale were administered. The patients were less likely than the professionals to agree that there was stigma associated with the terms 'UHR' and 'APS'. Significantly more patients with a family history of psychosis and those who had transitioned to psychosis agreed that there was stigma associated with the term 'UHR' and/or that this term should be changed. Patients who agreed with the negative attitude items for the three labeling terms and the need to change the terms 'UHR' and 'schizophrenia' showed significantly higher scores on the Stigma scale. In conclusion, patients at risk of psychosis may experience less stigma related to labels than expected by professionals, suggesting that mental health professionals may not be able to help patients unless they listen to their views on nosological and treatment issues rather than make assumptions. Previous stigmatising experiences may have strengthened the stigma attached to this label.


Tumour Necrosis Factor Alpha Antibody Affects Gastrin Release in Crohn Disease.
Gastrin plays an important role in the regulation of gastric acid secretion in humans. Tumour necrosis factor alpha (TNF-α) stimulates gastrin release from antral G cells in vitro. The aim was to determine whether gastrin release decreases in patients with Crohn disease treated with monoclonal antibody to TNF-α. Twenty-five consecutive patients with Crohn disease (10 M, 15 F; 18 with fistulas) were treated with a single intravenous infusion of the monoclonal antibody to TNF-α, infliximab, at a dose of 5 mg/kg. Basal and bombesin stimulated gastrin was measured after an overnight fast immediately before and 2 weeks after infliximab. Helicobacter pylori status was determined by serology. Twenty-two patients were H. pylori-negative. Basal plasma gastrin was 21 (16-26) pmol/L before and 19 (15-25) pmol/L after infliximab (NS). Bombesin stimulated gastrin decreased from 49 (40-62) pmol/L before to 36 (33-59) pmol/L (P < 0.005) 2 weeks after infliximab. Gastrin release in response to bombesin decreases in patients with Crohn disease treated with infliximab.


Wearable Kinematic Monitoring System Based on Piezocapacitive Sensors.
Measuring the kinematics of human body movements is important for several biomedical and non-biomedical uses, such as rehabilitation, sports medicine, control of virtual reality systems, etc. This is typically performed employing accelerometers, electrogoniometers, electromagnetic sensors or cameras, which however are usually bulky, or can cause discomfort to the user, or are insufficiently accurate, or require expensive instrumentation. As an alternative to those state-of-the-art systems, stretchable piezocapacitive sensors based on dielectric elastomers (DE) represent a recently described competitive technology, which might enable wearable, lightweight and cost-effective devices. DE sensors consist of stretchable capacitors whose mechanical deformation causes a change of capacitance, which can be measured and related to linear or angular motions, depending on the sensors' arrangement. Here, we present a wearable wireless system able to monitor the flexion and torsion of the lumbar region of the back. The system consists of two DE sensors arranged on shoulder straps, and a custom-made wireless electronics designed to measure the capacitance of the sensors and calibrate them when the user wears them for the first time. We describe preliminary results related to the characterisation of the sensors and the electronics.


Dispositional coping, coping effectiveness, and cognitive social maturity among adolescent athletes.
It is accepted among scholars that coping changes as people mature during adolescence, but little is known about the relationship between maturity and coping. The purpose of this paper was to assess a model, which included dispositional coping, coping effectiveness, and cognitive social maturity. We predicted that cognitive social maturity would have a direct effect on coping effectiveness, and also an indirect impact via dispositional coping. Two hundred forty-five adolescent athletes completed measures of dispositional coping, coping effectiveness, and cognitive social maturity, which has three dimensions: conscientiousness, peer influence on behavior, and rule following. Using structural equation modeling, we found support for our model, suggesting that coping is related to cognitive social maturity. This information can be used to influence the content of coping interventions for adolescents of different maturational levels.


[Professor V.F. Voĭno-Iasenetskiĭ (Holy Hierarch Lucus): his life and role in Russian dental school development].
The paper describes life and works of professor V.F. Voyno-Yaseneckiy (Holy Hierarch Lucas). Surgeon and Archibishop, he was officially glorified by the Patriarchate of Russia. Voyno-Yaseneckiy's early works represent the guidelines for regional anesthesia and his, Notes on Purulent Surgery, published in 1934 lad the foundation for an entire medical specialty.


Surgical treatment of acute and chronic anterior and posterior cruciate ligament and medial-side injuries of the knee.
KD-IIIM knee injuries are challenging injuries that can do well when anatomic reconstruction techniques are used. This article describes the authors preferred reconstructions, timing of surgery, and rehabilitation techniques. The reconstructions are generally initiated 3 or 4 weeks after the injury when the local soft tissue injury allows and associated fractures have already been stabilized. The posterior cruciate ligament, posteromedial corner, and meniscus injuries are addressed in the initial operation. The corresponding author prefers to come back 6 weeks later and reconstruct the anterior cruciate ligament and assure that acceptable progress has been made regarding knee motion.


Which muscle performance can be improved after arthroscopic Bankart repair?
There are no published reports available regarding neuromuscular control recovery in nonathletic patients after arthroscopic (A/S) Bankart repair. This study aimed to compare neuromuscular control and performance of the rotator cuff muscles between patients who underwent A/S Bankart repair and normal controls. In total, 32 nonathletic patients who underwent A/S Bankart repair were compared with 32 asymptomatic nonathletic volunteers. Neuromuscular control index (time to peak torque and acceleration time), muscle strength ratio, muscle strength, and muscle endurance of the internal rotators (IRs) and external rotators (ERs) were measured using an isokinetic device at an angular velocity of 180°/s, with 90° shoulder abduction. The neuromuscular control indices of both IRs and ERs were significantly lower in patients who underwent A/S Bankart repair than in normal controls (time to peak torque, IRs: 1059 ± 143 ms vs. 679 ± 226 ms, P = .011; ERs: 595 ± 286 ms vs. 379 ± 123 ms, P = .044; acceleration time, IRs: 75 ± 16 ms vs. 62 ± 15 ms, P = .039, ERs: 70 ± 19 ms vs. 54 ± 18 ms, P = .047). Muscle endurance was significantly lower in patients who underwent A/S Bankart repair than in normal controls (IRs: 670 ± 1 J vs. 718 ± 2 J, P = .002, ERs: 422 ± 6 J vs. 501 ± 2 J, P = .044). The neuromuscular control index showed a significant negative correlation with muscle endurance for both IRs and ERs after the operation (IRs: r = -0.737, P = .003, ERs: r = -0.617, P = .019). Compared with normal controls, patients who underwent A/S Bankart repair did not show complete recovery of neuromuscular control of IRs and ERs, although their muscle strength ratio and muscle strength had fully recovered.


Ventilator-associated events versus ventilator-associated respiratory infections-moving into a new paradigm or merging both concepts, instead?
Despite ventilator-associated respiratory infections (VARI) are reported as the most common and fatal complications related to mechanical ventilation (MV), they are not the unique occurrences. The new classification of ventilator-associated events (VAE) proposed by the centers for disease control and prevention (CDC) enhance the spectra of complications due to MV including both infection-related and non-infectious events. Both VAEs and VARIs are associated with prolonged duration of MV, longer stay in hospital and in the intensive care unit (ICU) and more antibiotic consumption, nonetheless patients with VAEs have worst outcomes. The VARI and VAE algorithms are focused on different targets and the correlation between both classifications is shown to be poor. The diagnostic criteria of the traditional classification have limited accuracy and the non-infectious complications may be misinterpreted as VARI. While the VAE surveillance enhances the spectra of MV complications but excludes less severe VARIs. Noninfective events explain up to 30% of VAEs, the main causes being atelectasis, acute respiratory distress syndrome, pulmonary edema and pulmonary embolism. The bundles assessing VAE are associated with less incidence of VAP and improved outcomes but they fail to reduce the rates of VAE. Automated VAE surveillance is efficient and useful as a quality indicator in the ICU while the differences in the interpretation of VARI criteria limit its role in the design of global protocols and preventive strategies. We suggest that a more comprehensive strategy should combine both algorithms with emphasis on clinical outcomes.


Effect of angiotensin-converting enzyme tag single nucleotide polymorphisms on the outcome of patients with traumatic brain injury.
Genetic variants appear to influence, at least to some degree, the extent of brain injury and the clinical outcome of patients who have sustained a traumatic brain injury (TBI). Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that is implicated in the regulation of blood pressure and cerebral circulation. ACE gene polymorphisms were found to regulate serum ACE enzyme activity. The present study aimed to investigate possible influence of ACE gene region variants on patients' outcome after TBI. In total, 363 TBI patients prospectively enrolled in the study were genotyped for five tag single nucleotide polymorphisms (SNPs) across the ACE gene. Using logistic regression analyses, tag SNPs and their constructed haplotypes were tested for associations with 6-month Glasgow Outcome Scale scores, after adjustment for age, sex, Glasgow Coma Scale scores at admission, and the presence of a hemorrhagic event in the initial computed tomography scan. Significant effects on TBI outcome were found for three neighboring tag SNPs in the codominant (genotypic) model of inheritance [rs4461142: odds ratio (OR) 0.26, 95% confidence interval (CI) 0.12-0.57, P = 0.0001; rs7221780: OR 2.67, 95% CI 1.25-5.72, P = 0.0003; and rs8066276: OR 3.82, 95% CI 1.80-8.13, P = 0.0002; for the heterozygous variants compared with the common alleles]. None of the constructed common tag SNPs haplotypes was associated with TBI outcome. The present study provides evidence of the possible influence of genetic variations in a specific region of the ACE gene on the outcome of TBI patients. This association may have pharmacogenetic implications in identifying those TBI patients who may benefit from ACE inhibition.


Waterpipe Smoke Exposure Triggers Lung Injury and Functional Decline in Mice: Protective Effect of Gum Arabic.
The prevalence of waterpipe (shisha) tobacco smoking has recently seen a substantial increase worldwide and is becoming a public health problem. Both human and animal studies have established that waterpipe smoke (WPS) increases airway reactivity and inflammation. Gum Arabic (GA) is a prebiotic agent that possesses antioxidant and anti-inflammatory properties. However, its effects on lung toxicity induced by WPS exposure are unknown. Thus, the aim of this study was to investigate the possible salutary effects and underlying mechanisms of GA on WPS-induced pulmonary pathophysiologic effects. C57BL/6 mice were exposed to air or WPS (30 minutes/day for one month) with or without GA treatment in drinking water (15%, w/v). Exposure to WPS induced an influx of neutrophil polymorphs in the peribronchiolar and interstitial spaces and an increase of tumor necrosis factor-α and 8-isoprostane, a marker of lipid peroxidation, concentrations in lung homogenates. The latter effects were significantly mitigated by GA treatment. Likewise, the lung DNA damage induced by WPS exposure was prevented by GA administration. Western blot analysis of the lung showed that GA inhibited nuclear factor kappa-B (NF-κB) expression caused by WPS and augmented that of nuclear factor erythroid 2-related factor 2 (Nrf2). Similarly, immunohistochemical analysis of bronchial epithelial cells and alveolar cells showed a parallel and significant increase in the nuclear expression of Nrf2 and cytoplasmic expression of glutathione in mice treated with GA and exposed to WPS. Moreover, GA administration has significantly prevented airway hyperreactivity to methacholine induced by WPS. We conclude that GA administration significantly declined the physiological, histological, biochemical, and molecular indices of lung toxicity caused by WPS exposure, indicating its beneficial respiratory impact. Considering that GA is a safe agent with health benefits in humans, our data suggest its potential usage in waterpipe smokers.


Augmentation strategies for clozapine resistance: a systematic review and meta-analysis.
Several augmentation strategies have been used to improve symptomatology in patients not adequately responding to clozapine. Several randomised controlled trials (RCTs) have evaluated the efficacy of different strategies to augment clozapine. This systematic review and meta-analysis reviewed the available RCTs that have evaluated the clinical efficacy of various pharmacological agents, non-pharmacological strategies (occupational therapy, cognitive behaviour therapy), and somatic treatment [electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation, etc.)] as augmenting agents to clozapine. Data were extracted using standard procedures, and risk of bias was evaluated. Effect sizes were computed for the individual studies. Forty-five clinical trials were evaluated. The pooled effect size for various antipsychotic medications was 0.103 (95% CI: 0.288-0.493, p < 0.001); when the effect size was evaluated for specific antipsychotics for which more than one trial was available, the effect size for risperidone was -0.27 and that for aripiprazole was 0.57. The effect size for lamotrigine was 0.145, and that for topiramate was 0.392. The effect size for ECT was 0.743 (CI: 0.094-1.392). Risk of bias was low (mean Jadad score - 3.93). Largest effect sizes were seen for mirtazapine (effect size of 5.265). Most of the studies can be considered underpowered and limited by small sample sizes. To conclude, based on the findings of the present systematic review and meta-analysis, it can be said that compared to other treatment strategies, clozapine non-responsive patients respond maximum to mirtazapine followed by ECT.


Bleeding Risk and Antithrombotic Strategy in Patients With Sinus Rhythm and Heart Failure With Reduced Ejection Fraction Treated With Warfarin or Aspirin.
We sought to assess the performance of existing bleeding risk scores, such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score or the Outpatient Bleeding Risk Index (OBRI), in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell C-statistic and net reclassification improvement index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly greater C-statistic (0.72 vs 0.61; p = 0.03) compared to HAS-BLED, although the net reclassification improvement for comparing OBRI to HAS-BLED was not significant (0.32, 95% confidence interval [CI] -0.18 to 0.37). Performance of the OBRI and HAS-BLED risk scores was similar for the aspirin arm. For participants with OBRI scores of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (hazard ratio [HR] 0.51, 95% CI 0.26 to 0.98, p = 0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66 to 2.30, p = 0.51). For those with OBRI score of ≥2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27 to 1.15, p = 0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99 to 8.22, p <0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in patients with HFrEF in SR and could be tested for potentially identifying patients with a favorable risk/benefit profile for antithrombotic therapy with warfarin.


Metallic behaviour in SOI quantum wells with strong intervalley scattering.
The fundamental properties of valleys are recently attracting growing attention due to electrons in new and topical materials possessing this degree-of-freedom and recent proposals for valleytronics devices. In silicon MOSFETs, the interest has a longer history since the valley degree of freedom had been identified as a key parameter in the observation of the controversial "metallic behaviour" in two dimensions. However, while it has been recently demonstrated that lifting valley degeneracy can destroy the metallic behaviour, little is known about the role of intervalley scattering. Here, we show that the metallic behaviour can be observed in the presence of strong intervalley scattering in silicon on insulator (SOI) quantum wells. Analysis of the conductivity in terms of quantum corrections reveals that interactions are much stronger in SOI than in conventional MOSFETs, leading to the metallic behaviour despite the strong intervalley scattering.


Breaking down brain barrier breaches in cerebral malaria.
Recent findings have linked brain swelling to death in cerebral malaria (CM). These observations have prompted a number of investigations into the mechanisms of this pathology with the goal of identifying potential therapeutic targets. In this issue of the JCI, Gallego-Delgado and colleagues present evidence that implicates angiotensin receptors and the relocation of β-catenin to the endothelial cell nucleus in CM. This study provides a renewed focus on infected erythrocyte debris as the cause of endothelial damage and challenges previous work implicating direct effects of infected erythrocyte sequestration in the brain as the major driver of disease. While this work provides potential therapeutic avenues for CM, it leaves a number of questions unanswered.


Immunoglobulin G4-related hypertrophic pachymeningitis involving cerebral parenchyma.
The authors report a case of IgG4-related hypertrophic pachymeningitis that involved cerebral parenchyma. The mass was removed surgically. Histopathological studies showed diffuse infiltration of lymphoplasmacytic cells without evidence of Langerhans histiocytes or meningothelial cells. Immunoglobulin G4 was strongly positive on immunohistochemical staining. The Gd-enhanced lesion deep inside brain parenchyma was completely resolved after 3 months of oral corticosteroid medication. A nodular type of hypertrophic pachymeningitis that mimics a meningioma is rare. Nevertheless, preoperative presumption is very important, and immunohistochemical studies for IgG4 may be helpful in the differential diagnosis.


Improved myelin water fraction mapping with deep neural networks using synthetically generated 3D data.
We introduce a generative model for synthesis of large scale 3D datasets for quantitative parameter mapping of myelin water fraction (MWF). Our model combines a MR physics signal decay model with an accurate probabilistic multi-component parametric T2 model. We synthetically generate a wide variety of high quality signals and corresponding parameters from a wide range of naturally occurring prior parameter values. To capture spatial variation, the generative signal decay model is combined with a generative spatial model conditioned on generic tissue segmentations. Synthesized 3D datasets can be used to train any convolutional neural network (CNN) based architecture for MWF estimation. Our source code is available at: https://github.com/quin-med-harvard-edu/synthmap Reduction of acquisition time at the expense of lower SNR, as well as accuracy and repeatability of MWF estimation techniques, are key factors that affect the adoption of MWF mapping in clinical practice. We demonstrate that the synthetically trained CNN provides superior accuracy over the competing methods under the constraints of naturally occurring noise levels as well as on the synthetically generated images at low SNR levels. Normalized root mean squared error (nRMSE) is less than 7% on synthetic data, which is significantly lower than competing methods. Additionally, the proposed method yields a coefficient of variation (CoV) that is at least 4x better than the competing method on intra-session test-retest reference dataset.


CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients.
Targeted T cell immunotherapies using engineered T lymphocytes expressing tumor-directed chimeric antigen receptors (CARs) are designed to benefit patients with cancer. Although incorporation of costimulatory endodomains within these CARs increases the proliferation of CAR-redirected T lymphocytes, it has proven difficult to draw definitive conclusions about the specific effects of costimulatory endodomains on the expansion, persistence, and antitumor effectiveness of CAR-redirected T cells in human subjects, owing to the lack of side-by-side comparisons with T cells bearing only a single signaling domain. We therefore designed a study that allowed us to directly measure the consequences of adding a costimulatory endodomain to CAR-redirected T cells. Patients with B cell lymphomas were simultaneously infused with 2 autologous T cell products expressing CARs with the same specificity for the CD19 antigen, present on most B cell malignancies. One CAR encoded both the costimulatory CD28 and the ζ-endodomains, while the other encoded only the ζ-endodomain. CAR+ T cells containing the CD28 endodomain showed strikingly enhanced expansion and persistence compared with CAR+ T cells lacking this endodomain. These results demonstrate the superiority of CARs with dual signal domains and confirm a method of comparing CAR-modified T cells within individual patients, thereby avoiding patient-to-patient variability and accelerating the development of optimal T cell immunotherapies.


Distinct psychological profiles among college students with substance use: A cluster analytic approach.
Substance use in youth is a central public health concern, related to deleterious consequences at psychological, social, and cognitive/cerebral levels. Previous research has identified impulsivity and consumption motives as key factors in the emergence of excessive substance use among college students. However, most studies have focused on a specific substance and have considered this population as a unitary group, ignoring the potential heterogeneity in psychological profiles. We used a cluster analytic approach to explore the heterogeneity in a large sample (N = 2741) of substance users (i.e., tobacco, alcohol, cannabis, ecstasy, cocaine, heroin) on impulsivity and consumption motives. We identified four clusters: The first two clusters, associated with good self-esteem, low anxiety, and moderate substance use, were respectively characterized by low impulsivity and consumption motives (Cluster 1) and by high social and enhancement motives without marked impulsivity (Cluster 2). The two other clusters were conversely related to low self-esteem and high anxiety, and characterized by high consumption motives (particularly conformity) together with elevated urgency (Cluster 3) and by globally increased impulsivity and consumption motives (Cluster 4). These two clusters were also associated with higher substance use. These results highlight the existence of distinct psychological profiles of substance users and underline the need to develop targeted prevention and intervention programs (e.g., focusing on the specific impulsivity facets and consumption motives presented by each subgroup). Based on these findings, we also suggest extending the exploration of distinct profiles of substance users by targeting other psychological variables (e.g., self-esteem).


Phenylhydrazine-mediated induction of haem oxygenase activity in rat liver and kidney and development of hyperbilirubinaemia. Inhibition by zinc-protoporphyrin.
Phenylhydrazine was found to be a potent inducer of microsomal haem oxygenase activity in rat liver and kidney, but not in spleen. The phenylhydrazine-mediated increase in haem oxygenase activity was time-dependent. Maximum activity was attained 12h after treatment in the liver, and 24h after treatment in the kidney. The increases in the activity of haem oxygenase in the liver and the kidney could be inhibited by cycloheximide. Furthermore, the increases could not be elicited by the treatment of microsomal preparations in vitro with phenylhydrazine. In consonance with the increased haem oxygenase activity, a marked increase (16-fold) was observed in the serum total bilirubin concentration in phenylhydrazine-treated rats. The mechanism of haem degradation promoted by phenylhydrazine in vivo appears to differ from that in vitro; only in the former case is bilirubin formed as the end-product of haem degradation. When rats were given zinc-protoporphyrin (40 mumol/kg) 12h before and after phenylhydrazine treatment, the phenylhydrazine-mediated increases in haem oxygenase activity in the liver and the kidney were effectively blocked. Treatment of rats in vivo with the metalloporphyrin also inhibited the activity of splenic haem oxygenase, and promoted a major decrease in the serum bilirubin levels. In phenylhydrazine-treated animals, the microsomal content of cytochrome P-450 was significantly decreased in the absence of a decrease in the microsomal haem concentration. The decrease in cytochrome P-450 content was accompanied by an increased absorption in the 420nm region of the reduced CO-difference spectrum, suggesting the conversion of the cytochrome to an inactive form. The marked depletion of cellular glutathione levels suggests that this conversion may be related to the action of active intermediates and free radicals formed in the course of the interaction of phenylhydrazine with the haem moiety of cytochrome P-450.


Three-dimensional particle imaging by defocusing method with an annular aperture.
We propose an annular-aperture-based defocusing technique for three-dimensional (3D) particle metrology from a single camera view. This simple configuration has high optical efficiency and the ability to deal with overlapped defocused images. Initial results show that an uncertainty in depth of 23 microm can be achieved over a range of 10 mm for macroscopic systems. This method can also be applied in microscopy for the measurement of fluorescently doped microparticles, thus providing a promising solution for 3D flow metrology at both macroscales and microscales.


The return of the leech.
Medicinal leeches (Hirudo medicinalis) have been used in medicine for thousands of years to treat a wide range of ailments. Nowadays, leeches are used successfully for only a few conditions, notably in the field of reconstructive or microsurgery, to salvage tissue flaps and skin grafts whose viability is threatened by venous congestion. The anticoagulant properties of hirudin, contained in leech saliva, may lead to wider therapeutic applications in the prevention and treatment of thromboembolic disease. Optimal care is needed when applying leeches, because their use can be complicated by serious bacterial infections.


Cryopreservation of spermatozoa from cynomolgus monkeys (Macaca fascicularis).
Three egg-yolk diluents, which have been used successfully in cryopreservation of human spermatozoa, were compared for their ability to protect macaque semen against cryodamage. TEST (Tes + Tris + egg yolk), TEST with 20% skim milk (TSM), and egg yolk-citrate (EYC), each with 3 or 5% glycerol were compared using 12 ejaculates from 6 male cynomolgus macaques. Computer-aided analysis of sperm motion was used to determine the percentage motility (%M), curvilinear velocity (VCL), and linearity (LIN) of spermatozoa after thawing. The supravital stain Hoechst 33258 and a fluoresceinated pea lectin were used to determine the % of viable spermatozoa with intact acrosomes. TSM and TEST were superior to EYC in terms of % M and of % viable, acrosome-intact spermatozoa. TSM and TEST produced equivalent VCL and LIN values, while EYC had clearly reduced VCL and LIN. There were no interactions between diluent and glycerol level. The 3% glycerol level gave superior results to 5% glycerol for %M. EYC, which is widely used for cryopreservation of human spermatozoa, was not suitable for cynomolgus monkey semen. Artificial insemination with semen cryopreserved in TSM resulted in a healthy, full-term infant.


Systematic Review of Food Addiction as Measured with the Yale Food Addiction Scale: Implications for the Food Addiction Construct.
The concept of food addiction attracts much interest in the scientific community. Research is mainly based on the Yale Food Addiction Scale (YFAS), a tool developed to assess food addiction. Substance use disorder criteria have been used to develop this scale. The aim of this paper was to review the clinical significance of food addiction diagnoses made with the YFAS and to discuss the results in light of the current debate on behavioral addictions. We performed a systematic review of the studies that assessed food addiction with the YFAS published between January 2014 and July 2017 by searching the electronic databases PsycINFO, MEDLINE, and PsycARTICLES. Sixty publications were included in the analysis. Thirty-three studies examined nonclinical samples and 27 examined clinical samples. All studies used YFAS scoring results to define food addiction. The prevalence of food addiction according to the YFAS varied largely by the studied samples. In general, a higher body mass index and the presence of eating disorders (EDs), especially binge eating disorder (BED), were associated with higher YFAS scores. The concept of food addiction has not been established to this day although it can be grouped with other EDs such as BED. More research is needed to understand this behavior and the differences between food addiction and other EDs. The criteria for food addiction should be revisited in light of the concepts currently used to examine behavioral addictions.


Predictors of plasma triglyceride elevation in patients participating in a coronary atherosclerosis treatment program.
Low-fat, high-carbohydrate diets have been used successfully to prevent and treat coronary heart disease, although these diets have been shown to cause elevations in fasting plasma triglyceride concentrations. The present study investigated metabolic factors (glucose, insulin, body weight) associated with changes in plasma triglyceride concentrations in patients participating in a comprehensive, multidisciplinary program, which included the use of a very low-fat diet designed to regress atherosclerotic cardiovascular disease. Thirty-six patients were entered into the study and placed on a 10% fat diet. Body mass index and fasting plasma insulin, glucose, lipids, and apolipoproteins were assessed at entrance into and after 3 months of participation in the program. Statistical analysis (discriminant function analysis) was used to identify factors that predicted elevations in plasma triglyceride that occurred during therapy. For the entire group, significant reductions in body weight (-2.4%), fasting glucose (-6%), total cholesterol (-8%), and low-density lipoprotein cholesterol (-11%) were observed, while insulin and triglycerides showed no significant changes. Twenty-one of the patients experienced an increase in fasting triglyceride concentration of 10% or greater. Three variables (baseline body mass index and fasting triglyceride and insulin concentrations) accurately classified 90% of those who would experience a > or = 10% elevation in triglycerides (P = 0.0002) and 67% of those who experienced no change. The present analysis provides a practical algorithm for clinicians to predict which patients will experience significant elevations in plasma triglyceride concentration when undergoing risk factor reduction that includes the consumption of a very low-fat, high-carbohydrate diet.


Prematurity and congenital heart disease.
Significant advances in technology and therapy have led to dramatic improvements in the survival of preterm babies over the last 2 decades. Similarly, improvements in surgical and cardiac intensive care techniques have increased the feasibility of supporting even very small babies to the point of surgical repair, leading some to adopt an approach of early and complete surgical repair in preterm infants, with the aim of minimizing potential preoperative morbidity associated with extended medical management or surgical palliation. (1,2) However, multiple diagnostic and therapeutic challenges complicate the care of premature infants. Major errors in echocardiography are more common in neonates weighing less than 2.5 kg, (3) and the ideal timing and type of surgical intervention in premature infants remains unknown. These problems are compounded by the need for critical care practices that optimize management of immature cardiopulmonary, gastrointestinal, and neurological systems. This review will summarize some of the recent advances in neonatal and perinatal medicine, which have the potential to contribute to improved management of preterm infants with critical cardiac disease.


Impulsivity relates to striatal gray matter volumes in humans: evidence from a delay discounting paradigm.
Time-stable personality traits, such as impulsivity and its relationship with functional and structural brain alterations, have gained much attention in the recent literature. Evidence from functional neuroimaging data implies an association between impulsivity and cortical as well as subcortical areas of the reward system. Discounting future rewards during impulsive decisions can be related to activation in the orbitofrontal cortex and striatum. Cortical structural changes in prefrontal regions have been found for introspective impulsivity measures. The present study focuses on brain regions associated with delay discounting to investigate structural manifestations of trait impulsivity. To test this, seventy subjects underwent structural magnetic resonance imaging (MRI) followed by a behavioral delay discounting task outside of the scanner to measure impulsivity with questions like: "Would you like to have 3€ immediately or 10€ in 5 days?". The amount of smaller-but-sooner decisions was calculated and used as a measure of behavioral impulsivity. Furthermore, we estimated subject's individual delay discounting parameter K reflecting the tendency to discount future rewards. Behaviorally, we found strong evidence in favor of a discounting utility model compared to a standard hyperbolic model of choice valuation. Neuronally, we focused on cortical and subcortical brain structure and investigated the association of behavioral impulsivity with delay discounting tendencies and gray matter volume. Voxel-based morphometric analyses showed positive correlations between delay discounting and gray matter volume in the striatum. Additional analyses using Freesurfer provided evidence for a positive correlation between delay discounting and gray matter volume of the caudate. Taken together, our study provides strong evidence for a structural manifestation of time-stable trait impulsivity in the human brain.


Raise the Flag I: the impact of a sepsis quality improvement programme on delivery of a sepsis resuscitation bundle at a tertiary hospital in New Zealand.
To study changes in sepsis resuscitation practice at a tertiary hospital before and after the introduction of a quality improvement programme, and to identify variables associated with its delivery. "Raise the Flag", a quality sepsis programme, including the Sepsis Six, was launched in 2018. Adult patients with sepsis were sampled prior to the intervention and during two subsequent periods. Clinicians were more likely to deliver the resuscitation bundle in the post-implementation period (adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.27-3.79, p=0.005). This was not sustained at 18-30 months (aOR 1.22, 95% CI 0.89-1.66, p=0.21). After adjusting for potential confounders, each additional decade of patient age was associated with reduced odds of receiving the bundle (aOR 0.83, 95% CI 0.73-0.95, p=0.005). Admission to intensive care increased in the combined post-implementation periods (aOR 2.81, 95% CI 1.13-6.97, p=0.03). The odds of receiving a resuscitation bundle improved immediately following the launch of the Raise the Flag programme. Resuscitation practice differed based on patient age. Odds of admission to intensive care were increased.


Passive transfer of respiratory syncytial virus (RSV) antiserum suppresses the immune response to the RSV fusion (F) and large (G) glycoproteins expressed by recombinant vaccinia viruses.
In young infants who possess maternally derived respiratory syncytial virus (RSV) antibodies, the antibody response to RSV glycoproteins is relatively poor, despite extensive replication of RSV. In the present study, it was found that cotton rat RSV hyperimmune antiserum suppressed the antibody response to the RSV glycoproteins but not the response to vaccinia virus antigens when the antiserum was passively transferred to cotton rats prior to infection with vaccinia recombinant viruses expressing the RSV envelope glycoproteins. The cotton rats which had their immune responses suppressed by passively transferred antibodies were more susceptible to infection with RSV than were animals inoculated with control serum lacking RSV antibodies. Furthermore, many of the immunosuppressed animals infected with the vaccinia recombinant viruses developed RSV glycoprotein antibodies which had abnormally low neutralizing activities. Thus, preexisting serum RSV antibodies had dramatic quantitative and qualitative effects on the immune response to RSV glycoproteins, which may explain, in part, the poor RSV antibody response of young human infants to infection with RSV. Our observations also suggest that immunosuppression by preexisting, passively acquired RSV antibodies may constitute a major obstacle to RSV immunoprophylaxis during early infancy, when immunization is most needed.


The epidemiology, prevention, and detection of melanoma.
We are seeing a record number of newly diagnosed skin cancers worldwide, with the incidence of melanoma increasing at a faster rate than almost all other cancers. As clinicians, we will have, by far, the greatest impact on reducing this incidence through better methods of early detection of melanoma and proven prevention methods and techniques. The medical community must enhance its efforts to increase its training of new health care personnel who are capable of diagnosing and treating this record number of patients with skin cancer. We must also try to increase the access to our limited number of dermatologists and provide novel ways of patient education such as through skin self-examinations, total body photography, and improved education for our children. By providing easier access to skin examinations, we will increase our chances of detecting melanoma in its earliest and most curable form. The dangers of indoor tanning beds and salons must be transparent to those that use them, focusing on expanding the oversight of such facilities by our local and federal governmental agencies while establishing legislation in several states to further limit their use to our youth, who are especially at high risk for developing melanoma in the future. This review will focus on the epidemiology, prevention, and detection of melanoma.