Sport specialization in Swedish football players: Investigating a model of antecedents and outcomes.
Drawing on data from the present and former football players (N = 1026) selected to a national football talent programme at the age of 15, this study explores a model of sport specialisation. We examined three specific aspects of sport specialisation including early football specialisation, participation in youth elite football training environments (i.e. academies) and enrolment in upper secondary football specialisation schools. Antecedents of these sport specialisation factors included gender (i.e. sociocultural), grit (i.e. personality) and perceptions of family finances (i.e. social). Outcomes focused on adult football participation at the age of 21 including elite skill acquisition (i.e. playing elite football) and personal development (i.e. participation in non-elite football). Findings revealed that females were less likely to gain access to elite football training or school specialisation environments. There was also a positive association between grit and participation in elite training environments. In terms of outcomes, players, who got trained in elite training environments during adolescence, were twice as likely to play elite football at the age of 21, while those who attended football specialisation schools were more likely to participate in non-elite football at the age of 21. Early specialisation was not associated with either adult participation outcome. This is one of the few studies to date addressing diverse antecedents and outcomes of sport specialisation factors. Understanding how sport specialisation practices relate to future skill acquisition and personal development can provide guidance for maximising the benefits of youth sport programming.HighlightsGirls had less opportunity to participate in elite training environments and school football classes.Early specialisation was unrelated to elite football participation at the age of 21.Participation in youth elite training increased the likelihood of elite status as an adult.Need for closer examination of sport specialisation disparities for female players.


Influence of interferon alpha on expression of Fas and Fas ligand in dendritic cells from patients with chronic myeloid leukemia.
The study was aimed to investigate the influence of interferon alpha (IFN-alpha) on the expressions of Fas and Fas ligand (FasL) in dendritic cells (DCs) from patients with chronic myeloid leukemia (CML). In addition to adding stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-alpha) and interleukin 4 (IL-4), the IFN-alpha was added to the serum-free medium for DCs. After culturing for 10 - 14 days, cell phenotype and percentage of Ph(1) chromosome were detected by different methods. The expression of Fas or FasL on CML-DCs and cell cycle of DCs labeled with propidium iodine (PI) were measured by flow cytometry. The concentration of sFas in supernatants was analyzed by enzyme-linked immunosorbent assay (ELISA). The results indicated that the expression of co-stimulatory molecules were improved significantly while the percentages of Ph(1) positive cells decreased. The level of Fas on cells was up-regulated and the concentration of sFas decreased. However, the expression of FasL was negative. The ratio of apoptosis rose gradually while the concentration of IFN-alpha increased. It is concluded that IFN-alpha can accelerate the apoptosis of Ph(1) positive cells through Fas/FasL pathway, so the number of Ph(1) negative cells increases relatively.


Non-autologous transplantation with immuno-isolation in large animals--a review.
Transplantation has become a successful method for the management of functional failure of a variety of tissues or organs. However, the majority of clinical transplantations use non-autologous allogeneic donor tissue implanted from one human to another. In order to prevent rejection of the allogeneic tissue, methods to overcome the immune barrier are necessary. Although prevention of organ rejection is currently achieved with pharmacological immune suppression, the undesirable side effects of this method have incited interest in novel methods to overcome the immune barrier. One such novel method of preventing immune reaction is immuno-isolation, in which the non-autologous tissues are physically isolated from the host tissues by placement in devices with perm-selective membranes. The membranes of these devices allow release of the therapeutic product required from the transplanted tissues, as well as diffusion of nutrients and waste necessary for survival of the non-autologous tissues. The membranes also prevent host immune mediators from contacting the non-autologous cells, thus preventing immune rejection. This technology has been tested for efficacy in large animal models, and is currently in the process of clinical trials in humans. This review will discuss the progress made in using immuno-isolation of non-autologous tissues in large animals. Immuno-isolation can be subdivided into two major areas of interest based on whether the non-autologous tissue used in the immuno-isolation device is genetically altered (gene therapy) or not. Studies using non-genetically altered non-autologous cells for immune-isolation have been dominated by the use of pancreatic islet cells for the treatment of diabetes. This work has been tested in large animal models of diabetes, including canine and primate model animals, and human clinical trials are underway. As well, there has also been work on treatment of neurological disorders such as Parkinson's disease or chronic pain using non-autologous immuno-isolated adrenal chromaffin cells or dopaminergic PC12 cells in large animals such as sheep and primates. This work will be reviewed in detail as to the types of disorders, immuno-isolation devices used and the type of large animals involved. Immune-isolation for gene therapy is a more recently developed field of research. In this case, the non-autologous cells used are first genetically altered to secrete a recombinant therapeutic product before placement in the immune-isolation devices. Genetic engineering of the non-autologous cells is beneficial, as it allows the use of a cell type that tolerates well the environment of the immune-isolation device, while still delivering the therapeutic product of interest. This form of gene therapy has been tested in our laboratory for delivery of marker products such as human growth hormone to canines. As several large animal models of human genetic disorders are available, such as canines affected with hemophilia or the lysosomal storage disease mucopolysaccharidosis, testing the efficacy of immuno-isolation for gene therapy in large animal models is an important prelude to human clinical trials. This review will discuss the topics outlined above, as well as some further considerations of the usefulness of large animal models in studying immune-isolation for non-autologous transplantation. Large animals may be more appropriate model organisms than rodents in which to study immune-isolation, as issues such as biocompatibility and immune response in a larger animal can be addressed. As well, large animal studies of immune isolation may provide data that are more relevant than rodent studies to the eventual application to human clinical trials.


Del Nido cardioplegia in adult cardiac surgery: Clinical outcomes in a single center all-comer study.
The use of Del Nido Cardioplegia (DNC) has been extended in the latest years from pediatrics to adult cardiac surgery with encouraging results. We sought to investigate clinical and biochemical outcomes in adult patients who underwent cardiac surgery with different degrees of complexity who received DNC for myocardial protection. Data on one-thousand patients were retrospectively collected from 2020 to 2022. The only exclusion criteria was off-pump adult cardiac surgery. Surgical procedures weight was categorized according EuroSCORE II in six groups: Single-CABG(G1), isolated non-CABG(mitral) (G2), isolated non-CABG(aortic) (G3), isolated non-CABG(any) (G4), 2-procedures(G5), 3/more-procedures(G6). Primary endpoint was to identify a binomial correlation between hs-TnT/CK-MB and the cross-clamp time (X-Clamp). A secondary endpoint was the comparison between the treatment groups of the vasoactive-inotropic score (VIS) and the need of mechanical circulatory support (MCS). A linear correlation was identified between hs-TnT and X-clamp in the overall population (rho:0.447, p< .001) and in the treatment groups (G1:rho=0.357, p< .001/G2:rho=0.455, p< .001/G3:rho=0.307, p= .001/G4:rho=0.165, p= .257/G5:rho=0.157, p= .031/G6:rho=0.226, p= .015). Similarly, a linear correlation between CK-MB and X-clamp in the overall population (rho=0.457, p< .001) and treatment group (G1:rho=0.282, p< .001/G2:rho=0.287, p= .025/G3:rho=0.211, p= .009/G4:rho=0.0878, p= .548/G5:rho=0.309, p< .001/G6: rho=0.212, p= .024) was identified. As regard for the secondary endpoint, no differences were reported between the treatment groups in terms of VIS and MCS (VIS G1:7; G2:4; G3:7; G4:7, G5:5.5, G6:6, p-value= .691) (MCS G1: 4.5%; G2:4.8%; G3:3.3%; G4:3.1%; G5:1.4%; G6:5.3%; p-value= .372). Del Nido Cardioplegia is a safe and useful tool in adult cardiac surgery allowing operators to achieve a stable and durable cardioplegic arrest. Despite accounting with different types of surgery, the six subgroups of our study population showed similar perioperative results.


[Identifying mental health service needs of persons with schizophrenia].
The present study aimed to identify the needs and describe the use of twenty mental health services in a population of chronic schizophrenic patients living in two regions in Quebec (Estrie and Centre-Sud). An attempt was also made to determine the principal reasons for which some services were not being used when they were identified as clinically required. The population considered was composed of the patients (N = 88) who had been discharged from the psychiatric care units of five general hospitals over a period of five months in 1982, and for whom the attending psychiatrist could confirm with certainty a diagnosis of chronic schizophrenia in accordance with the criteria of DSM-III. Medical files of these patients were reviewed, and the patients and psychiatrists themselves were interviewed separately regarding the patients' needs and use of twenty mental health services over the period from the seventh to the twelfth month after discharge from hospital. Results of the study show that services which were most often identified as clinically required were: 1) taking of neuroleptics, 2) organization of leisure activities, 3) case management, and 4) individual supportive therapy. At the same time, results indicate a poor fit between needs and use for most of rehabilitation and psychosocial services. The main reasons for non-use of services which were identified as clinically required are also presented. The implications of these results for the organization of mental health services for persons suffering from chronic schizophrenia are discussed, especially the importance of case management services.


Glomus Tumor of the Sciatic Nerve: An Extraspinal Cause of Sciatica.
Glomus tumors are small, benign tumors that arise from glomus bodies, structures found normally within the dermis that assist in temperature regulation via their vasoconstrictive response to sympathetic stimuli. Glomus tumors are found typically in the hand and are classically a cause of focal pain and temperature sensitivity. They often present as a small blue lesion seen under the nail bed of a finger or a toe and cause point tenderness. Glomus tumors of peripheral nerves are exceedingly rare and can lead to disability akin to compressive neuropathy when present. This case report explores the unusual presentation of a rare and large glomus tumor of the sciatic nerve. The patient presented with symptoms such as those mentioned above and was assumed to have sciatica emanating from spinal and neuroforaminal stenosis. Although she repeatedly and appropriately sought medical attention for her condition, she was improperly diagnosed and ultimately experienced a significant deterioration of her function, eventually undergoing an unnecessary surgical procedure. On referral to the authors' institution, the patient was evaluated and found to have a glomus tumor involving the sciatic nerve. This is the largest glomus tumor of a peripheral nerve that has been reported to date. Although the patient's presentation was insidious and her diagnosis was uncommon, this underscores the importance of developing a differential diagnosis based primarily on a thorough physical examination and, only then, correlating imaging to clinical findings. Additionally, given the atypical presentation and intractable course of this patient's condition, the examiner must consider neoplastic entities and space-occupying lesions as part of the differential diagnosis. [Orthopedics. 2018; 41(1):e151-e153.].


Congestive heart failure. New frontiers.
Congestive heart failure is a common syndrome with high mortality in its advanced stages. Current therapy includes the use of vasodilator drugs, which have been shown to prolong life. Despite current therapy, mortality remains high in patients with severe heart failure. Potent new inotropic vasodilators have improved ventricular performance but have not prolonged life in patients with end-stage heart failure. Serious arrhythmias are implicated in the sudden deaths of 30% to 40% of patients with severe heart failure, but the benefits of antiarrhythmic therapy have not been established. Upcoming trials will address this question. Ventricular remodeling and progressive dilatation after myocardial infarction commonly lead to congestive heart failure; early unloading of the ventricle with an angiotensin-converting enzyme inhibitor may attenuate these events. These findings support the concept that angiotensin-converting enzyme inhibitors may be useful in managing heart failure of all degrees of severity, including left ventricular dysfunction and end-stage heart failure. Part of the damage that may occur with acute myocardial infarction, particularly in this era of thrombolysis therapy, is reperfusion injury, which may be mediated by oxygen-derived free radicals. Better knowledge of the mechanisms and treatment of myocardial infarction, the leading cause of congestive heart failure, may help prevent or attenuate the development of this syndrome.


Midwifery and the LGBT midwife.
To identify, through searching the published literature, midwifery's attitudes to gay and lesbian midwives. A selective literature review. UK-based material was sparse. Items on midwifery and nursing and medicine and on midwifery in non-UK countries were accessed. Issues emerging include the salience of 'coming out', of education, of culture, of forming relationships with childbearing women and the difficulty of authoritative research. The midwifery literature on LGBT colleagues corresponds with that identified in nursing almost three decades ago. The lack of recognition of LGBT midwives carries personal and organisational implications. Discriminatory attitudes may be difficult to resolve by education. Research on LGBT colleagues is fraught with difficulties. Various aspects of culture affect the acceptance of the colleague who is gay or lesbian. It is uncertain whether the midwife-woman relationship is less easily achieved by the gay or lesbian midwife.


Does chemotherapy prevent HCV-related hepatocellular carcinoma? Pros.
Hepatitis C virus (HCV) infection, which seems to have spread worldwide recently, is now the leading cause of hepatocellular carcinoma (HCC) development in various geographic areas. The primary prevention of HCV-related HCC includes strategies for the prevention of HCV infection and those for viral eradication. Even after HCC development, short-term prognosis of patients has been much improved recently due to advances in early diagnosis and treatment. However, long-term prognosis is as yet far from satisfactory due to frequent recurrence of HCC even after apparently curative treatment, either local ablation or surgical resection. At least theoretically, strategies similar to those of primary prevention may be applicable to HCC recurrence. In this review, we summarized the reported favorable effects of chemotherapy on primary and tertiary prevention of HCC.


Is AML1/ETO gene expression a good prognostic factor in pediatric acute myeloblastic leukemia?
To assess the clinical significance of AML1/ETO gene detected by nested reverse transcriptase polymerase chain reaction, the outcome of 7 patients with acute myeloblastic leukemia between 3 and 14 years of age were presented. All patients had complete remission (CR) at the end of induction (AML-MRC 10 protocol) and 4 underwent unpurged autologous, 2 allogeneic (from matched siblings) non-T-cell-depleted bone marrow transplantations (BMT) in first CR. One patient died due to allogeneic BMT-related complications, and 4 patients relapsed at 13, 17, 18, and 26 months. Only one patient achieved second CR. All relapsed patients died between 18 and 36 months with resistant disease (n = 3) or infection during salvage chemotherapy (n = 1). Two patients who had autologous BMT are alive and disease free at 44 and 50 months. Although statistical significance could not be shown, event-free survival and overall survival rates of AML1/ETO-positive patients (28.57 and 28.57%, respectively) at 3.5 years were even lower than those of AML1/ETO-negative patients. The results confirm some previous reports that AML1/ETO gene in children and adolescents is not a favorable prognostic factor.


Psychoactive substance use disorders among seriously injured trauma center patients.
To assess the prevalence of psychoactive substance use disorders (PSUDs) among a large, unselected group of seriously injured trauma center patients, using a standardized diagnostic interview and criteria. Prevalence study. A level I regional trauma center. Trauma center patients fulfilling the following criteria were eligible subjects: aged 18 years or older, admission from injury scene, length of stay of 2 days or longer, and intact cognition. The PSUDs were diagnosed using the Structured Clinical Interview (SCID) for the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) and were categorized as abuse or dependence and past or current (within past 6 months). The SCID results were analyzed with respect to demographic factors, injury type, and blood alcohol concentration and urine toxicology results, using chi2 and logistic regression techniques. Of the 1220 patients approached for study, 1118 (91.6%) consented. More than half (54.2%) had a diagnosis of a PSUD in their lifetime. Approximately 90% of alcohol and other drug use diagnoses were for dependence and more than 62% were current. Overall, 24.1% of patients were currently alcohol dependent (men, 27.7%; women, 14.7%; P<.001), and 17.7% were currently dependent on other drugs (men, 20.2%; women, 11.2%; P<.001). Current alcohol dependence rates were not associated with race; rates of dependence on other drugs were higher among nonwhites and victims classified with intentional injuries. While 54.3% of blood alcohol-positive patients were currently alcohol dependent and 38.7% of patients with positive urine screening test results for drugs other than alcohol and nicotine were currently drug dependent, 11.7% of blood alcohol-negative and 3.9% of drug-negative patients, respectively, had current diagnoses of dependence on psychoactive substances. A high percentage of seriously injured trauma center patients are at risk of having current PSUDs. Patients with positive toxicology screening test results and/or positive screening questionnaire responses should be referred for formal evaluation and treatment.


A prospective comparative study of ASCA and pANCA in Chinese and Caucasian IBD patients.
Inflammatory bowel disease manifests throughout all ethnic groups. Antisaccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (pANCA) can aid in the differentiation between Crohn's disease (CD) and ulcerative colitis (UC), but their sensitivity may vary between races. This study compared the sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of pANCA and ASCA between Chinese and Caucasian IBD populations and identified disease subtype associations. Three hundred patients were prospectively recruited from Caucasian and Chinese populations (CD, n = 50, UC, n = 50, controls, n = 50 each). pANCA detection was greater in Caucasian than Chinese UC patients (p= 0.046). ASCA IgG detection was similar, but IgA was lower in Chinese CD patients (p < 0.001). Differentiation between UC and CD (+ve pANCA/-ve ASCA) demonstrated a PPV of 92% in isolated colonic disease. Logistic regression in CD identified positive pANCA had a lower association with ileal (OR = 6.8, p= 0.0067) and complicated disease (OR = 5.5, p= 0.015). Caucasian CD patients with positive ASCA IgA/IgG had a greater association with ileal (OR = 6.7, p= 0.022) or complicated disease (OR = 9.4, p= 0.0073) and in Chinese CD patients positive ASCA IgA/IgG was associated with isolated ileal disease (OR = 16.8, p= 0.032). Linear regression demonstrated that higher ASCA titers predicted complicated CD and isolated ileal disease. This study identified that pANCA is more sensitive in Caucasian than Chinese UC and that ASCA IgA has a low yield in Chinese CD. pANCA and ASCA are useful for differentiating between UC and CD in both populations, and ASCA IgG and IgA titers have potential use in determining the risk of developing complicated CD.


Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia.
Dual orexin receptor antagonists (DORAs) represent a novel type of sleep medication that provide an alternative to the traditionally used positive allosteric gamma-aminobutyric acid (GABA)-A receptor modulators. Daridorexant is a new DORA that exhibited in phase 3 trials in insomnia not only a beneficial effect on sleep variables, measured objectively and assessed subjectively, but also an improvement in daytime functioning. Daridorexant was discovered through a tailored research program aimed at identifying an optimized sleep-promoting molecule with pharmacokinetic properties appropriate for covering the whole night while avoiding next-morning residual activity at efficacious doses. By specific binding to both orexin receptors, daridorexant inhibits the actions of the wake-promoting orexin (also called hypocretin) neuropeptides. This mechanism avoids a more widespread inhibition of neuronal pathways and associated side effects that are intrinsic to positive allosteric GABA-A receptor modulators. Here, we review the general pharmacology of daridorexant, based on nonclinical pharmacology studies of daridorexant, unpublished or already described, or based on work with other DORAs. Some unique features of daridorexant will be highlighted, such as the promotion of natural and surmountable sleep, the preservation of memory and cognition, the absence of tolerance development or risk of physical dependence, and how it can benefit daytime functioning.


Dynamic Estimation of the Auditory Temporal Response Function From MEG in Competing-Speaker Environments.
A central problem in computational neuroscience is to characterize brain function using neural activity recorded from the brain in response to sensory inputs with statistical confidence. Most of existing estimation techniques, such as those based on reverse correlation, exhibit two main limitations: first, they are unable to produce dynamic estimates of the neural activity at a resolution comparable with that of the recorded data, and second, they often require heavy averaging across time as well as multiple trials in order to construct statistical confidence intervals for a precise interpretation of data. In this paper, we address the above-mentioned issues for estimating auditory temporal response function (TRF) as a parametric computational model for selective auditory attention in competing-speaker environments. The TRF is a sparse kernel which regresses auditory MEG data with respect to the envelopes of the speech streams. We develop an efficient estimation technique by exploiting the sparsity of the TRF and adopting an ℓ1-regularized least squares estimator which is capable of producing dynamic TRF estimates as well as confidence intervals at sampling resolution from single-trial MEG data. We evaluate the performance of our proposed estimator using evoked MEG responses from the human brain in an auditory attention experiment with two competing speakers. The TRFs are estimated dynamically over time using the proposed technique with multisecond resolution, which is a significant improvement over previous results with a temporal resolution of the order of a minute. Application of our method to MEG data reveals a precise characterization of the modulation of M50 and M100 evoked responses with respect to the attentional state of the subject at multisecond resolution. Our proposed estimation technique provides a high resolution real-time attention decoding framework in multispeaker environments with potential application in smart hearing aid technology.


[Target delivery of functional genes in gene therapy using carbohydrate containing vectors].
Various aspects of use of specific interactions with a participation of carbohydrate and oligosaccharide ligands to increase an efficiency of gene transfer into eukaryotic cells (including in vivo experiments) are considered in details. Data on addressed gene delivery with applying carbohydrate-containing ligands (such as asialoglycoproteins and galactosides) are discussed in the paper. Results on the usage of glycoside ligands, containing lactose, mannose, glucose residues, for receptor-mediated gene transfer, are analysed. Special attention is paid to application of chitosans for functional gene transfer into eukaryotic cells, which is considered by authors as a case of receptor-mediated gene transfer. It is notice that neo-oligosaccharide vectors, recognizing surface lectins, represent very perspective type of gene delivery systems.


Association of ambient air pollution with age-related macular degeneration and retinal thickness in UK Biobank.
To examine the associations of air pollution with both self-reported age-related macular degeneration (AMD), and in vivo measures of retinal sublayer thicknesses. We included 115 954 UK Biobank participants aged 40-69 years old in this cross-sectional study. Ambient air pollution measures included particulate matter, nitrogen dioxide (NO2) and nitrogen oxides (NOx). Participants with self-reported ocular conditions, high refractive error (< -6 or > +6 diopters) and poor spectral-domain optical coherence tomography (SD-OCT) image were excluded. Self-reported AMD was used to identify overt disease. SD-OCT imaging derived photoreceptor sublayer thickness and retinal pigment epithelium (RPE) layer thickness were used as structural biomarkers of AMD for 52 602 participants. We examined the associations of ambient air pollution with self-reported AMD and both photoreceptor sublayers and RPE layer thicknesses. After adjusting for covariates, people who were exposed to higher fine ambient particulate matter with an aerodynamic diameter <2.5 µm (PM2.5, per IQR increase) had higher odds of self-reported AMD (OR=1.08, p=0.036), thinner photoreceptor synaptic region (β=-0.16 µm, p=2.0 × 10-5), thicker photoreceptor inner segment layer (β=0.04 µm, p=0.001) and thinner RPE (β=-0.13 µm, p=0.002). Higher levels of PM2.5 absorbance and NO2 were associated with thicker photoreceptor inner and outer segment layers, and a thinner RPE layer. Higher levels of PM10 (PM with an aerodynamic diameter <10 µm) was associated with thicker photoreceptor outer segment and thinner RPE, while higher exposure to NOx was associated with thinner photoreceptor synaptic region. Greater exposure to PM2.5 was associated with self-reported AMD, while PM2.5, PM2.5 absorbance, PM10, NO2 and NOx were all associated with differences in retinal layer thickness.


In vitro and in vivo effects of 2,4 diaminoquinazoline inhibitors of the decapping scavenger enzyme DcpS: Context-specific modulation of SMN transcript levels.
C5-substituted 2,4-diaminoquinazoline inhibitors of the decapping scavenger enzyme DcpS (DAQ-DcpSi) have been developed for the treatment of spinal muscular atrophy (SMA), which is caused by genetic deficiency in the Survival Motor Neuron (SMN) protein. These compounds are claimed to act as SMN2 transcriptional activators but data underlying that claim are equivocal. In addition it is unclear whether the claimed effects on SMN2 are a direct consequence of DcpS inhibitor or might be a consequence of lysosomotropism, which is known to be neuroprotective. DAQ-DcpSi effects were characterized in cells in vitro utilizing DcpS knockdown and 7-methyl analogues as probes for DcpS vs non-DcpS-mediated effects. We also performed analysis of Smn transcript levels, RNA-Seq analysis of the transcriptome and SMN protein in order to identify affected pathways underlying the therapeutic effect, and studied lysosomotropic and non-lysosomotropic DAQ-DCpSi effects in 2B/- SMA mice. Treatment of cells caused modest and transient SMN2 mRNA increases with either no change or a decrease in SMNΔ7 and no change in SMN1 transcripts or SMN protein. RNA-Seq analysis of DAQ-DcpSi-treated N2a cells revealed significant changes in expression (both up and down) of approximately 2,000 genes across a broad range of pathways. Treatment of 2B/- SMA mice with both lysomotropic and non-lysosomotropic DAQ-DcpSi compounds had similar effects on disease phenotype indicating that the therapeutic mechanism of action is not a consequence of lysosomotropism. In striking contrast to the findings in vitro, Smn transcripts were robustly changed in tissues but there was no increase in SMN protein levels in spinal cord. We conclude that DAQ-DcpSi have reproducible benefit in SMA mice and a broad spectrum of biological effects in vitro and in vivo, but these are complex, context specific, and not the result of simple SMN2 transcriptional activation.


PDCD2 controls hematopoietic stem cell differentiation during development.
Programmed cell death 2 (Pdcd2) is a highly conserved protein of undefined function, and is widely expressed in embryonic and adult tissues. The observations that knockout of Pdcd2 in the mouse is embryonic lethal at preimplantation stages, and that in Drosophila, Zfrp8, the ortholog of Pdcd2, is required for normal lymph gland development suggest that Pdcd2 is important for regulating hematopoietic development. Through genetic and functional studies, we investigated pdcd2 function during the zebrafish ontogeny. Knockdown of pdcd2 expression in zebrafish embryos resulted in defects in embryonic hematopoietic development. Loss of pdcd2 function caused increased expression of progenitor markers, and accumulation of erythroid progenitors during primitive hematopoiesis. Additionally, hematopoietic stem cells (HSCs) failed to appear in the aorta-gonad mesonephros, and were not able to terminally differentiate or reconstitute hematopoiesis. Pdcd2 effects on HSC emergence were cell autonomous and P53-independent, and loss of pdcd2 function was associated with mitotic defects and apoptosis. Restoration of runx1 function(s) and modulation of apoptosis through the inhibition of Jak/Stat signaling rescued the hematopoietic and erythroid defects resulting from pdcd2 knockdown. Our studies suggest that pdcd2 plays a critical role in regulating the transcriptional hierarchy controlling hematopoietic lineage determination. Furthermore, the effects of pdcd2 in regulating mitotic cell death may contribute to its role(s) in directing hematopoietic differentiation during development.


An unusual case of penetrating head injury in a child.
Penetrating head injuries can be the result of numerous intentional or unintentional events, including missile wounds, stab wounds, and motor vehicle or occupational accidents (nails, screw-drivers). Penetrating head injuries in children constitute only a small part of the total number of traumatic head injuries seen in casualty. We report a case of neuro-trauma who was operated in our institution. Patient, 4 years male presented in casualty on 15/01/09 with a iron rod penetrating into the skull.


C5 palsy after insertion of a winged expandable cervical cage: a case report and literature review.
C5 nerve root palsy is a well-known complication after anterior or posterior cervical decompression. Many theories have been proposed but the etiology is still unclear. The use of a winged expandable cage after single or multiple corpectomy is among the used techniques in reconstructing the cervical spine. Herein we report a case of C5 palsy after a three-level corpectomy and reconstruction using this device for the treatment of cervical spondylosis. In our case the preexisting foraminal stenosis, wide anterior decompression and partial improvement of cervical alignment were factors supposed contributing to the palsy.


Follicular lymphoma transformation to dual translocated Burkitt-like lymphoma: improved disease control associated with radiation therapy.
Dual translocated (or "dual hit") lymphomas are highly aggressive B cell neoplasms associated with an extremely poor prognosis. The optimal treatment for these lymphomas remains undefined. We present two cases of follicular lymphoma with transformation to Burkitt-like lymphoma. In both cases dual translocations involving both the bcl-2 and c-myc loci were present. Each patient underwent intensive induction immunochemotherapy followed by autologous stem cell transplantation and radiation therapy. The first patient received post-transplant mediastinal radiation and developed recurrence in multiple areas outside of the radiation field. The second patient received total body irradiation as part of the conditioning regimen, and is without recurrence 18 months after transplant, and 24 months after diagnosis of the dual translocated lymphoma. We review dual translocation B cell lymphoma in the setting of transformation from follicular lymphoma, and suggest a potential role for total body irradiation in the management of this highly aggressive non-Hodgkin lymphoma.


Vancomycin-heteroresistant phenotype in invasive methicillin-resistant Staphylococcus aureus isolates belonging to spa type 041.
The aim of this study was to characterise invasive methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains from Italy and to investigate the presence of heteroresistant vancomycin-intermediate S. aureus (h-VISA). Eighty-two MSSA and 66 MRSA strains obtained from 19 laboratories were submitted to in vitro susceptibility testing; MRSA strains were also analysed by the macro Etest (MET) and vancomycin population analysis profiles (PAP) to detect the presence of h-VISA. Genotyping included the detection of agr locus, SCCmec typing, spa typing and multilocus sequence typing (MLST). By Etest, 66% of all isolates showed a minimum inhibitory concentration (MIC) >or=1.5 microg/ml and two MRSA strains were categorised as VISA (MIC = 3 microg/ml). Twelve MRSA strains were positive by MET; of these, 9 (14% of all MRSA) were confirmed as h-VISA by PAP. MRSA strains were assigned to 14 spa types, with t001, t008 and t041 including 77% of the isolates. The most common spa type, t041, characterised as ST228/273-MRSA-I (CC5) and comprising 24 isolates, included one VISA and eight h-VISA. This is the first description of a close association between h-VISA and t041, a spa type common in Italy and in other European countries, that highlights the importance of molecular typing to identify clones of special clinical relevance.


Assessment of the impact of implementation research on the Visceral Leishmaniasis (VL) elimination efforts in Nepal.
Nepal, Bangladesh, and India signed a Memorandum of Understanding (MoU) in 2005 to eliminate visceral leishmaniasis (VL) as a public health problem from the Indian subcontinent by 2015. By 2021, the number of reported VL cases in these countries had declined by over 95% compared to 2007. This dramatic success was achieved through an elimination programme that implemented early case detection and effective treatment, vector control, disease surveillance, community participation, and operational research that underpinned these strategies. The experience offered an opportunity to assess the contribution of implementation research (IR) to VL elimination in Nepal. Desk review and a stakeholder workshop was conducted to analyse the relationship between key research outputs, major strategic decisions in the national VL elimination programme, and annual number of reported new cases over time between 2005 and 2023. The results indicated that the key decisions across the strategic elements, throughout the course of the elimination programme (such as on the most appropriate tools for diganostics and treatment, and on best strategies for case finding and vector management), were IR informed. IR itself responded dynamically to changes that resulted from interventions, addressing new questions that emerged from the field. Close collaboration between researchers, programme managers, and implementers in priority setting, design, conduct, and review of studies facilitated uptake of evidence into policy and programmatic activities. VL case numbers in Nepal are now reduced by 90% compared to 2005. Although direct attribution of disease decline to research outputs is difficult to establish, the Nepal experience demonstrates that IR can be a critical enabler for disease elimination. The lessons can potentially inform IR strategies in other countries with diseases targeted for elimination.


Volatile components in fermented soybean (Glycine max) curds.
Volatile components of three commercial fermented soybean (Glycine max) curds (FSC) (A-C) were extracted using a simultaneous steam distillation and extraction apparatus, and extracts were analyzed by gas chromatography/mass spectrometry. A total of 111 compounds was found. Sixty-three compounds were common to all three brands. Brands A, B, and C contained 90, 90, and 82 components, respectively. Major classes of compounds included alcohols (32) and esters (25). Similarities and differences existed in the composition of the FSC samples. Twelve common compounds including six esters, four alcohols, one ketone, and one miscellaneous compound had a dry weight of >1000 microg/kg of sample. Quantitative differences existed among the commercial brands (p<0.05). The quantity of ethanol detected might produce large numbers of ethyl esters that contribute to the desirable fruity and floral notes for the final products.


Effect of polymer structure on micelles formed between siRNA and cationic block copolymer comprising thiols and amidines.
Small interfering RNA (siRNA) has great therapeutic potential for the suppression of proteins associated with disease, but delivery methods are needed for improved efficacy. Here, we investigated the properties of micellar siRNA delivery vehicles prepared with poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLL) comprising lysine amines modified to contain amidine and thiol functionality. Lysine modification was achieved using 2-iminothiolane (2-IT) [yielding PEG-b-PLL(N2IM-IM)] or dimethyl 3,3'-dithiobispropionimidate (DTBP) [yielding PEG-b-PLL(MPA)], with modifications aimed to impart disulfide cross-linking ability without compromising cationic charge. These two lysine modification reagents resulted in vastly different chemistry contained in the reacted block copolymer, which affected micelle formation behavior and stability along with in vitro and in vivo performance. Amidines formed with 2-IT were unstable and rearranged into a noncharged ring structure lacking free thiol functionality, whereas amidines generated with DTBP were stable. Micelles formed with siRNA and PEG-b-PLL(N2IM-IM) at higher molar ratios of polymer/siRNA, while PEG-b-PLL(MPA) produced micelles only near stoichiometric molar ratios. In vitro gene silencing was highest for PEG-b-PLL(MPA)/siRNA micelles, which were also more sensitive to disruption under disulfide-reducing conditions. Blood circulation was most improved for PEG-b-PLL(N2IM-IM)/siRNA micelles, with a circulation half-life 3× longer than naked siRNA. Both micelle formulations are promising for siRNA delivery applications in vitro and in vivo.


Total Flavonoids in Premna Fulva Craib Alleviates Brain Neurological Impairment and Influences Nrf2 and HO-1 Expressions in Rats with Ischemia-Reperfusion.
Total flavonoids in Premna fulva Craib (TFPFC) are a kind of flavonoid compound synthesized via photosynthesis extracted from Premna fulva Craib, which possess a strong anti-oxidative effect. Cerebral Ischemia-Reperfusion refers to the body's damage mainly caused by oxidative stress. This study aims to investigate the alleviating effect of TFPFC on brain neurological impairment and its influences on Nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expressions in rats with Ischemia-Reperfusion. The rat model of Ischemia-Reperfusion was established, and rats were treated with TFPFC or normal saline. At 24 h after reperfusion, the neurological score, volume of cerebral infarction and cerebral water content were analyzed in different groups. The influences of TFPFC treatment on the proliferative activity and apoptosis of oxygen and glucose deprivation/reoxygenation (OGD/R) neural stem cells were detected via methyl thiazolyl tetrazolium (MTT) assay and flow cytometry. Moreover, the malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured to evaluate the oxidative stress effect. The influences of TFPFC treatment on the protein and messenger ribonucleic acid (mRNA) expressions of Nrf2 and HO-1 were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The TFPFC treatment alleviated the neurological impairment in rats after Ischemia-Reperfusion and reduced the volume of cerebral infarction and cerebral edema status in rats with Ischemia-Reperfusion. TFPFC increased the proliferative activity of OGD/R neural stem cells and decreased damage and apoptosis. In addition, the TFPFC treatment reduced the MDA level, improved the SOD activity, and up-regulated the protein and mRNA expressions of Nrf2 and HO-1. The TFPFC treatment may improve oxidative damage and protect the nervous system through the up-regulation of expressions of transcription factors Nrf2 and HO-1.


Scientific Visualization as a Microservice.
In this paper, we propose using a decoupled architecture to create a microservice that can deliver scientific visualization remotely with efficiency, scalability, and superior availability, affordability and accessibility. Through our effort, we have created an open source platform, Tapestry, which can be deployed on Amazon AWS as a production use microservice. The applications we use to demonstrate the efficacy of the Tapestry microservice in this work are: (1) embedding interactive visualizations into lightweight web pages, (2) creating scientific visualization movies that are fully controllable by the viewers, (3) serving as a rendering engine for high-end displays such as power-walls, and (4) embedding data-intensive visualizations into augmented reality devices efficiently. In addition, we show results of an extensive performance study, and suggest how applications can make optimal use of microservices such as Tapestry.


Determining the clinical importance of treatment benefits for interventions for painful orthopedic conditions.
The overarching goals of treatments for orthopedic conditions are generally to improve or restore function and alleviate pain. Results of clinical trials are generally used to determine whether a treatment is efficacious; however, a statistically significant improvement may not actually be clinically important, i.e., meaningful to the patient. To determine whether an intervention has produced clinically important benefits requires a two-step process: first, determining the magnitude of change considered clinically important for a particular measure in the relevant population and, second, applying this yardstick to a patient's data to determine whether s/he has benefited from treatment. Several metrics have been devised to quantify clinically important differences, including the minimum clinically important difference (MCID) and clinically important difference (CID). Herein, we review the methods to generate the MCID and other metrics and their use and interpretation in clinical trials and practice. We particularly highlight the many pitfalls associated with the generation and utilization of these metrics that can impair their correct use. These pitfalls include the fact that different pain measures yield different MCIDs, that efficacy in clinical trials is impacted by various factors (population characteristics, trial design), that the MCID value is impacted by the method used to calculate it (anchor, distribution), by the type of anchor chosen and by the definition (threshold) of improvement. The MCID is also dependent on the population characteristics such as disease type and severity, sex, age, etc. For appropriate use, the MCID should be applied to changes in individual subjects, not to group changes. The MCID and CID are useful tools to define general guidelines to determine whether a treatment produces clinically meaningful effects. However, the many pitfalls associated with these metrics require a detailed understanding of the methods to calculate them and their context of use. Orthopedic surgeons that will use these metrics need to carefully understand them and be aware of their pitfalls.


In-depth Study of a Novel Class of Ditopic Gadolinium(III)-based MRI Probes Sensitive to Zwitterionic Neurotransmitters.
The efficacy of Gd-based low-molecular weight ditopic MRI probes on binding zwitterionic neurotransmitters (ZNTs) relies on their structural compatibility. ZNTs are challenging biomarkers for monitoring chemical neurotransmission due to their intrinsic complexity as target molecules. In this work, we focus on tuning the cyclen- and azacrown ether-based binding sites properties to increase the affinity toward ZNTs. Our approach consisted in performing structural modifications on the binding sites in terms of charge and size, followed by the affinity evaluation through T 1-weighted relaxometric titrations. We prepared and investigated six Gd3+ complexes with different structures and thus properties, which were found to be acetylcholine insensitive; moreover, two of them displayed considerably stronger affinity toward glutamate and glycine over hydrogencarbonate and other ZNTs. Complexes with small and non-charged or no substituents on the azacrown moiety displayed the highest affinities toward ZNTs, followed by strong decrease in longitudinal relaxivity r 1 of around 70%. In contrast, hosts with negatively charged substituents exhibited lower decrease in r 1 of nearly 30%. The thorough investigations involving relaxometric titrations, luminescence, and NMR diffusion experiments, as well as theoretical density functional theory calculations, revealed that the affinity of reported hosts toward ZNTs is greatly affected by the remote pendant on the azacrown derivative.


The Zurich Study. VI. A continuum from depression to anxiety disorders?
A representative sample of 456 persons from the normal population aged 22 and 23 years was used to study the overlap of depression with anxiety disorders. The 1-year prevalence rate for major depression (DSM-III), minor depression, and anxiety disorder together was 16.4%. The observed cases of major depression occurred in 36% with anxiety disorder, the cases with minor depression in 60%. On the level of symptoms assessed by a semistructured clinical interview and on the level of self-assessed items of the symptom check list SCL-90, the overlap was even greater. The main finding was that subjects with both diagnoses, depression and anxiety disorder, were more severely affected in general. Discriminant analyses of the SCL-90 scales together with the qualitative distribution of SCL items characterizing depression, anxiety, or phobia, did not disprove the hypothesis of a continuum.


A urinary metabolomics study of rats after the exposure to acrylamide by ultra performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.
Acrylamide (ACR) is known to induce neurotoxicity in humans and occupational exposure to ACR has an effect on human health. Since some animal experiments indicate the metabolic change caused by the ACR based on the metabolomics, increasing concern is the change of metabolite profiles by the low-dose ACR. In the present study, a low-dose of ACR (18 mg kg(-1)) was administered to male Wistar rats for 40 days. Ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-Q-TOF MS) was used to examine urine samples from ACR-dosed and control animals. Multiple statistical analyses with principal component analysis (PCA) were used to investigate metabolite profile changes in urine samples, and to screen for potential neurotoxicity biomarkers. PCA showed differences between the ACR-dosed and control groups 20 days after the start of dosing; a bigger separation between the two groups was seen after dosing for 40 days. Levels of 4-guanidinobutanoic acid and 2-oxoarginine were significantly higher in urine from the ACR-dosed group than in urine from the control group after 10 days (p < 0.05). Receiver operator characteristic (ROC) curve analysis suggested that 4-guanidinobutanoic acid and 2-oxoarginine were the major metabolites. Our results suggest that high levels of 4-guanidinobutanoic acid and 2-oxoarginine may be related to ACR neurotoxicity. These metabolites could, therefore, act as sensitive biomarkers for ACR exposure and be useful for investigating toxic mechanisms. They may also provide a scientific foundation for assessing the effects of chronic low-dose ACR exposure on human health.


"The First Thousand Days" Define a Fetal/Neonatal Neurology Program.
Gene-environment interactions begin at conception to influence maternal/placental/fetal triads, neonates, and children with short- and long-term effects on brain development. Life-long developmental neuroplasticity more likely results during critical/sensitive periods of brain maturation over these first 1,000 days. A fetal/neonatal program (FNNP) applying this perspective better identifies trimester-specific mechanisms affecting the maternal/placental/fetal (MPF) triad, expressed as brain malformations and destructive lesions. Maladaptive MPF triad interactions impair progenitor neuronal/glial populations within transient embryonic/fetal brain structures by processes such as maternal immune activation. Destructive fetal brain lesions later in pregnancy result from ischemic placental syndromes associated with the great obstetrical syndromes. Trimester-specific MPF triad diseases may negatively impact labor and delivery outcomes. Neonatal neurocritical care addresses the symptomatic minority who express the great neonatal neurological syndromes: encephalopathy, seizures, stroke, and encephalopathy of prematurity. The asymptomatic majority present with neurologic disorders before 2 years of age without prior detection. The developmental principle of ontogenetic adaptation helps guide the diagnostic process during the first 1,000 days to identify more phenotypes using systems-biology analyses. This strategy will foster innovative interdisciplinary diagnostic/therapeutic pathways, educational curricula, and research agenda among multiple FNNP. Effective early-life diagnostic/therapeutic programs will help reduce neurologic disease burden across the lifespan and successive generations.


[Reproductive pattern and mean size of sexual maturity of female lobsters Panulirus gracilis (Decapoda: Palinuridae) in Playa Lagarto, Guanacaste, Costa Rica].
The lobster P. gracilis is important as a fishery resource and also contributes to food security of fishers in coastal communities in the North Pacific of Costa Rica. Due to the importance of updating knowledge related to the reproductive pattern of this species, we analyzed 357 specimens of female lobsters caught by the fishing methods of "hookah" and lung diving, from November 2007 to October 2008 in Playa Lagarto. Furthermore, we examined the size composition by depth; monthly pattern of reproductive activity (RAI) associated with the relative increase in sea surface temperature, and also the mean size at maturity using Generalized Linear Models. Four physiological states of sexual maturity showed that females with no signs of mating or sexual maturity have a minimum mean size of 62.3mm of cephalothorax length (CL). There are characteristics of functional maturity from very small sizes ranging from 30 to 50mm CL, being the smallest berried female reported for this specie of 35.8mm CL and the highest percentage of mature females between 70 and 80mm CL. Percentages of RAI remained above 50% during the year except October and January. In addition, it observed an increase in the RAI that started from April and continued until August associated with a relative increase in temperature on March, although the correlation was not significant (r2=0.49, p>0.05). It is possible that the low mean size at maturity (70.2mm LC) for P. gracilis in this region is related to the fishing activity. It recommends the establishment of a ban in the region of at least five months (April-August) in order to protect the reproductive seasonality of the species and to promote a recruitment increase in the fishing areas.


Effective measures to improve influenza vaccination coverage among healthcare workers during and after COVID-19.
The influenza vaccine is the most effective measure to prevent influenza. The aim of this study was to evaluate the impact of measures taken by the hospital on the influenza vaccination coverage of medical staff after implementation. We collected and compared the influenza vaccination of staff in key departments from 2018 to 2022. As the results, in 2018 and 2019, the influenza vaccination rates of staff in key departments in our hospital were generally as low as 10.3% and 11.6%, respectively. After the policy of free vaccination for staff in key departments was adopted in 2020 and other incentive measures, the overall influenza vaccination rates of key departments from 2020 to 2022 were 77.2%, 71.4%, and 81.3%, respectively, which were significantly higher than the pre-2020 vaccination rates in our hospital and healthcare workers in most regions of China. In conclusion, with the implementation of several measures to promote influenza vaccination, the rate of influenza vaccination among medical staff has significantly increased.


Reduced adolescent-age spatial learning ability associated with elevated juvenile-age superoxide levels in complex I mouse mutants.
Large-scale, heteroplasmic and generally pathogenic mtDNA defects (as induced by defective mitochondrial DNA polymerase, clonal mutations or DNA deletions) are known to negatively impact on life span and can result in apoptosis and tissue loss in, e.g., skeletal muscle or reduce learning abilities. The functional impact of homoplasmic specific mtDNA point mutations, e.g., in genes coding for the electron transport chain, however, remains a matter of debate. The present study contributes to this discussion and provides evidence that a single point mutation in complex I of the respiratory chain is associated with impairment of spatial navigation in adolescent (6-month-old) mice, i.e., reduced performance in the Morris Water Maze, which goes along with increased production of reactive oxygen species (ROS) in juvenile mice (3 months) but not at the age of phenotype expression. A point mutation in complex III goes along with only a mild and non-significant negative effect on cognitive performance and no significant changes in ROS production. These findings suggest to also consider the ontogenetic development of phenotypes when studying mtDNA mutations and highlights a possible impact of complex I dysfunction on the emergence of neurological deficits.


Baseline assessment of prevalence and geographical distribution of HPV types in Chile using self-collected vaginal samples.
Chile has broad variations in weather, economics and population from the far desert north (Region 1) to the cold, icy south (Region 12). A home-based self-collected vaginal sampling was nested in the 2003 Chilean population-based health survey in order to explore the possibility of a type-specific geographical variation for human papillomavirus The population was a national probability sample of people 17 years of age and over. Consenting women provided self-collected cervicovaginal swabs in universal collection media (UCM). DNA was extracted and typed to 37 HPV genotypes using PGMY consensus PCR and line blot assay. Weighted prevalence rates and adjusted OR were calculated. Of the 1,883 women participating in the health survey, 1,219 (64.7%) provided a cervicovaginal sample and in 1,110 (56.2% of participants and 66.5% of those eligible) the samples were adequate for analysis. Refusal rate was 16.9%. HPV prevalence was 29.2% (15.1% high-risk HPV and 14.1% low-risk HPV). Predominant high-risk types were HPV 16, 52, 51, 56 and 58. Predominant low-risk HPVs were HPV 84, CP6108, 62, 53 and 61. High-risk and low-risk HPV rates were inversely correlated between the regions. High-risk HPV prevalence was highest among the youngest women, whereas low-risk HPV increased slightly with age. Self-obtained vaginal sampling is adequate for monitoring HPV in the community, for identifying high-risk areas, and for surveying the long term impact of interventions.


Independence of Anaplasma marginale strains with high and low transmission efficiencies in the tick vector following simultaneous acquisition by feeding on a superinfected mammalian reservoir host.
Strain superinfection occurs when a second pathogen strain infects a host already carrying a primary strain. Anaplasma marginale superinfection occurs when the second strain carries a variant repertoire different from that of the primary strain, and the epidemiologic consequences depend on the relative efficiencies of tick-borne transmission of the two strains. Following strain superinfection in the reservoir host, we tested whether the presence of two A. marginale (sensu lato) strains that differed in transmission efficiency altered the transmission phenotypes in comparison to those for single-strain infections. Dermacentor andersoni ticks were fed on animals superinfected with the Anaplasma marginale subsp. centrale vaccine strain (low transmission efficiency) and the A. marginale St. Maries strain (high transmission efficiency). Within ticks that acquired both strains, the St. Maries strain had a competitive advantage and replicated to significantly higher levels than the vaccine strain. The St. Maries strain was subsequently transmitted to naïve hosts by ticks previously fed either on superinfected animals or on animals singly infected with the St. Maries strain, consistent with the predicted transmission phenotype of this strain and the lack of interference due to the presence of a competing low-efficiency strain. The vaccine strain was not transmitted by either singly infected or coinfected ticks, consistent with the predicted transmission phenotype and the lack of enhancement due to the presence of a high-efficiency strain. These results support the idea that the strain predominance in regions of endemicity is mediated by the intrinsic transmission efficiency of specific strains regardless of occurrence of superinfection.


The dynamics of help-seeking in men and women: a national survey study.
This paper will integrate a number of intriguing results from a study of help-seeking in a national representative sample of Americans. It began as a search for an explanation of why women seek professional help at a greater rate than men. I expected two general findings: various facets of demoralization would be correlated with the search for help in both men and women; and women would express more demoralization than men. The results were not so straightforward. As the analyses unfolded, especially as education and age differences were also considered, it became increasingly clear that help-seeking is not singularly dependent on feelings of demoralization and that women are not necessarily more distressed about facets of their lives that should contribute to demoralization. I have attempted to develop a more complex model of professional help-seeking for both men and women suggested by the findings of this study.


Whole-genome analyses reveals the animal origin of a rotavirus G4P[6] detected in a child with severe diarrhea.
Group A rotaviruses are a major cause of severe gastroenteritis in children worldwide. Currently, two rotavirus vaccines are being used in vaccination programs, and one of the factors involved in lower vaccine efficacy is the mismatch among the circulating strains and the vaccine strains. Thus, the emergence of animal strains in the human population could affect the efficacy of vaccination programs. Here we report the presence of a G4P[6] strain in a Paraguayan child presenting acute gastroenteritis in 2009. Genomic analyses revealed that the strain presents a porcine-like genome (G4-P[6]-I1-R1-C1-M1-A8-N1-T7-E1-H1), suggesting a direct animal-to-human transmission. Continuous surveillance of rotaviruses in humans and animals will help us to better understand rotavirus epidemiology and evolution.


[Comparative aspects of penal sanctions].
A conference on comparative aspects of criminal sanctions has been held at the Aspen Institute, Berlin, on February 2 to 6, 1976, assembling experts from Europe and from the United States, The focus has been on guidelines for prevention of crime and treatment of offenders, with a view to examine differences and convergences among various national criminal justice systems. Specific tropics under discussion have been: the goals of dention, alternatives to detention, sentencing and releasethe conditions of detention, the future of research in the field. Priority areas for further study were considered to be: prevention of crime, arrest and sentencing procedures, grievances procedures, the dangerous offender, protection of victims, of jurors and of witnesses, treatment of juveniles, information of the public.


Powerful statistical method to detect disease-associated genes using publicly available genome-wide association studies summary data.
Genome-wide association studies (GWAS) have thus far achieved substantial success. In the last decade, a large number of common variants underlying complex diseases have been identified through GWAS. In most existing GWAS, the identified common variants are obtained by single marker-based tests, that is, testing one single-nucleotide polymorphism (SNP) at a time. Generally, the basic functional unit of inheritance is a gene, rather than a SNP. Thus, results from gene-level association test can be more readily integrated with downstream functional and pathogenic investigation. In this paper, we propose a general gene-based p-value adaptive combination approach (GPA) which can integrate association evidence of multiple genetic variants using only GWAS summary statistics (either p-value or other test statistics). The proposed method could be used to test genetic association for both continuous and binary traits through not only one study but also multiple studies, which would be helpful to overcome the limitation of existing methods that can only be applied to a specific type of data. We conducted thorough simulation studies to verify that the proposed method controls type I errors well, and performs favorably compared to single-marker analysis and other existing methods. We demonstrated the utility of our proposed method through analysis of GWAS meta-analysis results for fasting glucose and lipids from the international MAGIC consortium and Global Lipids Consortium, respectively. The proposed method identified some novel trait associated genes which can improve our understanding of the mechanisms involved in β -cell function, glucose homeostasis, and lipids traits.


Anticoagulation after Iliofemoral Vein Stenting - Old Versus New.
In recent years, there has been an increasing interest in endovascular iliofemoral vein stenting to prevent/ alleviate symptoms related to proximal venous outflow obstruction. Maintaining long-term stent patency is one of the main challenges, and risk factors for the development of re-thrombosis are not well understood. Published data on the safety and efficacy of the procedure predominantly come from cohort studies mainly focusing on mechanical aspects relating to stent placement and flow. Aetiology of thrombus formation and thrombotic tendencies of patients due to underlying medical conditions are not captured well or linked to clinical outcomes, and the impact of choice and length of antithrombotic therapy have not been specifically investigated. Here, we review different procedure-related factors and patient characteristics that might increase the risk of re-thrombosis and the utility of antithrombotic treatment options currently available.


[Relation between drug intolerance and immunologic disorders in patients with pulmonary tuberculosis].
Data are given on the examination of 128 tuberculosis patients and 30 apparently healthy subjects. The basic parameters of T-cell immunity in tuberculosis patients associated with drug intolerance have been studied. Side effects of chemopreparations arise significantly more often with the initially impaired immunity parameters. A sharp imbalance of basic immune-regulatory T-cell subpopulations was noted prior to the development of clinical manifestations of immunity. The traditionally used methods for relieving drug intolerance fail to normalize T-system parameters. Patients with tuberculin anergy were noted to have an increased tendency to adverse reactions. The findings obtained help in recording the basic mechanisms of drug intolerance formation and development of methods for its prevention and correction.


Fatty acid metabolism in hepatocytes cultured with hypolipidaemic drugs. Role of carnitine.
The direct effects of clofibrate analogues on carnitine acyltransferase activities and fatty acid metabolism were studied in cultured hepatocytes. Rat hepatocytes cultured with bezafibrate or ciprofibrate (0.1-10 micrograms/ml) for 48 h had increased activities of carnitine acetyltransferase (CAT; 4-6-fold) and carnitine palmitoyltransferase (CPT; 12-34%). The increase in CAT was higher in hepatocytes from the periportal zone (440%) of rat liver compared with cells from the perivenous zone (266%). In human hepatocytes, in contrast with rat, the fibrates did not cause a marked increase in CAT activity. The effects of fibrates on palmitate metabolism were dependent on the carnitine status. In the presence of exogenous carnitine (1 mM), rat hepatocytes cultured with bezafibrate had higher rates of total palmitate metabolism (29-34%) without increased partitioning of palmitate towards beta-oxidation, relative to control cultures. At low endogenous carnitine concentrations, cells cultured with bezafibrate had a greater increase in palmitate metabolism, esterification and cellular accumulation of triacylglycerol compared with the corresponding increases in the presence of carnitine. The changes in palmitate metabolism at either high or low carnitine concentrations were small in comparison with the changes in CAT activity. It is concluded that the increase in hepatic carnitine that occurs in vivo after fibrate feeding probably plays the major role in the changes in partitioning of fatty acid between beta-oxidation and esterification.


Treatment of cocaine overdose with lipid emulsion.
We describe the management and recovery of a 28-year-old man following a history of overdose by nasal inhalation of cocaine. The patient was presented in a comatose state suffering from seizures and marked cardiovascularly instability. Intravenous lipid emulsion was administered following initial resuscitation and tracheal intubation, as a means of treating persistent cardiac arrhythmias and profound hypotension. Following lipid emulsion therapy, the patient's life-threatening cardiovascular parameters rapidly improved and he recovered well without any side effects, thus being discharged within 2 days.


Tomoregulin-1 prevents cardiac hypertrophy after pressure overload in mice by inhibiting TAK1-JNK pathways.
Cardiac hypertrophy is associated with many forms of heart disease, and identifying important modifier genes involved in the pathogenesis of cardiac hypertrophy could lead to the development of new therapeutic strategies. Tomoregulin-1 is a growth factor that is primarily involved in embryonic development and adult central nervous system (CNS) function, and it is expressed abnormally in a variety of CNS pathologies. Tomoregulin-1 is also expressed in the myocardium. However, the effects of tomoregulin-1 on the heart, particularly on cardiac hypertrophy, remains unknown. The aim of the study is to examine whether and by what mechanism tomoregulin-1 regulates the development of cardiac hypertrophy induced by pressure overload. In this study, we found that tomoregulin-1 was significantly upregulated in two cardiac hypertrophy models: cTnT(R92Q) transgenic mice and thoracic aorta constriction (TAC)-induced cardiac hypertrophy mice. The transgenic overexpression of tomoregulin-1 increased the survival rate, improved the cardiac geometry and functional parameters of echocardiography, and decreased the degree of cardiac hypertrophy of the TAC mice, whereas knockdown of tomoregulin-1 expression resulted in an opposite phenotype and exacerbated phenotypes of cardiac hypertrophy induced by TAC. A possible mechanism by which tomoregulin-1 regulates the development of cardiac hypertrophy in TAC-induced cardiac hypertrophy is through inhibiting TGFβ non-canonical (TAK1-JNK) pathways in the myocardium. Tomoregulin-1 plays a protective role in the modulation of adverse cardiac remodeling from pressure overload in mice. Tomoregulin-1 could be a therapeutic target to control the development of cardiac hypertrophy.


Pseudorabies virus antibodies in swine slaughtered in Iowa.
Sera from butcher swine (1,246 total) were evaluated qualitatively by the microimmunodiffusion test and quantitatively by the virus neutralization test for antibody to pseudorabies virus. Ten percent of the sera had antibody to pseudorabies virus. Follow-up contact with veterinarians whose clients included the farms from which the positive swine originated revealed that few feeder swine are vaccinated against pseudorabies and that most infections with pseudorabies virus are subclinical.


Ribonucleic acid synthesis dependent on exogenous triphosphates in nystatin-treated cells of of Kluyveromyces latis.
Kluyveromyces lactis cells treated with nystatin became permeable to ribonucleoside triphosphates. Although not viable, nystatin-treated cells were capable of sustaining ribonucleic acid synthesis. The system depended on the presence of divalent ions and the four nucleoside triphosphates, and was strongly stimulated by ammonium sulfate. The system utilized endogenous deoxyribonucleic acid as template. Synthesis of ribonucleic acid was associated with the cells and probably occurred internally.


Loss of GATA1 and gain of FLI1 expression during thrombocyte maturation.
In this paper, we characterized expression of GATA1 and FLI1 gene promoters in thrombocytes of zebrafish transgenic lines, G1-GM2 and TG(fli1:EGFP)y1 that carry transgenes of GATA1 and FLI1 gene promoters driving GFP. We found two discrete populations of thrombocytes verified by morphology, labeled with GFP in both G1-GM2 and TG(fli1:EGFP)y1 lines: (1) the more intensely labeled GFP+ thrombocyte, and (2) the less intensely labeled GFP+ thrombocytes. The more intensely labeled GFP+ thrombocyte in G1-GM2 line and the less intensely labeled GFP+ thrombocytes in the TG(fli1:EGFP)y1 line corresponded to young thrombocytes. These results showed that young thrombocytes have higher GATA1 promoter activity, while mature thrombocytes have more FLI1 gene promoter transcription. This finding suggests that there is a gradual loss of GATA1 and gain of FLI1 expression as the thrombocytes mature, and this overexpression of FLI1 may help maintain the thrombocyte lineage. Furthermore, the presence of transcriptional factors similar to those found in megakaryocytes raises the possibility that vertebrate thrombocytes may be the forerunners of mammalian megakaryocytes and, therefore, could serve as a model to study megakaryocyte maturation.


Lumbar Spinal Stenosis Treatment: Is Surgery Better than Non-Surgical Treatments in Afro-Descendant Populations?
(1) Background: Limited data are available on lumbar spine stenosis management in sub-Saharan African populations and Afro-descendant patients are underrepresented in European and US clinical trials. We aimed to compare the clinical response between decompressive surgery and conservative treatments in a population of self-reported Afro-Caribbean patients with lumbar spine stenosis over a 2-year follow-up period. (2) Methods: Prospective cohort of 137 self-reported Afro Caribbeans with lumbar spine stenosis based on clinical and radiological criteria. Patients were assigned to decompression surgery or to conservative treatments according to their outcome after a first course of steroid epidural injection and their preferences. The primary outcome was evolution of the Oswestry disability index at 3 months (3 M), 12 M, 18 M and 24 M follow-up. (3) Results: Decrease of ODI was significantly more important in the "decompression surgery" arm compared to "conservative treatment" arm at 3 M, 12 M and 18 M: −17.36 vs. 1.03 p < 10−4; −16.38 vs. −1.53 p = 0.0059 and −19.00 vs. −4.52 p = 0.021, respectively. No difference was reported at 24 M. (4) Conclusions: In this first comparative study between surgery and conservative treatments in an exclusively afro-descendant lumbar spine stenosis cohort, we report long term superiority of decompression surgery versus conservative treatments over an 18-month period.


Hypoxia/reoxygenation alters essential fatty acids metabolism in cultured rat cardiomyocytes: protection by antioxidants.
Peroxidation of membrane lipids, altering cell integrity and function, plays an important part in the onset and development of cardiac damage following ischemia and reperfusion. Cells maintain their membrane lipid homeostasis by substituting peroxidized lipids with new polyunsaturated fatty acids. The microsomal enzymatic system converting essential fatty acids to highly unsaturated fatty acids (HUFAs) contributes to this repairing mechanism. The membrane of the endoplasmic reticulum could be one of the potential targets of free radicals generated in ischemia/reperfusion, thus causing a reduced efficacy of the system required for HUFA biosynthesis. To verify this hypothesis, and the consequent modification in fatty acid composition, we exposed cultured rat cardiomyocytes to different periods of hypoxia (H), eventually followed by reoxygenation (R). Furthermore, the effectiveness of antioxidants like alpha-tocopherol and a green tea extract in counteracting H/R damage towards HUFA biosynthesis was tested. Linoleic (LA) and alpha-linolenic acid (ALA) conversion was measured by pre-labelling cells with [1-14C]LA or [1-14C]ALA for 1 h; total lipid fatty acid composition was determined by gas chromatographic analysis. H profoundly affected HUFA biosynthesis, and this effect was much more evident on LA than on ALA. Conversion of both substrates was partially restored during R due to the readmission of the final acceptor of the desaturating complex. Fatty acid composition data were in agreement with the modifications observed in essential fatty acid conversion. Antioxidant protection appeared to be related to the duration of H, and to be more effective during H than during R. This study points out the importance of possessing good antioxidant defenses not only after, but mainly prior to the onset of H.


Ultrafast ring-opening and solvent-dependent product relaxation of photochromic spironaphthopyran.
The ultrafast dynamics of unsubstituted spironaphthopyran (SNP) were investigated using femtosecond transient UV and visible absorption spectroscopy in three different solvents and by semi-classical nuclear dynamics simulations. The primary ring-opening of the pyran unit was found to occur in 300 fs yielding a non-planar intermediate in the first singlet excited state (S1). Subsequent planarisation and relaxation to the product ground state proceed through barrier crossing on the S1 potential energy surface (PES) and take place within 1.1 ps after excitation. Simulations show that more than 90% of the trajectories involving C-O bond elongation lead to the planar, open-ring product, while relaxation back to the S0 of the closed-ring form is accompanied by C-N elongation. All ensuing spectral dynamics are ascribed to vibrational relaxation and thermalisation of the product with a time constant of 13 ps. The latter shows dependency on characteristics of the solvent with solvent relaxation kinetics playing a role.


Executive function and dangerous driving behaviors in young drivers.
The purpose of the present study was to investigate the behavioral and cognitive processes underlying dangerous driving behaviors. We used a survey to assess levels of executive function in college students. The sample consisted of 59 males and 77 females and their age ranged from 18 to 24. We stratified the students into two groups based on executive function scores and compared the extent to which each group engaged in four dangerous driving behaviors (texting while driving, driving without a seat belt, driving while intoxicated, and speeding) as well as how often they experienced three negative driving outcomes (crashes, pulled over, and ticketed). We also investigated how these driving behaviors and outcomes are correlated with subcategories of executive function. The results show that students with a low level of executive function were more likely to engage in dangerous driving behaviors and more likely to experience negative driving outcomes. The results also show that texting while driving, driving while intoxicated, and speeding were most strongly correlated with the executive function subcategory of Impulse Control, whereas driving without a seat belt was most strongly correlated with the executive function subcategory of Strategic Planning. These results suggest that different behavioral or cognitive processes are involved in different dangerous driving behaviors and different interventions may be needed to target each underlying process.


Dapagliflozin's Effects on Glycemia and Cardiovascular Risk Factors in High-Risk Patients With Type 2 Diabetes: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With a 28-Week Extension.
To assess the efficacy and safety of dapagliflozin, a selective sodium-glucose cotransporter 2 inhibitor, compared with placebo in patients with type 2 diabetes (T2D), documented pre-existing cardiovascular disease (CVD), and a history of hypertension. Patients (N = 922) were randomized to receive 10 mg dapagliflozin or placebo in a double-blind trial for 24 weeks, followed by a 28-week extension period. In patients receiving insulin, the insulin dose was reduced by 25% at randomization. Patients were stratified by age, insulin use, and time from the most recent qualifying cardiovascular (CV) event. Co-primary end points were a change from baseline in hemoglobin A1c (HbA1c) and the proportion of patients achieving a combined reduction in HbA1c of ≥0.5% (5.5 mmol/mol), body weight (BW) of ≥3%, and systolic blood pressure (SBP) of ≥3 mmHg. At 24 weeks, dapagliflozin significantly reduced HbA1c (-0.38% [-4.2 mmol/mol]) from baseline (8.18%) compared with a slight increase with placebo from baseline (8.08%) (0.08% [0.9 mmol/mol]). Significantly more patients met the three-item end point with treatment with dapagliflozin than with placebo (11.7% vs. 0.9%, respectively). Changes were maintained over 52 weeks. Although ∼42% of patients were ≥65 years old, similar results were observed in both age-stratified groups. Serious adverse events, hypoglycemia, urinary tract infections, and cardiac disorders were similar between groups. Adverse events of hypotension, dehydration, hypovolemia, genital infection, and renal failure or impairment occurred more often with dapagliflozin treatment. In this study that evaluated T2D patients who were at high risk for future CVD events, dapagliflozin administration had significantly greater effects in reducing HbA1c, BW, and SBP, without adversely impacting CV safety when compared with placebo treatment.


Developing capable quality improvement leaders.
Cincinnati Children's Hospital Medical Center created the Intermediate Improvement Science Series (I(2)S(2)) training course to develop organisational leaders to do improvement, lead improvement and get results on specific projects. Each multidisciplinary class consists of 25-30 participants and 12 in-class training days over 6 months. Instructional methods include lectures, case studies, interactive application exercises and dialogue, participant reports and assigned readings. Participants demonstrate competence in improvement science by completing a project with improvement in outcome and/or process measures. They present on their projects and receive feedback during each session and one-on-one coaching between sessions. Since 2006, 279 participants in 11 classes have completed the I(2)S(2) course. Participant evaluations have consistently rated satisfaction, learning, application, impact and value very high. Large and statistically significant changes were observed in pre-course to post-course self-assessment of knowledge of five quality improvement topics. Approximately 85% of the projects demonstrated measurable improvement. At follow-up, 72% of improvement projects were completed and made a part of everyday operations in the participant's unit or were the focus of continuing improvement work. Many changes were spread to other units or programmes. Most (88%) responding graduates continued to participate in formal quality improvement efforts and many led other improvement projects. Nearly half of the respondents presented their results at one or more professional conference. Through the I(2)S(2) course, the authors are developing improvement leaders, accelerating the shift in the culture from a traditional academic medical centre to an improvement-focused culture, and building cross-silo relationships by developing leaders who understand the organisation as a large system of interdependent subsystems focused on improving health.


Surface properties of Streptococcus sanguis FW213 mutants nonadherent to saliva-coated hydroxyapatite.
Seventeen mutants of Streptococcus sanguis FW213 nonadherent to saliva-coated spheroidal hydroxyapatite were isolated after mutagenesis with ethyl methanesulfonate, nitrosoguanidine, nitrous acid, hydroxylamine, or 2-aminopurine. Enrichment for nonadherent mutants was accomplished by successive adsorptions of the adherent strains to saliva-coated hydroxyapatite. After enrichment, variant colonial morphology on tryptic agar was used as a screening technique for selection of nonadherent mutants, with loss of colonial opacity frequently associated with loss of adherence ability. These mutants were further characterized for additional surface properties, including twitching motility, saliva-induced aggregation, coaggregation with Actinomyces species, surface hydrophobicity, and presence of fimbriae. Results from these assays indicated that the nonadherent mutants fell into six phenotypic groups. A correlation between the loss of adherence ability, a decrease in cell fimbriation, and a decrease in surface hydrophobicity is apparent.


The effect of mangrove restoration on avian assemblages of a coastal lagoon in southern Mexico.
Mangrove forests provide many ecosystem services, including the provision of habitat that supports avian biodiversity. However, hurricanes can knock down trees, alter hydrologic connectivity, and affect avian habitat. In 1995, Hurricanes Opal and Roxanne destroyed approximately 1,700 ha of mangrove forest in Laguna de Términos, Mexico. Since then, hydrological restoration has been implemented to protect the mangrove forest and its biodiversity. Since avian communities are often considered biological indicators of ecosystem quality, avian diversity and species relative abundance were evaluated as indicators of mangrove restoration success by comparing undisturbed mangrove patches with those affected by the hurricanes. Using bird surveys, similarity analyses, and generalized linear models, we evaluated the effects of water quality variables and forest structure on the relative abundance and diversity of the avian community in disturbed, restored, and undisturbed mangrove patches. Higher bird species richness and relative abundances were found in disturbed and restored sites compared to the undisturbed site. After restoration, values of frequency of flooding, water temperature, tree density, and the number of tree species were more similar to that of the undisturbed site than to the values of the disturbed one. Such variables influenced the relative abundance of bird guilds in the different habitat conditions. Furthermore, some insectivorous bird species, such as the Yellow Warbler and Tropical Kingbird, were found to be similarly abundant in both undisturbed and restored sites, but absent or very low in occurrence at the disturbed site. Collectively, our results strongly suggest that hydrologic restoration helps to enhance niche availability for different bird guilds, including water and canopy bird species. Our work can help inform management strategies that benefit avian communities in mangrove forests and wetland systems.


No alteration in the PFA-100 in vitro bleeding time induced by the Ginkgo biloba special extract, EGb 761, in elderly patients with mild cognitive impairment.
EGb 761 is widely used in the management of mild cognitive impairment in the elderly population. Elucidation of the effects of EGb 761 on primary haemostasis via PFA-100 could represent an important step for better understanding of the haemostatic safety of EGb 761. The purpose of this prospective study is to assess the effects of Ginkgo biloba special extract, EGb 761, on PFA-100 in vitro bleeding time in elderly patients with mild cognitive impairment. A total of 40 elderly patients aged 65-79 years who were referred for geriatric assessment and who were diagnosed as having mild cognitive impairment were included. Patients were started on 80 mg EGb-761 three times daily. The complete set of PFA-100 in vitro bleeding time and coagulation parameters including prothrombin time, activated partial thromboplastin time and International Normalized Ratio were assessed before and on the seventh day of treatment with EGb 761. There was no statistically significant prolongation in PFA-100 in vitro bleeding time or coagulation parameters in patients receiving EGb 761 after 7 days. The data about the safety of EGb 761 from the point of primary haemostasis in our elderly patient population with mild cognitive impairment casts hope for the future management of this 'difficult-to-treat' population with the promising Ginkgo extracts.


Key components of a school-located vaccination clinic: lessons learned from fall 2009.
The 2009 H1N1 influenza A virus vaccination campaign focused on use of school-located vaccination (SLV) clinics because of the ability of SLV to reach targeted populations. Large numbers of children are found in schools, and schools are conveniently located throughout communities. Communities are generally familiar with and trust schools, and school facilities can generally accommodate mass vaccination clinics. School nurses are familiar with the health of individual students and may be available to assist in vaccination activities. In addition, schools have access to parental contact information, which can facilitate communications. Challenges faced by local health departments (LHDs) and schools in implementing 2009 H1N1 SLV clinics, including disruption of educational activities, locating adequate staff, tailoring immunization activities to meet the needs of each school district, and transportation and administration of vaccine, are explored.


Modeling of thermal transport in pillared-graphene architectures.
Carbon nanotubes (CNT) and graphene are considered as potential future candidates for many nano/microscale integrated devices due to their superior thermal properties. Both systems, however, exhibit significant anisotropy in their thermal conduction, limiting their performance as three-dimensional thermal transport materials. From thermal management perspective, one way to tailor this anisotropy is to consider designing alternative carbon-based architectures. This paper investigates the thermal transport in one such novel architecture-a pillared-graphene (PG) network nanostructure which combines graphene sheets and carbon nanotubes to create a three-dimensional network. Nonequilibrium molecular dynamics simulations have been carried out using the AIREBO potential to calculate the thermal conductivity of pillared-graphene structures along parallel (in-plane) as well as perpendicular (out-of-plane) directions with respect to the graphene plane. The resulting thermal conductivity values for PG systems are discussed and compared with simulated values for pure CNT and graphite. Our results show that in these PG structures, the thermal transport is governed by the minimum interpillar distance and the CNT-pillar length. This is primarily attributed to scattering of phonons occurring at the CNT-graphene junctions in these nanostructures. We foresee that such architecture could potentially be used as a template for designing future structurally stable microscale systems with tailorable in-plane and out-of-plane thermal transport.


Codeine for acute cough in children.
Owing to Health Canada's recent recommendations to avoid the use of over-the-counter cough and cold medications in preschool children, I was looking at other antitussive medications for acute cough. Codeine was recommended in the past for this indication. What is the evidence for its use and how effective and safe is it? Cough is one of the most common symptoms in children, and the opioid codeine has known antitussive qualities mediated by a central nervous system pathway. However, current evidence finds codeine to be no more effective than placebo for acute cough in children. Its safety profile and recent advances in understanding codeine's variable effectiveness prohibit recommending codeine for cough in children.


Novel phospholipolytic activities associated with electronegative low-density lipoprotein are involved in increased self-aggregation.
Electronegative low-density lipoprotein (LDL(-)) is a minor LDL subfraction present in plasma with increased platelet-activating factor acetylhydrolase (PAF-AH) activity. This activity could be involved in the proinflammatory effects of LDL(-). Our aim was to study the presence of additional phospholipolytic activities in LDL(-). Total LDL was fractionated into electropositive (LDL(+)) and LDL(-) by anion-exchange chromatography, and phospholipolytic activities were measured by fluorometric methods. Phospholipolytic activity was absent in LDL(+) whereas LDL(-) presented activity against lysophosphatidylcholine (LPC, 82.4 +/- 34.9 milliunits/mg of apoB), sphingomyelin (SM, 53.3 +/- 22.5 milliunits/mg of apoB), and phosphatidylcholine (PC, 25.7 +/- 4.3 milliunits/mg of apoB). LDL(-), but not LDL(+), presented spontaneous self-aggregation at 37 degrees C in parallel to phospholipid degradation. This was observed in the absence of lipid peroxidation and suggests the involvement of phospholipolytic activity in self-aggregation of LDL(-). Phospholipolytic activity was not due to PAF-AH, apoE, or apoC-III and was not increased in LDL(+) modified by Cu (2+) oxidation, acetylation, or secretory phospholipase A 2 (PLA 2). However, LDL(-) efficiently degraded phospholipids of lipoproteins enriched in LPC, such as oxidized LDL or PLA 2-LDL, but not native or acetylated LDL. This finding supports that LPC is the best substrate for LDL(-)-associated phospholipolytic activity. These results reveal novel properties of LDL(-) that could play a significant role in its atherogenic properties.


Iron K-edge X-ray absorption spectroscopy of the iron-molybdenum cofactor of nitrogenase from Klebsiella pneumoniae.
Iron K-edge X-ray absorption data for the iron-molybdenum cofactor ('FeMoco') from Klebsiella pneumoniae reported here provide the first evidence for long-range structural order in the cofactor [Fe...Fe(Mo) = 0.368 nm in addition to Fe...S = 0.22 nm and Fe...Fe(Mo) = 0.27 nm] and, in contrast with previously published data [Antonio, Teo, Orme-Johnson, Nelson, Groh, Lindahl, Kauzlarich & Averill (1982) J. Am. Chem. Soc. 104, 4703-4705], indicate that most of the iron centres are not co-ordinated to light (oxygen, nitrogen) atoms. This demonstrates that presently available chemical models for FeMoco are inadequate.


Novel drug targets for asthma and COPD: lessons learned from in vitro and in vivo models.
Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent respiratory diseases characterized by airway inflammation, airway obstruction and airway hyperresponsiveness. Whilst current therapies, such as β-agonists and glucocorticoids, may be effective at reducing symptoms, they do not reduce disease progression. Thus, there is a need to identify new therapeutic targets. In this review, we summarize the potential of novel targets or tools, including anti-inflammatories, phosphodiesterase inhibitors, kinase inhibitors, transient receptor potential channels, vitamin D and protease inhibitors, for the treatment of asthma and COPD.


Draft genome sequences of two Aeromonas salmonicida subsp. salmonicida isolates harboring plasmids conferring antibiotic resistance.
The bacterium Aeromonas salmonicida is the etiological agent of furunculosis, a widespread fish disease causing important economic losses to the fish farming industry. Antibiotic treatments in fish farms may be challenging given the existence of multidrug-resistant isolates of this bacterium. Here, we report the draft genome sequences of the 2004-05MF26 and 2009-144K3 isolates, which harbor plasmids conferring antibiotic resistance. Both isolates also carry the large plasmid pAsa5, which is known to encode a type three secretion system (TTSS) and the pAsal1 plasmid which has the aopP gene producing a TTSS effector. These two isolates are good representatives of the plasmid diversity in A. salmonicida subsp. salmonicida.


Prosthetic Rehabilitation of Rhino Orbital Mucormycosis Associated with COVID-19: A Case Series.
Mucormycosis, a rare fungal infection seen in diabetes, is now very frequent owing to the deadly triad of COVID-19 infection, diabetes, and rampant use of corticosteroids. Immediate management revolves around therapeutic drugs like antifungals, antibiotics, and aggressive surgical debridement. The cases described in the article explain prosthetic rehabilitation of maxillectomy defects. The findings focus on prosthetic rehabilitation of patients with acquired maxillectomy defects after mucormycotic necrosis post-COVID-19 infection and the techniques to overcome the complications like lack of supporting tissues and post-surgical microstomia. The maxillectomies were performed on patients who suffered a superinfection of mucormycosis after COVID-19 contraction and uncontrolled blood sugar levels. Case 1 elaborates a technique to overcome the complications like lack of supporting structures and microstomia by fabrication of sectional and hollow obturator prostheses using sectional impression technique and lost salt technique. Case 2 explains the management of an extensive defect with a mobile soft tissue flap and lone standing tooth by using a functional impression technique to gain retention and support from the remaining soft and hard tissues. Both the techniques overcome the clinical complications and give predictable outcomes. Prosthetic rehabilitation of such challenging cases needs modifications depending upon the clinical challenges encountered.