A diagnostic rule for tuberculous meningitis.
Diagnostic confusion often exists between tuberculous meningitis and other meningoencephalitides. Newer diagnostic tests are unlikely to be available in many countries for some time. This study examines which clinical features and simple laboratory tests can differentiate tuberculous meningitis from other infections. Two hundred and thirty two children (110 tuberculous meningitis, 94 non-tuberculous meningitis, 28 indeterminate) with suspected meningitis and cerebrospinal fluid (CSF) pleocytosis were enrolled. Tuberculous meningitis was defined as positive CSF mycobacterial culture or acid fast bacilli stain, or basal enhancement or tuberculoma on computed tomography (CT) scan with clinical response to antituberculous treatment. Non-tuberculous meningitis was defined as positive CSF bacterial culture or Gram stain, or clinical response without antituberculous treatment. Thirty clinical/laboratory features of patients with tuberculous meningitis and non-tuberculous meningitis were compared by univariate and multiple logistic regression analysis. Five features were independently predictive of the diagnosis of tuberculous meningitis (p < 0.007): prodromal stage >/= 7 days, optic atrophy on fundal examination, focal deficit, abnormal movements, and CSF leucocytes < 50% polymorphs. When validated on another set of 128 patients, if at least one feature was present, sensitivity was 98.4% and, if three or more were present, specificity was 98.3%. This simple rule would be useful to physicians working in regions where tuberculosis is prevalent.


Lessons from intensified surveillance of viral hepatitis A, Israel, 2017 and 2018.
IntroductionUniversal vaccination of toddlers has led to very low hepatitis A (HAV) endemicity in Israel. However, sporadic outbreaks still occur, necessitating better surveillance.AimTo implement a comprehensive HAV surveillance programme.MethodsIn 2017 and 2018, sera from suspected HAV cases that tested positive for anti-HAV IgM antibodies were transferred to the Central Virology Laboratory (CVL) for molecular confirmation and genotyping. Sewage samples were collected in Israel and Palestine* and were molecularly analysed. All molecular (CVL), epidemiological (District Health Offices and Epidemiological Division) and clinical (treating physicians) data were combined and concordantly assessed.ResultsOverall, 146 cases (78 in 2017 and 68 in 2018, median age 34 years, 102 male) and 240 sewage samples were studied. Most cases (96%) were unvaccinated. In 2017, 89% of cases were male, 45% of whom were men who have sex with men (MSM). In 2018, 49% were male, but only 3% of them were MSM (p < 0.01). In 2017, 82% of cases and 63% of sewage samples were genotype 1A, phylogenetically associated with a global MSM-HAV outbreak. In 2018, 80% of cases and 71% of sewage samples were genotype 1B, related to the endemic strain previously identified in Israel and Palestine*. Environmental analysis revealed clustering of sewage and cases' sequences, and country-wide circulation of HAV.ConclusionsMolecular confirmation of HAV infection in cases and analysis of environmental samples, combined with clinical and epidemiological investigation, may improve HAV surveillance. Sequence-based typing of both clinical and sewage-derived samples could assist in understanding viral circulation.


Mechanism of central hyperglycemic effect of cholinergic agonists in fasted rats.
The influence of cholinergic agonists on central nervous system (CNS) regulation of blood sugar homeostasis was studied in fasted rats. When carbachol, muscarine, bethanechol, methacholine, or neostigmine was injected into the third cerebral ventricle, it caused a dose-dependent increase in the hepatic venous plasma glucose concentration. However, in the case of 1,1-dimethylphenyl-4-piperazinium iodide (DMPP) or nicotine, the level of hepatic venous glucose did not differ from that of the saline-treated control rats. The increase in glucose level caused by neostigmine was dose-dependently suppressed by coadministration of atropine. These facts suggest that cholinergic activation of muscarinic receptors in the CNS plays a role in increasing hepatic glucose output. Injection of neostigmine (5 X 10(-8) mol), an inhibitor of cholinesterase, into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norepinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through a femoral vein completely prevented the increase of glucagon after administration of neostigmine, although the increase of hepatic venous glucose and epinephrine levels were still observed. Neostigmine-induced increments in glucose did not occur in adrenalectomized rats. This suggests that the secreted epinephrine acts directly on the liver to increase hepatic glucose output.


Evaluation of percutaneous absorption of midazolam by terpenes.
Midazolam is a highly lipophilic drug that is widely used in preanesthetic medication. Recently, terpenes have been reported to show an enhancing effect on percutaneous absorption of drugs. The effect of terpenes (l-menthol, d-limonene, RS-(+/-)-beta-citronellol, geraniol) on the in vitro percutaneous absorption of midazolam through rat skin was evaluated using unjacketed Franz diffusion cells. Since midazolam is a lipophilic drug, percutaneous penetration is low and a percutaneous penetration enhancer is necessary for its percutaneous absorption. The terpenes (5%, w/v) in combination with 30% ethanol, and 20% propylene glycol significantly increased the percutaneous absorption of midazolam in comparison to the control. In vitro data suggested that d-limonene is the most effective enhancer among terpenes and other penetration enhancers such as Azone. In in vivo percutaneous absorption assays, the midazolam formulation using d-limonene could penetrate through rat skin, but the other terpenes could not penetrate. In conclusion, d-limonene in combination with ethanol can be used to enhance the percutaneous absorption of the highly lipophilic drug midazolam.


The Bacterial Gq Signal Transduction Inhibitor FR900359 Impairs Soil-Associated Nematodes.
The cyclic depsipeptide FR900359 (FR) is derived from the soil bacterium Chromobacterium vaccinii and known to bind Gq proteins of mammals and insects, thereby abolishing the signal transduction of their Gq protein-coupled receptors, a process that leads to severe physiological consequences. Due to their highly conserved structure, Gq family of proteins are a superior ecological target for FR producing organisms, resulting in a defense towards a broad range of harmful organisms. Here, we focus on the question whether bacteria like C. vaccinii are important factors in soil in that their secondary metabolites impair, e.g., plant harming organisms like nematodes. We prove that the Gq inhibitor FR is produced under soil-like conditions. Furthermore, FR inhibits heterologously expressed Gαq proteins of the nematodes Caenorhabditis elegans and Heterodera schachtii in the micromolar range. Additionally, in vivo experiments with C. elegans and the plant parasitic cyst nematode H. schachtii demonstrated that FR reduces locomotion of C. elegans and H. schachtii. Finally, egg-laying of C. elegans and hatching of juvenile stage 2 of H. schachtii from its cysts is inhibited by FR, suggesting that FR might reduce nematode dispersion and proliferation. This study supports the idea that C. vaccinii and its excreted metabolome in the soil might contribute to an ecological equilibrium, maintaining and establishing the successful growth of plants.


Metabolism of L-threonine and its relationship to sclerotium formation in Sclerotium rolfsii.
The activities of L-threonine dehydrogenase (I), 2-amino-3-oxybutyrate:CoA ligase (II), malate synthetase (III), isocitrate lyase (IV), glyoxylate dehydrogenase (V), glycine decarboxylase (VI), L-serine hydroxymethyltransferase (VII), glucan synthetase (VIII), glucose 6-phosphate dehydrogenase (IX) and succinic dehydrogenase (X) were detected in cell-free extracts prepared from the mycelium of the fungus Sclerotium rolfsii type R. Transfer of S. rolfsii to a threonine-containing medium resulted in a significant increase in the intracellular concentrations of L-threonine, glycine, serine and glyoxylate, and a decrease in oxalate. Incubation with 14C-labelled L-threonine resulted in an immediate output of 14CO2, and an accumulation of labelled glycine and serine in the mycelium. L-Threonine (10(-2)M) increased branching, favoured formation of sclerotia, and induced the formation of enzymes I to VIII, but not IX and X. Sodium oxalate (1-5 X 10(-2)M) inhibited branching, sclerotium formation and the activity of enzymes III and IV. Glycine (10(-1) M) inhibited branching, sclerotium formation and activity of I and II. Ammonium chloride (10(-1) to 10(-2) M) inhibited formation of sclerotia, threonine uptake and activity of III. Acetyl-CoA inhibited V and L-cysteine inhibited I as well as sclerotium formation and branching. It is suggested that hyphal morphogenesis and formation of sclerotia in S. rolfsii require an increased supply of carbohydrate intermediates and energy and that these are mainly supplied by the glyoxylate pathway.


Calcium supplementation and bone mineral accretion in Chinese adolescents aged 12-14 years: a 12-month, dose-response, randomised intervention trial.
A 12-month, dose-response, randomised, intervention trial was conducted to determine adequate Ca intake levels for Chinese adolescents by investigating the effect of Ca supplementation on bone mineral accretion. A total of 220 Han adolescents (111 girls and 109 boys) aged 12-14 years were recruited. All subjects were randomly divided into three groups. The bone mineral content (BMC) and bone mineral density (BMD) of the whole body, lumbar spine (L1-L4), left hip and femoral neck were measured by dual-energy X-ray absorptiometry. Girls in the high-Ca group (actual Ca intake: 1243 (sd 193) mg/d) exhibited greater increases in the femoral neck BMC compared with those in the low-Ca group (9·7 v. 6·4 %, P =0·04) over the 1-year intervention period. The increases in femoral neck BMC were greater in boys in the high-Ca and medium-Ca groups (actual Ca intake: 985 (sd 168) mg/d) than in those in the low-Ca group (15·7 v. 11·7 %, P =0·03; 15·8 v. 11·7 %, P =0·03). Ca supplementation had significant effects on the whole-body BMC and BMD in subjects with physical activity levels>34·86 metabolic equivalents and on the spine BMD and BMC and BMD of most sites in subjects with Tanner stage < 3. Increasing Ca intake levels with Ca supplementation enhanced femoral neck mineral acquisition in Chinese adolescents. Furthermore, high physical activity levels and low Tanner stage appeared to significantly contribute to the effect of Ca supplementation on bone mass. Whether this is a lasting beneficial effect leading to the optimisation of peak bone mass needs to be determined in other long-term prospective studies.


Independent verification of transferred delivery sinogram between two dosimetrically matched helical tomotherapy machines: a protocol for patient-specific quality assurance.
The purpose of this study was to independently verify the transferred delivery sinogram between two dosimetrically matched helical tomotherapy machines with the goal of eliminating redundant quality assurance (QA) measurements on the second machine. The equivalence of the two machines was evaluated based on both geometric and dosimetric beam characteristics, including measuring open field per cent depth doses (PDD), longitudinal and transverse profiles and helical delivery of clinical patient treatment plans measured in phantoms. QA of 56 patient plans was studied. The delivery sinogram on the secondary machine was computed by accounting for the differences in the MLC characteristics of the two machines. Computed sinograms were compared against the transferred sinograms by tomotherapy's data management system for the same 56 patient plans. The PDD, transverse and longitudinal dose profiles agreed within ±1% between the two machines. Ionization chamber and planar dose measurements with the Iba MatriXX device on both machines for the 56 patients were found to be within ±3% of the doses computed by the tomotherapy treatment planning system. For all 56 patients, the differences between computed sinograms and DMS-converted sinograms were within ±2%. The matched tomotherapy machines had similar beam characteristics. The sinogram-based QA was validated using point and planar dose measurements and found to be acceptable for clinical use.


The therapeutic relationship between a client and dietitian: A systematic integrative review of empirical literature.
Scientific evidence underpins dietetics practice; however, evidence of how the therapeutic relationship influences outcomes is limited. This integrative review aims to provide a comprehensive overview of the topic of the therapeutic relationship between clients and dietitians in the individual counselling context by summarising empirical literature into qualitative themes. An electronic literature search of the Cumulative Index of Nursing and Allied Health Literature, PsychInfo, Scopus and Web of Science databases was conducted in October 2018 and repeated in February 2021. Studies were included if they explicitly referred to the therapeutic relationship (or associated terms), were based on study data and available in full text. Extracted data were checked by a second researcher and the methodological quality was evaluated independently by two researchers using the Mixed Methods Appraisal Tool. An iterative process of qualitatively coding, categorising and comparing data to examine recurring themes was applied. Seventy-six studies met the inclusion criteria. Five themes were identified which showed the extent and nature of research in this area. Studies revealed the therapeutic relationship: (i) is valued within clinical dietetic practice, (ii) involves complex and multifactorial interactions, (iii) is perceived as having a positive influence, (iv) requires skills training and (v) is embedded in practice models and tools. Studies show the therapeutic relationship is a valued and multifactorial component of clinical dietetic practice and is perceived to positively influence the client and dietitian. Observational data are needed to assess the extent to which the strength of the therapeutic relationship might contribute to clients' health outcomes.


Excited-state symmetry breaking in quadrupolar pull-push-pull molecules: dicyanovinyl vs. cyanophenyl acceptors.
A significant number of quadrupolar dyes behave as their dipolar analogues when photoexcited in polar environments. This is due to the occurrence of excited-state symmetry breaking (ES-SB), upon which the electronic excitation, initially distributed over the whole molecule, localises preferentially on one side. Here, we investigate the ES-SB properties of two A-D-A dyes, consisting of a pyrrolo-pyrrole donor (D) and either cyanophenyl or dicyanovinyl acceptors (A). For this, we use time-resolved vibrational spectroscopy, comparing IR absorption and femtosecond stimulated Raman spectroscopies. Although dicyanovinyl is a stronger electron-withdrawing group, ES-SB is not observed with the dicyanovinyl-based dye even in highly polar media, whereas it already takes place in weakly polar solvents with dyes containing cyanophenyl accepting groups. This difference is attributed to the large electronic coupling between the D-A branches in the former dye, whose loss upon symmetry breaking cannot be counterbalanced by a gain in solvation energy. Comparison with analogues of the cyanophenyl-based dye containing different spacers reveals that interbranch coupling does not so much depend on the distance between the D-A subunits than on the nature of the spacer. We show that transient Raman spectra probe different modes of these centrosymmetric molecules but are consistent with the transient IR data. However, lifetime broadening of the Raman bands, probably due to the resonance enhancement, may limit the application of this technique for monitoring ES-SB.


simpleaf: A simple, flexible, and scalable framework for single-cell transcriptomics data processing using alevin-fry.
The alevin-fry ecosystem provides a robust and growing suite of programs for single-cell data processing. However, as new single-cell technologies are introduced, as the community continues to adjust best practices for data processing, and as the alevin-fry ecosystem itself expands and grows, it is becoming increasingly important to manage the complexity of alevin-fry 's single-cell preprocessing workflows while retaining the performance and flexibility that make these tools enticing. We introduce simpleaf , a program that simplifies the processing of single-cell data using tools from the alevin-fry ecosystem, and adds new functionality and capabilities, while retaining the flexibility and performance of the underlying tools. Simpleaf is written in Rust and released under a BSD 3-Clause license. It is freely available from its GitHub repository https://github.com/COMBINE-lab/simpleaf , and via bioconda. Documentation for simpleaf is available at https://simpleaf.readthedocs.io/en/latest/ and tutorials for simpleaf are being developed that can be accessed at https://combine-lab.github.io/alevin-fry-tutorials .


Focus on clinical practice: angiotensin-converting enzyme 2 and corona virus disease 2019: pathophysiology and clinical implications.
: ACE2 receptor has a broad expression pattern in the cellular membrane and provides a protective action against the development of cardiovascular diseases. Recently, this enzyme has become of extreme interest during the pandemic infection of COVID-19 (coronavirus disease 2019). This virus invades alveolar epithelium and cardiomyocytes using ACE2 as a transmembrane receptor. ACE2 is a counter-regulatory peptide that degrades Ang II into Ang 1-7, thereby attenuating the biological effects of the AT1 receptor. The binding between the spike protein of COVID-19 and the enzyme is crucial for the virus to enter the target cells, but whether an increase in ACE2 activity could facilitate the infection is not yet demonstrated. However, this aspect has raised many concerns about the use of ACE inhibitors or ARBs in infected patients or patients at risk of infection. It appears that cellular infection leads to a reduction in ACE2 expression and an increase in the activity of the Ang II--AT1 axis, which leads to the release of pro-inflammatory cytokines, ARDS, myocarditis, and hypercoagulability with the possibility of exacerbation of acute coronary syndrome, induction of pulmonary embolism, or appearance of disseminated intravascular coagulation. Therefore, ACE inhibitors or angiotensin receptor blocker drugs should be continued in infected patients, as their discontinuation can increase Ang II activity and induce injury to the lungs or cardiovascular system.


Discriminatory Value of Self-reported Olfactory Dysfunction in the Prediction of Coronavirus Disease 2019.
Objective Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), remains the world's largest public health concern in 2021. A history of close contact with infectious patients is a factor that predicts a positive SARS-CoV-2 test result. Meanwhile, the precise predictive value of symptoms suggestive of COVID-19 has not been fully elucidated. This study aimed to clarify the predictive and discriminatory value of each clinical symptom suggestive of COVID-19. Methods This study enrolled participants who were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction using a nasopharyngeal swab between November 2020 and January 2021. All enrolled patients were evaluated for data regarding the presence and closeness of contact with infectious patients and comprehensive clinical features (i.e., fever, cough, dyspnea, fatigue, dysosmia, and dysgeusia). Results Among the 1,744 tested participants, 144 tested positive for SARS-CoV-2. In the test-positive group, self-reported cough, fatigue, dysosmia, and dysgeusia were significant predictors of COVID-19, independent from a history of close contact. In particular, the presence of dysosmia was the strongest predictor of COVID-19 in both univariate and multivariate analyses. Among the 42 patients with self-reported dysosmia, 25 (59.5%) were SARS-CoV-2 test-positive. Self-reported dysosmia was reported by 25 (17.4%) of the 144 patients who tested positive for SARS-CoV-2, and 15 (60.0%) of the 25 COVID-19 patients with dysosmia had accompanying dysgeusia. Conclusion The presence of dysosmia was reported by 10-25% of patients with COVID-19, and is a significant predictor of COVID-19 infection, independent from a history of close contact.


Pax6 is implicated in murine pituitary endocrine function.
Pax6, an evolutionarily conserved transcription factor, is expressed in the murine and zebrafish embryonic pituitary, but its role in pituitary development and endocrine function has not been described. To study the role of Pax6 in vivo, we examined Pax6 mutant mouse (SeyNeu) pituitaries. Mice homozygous for the SeyNeu mutation die at birth; therefore, we examined peptide hormone expression by the differentiated pituitary cell types as well as developmental marker expression in the intermediate and anterior lobes of the embryonic pituitary. GH- and PRL-immunopositive cells appear severely decreased in an outbred ICR background at embryonic d 17.5, although mRNA expression of these peptide hormones is present, as is expression of other pituitary markers. This suggests that pituitary cell types are able to differentiate in mutant embryos. To identify the cellular or physiologic mechanism responsible for less GH- and PRL-immunoreactivity in Pax6 mutant mice, we tested serum levels of GH and PRL. Pax6 homozygous mutant mice have GH serum levels one fifth that of controls at embryonic d 17.5, and one-third that of controls at postnatal d 0. PRL serum levels, which are very low during embryonic and neonatal stages, were below assay detection limits in both the wild-type and mutant groups. Taken together, these data suggest that Pax6 is not essential for pituitary differentiation, but rather functions to establish appropriate neonatal homeostatic levels of GH and PRL, possibly through regulation of translational or secretory mechanisms.


Prospects and Aspirations for Workforce Training and Education in Social Prescribing.
A social prescribing (SP) link worker (LW) is responsible for enabling and supporting individuals, by assessing their personal goals and co-producing solutions to make use of appropriate local non-clinical resources or interventions. As an emerging new role, LWs are not regulated by professional bodies associated with SP. Therefore, currently there is no standardised training for LWs who are from varied backgrounds. As such, LWs have varying knowledge about how to deal with individuals with complex needs, which can impact on their decision-making capabilities to seek solutions and navigate complex systems. The purpose of the research was to explore LWs' level of education, past and current training requirements as well as elicit how much LWs were willing to pay (WTP) to access and undertake training to improve their skill set. A rigorous mixed method research design was employed which included semi-structured interviews with key stakeholders and quantitative questionnaires including contingent valuation (CV) questions to a population of LWs across Wales from March to June 2020. Qualitative interviews with key stakeholders who commission and deliver social prescribing interventions employing LWs identified perceived link worker qualities and requirements for LW roles. Purposive sampling was used to identify and select individuals that have experience in managing LWs. Due to the COVID-19 pandemic, interviews were carried out exclusively online. LWs self-selected to complete the online questionnaires. Questionnaires gathered data on LW qualifications and demographic information with the CV questions gathering data on the value LW placed on accessing training in SP. Thematic narrative analysis was applied to interpret the data from the semi-structured interviews. Descriptive frequency analysis was conducted on the quantitative data generated from the online questionnaire. SP coordinators (n = 6) reported that 'personal skills' are the most essential skills required by LWs in SP intervention. Training is available for LWs; however, the training undertaken varies depending on the type of intervention delivered, with 70% of LWs previously undertaking training to facilitate their development as an LW. The results from the contingent valuation questionnaire (n = 54) indicated that 100% of the respondents would avail of training. LWs were asked how much they were willing to pay as a single payment for professional training; on average, LWs were WTP GBP 58 from their personal funds to access training and the associated benefits to enhance their skills and knowledge. The semi-structured interviews conducted with the key SP stakeholders yielded rich information and novel insight into LW training. External funding for the salary of the LW is an obstacle for LW development through training. In addition, the questionnaire results regarding stated preference techniques demonstrate that LWs place value on their professional development and would be willing to spend their own money on training to improve their knowledge and skills.


Social Cognitive Processes Underlying Normative Misperception of Sexual Judgments.
Acquaintance-initiated sexually aggressive behavior (SAB) is a widespread problem on college campuses, and intervention strategies thus far have not produced sustained reductions in SAB. Peer-related social norms and cognitive processes underlying sexual decision-making have separately been implicated in SAB. The present study integrates this work by examining the effect of perspective (self vs. typical college male referent) on college men's judgments of the justifiability of unwanted sexual advances, determining the cognitive processes underlying men's misperceptions, and evaluating rape-supportive attitudes (RSA) as a correlate of the implicated processes. College men attracted to women (n = 217) completed the Heterosocial Perception Survey-Revised, in which they judged the justifiability of a man's increasingly intimate sexual advances as a woman responds increasingly negatively. Participants completed the Heterosocial Perception Survey-Revised from their own perspective and from the typical college male perspective. Participants also completed questionnaires assessing RSA and demographics. Undergraduate men, and particularly those endorsing more RSA, greatly overestimated how much the typical college male perceives increasingly nonconsensual behavior as justified. Three cognitive processes were strongly implicated in this misperception. When responding from the self-perspective, RSA correlated significantly with all cognitive processes. These findings illustrate the utility of integrating work on social norms and cognitive processing to document the global effect of perspective on average justifiability ratings and the perspective effect on cognitive processes underlying the ratings. Future work should evaluate personalized normative feedback and cognitive-training approaches to target misperceptions of peers' sexual judgments, given the well-established relation between sexual misperception and SAB risk.


MiRNA-130a promotes inflammation to accelerate atherosclerosis via the regulation of proliferator-activated receptor γ (PPARγ) expression.
In this study, we aimed to evaluate the possible function of miR-130a in atherosclerosis (AS), protection against AS, and its molecular biological mechanism. Apoe-/- mice were fed a high-fat diet as the AS mice model. Human umbilical vein endothelial cells (HUVECs) were used as in vitro model. Serum samples or cells were used to measure the expression of inflammation. Serum samples or cells were used to determine MiRNA expression profiles using the edgeR tool from Bioconductor. Western Blot analysis was used to assess protein expressions of proliferator-activated receptor γ (PPARγ) and nuclear factor (NF)-κB. MiRNA-130a expression was up-regulated in atherosclerotic mice. In addition, over-expression of miRNA-130a promoted inflammation factors [tumor necrosis factor (TNF)-α and interleukin (IL)-1β, IL-6, and IL-8] in the in vitro model of AS. However, down-regulation of miRNA-130a reduced inflammation (suppressed TNF-α, IL-1β, IL-6 and IL-8) in the in vitro model. Furthermore, over-expression of miRNA-130a could also suppress the protein expression of PPARγ and induce NF-κB protein expression in the in vitro model. However, suppression of miRNA-130a induced the protein expression of PPARγ and suppressed NF-κB protein expression in the in vitro model of AS. Activation of PPARγ reduced the pro-inflammatory effects of miRNA-130a on the AS-induced in vitro model. These results strongly support that miRNA-130a suppression can protect against atherosclerosis through inhibiting inflammation by regulating the PPARγ/ NF-κB expression.


Probing the contribution of individual polypeptide GalNAc-transferase isoforms to the O-glycoproteome by inducible expression in isogenic cell lines.
The GalNAc-type O-glycoproteome is orchestrated by a large family of polypeptide GalNAc-transferase isoenzymes (GalNAc-Ts) with partially overlapping contributions to the O-glycoproteome besides distinct nonredundant functions. Increasing evidence indicates that individual GalNAc-Ts co-regulate and fine-tune specific protein functions in health and disease, and deficiencies in individual GALNT genes underlie congenital diseases with distinct phenotypes. Studies of GalNAc-T specificities have mainly been performed with in vitro enzyme assays using short peptide substrates, but recently quantitative differential O-glycoproteomics of isogenic cells with and without GALNT genes has enabled a more unbiased exploration of the nonredundant contributions of individual GalNAc-Ts. Both approaches suggest that fairly small subsets of O-glycosites are nonredundantly regulated by specific GalNAc-Ts, but how these isoenzymes orchestrate regulation among competing redundant substrates is unclear. To explore this, here we developed isogenic cell model systems with Tet-On inducible expression of two GalNAc-T genes, GALNT2 and GALNT11, in a knockout background in HEK293 cells. Using quantitative O-glycoproteomics with tandem-mass-tag (TMT) labeling, we found that isoform-specific glycosites are glycosylated in a dose-dependent manner and that induction of GalNAc-T2 or -T11 produces discrete glycosylation effects without affecting the major part of the O-glycoproteome. These results support previous findings indicating that individual GalNAc-T isoenzymes can serve in fine-tuned regulation of distinct protein functions.


Dental caries in South Pacific populations: a review.
Dental caries (tooth decay) was uncommon in Pacific Island communities before European trading and migration expanded into the Region. The etiology of this oral microbial disease is a consequence of changed diets, food preparation and lifestyle. In particular, the easy availability of a high level of frequent dietary supplementation with refined sucrose (sugar) and carbohydrates is the key factor in the etiology of tooth decay. While tooth decay initially developed as a health problem in the more accessible Pacific islands over a century ago, it has spread increasingly as trading, travel and cash economies have developed to include even the more geographically remote communities. In this review selected epidemiological data are presented to show the magnitude, variation and secular changes in the prevalence of tooth decay in different communities. Tooth decay in conjunction with the historically endemic adult gum diseases poses a major public health problem in terms of pain, premature loss of teeth and the need for oral rehabilitation. Implementation and monitoring of caries control programs is a priority need in most communities. It is impractical to consider a return to indigenous diets and lifestyles as a strategy for caries prevention. Instead promotion of proven modern community preventive programmes, notably appropriate use of fluorides, 'fissure sealants' together with control of excessive consumption of diets rich in refined sugar is required if a significant increase in the levels of tooth decay is to be avoided.


Tension-compression loading with chemical stimulation results in additive increases to functional properties of anatomic meniscal constructs.
This study aimed to improve the functional properties of anatomically-shaped meniscus constructs through simultaneous tension and compression mechanical stimulation in conjunction with chemical stimulation. Scaffoldless meniscal constructs were subjected to simultaneous tension and compressive stimulation and chemical stimulation. The temporal aspect of mechanical loading was studied by employing two separate five day stimulation periods. Chemical stimulation consisted of the application of a catabolic GAG-depleting enzyme, chondroitinase ABC (C-ABC), and an anabolic growth factor, TGF-β1. Mechanical and chemical stimulation combinations were studied through a full-factorial experimental design and assessed for histological, biochemical, and biomechanical properties following 4 wks of culture. Mechanical loading applied from days 10-14 resulted in significant increases in compressive, tensile, and biochemical properties of meniscal constructs. When mechanical and chemical stimuli were combined significant additive increases in collagen per wet weight (4-fold), compressive instantaneous (3-fold) and relaxation (2-fold) moduli, and tensile moduli in the circumferential (4-fold) and radial (6-fold) directions were obtained. This study demonstrates that a stimulation regimen of simultaneous tension and compression mechanical stimulation, C-ABC, and TGF-β1 is able to create anatomic meniscus constructs replicating the compressive mechanical properties, and collagen and GAG content of native tissue. In addition, this study significantly advances meniscus tissue engineering by being the first to apply simultaneous tension and compression mechanical stimulation and observe enhancement of tensile and compressive properties following mechanical stimulation.


Contemporary evaluation and management of parapharyngeal space neoplasms.
This review summarises the contemporary, multidisciplinary approach to managing parapharyngeal space neoplasms. Parapharyngeal space neoplasms are uncommon head and neck tumours and are most often benign. Most tumours are of either salivary gland or neurogenic origin. Patients tend to be asymptomatic even when tumours reach large sizes. Patients may present with a mass in the pharynx or neck, although frequently the tumour is found incidentally on an imaging study. Due to the limitations of physical examination in this anatomical area, imaging studies are essential to the evaluation of parapharyngeal space neoplasms. Cytopathology may provide additional diagnostic information. Open biopsy is rarely necessary and can be hazardous. Treatment is primarily surgical, and various surgical approaches can be tailored for a given neoplasm. Recently, a trend toward observation of select patients with asymptomatic neurogenic tumours has been advocated. The evaluation and management of parapharyngeal space tumours is best done by a multidisciplinary team. Treatment should be individualised, and the risks and benefits of surgical intervention need to be carefully weighed. Complications are best avoided by careful surgical planning.


The effect of H2 : N2 ratio on the NH3 synthesis rate and on process economics over the Co3Mo3N catalyst.
In this study, the process economics of ammonia synthesis over Co3Mo3N was investigated by searching for an optimum feed stoichiometry. From ammonia synthesis rate measurements at atmospheric pressure and 400 °C over Co3Mo3N, it was found that the rate was independent of H2 : N2 stoichiometry for stoichiometries above 0.5 : 1. For H2 : N2 stoichiometries below 0.5 : 1, there was a linear dependency of ammonia synthesis rate on the H2 : N2 stoichiometry. Static measurements of hydrogen adsorption isotherms at 25, 50, and 100 °C revealed that the adsorbed amounts of strongly bound hydrogen over the Co3Mo3N surface were saturated at around 100 Torr hydrogen pressure. This pressure corresponds to the partial pressure of hydrogen when the H2 : N2 stoichiometry is around 0.5 : 1, confirming the role of strongly bound hydrogen in ammonia synthesis. These results were used to modify an existing kinetic expression to be used in a conceptual design, based on a late mixing strategy for the hydrogen stream. This conceptual design and its economic analysis revealed that using low hydrogen stoichiometries can cut the investment and operating costs by a factor of 2.


Perceptions and practice of health care workers regarding hepatitis B vaccination, Bouaké, Côte d'Ivoire, 2016.
Barriers to immunization are seen in both the general population and the health care workforce. We conducted this study to determine the perception of health workers on vaccination and the immunization of their patients. This cross-sectional descriptive analytical study was carried out among the medical staff in Bouaké, from 10 January to 07 March 2016. The data collected from the interviews were analyzed using Epi info 2000 software and SPSS 17.0. The Chi-2 test and logistic regression were performed and the significance threshold of the tests was 5%. The vaccination status of the 291 health care workers (HCWs) for the hepatitis B virus (HBV) was statistically related to their participation in the course in vaccination during their training (ORa = 1.69, 95% CI: 1.04-2.75 P<0.05) and the systematic verification of the vaccination status of the patient was statistically related to the vaccination status of the HCW (ORa = 4.33, 95% CI: 2.97-8.18, P<0.05). Promoting the vaccination among the population should be dependent on the promotion among HCWs.


Stochastic motion and transcriptional dynamics of pairs of distal DNA loci on a compacted chromosome.
Chromosomes in the eukaryotic nucleus are highly compacted. However, for many functional processes, including transcription initiation, the pairwise motion of distal chromosomal elements such as enhancers and promoters is essential and necessitates dynamic fluidity. Here, we used a live-imaging assay to simultaneously measure the positions of pairs of enhancers and promoters and their transcriptional output while systematically varying the genomic separation between these two DNA loci. Our analysis reveals the coexistence of a compact globular organization and fast subdiffusive dynamics. These combined features cause an anomalous scaling of polymer relaxation times with genomic separation leading to long-ranged correlations. Thus, encounter times of DNA loci are much less dependent on genomic distance than predicted by existing polymer models, with potential consequences for eukaryotic gene expression.


[Development and use of periodontal dressing of collagen and Lactobacillus casei 37 cell suspension in combined treatment of periodontal disease of inflammatory origin (a microbiological study)].
Periodontal dressing consisting of collagen and Lactobacillus casei 37 cell suspension (cell concentration 108 cells/ml) was created and used in combined treatment of patients with chronic generalized parodontitis. Efficacy of the developed isolation was explained by a considerable decrease of the number and frequency of isolation of aggressive microbial representatives (pigment synthesizing Bacteroids, Actinomyces and Str. intermedius) in periodontal pockets and also Fungus (Candida albicans). This periodontal dressing provided remission up to 10-12 months.


RNTCP 2007: looking ahead to future challenges.
The largest TB control programme in terms of patients treated is India's Revised National Tuberculosis Control Programme (RNTCP). The treatment success of new smear positive TB cases under RNTCP has exceeded the global benchmark of 85%. Also there are some challenges in TB control programme eg, addressing TB in HIV-infected persons and accurate diagnosis and management of multidrug resistant TB (MDR-TB). Diagnosis of MDR-TB requires sophisticated laboratories. If MDR-TB is not managed effectively, then there is possibility to emerge drug-resistant TB which is virtually untreatable. The Public-Private mix initiatives of RNTCP attempt to make quality assured treatment for TB for all patients, regardless of healthcare providers they choose. The International Standards of TB Care (ISTC) is an international effort which has articulated the diagnostic, treatment and public health standards which all providers should hold themselves and their peers accountable to. For providers the path to practise the ISTC is to diagnose and treat patients in collaboration with RNTCP. The IMA has taken up the cause of TB control in India very seriously. This organisation of the doctors (IMA) deserves recognition for becoming the first professional association to endorse the ISTC in India. All health providers should work with and support the RNTCP, so that the programme can be made into a genuine mass movement to fight TB.


Perioperative immunonutrition ameliorates the postoperative immune depression in patients with gastrointestinal system cancer (prospective clinical study in 42 patients).
Cancer surgery is a major challenge for patients to develop immune depression in postoperative period. Several cytokines can depress immune cell subpopulations. Increased cytokine response after surgery is assumed to arise mainly from lipooxygenase pathway acting on membrane arachidonic acid. Therefore; investigators focused their efforts to alter the membrane fatty acid profile by changing the nutritional regimen with epsilon-3 fatty acid supplementation and encouraging results were obtained after surgery. Despite the theoretical and clinical advantage of enteral nutrition many surgeons remain committed to parenteral nutrition for feeding of patients due to maintain bowel rest and fear of anastomosis leakage at the postoperative period. Several studies investigating role of the postoperative immunonutrition reported that beneficial immunological changes were associated with reduction of infectious complications. Interestingly; these findings were observed at least five days after the surgery in which the highest incidence of complications was seen. In this prospective study including 42 patients eligible for curative gastric or colon cancer surgery; we investigated the beneficial effect of enteral immunonutrition (EEN) compared to total parenteral hyperalimentation (TPN) beginning from the preoperative period. Cortisol and CRP levels as stress parameters significantly increased one day after surgery in both groups but they rapidly returned to (on POD1) preoperative baseline level in EEN group whereas these values remained high in the TPN group. Additionally a significant decrease in natural killer (NK) cells and CD8+ levels were observed in both groups. However they recovered on POD3 in EEN group and on POD6 in TPN group. CD4+ subset remained almost same as preoperative value in the TPN group whereas it increased from (%) 40.14 to 46.40, 51.29 and 54.7 on PO 6th hr, POD3 and POD6 in the EEN group. Our findings suggest that preoperative nutrition via the enteral route provided better regulation of postoperative immune system restoration than parenteral nutrition. On the basis of our findings we recommend enteral immunonutrition to be started at the preoperative period rather than postoperatively before a major operation whenever the enteral route is feasible.


Outcome and prognosis of myelopathy and radiculopathy from osteochondroma in the mobile spine: a report on 14 patients.
A retrospective study of 14 spinal osteochondroma (OC) patients with compressive myelopathy or radiculopathy who underwent excision of the lesions. To evaluate the surgical results of a series of cases of symptomatic OCs and the risk of recurrence and malignant transformation in the mobile spine. Intraspinal OC with symptomatic spinal cord or nerve root compression is a rare disease. Most of the lesions require surgical treatment. However, some patients may relapse or malignant transformation may occur after surgery. Fourteen symptomatic spinal OC cases, including 2 hereditary multiple exostoses, were treated surgically from 2001 to 2010. The clinical history, plain radiographs, computed tomography, magnetic resonance imaging, pathologic characteristics, surgical treatments, and outcomes were reviewed. All the patients were followed up for an average of 48.9 months. The 14 patients included 8 with lesions in the cervical spine, 3 with lesions in the thoracic spine, and 2 with lesions in the lumbar spine. One patient had a particularly large lesion which extended from C7 to T6. The OCs originated from the lamina (4), lateral mass (3), vertebral body (3), processus transversus (1), spinous process (1), pedicle of vertebral arch (1), and an indeterminate location (1). Six patients presented with myelopathy from spinal cord compression and 8 with radiculopathy from nerve root compression. Operative approaches included posterior (11) and combined posterior anterior (3) patients. The surgical outcome was satisfactory in 79% (11) of patients. Two recurrent lesions were notable for sarcomatous transformation. We recommend gross total resection of all diagnosed OCs involving the mobile spine because of the risk of malignant transformation. Early detection and total excision of symptomatic spinal lesions in these cases may be the key to providing the best outcome. The neurological defect arising from OC can be improved by surgical intervention in most patients.


[Effect of 2 methods of occlusion adjustment on occlusal balance and muscles of mastication in patient with implant restoration].
To compare the effect of 2 methods of occlusion adjustment on occlusal balance and muscles of mastication in patients with dental implant restoration. Twenty patients, each with a single edentulous posterior dentition with no distal dentition were selected, and divided into 2 groups. Patients in group A underwent original occlusion adjustment method and patients in group B underwent occlusal plane reduction technique. Ankylos implants were implanted in the edentulous space in each patient and restored with fixed prosthodontics single unit crown. Occlusion was adjusted in each restoration accordingly. Electromyograms were conducted to determine the effect of adjustment methods on occlusion and muscles of mastication 3 months and 6 months after initial restoration and adjustment. Data was collected and measurements for balanced occlusal measuring standards were obtained, including central occlusion force (COF), asymmetry index of molar occlusal force(AMOF). Balanced muscles of mastication measuring standards were also obtained including measurements from electromyogram for the muscles of mastication and the anterior bundle of the temporalis muscle at the mandibular rest position, average electromyogram measurements of the anterior bundle of the temporalis muscle at the intercuspal position(ICP), Astot, masseter muscle asymmetry index, and anterior temporalis asymmetry index (ASTA). Statistical analysis was performed using Student 's t test with SPSS 18.0 software package. Three months after occlusion adjustment, parameters of the original occlusion adjustment method were significantly different between group A and group B in balanced occlusal measuring standards and balanced muscles of mastication measuring standards. Six months after occlusion adjustment, parameters of the original occlusion adjustment methods were significantly different between group A and group B in balanced muscles of mastication measuring standards, but was no significant difference in balanced occlusal measuring standards. Using occlusion plane reduction adjustment technique, it is possible to obtain occlusion index and muscles of mastication's electromyogram index similar to the opposite side's natural dentition in patients with single unit fix prosthodontics crown and single posterior edentulous dentition without distal dentitions.


Improvements in Classification of Left and Right Foot Motor Intention Using Modulated Steady-State Somatosensory Evoked Potential Induced by Electrical Stimulation and Motor Imagery.
In recent years, motor imagery-based brain-computer interface (MI-BCI) has been applied to motor rehabilitation in patients with motor dysfunction. However, traditional MI-BCI is rarely used for foot motor intention recognition because the motor cortex regions of both feet are anatomically close to each other, and traditional event-related desynchronization (ERD) patterns for MI-BCI have insufficient spatial discrimination. This study introduced steady-state somatosensory evoked potentials (SSSEPs) by synchronous bilateral feet electrical stimulation at different frequencies, which were used as carrier signals modulated by unilateral foot motor intention. Fifteen subjects participated in MI and MI-SSSEP tasks. A Riemannian geometry classifier with a task-related component analysis (TRCA) spatial filter was proposed to demodulate the variation in SSSEP features and discriminate the left and right foot motor intentions. The feature outcomes indicated that the amplitude and phase synchronization of the SSSEPs could be well modulated by unilateral foot MI tasks under the MI-SSSEP paradigm. The classification results revealed that the modulated SSSEP features played an important role in the recognition of left-right foot discrimination. Moreover, the proposed TRCA-based method outperformed the other three methods and improved the foot average classification accuracy to 81.07± 13.29%, with the highest accuracy attained at 97.00%. Compared with the traditional MI paradigm, the foot motor intention recognition accuracy of the MI-SSSEP paradigm was significantly improved, from nearly 60% to more than 80%. This work provides a practical method for left-right foot motor intention recognition and expands the application of MI-BCI in the field of lower-extremity motor function rehabilitation.


Elderly trauma patients with rib fractures are at greater risk of death and pneumonia.
The purpose of this study was to show that elderly patients admitted with rib fractures after blunt trauma have increased mortality. Demographic, injury severity, and outcome data on a cohort of consecutive adult trauma admissions with rib fractures to a tertiary care trauma center from April 1, 1993, to March 31, 2000, were extracted from our trauma registry. Among 4,325 blunt trauma admissions, there were 405 (9.4%) patients with rib fractures; 113 were aged > or = 65. Injuries were severe, with Injury Severity Score (ISS) > or = 16 in 54.8% of cases, a mean hospital stay of 26.8 +/- 43.7 days, and 28.6% of patients requiring mechanical ventilation. Mortality (19.5% vs. 9.3%; p < 0.05), presence of comorbidity (61.1% vs. 8.6%; p < 0.0001), and falls (14.6% vs. 0.7%; p < 0.0001) were significantly higher in patients aged > or = 65 despite significantly lower ISS (p = 0.031), higher Glasgow Coma Scale score (p = 0.0003), and higher Revised Trauma Score (p < 0.0001). After adjusting for severity (i.e., ISS and Revised Trauma Score), comorbidity, and multiple rib fractures, patients aged > or = 65 had five times the odds of dying when compared with those < 65 years old. Despite lower indices of injury severity, even after taking account of comorbidities, mortality was significantly increased in elderly patients admitted to a trauma center with rib fractures.


Impedance-Based Single-Cell Pipetting.
Many biological methods are based on single-cell isolation. In single-cell line development, the gold standard involves the dilution of cells by means of a pipet. This process is time-consuming as it is repeated over several weeks to ensure clonality. Here, we report the modeling, designing, and testing of a disposable pipet tip integrating a cell sensor based on the Coulter principle. We investigate, test, and discuss the effects of design parameters on the sensor performances with an analytical model. We also describe a system that enables the dispensing of single cells using an instrumented pipet coupled with the sensing tip. Most importantly, this system allows the recording of an impedance trace to be used as proof of single-cell isolation. We assess the performances of the system with beads and cells. Finally, we show that the electrical detection has no effect on cell viability.


Discovery and Structure-Activity-Relationship Study of N-Alkyl-5-hydroxypyrimidinone Carboxamides as Novel Antitubercular Agents Targeting Decaprenylphosphoryl-β-d-ribose 2'-Oxidase.
Magnesium plays an important role in infection with Mycobacterium tuberculosis ( Mtb) as a signal of the extracellular environment, as a cofactor for many enzymes, and as a structural element in important macromolecules. Raltegravir, an antiretroviral drug that inhibits HIV-1 integrase is known to derive its potency from selective sequestration of active-site magnesium ions in addition to binding to a hydrophobic pocket. In order to determine if essential Mtb-related phosphoryl transfers could be disrupted in a similar manner, a directed screen of known molecules with integrase inhibitor-like pharmacophores ( N-alkyl-5-hydroxypyrimidinone carboxamides) was performed. Initial hits afforded compounds with low-micromolar potency against Mtb, acceptable cytotoxicity and PK characteristics, and robust SAR. Elucidation of the target of these compounds revealed that they lacked magnesium dependence and instead disappointingly inhibited a known promiscuous target in Mtb, decaprenylphosphoryl-β-d-ribose 2'-oxidase (DprE1, Rv3790).


Perspectives in medical education. 3. Reforming medical education to change healthcare practice in Japan.
The enviable health status of Japanese citizens is one of the reasons for obdurate opposition to reform of Japanese healthcare practice. Change is widely believed to be unnecessary for a system that is both successful and profitably exploited to universal benefit. However, societal trends are conspiring to make current healthcare practice patterns and expenditures unsustainable in the future. In particular, Japan has undergone an unprecedented demographic shift from a society of young (and healthy) workers to one of older retirees with a higher prevalence of obesity. As a result, an equally dramatic future increase can be anticipated in the prevalence of age- and obesity-related disorders. The traditional paradigm of Japanese healthcare is not conducive to the restraint necessary for preserving its future viability, given these trends. Japanese healthcare does not reward clinical problem-solving skills, values specialists over generalists, places a heavy reliance on expensive technology, does not require interventions to be evidence-based, and provides no incentives to improve quality or efficiency. If this paradigm endures, Japanese healthcare faces the real prospect of bankruptcy. The failure of Japanese medical education to inculcate clinical skills and stress evidence-based medical practice lies at the heart of the impending crisis in healthcare. To solve the crisis, medical education in Japan must change its focus to training and developing a cadre of physicians with the broad-based expertise and clinical skills to make evidence-based decisions in a medically and fiscally responsible manner. The future health of the system and of the Japanese people depends on it.


Serum bisphenol A and progression of type 2 diabetic nephropathy: a 6-year prospective study.
Bisphenol A (BPA) is associated with diabetes and cardiovascular diseases. The aim of our study was to evaluate whether serum BPA could predict the progression of chronic kidney disease (CKD) in patients with type 2 diabetes (T2D). In this prospective study, a total of 121 patients with T2D and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m(2) were followed up for 6 years. The baseline values of serum BPA were measured. Renal function was measured as eGFR calculated by the Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation. Development of CKD was defined as eGFR < 60 mL/min/1.73 m(2) at the last follow-up. Regression models were used to analyze the associations of serum BPA with the change in eGFR and the risk of CKD development. Baseline serum BPA concentration was 0.40 (0.17, 1.40) ng/mL. Duration of T2D, baseline waist circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, and serum BPA level were significantly negatively associated with the annual change and percentage change in eGFR. After adjusting for clinical factors, baseline serum BPA level had a significant negative association with the annual change in eGFR (β = -0.371, P < 0.001) and percentage change in eGFR (β = -0.391, P = <0.001). Multivariate logistic regression analysis showed that patients with high levels of serum BPA exhibited about a sevenfold increased risk of developing CKD compared to patients with low levels of serum BPA [odds ratio (OR) 6.65 (95 % CI 1.47, 30.04), P = 0.014]. Serum BPA may be a predictor of CKD in patients with T2D.


High SGO2 predicted poor prognosis and high therapeutic value of lung adenocarcinoma and promoted cell proliferation, migration, invasion, and epithelial-to-mesenchymal transformation.
Background: Shugoshin 2 (SGO2), a component of the cell division cohesion complex, is involved in both mitotic and meiotic processes. Despite being overexpressed in various malignant tumors and is associated with poor prognosis, its exact role in lung adenocarcinoma (LUAD) and its biological effects on lung cancer cells are not well understood. Methods: The transcriptomics data and clinical information for LUAD were obtained from TCGA and GEO, and DEGs associated with prognostic risk factors were screened using Cox regression analysis and chi-square testing. Identify these gene functions using correlation heatmaps, protein interaction networks (PPIs), and KEGG enrichment assays. The expression of SGO2 in tissues was verified by PCR and IHC, and the prognostic value of SGO2 in LUAD was evaluated by survival analysis. In addition, the effects of SGO2 knockdown on lung cancer cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) were studied in vitro. After that, the TIMER database and single-sample GSEA (ssGSEA) analysis were used to investigate the correlation between SGO2 and immune infiltration. Finally, the tumor mutational burden (TMB) of different SGO2 clusters and the efficacy of the two clusters in multiple treatments were evaluated. Results: High-risk genes associated with poor prognosis in LUAD are involved in cell cycle regulation and proliferation. Among these genes, SGO2 exhibited high expression in LUAD and corresponded with the TNM stage. Furthermore, the knockdown of SGO2 led to a decrease in the proliferation, migration, invasion, and EMT processes of lung cancer cells. Notably, high SGO2 expression may have poorer anti-tumor immunity and may therefore be more suitable for immunotherapy to re-establish immune function, while its high expression with a higher TMB could enable LUAD to benefit from multiple therapies. Conclusion: Our findings suggest that SGO2 may be a promising prognostic biomarker for LUAD, particularly in regulating the cell cycle and benefiting from multiple therapies.


Malignant solitary fibrous tumor with high-grade nuclear atypia: an alternate entity for the undetermined tumor group.
Recently, a novel fusion transcript, NAB2-STAT6, and its variants have also been reported to be specific diagnostic markers for solitary fibrous tumors (SFTs). In this study, we validated the existence of the NAB2-STAT6 fusion gene in SFTs and examined its relation with the pathological features. Frozen samples from 9 tumors were assessed for fusion gene. The detected fusion genes exhibited large intron sequences and the insertion of unknown and previously unreported sequences. The fusion genes were not detected in the 2 malignant cases with high-grade nuclear atypia, nuclear pleomorphism and necrosis, that was confirmed by multiplex PCR method. In addition, 1 of the 2 NAB2-STAT6 fusion gene-negative tumors showed amplification of the MDM2 and CDK4 genes. It was suggested that a certain proportion of tumors previously diagnosed as malignant SFTs with high-grade nuclear atypia lacking NAB2-STAT6 should be categorized into a special subtype of SFT, which is genetically different from conventional SFTs, and which cannot be apparently distinguished from dedifferentiated liposarcoma or undifferentiated pleomorphic sarcoma.


The Impact of a Care Recipient's Pet on the Instrumental Caregiving Experience.
Older adults report strong emotional bonds with their pets which often become increasingly important as health declines and dependence upon others increases. Individuals requiring assistance meeting their own needs are likely to need assistance in meeting the needs of their pet. The care recipient's pet may be an important, though presently overlooked, factor in the caregiving experience. This study measured the amount of care tasks/ activities informal caregivers of older adults devoted to their care recipients' pet. Caregivers for an individual aged 50 and older who did not consider the care recipient's pet to be his/her own animal completed an online questionnaire. Descriptive statistics and Pearson correlations were used in analyses. Caregivers (N = 34) performed an average of 14.9 (SD = 5.4) different pet care tasks/activities and an average of 11.21 (SD = 1.33) hours per week in pet care. The total number of tasks/activities performed was significantly and positively correlated with the care recipients' degree of functional limitation (r = 0.49, p = 0.004). Care recipients' pets may be a significant factor in shaping the instrumental caregiving experience.


Health care seeking for maternal and newborn illnesses in low- and middle-income countries: a systematic review of observational and qualitative studies.
Background: In low- and middle-income countries, a large number of maternal and newborn deaths occur due to delays in health care seeking. These delays occur at three levels i.e. delay in making decision to seek care, delay in access to care, and delay in receiving care. Factors that cause delays are therefore need to be understand to prevent and avoid these delays to improve health and survival of mothers and babies. Methods: A systematic review of observational and qualitative studies to identify factors and barriers associated with delays in health care seeking. Results: A total of 159 observational and qualitative studies met the inclusion criteria. The review of observational and qualitative studies identified social, cultural and health services factors that contribute to delays in health care seeking, and influence decisions to seek care. Timely recognition of danger signs, availability of finances to arrange for transport and affordability of health care cost, and accessibility to a health facility were some of these factors. Conclusions: Effective dealing of factors that contribute to delays in health care seeking would lead to significant improvements in mortality, morbidity and care seeking outcomes, particularly in countries that share a major brunt of maternal and newborn morbidity and mortality. Registration: PROSPERO CRD42012003236.


Continuous Negative Abdominal Pressure Reduces Ventilator-induced Lung Injury in a Porcine Model.
In supine patients with acute respiratory distress syndrome, the lung typically partitions into regions of dorsal atelectasis and ventral aeration ("baby lung"). Positive airway pressure is often used to recruit atelectasis, but often overinflates ventral (already aerated) regions. A novel approach to selective recruitment of dorsal atelectasis is by "continuous negative abdominal pressure." A randomized laboratory study was performed in anesthetized pigs. Lung injury was induced by surfactant lavage followed by 1 h of injurious mechanical ventilation. Randomization (five pigs in each group) was to positive end-expiratory pressure (PEEP) alone or PEEP with continuous negative abdominal pressure (-5 cm H2O via a plexiglass chamber enclosing hindlimbs, pelvis, and abdomen), followed by 4 h of injurious ventilation (high tidal volume, 20 ml/kg; low expiratory transpulmonary pressure, -3 cm H2O). The level of PEEP at the start was ≈7 (vs. ≈3) cm H2O in the PEEP (vs. PEEP plus continuous negative abdominal pressure) groups. Esophageal pressure, hemodynamics, and electrical impedance tomography were recorded, and injury determined by lung wet/dry weight ratio and interleukin-6 expression. All animals survived, but cardiac output was decreased in the PEEP group. Addition of continuous negative abdominal pressure to PEEP resulted in greater oxygenation (PaO2/fractional inspired oxygen 316 ± 134 vs. 80 ± 24 mmHg at 4 h, P = 0.005), compliance (14.2 ± 3.0 vs. 10.3 ± 2.2 ml/cm H2O, P = 0.049), and homogeneity of ventilation, with less pulmonary edema (≈10% less) and interleukin-6 expression (≈30% less). Continuous negative abdominal pressure added to PEEP reduces ventilator-induced lung injury in a pig model compared with PEEP alone, despite targeting identical expiratory transpulmonary pressure.


Restoring Vision in Adverse Weather Conditions With Patch-Based Denoising Diffusion Models.
Image restoration under adverse weather conditions has been of significant interest for various computer vision applications. Recent successful methods rely on the current progress in deep neural network architectural designs (e.g., with vision transformers). Motivated by the recent progress achieved with state-of-the-art conditional generative models, we present a novel patch-based image restoration algorithm based on denoising diffusion probabilistic models. Our patch-based diffusion modeling approach enables size-agnostic image restoration by using a guided denoising process with smoothed noise estimates across overlapping patches during inference. We empirically evaluate our model on benchmark datasets for image desnowing, combined deraining and dehazing, and raindrop removal. We demonstrate our approach to achieve state-of-the-art performances on both weather-specific and multi-weather image restoration, and experimentally show strong generalization to real-world test images.


The Second Case of Saposin A Deficiency and Altered Autophagy.
Krabbe disease is a lysosomal storage disease caused by galactosylceramidase deficiency, resulting in neurodegeneration with a rapid clinical downhill course within the first months of life in the classic infantile form. This process may be triggered by the accumulation of galactosylceramide (GalCer) in nervous tissues. Both the enzyme galactosylceramidase and its in vivo activator molecule, saposin A, are essential during GalCer degradation. A clinical manifestation almost identical to Krabbe disease is observed when, instead of the galactosylceramidase protein, the saposin A molecule is defective. Saposin A results from posttranslational processing of the precursor molecule, prosaposin, encoded by the PSAP gene. Clinical and neuroimaging findings in a 7-month-old child strongly suggested Krabbe disease, but this condition was excluded by enzymatic and genetic testing. However, at whole exome sequencing, the previously undescribed homozygous, obviously pathogenic PSAP gene NM_002778.3:c.209T>G(p.Val70Gly) variant was determined in the saposin A domain of the PSAP gene. Fibroblast studies showed GalCer accumulation and the activation of autophagy for the first time in a case of human saposin A deficiency. Our patient represents the second known case in the literature and provides new information concerning the pathophysiology of saposin A deficiency and its intralysosomal effects.


Effects of tetrandrine on cAMP and cGMP levels in rabbit corpus cavernosum in vitro.
The aim of this study was to further investigate the relaxation mechanism of tetrandrine (Tet), a bis-benzylisoquinoline alkaloid isolated from the Chinese medicinal herb-root of Stephania tetrandra S Moore, on rabbit corpus cavernosum tissue in vitro. The effects of Tet on the concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in isolated and incubated rabbit corpus cavernosum tissue were recorded by means of (125)I radioimmunoassay. The basal concentration of cAMP in corpus cavernosum tissue was 5.67 +/- 0.97 pmol mg(-1). Tet increased the cAMP concentration in a dose-dependent manner (p < 0.05), but this effect was not inhibited by an adenylate cyclase inhibitor (cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine, MDL-12, 330A) (p > 0.05). The accumulation of cAMP induced by prostaglandin E(1) (PGE(1), a stimulator of cAMP production) was also augmented by Tet in a dose-dependent manner (p < 0.05). The basal concentration of cGMP in corpus cavernosum tissue is 0.44 +/- 0.09 pmol mg(-1). Tet did not affect this concentration of cGMP, neither in the presence nor the absence of a guanyl cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) (p > 0.05). Further, sodium nitroprusside (SNP, a stimulator of cGMP production)-induced cGMP production was not enhanced by Tet (p > 0.05). Tet, with its relaxation mechanism, can enhance the concentration of cAMP in rabbit corpus cavernosum tissue, probably by inhibiting PDEs activity.


Exposure to virtual social interactions in the treatment of social anxiety disorder: A randomized controlled trial.
This randomized controlled trial investigated the efficacy of a stand-alone virtual reality exposure intervention comprising verbal interaction with virtual humans to target heterogeneous social fears in participants with social anxiety disorder. Sixty participants (Mage = 36.9 years; 63.3% women) diagnosed with social anxiety disorder were randomly assigned to individual virtual reality exposure therapy (VRET), individual in vivo exposure therapy (iVET), or waiting-list. Multilevel regression analyses revealed that both treatment groups improved from pre-to postassessment on social anxiety symptoms, speech duration, perceived stress, and avoidant personality disorder related beliefs when compared to the waiting-list. Participants receiving iVET, but not VRET, improved on fear of negative evaluation, speech performance, general anxiety, depression, and quality of life relative to those on waiting-list. The iVET condition was further superior to the VRET condition regarding decreases in social anxiety symptoms at post- and follow-up assessments, and avoidant personality disorder related beliefs at follow-up. At follow-up, all improvements were significant for iVET. For VRET, only the effect for perceived stress was significant. VRET containing extensive verbal interaction without any cognitive components can effectively reduce complaints of generalized social anxiety disorder. Future technological and psychological improvements of virtual social interactions might further enhance the efficacy of VRET for social anxiety disorder.


[Changes in the contractile activity of the left heart ventricle and blood content of free fatty acids during acute focal myocardial ischemia in rabbits at different times of the day].
Left-ventricular contractility and arterial blood levels of free fatty acids were studied experimentally in rabbits with acute focal myocardial ischemia at different hours of the day (12 a. m., 6 p. m., 12 p. m.). All parameters were measured before a myocardial acute-ischemia focus was created, and 15, 20 and 40 minutes after coronary artery ligation. Heart contractility and blood free fatty acid levels were shown to vary throughout the day. In acute focal myocardial ischemia, these parameters also show different patterns of variation. A relationship was demonstrated between the pattern of changes in some contractility indices under acute focal ischemia and blood baseline levels of free fatty acids, which was particularly manifest at 12 p. m., and grew very weak at 12 a. m.


Pulmonary function before and after prolonged continuous positive airway pressure by mask.
This investigation examined whether prolonged continuous positive airway pressure (CPAP) applied by face mask could sustain an increase in functional residual capacity (FRC). Before median sternotomy, nine adults performed multiple-breath nitrogen washout to determine FRC and spirometry. The day after operation, lung volumes were measured before and 10 min after the 4-h application of 7.5 cm H2O of CPAP with a mask. Mean FRC, forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), and FEV1/FVC after CPAP were similar to pretreatment values. Although CPAP can restore FRC to preoperative values, and did increase FRC in these patients, FRC deteriorates within 10 min after CPAP is removed. Therefore, when a sustained increase in FRC is desired after median sternotomy, CPAP should be applied without interruption.


Encouraging Digital Technology in Neuropsychology: The Theory of Visual Attention on Tablet Devices.
Visual attention helps us to selectively process relevant information and is crucial in our everyday interactions with the environment. Not surprisingly, it is one of the cognitive domains that is most frequently affected by acquired brain injury. Reliable assessment of attention deficits is pivotal to neuropsychological examination and helps to optimize individual rehabilitation plans. Compared with conventional pen-and-paper tests, computerized tasks borrowed from the field of experimental psychology bring many benefits, but lab-based experimental setups cannot be easily incorporated in clinical practice. Light-weight and portable mobile tablet devices may facilitate the translation of computerized tasks to clinical settings. One such task is based on the Theory of Visual Attention (TVA), a mathematical model of visual attention. TVA-based paradigms have been widely used to investigate several aspects of visual attention in both fundamental and clinical research, and include measures for general processing capacity as well as stimulus-specific attentional parameters. This article discusses the benefits of TVA-based assessments compared with frequently used neuropsychological tests of visual attention, and examines the reliability of a tablet-based TVA-based assessment in 59 neurologically healthy participants. Pearson's correlations indicate that the tablet-based TVA assessment and the conventional lab-based TVA assessment have a comparable parallel-form (range: .67-.93), test-retest (range: .61-.78), and internal reliability (range: .56-.97). Our results suggest that tablet-based TVA assessment may be a promising tool to acquire clinical measures of visual attention at low cost at the bedside of the patient.


Handicaps and the development of skills between childhood and early adolescence in young people with severe intellectual disabilities.
While a number of studies have examined the development of skills in children with intellectual disabilities (ID), most have been cross-sectional, most have been concerned with particular syndromes such as Down's syndrome or autism and few have attempted to identify factors associated with improvements in skills. From a sample of 111 children with severe ID who had been identified from the registers of six special schools at 4-11 years of age, 82 were traced and reassessed 5 years later at the age of 11-17 years. On both occasions, information on the children's handicaps and skills was collected by interviewing their main carers using a shortened version of the Vineland Adaptive Behaviour Scales and the Disability Assessment Schedule. There were small but statistically significant improvements in Vineland age-equivalent communication and daily living skills scores, but not in Vineland Socialization scores, over the 5-year period of follow-up. This pattern of improvement was observed in most aetiological subgroups. Improvement in skills was greatest in younger children, and was associated with reductions in behaviour problems and in levels of parental stress. In spite of the improvements in age-equivalent scores, Vineland standard scores showed significant declines over the same period of time, indicating that the improvements observed were smaller than would be expected in a general population sample of children of the same age. The dangers of using standard scores or quotients to quantify the level of functioning of children with severe ID are highlighted.


Worldwide safety experience with nabumetone.
Nabumetone has undergone human clinical premarketing and postmarketing testing for efficacy and safety for about 10 years. In the United States and elsewhere, 7,241 patients were evaluated in clinical trials and comparative information with placebo, aspirin, and other nonsteroidal antiinflammatory drugs (NSAID) was gathered. Postmarketing surveillance information was gathered for 37,712 patients in the United Kingdom and Germany. Withdrawal rates due to adverse effects ranged from 3 to 13%. The cumulative incidence of nabumetone-induced perforations, ulcers, or bleeds varied from 0.02 to 0.95%. In all patients evaluated, only 2 deaths and 15 hospitalizations could be attributed to nabumetone therapy. Bone marrow suppression, liver necrosis, serious central nervous system conditions, or life-threatening dermatologic reactions did not occur. No increase in toxicity was noted with increased dose (up to 2000 mg/day) or age. Nabumetone was determined to be a safe NSAID that causes a low incidence of ulcers.


[Physicochemical parameters of the surface of bacteria and the penicillin-binding capacity in relation to the sensitivity to penicillins and streptomycin].
Development of resistance to penicillins and streptomycin in bacteria results in an increase in the electrokinetic potential changes in the hydratation rate and isoelectric levels of pH. Changes in the physico-chemical properties of the surface of penicillin-resistant Escherichia depends mainly on the accompanying dissociation. The ability of Escherichia to bind labeled benzylpenicillin is shown. Binding of 35S-benzylpenicillin by Escherichia in S-form correlates with sensitivity of the culture to the antibiotic. The penicillin-resistant mutants in R-form bound the antibiotic to a greater extent than sensitive R-cultures. The role of penicillinase in binding 35S-benzylpenicillin by Escherichia was not shown experimentally. Only increased synthesis of the enzyme by the penicillin-resistant mutants was observed. The ability of Escherichia to bind 35S-benzylpenicillin does not depend on the physico-chemical properties of the cell surface and dissociation.


Tailoring Large Pores of Porphyrin Networks on Ag(111) by Metal-Organic Coordination.
The engineering of nanoarchitectures to achieve tailored properties relevant for macroscopic devices is a key motivation of organometallic surface science. To this end, understanding the role of molecular functionalities in structure formation and adatom coordination is of great importance. In this study, the differences in formation of Cu-mediated metal-organic coordination networks based on two pyridyl- and cyano-bearing free-base porphyrins on Ag(111) are elucidated by use of low-temperature scanning tunneling microscopy (STM). Distinct coordination networks evolve via different pathways upon codeposition of Cu adatoms. The cyano-terminated module directly forms 2D porous networks featuring fourfold-coordinated Cu nodes. By contrast, the pyridyl species engage in twofold coordination with Cu and a fully reticulated 2D network featuring a pore size exceeding 3 nm2 only evolves via an intermediate structure based on 1D coordination chains. The STM data and complementary Monte Carlo simulations reveal that these distinct network architectures originate from spatial constraints at the coordination centers. Cu adatoms are also shown to form two- and fourfold monoatomic coordination nodes with monotopic nitrogen-terminated linkers on the very same metal substrate-a versatility that is not achieved by other 3d transition metal centers but consistent with 3D coordination chemistry. This study discloses how specific molecular functionalities can be applied to tailor coordination architectures and highlights the potential of Cu as coordination center in such low-dimensional structures on surfaces.


Evaluation of novel tools to facilitate the detection and characterization of leprosy patients in China.
Leprosy is the disabling outcome of chronic infection with Mycobacterium leprae. The disease often evades early detection, particularly now that fewer clinicians are able to confidently diagnose the disease following the integration of leprosy control measures within general health services in many countries. Although leprosy is officially eliminated in China, endemic regions remain in some difficult-to-reach, underdeveloped areas in Southwest China. In order to better understand the extent of M. leprae infection and identify new leprosy cases in a timely manner, simple tools that can detect infection and the early disease are required. In this report we evaluated the performance of antigen-specific ELISA, the NDO-LID rapid diagnostic test, and antigen-specific whole blood assays (WBA) as potential diagnostic tools. Our data support the use of antibody detection tests and WBA to facilitate the diagnosis of multibacillary and paucibacillary leprosy, respectively. These tools could be invaluable for increased, but simplified, monitoring of individuals in order to provide referrals for clinical exam and early leprosy diagnosis.


Gender-Moderated Pathways From Childhood Abuse and Neglect to Late-Adolescent Substance Use.
Substantial research has linked childhood maltreatment to the development of substance use in adolescence. However, gender differences in the mechanisms that connect child abuse and neglect to substance use remain unclear. In this study, we applied multiple-group structural equation modeling in a sample of 1,161 youths (boys, n = 552; girls, n = 609) from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN) to examine gender differences in the associations between childhood abuse and neglect exposure from ages 0-12 years and substance use severity at age 18 as mediated by early substance use at age 14 and psychological symptoms (anger, anxiety, and depression) at age 16. In both genders, neglect directly predicted substance use severity, β = .25, p < .001 for boys and β = .17, p = .007 for girls; and early substance use, β = .03, p = .002 for boys and β = .06, p = .005 for girls; and anger mediated this association, β = .10, p < .001 for boys and β = .06, p = .005 for girls. Anger mediated paths from abuse in boys, β = .06, p = .018. In girls, early substance use mediated the path from abuse to substance use severity, β = .06, p = .008, with the mediated effect and direct path from abuse to early substance use significantly moderated by gender. For substance use severity, R2 = .26 for girls and R2 = .27 for boys. These findings demonstrate the prominence of neglect in predicting substance use severity and gender differences in paths from abuse.


Resting metabolic rate and protein turnover in apparently healthy elderly Gambian men.
Body composition, resting energy expenditure (REE), and whole body protein metabolism were studied in 26 young and 28 elderly Gambian men matched for body mass index during the dry season in a rural village in The Gambia. REE was measured by indirect calorimetry (hood system) in the fasting state and after five successive meals. Rates of whole body nitrogen flux, protein synthesis, and protein breakdown were determined in the fed state from the level of isotopic enrichment of urinary ammonia over a period of 12 h after a single oral dose of [15N]glycine. Expressed in absolute value, REE was significantly lower in the elderly compared with the young group (3.21 +/- 0.07 vs. 4.04 +/- 0.07 kJ/min, P < 0.001) and when adjusted to body weight (3.29 +/- 0.05 vs. 3.96 +/- 0.05 kJ/min, P < 0.0001) and fat-free mass (FFM; 3.38 +/- 0.01 vs. 3.87 +/- 0.01 kJ/min, P < 0.0001). The rate of protein synthesis averaged 207 +/- 13 g protein/day in the elderly and 230 +/- 13 g protein/day in the young group, whereas protein breakdown averaged 184 +/- 13 g protein/day in the elderly and 203 +/- 13 g protein/day in the young group (nonsignificant). When values were adjusted for body weight or FFM, they did not reveal any difference between the two groups. It is concluded that the reduced REE adjusted for body composition observed in elderly Gambian men is not explained by a decrease in protein turnover.


Proteo-Trancriptomic Analyses Reveal a Large Expansion of Metalloprotease-Like Proteins in Atypical Venom Vesicles of the Wasp Meteorus pulchricornis (Braconidae).
Meteorus pulchricornis (Ichneumonoidea, Braconidae) is an endoparasitoid wasp of lepidopteran caterpillars. Its parasitic success relies on vesicles (named M. pulchricornis Virus-Like Particles or MpVLPs) that are synthesized in the venom gland and injected into the parasitoid host along with the venom during oviposition. In order to define the content and understand the biogenesis of these atypical vesicles, we performed a transcriptome analysis of the venom gland and a proteomic analysis of the venom and purified MpVLPs. About half of the MpVLPs and soluble venom proteins identified were unknown and no similarity with any known viral sequence was found. However, MpVLPs contained a large number of proteins labelled as metalloproteinases while the most abundant protein family in the soluble venom was that of proteins containing the Domain of Unknown Function DUF-4803. The high number of these proteins identified suggests that a large expansion of these two protein families occurred in M. pulchricornis. Therefore, although the exact mechanism of MpVLPs formation remains to be elucidated, these vesicles appear to be "metalloproteinase bombs" that may have several physiological roles in the host including modifying the functions of its immune cells. The role of DUF4803 proteins, also present in the venom of other braconids, remains to be clarified.


Do musicians learn a fine sequential hand motor skill differently than non-musicians?
Do professional musicians learn a fine sequential hand motor skill more efficiently than non-musicians? Is this also the case when they perform motor imagery, which implies that they only mentally simulate these movements? Musicians and non-musicians performed a Go/NoGo discrete sequence production (DSP) task, which allows to separate sequence-specific from a-specific learning effects. In this task five stimuli, to be memorized during a preparation interval, signaled a response sequence. In a practice phase, different response sequences had to be either executed, imagined, or inhibited, which was indicated by different response cues. In a test phase, responses were required to familiar (previously executed, imagined, or inhibited) and unfamiliar sequences. In both phases, response times and response accuracy were measured while the electroencephalogram (EEG) was only registered during the practice phase to compare activity between motor imagery, motor execution, and motor inhibition for both groups. Results in the practice phase revealed that musicians learned the response sequences faster and more accurately than non-musicians although no difference in initiation time was found. EEG analyses revealed similar lateralized activity during learning a motor skill for both groups. Our results from the test phase showed better sequence-a-specific learning effects (i.e., faster response times and increased accuracy) for musicians than for non-musicians. Moreover, we revealed that non-musicians benefit more from physical execution while learning a required motor sequence, whereas sequence-specific learning effects due to learning with motor imagery were very similar for musicians and non-musicians.


Parental coping in raising children who have spina bifida cystica.
In this study of 40 married couples who are rising a child with spina bifida cystica, the family stress theory was used to assess family regenerative power and vulnerability to stress. The reserach tested for differences between high and low stress families in the family environment, coping strategies, and severity of the child's problem. When compared with the high stress families, the low stress families appeared to be more cohesive, be better organised, have a more active recreation orientation, be lower in family conflict, utilise more family community relationships, and have children who have less severe physical problems. The practical implications of this study include the potentiality for applied usage of family diagnostic tests, the clinical and research application of the findings on family coping strategies for improved patient outcomes, and the need for additional social-medical research to assess accurately family concerns about health care policies.


Risk factor analysis for cytomegalovirus reactivation under prophylaxis with letermovir after allogeneic hematopoietic stem cell transplantation.
Letermovir has been approved as a novel cytomegalovirus (CMV) prophylactic agent after allogeneic hematopoietic stem cell transplantation (HSCT). However, there are still insufficient data to properly evaluate the real-world role of letermovir, and the risk factors for CMV reactivation under letermovir prophylaxis have not been clarified. We performed a single-institution retrospective analysis of patients under prophylaxis with or without letermovir who underwent allogeneic HSCT between March 2012 and December 2019. In August 2018, letermovir was added to the clinical practice at our institution for the prophylaxis of CMV reactivation in allogeneic HSCT recipients. Patients who underwent HSCT without prophylactic letermovir from March 2012 until September 2018 served as a historical control. The cumulative incidence of clinically significant CMV infection (CS-CMVi) was significantly lower in the letermovir group than in the historical control group not receiving letermovir (30.2% vs. 71.6%, p < .05, at 100 days). In addition, the cumulative incidence of non-relapse mortality (NRM) at day 500 was significantly lower in the letermovir group (4.7% vs. 19.8%, p < .05). We then performed a risk factor analysis for developing CS-CMVi in the letermovir group. The only significant factor identified by this multivariable analysis was transplantation from a CMV seronegative donor to a seropositive recipient (Hazard ratio = 2.76, 95% confidence interval 1.14-6.68, p < .05). Our study showed that letermovir prophylaxis significantly reduced the incidence of CS-CMVi and NRM in a real-world setting and that the CMV serostatus of the donor remained as a risk factor for CS-CMVi even under letermovir prophylaxis.


Point-of-care B-type natriuretic peptide and neutrophil gelatinase-associated lipocalin measurements for acute resuscitation: a pilot study.
Adequate resuscitation is paramount to burn patient survival and recovery. Novel biomarkers of intravascular volume and renal perfusion may augment resuscitation strategies. The purpose of this study is to characterize serum B-type natriuretic peptide (BNP) and neutrophil gelatinase-associated lipocalin (NGAL) during burn resuscitation and correlate to clinical assessments of volume status. We hypothesize that BNP and NGAL will help predict inadequate resuscitation during the first 48 hours following burn injury. We conducted a pilot observational study recruiting 15 adult (age ≥18 years) patients with ≥20% TBSA burns. Paired serial BNP, NGAL, and creatinine measurements were performed using point-of-care testing. Samples were tested every 4 hours for the first 48 hours following admission. Acute kidney injury (AKI) was defined by the RIFLE criteria. Over-resuscitation was defined as developing compartment syndrome. Demographics and TBSA were similar between AKI (n = 7) vs non-AKI (n = 8), and over-resuscitated (n = 5) vs adequately resuscitated groups (n = 10). NGAL (184.9 ± 72.2 vs 110.8 ± 35.8 ng/ml, P = .004) and BNP (25.3 ± 17.3 vs 8.8 ± 5.2 pg/ml, P = .033) values were significantly higher in AKI patients. Creatinine values were similar between AKI and non-AKI patients. NGAL levels suggested presence of AKI 12 hours earlier than creatinine levels. BNP values (23.1 ± 21.9 vs 13.9 ± 13.4 pg/ml, P < .001) were significantly higher in over-resuscitated patients. Point-of-care BNP, NGAL, and creatinine measurements aid in the assessment of vascular volume and renal function during acute burn resuscitation. Further studies are warranted to determine BNP and NGAL cut-offs for guiding burn resuscitation.


Resonance-induced wave penetration through electromagnetic opaque object.
The enhanced transmission of electromagnetic waves through an opaque object is reported in this paper. The samples are constructed as two different configurations: a subwavelength metallic mesh sandwiched either between two metallic plates with periodic fractal slots (ABA for short) or between two plastic plates with periodic metallic fractals (CBC for short). Such ABA or CBC configuration exhibits multiple transmission peaks, indicating the wave penetrations through the opaque metallic mesh. The experimental observations and theoretical simulations demonstrate that the transmission enhancements for two configurations are induced by local resonances in the sandwiching layers.


The importance of porcine sperm parameters on fertility in vivo.
It would be desirable to use semen parameters to predict the in vivo fertilizing capacity of a particular ejaculate. In animal production, an ejaculate is divided into multiple doses for artificial insemination (AI); therefore, it would be economically beneficial to know the functional quality (i.e., fertility) of the semen before it is inseminated. To identify a predictive assay of the fertilizing capacity of a porcine ejaculate, we performed 4 rapid assays of sperm quality (motility, viability, physiological status as assessed by chlortetracycline fluorescence, and ATP content) on samples from 9 ejaculates, before and after a thermal stress test (42.5 degrees C, 45 min). These parameters were subsequently correlated with in vivo fertility resulting from AI with 2 sperm doses, 3 x 10(9) or 0.3 x 10(9) motile cells in 70 mL (optimal or suboptimal sperm number per insemination, respectively) from these same ejaculates. No parameter was correlated to the fertility rates obtained after inseminating with the optimal semen doses, either before or after the thermal stress test (P > 0.05). However, with respect to the animals inseminated with the suboptimal semen dose, sperm motility (the percentage of motile spermatozoa as assessed visually by microscopy) prior to thermal stress was well-correlated to fertility rates (r = 0.783, P = 0.01). The percentage of spermatozoa displaying the chlortetracycline Pattern AR (acrosome reaction) was also statistically related to fertility (r = 0.05, P = 0.04), but the biological importance of this relationship is questionable given the small variation among ejaculates (range: 0 to 2%). No other sperm parameter was significantly related to fertility rates in this group (P > 0.05). These data, therefore, indicate that sperm motility is a useful indicator of sperm fertilizing capacity in vivo. Moreover, to identify a predictor of semen fertility it is critical that the number of spermatozoa used during insemination is sufficiently low to detect differences in sperm fertilizing efficiency.


Controlled release levodopa-carbidopa (CR-5) in the management of parkinsonian motor fluctuations.
Parkinsonian patients receiving long-term levodopa-carbidopa (Sinemet) therapy often develop fluctuations in motor performance. Although maintenance of stable levels of plasma levodopa by means of its continuous intravenous infusion diminishes these fluctuations, practical limitations attending this therapeutic approach have prompted continuing attempts to develop oral controlled release levodopa-carbidopa formulations. In a double-blind, crossover clinical trial, one such preparation, CR-5 (Merck, Sharp & Dohme), produced significantly less plasma levodopa variations and substantially improved motor performance over Sinemet in 15 patients with mild to moderate fluctuations, all but one of whom chose to continue on CR-5 therapy after the study. Eight patients with severe motor fluctuations could not adjust to this preparation during the open phase and consequently withdrew from the study. Subjectively, most patients noted the convenience of less frequent dosing, improved sleep, and the amelioration of early morning akinesia and dystonia.


Survivorship of a Medialized Glenoid and Lateralized Onlay Humerus Reverse Shoulder Arthroplasty Is High at Midterm Follow-up.
Reverse shoulder arthroplasty (RSA) is a common treatment of a variety of disabling shoulder conditions. The purpose of this study was to determine revision-free survivorship after RSA using a medialized glenoid and lateralized onlay-type humerus implant and to identify etiologies of revision. All RSAs performed using the Comprehensive® Reverse Shoulder System (Zimmer Biomet, Inc.; Warsaw, IN, USA) at one institution from 2008 to 2014 were identified through a retrospective review. Charts were reviewed to determine whether the RSA was a primary or revision surgery. Patients were contacted by telephone, and survivorship was defined as no subsequent surgery after RSA. Of the 526 RSAs performed, responses were obtained from 403 patients (77%). A Kaplan-Meier analysis was performed to determine survivorship over time. A χ 2 test was used to determine differences between revision rates after RSA. Minimum follow-up was 3 years, and average follow-up was 4.83 ± 1.60 years. Survivorship was 96% at 2 years and 93% at 5 years after RSA. Revisions were performed for instability (n = 8), humeral tray-taper junction failure (n = 5), acute fracture (n = 4), infection (n = 3), glenoid loosening (n = 3), osteolysis (n = 1), or notching (n = 1). Fourteen of the 151 patients (9.2%) who had surgery prior to RSA required revision after RSA. Having shoulder surgery prior to RSA was associated with higher rates of subsequent revision after RSA. Overall, survivorship after RSA using a medialized glenoid and lateralized onlay-type humerus RSA is high, and prostheses implanted in native shoulders have lower rates of revision at midterm follow-up. Instability (1.9%) was the most common reason for revision.