Methylophaga aminisulfidivorans sp. nov., a restricted facultatively methylotrophic marine bacterium.
A novel restricted facultatively methylotrophic marine strain, MP(T), possessing the ribulose monophosphate pathway of C(1)-carbon compound assimilation was isolated from a seawater sample obtained from Mokpo, South Korea. The novel isolate is aerobic, Gram-negative, asporogenous and a non-motile short rod. It grows well on methanol, methylated amines, dimethylsulfide and DMSO. Optimal growth occurs with 3 % NaCl at 30 degrees C and pH 7.0. Fructose is utilized as a multicarbon source. Growth factors are not required and vitamin B(12) does not stimulate growth. The cellular fatty acid profile of the novel strain consists primarily of straight-chain saturated C(16 : 0) and unsaturated C(16 : 1) acids. The major ubiquinone is Q-8. The dominant phospholipids are phosphatidylethanolamine and phosphatidylglycerol. The DNA G+C content is 44.9 mol% (T(m)). Based on 16S rRNA gene sequence analysis and DNA-DNA relatedness (25-41 %) with the type strains of marine methylotrophs belonging to the genus Methylophaga, it is suggested that isolate MP(T) represents a novel species, Methylophaga aminisulfidivorans sp. nov. (type strain MP(T)=KCTC 12909(T)=VKM B-2441(T)=JCM 14647(T)).


Streptococcus pneumoniae is desiccation tolerant and infectious upon rehydration.
Streptococcus pneumoniae (pneumococcus) is a frequent colonizer of the nasopharynx and one of the leading causative agents of otitis media, pneumonia, and meningitis. The current literature asserts that S. pneumoniae is transmitted person to person via respiratory droplets; however, environmental surfaces (fomites) have been linked to the spread of other respiratory pathogens. Desiccation tolerance has been to shown to be essential for long-term survival on dry surfaces. This study investigated the survival and infectivity of S. pneumoniae following desiccation under ambient conditions. We recovered viable bacteria after all desiccation periods tested, ranging from 1 h to 4 weeks. Experiments conducted under nutrient limitation indicate that desiccation is a condition separate from starvation. Desiccation of an acapsular mutant and 15 different clinical isolates shows that S. pneumoniae desiccation tolerance is independent of the polysaccharide capsule and is a species-wide phenomenon, respectively. Experiments demonstrating that nondesiccated and desiccated S. pneumoniae strains colonize the nasopharynx at comparable levels, combined with their ability to survive long-term desiccation, suggest that fomites may serve as alternate sources of pneumococcal infection. Even with the advent of multivalent capsular polysaccharide conjugate vaccines, S. pneumoniae continues to be a major cause of morbidity and mortality worldwide. Every year, there are approximately 7 million cases of pneumococcus-based otitis media in the United States alone, while pneumococcal invasive diseases are responsible for more than 1 million deaths globally. It is believed that the human upper respiratory tract is the sole niche of S. pneumoniae and, thus, that spread occurs via close contact with an infected individual. In this study, we characterized the desiccation tolerance of S. pneumoniae and found that it can survive for many weeks postdehydration and retain infectivity. Our results suggest that desiccation tolerance is an inherent trait of this genetically variable species and that fomites may be a source of transmission.


Early Steroid Withdrawal Compared With Standard Immunosuppression in Kidney Transplantation - Interim Analysis of the Amsterdam-Leiden-Groningen Randomized Controlled Trial.
The optimal immunosuppressive regimen in kidney transplant recipients, delivering maximum efficacy with minimal toxicity, is unknown. The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in 305 kidney transplant recipients, in which 2 immunosuppression minimization strategies-one consisting of early steroid withdrawal, the other of tacrolimus minimization 6 months after transplantation-were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. The primary endpoint was kidney function. Secondary endpoints included death, primary nonfunction, graft failure, rejection, discontinuation of study medication, and a combined endpoint of treatment failure. An interim analysis was scheduled at 6 months, that is, just before tacrolimus minimization. This interim analysis revealed no significant differences in Modification of Diet in Renal Disease between the early steroid withdrawal group and the standard immunosuppression groups (43.2 mL/min per 1.73 m2 vs 45.0 mL/min per 1.73 m2, P = 0.408). There were also no significant differences in the secondary endpoints of death (1.0% vs 1.5%; P = 0.737), primary nonfunction (4.1% vs 1.5%, P = 0.159), graft failure (3.1% vs 1.5%, P = 0.370), rejection (18.6% vs 13.6%, P = 0.289), and discontinuation of study medication (19.6% vs 12.6%, P = 0.348). Treatment failure, defined as a composite endpoint of these individual secondary endpoints, was more common in the early steroid withdrawal group (P = 0.027), but this group had fewer serious adverse events and a more favorable cardiovascular risk profile. Based on these interim results, early steroid withdrawal is a safe short-term immunosuppressive strategy. Long-term outcomes, including a comparison with tacrolimus minimization after 6 months, will be reported in the final 2-year analysis.


Pathologic diagnosis of malignant mesothelioma: chronological prospect and advent of recommendations and guidelines.
Malignant mesothelioma (MM) is rare and difficult to diagnose. Its identification depends upon pathological investigation (cyto-histological assessment and immunohistochemistry) supported by clinical and radiological evidence. In the last decade, the standardization of diagnostic methods has become a major focus of debate among pathologists and clinicians. This has led to the writing of guidelines and recommendation for the diagnosis to achieve the goal of a standard diagnosis. In this article, a chronological view relating to the pathological diagnosis of MM is presented together with a review of guidelines and recommendations.


The landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions.
Activated myeloid cells and astrocytes are the predominant cell types in active multiple sclerosis (MS) lesions. Both cell types can adopt diverse functional states that play critical roles in lesion formation and resolution. In order to identify phenotypic subsets of myeloid cells and astrocytes, we profiled two active MS lesions with thirteen glial activation markers using imaging mass cytometry (IMC), a method for multiplexed labeling of histological sections. In the acutely demyelinating lesion, we found multiple distinct myeloid and astrocyte phenotypes that populated separate lesion zones. In the post-demyelinating lesion, phenotypes were less distinct and more uniformly distributed. In both lesions cell-to-cell interactions were not random, but occurred between specific glial subpopulations and lymphocytes. Finally, we demonstrated that myeloid, but not astrocyte phenotypes were activated along a lesion rim-to-center gradient, and that marker expression in glial cells at the lesion rim was driven more by cell-extrinsic factors than in cells at the center. This proof-of-concept study demonstrates that highly multiplexed tissue imaging, combined with the appropriate computational tools, is a powerful approach to study heterogeneity, spatial distribution and cellular interactions in the context of MS lesions. Identifying glial phenotypes and their interactions at different lesion stages may provide novel therapeutic targets for inhibiting acute demyelination and low-grade, chronic inflammation.


Measurement of cell numbers by means of the endogenous enzyme hexosaminidase: applications to cell adhesion assays in endometrial and ovarian carcinoma cell lines.
Using a chromogenic substrate for the lysosomal enzyme, hexosaminidase to estimate cell numbers, a sensitive, simple, and non-radioactive procedure has been previously developed (1) in which microtiter reaction wells are directly scanned using a spectrophotometer. The applications of this method to quantitation of cell numbers and adhesion assays to coated substrates in endometrial adenocarcinoma (Ishikawa) and epithelial ovarian cancer (Ovcar) cells are discussed. The methods are safe, cheap, and easily applicable to biological researches particularly in developing countries.


A chimeric hairpin DNA aptamer-based biosensor for monitoring the therapeutic drug bevacizumab.
The accurate and rapid detection of specific antibodies in blood is very important for efficient diagnosis and precise treatment. Conventional methods often suffer from time-consuming operations and/or a narrow detection range. In this work, for the rapid determination of bevacizumab in plasma, a series of chimeric hairpin DNA aptamer-based probes were designed by the modification, labeling and theoretical computation of an original aptamer. Then, the dissociation constant of the modified hairpin DNA to bevacizumab was measured and screened using microscale thermophoresis. The best chimeric hairpin DNA aptamer-based probe was then selected, and a one-step platform for the rapid determination of bevacizumab was constructed. This strategy has the advantages of being simple, fast and label-free. Because of the design and screening of the hairpin DNA, as well as the optimization of the concentration and electrochemical parameters, a low detection limit of 0.37 pM (0.054 ng mL-1) with a wide linear range (1 pM-1 μM) was obtained. Finally, the rationally constructed biosensor was successfully applied to the determination of bevacizumab in spiked samples, and it showed good accuracy and precision. This method is expected to truly realize accurate and rapid detection of bevacizumab and provides a new idea for the precise treatment of diseases.


Advantage of precision metagenomics for urinary tract infection diagnostics.
Urinary tract infections (UTIs) remain a diagnostic challenge and often promote antibiotic overuse. Despite urine culture being the gold standard for UTI diagnosis, some uropathogens may lead to false-negative or inconclusive results. Although PCR testing is fast and highly sensitive, its diagnostic yield is limited to targeted microorganisms. Metagenomic next-generation sequencing (mNGS) is a hypothesis-free approach with potential of deciphering the urobiome. However, clinically relevant information is often buried in the enormous amount of sequencing data. Precision metagenomics (PM) is a hybridization capture-based method with potential of enhanced discovery power and better diagnostic yield without diluting clinically relevant information. We collected 47 urine samples of clinically suspected UTI and in parallel tested each sample by microbial culture, PCR, and PM; then, we comparatively analyzed the results. Next, we phenotypically classified the cumulative microbial population using the Explify® data analysis platform for potential pathogenicity. Results revealed 100% positive predictive agreement (PPA) with culture results, which identified only 13 different microorganisms, compared to 19 and 62 organisms identified by PCR and PM, respectively. All identified organisms were classified into phenotypic groups (0-3) with increasing pathogenic potential and clinical relevance. This PM can simultaneously quantify and phenotypically classify the organisms readily through bioinformatic platforms like Explify®, essentially providing dissected and quantitative results for timely and accurate empiric UTI treatment. PM offers potential for building effective diagnostic models beyond usual care testing in complex UTI diseases. Future studies should assess the impact of PM-guided UTI management on clinical outcomes.


Adrenocorticotropic hormone-secreting phaeochromocytoma as a cause of treatment-resistant hypertension and recurrent pulmonary emboli.
We report an unusual case of a patient presenting with Cushing's syndrome caused by a phaeochromocytoma secreting adrenocorticotropic hormone (ACTH). The patient had a history of treatment-resistant hypertension, secondary amenorrhoea and tendency towards hypokalaemia. She had multiple signs of Cushing's syndrome, such as swelling, bruising, abdominal striae and proximal myopathy. Hypokalaemia is more common in patients with ectopic ACTH-secretion than other causes of Cushing's syndrome. Computed tomography, adrenal vein sampling and biochemistry could confirm an ACTH-secreting phaeochromocytoma. It is important to consider that hypersecretion of more than one hormone may exist in a unilateral adrenal adenoma. This patient also presented with recurrent pulmonary emboli, and there is an increased risk of venous thromboembolism in patients with ACTH-secreting phaeochromocytoma. Anticoagulation should be considered for as long as the disease is active. We demonstrate that unilateral adrenalectomy can be curative in patients with ACTH-secreting phaeochromocytoma.


A rapid diagnostic workflow for cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae detection from blood cultures by MALDI-TOF mass spectrometry.
Nowadays, the global spread of resistance to oxyimino-cephalosporins in Enterobacteriaceae implies the need for novel diagnostics that can rapidly target resistant organisms from these bacterial species. In this study, we developed and evaluated a Direct Mass Spectrometry assay for Beta-Lactamase (D-MSBL) that allows direct identification of (oxyimino)cephalosporin-resistant Escherichia coli or Klebsiella pneumoniae from positive blood cultures (BCs), by using the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) technology. The D-MSBL assay was performed on 93 E. coli or K. pneumoniae growing BC samples that were shortly co-incubated with cefotaxime (CTX) as the indicator cephalosporin. Susceptibility and resistance defining peaks from the samples' mass spectra were analyzed by a novel algorithm for bacterial organism classification. The D-MSBL assay allowed discrimination between E. coli and K. pneumoniae that were resistant or susceptible to CTX with a sensitivity of 86.8% and a specificity of 98.2%. The proposed algorithm-based D-MSBL assay, if integrated in the routine laboratory diagnostic workflow, may be useful to enhance the establishment of appropriate antibiotic therapy and to control the threat of oxyimino-cephalosporin resistance in hospital.


Risk factors of portal vein system thrombosis after splenectomy: a meta-analysis.
The primary aim of the present study was to explore risk factors for portal vein system thrombosis following splenectomy. A systematic search of PubMed, Embase and Cochrane libraries was conducted to identify original studies that fulfilled the inclusion criteria. Raw data on potential risk factors for portal vein system thrombosis after splenectomy were extracted for meta-analysis. Subsequently, a sensitivity analysis was conducted to verify the stability of the results. Eighteen studies with 626 thrombosis events from 1807 splenectomy met the inclusion criteria. Larger spleen volume (SMD 0.44, P = 0.000), broader splenic vein diameter (WMD 2.30, P = 0.000), broader portal vein diameter (WMD 2.08, P = 0.000), a lower velocity of portal blood flow (WMD -0.91, P = 0.001), decreased platelet count (WMD -5.14, P = 0.007), decreased white blood cell (WMD -0.40, P = 0.027), decreased haemoglobin (WMD -9.14, P = 0.002), ascites (OR 1.81, P = 0.003) and bleeding history before surgery (OR 1.88, P = 0.002) were identified to be factors that exacerbated the risk of portal vein system thrombosis after splenectomy. Sex, age, preoperative prothrombin time, postoperative platelet count, postoperative D-dimer, operation time and intraoperative blood loss, did not increase the risk of thrombosis. Larger spleen volume, broader splenic vein diameter, broader portal vein diameter, a lower velocity of portal blood flow, ascites, bleeding history before surgery, decreased platelet count, white blood cell and haemoglobin may increase the risk of portal vein system thrombosis.


CD1a expression by Barrett's metaplasia of gastric type may help to predict its evolution towards cancer.
As emerging in the recent literature, CD1a has been regarded as a molecule whose expression may reflect tumour evolution. The aim of the present work was to investigate the expression of CD1a in a series of Barrett's metaplasia (BM), gastric type (GTBM), with and without follow-up, in order to analyse whether its expression may help to diagnose this disease and to address the outcome. Indeed, GTBM may be confused sometimes with islets of ectopic gastric mucosa and its evolution towards dysplasia (Dy) or carcinoma (Ca) could not be foreseen. We showed a significant higher expression of CD1a in GTBM than in both Dy and Ca; nevertheless, the number of positive GTBM was significantly lower in the group of cases that at follow-up underwent Dy or Ca. Our data address that CD1a may be a novel biomarker for BM and that its expression may help to predict the prognosis of this pathology.


Preclinical evaluation of RQ3013, a broad-spectrum mRNA vaccine against SARS-CoV-2 variants.
The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike (S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the wild-type, B.1.1.7, B.1.351, B.1.617.2, and the newly emerging Omicron variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. Furthermore, our safety assessment of RQ3013 in NHP showed no observable adverse effects. These results provide strong support for the evaluation of RQ3013 in clinical trials and suggest that it may be a promising candidate for broad protection against COVID-19 and its variants.


Access to the cavernous sinus through the vertebral artery: technical case report.
The cavernous sinus in 3 of a series of 147 fast-flow direct carotid-cavernous fistulae was best reached through the vertebral artery. All three patients were anatomically cured without morbidity.


The relationship between phenolic compounds from diet and microbiota: impact on human health.
The human intestinal tract is home to a complex microbial community called microbiota. This gut microbiota, whilst playing essential roles in the maintenance of the health of the host, is exposed to the impact of external factors such as the use of medication or dietary patterns. Alterations in the composition and/or function of the microbiota have been described in several disease states, underlining the role of the gut microbiota in keeping the health status. Among the different dietary compounds, polyphenols constitute a very interesting group as some of them have been found to possess important biological activities, including antioxidant, anticarcinogenic or antimicrobial activities. The term polyphenol comprises thousands of molecules presenting a phenol ring and are widely distributed in plant foods. The bioactivity of these compounds is highly dependent on their intestinal absorption and often they are ingested as non-absorbable precursors that are transformed into bioactive forms by specific microorganisms in the intestine. Some of these microorganisms have been identified and the enzymatic steps involved have been elucidated. However, little is known about the impact of these ingested polyphenols upon the human gut microbiota. The heterogeneity of the polyphenol compounds and their food sources, as well as their coexistence with other bioactive compounds within a normal diet, together with the complexity of the human gut microbiota make difficult the understanding of the interactions between dietary polyphenols and gut microbes. This is, however, an important area of research which promises to expand our knowledge on the food functionality area through understanding the microbiota-food component interaction.


Hand and wrist tuberculosis in paediatric patients - our experience in 44 patients.
Skeletal tuberculosis (TB) of the hand and wrist is rare, accounting for less than 1% of all osteoarticular TB. Although rare, TB of the hand and wrist is a cause of major morbidity. A common feature among all available reports on TB of the hand and wrist was a delay in diagnosis, causing residual stiffness and pain after treatment. Minimal initial symptoms, rarity of the lesion and ability of wrist TB to mimic more common pathologies account for the delay. Skeletal TB may behave differently in this age compared with the adult population. Further, the disease may affect the growing bone, causing residual deformities. The paucity of studies from different countries, coupled with a difficulty in diagnosis resulting in major morbidity, led us to carry out a study on this topic. A total of 44 patients with skeletal lesions in the hand and wrist were studied. The diagnosis was confirmed by biopsy. Patients were started on multidrug antitubercular treatment (ATT). Those not responding were scheduled for debridement. All patients were assessed using the Green O'Brian scoring system. All these patients were studied separately for clinical presentation, nutritional status (Rainey-Mcdonald nutritional index), time from onset of symptoms to presentation, treatment required, prognosis and complications. The proximal phalanx of the fourth digit and the metacarpal of the fifth digit were the most commonly involved bones in our series, with five cases of each. The capitate was the most common carpal bone, followed by the lunate. The duration of symptoms ranged from 5 weeks to 24 weeks (mean: 7.6 weeks). Most of these patients presented with complaints of pain, followed by swelling. 13 patients did not respond favourably to ATT over an 8-week period and were scheduled for surgery. Three of these patients had multidrug resistance. There was one case of a pathological fracture in our series and seven cases of arthritis/residual significant pain at the end of follow-up. For all the other patients, the results were excellent. A very high index of suspicion, MRI and early biopsy are required for a timely diagnosis of skeletal TB of the hand and wrist. Early commencement of ATT was the most important factor for good results. The possibility of multidrug resistance should be kept in mind for patients not responding to treatment.


[Morphofunctional state of hepatocytes nuclear apparatus in Mongolian herbils after the flight on space apparatus Foton-M3].
Morphofunctional state of hepatocytes nuclear apparatus was analyzed in the liver of Mongolian gerbils Meriones unguiculatus returned from 12-d space flight of Foton-M3 (SF) and their vivarium and ground synchronous controls. Volume, ploidy and number of hepatocyte nuclei, nucleolus dimensions and number as well as contacts with karyolemma were determined in the central, intermediate and peripheral areas of the liver classical lobe. Also, total number of mitoses and amitoses was determined in the liver parenchyma. The vivarium control animals displayed specifics of the nucleus apparatus structure that depended on intralobe topography. Based on the selected criteria, high functional activity was characteristic of cells in the intermediate area. According to the criteria, nuclear apparatus in the synchronous control tended to down the functional activity The adaptive adjustment of nuclei in SF seemed to have been initiated by changes in the hepatic blood flow: volumes of hepatocyte nuclei and nucleoli increased as did the number of nuclei in cell, whereas ploidy made a decrease, especially in the intermediate area. Under the SF conditions, particularly important compensatory mechanism for the liver function was intensification of amitosis and consequent increase of the population of dinuclear hepatocytes.


[Treatment of hypertensive diseases in pregnancy--general recommendations and long-term oral therapy].
Hypertensive disorders are among the most common causes of maternal and perinatal mortality. Mild and uncomplicated chronic hypertension has a better prognosis than preeclampsia. The primary aims of therapy are to prevent cerebrovascular complications and to avoid the progression of chronic hypertension into superimposed preeclampsia with worse prognosis. In mild courses of the disease bedrest, whether at home or in the hospital, is commonly recommended. A special diet is not required neither for prevention nor for therapy. This also applies for the use of aspirin. Calcium supplementation during pregnancy seems to be effective in reducing the risk of hypertension and to a smaller extent of preeclampsia. Diuretic therapy is only indicated in exceptional cases. Antihypertensive drugs are recommended, if a sustained blood pressure of diastolic > or = 110 mmHg is recorded, in cases of superimposed preeclampsia even if the diastolic blood pressure is > or = 100 (> or = 90) mmHg. alpha-Methyl-dopa is the initial drug of choice for oral antihypertensive therapy. Neither short-term effects on the fetus or neonate nor long-term effects during infancy have been reported after long-term use of alpha-methyl-dopa in pregnancy. The oral application of beta-adrenergic-antagonist drugs is well-tolerated, but should be avoided in cases of severe fetal growth retardation. Dihydralazine treatment is not suitable for oral therapy, since its medication is associated with maternal side effects such as headache and tachycardia. Administration of drugs that inhibit angiotensin-converting enzyme during pregnancy is contra-indicated. Calcium-channel-blocking drugs are frequently used in the USA and in the UK as "second-line" antihypertensive medication, however there is little experience with the long-term administration of these drugs to pregnant women with hypertension. The indication for hospitalization are of particular clinical importance, since a delay in admission associated with maternal complications may lead to juridical troubles. The antihypertensive treatment is only a symptomatic therapy; the obstetrician must be aware that delivery is the ultimate cure of hypertensive disorders in pregnancy. In women with mild chronic hypertension or mild preeclampsia antihypertensive therapy is unlikely to be beneficial regarding the perinatal results, while in severe forms drug therapy is mandatory to avoid life-threatening maternal complications.


New Role for Interleukin-13 Receptor α1 in Myocardial Homeostasis and Heart Failure.
The immune system plays a pivotal role in myocardial homeostasis and response to injury. Interleukins-4 and -13 are anti-inflammatory type-2 cytokines, signaling via the common interleukin-13 receptor α1 chain and the type-2 interleukin-4 receptor. The role of interleukin-13 receptor α1 in the heart is unknown. We analyzed myocardial samples from human donors (n=136) and patients with end-stage heart failure (n=177). We found that the interleukin-13 receptor α1 is present in the myocardium and, together with the complementary type-2 interleukin-4 receptor chain Il4ra, is significantly downregulated in the hearts of patients with heart failure. Next, we showed that Il13ra1-deficient mice develop severe myocardial dysfunction and dyssynchrony compared to wild-type mice (left ventricular ejection fraction 29.7±9.9 versus 45.0±8.0; P=0.004, left ventricular end-diastolic diameter 4.2±0.2 versus 3.92±0.3; P=0.03). A bioinformatic analysis of mouse hearts indicated that interleukin-13 receptor α1 regulates critical pathways in the heart other than the immune system, such as extracellular matrix (normalized enrichment score=1.90; false discovery rate q=0.005) and glucose metabolism (normalized enrichment score=-2.36; false discovery rate q=0). Deficiency of Il13ra1 was associated with reduced collagen deposition under normal and pressure-overload conditions. The results of our studies in humans and mice indicate, for the first time, a role of interleukin-13 receptor α1 in myocardial homeostasis and heart failure and suggests a new therapeutic target to treat heart disease.


Control of Salmonella Newport on cherry tomato using a cocktail of lytic bacteriophages.
Bacteriophages have been envisioned as tools to control a variety of foodborne pathogenic bacteria. Salmonella is a foodborne pathogen that is a threat to public health around the world. Contaminated tomatoes have been associated with several Salmonella outbreaks. Hence, the objective of this work was to identify and characterize different lytic bacteriophages against Salmonella Newport, as one of top ten Salmonella serovars associated with human salmonellosis in North America, and then apply these phages to enhance the safety of cherry tomatoes. Four lytic phages against Salmonella Newport were selected based on their ability to lyse a majority of the 26 screened Salmonella serovars. The selected phages belong to Myoviridae (vB_SnwM_CGG4-1, vB_SnwM_CGG4-2) and Siphoviridae (vB_SnwM_CGG3-1, vB_SnwM_CGG3-2) families. They were found to be stable at different temperatures and pH, have latent periods ranging from 53 to 65 min and burst sizes from 92 to 177. In addition, the two Myoviridae phages have a lower frequency of developing bacteriophage insensitive mutants when compared with the Siphoviridae phages. No significant change in virulence gene expression was observed in the developed bacteriophage insensitive mutants when compared to the parental phage sensitive strain. Furthermore, the vB_SnwM_CGG4-1 genome revealed no homology to virulence or lysogenic genes. A phage cocktail was used to control the growth of S. Newport in broth medium and on contaminated cherry tomato. Complete inhibition of bacterial growth in broth medium was observed at 25 °C for 24 h. In addition, a 4.5 log10 unit reduction in the bacterial count was observed when applying the phage cocktail onto contaminated tomatoes stored at 22 °C for 3 days. These findings suggest that the isolated phages can be used for biocontrol of S. Newport to improve the safety of ready-to-eat (RTE) produce.


Sex differences in total cholesterol of Vietnamese adults.
The mid-life emergence of higher levels of total cholesterol (TC) for women than for men has been observed in different Western and Asian populations. The aim of this study was to investigate whether there is evidence of this in Vietnam and, if so, whether it can be explained by ageing, by body size and fatness, or by socio-demographic characteristics and behavioural factors. Participants (n = 14706, 50.9% females) aged 25-64 years were selected by multi-stage stratified cluster sampling from eight provinces each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Linear regression was used to assess the independent contributions of potential explanatory factors to mean levels of TC. Data were analysed using complex survey methods. Men and women had similar mean levels of body mass index (BMI), and men had modestly higher mean levels of waist circumference (WC), in each 5-year age category. The mean TC of women increased more or less continuously across the age range but with a step-up at age 50 years to reach higher concentrations on average than those of their male counterparts. The estimated step-up was not eliminated by adjustment for anthropometric indices including BMI or WC, or by adjustment for socio-demographic characteristics or behavioural factors. The estimated step-up was least for women with the greatest weight. There is a marked step-up in TC at age 50 years for Vietnamese women that cannot be explained by their age, or by their body fatness or its distribution, or by their socio-demographic characteristics or behavioural factors, and which results in greater mean levels of TC for middle-aged women than for their male counterparts in Vietnam.


How treatment affects the brain: meta-analysis evidence of neural substrates underpinning drug therapy and psychotherapy in major depression.
The idea that modifications of affect, behavior and cognition produced by psychotherapy are mediated by biological underpinnings predates the advent of the modern neurosciences. Recently, several studies demonstrated that psychotherapy outcomes are linked to modifications in specific brain regions. This opened the debate over the similarities and dissimilarities between psychotherapy and pharmacotherapy. In this study, we used activation likelihood estimation meta-analysis to investigate the effects of psychotherapy (PsyTh) and pharmacotherapy (DrugTh) on brain functioning in Major Depression (MD). Our results demonstrate that the two therapies modify different neural circuits. Specifically, PsyTh induces selective modifications in the left inferior and superior frontal gyri, middle temporal gyrus, lingual gyrus and middle cingulate cortex, as well as in the right middle frontal gyrus and precentral gyrus. Otherwise, DrugTh selectively affected brain activation in the right insula in MD patients. These results are in line with previous evidence of the synergy between psychotherapy and pharmacotherapy but they also demonstrate that the two therapies have different neural underpinnings.


Clinic- rather than self-monitoring of home blood samples: relevance of day-to-day variability to decision making.
The day-to-day variability of blood glucose concentrations in juvenile diabetes means that it is often more reasonable to aim to achieve a generally good pattern of blood glucose control, rather than regularly to assess the next insulin dose after each blood glucose measurement. This means that immediate assessment by the patient of his blood glucose concentrations is not always necessary. We have investigated control in 22 insulin-requiring diabetic patients by means of a monthly series of four blood samples taken during a day into collector bottles and transported to a laboratory for blood glucose assay. The overall means before breakfast, before lunch, before dinner, and before bed were 6.1, 5.8, 7.3, and 7.2 mmol/L, respectively. In many patients, sufficiently good control can be obtained by this method so that it is not necessary to ask them to measure their own blood glucose concentrations or to ask them to obtain the fairly expensive meters for reading glucose oxidase strips. Control would then probably be best assessed by a series of three daily profiles taken once per month, with, if necessary, the results being discussed with the patient. On the other hand, in more unstable diabetes, home assessment by patients of blood glucose measurements is indicated.


Mapping of PRM1 to human chromosome 16 and tight linkage of Prm-1 and Prm-2 on mouse chromosome 16.
The protamines are small, arginine-rich nuclear proteins that replace histones and transition proteins late in the haploid phase of spermatogenesis in mammals. The two mouse genes encoding protamines--Prm-1 and Prm-2--have been molecularly cloned and mapped to mouse chromosome 16 (MMU 16). A cDNA clone of mouse Prm-1 that hybridized to the corresponding human gene was used to analyze a panel of somatic cell hybrids made between human lymphoblasts and the E36 hamster cell line. The human gene, which we have designated PRM 1, was syntenic with human chromosome 16 (HSA 16) and discordant with all other human chromosomes. Linkage analysis in the mouse was accomplished using the backcross (Czech II x BALB/c Pt) x Czech II to map Prm-1 and Prm-2 to a position near the 5' terminus of MMU 16. No recombination between Prm-1 and Prm-2 was observed among 89 progeny of the Czech II x BALB/c cross or among 94 progeny of the backcross (CBA/J x BALB/cJ) x BALB/cJ, demonstrating that the two loci are separated by less than 1.6 cM on MMU 16. This tight linkage may be of functional significance, as Prm-1 and Prm-2 are among a limited number of genes known to be expressed postmeiotically in male haploid germ cells.


The 5-HT7 receptor system as a treatment target for mood and anxiety disorders: A systematic review.
Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this systematic review, we aimed to review the relationship between the 5-HT7 receptor system and mood and anxiety disorders, and to explore the pharmacology and therapeutic potential of medications that target the 5-HT7 receptor for their treatment. Medline, Cochrane Library, EMBASE, PsycINFO databases, the National Institute of Health website Clinicaltrials.gov, controlled-trials.com, and relevant grey literature were used to search for original research articles, and reference lists of included articles were then hand searched. Sixty-four studies were included in the review: 52 animal studies and 12 human studies. Studies used a variety of preclinical paradigms and questionnaires to assess change in mood, and few studies examined sleep or cognition. Forty-four out of 47 (44/47) preclinical 5-HT7 modulation studies identified potential antidepressant effects and 20/23 studies identified potential anxiolytic effects. In clinical studies, 5/7 identified potential antidepressant effects in major depressive disorder, 1/2 identified potential anxiolytic effects in generalized anxiety disorder, and 3/3 identified potential antidepressant effects in bipolar disorders. While there is some evidence that the 5-HT7 receptor system may be a potential target for treating mood and anxiety disorders, many agents included in the review also bind to other receptors. Further research is needed using drugs that bind specifically to 5-HT7 receptors to examine treatment proof of concept further.


The seasonal activity of Rhipicephalus appendiculatus Neumann 1901 (Acarina: Ixodidae) in the highveld of Zimbabwe Rhodesia.
Rhipicephalus appendiculatus passes through one generation per annum in the highveld of Zimbabwe, Rhodesia and shows a well-defined pattern of seasonal activity. Peak adult activity occurs in the rainy season, whereas peak larval and nymphal activity occurs in the dry season. Adult activity is regulated by the combined influences of temperature, humidity, and day length. Climatic factors have little or no direct influence on the activity of larvae and nymphs. The occurrence of the larval and nymphal activity peaks is determined by the timing of the adult activity peak and the duration of the preceeding developmental periods, which are temperature dependent. In the early rainy season, unfed adults climb to the tips of the grass and enter a period of quiescence prior to becoming active.


Detecting Sepsis: Are Two Opinions Better Than One?
The diagnosis of sepsis requires that objective criteria be met with a corresponding subjective suspicion of infection. We conducted a study to characterize the agreement between different providers' suspicion of infection and the correlation with patient outcomes using prospective data from a general medicine ward. Registered nurse (RN) suspicion of infection was collected every 12 hours and compared with medical doctor or advanced practice professional (MD/APP) suspicion, defined as an existing order for antibiotics or a new order for blood or urine cultures within the 12 hours before nursing screen time. During the study period, 1386 patients yielded 11,489 screens, 3744 (32.6%) of which met at least 2 systemic inflammatory response syndrome (SIRS) criteria. Infection was suspected by RN and MD/APP in 5.8% of cases, by RN only in 22.2%, by MD/APP only in 7.2%, and by neither provider in 64.7%. Overall agreement rate was 80.7% for suspicion of infection (κ = 0.11, P < 0.001). Progression to severe sepsis or shock was highest when both providers suspected infection in a SIRS-positive patient (17.7%), was substantially reduced with single-provider suspicion (6.0%), and was lowest when neither provider suspected infection (1.5%) (P < 0.001). Provider disagreement regarding suspected infection is common, with RNs suspecting infection more often, suggesting that a collaborative model for sepsis detection may improve timing and accuracy. Journal of Hospital Medicine 2017;12:256-258.


Growth and differentiated properties of a kidney epithelial cell line (MDCK).
The MDCK dog kidney epithelial cell line has been shown to retain the capacity for vectorial salt and fluid transport, sensitivity to growth regulation, and the ability to regenerate kidney tubular-like structures when injected into athymic nude mice. MDCK cells grown in tissue culture or in baby nude mice have the morphological properties of distal tubular cells, form tight and gap junctions, lack proximal tubular enzyme markers, and possess appreciable activities of Na+-K4-ATPase, ectoleucine aminopeptidase, and ectoalkaline phosphatase. Adenylate cyclase in intact cells is responsive to vasopressin, prostaglandins E1 and E2, and glucagon. Two Na+ transport systems have been characterized: a Na+-H+ antiport system, sensitive to amiloride inhibition, and a NaCl-KCl cotransport system, dependent on metabolic energy and sensitive to furosemide inhibition. Genetic techniques have been used to modify the properties of the cells. The results suggest that the MDCK cell line has retained the differentiated properties of the kidney epithelial cells of origin and that a clonally isolated cell possesses the receptor, transmission, and target enzyme systems necessary for the regulation of transcellular salt and fluid transport.


COVID-19 pandemic impact on antibiotics sensitivity of E. coli and K. pneumoniae from urine specimens: a retrospective study.
Escherichia coli and Klebsiella pneumoniae are common organisms associated with urinary tract infections. The COVID-19 pandemic has had a negative impact on antibiotics misuse globally. This study analyzed the antibiotic susceptibility for these two pathogens isolated from urine samples during the period of 18 months before and after the COVID-19 pandemic. This retrospective study was conducted in Al-Karak government referral and teaching hospital in Jordan. The study included two groups; group A included urine samples from September 2018 to March 11, 2020, while group B from March 12, 2020 to August 2021. Samples were analyzed using the automated VITEK 2 system and the analysis of results was done using the WHONET version 5.6. A total of 642 E. coli and 113 K. pneumoniae were isolated and analyzed. The antibiogram showed a significant overall increase in antibiotic susceptibility of both bacteria during the pandemic period (group B). The sensitivity has significantly increased by 75% (15/20) and 50% (10/20) for all antibiotics used for E. coli and K. pneumoniae respectively. On the other hand, E. coli showed a significant increase in resistance to ceftriaxone (13.4%) and gentamicin (6.4%). A similar trend of an increase in resistance to gentamicin (17.4%) was also noticed among K. pneumoniae isolates. The antimicrobial susceptibility pattern for urine isolates showed an increased overall sensitivity and an increased resistance to ceftriaxone and gentamicin during the pandemic period. Our results highlight the need for revising and updating the antimicrobial stewardship programs post-COVID pandemic utilizing local data.


Exceptionally preserved stomach contents of a young tyrannosaurid reveal an ontogenetic dietary shift in an iconic extinct predator.
Tyrannosaurids were large carnivorous dinosaurs that underwent major changes in skull robusticity and body proportions as they grew, suggesting that they occupied different ecological niches during their life span. Although adults commonly fed on dinosaurian megaherbivores, the diet of juvenile tyrannosaurids is largely unknown. Here, we describe a remarkable specimen of a juvenile Gorgosaurus libratus that preserves the articulated hindlimbs of two yearling caenagnathid dinosaurs inside its abdominal cavity. The prey were selectively dismembered and consumed in two separate feeding events. This predator-prey association provides direct evidence of an ontogenetic dietary shift in tyrannosaurids. Juvenile individuals may have hunted small and young dinosaurs until they reached a size when, to satisfy energy requirements, they transitioned to feeding on dinosaurian megaherbivores. Tyrannosaurids occupied both mesopredator and apex predator roles during their life span, a factor that may have been key to their evolutionary success.


[The taxonomic position, ecological aspects and physiological-biochemical characteristics of microorganisms having industrial importance].
The paper presents fundamental results of the investigations obtained in the Department of Physiology of Industrial Microorganisms at the Institute of Microbiology and Virology of the National Academy of Sciences of Ukraine for the recent 15-20 years, as well as the Department developments directed to creation of biotechnological preparations, products and processes, most of which have been put into practice of the national economy and health protection. Data have been presented concerning the study of systematics, biology and ecology of nocardioform and coryneform bacteria, lactic acid bacteria and yeasts. When studying physiological-biochemical peculiarities and biological effect of the studied microorganisms, considerable attention has been paid to growth physiology of lactic acid bacteria, yeasts, lectin-forming bacteria, to processes of shaping of fungal mycelium under the conditions of batch cultivation as well as to microorganisms which take part in sewage treatment for heavy metals and oil products. The work also deals with the problems of creation and application in the economy of preparations intended for treatment and prophylaxis of gastro-intestinal diseases of cattle, poultry and swine, for siloing fodder, of new lactic acid preparations of functional direction, technological grounds of sewage treatment for oil products and six-valent toxic chrome.


Practical Management of Lumps and Bumps of the Fingers, Hand, and Wrist.
Primary care physicians encounter many patients who present with lumps and bumps on their fingers, hands, and wrists. Some benign lesions including ganglion cysts, epidermal inclusion cysts, and giant cell tumors of the tendon sheath that are benign and can be managed by primary care clinicians most of the time in an outpatient setting. We conducted a narrative of review of literature on the clinical presentation, diagnosis, prognosis, and management of common types of lumps and bumps found on the fingers, hand, and wrist. Based on the literature review and our clinical practice, we provide indications for referral to plastic surgeons or other specialists for these lesions.


[The spread of aerosols and splashes during the removal of dental deposits with an ultrasonic scaler].
There is an increased prevalence of respiratory infections among dentists, which is associated with a heavily polluted breathing area in the dental office. Patients and dentists are at high risk of cross-infection due to the spread of aerosols in the form of droplets suspended in the air. The ultrasonic scaler is the largest source of aerosols and spatter in the dental office. Aerosols remain in the air for a long time even after the completion of a dental procedure and have a potential risk of inhalation. To evaluate the spatial distribution of aerosols and splashes during a dental appointment during ultrasonic dental treatment. The study was conducted on a mannequin equipped with phantom jaws, where dental plaque removal was simulated using an ultrasonic scaler filled with fluorescein. The amount of contamination was measured using a transparent grid with a square marking of 1 cm2. The grid was placed on top of a disk of filter paper and the area of contamination was measured by counting the number of soiled squares. If a square had at least 1 yellow area, then it was considered polluted. Aerosols and splashes were distributed up to 60 cm from the head restraint. Aerosols can spread over more than 1 m. The study showed the spread of aerosols and splashes during dental appointments. The risk of infection can be minimized by following simple protective measures.


Model-assisted measurements of suspension-feeding flow velocities.
Benthic marine suspension feeders provide an important link between benthic and pelagic ecosystems. The strength of this link is determined by suspension-feeding rates. Many studies have measured suspension-feeding rates using indirect clearance-rate methods, which are based on the depletion of suspended particles. Direct methods that measure the flow of water itself are less common, but they can be more broadly applied because, unlike indirect methods, direct methods are not affected by properties of the cleared particles. We present pumping rates for three species of suspension feeders, the clams Mya arenaria and Mercenaria mercenaria and the tunicate Ciona intestinalis, measured using a direct method based on particle image velocimetry (PIV). Past uses of PIV in suspension-feeding studies have been limited by strong laser reflections that interfere with velocity measurements proximate to the siphon. We used a new approach based on fitting PIV-based velocity profile measurements to theoretical profiles from computational fluid dynamic (CFD) models, which allowed us to calculate inhalant siphon Reynolds numbers (Re). We used these inhalant Re and measurements of siphon diameters to calculate exhalant Re, pumping rates, and mean inlet and outlet velocities. For the three species studied, inhalant Re ranged from 8 to 520, and exhalant Re ranged from 15 to 1073. Volumetric pumping rates ranged from 1.7 to 7.4 l h-1 for M. arenaria, 0.3 to 3.6 l h-1 for M. mercenaria and 0.07 to 0.97 l h-1 for C. intestinalis We also used CFD models based on measured pumping rates to calculate capture regions, which reveal the spatial extent of pumped water. Combining PIV data with CFD models may be a valuable approach for future suspension-feeding studies.


Arctiin regulates collagen type 1α chain 1 mRNA expression in human dermal fibroblasts via the miR‑378b‑SIRT6 axis.
Arctiin, a lignin isolated from Arctium lappa, exhibits a variety of biological effects, including anti‑viral, anti‑inflammatory, and anti‑proliferative actions, in mammalian cells. In a previous study, arctiin was demonstrated to induce procollagen type I synthesis and exhibited protective effects against ultraviolet B (UVB) radiation in normal human dermal fibroblasts (nHDFs). However, the underlying molecular mechanism of arctiin‑mediated collagen synthesis remains unknown. In the present study, the mechanism for increased expression of collagen type 1α 1 chain (COL1A1) mRNA in arctiin‑induced nHDFs was identified. The expression of microRNA‑378b (miR‑378b), downregulated by arctiin, was correlated with the expression of sirtuin‑6 (SIRT6) mRNA, a regulator of COL1A1 mRNA. Furthermore, it was revealed that arctiin protected the UVB radiation‑mediated decrease in COL1A1 mRNA expression, through the miR‑378b/SIRT6 signaling pathway. In conclusion, these results suggest that arctiin regulates COL1A1 through the miR‑378b‑SIRT6 axis.


In vivo growth inhibition of sarcoma 180 by piperlonguminine, an alkaloid amide from the Piper species.
Many authors have already emphasized that phytochemicals from spices have biological applications. Piperlonguminine is a known alkaloid amide from peppers, including Piper divaricatum. The aim of this study was to investigate the in vitro and in vivo antitumor effects of piperlonguminine in experimental models. In order to evaluate the toxicological aspects related to piperlonguminine treatment, hematological, biochemical, histopathological and morphological analyses of treated animals were performed. Piperlonguminine did not show any significant in vitro cytotoxic effect at experimental exposure levels, but showed an in vivo antitumor effect. After 7 days of treatment, the inhibition rates were 38.71% and 40.68% at doses of 25 mg kg(-1) and 50 mg kg(-1), respectively. The histopathological analysis suggests that the liver and kidney were only weakly affected by piperlonguminine treatment. Neither the enzymatic activity of transaminases (AST and ALT) nor the urea levels were significantly altered. In the hematological analysis, all parameters analysed remained constant after piperlonguminine treatment. In conclusion, these data reinforce the anticancer potential of spice components.


Does pharmacological castration as adjuvant therapy for prostate cancer after radiotherapy affect anxiety and depression levels, cognitive functions and quality of life?
Adjuvant hormonotherapy for prostate cancer patients after radical radiotherapy has a well-established value. However, the impact of such treatment on the patients' quality of life remains to be elucidated. The objective is to assess the impact of adjuvant hormonotherapy with luteinizing hormone-releasing hormone analogue after radical radiotherapy on anxiety and depression levels, cognitive function, sexual function and quality of life of prostate cancer patients. Two groups of patients were tested: men treated with adjuvant hormonotherapy (88 patients) and men without hormonotherapy (61 patients). Anxiety, depression and cognitive functions were evaluated. Patients answered questions addressing problems linked to hormonal equilibrium. The patients rated their mental status, physical status, quality of life and quality of their relationship. There were no statistically significant differences between patients on hormonotherapy and without hormonotherapy in the level of anxiety and depression (p = 0.844 and p = 0.954) as well as in cognitive function (p = 0.661). Satisfactory sexual performance was preserved in 9/65 patients (14%) on hormonotherapy and the same was applied to 19/49 patients (39%) without hormonotherapy. The difference was statistically significant (p = 0.003). Hormonotherapy was associated with decreased libido (p = 0.031), hot flushes (p < 0.001) and sweating (p < 0.001). No statistically significant differences were found between the groups in the self-rated physical and psychological well-being (p = 0.476 and p = 0.597), quality of life (p = 0.622) and quality of relationship (p = 0.064). Adjuvant hormonotherapy enhances neither anxiety nor depression, does not impair cognitive function but has a negative effect on the patients' sexual function. It does not worsen self-rated quality of relationship and quality of life.


Cluster Detection Tests in Spatial Epidemiology: A Global Indicator for Performance Assessment.
In cluster detection of disease, the use of local cluster detection tests (CDTs) is current. These methods aim both at locating likely clusters and testing for their statistical significance. New or improved CDTs are regularly proposed to epidemiologists and must be subjected to performance assessment. Because location accuracy has to be considered, performance assessment goes beyond the raw estimation of type I or II errors. As no consensus exists for performance evaluations, heterogeneous methods are used, and therefore studies are rarely comparable. A global indicator of performance, which assesses both spatial accuracy and usual power, would facilitate the exploration of CDTs behaviour and help between-studies comparisons. The Tanimoto coefficient (TC) is a well-known measure of similarity that can assess location accuracy but only for one detected cluster. In a simulation study, performance is measured for many tests. From the TC, we here propose two statistics, the averaged TC and the cumulated TC, as indicators able to provide a global overview of CDTs performance for both usual power and location accuracy. We evidence the properties of these two indicators and the superiority of the cumulated TC to assess performance. We tested these indicators to conduct a systematic spatial assessment displayed through performance maps.


Manipulating the Assembly of Spray-Deposited Nanocolloids: In Situ Study and Monolayer Film Preparation.
Fabrication of nanoparticle arrays on a substrate is one of the most concerned aspects for manipulating assembly of nanoparticles and preparing functional nanocomposites. Here, we studied in situ the assembly kinetics of polystyrene nanocolloids by using grazing incidence small-angle X-ray scattering. The structure formation of the nanoparticle film is monitored during air-brush spraying, which provides a rapid and scalable preparation. By optimizing the substrate temperature, the dispersion of the nanocolloids can be tailored to prepare monolayer film. The success of the monolayer preparations is attributed to the fast solvent evaporation which inhibits the aggregation of the nanocolloids. The present study may open a new avenue for the manufacture-friendly preparation of well-dispersed nanoparticle thin films.


Ab initio study of the circular intensity difference in electric-field-induced second harmonic generation of chiral natural amino acids.
We present a systematic computational study of circular intensity difference (CID) in electric-field-induced second harmonic generation (EFISHG) of some representative chiral natural amino acids (Alanine, Arginine, Aspartic Acid, Cysteine and Tryptophan), taking into account the electric-dipole, electric-quadrupole and magnetic-dipole interactions. The calculations are performed by applying cubic response theory at both Hartree-Fock and Density Functional theory levels, the latter with the popular Becke-three parameters, Lee, Yang and Parr (B3LYP) functional. Special focus is given to the basis set, electron correlation and origin dependence of the properties. The full set of molecular parameters defined by Lam and Thirunamachandran in their reference theoretical paper published in 1982 [J. Chem. Phys., 1982, 77, 3810] is obtained and discussed. This permits the prediction of the CID observable for different possible experimental setups.


DICE: A Drug Indication Classification and Encyclopedia for AI-Based Indication Extraction.
Drug labeling contains an 'INDICATIONS AND USAGE' that provides vital information to support clinical decision making and regulatory management. Effective extraction of drug indication information from free-text based resources could facilitate drug repositioning projects and help collect real-world evidence in support of secondary use of approved medicines. To enable AI-powered language models for the extraction of drug indication information, we used manual reading and curation to develop a Drug Indication Classification and Encyclopedia (DICE) based on FDA approved human prescription drug labeling. A DICE scheme with 7,231 sentences categorized into five classes (indications, contradictions, side effects, usage instructions, and clinical observations) was developed. To further elucidate the utility of the DICE, we developed nine different AI-based classifiers for the prediction of indications based on the developed DICE to comprehensively assess their performance. We found that the transformer-based language models yielded an average MCC of 0.887, outperforming the word embedding-based Bidirectional long short-term memory (BiLSTM) models (0.862) with a 2.82% improvement on the test set. The best classifiers were also used to extract drug indication information in DrugBank and achieved a high enrichment rate (>0.930) for this task. We found that domain-specific training could provide more explainable models without performance sacrifices and better generalization for external validation datasets. Altogether, the proposed DICE could be a standard resource for the development and evaluation of task-specific AI-powered, natural language processing (NLP) models.


Rapeseed meal in complete feeds for dairy cows.
Three complete feeds containing low glucosinolate, low erucic acid rapeseed meal (Cultivar "1788"), high glucosinolate, low erucic acid rapeseed meal (Cultivar "Span"), or soybean meal as protein supplement were evaluated with lactating Holstein cows in a double 3 X 3 Latin square design. Lactation performance, hematology, blood chemistry, serum-free amino acids, rumen volatile fatty acid concentrations, and milk fatty acid composition were measured. The 1788 ration tended to increase yield of milk and of total solids. Hematology, blood chemistry, and serum-free amino acid data showed no differencein utilization of nitrogen. Concentrations of volatile fatty acids were not different. Feeding of the high glucosinolate Span ration did not reduce feed intake. However, there were indications that Span-fed cows may have experienced hypothyroidism. No differences were in erucic acid content of milk fat, and concentrations were low. Rapeseed meals 1788 and Span and soybean meal were equal as protein supplements.


Being on sick leave due to heart failure: Encounters with social insurance officers and associations with sociodemographic factors and self-estimated ability to return to work.
Little is known about sick leave and the ability to return to work (RTW) for people with heart failure (HF). Previous research findings raise questions about the significance of encounters with social insurance officers (SIOs) and sociodemographics in people sick-listed due to HF. To investigate how people on sick leave due to HF experience encounters with SIOs and associations between sociodemographic factors, experiences of positive/negative encounters with SIOs, and self-estimated ability to RTW. This was a population-based study with a cross-sectional design. The sample consisted of 590 sick-listed people with HF in Sweden. A register-based investigation supplemented with a postal survey questionnaire was conducted. Bivariate correlations and logistic regression analysis was used to test associations between sociodemographic factors, positive and negative encounters, and self-estimated ability to RTW. People with low income were more likely to receive sickness compensation. A majority of the responders experienced encounters with SIOs as positive. Being married was significantly associated with positive encounters. Having a low income was related to negative encounters. More than a third of the responders agreed that positive encounters with SIOs facilitated self-estimated ability to RTW. High income was strongly associated with the impact of positive encounters on self-estimated ability to RTW. Encounters between SIOs and people on sick leave due to HF need to be characterized by a person-centred approach including confidence and trust. People with low income need special attention.


The effects of tonic locus ceruleus output on sensory-evoked responses of ventral posterior medial thalamic and barrel field cortical neurons in the awake rat.
In mammals, the pontine nucleus locus ceruleus (LC) is the sole source of norepinephrine (NE) projections to the forebrain. Increasing tonic discharge of LC neurons elevates extracellular levels of NE in the cortex and thalamus. Tonic LC discharge is linked to the level of wakefulness and behavioral performance, demonstrating an optimal firing rate during sustained attention tasks. Iontophoretic application of NE to target neurons in the forebrain has been shown to produce a diverse set of neuromodulatory actions, including augmentation of synaptically evoked discharge as well as suppression of spontaneous and stimulus-evoked firing patterns. Iontophoretic studies cataloged potential NE effects; however, the context in which such actions could occur in awake behaving animals remained controversial. To address this issue, the current study examined the effects of increasing tonic LC output on spontaneous and stimulus-evoked discharge of neurons within the ventroposterior medial (VPM) thalamus and barrel field (BF) somatosensory cortex of awake animals using multichannel extracellular recording strategies. The present findings indicate two primary outcomes that result from increasing frequencies of LC stimulation, either an inverted-U facilitating response profile or monotonic suppression of sensory-evoked neuronal responses. Increased tonic LC output generally decreased neuronal response latency measures for both BF cortical and VPM thalamic cells. LC-mediated effects on target VPM and BF cortical neuron sensory processing are consistent with previous demonstrations of NE modulatory actions on central neurons but indicate that such actions are cell specific. Moreover, clear differences were observed between the modulation of VPM and BF cortical cells. These data suggest that sensory signal processing is continually altered over the range of tonic LC discharge frequencies that occur in the waking animal. Such changes may account for LC-mediated shifts in sensory network performance across multiple stages of arousal and attention.


Increased nuchal translucency as a prenatal manifestation of congenital adrenal hyperplasia.
We present two cases of pregnant women with a previous history of congenital adrenal hyperplasia. In both cases the only abnormal feature in the initial pregnancy had been increased nuchal translucency at 10-14 weeks of gestation. The fetal karyotype was normal and a diagnosis of congenital adrenal hyperplasia was made after delivery. In their current pregnancies, both fetuses also had increased nuchal translucency and normal fetal karyotype. Diagnosis of 21-hydroxylase deficiency was made prenatally by DNA analysis. These findings in four affected fetuses suggest that congenital adrenal hyperplasia should be added to the list of genetic anomalies associated with an increase in nuchal translucency.


Human papillomavirus clearance among males is associated with HIV acquisition and increased dendritic cell density in the foreskin.
The association between human papillomavirus (HPV) infection and the risk of human immunodeficiency virus (HIV) seroconversion is unclear, and the genital cellular immunology has not been evaluated. A case-control analysis nested within a male circumcision trial was conducted. Cases consisted of 44 male HIV seroconverters, and controls were 787 males who were persistently negative for HIV. The Roche HPV Linear Array Genotype Test detected high-risk HPV (HR-HPV) and low-risk HPV (LR-HPV) genotypes. Generalized estimating equations logistic regression was used to estimate adjusted odds ratios (aORs) of HIV seroconversion. In addition, densities of CD1a(+) dendritic cells, CD4(+) T cells, and CD8(+) T cells were measured using immunohistochemistry analysis in foreskins of 79 males randomly selected from participants in the circumcision trial. HR-HPV or LR-HPV acquisition was not significantly associated with HIV seroconversion, after adjustment for sexual behaviors. However, HR-HPV and LR-HPV clearance was significantly associated with HIV seroconversion (aOR, 3.25 [95% confidence interval {CI}, 1.11-9.55] and 3.18 [95% CI, 1.14-8.90], respectively). The odds of HIV seroconversion increased with increasing number of HPV genotypes cleared (P < .001, by the test for trend). The median CD1a(+) dendritic cell density in the foreskin epidermis was significantly higher among males who cleared HPV (72.0 cells/mm(2) [interquartile range {IQR}, 29.4-138.3 cells/mm(2)]), compared with males who were persistently negative for HPV (32.1 cells/mm(2) [IQR, 3.1-96.2 cells/mm(2)]; P = .047), and increased progressively with the number of HPV genotypes cleared (P = .05). HPV clearance was associated with subsequent HIV seroconversion and also with increased epidermal dendritic cell density, which potentially mediates HIV seroconversion.


Equivalence of the EMD- and NEMD-based decomposition of thermal conductivity into microscopic building blocks.
Thermal conductivity of a material can be comprehended as being composed of microscopic building blocks relevant to the energy transfer due to a specific microscopic process or structure. The building block is called the partial thermal conductivity (PTC). The concept of PTC is essential to evaluate the contributions of various molecular mechanisms to heat conduction and has been providing detailed knowledge of the contribution. The PTC can be evaluated by equilibrium molecular dynamics (EMD) and non-equilibrium molecular dynamics (NEMD) in different manners: the EMD evaluation utilizes the autocorrelation of spontaneous heat fluxes in an equilibrium state whereas the NEMD one is based on stationary heat fluxes in a non-equilibrium state. However, it has not been fully discussed whether the two methods give the same PTC or not. In the present study, we formulate a Green-Kubo relation, which is necessary for EMD to calculate the PTCs equivalent to those by NEMD. Unlike the existing theories, our formulation is based on the local equilibrium hypothesis to describe a clear connection between EMD and NEMD simulations. The equivalence of the two derivations of PTCs is confirmed by the numerical results for liquid methane and butane. The present establishment of the EMD-NEMD correspondence makes the MD analysis of PTCs a robust way to clarify the microscopic origins of thermal conductivity.


Asthenospermia in hay fever patients improved by stopping treatment with histamine H1 receptor antagonists.
We report two cases of asthenospermia, which appeared to be associated with exposure to histamine H1 receptor antagonists. A 44-year-old man and a 35-year-old man had continued the treatment with fexofenadine hydrochloride and cetirizine hydrochloride, respectively, under the diagnosis of hay fever. They and their wives had been examined as infertile couples. Infertility evaluations revealed no problems with their wives; the patients, however, were found to have a low sperm motility (<10%). On suspicion of adverse effects of the histamine H1 receptor antagonists, they stopped treatment with these drugs, which resulted in a complete reversal of spermatic dysfunction. Current information identifies the potential fertility hazards of histamine H1 receptor antagonists.


Detailed characterization of metastatic lymph nodes improves the prediction accuracy of currently used risk stratification systems in N1 stage papillary thyroid cancer.
The characteristics of metastatic lymph nodes (MLNs) have been investigated as important predictors of recurrence and progression in papillary thyroid cancer (PTC). However, clinically applicable risk stratification systems are limited to the assessment of size and number of MLNs. This study investigated the predictive value of detailed characteristics of MLNs in combination with currently used risk stratification systems. We retrospectively characterized 2811 MLNs from 9014 harvested LNs of 286 patients with N1 PTC according to the maximum diameter of MLN (MDLN), maximum diameter of metastatic focus (MDMF), ratio of both diameters (MDMFR), lymph node ratio (LNR, number of MLNs/number of total harvested LNs), presence of extranodal extension (ENE), desmoplastic reaction (DR), cystic component, and psammoma body. Factors related to the size and number of MLNs were associated with increased risk of recurrence and progression. Extensive presence of ENE (>40%) and DR (≥50%) increased the risk of recurrence/progression. The combination of MDLN, LNR, ENE, and DR had the highest predictive value among MLN characteristics. Combination of these parameters with ATA risk stratification or 1-year response to therapy improved the predictive power for recurrence/progression from a Harrell's C-index of 0.781 to 0.936 and 0.867 to 0.960, respectively. The combination of currently used risk stratification systems with detailed characterization of MLNs may improve the predictive accuracy for recurrence/progression in N1 PTC patients.


Photobleaching through glass micropipettes: sodium channels without lateral mobility in the sarcolemma of frog skeletal muscle.
Sodium currents were recorded from frog skeletal muscle by using fire-polished micropipettes to electrically isolate and voltage clamp a small patch of sarcolemma. Sodium current amplitude served as an assay for the number of functional sodium channels in the patch. With the pipette as a light guide, these channels were irradiated with ultraviolet (UV) light directed through a quartz fiber into the back end of the pipette. The UV light emerging from the pipette tip caused localized destruction of the sodium channels in the patch, reducing sodium current 3- to 5-fold during a 30-90 s irradiation. If sodium channels could diffuse laterally in the membrane, current from the patch should recover with time as fresh channels enter from neighboring areas. No such recovery was observed during observation for 1 hr after irradiation. Our results set an upper limit of 10(-12) cm2/s for the diffusion coefficient--1/1000th that of rhodopsin, a membrane protein in the cell membrane of retinal rods. It is suggested that sodium channels are anchored in the sarcolemma.


Use of pregabalin for nonconvulsive seizures and nonconvulsive status epilepticus.
To determine the efficacy of pregabalin (PGB) in treatment of frequent nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE) in critically ill patients. In this retrospective study, 21 patients were identified as having received pregabalin for the treatment of NCS as determined by continuous electroencephalographic monitoring. The patients were considered to be responders if their seizures were terminated within 24h of initiation of PGB without the addition of another antiepileptic agent. Of the 21 patients who received PGB for treatment of NCS or NCSE, 11 (52%) were responders. PGB was administered via a nasogastric tube or orally and was the 2nd to 4th agent used. The average initial dose and total daily dose of PGB was similar in the responders and non-responders (342mg vs. 360mg, respectively). PGB was more effective in aborting NCS (9 patients, 82%) than NCSE (2 patients, 18%). Of the 9 brain tumor patients, PGB resulted in seizure cessation in 67% (6 patients). In contrast, all patients with hypoxic injury (4) did not respond to PGB. The responders were noted to have better clinical outcome (64% vs. 9% discharged home). Most of the patients tolerated the medication without any significant short term adverse effects, except two patients who were noted to have dizziness and sedation. Pregabalin may be safe option for add-on treatment for nonconvulsive seizures in critically ill patients when conventional therapy fails.


A comprehensive review of epilepsy in the Arab world.
We conducted a comprehensive review of the epidemiology of epilepsy in the Arab world. Epidemiological literature about epilepsy from 22 countries of the Arab League was searched in French and English using several keywords (specific and wider) and combinations, individually for each country. The search was conducted on Google first and then on PubMed. The results are presented as counts, proportions, and medians along with 95% confidence intervals (CI). Unpaired t-test with unequal variance and regressions were performed, altogether and individually, for lifetime and active epilepsy prevalence as well as incidence. Google provided 21 prevalence, four camp and nine incidence estimates while PubMed provided ten such estimates; none of them was identified by Google. No epidemiological data about epilepsy was found from 10/22 countries. Excluding pediatric studies, 13 prevalence estimates from six countries were identified. Including pediatric studies, 21 estimates from nine countries were found. Median lifetime and active epilepsy prevalence were 7.5/1000 (95% CI 2.6-12.3, range 1.9-12.9) and 4.4/1000 (95% CI 2.1-9.3, range 2.1-9.3), respectively, excluding pediatric studies (1984-2014, N=244081). Median incidence was 56.0/100,000 (n=9, N=122484, 95% CI 13.7-147.9, range 10.4-190). The fact that no epidemiological data about epilepsy is available in the public domain for almost one half of all Arab countries offers opportunities for future research. This thorough review of existing literature demonstrates a prevalence of epilepsy three times higher than previously reported for this region. The median incidence is similar to other regions of the world, e.g. North America. Google yielded additional valuable sources not indexed in PubMed and provided pertinent references more quickly.


Quality care in seniors with new-onset rheumatoid arthritis: a Canadian perspective.
To estimate the percentage of seniors with rheumatoid arthritis (RA) receiving disease-modifying antirheumatic drugs (DMARDs) within the first year of diagnosis. We assembled an incident RA cohort from Ontario physician billing data for 1997-2006. We used a standard algorithm to identify 24,942 seniors with RA based on ≥ 2 billing codes ≥ 60 days apart but within 5 years. Drug exposures were obtained from pharmacy claims data. We followed subjects for 1 year, assessing if they had been exposed (defined as ≥ 1 prescription) to 1 or more DMARDs within the first year of RA diagnosis. We assessed secular trends and differences for subjects who had received rheumatology care (defined as ≥ 1 rheumatology encounter) versus those who had not. In total, only 39% of the 24,942 seniors with new-onset RA identified over 1997-2006 were exposed to DMARD therapy within 1 year of diagnosis. This increased from 30% in 1997 to 53% in 2006. Patients whose care involved a rheumatologist were more likely to be exposed to DMARDs than those who had no rheumatology care. In 2006, 67% of subjects receiving rheumatology care were exposed to DMARDs versus 21% of those with no rheumatology care. Improvements in RA care have occurred, but more efforts are needed. Subjects receiving rheumatology care are much more likely to receive DMARDs as compared to those with no rheumatology care. This emphasizes the key role of rheumatologists.


Hospitalizations for infections by age and sex: register-based study of Danish children 1977-2014.
Background: Infectious diseases are a major cause of hospitalizations in children and there is increasing interest in sex differences in immunity during childhood. Therefore, we examined hospital admission rates for infectious diseases in Danish children by age and sex.Methods: Register-based cohort study of all Danish residents aged 0-14 years from 1977 to 2014. We examined total admission rate for infections and rates of admission by types of infection.Results: This study included 3,689,999 children and 1,080,750 admissions for infections. The admission rates peaked at age 0 months (boys, 197.9 admissions per 1000 person-years; girls, 160.9) and age 11 months (boys, 155.5; girls, 113.9). The male-female ratio of admissions was 1.25 for children aged 0-14 years, but varied by age and type of infection. Boys had the highest admission rate for any infection until 9 years of age after which girls had a higher rate. Boys had higher admission rates for gastrointestinal infections and lower respiratory tract infections than girls at all ages. The admission rates for upper respiratory tract infections and 'Other infections' for girls were higher than the rates for boys at age 10 and 4 years, respectively.Conclusions: Overall, boys had around 25% higher admission rates for infections than girls, with some variation according to age and type of infection.


Core versus specialty rotations do not affect students' surgical development.
Research is scarce on how the diversity of surgical rotations affects students. We sought to assess the effect of core rotations compared to specialty rotations on students' development. Students were given a suturing workshop at the beginning of their surgical clerkship along with a questionnaire. They performed both a simple and a complex suturing task at the beginning and end of the 2-month clerkship. The students were divided into 2 groups based on their surgical rotations. Technical skill and exam scores were compared. Thirty-eight students were included in the study. Objective scores increased for the simple task (14.2, standard deviation 4.5 vs 16.4, standard deviation 4.2, P = .04) and the complex task (12.9, standard deviation 5.3 vs 16.5, standard deviation 4.1, P < .01). Times decreased for the simple task (5.1, standard deviation 1.8 vs 4.1, standard deviation 1.3, min, P < .01) and the complex task (7.9, standard deviation 2.7 vs 6.3, standard deviation 1.5, min, P < .01). Using multivariate analysis, we found that reported hours in the operating room per week and previous hands-on experience affected proficiency of the simple suturing task only. Sixteen students had predominantly core surgical rotations. When compared to the 22 students with more specialty rotations, the only difference was gender (87.5% male vs 50.0% male, P = 0.02). There was no significant difference in the completion times (P = .96, .82), the objective scores (P = .06, .120), the written exam scores (P = .57), or the oral exam scores (P = .89). In this small study, it was found that the type of students' rotations does not affect surgical skill or knowledge acquisition.


Audiovisual Interactions in Stereo Sound Localization for Individuals With Unilateral Hearing Loss.
This study investigated the effects of unilateral hearing loss (UHL), of either conductive or sensorineural origin, on stereo sound localization and related visual bias in listeners with normal hearing, short-term (acute) UHL, and chronic UHL. Time-delay-based stereophony was used to isolate interaural-time-difference cues for sound source localization in free field. Listeners with acute moderate (<40 dB for tens of minutes) and chronic severe (>50 dB for more than 10 years) UHL showed poor localization and compressed auditory space that favored the intact ear. Listeners with chronic moderate (<50 dB for more than 12 years) UHL performed near normal. These results show that the auditory spatial mechanisms that allow stereo localization become less sensitive to moderate UHL in the long term. Presenting LED flashes at either the same or a different location as the sound source elicited visual bias in all groups but to different degrees. Hearing loss led to increased visual bias, especially on the impaired side, for the severe and acute UHL listeners, suggesting that vision plays a compensatory role in restoring perceptual spatial symmetry.


Bacterial flora in relation to cataract extraction. V. Effects of topical antibiotics on the preoperative conjunctival flora.
In a randomized study comprising 60 patients, six different prophylactic regimens were evaluated for their effectiveness in eradicating bacteria on the conjunctivas before surgery. Gentamicin sulfate ophthalmic solution was the only antibiotic able to eliminate bacteria in almost all of the examined patients. The other drugs (chloramphenicol solution, oxytetracycline-polymyxin B ointment, sulphamethizole, bacitracin-neomycin and ristocetin-polymyxin B solutions) were not effective, although most of the isolated strains were sensitive to the respective antibiotics, probably because of the short treatment period (18 h). The problem of prophylactic therapy of ophthalmology is discussed, and some guide lines are given.


3H-batrachotoxinin-A benzoate binding to voltage-sensitive sodium channels: inhibition by the channel blockers tetrodotoxin and saxitoxin.
The sodium channel blockers tetrodotoxin (TTX) and saxitoxin (STX) and the channel activator batrachotoxin (BTX) produce their effects by binding to separate and distinct sites on the channel protein. The fact that TTX- and STX-modified sodium channels are blocked to sodium flux has precluded drawing any direct conclusions regarding the effect of TTX/STX on BTX binding based on electrophysiological or 22Na flux measurements. Nevertheless, these sites have been presumed to be non-interacting. In this study, 3H-batrachotoxinin-A benzoate (BTX-B), a tritiated congener of BTX, has been used to provide a direct assessment of these binding interactions. Equilibrium specific binding of 3H-BTX-B to sodium channels in vesicular preparations of mouse brain in the presence of scorpion toxin was measured using a filtration assay procedure. At 25 degrees C both TTX and STX inhibit 3H-BTX-B binding in a concentration-dependent and noncompetitive manner. This inhibition is markedly temperature-dependent, being negligible at 37 degrees C and maximal at 18 degrees C, the lowest temperature investigated. Scatchard analysis of BTX-B binding isotherms at 25 degrees C in the presence and absence of 1 microM TTX revealed that inhibition is due to a 3-fold decrease in the affinity of BTX-B binding with no change in the number of binding sites (Bmax). The concentration dependence for TTX inhibition of both specific 3H-STX and 3H-BTX-B binding is identical, suggesting that inhibition of 3H-BTX-B binding is due to a direct effect of TTX/STX binding at their specific sodium channel site. The channel blockers did not alter the binding of scorpion toxin under these assay conditions, nor did BTX-B affect the binding of 3H-STX.(ABSTRACT TRUNCATED AT 250 WORDS)


Participation of the S4 voltage sensor in the Mg2+-dependent activation of large conductance (BK) K+ channels.
The S4 transmembrane segment is the primary voltage sensor in voltage-dependent ion channels. Its movement in response to changes in membrane potential leads to the opening of the activation gate, which is formed by a separate structural component, the S6 segment. Here we show in voltage-, Ca2+-, and Mg2+-dependent, large conductance K+ channels that the S4 segment participates not only in voltage- but also Mg2+-dependent activation. Mutations in S4 and the S4-S5 linker alter voltage-dependent activation and have little or no effect on activation by micromolar Ca2+. However, a subset of these mutations in the C-terminal half of S4 and in the S4-S5 linker either reduce or abolish the Mg2+ sensitivity of channel gating. Cysteine residues substituted into positions R210 and R213, marking the boundary between S4 mutations that alter Mg2+ sensitivity and those that do not, are accessible to a modifying reagent [sodium (2-sulfonatoethyl)methane-thiosulfonate] (MTSES) from the extracellular and intracellular side of the membrane, respectively, at -80 mV. This implies that interactions between S4 and a cytoplasmic domain may be involved in Mg2+-dependent activation. These results indicate that the voltage sensor is critical for Mg2+-dependent activation and the coupling between the voltage sensor and channel gate is a converging point for voltage- and Mg2+-dependent activation pathways.


Distribution and prevalence of leukocyte phenotypes in brains of lupus-prone mice.
Autoantibody-mediated compromise of central neurotransmission is a pathogenic mechanism proposed in etiology of neuropsychiatric lupus (NP-SLE). Recent experimental data support the hypothesis that intrathecally-synthesized antibodies play a key role in brain damage and behavioral dysfunction. However, autoantibody-producing plasma cells have not yet been detected in brain tissue. We presently use contemporary immunohistochemical markers and flow cytometry to assess distribution and prevalence of plasma cells and other phenotypes, which infiltrate brains of lupus-prone MRL-lpr mice. The functional status of infiltrates was confirmed by in situ hybridization for TNF-alpha mRNA. Consistent with the notion of breached blood-CSF and blood-brain barriers, CD3+ T-cells (approximately 20% of the mononuclear cell infiltrate) were plentiful in choroid plexuses and commonly seen around blood vessels. The CD138+ plasma cells were restricted to the choroid plexus and stria medullaris of diseased MRL-lpr mice. Although accounting for less than 1% of the total cell infiltrate, CD19+IgM+ B-cells increased with age in brains of MRL-lpr mice. Severe mononuclear cell infiltration was accompanied by splenomegaly and retarded brain growth. The results obtained support the hypothesis of progressive neurodegeneration as a consequence of leukocyte infiltration and intrathecal autoantibody synthesis. Further characterization of neuroactive antibodies and their targets may contribute to a better understanding of brain atrophy and behavioral dysfunction in the MRL model, and potentially in NP-SLE.


[Treatment practice in primary hyperparathyroidism].
A recent study found considerable regional differences in treatment of primary hyperparathyroidism in Norway. There is no consensus on specific indications for operation in these patients. We surveyed opinions among Norwegian endocrine surgeons and endocrinologists on the indications for surgical treatment of primary hyperparathyroidism. A questionnaire on preoperative evaluation, indications for surgery and treatment of patients with primary hyperparathyroidism was sent to the chief consultants of surgical departments that operated on parathyroid glands in 2005. The questionnaire was also sent to endocrinologists at the same hospitals. In 2006, 415 parathyroid gland operations were performed in 17 Norwegian hospitals, with a median of 18 operations per hospital. A total of 46 surgeons operated on the parathyroid glands, with a median of two surgeons per hospital. Hospitals differed with respect to preoperative evaluations and indications for operative treatment; but these differences did not coincide with regional differences in the frequency of parathyroid surgery. There was a good correlation between endocrine surgeons and endocrinologists on the indications for surgery in primary hyperparathyroidism, but neither group adhered unconditionally to the international guidelines for surgical treatment of patients with primary hyperparathyroidism. Patients in the hospitals that operated most frequently were initially diagnosed in a surgical department. Our survey did not reveal differences that could explain the large regional variations in the frequency of parathyroid surgery.


Communication technology use and mHealth acceptance among HIV-infected men who have sex with men in Peru: implications for HIV prevention and treatment.
The HIV epidemic in Peru is concentrated among men who have sex with men (MSM). Given that MSM have been documented as early adopters of emerging technology, we examined communication technology access and utilization, and mobile health (mHealth) acceptance among Peruvian MSM and transgender women (TGW) in order to gauge opportunities for mHealth-enabled HIV interventions. A convenience sample of 359 HIV-infected MSM and TGW recruited from three sites in Lima, Peru completed standardized assessments of alcohol use disorders (AUDs), risky sexual behavior, and antiretroviral therapy (ART) adherence along with self-constructed measures of communication technology access and utilization, and mHealth acceptance. Most participants (86%) had daily access to any cell phone, including smartphones (30%). The most frequent communication activities were receiving and making calls, and receiving and sending text messages using cell phones. On a 5-point Likert scale, participants expressed interest in using mHealth for medication reminders (M = 3.21, SD = 1.32) and engaging in anonymous online interactions with health professionals to discuss HIV-related issues (M = 3.56, SD = 1.33). Importantly, no significant differences were found in communication technology use and mHealth acceptance among participants with AUDs, depression, and suboptimal ART adherence, all of which are associated with poor HIV treatment outcomes. Findings show support for implementing mHealth-based intervention strategies using cell phones to assess and reduce HIV-risk behaviors among HIV-infected MSM and TGW.


PGC-1α integrates glucose metabolism and angiogenesis in multiple myeloma cells by regulating VEGF and GLUT-4.
Human peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) is a key coactivator in the regulation of gene transcriptional activity in normal tissues. However, it is not clear whether it is involved in the angiogenesis and metabolism of multiple myeloma (MM). The aim of the present study was to investigate the role of PGC-1α in MM. Small interfering RNA (siRNA) was used to inhibit PGC-1α expression in RPMI-8226 cells. An endothelial cell migration assay was performed using transwell chambers and the expression of PGC-1α, estrogen-related receptor-α (ERR-α), vascular endothelial growth factor (VEGF) and glucose transporter-4 (GLUT-4) was tested by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of PGC-1α, ERR-α and GLUT-4 was assayed by western blot analysis. Lastly, RPMI-8226 cell proliferation was evaluated using CCK-8 assay. VEGF and GLUT-4 mRNA levels were decreased in cells treated with siRNA targeting PGC-1α, as was the level of GLUT-4 protein. Endothelial cell migration was significantly reduced when these cells were cultured with culture medium from RPMI-8226 cells treated with siPGC-1α. The proliferation rates at 24 and 48 h were suppressed by PGC-1α inhibition. Our results showed that inhibition of PGC-1α suppresses cell proliferation probably by downregulation of VEGF and GLUT-4. The present study suggests that PGC-1α integrates angiogenesis and glucose metabolism in myeloma through regulation of VEGF and GLUT-4.


Suicidal Mental Imagery in Psychiatrically Hospitalized Adolescents.
Suicide is the second leading cause of death in adolescents and suicide rates in this population have increased in recent years. A critical step in preventing suicide is improving the accuracy of suicide risk assessment. Measurement of suicidal cognitions typically emphasizes assessment of verbal thoughts about suicide. Recent research suggests, however, that suicidal mental imagery, or mentally imagining suicide-related content, may be even more strongly associated with suicidal behavior. No research has evaluated suicidal mental imagery in adolescents, however. The present study evaluated suicidal mental imagery and suicidal verbal thoughts in a sample of adolescents (N = 159) admitted to an adolescent psychiatric inpatient unit. Of those adolescents who reported suicidal cognitions, 63.73% reported suicidal mental imagery. Adolescents who reported suicidal mental imagery had 2.40 greater odds of having made a suicide attempt, after accounting for history of suicidal verbal thoughts and relevant covariates. Findings suggest that suicidal mental imagery should be directly assessed when evaluating suicide risk, and that treatments may be optimized by targeting both suicidal verbal thoughts and suicidal mental imagery.


Correlation between overexpression of c-met gene and the progression of gastric cancer.
The c-met oncogene encodes a receptor of hepatocyte growth factor (HGF), which has both mitogenic and motogenic activities. We have studied the c-met gene expression in gastric cancer by immunohistochemical method using an antibody specific to the c-met beta-chain. c-met immunoreactivity was preferentially localize on the cell membrane, and 55 (43%) of 127 primary gastric cancers showed c-met immunoreactivity. Strong correlation was found between c-met expression in large tumors, lymph node involvement, serosal invasion, as well as peritoneal dissemination. Furthermore, c-met positive tumors had a tendency to metastasize to more distant lymph node sites. Regarding the macroscopic type, Borrmann type 4 gastric cancer showed the highest incidence (12/16, 76%) of positive c-met expression. Patients with c-met positive tumor ran a significantly poorer prognosis than those with c-met negative one. These results indicate that the c-met protein participates in the progression and invasion of stomach cancer, and that c-met tissue status is a useful biological marker in gastric cancer.


Procurement of information systems effectively (POISE): using the new UK guidelines to purchase an integrated clinical laboratory system.
Open tendering for medical informatics systems in the UK has traditionally been lengthy and, therefore, expensive on resources for vendor and purchaser alike. Events in the United Kingdom (UK) and European Community (EC) have led to new Government guidance being published on procuring information systems for the public sector: Procurement of Information Systems Effectively (POISE). This innovative procurement process, launched in 1993, has the support of the Computing Services Association (CSA) and the Federation of the Electronics Industry (FEI). This paper gives an overview of these new UK guidelines on healthcare information system purchasing in the context of a recent procurement project with an NHS Trust Hospital. The aim of the project was to replace three aging, separate, and different laboratory computer systems with a new, integrated turnkey system offering all department modules, an Open modern computer environment, and on-line electronic links to key departmental systems, both within and external to the Trust by the end of 1994. The new system had to complement the Trust's strategy for providing a modern clinical laboratory service to the local population and meet a tight budget.