Screening rate for hepatitis B virus infection in patients undergoing chemotherapy in Japan.
The aim of this study was to investigate the screening rate for hepatitis B virus (HBV) infection, which is recommended by some guidelines for the prevention of HBV reactivation, in patients undergoing chemotherapy for malignancy in Japan. The study subjects were 3302 patients who had received first-line chemotherapy for malignancy from Apr 2008 through Mar 2013 utilizing the Claims Database of the Japan Medical Data Center. The proportion of patients who had been tested for HBsAg (P-HBsAg) and the proportion of HBsAg-negative patients who had undergone tests for anti-HBc and anti-HBs (P-HBc/HBsAb) before chemotherapy were investigated. P-HBsAg and P-HBc/HBsAb in all 3302 patients were 66.3 and 19.9 %, respectively. P-HBsAg in patients with solid tumors and those with hematological malignancies were 66.1 and 67.5 % (p = 0.61), respectively, and P-HBc/HBsAb were 12.3 and 75.8 % (p < 0.0001), respectively. P-HBsAg in patients from cancer centers and non-cancer centers were 66.9 and 65.5 % (p = 0.43), respectively, and P-HBc/HBsAb were 25.1 and 12.4 % (p < 0.0001), respectively. P-HBsAg in patients encountered before and after the announcement of the Japanese guideline were 51.3 and 67.1 % (p < 0.001), respectively, and P-HBc/HBsAb were 7.9 and 20.4 % (p = 0.01), respectively. The screening rate for HBV among cancer patients scheduled for chemotherapy remains unsatisfactory, especially in patients with solid tumors and those from non-cancer centers. Although the figures are improving after the announcement of the Japanese guideline, intensive measures to improve awareness about HBV reactivation during/after chemotherapy are needed.


Can inpatient pharmacists move the needle on smoking cessation? Evaluating reach and representativeness of a pharmacist-led opt-out smoking cessation intervention protocol for hospital settings.
Hospitalization affords an opportunity to reduce smoking, but fewer than half of patients who smoke receive evidence-based cessation treatment during inpatient stays. This study evaluated a pharmacist-led, electronic health record (EHR)-facilitated opt-out smoking cessation intervention designed to address this need. Analyses of EHR records for adult patients who smoked in the past 30 days admitted to an academic medical center in the upper Midwest were conducted using the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework. The reach of a pharmacist-led, EHR-facilitated protocol for smoking cessation treatment was assessed by comparing patients' receipt of nicotine replacement therapy (NRT) and tobacco quitline referral before and after implementation. χ2 tests, t tests, and multiple logistic regression models were used to compare reach across patient demographic groups to assess treatment disparities and the representativeness of reach. Adoption of the program by hospital services was also assessed. Of the 70 hospital services invited to implement the program, 88.6% adopted it and 78.6% had eligible admissions. Treatment reach increased as rates of delivering NRT rose from 43.6% of eligible patients before implementation to 50.4% after implementation (P < 0.0001) and quitline referral rates rose from 0.9% to 11.9% (P < 0.0001). Representativeness of reach by sex and ethnicity improved after implementation, although disparities by race and age persisted after adjustment for demographics, insurance, and primary diagnosis. Pharmacists addressed tobacco use for eligible patients in 62.5% of cases after protocol implementation. Smoking cessation treatment reach and representativeness of reach improved after implementation of a proactive, pharmacist-led, EHR-facilitated opt-out smoking cessation treatment protocol in adult inpatient services.


Laryngeal myofascial pain syndrome as a new diagnostic entity of dysphonia.
To consider the feasibility of diagnosing intrinsic laryngeal muscle myofascial pain syndrome (MPS) in dysphonic patients who demonstrated immediate symptom and stroboscopic finding improvement after laryngeal electromyography (LEMG) without further treatment. A chart review of patients who showed subtle vocal fold movement abnormalities on a stroboscopic examination and underwent ultrasonography (US)-guided LEMG was performed. Patients with vocal fold paralysis, mucosal lesions, spasmodic dysphonia, and vocal tremor on stroboscopic examination were excluded. Among them, patients with normal EMG findings were included in this study. The patients who reported voice symptom improvement after LEMG without further treatment were placed in laryngeal MPS (LMPS) group and the other patients were placed in non-laryngeal MPS (non-MPS) group. Predisposing factors, voice symptom, symptom-duration, and stroboscopic findings of these patients were reviewed. Among the 16 patients, LEMG findings were normal, five (31%) were included in the LMPS group and the other 11 patients (69%) were included in the non-MPS group. All LMPS group patients had a history of voice abuse and reported odynophonia. The Korean Voice Handicap Index-10 score decreased significantly after US-guided LEMG without additional treatment in the LMPS group. The stroboscopic findings revealed that vocal fold hypomobility was the most common finding in the LMPS group, and two patients showed a muscle tension dysphonia pattern. The LMPS groups showed improvement of vocal fold mobility on 1-week stroboscopic evaluation. LMPS is a potential diagnosis for patients with vocal fold hypomobility finding on stroboscopic findings but with normal EMG results. Diagnosis of LMPS could be considered in patients who showed symptom and vocal fold movement improvement after LEMG.


Melatonin effects on sleep quality of COVID-19 patients: a protocol for systematic review and meta-analysis of randomised controlled trials with trial sequential analysis.
Sleep disturbance is one of the common complaints of patients with COVID-19 infection. Melatonin is a physiological indoleamine involved in circadian rhythm regulation and it is currently used for secondary sleep disorders caused by various diseases. Some clinical randomised controlled trials (RCTs) have obtained a small amount of evidence and controversial results in support of their therapeutic effect on sleep disorders, but no studies have summarised and evaluated RCTs in all current databases to obtain conclusive results. Therefore, the aim of this systematic review and meta-analysis was to determine the efficacy and safety of melatonin in the treatment of sleep disturbances in patients with COVID-19. We will search for RCT-type studies of melatonin in the treatment of sleep disturbances in patients with COVID-19. From inception to October 2022 will be available on PubMed/MEDLINE, Web of Science, Embase, CINAHL, PsycINFO, LILACS, SCOPUS, Cochrane Central Register of Controlled Trials, ICTRP, Wanfang Data, VIP database and CNKI, VIP database, China Biomedical Literature Database to search for eligible studies. There are no language and geographical restrictions. Two authors will independently screen and select eligible studies, assess methodological quality and perform data extraction. Two additional authors will independently extract data from each study. Then, meta-analysis will then be carried out using a fixed-effects or random-effects model, using the mean difference for continuous outcomes and the relative risk for dichotomous outcomes. Risk of bias assessment will be assessed using the Cochrane risk-of-bias tool. Heterogeneity between studies was assessed by Cochrane Q-test and I2. The quality of evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Funnel plots, Begg's test and Egger's test will be used to assess the risk of publication bias. Subgroup analysis, data synthesis, meta-analysis and overall incidence of adverse events will be performed using Review Manager V.5.4 software and Stata software. Trial sequential analysis will be performed if appropriate. This study is an extraction review of data from existing studies, and thus it is unnecessary to obtain ethical approval. The results of this systematic review will be published in a peer-reviewed journal. CRD42022359221.


Secretion patterns of plasma-progesterone, 17-hydroxyprogesterone and 20 alpha hydroxypregn-4-en-3-one in early normal pregnancy.
Plasma levels of progesterone, 17-hydroxyprogesterone and 20 alpha hydroxypregn-4-en-3-one were established from 4 to 16 weeks gestation by sampling 15 normal patients twice weekly. Apart from a peak at week 5, the mean levels of progesterone remained constant at about 24 ng/ml until week 10 and then rose progressively to 40 ng/ml at week 16.20 alpha hydroxypregn-4-en-3-one remained within the 7 to 9 ng/ml range apart from a peak at week 5. A significant decrease in mean levels of 17-hydroxy-progesterone was noted from week 5 to a nadir of 3 ng/ml at week 11. It would appear that the main hormone production of progesterones in pregnancy has been taken over by the placental unit by the 10th week.


Economic burden of symptomatic iron deficiency - a survey among Swiss women.
Symptomatic iron deficiency (ID) is a disorder affecting 10-20% of menstruating women. ID is diagnosed by measuring serum ferritin, a protein helping to store iron in the body. A deeper understanding of the association between ID and its societal and economic burden is relevant for patients, physicians, health care decision makers. An online household survey was carried out among Swiss women aged 18-50 years suffering from debilitating symptoms due to ID. The data was population-weighted for age and region. The costs of misdiagnosis and the ID-related economic burden (i.e. days of sick leave) from productivity losses on the labor market were determined and extrapolated to the Swiss population. Furthermore, the patient burden was assessed based on quality of life daily measurements. The total sample included 1010 women who received an ID diagnosis with a blood test in the last 2 years (mean age: 33.5 years). Most named symptoms were "being tired or exhausted" (96.4%) and reduced physical energy level (41.0%). In total, 354 (35.0% of the total sample) patients received an initial diagnosis other than ID. Of those, 46.8% were treated prior to the ID diagnosis with a pharmacological medical therapy or psychotherapy. Extrapolating these numbers to the Swiss female population aged 18-50 years, the direct medical costs would be CHF 78 million (assuming an annual ID incidence of ID diagnosis of 9.5%). On average, 28.5% of participants in the work-force had to take sick leave due to ID symptoms within a period of 2 years (mean: 5.2 days, i.e. 2.6 days/year). The estimated annual indirect costs in Switzerland would be CHF 33 million (human capital approach) or CHF 26 million (friction cost method), respectively. Being exhausted and impaired concentration appear to be the most important factors negatively impacting daily living and hence quality of life. The societal and economic burden among women due to debilitating symptoms of ID in Switzerland is substantial. Timely, correct diagnosis and treatment of ID may contribute to reducing this burden. Further studies are needed in this area to validate our results.


India: constitutional challenge to anti-sodomy law.
On 7 December 2001, the Naz Foundation India Trust filed a petition with the Delhi High Court alleging that the prohibitions on sodomy in Indian law are unconstitutional.


Periodontal disease as a primary cause of surgical site infection in fractures of the mandible: is smoking a confounding variable?
Fractures of the mandible are common in contemporary oral and maxillofacial practice. Wound infection is the most common complication after open reduction and internal fixation, and the management of these is complex and costly in terms of morbidity to the patient, and in fiscal terms. Whilst numerous epidemiological studies implicate smoking, alcohol, drug use, and adverse behaviour, as well as fracture complexity and diabetes, as important risk factors, the role of periodontal disease is only occasionally mentioned and not formally investigated. The aim of this study therefore was to assess the presence of periodontal disease and its severity according to the 2018 EFP/AAP periodontitis case classification in patients with fractured mandibles who presented to a single level 1 trauma centre, and to look for a possible association with surgical site infection. A total of 305 patients were assessed retrospectively following open reduction and internal fixation via transoral incisions with load-sharing osteosynthesis. The postoperative infection rate was 22.95%. Multivariate and multiple logistic regression revealed that there was a strong association between periodontal staging and postoperative surgical site infection. Crucially, the study predicts that patients with severe periodontal disease (periodontal stage III and IV) are over seven times more likely to develop a wound infection than disease-negative individuals. This has implications for risk adjustment, prognostication, treatment planning, and postoperative care. Surprisingly in this study, cigarette smoking, an established risk factor in the pathogenesis of periodontal disease, did not achieve statistical significance, potentially conflicting with the established literature.


Extension of a gaseous dry deposition algorithm to oxidized volatile organic compounds and hydrogen cyanide for application in chemistry transport models.
The dry deposition process refers to flux loss of an atmospheric pollutant due to uptake of the pollutant by the Earth's surfaces, including vegetation, underlying soil, and any other surface types. In chemistry transport models (CTMs), the dry deposition flux of a chemical species is typically calculated as the product of its surface layer concentration and its dry deposition velocity (V d); the latter is a variable that needs to be highly empirically parameterized due to too many meteorological, biological, and chemical factors affecting this process. The gaseous dry deposition scheme of Zhang et al. (2003) parameterizes V d for 31 inorganic and organic gaseous species. The present study extends the scheme of Zhang et al. (2003) to include an additional 12 oxidized volatile organic compounds (oVOCs) and hydrogen cyanide (HCN), while keeping the original model structure and formulas, to meet the demand of CTMs with increasing complexity. Model parameters for these additional chemical species are empirically chosen based on their physicochemical properties, namely the effective Henry's law constants and oxidizing capacities. Modeled V d values are compared against field flux measurements over a mixed forest in the southeastern US during June 2013. The model captures the basic features of the diel cycles of the observed V d. Modeled V d values are comparable to the measurements for most of the oVOCs at night. However, modeled V d values are mostly around 1 cm s-1 during daytime, which is much smaller than the observed daytime maxima of 2-5 cm s-1. Analysis of the individual resistance terms and uptake pathways suggests that flux divergence due to fast atmospheric chemical reactions near the canopy was likely the main cause of the large model-measurement discrepancies during daytime. The extended dry deposition scheme likely provides conservative V d values for many oVOCs. While higher V d values and bidirectional fluxes can be simulated by coupling key atmospheric chemical processes into the dry deposition scheme, we suggest that more experimental evidence of high oVOC V d values at additional sites is required to confirm the broader applicability of the high values studied here. The underlying processes leading to high measured oVOC V d values require further investigation.


A Rare Case of Tubercular Osteomyelitis of Maxilla: A Case Report.
Tuberculosis (TB) is a chronic granulomatous infection which primarily affects lungs. It is caused by Mycobacterium tuberculosis which was discovered by Dr Robert Koch. It can also affect other organs. Tuberculosis is a major cause of morbidity and mortality in developing countries. Early detection and initiation of antitubercular therapy are important in the management of TB. Extrapulmonary TB might not exhibit same features as pulmonary tuberculosis. Tuberculosis of maxilla is an extremely rare entity which can be misdiagnosed as carcinoma of maxillary sinus or other infectious conditions. We are presenting a case of tuberculous osteomyelitis of maxilla in a 14-year-old female who came with a discharging sinus over the right cheek. She underwent endoscopic debridement of sinuses and histopathological examination was suggestive of Koch's infection. Patient was further treated with antitubercular therapy and showed significant improvement at four weeks follow up.


Projections to areas of the nucleus tractus solitarii related to circulatory and respiratory responses in cats.
Using chloralose-anesthetized cats, afferent projections to the nucleus tractus solitarii (NTS) were studied in relation to circulatory and respiratory responses. Horseradish peroxidase (HRP) was injected into 3 distinct regions of the NTS: the rostral regions from which electrical stimulation elicited pressor and apneustic responses: the intermediate regions from which stimulation elicited depressor and apneic responses; the commissure regions from which stimulation elicited depressor and hypopneic responses. HRP-labeled cells were sought throughout the medulla oblongata upward including the telencephalon. The results indicate that: many neurons of the frontal cortex (sigmoid gyrus, anterior ectosylvian gyrus, anterior sylvian gyrus, and anterior suprasylvian gyrus) project bilaterally to the 3 regions, predominantly to the rostral regions; a few neurons of the bed nucleus of the stria terminalis project almost ipsilaterally to the 3 regions; a few neurons of the nucleus amygdalae centralis project almost ipsilaterally to the 3 regions; many neurons of the paraventricular nucleus project bilaterally to the 3 regions, predominantly to the ipsilateral commissure regions; a moderate number of neurons of the fastigial nucleus project contralaterally to the rostral regions. These findings suggest that there are some specific projections to each region of the NTS from various supramedullary nuclei, which may be involved in modulation of the cardiovascular and respiratory systems.


Socio-demographic and Clinical Profile of Substance Abusers Attending a Regional Drug De-addiction Centre in Chronic Conflict Area: Kashmir, India.
The menace of substance abuse is not only a socially unacceptable reality, but in its entirety is a disease and emerging as a major public health challenge. To study the socio-demographic and clinical profile of patients attending the drug de-addiction centre. A descriptive study was undertaken in a drug de-addiction centre at the Police Hospital in Srinagar, and all patients (198) who were admitted during this period were interviewed. The mean (SD) age of patients was 26.8 years (SD 7.37), and over half (56%) belonged to the lower-middle social class. Poly-substance abuse was seen in 91.9%; medicinal opioids and cannabis were the most common substances abused. Most common age of initiation was 11-20 years (76.8%), with peer pressure and relief from a negative mood state being the most common reasons given for starting the drug(s). Prevalence of a co-morbid psychiatric disorder was high, on the order of 49.5%. A high rate of volatile substance use was observed among adolescents (54.5%). A pattern of poly-substance abuse was found to be quite common in patients, and use of volatile substances at a very young age emerged as a new trend. The dreadful repercussions of substance abuse justify the urgency to evolve a comprehensive strategy.


The remoulding of dietary effects on the fecundity / longevity trade-off in a social insect.
In many organisms increased reproductive effort is associated with a shortened life span. This trade-off is reflected in conserved molecular pathways that link nutrient-sensing with fecundity and longevity. Social insect queens apparently defy the fecundity / longevity trade-off as they are both, extremely long-lived and highly fecund. Here, we have examined the effects of a protein-enriched diet on these life-history traits and on tissue-specific gene expression in a termite species of low social complexity. On a colony level, we did not observe reduced lifespan and increased fecundity, effects typically seen in solitary model organisms, after protein enrichment. Instead, on the individual level mortality was reduced in queens that consumed more of the protein-enriched diet - and partially also in workers - while fecundity seemed unaffected. Our transcriptome analyses supported our life-history results. Consistent with life span extension, the expression of IIS (insulin/insulin-like growth factor 1 signalling) components was reduced in fat bodies after protein enrichment. Interestingly, however, genes involved in reproductive physiology (e.g., vitellogenin) were largely unaffected in fat body and head transcriptomes. These results suggest that IIS is decoupled from downstream fecundity-associated pathways, which can contribute to the remoulding of the fecundity/longevity trade-off in termites as compared to solitary insects.


6-Phosphogluconate dehydrogenase regulates tumor cell migration in vitro by regulating receptor tyrosine kinase c-Met.
6-Phosphogluconate dehydrogenase (6PGD) is the third enzyme in the oxidative pentose phosphate pathway (PPP). Recently, we reported that knockdown of 6PGD inhibited lung tumor growth in vitro and in a xenograft model in mice. In this study, we continued to examine the functional role of 6PGD in cancer. We show that 6PGD expression positively correlates with advancing stage of lung carcinoma. In search of functional signals related to 6PGD, we discovered that knockdown of 6PGD significantly inhibited phosphorylation of c-Met at tyrosine residues known to be critical for activity. This downregulation of c-Met phosphorylation correlated with inhibition of cell migration in vitro. Overexpression of a constitutively active c-Met specifically rescued the migration but not proliferation phenotype of 6PGD knockdown. Therefore, 6PGD appears to be required for efficient c-Met signaling and migration of tumor cells in vitro.


Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis: A diagnostic accuracy study from India.
Studies evaluating Xpert MTB/RIF Ultra assay (Xpert Ultra) for diagnosing tuberculous meningitis (TBM) are scarce and have reported contrasting results in comparison to Xpert MTB/RIF assay (Xpert). To evaluate the performance of Xpert Ultra in diagnosing TBM and compare it with Xpert and multiplex polymerase chain reaction (MPCR). Xpert Ultra was performed on 244 cerebrospinal fluid (CSF) samples: 56 definite TBM, 148 probable TBM and 40 non-TBM controls. 105/244 CSF samples were also subjected to Xpert and MPCR (IS6110, MPB64, protein B). The overall sensitivity of Xpert Ultra in diagnosing TBM from 244 CSF samples was 72.05% (96.42% - definite TBM, 62.83% - probable TBM) with a specificity of 100%. 18 (12.24%) cases [8 definite TBM, 10 probable TBM] were reported rifampicin resistant (RifR) by Xpert Ultra and confirmed by rpoB sequencing. 60 (40.81%) cases [9 definite TBM, 51 probable TBM] were reported rifampicin indeterminate (RifI) by Xpert Ultra (all trace category), out of which 45 [8 definite, 37 probable) were rifampicin susceptible (RifS) and 5 probable cases were RifR on rpoB sequencing. Out of 105 CSF samples subjected to all three techniques, TBM was diagnosed in 70.66%, 28% and 88% by Xpert Ultra, Xpert and MPCR, respectively. Xpert Ultra detected TBM with higher sensitivity than Xpert. Among trace category, constituting 40% of TBM cases, rpoB gene sequencing confirmed 5 RifR cases.


Mirror therapy in a patient with a fractured wrist and no active wrist extension.
We report a patient in whom mirror therapy, training moving both hands while watching the reflection of the present or good hand in a parasaggital mirror - a method used for phantom limb and stroke patients - was extremely useful after a fractured wrist with good passive, but no active, extension.


The HOME network: an Australian national initiative for home therapies.
Longer, more frequent dialysis at home can improve life expectancy for patients with chronic kidney disease. Increased use of home dialysis therapies also benefits the hospital system, allowing for more efficient allocation of clinic resources. However, the Australian and New Zealand Data Registry statistics highlight the low uptake of home haemodialysis and peritoneal dialysis across Australia. In August 2009, the Australia's HOME Network was established as a national initiative to engage and empower healthcare professionals working in the home dialysis specialty. The aim was to develop solutions to advocate for and ultimately increase the use of home therapies. This paper describes the development, achievement and future plan of the Australian HOME Network. Achievements to date include: a survey of HOME Network members to assess the current state of patient and healthcare professional-targeted education resources; development of two patient case studies and activities addressing how to overcome the financial burden experienced by patients on home dialysis. Future projects aim to improve patient and healthcare professional education, and advocacy for home dialysis therapies. The HOME Network is supporting healthcare professionals working in the home dialysis specialty to develop solutions and tools that will help to facilitate greater utilisation of home dialysis therapies.


Alternative 2-keto acid oxidoreductases in Trichomonas vaginalis: artifact of histochemical staining.
Trichomonas vaginalis has been reported to possess alternative 2-keto acid oxidoreductases (KORs). These enzymes preferentially used indolepyruvate in a reaction that resembled that of pyruvate:ferredoxin oxidoreductase (PFO). However, the KORs did not reduce ferredoxin and remained active in metronidazole-resistant trichomonads lacking PFO. Therefore, it was proposed that the KORs may help trichomonads to survive in the presence of metronidazole. The KORs were identified using activity staining on native gels (Brown DM, Upcroft JA, Dodd HN, et al. Alternative 2-keto acid oxidoreductase activities in T. vaginalis. Mol Biochem Parasitol 1999;98:203-14). In the current study, we showed that the apparent KOR activity was caused by the non-enzymatic reduction of the indicator dye, nitroblue tetrazolium, by indolepyruvate, which is facilitated by Triton X-100 used to prepare the membrane fractions. We could not confirm the presence of KORs in metronidazole-resistant T. vaginalis. The low level indolepyruvate-dependent activity that is present in T. vaginalis strains sensitive to metronidazole is catalyzed by PFO, which was verified using the pure enzyme. Therefore, our results suggest that alternative 2-keto acid oxidoreductases do not exist in T. vaginalis.


A rare cause of foot pain in an adolescent due to os paracuneiforme: a case report and review of the literature.
Os paracuneiforme is an extremely rare accessory ossicle located at the medial aspect of the medial cuneiform bone. Although foot pain secondary to accessory ossicles is well known, symptomatic os paracuneiforme that requires surgical excision is rarely reported in the current literature. Herein, a 12-year-old boy with symptomatic os paracuneiforme is presented, and its clinical and imaging findings as well as the treatment are discussed.


Dietary trans fatty acids increase serum cholesterylester transfer protein activity in man.
The average diet may provide some 8-10 g/day of unsaturated fatty acids with a trans double bond. Previous studies showed that dietary trans fatty acids may simultaneously raise low-density lipoprotein (LDL) cholesterol and reduce high-density lipoprotein (HDL) cholesterol. Human plasma contains a protein (CETP) which transfers cholesterylesters from HDL to lipoproteins of lower density. We hypothesized that CETP could play a role in the effect of trans fatty acids on lipoproteins and measured the activity levels of CETP in serum samples from a 9-week study in which 55 volunteers were fed three controlled diets with different fatty acid profiles. Mean activity was 114 (% of reference serum) after consumption of a high trans fatty acid diet, as opposed to 96 after linoleic acid and 97 after stearic acid (P < 0.02). We conclude that the increased activity of CETP may contribute to the rise in LDL cholesterol and the fall in HDL cholesterol seen on diets with high contents of trans fatty acids.


Carotid extra-medial thickness in childhood: early life effects on the arterial adventitia.
Structural modification of the arterial adventitia may be an early event in atherosclerosis. Carotid extra-medial thickness is a new measure of arterial adventitial thickness. We examined the association of cardiovascular risk factors with extra-medial thickness, in childhood. Carotid extra-medial thickness was assessed by high-resolution ultrasound in 389 non-diabetic children aged 8-years. A non-fasting blood sample was collected from 314 participants. Associations of gender, age, lipoproteins, blood pressure, BMI z-score, waist:height ratio and parental history of early vascular disease, with extra-medial thickness were examined. Carotid extra-medial thickness was lower in girls (r=-.163, P=.001) and directly associated with systolic (r=.128, P=.009), diastolic blood pressure (r=.130, P=.009), and height (r=.170, P=.0006). These associations remained after adjustment for carotid intima-media thickness. In multivariable analysis including carotid intima-media thickness, only gender and height were significantly associated with carotid extra-medial thickness. In gender-stratified analysis, the strongest associations with extra-medial thickness were BMI z-score (r=.181, P=.01), height (r=.210, P=.003) and diastolic blood pressure (r=.167, P=.02) for boys; and systolic blood pressure (r=.153, P=.03) and parental history of premature cardiovascular disease (r=.139, P=.05) for girls. The association of BMI z-score with extra-medial thickness differed by gender (P-interaction=.04). Carotid extra-medial thickness is independently associated with gender and height in childhood. Extra-medial thickness may provide important information concerning early arterial health, particularly related to the arterial adventitia.


Improvement of osseointegration of titanium dental implant surfaces modified with CO ions: a comparative histomorphometric study in beagle dogs.
The aim of this study was to compare carbon-oxygen (CO) ion implantation as a surface treatment with diamond-like carbon and commercially treated implants, including double acid-etched (Osseotite), oxidized (TiUnite) and sandblasted and acid-etched (SLA), using machine-turned titanium implants as control. A total of 72 dental implants divided into 6 groups were placed in the mandibles of 12 beagle dogs. Evaluation was performed by conventional light transmission microscopy and environmental scanning electron microscopy (ESEM). The histological results obtained via ESEM demonstrated bone-implant contact percentage (%BIC) for implants treated with CO ion implantation of 61% and 62% at 3 and 6 months, respectively. At the same time points, the values were 48% and 45% for double acid-etched, 46% and 52% for sandblasted and acid-etched, 55% and 46% for oxidized, and 33% and 49% for machine-turned titanium control implants. Values of %BIC were statistically significantly higher in implants treated with CO ion implantation compared to the commercially treated implant group (p=0.002 and p=0.025) and the control implants (p=0.001 and p=0.032) at 3 and 6 months, respectively. No significant differences were observed between the three groups of commercially treated implants. The larger %BIC of the ion-implanted group was observable at an early stage.


Conventional Matrices Loaded Onto a Graphene Layer Enhances MALDI-TOF/TOF Signal: Its Application to Improve Detection of Phosphorylated Peptides.
This is the first study where graphene is used as a MALDI adjuvant in combination with the traditional matrix α-cyano-4-hydroxycinnamic acid (CHCA) to improve the signal intensity of peptide samples. Use of this amended matrix not only leads to increased signals but also to a higher number of peaks detected in complex samples. Additionally, the use of graphene has a stabilizing effect that can also be exploited to improve the detection of easily cleavable molecules. Graphical Abstract .


New target for rice lodging resistance and its effect in a typhoon.
We demonstrated the new target for lodging resistance in rice (Oryza sativa L.) by the analysis of physiological function of a locus for lodging resistance in a typhoon (lrt5) with the near isogenic line under rice "Koshihikari" genetic background (tentatively named S1). The higher lodging resistance of S1 was observed during a typhoon in September 2004 (28 days after heading), when most other plants in "Koshihikari" became lodged. Visual observations showed that bending of the upper stems triggered lodging during the typhoon; the upper stem of "Koshihikari" buckled completely, whereas that of S1 remained straight. In addition to the strong rain and winds during the typhoon, the weight of the buckled upper plant parts increased the pressure on adjacent plants and caused a domino effect in "Koshihikari". Young's modulus, an indicator of the rigidity of the culm, was significantly higher in S1 than in "Koshihikari". In the upper culm, the starch content in S1 was 4.8 times the value in "Koshihikari", and senescence was delayed in the upper leaves of S1. These results suggest that the rigidity of the upper culm by the higher starch content (as a result of delayed senescence in the upper leaves) may be responsible for the higher lodging resistance during a typhoon in rice.


Simultaneous Cr(VI) reduction and non-ionic surfactant oxidation by peroxymonosulphate and iron powder.
Some industrial wastewaters contain both hexavalent chromium and surfactants. In this work, their removal from aqueous solution by zero-valent iron (ZVI) and peroxymonosulphate (PMS) was studied using Brij 35 as a representative non-ionic surfactant. The performance of the ZVI/PMS system in the simultaneous removal of both pollutants was compared to that achieved with control solutions containing either Cr(VI) or Brij 35 separately. Reactions were carried out over 24h at initial pH=2.3 with variable initial amounts of Cr(VI) and Brij 35. The results showed that surfactant removal was enhanced in the system also containing Cr(VI). Surfactant degradation followed zero-order kinetics and produced formic acid as the main by-product, together with hydroxylated aldehydes, formates and alcohols that were identified by LC/MS. The presence of surfactant similarly enhanced Cr(VI) reduction, which also followed zero-order kinetics. Chromium removal was quantitative only when the initial chromium concentration was lower than 140 mg L(-1). Reduced chromium was mainly in the solution phase together with dissolved iron. Precipitation with NaOH was therefore required to definitively remove dissolved metals from the investigated system.


Molecular characterization of DnaJ 5 homologs in silkworm Bombyx mori and its expression during egg diapause.
A comparison of the cDNA sequences (1 056 bp) of Bombyx mori DnaJ 5 homolog with B. mori genome revealed that unlike in other Hsps, it has an intron of 234 bp. The DnaJ 5 homolog contains 351 amino acids, of which 70 contain the conserved DnaJ domain at the N-terminal end. This homolog of B. mori has all desirable functional domains similar to other insects, and the 13 different DnaJ homologs identified in B. mori genome were distributed on different chromosomes. The expressed sequence tag database analysis of Hsp40 gene expression revealed higher expression in wing disc followed by diapause-induced eggs. Microarray analysis revealed higher expression of DnaJ 5 homolog at 18th h after oviposition in diapause-induced eggs. Further validation of DnaJ 5 expression through qPCR in diapause-induced and nondiapause eggs at different time intervals revealed higher expression in diapause eggs at 18 and 24 h after oviposition, which coincided with the expression of Hsp70 as the Hsp 40 is its co-chaperone. This study thus provides an outline of the genome organization of Hsp40 gene, and its role in egg diapause induction in B. mori.


Tumor-targeted induction of intrinsic apoptosis in colon cancer cells by Lactobacillus plantarum and Lactobacillus rhamnosus strains.
Colorectal cancer is one of the widespread and lethal types of malignancies. Recently, antineoplastic attributes of probiotics have attracted lots of attention. Here, we investigated anti-proliferative potential of the non-pathogenic strains Lactobacillus plantarum ATCC 14,917 and Lactobacillus rhamnosus ATCC 7469 on human colorectal adenocarcinoma-originated Caco-2 cells. Caco-2 and HUVEC control cells were treated with ethyl acetate extracts of the two Lactobacillus strains to assess cell viability by MTT assay. Annexin/PI staining flow cytometry, and caspase-3, -8 and - 9 activity assays were performed to determine the type of cell death induced in extract-treated cells. Expression levels of apoptosis-related genes were evaluated by RT-PCR. Extracts from both L. plantarum and L. rhamnosus specifically targeted the Caco-2 cells and not HUVEC controls, and significantly affected the viability of the colon cancer cell line in a time- and dose-dependent manner. This effect was shown to occur through activation of the intrinsic apoptosis pathway, as indicated by the increased caspase-3 and - 9 activities. While there are limited and conflicting data about the mechanisms underlying the specific antineoplastic attributes of Lactobacillus strains, we clarified the overall induced mechanism. The Lactobacillus extracts specifically down-regulated the expression of the anti-apoptotic bcl-2 and bcl-xl, and simultaneously up-regulated the pro-apoptotic bak, bad, and bax genes in treated Caco-2 cells. Ethyl acetate extracts of L. plantarum and L. rhamnosus strains could be considered as targeted anti-cancer treatments specifically inducing the intrinsic apoptosis pathway in colorectal tumor cells.


Highly adaptive RF excitation scheme based on conformal resonant CRLH metamaterial ring antennas for 7-Tesla traveling-wave magnetic resonance imaging.
We propose an adaptive RF antenna system for the excitation (and manipulation) of the fundamental circular waveguide mode (TE(11)) in the context of high-field (7T) traveling-wave magnetic resonance imaging (MRI). The system consists of <<flat>> composite right-/left-handed (CRLH) meta-material ring antennas that fully conforms to the inner surface of the MRI bore. The specific use of CRLH metamaterials is motivated by its inherent dispersion engineering capabilities, which is needed when designing resonant ring structures for virtually any predefined diameter operating at the given Larmor frequency (i.e. 298 MHz). Each functional group of the RF antenna system consists of a pair of subsequently spaced and correspondingly fed CRLH ring antennas, allowing for the unidirectional excitation of propagating, circularly polarized B(1) mode fields. The same functional group is also capable to simultaneously mold an incoming, counter-propagating mode. Given these functionalities we are proposing now a compound scheme (i.e. periodically arranged multiple antenna pairs)--termed as "MetaBore"--that is apt to provide a tailored RF power distribution as well as full wave reflection compensation virtually at any desired location along the bore.


A nonlinear cascade model for action potential encoding in an insect sensory neuron.
Action potential encoding in the cockroach tactile spine neuron can be represented as a single-input single-output nonlinear dynamic process. We have used a new functional expansion method to characterize the nonlinear behavior of the neural encoder. This method, which yields similar kernels to the Wiener method, is more accurate than the latter and is efficient enough to obtain reasonable kernels in less than 15 min using a personal computer. The input stimulus was band-limited white Gaussian noise and the output consisted of the resulting train of action potentials, which were unitized to give binary values. The kernels and the system input-output signals were used to identify a model for encoding comprising a cascade of dynamic linear, static nonlinear, and dynamic linear components. The two dynamic linear components had repeatable and distinctive forms with the first being low-pass and the second being high-pass. The static nonlinearity was fitted with a fifth-order polynomial function over several input amplitude ranges and had the form of a half-wave rectifier. The complete model gave a good approximation to the output of the neuron when both were subjected to the same novel white noise input signal.


The role of lipid-protein interactions in NADH-cytochrome c reductase (rotenone-insensitive) of rat liver mitochondria.
The phospholipid depletion of rat liver mitochondria, induced by acetoneextraction or by digestion with phospholipase A2 or phospholipase C, greatly inhibited the activity of NADH-cytochrome c reductase (rotenone-insensitive). A great decrease of the reductase activity also occurred in isolated outer mitochondrial membranes after incubation with phospholipase A2. The enzyme activity was almost completely restored by the addition of a mixture of mitochondrial phospholipids to either lipid-deficient mitochondria, or lipid-deficient outer membranes. The individual phospholipids present in the outer mitochondrial membrane induced little or no stimulation of the reductase activity. Egg phosphatidylcholine was the most active phospholipid, but dipalmitoyl phosphatidylcholine was almost ineffective. The lipid depletion of mitochondria resulted in the disappearance of the non-linear Arrhenius plot which characterized the native reductase activity. A non-linear plot almost identical to that of the native enzyme was shown by the enzyme reconstituted with mitochondrial phospholipids. Triton X-100, Tween 80 or sodium deoxycholate induced only a small activation of NADH-cytochrome c reductase (rotenone-insensitive) in lipid-deficient mitochondria. The addition of cholesterol to extracted mitochondrial phospholipids at a 1 : 1 molar ratio inhibited the reactivation of NADH-cytochrome c reductase (rotenone-insensitive) but not the binding of phospholipids to lipid-deficient mitochondria or lipid-deficient outer membranes. These results show that NADH-cytochrome c reductase (rotenone-insensitive) of the outer mitochondrial membrane requires phospholipids for its activity. A mixture of phospholipids accomplishes this requirement better than individual phospholipids or detergents. It also seems that the membrane fluidity may influence the reductase activity.


Role of the ubiquitin-proteasome system in nervous system function and disease: using C. elegans as a dissecting tool.
In addition to its central roles in protein quality control, regulation of cell cycle, intracellular signaling, DNA damage response and transcription regulation, the ubiquitin-proteasome system (UPS) plays specific roles in the nervous system, where it contributes to precise connectivity through development, and later assures functionality by regulating a wide spectrum of neuron-specific cellular processes. Aberrations in this system have been implicated in the etiology of neurodevelopmental and neurodegenerative diseases. In this review, we provide an updated view on the UPS and highlight recent findings concerning its role in normal and diseased nervous systems. We discuss the advantages of the model organism Caenorhabditis elegans as a tool to unravel the major unsolved questions concerning this biochemical pathway and its involvement in nervous system function and dysfunction, and expose the new possibilities, using state-of-the-art techniques, to assess UPS function using this model system.


Faecal calprotectin testing for identifying patients with organic gastrointestinal disease: systematic review and meta-analysis.
To assess the clinical effectiveness of faecal calprotectin (FC) testing for distinguishing between organic gastrointestinal diseases (organic GID), such as inflammatory bowel disease (IBD), and functional gastrointestinal disorders (functional GIDs). Studies that assessed the accuracy of FC testing for differentiating between IBD or organic GID and functional GIDs were reviewed. Articles published in English during January 1998 - June 2018 that compared diagnostic FC testing in primary care and outpatient hospital settings with a reference test and employed the standard enzyme-linked immunosorbent FC assay method with a cut-off of 50 or 100 μg/g faeces were included. Study quality was assessed with QUADAS-2, an evidence-based quality assessment tool for diagnostic accuracy studies. MEDLINE and EMBASE; reference lists of screened articles. Eighteen relevant studies were identified. For distinguishing patients with organic GID (including IBD) from those with functional GIDs (16 studies), the estimated sensitivity of FC testing was 81% (95% CI, 74-86%), the specificity 81% (95% CI, 71-88%); area under the curve (AUC) was 0.87. For distinguishing IBD from functional GIDs (ten studies), sensitivity was 88% (95% CI, 80-93%), specificity 72% (95% CI, 59-82%), and AUC 0.89. Assuming a population prevalence of organic GID of 1%, the positive predictive value was 4.2%, the negative predictive value 100%. The difference in sensitivity and specificity between FC testing cut-offs of 50 μg/g and 100 μg/g faeces was not statistically significant (P = 0.77). FC testing is clinically useful for distinguishing organic GID (including IBD) from functional GIDs, and its incorporation into clinical practice for evaluating patients with lower gastrointestinal symptoms could lead to fewer patients with functional GIDs undergoing colonoscopy, reducing costs for both patients and the health system. CRD4201810507.


Purification of phospholipase-C from Bacillus cereus by affinity chromatography on 2-(4-aminophenylsulphonyl)ethyl-cellulose.
A new method for the purification of phospholipase-C (phosphatidylcholine cholinephosphohydrolase, EC 184.108.40.206) from Bacillus cereus has been developed, based on its affinity to 2-(4-aminophenylsulphonyl)ethyl derivative of beaded cellulose. The enzyme was adsorbed on the affinity sorbent through a site(s) that was clearly distinct from its catalytically active site, because it was still active in the immobilized state. A possible role of enzyme-inhibitor interaction in enzyme binding to the ligand used is discussed.


Multiplier method for limb-length prediction in the upper extremity.
Limb-length discrepancy occurs in both the upper and lower extremities. Methods of predicting discrepancies at skeletal maturity have generally focused on the lower limbs. Paley et al devised the multiplier method to predict lower-limb-length discrepancy at skeletal maturity. The purpose of this study was to generate a similar methodology applicable for the upper limb. Using radiographic, clinical, and anthropologic databases, we divided humeral, radial, and ulnar lengths at skeletal maturity by the humeral, radial, and ulnar lengths at each age and for each percentile given. The multipliers for the radius, the ulna, and the humerus were compared with each other. The multipliers also were compared based on percentile, ethnic and racial group, nationality, and anthropologic data. The multipliers for the humerus, radius, and ulna were equivalent in all percentile groups, varying only by age and gender after 1 year of age. The multipliers of different national and racial groups also were the same. The upper-extremity multipliers calculated from anthropologic data were very similar. The multiplier method is a quick and easy method of predicting upper-limb growth. It is simpler to use than previous methods and is independent of percentile, generation, ethnicity, nationality, and race. The upper-extremity multiplier can be used to determine timing of epiphysiodesis and predict bone length at skeletal maturity, growth remaining, and congenital and developmental limb-length discrepancy. Prognostic II.


Low-dose rituximab is effective in pemphigus.
Rituximab, an anti-CD20 antibody, was shown in open series studies to be effective in treating pemphigus at a dose of 4 × 375 mgm(-2) as approved for B-cell malignancies. We investigated whether a lower dose of rituximab is also effective for pemphigus. Patients with pemphigus were treated with a single course of two infusions of rituximab (500 mg each) at an interval of 2 weeks. Clinical consensus late end points, B-cell number, desmoglein 1 and desmoglein 3 indices were monitored. We enrolled 15 patients in the study: three with pemphigus foliaceus (PF) and 12 with pemphigus vulgaris (PV). The follow-up was 32-152 weeks (median 94). All 15 patients responded to therapy. Eight patients achieved complete remission in a median period of 5 weeks (four on minimal therapy, four off therapy). Seven patients achieved partial remission in a median period of 34·5 weeks (five on minimal therapy, two off therapy). Relapses (40%) were seen between 53 and 103 weeks (median 97) after start of therapy. B-cell numbers dropped to <1% after first infusion, and remained undetectable in patients with sustained remission. The antidesmoglein 1 index correlated well with the clinical severity in PF, but this was less obvious in PV. A low dose of rituximab is an effective and safe treatment for pemphigus. Relapses may occur, mostly at the end of the second year. Cost-effectiveness studies with a long follow-up are required to determine the proper dosage of this expensive drug in pemphigus.


Metagenome approaches revealed a biological prospect for improvement on mesophilic cellulose degradation.
Improvement on the bioconversion of cellulosic biomass depends much on the expanded knowledge on the underlying microbial structure and the relevant genetic information. In this study, metagenomic analysis was applied to characterize an enriched mesophilic cellulose-converting consortium, to explore its cellulose-hydrolyzing genes, and to discern genes involved in methanogenesis. Cellulose conversion efficiency of the mesophilic consortium enriched in this study was around 70 %. Apart from methane, acetate was the major fermentation product in the liquid phase, while propionate and butyrate were also detected at relatively high concentrations. With the intention to uncover the biological factors that might shape the varying cellulose conversion efficiency at different temperatures, results of this mesophilic consortium were then compared with that of a previously reported thermophilic cellulose-converting consortium. It was found that the mesophilic consortium harbored a larger pool of putative carbohydrate-active genes, with 813 of them in 54 GH modules and 607 genes in 13 CBM modules. Methanobacteriaceae and Methanosaetaceae were the two methanogen families identified, with a preponderance of the hydrogenotrophic Methanobacteriaceae. In contrast to its relatively high diversity and high abundance of carbohydrate-active genes, the abundance of genes involved in the methane metabolism was comparatively lower in the mesophilic consortium. A biological enhancement on the methanogenic process might serve as an effective option for the improvement of the cellulose bioconversion at mesophilic temperature.


Gene expression of inflammasome components in peripheral blood mononuclear cells (PBMC) of vascular patients increases with age.
Chronic low-grade inflammation is considered a driver of many age-related disorders, including vascular diseases (inflammaging). Inhibition of autophagic capacity with ageing was postulated to generate a pro-inflammatory condition via activation of inflammasomes, a group of Interleukin-1 activating intracellular multi-protein complexes. We thus investigated gene expression of inflammasome components in PBMC of 77 vascular patients (age 22-82) in association with age. Linear regression of real-time qRT-PCR data revealed a significant positive association of gene expression of each of the inflammasome components with age (Pearson correlation coefficients: AIM2: r = 0.245; P = 0.032; NLRP3: r = 0.367; P = 0.001; ASC (PYCARD): r = 0.252; P = 0.027; CASP1: r = 0.296; P = 0.009; CASP5: r = 0.453; P = 0.00003; IL1B: r = 0.247; P = 0.030). No difference in gene expression of AIM2, NLRP3, ASC CASP1, and CASP5 was detected between PBMC of patients with advanced atherosclerosis and other vascular patients, whereas IL1B expression was increased in PBMC of the latter group (P = 0.0005). The findings reinforce the systemic pro-inflammatory phenotype reported in elderly by demonstrating an increased phase-1 activation of inflammasomes in PBMC of vascular patients.


Assessing the similarity of nanoforms based on the biodegradation of organic surface treatment chemicals.
A substance may have one or more nanoforms, defined for regulatory purposes under EU chemicals legislation REACH based on differences in physicochemical properties such as size, shape, specific surface area and surface chemistry including coatings. To reduce the burden of testing each unique nanoform for the environmental risk assessment of nanomaterials, grouping approaches allow simultaneous assessment of multiple nanoforms. Nanoforms with initially different intrinsic properties, could still be considered similar if their environmental fate and effects can be demonstrated to be similar. One hypothesis to group nanoforms with different organic surface modifications is to use parameters linked to biodegradation of the organic surface. The hypothesis contends that nanoforms with a similar core chemistry, but different organic surface treatments may be grouped, if the surface treatment is likely to be lost through biodegradation rapidly upon entering an environmental compartment, such that it no longer modulates fate, exposure and toxicity of the nanoform. To implement grouping according to surface treatment biodegradability, a robust approach to measure the breakdown of particle surface treatments is needed. We present a tiered testing strategy to assess the biodegradation of organic surface treatments used with nanomaterials that can be implemented as part of an Integrated Approach to Testing and Assessment (IATA) for grouping based on surface treatment stability. The tiered approach consists of an initial pre-screening MT2 colorimetric carbon substrate utilisation assay, to provide a rapid assessment of coating degradation, and a second tier of testing using OECD Test Guideline 301F for assessing organic chemical biodegradability. Six common surface treatment substances are assessed using the tiered testing strategy to refine rules for escalating between tiers. Similarity assessment using absolute Euclidean distances and x-fold difference concluded that the Tier 1 assessment can be used as conservative binary screening for biodegradability (no false positive results in Tier 1), whilst for substances showing intermediate biodegradation (10-60% in OECD 301F, Tier 2), similarity assessments can be informative for grouping surface treatments not considered readily biodegradable. Further validation using higher tier tests (e.g., mesocosms) is needed to define acceptable limits of similarity between intermediately biodegradable substances, where differences in biodegradability of the surface coating lead to negligible differences in fate, behaviour and toxicity of the nanoforms, and this is critically discussed.


Transfusion-associated graft vs. host disease in a patient with high-grade B-cell lymphoma. Should cellular products for patients with non-Hodgkin's lymphoma be irradiated?
We present the case of a 64-year-old man who died from transfusion-associated graft vs. host disease (TA-GVHD) having been treated 2 years earlier for a high-grade, non-Hodgkin's lymphoma (NHL). We suggest that he was at increased risk of developing TA-GVHD as a result of the NHL and its subsequent treatment, and propose that patients with NHL should be added to those 'at risk' groups who receive irradiated cellular blood components.


Effect of potassium loading on bone sodium and total exchangeable sodium in sheep.
1. The effect of potassium (K) loading for 10 days on bone sodium (Na) and total exchangeable Na in sheep was examined. 2. There were no significant changes in Na space or exchangeable Na after K loading. 3. Bone Na concentration decreased by approximately 20% after K loading. 4. The degree of mobilization of Na from both the non-exchangeable and exchangeable pools in bone is sufficient to account to a large degree for the observed increase in extracellular fluid volume and the net negative sodium balance which is observed during K loading.


Zinc deficiency and lung converting enzyme activity in rats.
Angiotensin converting enzyme activity was found to be significantly decreased in the isolated perfused lung from zinc-deficient rats when compared with that of controls. Addition of zinc ion to the superfusion medium did not cause a recovery in this decreased activity of the enzyme. It is postulated that zinc deficiency probably produces a structural change in the lung angiotensin converting enzyme.


An observed rise in γ-hydroxybutyrate-associated deaths in London: Evidence to suggest a possible link with concomitant rise in chemsex.
Gamma-hydroxybutyrate (GHB) is the drug most linked to acute harm out of those used in chemsex, the incidence of which is reported to be increasing. However, there have been few systematic studies of the harms associated with GHB use. We investigated GHB-associated deaths from London coroners' jurisdictions between 2011 and 2015. Blood and urine samples were collected by pathologists and submitted for toxicological analysis at the request of coroners. Data from the Toxicology Unit, Imperial College London was retrospectively analysed. This comprised of 6633 cases from seven out of eight coroners' jurisdictions in London that underwent toxicological analysis between January 2011 and December 2015. A total of 61 GHB-associated deaths (0.92% of total cases), 184 cocaine-associated deaths (2.8% of total cases) and 83 MDMA-associated deaths (1.3% of total cases) were identified. There was a 119% increase in the proportion of GHB-associated deaths detected in 2015 compared to 2014. Over the same time period there was a 25% increase in cocaine-associated deaths and a 10% decrease in MDMA-associated deaths. Our data suggest that GHB-associated deaths are increasing in London, and that this is likely at least in part due to increasing use of GHB for chemsex. Further studies on the use of GHB are urgently required to understand the extent of its use, whether this is as prevalent in other major urban areas in the UK, and the full extent of the harms it causes.


Viral metagenomics of six bat species in close contact with humans in southern China.
Accumulating studies have shown that bats could harbor various important pathogenic viruses that could be transmitted to humans and other animals. Extensive metagenomic studies of different organs/tissues from bats have revealed a large number of novel or divergent viruses. To elucidate viral diversity and epidemiological and phylogenetic characteristics, six pooled fecal samples from bats were generated (based on bat species and geographic regions characteristic for virome analysis). These contained 500 fecal samples from six bat species, collected in four geographic regions. Metagenomic analysis revealed a plethora of divergent viruses originally found in bats. Multiple contigs from influenza A virus and coronaviruses in bats shared high identity with those from humans, suggesting possible cross-species transmission, whereas a number of contigs, whose sequences were taxonomically classifiable within Alphapapillomavirus, Betaretrovirus, Alpharetrovirus, Varicellovirus, Cyprinivirus, Chlorovirus and Cucumovirus had low identity to viruses in existing databases, which indicated possible evolution of novel viral species. None of the established caliciviruses and picornaviruses were found in the 500 fecal specimens. Papillomaviruses with high amino acid identity were found in Scotophilus kuhlii and Rhinolophus blythi, challenging the hypotheses regarding the strict host specificity and co-evolution of papillomaviruses. Phylogenetic analysis showed that four bat rotavirus A strains might be tentative G3 strains, according to the Rotavirus Classification Working Group classification.


Rapid immunoblot method for diagnosis of acute Mycoplasma pneumoniae infection.
A rapid immunoblotting technique based on the IgM response to a major immunogenic protein is described for the diagnosis of Mycoplasma pneumoniae infection. Using results of the complement fixation test as the criterion for diagnosis, the rapid immunoblot method was positive in 95.7% of patients. The sensitivity was reduced to 81.9% if the test was performed on either single sera or acute sera only from serum pairs. Although the few sera that failed to demonstrate a positive IgM response were more likely to be from older patients, there was a consistent IgM response recorded for both younger (less than 20 years) and older (greater than or equal to 20 years) patients.


The effect of two different biochars on remediation of Cd-contaminated soil and Cd uptake by Lolium perenne.
Biochar can be widely used to reduce the bioavailability of heavy metals in contaminated soil because of its adsorption capacity. But there are few studies about the effects of biochar on cadmium uptake by plants in soil contaminated with cadmium (Cd). Therefore, an incubation experiment was used to investigate the effects of rice straw biochar (RSBC) and coconut shell biochar (CSBC) on Cd immobilization in contaminated soil and, subsequently, Cd uptake by Lolium perenne. The results showed that the microbial counts and soil enzyme activities were significantly increased by biochar in Cd-contaminated soil, which were consistent with the decrease of the bioavailability of Cd by biochar. HOAc-extractable Cd in soil decreased by 11.3-22.6% in treatments with 5% RSBC and by 7.2-17.1% in treatments with 5% CSBC, respectively, compared to controls. The content of available Cd in biochar treatments was significantly lower than in controls, and these differences were more obvious in treatment groups with 5% biochar. The Cd concentration in L. perenne reduced by 4.47-26.13% with biochar. However, the biomass of L. perenne increased by 1.35-2.38 times after adding biochar amendments. So, Cd uptake by whole L. perenne was augmented by RSBC and CSBC. Accordingly, this work suggests that RSBC and CSBC have the potential to be used as a useful aided phytoremediation technology in Cd-contaminated soil.


Dynamics of cerebrospinal fluid pressure alterations and bilateral transverse-sigmoid sinus morphologies in Asian patients with venous pulsatile tinnitus.
This study was performed to investigate the dynamics of intracranial pressure (ICP) alterations and bilateral transverse-sigmoid sinus morphologies in patients with venous pulsatile tinnitus (PT). This retrospective study involved 27 patients with venous PT associated with sigmoid sinus wall anomalies. ICP and ICP metrics were measured by cerebrospinal fluid manometry and internal jugular vein compression tests. Correlation analysis was performed to determine the statistical correlation between ICP and the morphological metrics. The mean ICP was 212.5 ± 47.3 mmH2O. The median ΔICPtotal was 130 (range, 55-150) mmH2O. The ΔICPtotal was linearly correlated with the open lumbar pressure, and a significant difference was found between patients with normal and elevated cerebrospinal fluid pressure. The ΔICPdifference was linearly correlated with the Lendifference and Voldifference. ΔICP was linearly correlated with Lendifference. Complete obstruction of flow patency should be avoided in patients with low ICP and large volumetric/patency differences in the bilateral transverse-sigmoid sinus systems.


Surgical treatment of metastatic tumors to the pancreas: a single center experience and review of the literature.
Unlike primary pancreatic carcinoma, metastases to the pancreas are rare, and their resection may be performed as palliative treatment. The aim of this study was to review our experience with the operative management of pancreatic metastases. Between January 1994 and December 2004 13 patients (nine women and four men; median age: 59 years; range: 36-79 years) were admitted to our institution with metastatic lesion to the pancreas. The clinical features of the treatment and results were examined. Primary tumors were renal cell carcinoma (n=5), lobular carcinoma of the breast (n=3), endometrioid carcinoma of the ovary (n=1), colonic adenocarcinoma (n=1), jejunal leiomyosarcoma (n=1), melanoma (n=1), and non-small-cell lung cancer (n=1). The median interval between primary tumor and pancreatic metastases was 36 months (range: 5-192 months). Six patients (46%) were asymptomatic, while the other seven patients presented with jaundice, pain, and duodenal obstruction. Two patients with extrapancreatic disease underwent palliative surgery, and the remaining 11 patients underwent operative procedures that included seven pancreaticoduodenectomy and four distal pancreatectomies with splenectomy. Postoperative mortality was nil, and the morbidity rate was 30%. The two patients who underwent palliative surgery died after 7 and 9 months, respectively. The median survival of the resected patients was 26 months (range: 13-95 months). Five patients died of disease, eight are alive at the time of this report. A trend towards improved survival, even if not statistically significant, was observed in the renal carcinoma patients reported here. Surgical resection can be performed safely in selected patients with isolated metastases to the pancreas, achieving long-term survival as well as good palliation.


Potentiation of liposome-induced complement activation by surface-bound albumin.
Large anionic multilamellar liposomes containing 71% membrane cholesterol (MLV) caused complement (C) activation in human serum in vitro, as reflected in significant rises in S protein-bound terminal complex (SC5b-9) and C3a-desarg levels. Increasing the albumin content in serum by 1-4 g/100 ml led to 50-100% further increase in MLV-induced C activation, while higher amounts of exogenous human serum albumin (HSA) gradually lost the capability to potentiate liposomal C activation. HSA alone had no influence on SC5b-9 formation at any level below 12%. Complement activation by liposomes and the potentiating effect of supplemental HSA were greatly reduced or eliminated in the absence of C1q or in the presence of 10 mM EGTA/2.5 mM Mg(2+), pointing to the involvement of the classical pathway. Potentiation of C activation by supplemental HSA was not unique to MLV-induced activation, as deposition of HSA on the membrane of "Centricon" ultrafiltration units also potentiated the C-activating effect of the polycarbonate membrane. Fatty acid (FA) or non-monomeric protein contamination in HSA were unlikely to be playing a role in the described effects, as 96% pure, FA-rich (Buminate) and 99% pure, FA-free HSA had identical effects on liposomal C activation. While highlighting a new modulatory mechanism on liposomal C activation, the above data raise the possibility that deposition of extravasated HSA at sites of tissue injury may serve a hitherto unrecognized proinflammatory function.


Influence of aluminate and silicate on selenate immobilization using alkaline-earth metal oxides and ferrous salt.
Effects of aluminate and silicate species on the SeO42- immobilization using alkali-earth metal oxides and ferrous species have not been clearly elucidated. In the present study, Al and Si species were separately added into MgO/Fe(II) and CaO/Fe(II) reactions containing SeO42-, studied by toxicity characteristic leaching procedure (TCLP), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray absorption fine structure (XAFS), and PHREEQC simulation. Approximately 42 % of SeO42- was reduced to SeO32- for MgO/Fe(II) reaction in the presence of Al species, being consistent with the case without Al species. The Al species only showed slight inhibition of Se leaching for the MgO/Fe(II) reaction. Most of Se oxyanions were adsorbed onto Mg(OH)2 through outer-sphere complexation. For CaO/Fe(II) reaction, all of SeO42- was reduced to SeO32- with or without Al species. However, the Se leaching amount (3 %) of sample added with Al species (CE3) is much lower than that (12 %) of sample without Al species (CE2). This is mainly because SeO32- can be sorbed onto the iron-based minerals through binuclear bidentate corner-sharing (2C) complexation instead of monodentate mononuclear corner-sharing (1V) complexation of the case without Al species. On the other hand, SeO42- was not reduced to SeO32- in the presence of silicate, and almost all of Se was leached out for silicate-contained samples except CaO/Fe(II) reaction with the addition of Al species. This is due to the polymerization of Al and Si species under a high-alkalinity environment, thereby stabilizing SeO42- in the amorphous silicon-aluminum structure and contributing to the decrease of Se leaching.


Per- and Polyfluoroalkyl Substances (PFAS) and Lipid Trajectories in Women 45-56 Years of Age: The Study of Women's Health Across the Nation.
Per- and polyfluoroalkyl substances (PFAS) are associated with less favorable blood lipid profiles in epidemiological studies. However, little is known about the potential role of PFAS in longitudinal changes in lipids among midlife women even though women become more susceptible to metabolic alterations during the menopausal transition. To examine associations of serum PFAS concentrations with longitudinal trajectories of blood total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides in midlife women undergoing menopausal transition. The sample included 1,130 women from the Study of Women's Health Across the Nation 45-56 y of age at baseline (1999-2000). We measured serum PFAS concentrations including linear perfluorooctanoic acid (n-PFOA), perfluorononanoic acid (PFNA), linear and branched perfluorooctanesulfonic acid (n-PFOS and Sm-PFOS, respectively), and perfluorohexanesulfonic acid (PFHxS) at baseline. We used k-means clustering to identify subgroups with different patterns of PFAS mixture. Blood lipids were measured annually or biannually through 2016 with an average follow-up of 14.8 y. We identified longitudinal trajectories of each lipid using latent class growth models. We used multinomial log-linear models adjusted for covariates to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of lipid trajectory classes by PFAS and their mixtures. Three distinct trajectories (low, middle, high) of total, LDL, and HDL cholesterol and two distinct trajectories (low and high) of triglycerides were identified. n-PFOS, Sm-PFOS, and PFHxS were positively associated with total and LDL cholesterol trajectories. n-PFOS was inversely associated with triglycerides trajectories. PFAS mixtures (high vs. low) showed positive associations with total and LDL cholesterol trajectories (high vs. low), showing ORs (95% CIs) of 1.69 (95% CI: 1.36, 2.12) and 1.79 (95% CI: 1.44, 2.22), respectively. Concentrations of serum PFAS were positively associated with trajectories of total and LDL cholesterol, providing a line of evidence supporting adverse effects of PFAS on lipid homeostasis. https://doi.org/10.1289/EHP12351.


Distinguishing Gender Identity From Biological Sex in Dermatologic Health Care: Methods, Harms, and Paths Forward.
Accurate assessment of gender identity and biological sex in dermatology research is crucial since their conflation or poor demarcation undermines patient respect and study accuracy. Clearer guidance is needed for health care researchers, particularly in light of the notable disparities in skin disease rates, skincare practices, literature representation, and the persistent underrepresentation of transgender and nonbinary patients.


Validity of partial protocols to evaluate the prevalence of developmental defects of enamel in permanent dentition: a birth cohort study in Southern Brazil.
To evaluate the validity of partial protocols (PP) to assess the prevalence of developmental defects of enamel (DDE) in permanent teeth and identify the strength of the association between DDE and some risk factors, using PP compared to the full-mouth (FM) exam. This study was conducted in a population-based birth cohort of children born in 2004 in Pelotas, Southern Brazil. Socioeconomic, demographic, pre-, per-, and post-birth variables were collected. A subsample of 994 children was clinically examined for DDE in 2017, using the modified DDE index, using the "full- mouth" (FM) protocol. After FM had been performed, a dataset was created. Two different partial protocols (PP) were simulated from FM data: "only buccal surfaces (BS)" and "incisive and molars only (IM)." Sensitivity, absolute and relative bias, and inflation factors were calculated. For any DDE, FM had prevalence of 40.8%. The prevalence of DDE was 38.8% and 36.0%, for BS and IM protocols, respectively. When tested for any DDE, PP "BS" and "IM" showed high sensitivity. The underestimation of the true prevalence did not exceed 6.9% for PP "BS" and 16.1% for PP "IM." All protocols showed similar magnitude of association with the selected risk factors. Both PP "BS" and "IM" can be used to estimate the prevalence of DDE in epidemiological studies. Oral health surveys now have the option of using PP to collect DDE prevalence and investigate their association with risk factors, being less time-consuming, expensive, and labor intensive.


Neighbourhood characteristics as a predictor of adherence to dietary recommendations: A population-based cohort study of Finnish adults.
Aims: To investigate the association of six-year cumulative level of socioeconomic neighbourhood disadvantage and population density with subsequent adherence to dietary recommendations, controlling for preceding dietary adherence, in adults in Finland. Methods: Population-based Health and Social Support (HeSSup) study participants from four age groups (20-24, 30-34, 40-44 and 50-54 years at baseline in 1998). Data on diet and alcohol consumption were obtained from the 2003 and 2012 surveys and information on neighbourhoods from Statistics Finland Grid database (n = 10,414 men and women). Participants diet was measured as adherence to Nordic Nutrition recommendation (score range 0-100). Neighbourhood disadvantage was measured by median household income, proportion of those with primary education only and unemployment rate, and population density by the number of adult population between years 2007 and 2012. Linear models were used to assess the associations of neighbourhood characteristics with the score for adherence to dietary recommendations in 2012. Results: Cumulative neighbourhood socioeconomic disadvantage was associated with slightly weaker (1.49 (95% confidence interval (CI) -1.89 to -1.09) point decrease in dietary score) adherence while higher population density was associated with better (0.70 (95% CI 0.38-1.01) point increase in dietary score) adherence to dietary recommendations. These associations remained after controlling for prior dietary habits, sociodemographic, chronic cardio-metabolic diseases, and severe life events. Conclusions: These longitudinal findings support the hypothesis that neighbourhood characteristics affect dietary habits.


Analgesic and anti-inflammatory therapy in the elderly.
In the United States today, the number of persons 65 years of age or older is about 25 million. Two thirds of this group have musculoskeletal complaints severe enough to cause them to use considerable quantities of over-the-counter medications to alleviate discomfort. In treating elderly patients with osteoarthritis, one of the most common rheumatic diseases of the elderly, it is imperative for physicians to be aware of the numerous physiologic aspects of aging and how these may affect the pharmacokinetic activity of various prescribed agents. Drug therapy in the elderly should be determined by the principle of least toxicity. Dosage titration is particularly advisable when pharmacokinetic activity of a drug is not known.


Intrinsic Risk Factors for Ankle Sprain Differ Between Male and Female Athletes: A Systematic Review and Meta-Analysis.
Ankle sprains remain prevalent across most team sports. However, despite divergent ankle sprain injury rates in male and female athletes, little is known about potential sex-specific risk factors for ankle sprain. To systematically investigate the sex-specific risk factors for ankle sprain. Combinations of the key terms were entered into PubMed, Web of Science, Embase and Cochrane Library databases, and prospective studies reporting ankle sprain risk factors in males or females were included for meta-analysis. Sixteen studies were eligible for inclusion, for a total of 3636 athletes (735 female) and 576 ankle sprains (117 female). Out of 21 prognostic factors, previous ankle sprain injury (odds ratio = 2.74, P < .001), higher body mass index (SMD = 0.50, P < 0.001), higher weight (SMD = 0.24, P = 0.02), lower isometric hip abduction strength (SMD = - 0.52, P < 0.0001) and lower dynamic balance performance (SMD = - 0.48 to - 0.22, P < 0.001-0.04) were identified as risk factors in male athletes. In female athletes, out of 18 factors eligible for meta-analysis, only lower concentric dorsiflexion strength was identified as a risk factor (SMD = - 0.48, P = 0.005). This meta-analysis provides novel evidence for different risk factor profiles for ankle sprain injuries between female and male athletes. Further studies, particularly in female athletes, are needed to strengthen the evidence.


High-yield roentgenographic criteria for cervical spine injuries.
All trauma patients undergoing cervical radiography at an urban referral teaching hospital emergency department during 12 consecutive months were analyzed for indications and results of cervical spine radiograph studies. Demographic characteristics of the study group were consistent with results in the literature (55% men, mean age, 27). Cases were reviewed for 27 commonly accepted indications in the literature for cervical spine studies under these circumstances. The following radiograph findings were considered as positive studies: fracture, subluxation, spondylolisthesis, straightening, spasm, foreign body, compression, fusion, narrowing, or soft tissue swelling. Seventeen percent of radiographs were positive. Motor vehicle accidents (P less than .009), a history of direct cervical trauma (P less than .002), loss of consciousness (P less than .001), cervical tenderness (P less than .05), and drug ingestion (P less than .08) were associated with or suggestive of positive radiographs. No patients wearing seatbelts had positive radiographs (P less than .001). Only 2.4% (18 of 749) of radiographic examinations revealed clinically significant findings, and no criteria were statistically correlated with clinically significant findings. While our study suggests up to two-thirds of radiographs might be deferred without missing a clinically significant injury using these high-yield criteria, a flexible approach to cervical roentgenographs is justified pending confirmation of our results by a large, multicenter, prospective study currently under way.


Sonoanatomy relevant for lumbar plexus block in volunteers correlated with cross-sectional anatomic and magnetic resonance images.
Ultrasound imaging of the anatomy relevant for lumbar plexus block (LPB) is challenging because of its deep anatomic location and the "acoustic shadow" of the overlying transverse processes. A paramedian transverse scan (PMTS) of the lumbar paravertebral region with the ultrasound beam being insonated through the intertransverse space (ITS) and directed medially toward the intervertebral foramen (PMTS-ITS) may overcome the problem of the "acoustic shadow" and allow clear visualization of the anatomy relevant for LPB. This study assessed the feasibility of using PMTS-ITS for imaging the anatomy relevant for LPB in healthy volunteers. Thirty young volunteers underwent a PMTS-ITS of the right lumbar paravertebral region. The sonoanatomy was defined in corresponding cadaver anatomic sections and magnetic resonance images. Visibility of the paravertebral structures in the sonograms was assessed by 4 independent observers using a 4-point Likert scale (0, not visible; 1, hardly visible; 2, well visible; 3, very well visible), and the mean total ultrasound visibility score (UVS; maximum score possible, 30) was determined. Overall ultrasound visibility was judged as good if the total UVS was greater than 20, average if it was 10 to 20, and poor if it was less than 10. Ultrasound imaging of the right lumbar paravertebral region at the L3-L4-L5 vertebral level was successfully performed through the PMTS-ITS scan window in all volunteers studied. The lumbar nerve root, lumbar paravertebral space, lumbar plexus, and the psoas compartment were delineated in 57%, 27%, 57%, and 87% of volunteers, respectively. Overall ultrasound visibility of the lumbar paravertebral structures was judged as "good" (mean [SD] total UVS, 20.4 [3]). A PMTS-ITS can be used to image the sonoanatomy relevant for LPB including the lumbar nerve root, lumbar paravertebral space, lumbar plexus, and the psoas compartment.


Stereospecific and non-stereospecific effects of ibuprofen on human platelet and polymorphonuclear leukocyte functions.
This study compares biological activities of racemic ibuprofen (rac-IBU) and its S(+) and R(-) enantiomeres in human platelet and polymorphonuclear cells (PMN). Rac-IBU inhibited cyclooxygenase-related platelet functions (aggregation, thromboxane (TX) B2 formation) in vitro, the S-(+) enantiomer being 40-100-times more active than the R-(-) form. rac-IBU also inhibited PMN functions (O2- generation, beta-glucuronidase release). These effects in PMN were not stereospecific. The data suggest cyclooxygenase-independent actions of ibuprofen in human PMN which may contribute to its antiinflammatory effects in vivo.


Evolution of trimethoprim/sulfamethoxazole resistance in Shewanella algae from the perspective of comparative genomics and global phylogenic analysis.
Shewanella algae is a zoonotic marine bacterium that causes a variety of infections in immunocompromised patients or those who have been exposed to seawater. The development of trimethoprim/sulfamethoxazole (TMP/SMX) resistance in S. algae are found in human and environment isolates during the past ten years, and thus the treatment options are decreasing. In the study, we conduct a comparative genomic study to identify the resistant mechanism of TMP/SMX-resistance in S. algae. We found the resistance of TMP/SMX in S. algae is associated with the existence of sul1 and dfrA12 within the class 1 integron. The gene cassette dfra12-aadA2-qacEΔ1/sul1 within the class 1 integron is highly conserved. In addition, the class 1 integron and encapsulated sul1 are significantly enriched in Enterobacteriaceae in NCBI and UniProt databases. Our study suggests that the horizontal transfer of TMP/SMX resistance via class 1 integron is most frequently occurred within Enterobacteriaceae and has spread to a wide range of sources including soil, poultry, and marine water.


Principal component analysis and the scaled subprofile model compared to intersubject averaging and statistical parametric mapping: I. "Functional connectivity" of the human motor system studied with [15O]water PET.
Using [15O]water PET and a previously well studied motor activation task, repetitive finger-to-thumb opposition, we compared the spatial activation patterns produced by (1) global normalization and intersubject averaging of paired-image subtractions, (2) the mean differences of ANCOVA-adjusted voxels in Statistical Parametric Mapping, (3) ANCOVA-adjusted voxels followed by principal component analysis (PCA), (4) ANCOVA-adjustment of mean image volumes (mean over subjects at each time point) followed by F-masking and PCA, and (5) PCA with Scaled Subprofile Model pre- and postprocessing. All data analysis techniques identified large positive focal activations in the contralateral sensorimotor cortex and ipsilateral cerebellar cortex, with varying levels of activation in other parts of the motor system, e.g., supplementary motor area, thalamus, putamen; techniques 1-4 also produced extensive negative areas. The activation signal of interest constitutes a very small fraction of the total nonrandom signal in the original dataset, and the exact choice of data preprocessing steps together with a particular analysis procedure have a significant impact on the identification and relative levels of activated regions. The challenge for the future is to identify those preprocessing algorithms and data analysis models that reproducibly optimize the identification and quantification of higher-order sensorimotor and cognitive responses.


Darbepoetin alfa (KRN321) is safe and effective when administered subcutaneously once every 2 or 4 weeks to patients on peritoneal dialysis in Japan.
Darbepoetin alfa (KRN321) is a recombinant protein that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. Due to its longer half-life and greater biological activity than recombinant human erythropoietin (rHuEPO), KRN321 maintains an effective hemoglobin (Hb) level at extended dose intervals compared with rHuEPO. The efficacy and safety of KRN321 administered subcutaneously to patients on peritoneal dialysis (PD) were tested. In a multicenter, open-label, single-arm study, KRN321 was administered subcutaneously to patients on PD for 26-28 weeks. Ninety-six patients initially were given a 60 μg subcutaneous dose once every 2 weeks until a target of Hb (11.0-13.0 g/dL) was achieved. Thereafter, their dose was every 2 or 4 weeks. After the target of Hb was reached in most subjects (96.9%), it was maintained with KRN321 administered every 2 or 4 weeks. On completion of (or withdrawal from) study, 65 subjects (67.7%) maintained the target Hb. Although a number of adverse event related to hypertension occurred, their incidence did not appear to be related to Hb or its rate of increase. These events could be controlled adequately by interrupting or reducing the dose, and/or treatment with antihypertensives. The efficacy and safety of KRN321 when administered subcutaneously for 28 weeks to PD patients were confirmed. It was suggested that the quality of life of patients can be improved by treatment with KRN321 due to the reduced frequency of administration.


Evaluating the Impact of Parent-Reported Medical Home Status on Children's Health Care Utilization, Expenditures, and Quality: A Difference-in-Differences Analysis with Causal Inference Methods.
To evaluate the effects of the parent-reported medical home status on health care utilization, expenditures, and quality for children. Medical Expenditure Panel Survey (MEPS) during 2004-2012, including a total of 9,153 children who were followed up for 2 years in the survey. We took a causal difference-in-differences approach using inverse probability weighting and doubly robust estimators to study how changes in medical home status over a 2-year period affected children's health care outcomes. Our analysis adjusted for children's sociodemographic, health, and insurance statuses. We conducted sensitivity analyses using alternative statistical methods, different approaches to outliers and missing data, and accounting for possible common-method biases. Compared with children whose parents reported having medical homes in both years 1 and 2, those who had medical homes in year 1 but lost them in year 2 had significantly lower parent-reported ratings of health care quality and higher utilization of emergency care. Compared with children whose parents reported having no medical homes in both years, those who did not have medical homes in year 1 but gained them in year 2 had significantly higher ratings of health care quality, but no significant differences in health care expenditures and utilization. Having a medical home may help improve health care quality for children; losing a medical home may lead to higher utilization of emergency care.


[Eugenics: progress or backward movement?].
Throughout this article there is a critical analysis of how genetics presents a dilemma for "human progress". So much so, that the legal world aims to create unequivocal norms and guarantees in relation with eugenics in order to avoid attempting against human dignity. The document makes the reader reflect on the ethical problems that eugenics can entail.


Self-expanding stent for complex percutaneous coronary interventions: A real life experience.
Self-expanding stents represent a re-emerging option for percutaneous coronary interventions. Their application covers a wide spectrum of angiographic situations, i.e., coronary bifurcations, acute coronary syndromes with large thrombotic burden and stenosis of ectatic coronaries. We review our experience with self-expanding stents for different clinical and angiographic indications, with long clinical follow-up. From 2011 to 2013 we used self-expanding STENTYS® stents in 40 consecutive patients followed-up for death from any cause and from cardiovascular cause, myocardial infarction, target lesion revascularization (TLR), stent thrombosis (mean 21±13months). We also revised rate of procedural outcomes, acute stent thrombosis and TLR in patients treated with conventional stents for similar clinical/angiographic situations, in the same period at our institution. We identified three anatomical settings of STENTYS® use: coronary bifurcations with proximal/distal main branch diameter discrepancy (55% of cases), massive thrombotic burden in the setting of acute coronary syndrome (35% of cases) and stenosis of ectatic coronaries (15%). We observed one death related to acute heart failure and 1 case (2.5%) of acute stent thrombosis (2.5% in the control group). During follow-up 2 cases of stent restenosis leading to TLR (5%) occurred (6.25% in the control group). According to our real life experience, self-expanding STENTYS® stents appear to be an effective tool for different angiographic situations in which they may be preferable to balloon-expandable stents, showing a low rate of complications and good results at long term follow-up.


In vivo neutron activation analysis for bone calcium (INVAA) in malignant hyperthermia susceptible patients.
Some non-rigid Malignant Hyperthermia Susceptible (MHS) patients have a greater than normal incidence of fractures. Radiologically their long bones are slightly thinner than normal. Excessive numbers of caries because of thin dental enamel may also be present. The Malignant Hyperthermic (MH) defects thus appears to involve cells of bone appendages as well as of muscle. We have measured the concentration of calcium in bone by neutron activation analysis and have found it to be reduced in both non-rigid and rigid malignant hyperthermia susceptible patients. The reductions were particularly marked for the non-rigid patients. Bone calcium concentrations were lower in males than in females and in those under 16 and over 60 years of age. This is additional evidence is favour of the hypothesis that malignant hyperthermia is a widespread defect affecting tissues and organs throughout the body.


Acute oligohydramnios in postdate pregnancy.
The evaluation of amniotic fluid volume plays a major role in antepartum fetal surveillance. Although the definition of diminished amniotic fluid volume varies, this sign is considered by itself an indication for intervention in the near-term fetus. The interval of testing is predicated on the concept that amniotic fluid volume diminishes slowly (unquantified) as a result of developing hypoxia. We present six postterm pregnancies in which amniotic fluid volume diminished abruptly over 24 hours. Although one fetus died, the three babies delivered by cesarean section and the two babies delivered after a 2-day labor did well, despite obvious postmaturity syndrome, meconium staining, and variable decelerations. Apgar scores in the survivors were above 8, and pH results failed to confirm hypoxia. These data suggest the need to better understand the mechanisms regulating amniotic fluid volume.


Thermodynamic nonideality as a probe of macromolecular isomerizations: application to the acid expansion of bovine serum albumin.
The potential use of thermodynamic nonideality as an index of the coexistence of two isomeric protein states in equilibrium is explored in relation to the effect of inert space-filling macromolecular solutes on the gel chromatographic behavior of the system. Frontal gel chromatography, on Sephadex G-100, of bovine serum albumin at pH 3.2 in the presence and absence of a moderately high (15 g/liter) concentration of either Dextran T70 or Dextran T10 is then employed to establish that the progressive increase in the Stokes radius of albumin as the pH is lowered from 5 to 2 should not be viewed as a pH-dependent isomerization equilibrium between native and acid-expanded states. In addition, calculations based on parameters for the aspartate transcarbamoylase system point to the possible use of the present methodology to distinguish between preexistence and ligand induction of an isomerization equilibrium as the source of a sigmoidal effect in allosteric systems.


Aberrant protein trafficking in retinal degenerations: The initial phase of retinal remodeling.
Retinal trafficking proteins are involved in molecular assemblies that govern protein transport, orchestrate cellular events involved in cilia formation, regulate signal transduction, autophagy and endocytic trafficking, all of which if not properly controlled initiate retinal degeneration. Improper function and or trafficking of these proteins and molecular networks they are involved in cause a detrimental cascade of neural retinal remodeling due to cell death, resulting as devastating blinding diseases. A universal finding in retinal degenerative diseases is the profound detection of retinal remodeling, occurring as a phased modification of neural retinal function and structure, which begins at the molecular level. Retinal remodeling instigated by aberrant trafficking of proteins encompasses many forms of retinal degenerations, such as the diverse forms of retinitis pigmentosa (RP) and disorders that resemble RP through mutations in the rhodopsin gene, retinal ciliopathies, and some forms of glaucoma and age-related macular degeneration (AMD). As a large majority of genes associated with these different retinopathies are overlapping, it is imperative to understand their underlying molecular mechanisms. This review will discuss some of the most recent discoveries in vertebrate retinal remodeling and retinal degenerations caused by protein mistrafficking.


MicroRNA-323-3p: a new biomarker and potential therapeutic target for rheumatoid arthritis.
Increased expression of microRNA-323-3p (miR-323-3p) has been demonstrated in rheumatoid arthritis synovial fibroblast. The gene encoding miR-323-3p, which is a biomarker in immune and inflammatory responses, occurs in an miRNA cluster in chromosomal region 14q32.31.


Amplification of c-Ki-ras-2 oncogene sequences in human carcinoma of pancreas.
c-Ki-ras-2 sequences were visualized in paraffin embedded sections from normal adult human pancreases and 24 carcinomas of pancreas by an in situ hybridization technique. A biotinylated 1 kbp EcoRI fragment of pHiHi3 DNA was used as probe and the oncogene was visualized as one or two large grains of reaction products produced in more than 9% of normal pancreas nuclei by streptavidin-peroxidase complex and diaminobenzidine tetrachloride. Its amplification in pancreatic carcinomas was detected as one or more large grains in 54% of the nuclei. In addition, tumor cells showed small nuclear and cytoplasmic grains scarcely seen in normal pancreatic cells. The differential transcriptional activity of this oncogene in cancer cells and the adjacent normal pancreatic cells on the same section was evident in sections from 5 cases where normal pancreas was present.


Human arginase I: a potential broad-spectrum anti-cancer agent.
With high rates of morbidity and mortality, cancer continues to pose a serious threat to public health on a global scale. Considering the discrepancies in metabolism between cancer and normal cells, metabolism-based anti-cancer biopharmaceuticals are gaining importance. Normal cells can synthesize arginine, but they can also take up extracellular arginine, making it a semi-essential amino acid. Arginine auxotrophy occurs when a cancer cell has abnormalities in the enzymes involved in arginine metabolism and relies primarily on extracellular arginine to support its biological functions. Taking advantage of arginine auxotrophy in cancer cells, arginine deprivation, which can be induced by introducing recombinant human arginase I (rhArg I), is being developed as a broad-spectrum anti-cancer therapy. This has led to the development of various rhArg I variants, which have shown remarkable anti-cancer activity. This article discusses the importance of arginine auxotrophy in cancer and different arginine-hydrolyzing enzymes that are in various stages of clinical development and reviews the need for a novel rhArg I that mitigates the limitations of the existing therapies. Further, we have also analyzed the necessity as well as the significance of using rhArg I to treat various arginine-auxotrophic cancers while considering the importance of their genetic profiles, particularly urea cycle enzymes.