Are low ultraviolet B and vitamin D associated with higher incidence of multiple myeloma?
The purpose of this study was to determine whether an inverse association exists between latitude, solar ultraviolet B (UVB) irradiance, and incidence rates of multiple myeloma.Methods Associations of latitude and UVB irradiance with age-standardized incidence rates of multiple myeloma were analyzed for 175 countries while controlling for sex-specific obesity prevalence, cigarette consumption, and alcohol consumption using multiple linear regression.Results Incidence rates of multiple myeloma were greater at higher latitudes (R(2) for latitude for males=0.31, p<0.0001; females R(2)=0.27, p<0.0001). In regression models for males (R(2)=0.62, p<0.0001) and females (R(2)=0.51, p<0.0001), UVB irradiance was independently inversely associated with incidence rates.Conclusions Age-adjusted incidence rates of multiple myeloma were higher in countries with lower solar UVB irradiance. Further investigation is warranted in individuals of the association of prediagnostic serum 25(OH)D with risk.


Artificial Organs 2016: A Year in Review.
In this Editor's Review, articles published in 2016 are organized by category and briefly summarized. We aim to provide a brief reflection of the currently available worldwide knowledge that is intended to advance and better human life while providing insight for continued application of technologies and methods of organ Replacement, Recovery, and Regeneration. As the official journal of The International Federation for Artificial Organs, The International Faculty for Artificial Organs, the International Society for Mechanical Circulatory Support, the International Society for Pediatric Mechanical Cardiopulmonary Support, and the Vienna International Workshop on Functional Electrical Stimulation, Artificial Organs continues in the original mission of its founders "to foster communications in the field of artificial organs on an international level." Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery, and Regeneration from all over the world. We were pleased to publish our second Virtual Issue in April 2016 on "Tissue Engineering in Bone" by Professor Tsuyoshi Takato. Our first was published in 2011 titled "Intra-Aortic Balloon Pumping" by Dr. Ashraf Khir. Other peer-reviewed Special Issues this year included contributions from the 11th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion edited by Dr. Akif Ündar and selections from the 23rd Congress of the International Society for Rotary Blood Pumps edited by Dr. Bojan Biocina. We take this time also to express our gratitude to our authors for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide meaningful suggestions to the author's work whether eventually accepted or rejected. Without these excellent and dedicated reviewers the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, John Wiley & Sons for their expert attention and support in the production and marketing of Artificial Organs. We look forward to reporting further advances in the coming years.


A Comparative Study of Bacterial Infections Between COVID-19 and Non-COVID-19 Patients With Respect to Different Isolates and Their Antibiotic Sensitivity Pattern.
Background Following the pandemic caused by SARS-CoV-2, the emergence of and following the pandemic has required major modifications to healthcare systems and frameworks. Antimicrobials have more than a few potential roles in managing COVID-19. Experimental cures for the treatment of SARS-CoV-2 are being explored. The availability of limited data suggests that nosocomial infections are associated with a higher risk of death and severity of COVID-19. To fill this knowledge gap, we conducted a study to assess the spectrum of bacteriological isolates in different samples from COVID-19 patients. Our study aimed to evaluate the antibiotic resistance pattern of these bacterial isolates and compare the spectrum of bacteriological isolates in different samples and their antibiotic sensitivity pattern between COVID-19 and non-COVID-19 patients. Methodology An observational cross-sectional, partly retrospective, and partly prospective study was carried out in the bacteriology section of the Department of Microbiology, Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, for a total duration of six months from February 2021 to July 2021. The profile of pathogens isolated from 105 clinical samples from COVID-19 patients was studied. To detect COVID-19, RT-PCR was performed. All clinical specimens (urine, blood, pus, respiratory sample, etc.) were processed and cultured on different media to support the growth of the bacteria as per our standard operating procedures (SOP) for bacteriology samples. Antimicrobial susceptibility testing was carried out based on the Clinical and Laboratory Standards Institute. Results A total of 105 clinical samples were received in the bacteriology section of the Department of Microbiology, IGIMS, Patna, Bihar, from admitted COVID-19 patients. The mean age of study participants was 51.57 ± 14.76 years, and males (66.7%, 70/105) were more than females (33.3%, 35/105). The majority of the patients were 91 out of 105 (86.67%) from the ward and 14 from the ICU (13.33%). Of the total samples tested, 62 (59%) were urine samples, 26 (24.8%) were respiratory specimens, 13 (12.4%) were pus samples, 3 (2.9%) were body fluids, and 1 (1%) were tissue samples. Among the total pathogen isolates (n=57) obtained from patients with SARS-CoV-2 admitted to the ward and ICU, 56.14% (32) were gram-negative, 26.31% (15) were Candida, and 17.54% (10) were gram-positive pathogens. The most isolated pathogen was Escherichia coli (39.02%, 16/41) followed by Klebsiella pneumoniae (29.26%, 12/41), Acinetobacter baumannii (7.31%, 3/41), and Enterobacter cloacae (2.43%, 1/41). Enterococcus spp. as gram-positive bacteria were isolated in 21.95% (9/41) of patients. Among the gram-negative bacteria (Enterobacterales), the highest resistance was seen in ampicillin (100%,29/29). For non-Enterobacterales, the highest resistance was seen in ceftriaxone (66.66%,2/3). Enterococcus spp. showed maximum ciprofloxacin, and gentamicin (high level) resistance was 100% (9/9). Conclusion Secondary infections with resistant pathogens in COVID-19 patients highlight the importance of antimicrobial management programs focused on the optimal selection of empirical treatments based on culture reports.


Successful treatment of Brucella endocarditis with aortic root abscess.
Brucella endocarditis is a rare but fatal complication of Brucellosis, it causes destructive valvular lesions. The aortic valve is the most common affected site. We present a case of Brucella endocarditis with aortic root abscess, the patient received a prolonged combination of antibiotic therapy, and underwent aortic valve replacement. After one and a half years of follow up, the patient is still without signs of recurrence. The high mortality in Brucella endocarditis can be overcome by early diagnosis and aggressive therapy.


Impact of Fatty Liver on Acute Pancreatitis Severity.
Aim. Acute pancreatitis is typically a mild disease, but some patients develop severe courses. Fatty liver changes are seen in patients with acute pancreatitis, but its clinical significance has not been well-studied. We aimed to investigate the relationship between fatty liver and the severity of acute pancreatitis. Methods. Unenhanced CT images of patients with acute pancreatitis were retrospectively reviewed by a radiologist, and mean hepatic and splenic attenuation was measured in Hounsfield units (HU). Fatty liver was defined as mean hepatic/splenic HU < 1. Results. Among 200 patients, fatty liver was found in 67 (33.5%) and nonfatty liver in 133 (66.5%). Compared with patients without fatty liver, the severity of pancreatitis and levels of serum C-reactive protein were higher in fatty liver patients. The prevalence of local complications, persistent organ failure, and mortality were also higher in patients with fatty liver. Even after adjusting for age, sex, body mass index, and cause of pancreatitis, fatty liver was significantly associated with moderately severe or severe acute pancreatitis. Conclusions. Fatty liver may play a prognostic role in acute pancreatitis. Fatty liver could be incorporated into future predictive scoring models.


Semimacroscopic examinations of the surface pattern of small intestinal mucosa in Crohn's disease.
The mucosal surface pattern of surgical specimens from small intestine affected by Crohn's disease are studied using Alcian-green staining of whole mounts. The semimacroscopic appearance of the mucosa is described. Our findings include i.a. malformation and enlargement of villi-often to extreme degree-villi frequently showing small vesicles on their apical region. Polypoid structures were found to be avillous as well as covered by normal or abnormal villi. The semimacroscopic observations are compared with observations from conventional light microscopy. The villus enlargement is in the first stages caused by lymphatic dilatation and later by oedema and inflammation.


Transient and resident microflora of burn unit personnel and its influence on burn wound sepsis.
The exogenous contamination of a thermally injured patient by contact with the health are team has been a major concern of all burn units. Since the University of Chicago Burn Center routinely monitors each burn injury for sepsis by quantitative bacteriology and recently examined the microbial population present on the hands of the health care team, it was felt that these combined data would shed some pertinent information on exogenous burn wound sepsis. Twenty-nine patients with clinical burn wound sepsis and a bacterial level of greater than 10(5) bacteria/gram of tissue were studied. These patients yielded a variety of microorganisms with P. aeruginosa and Staphylococcus aureus being predominant, followed in incidence by Candida albicans. The resident and transient microflora isolated from each member of the health care team treating the specific individual concerned did not correlate with the causative agent of burn wound sepsis. The most frequent isolate from the staff personnel was Staphylococcus epidermidis followed by Micrococcus species. Though colonization of the thermally injured individual has been reported, these data strongly suggest that colonization is primarily one of an endogenous source rather than that of an exogenous one.


Human interstitial retinoid binding protein. A potent uveitopathogenic agent for the induction of experimental autoimmune uveitis.
Human interstitial retinoid binding protein (HIRBP) is a 136,000 m.w. photoreceptor cell protein which transports retinoids between the retina and the retinal pigment epithelium of the eye. The amino acid sequence of HIRBP suggests that the molecule consists of four continuous homology domains which arose by several gene duplications some 600 to 800 million years ago. When injected into susceptible animal species, including primates, it induces an experimental autoimmune uveitis (EAU), a predominantly T cell-mediated autoimmune disease of the retina and uveal tract of the eye, and the pineal gland. In order to further refine specific sites in HIRBP responsible for its uveitopathogenicity, we synthesized 120 overlapping peptide corresponding to its entire 1262 amino acid sequence, and tested each peptide for its ability to induce an EAU in Lewis rats. Five peptides with extensive amino acid sequence homology, designated HIRBP 715, HIRBP greater than 730 and HIRBP 745, HIRBP 778, and HIRBP 808 were uveitopathogenic when used at a 50 micrograms immunizing dose. The most potent peptide for the induction of EAU was HIRBP 715 (amino acid positions 521 to 540). In dose response studies as little as 0.1 microgram/animal was capable of inducing an inflammatory response. In addition, peptide HIRBP 946 which corresponds to the mid portion of peptide HIRBP 715 and contains only eight amino acids (RTATAAEE) was uveitopathogenic under our experimental conditions. Our study identifies multiple uveitopathogenic sites in HIRBP and further defines the amino acids necessary for the induction of EAU in one of these sites.


Impact of climatic factors on temporal variability of sand fly abundance in Sri Lanka: Longitudinal study (2018 to 2020) with two-stage hierarchical analysis.
Phlebotomine sand flies serve as vectors for leishmaniasis, a major health concern, but a neglected tropical disease. The risk of vector activity is governed by climatic factors that vary in different geographic zones in the country. Thus, we aimed to quantify the effect of climatic variables on sand fly vector activity in ten sentinel sites across Sri Lanka. Mean rainfall, ambient temperature, relative humidity, wind speed, soil temperature, evaporation, sunshine hours, and vector densities were recorded at monthly intervals in each location from March 2018 to February 2020. The association between weather variables and sand fly densities was analysed using a two-staged hierarchical procedure; Distributed Lag Non-Linear (DLNM) modelling framework and the DLNM method implemented in the R package dlnm (version number 2.4.6). Moderate rainfall values up to 120 mm per month and increasing RH up to 82 at lag of 0 months along with increasing soil temperature and evaporation rate at lag of 2 months were associated with statistically significant increase in the sand fly activity. These associations were heterogeneous across study settings. Whereas increasing ambient and soil temperature, sunshine hours, evaporation rate appeared to reduce the sand fly activity homogeneously at lag of 0 month in all the study settings. The abundance of sand fly vectors varied in relation to selected climatic variables, either in real-time or with a time lag. This information can be utilized for predicting sand fly densities and for the development of effective strategies to prevent leishmaniasis transmission in specific settings.


Cutaneous and pleural involvement in a patient with multiple myeloma.
Multiple myeloma (MM) is a malignant proliferation of a single clone of plasma cells and an excess of monoclonal immunoglobulin production. It is rarely associated with cutaneous and pleural involvement. We report a new case of a 62-year-old woman with a history of a symptomatic MM. Three months after chemotherapy initiation, she presented with subcutaneous nodules. Ultrasound-guided needle biopsy confirmed the diagnosis of cutaneous plasmacytomas. She underwent local radiation therapy leading to complete regression of subcutaneous nodules. One month later, she developed dyspnoea. Thoracic CT scan showed pleural thickening associated with pleural effusion. Pleural biopsy confirmed the diagnosis of pleural plasmacytoma. Chemotherapy including vincristine, doxorubicin and dexamethasone was administered. Cutaneous involvement and pleural effusion accompanying MM are uncommon. They are associated with poor prognosis.


Gene expression profiling in the human alcoholic brain.
Long-term alcohol use causes widespread changes in gene expression in the human brain. Aberrant gene expression changes likely contribute to the progression from occasional alcohol use to alcohol use disorder (including alcohol dependence). Transcriptome studies have identified individual gene candidates that are linked to alcohol-dependence phenotypes. The use of bioinformatics techniques to examine expression datasets has provided novel systems-level approaches to transcriptome profiling in human postmortem brain. These analytical advances, along with recent developments in next-generation sequencing technology, have been instrumental in detecting both known and novel coding and non-coding RNAs, alternative splicing events, and cell-type specific changes that may contribute to alcohol-related pathologies. This review offers an integrated perspective on alcohol-responsive transcriptional changes in the human brain underlying the regulatory gene networks that contribute to alcohol dependence. This article is part of the Special Issue entitled "Alcoholism".


Neural network learning of optimal Kalman prediction and control.
Although there are many neural network (NN) algorithms for prediction and for control, and although methods for optimal estimation (including filtering and prediction) and for optimal control in linear systems were provided by Kalman in 1960 (with nonlinear extensions since then), there has been, to my knowledge, no NN algorithm that learns either Kalman prediction or Kalman control (apart from the special case of stationary control). Here we show how optimal Kalman prediction and control (KPC), as well as system identification, can be learned and executed by a recurrent neural network composed of linear-response nodes, using as input only a stream of noisy measurement data. The requirements of KPC appear to impose significant constraints on the allowed NN circuitry and signal flows. The NN architecture implied by these constraints bears certain resemblances to the local-circuit architecture of mammalian cerebral cortex. We discuss these resemblances, as well as caveats that limit our current ability to draw inferences for biological function. It has been suggested that the local cortical circuit (LCC) architecture may perform core functions (as yet unknown) that underlie sensory, motor, and other cortical processing. It is reasonable to conjecture that such functions may include prediction, the estimation or inference of missing or noisy sensory data, and the goal-driven generation of control signals. The resemblances found between the KPC NN architecture and that of the LCC are consistent with this conjecture.


High doses of antipsychotic polypharmacy are related to an increase in serum levels of pentosidine in patients with schizophrenia.
Carbonyl stress in patients with schizophrenia has been reported to be reflected by an increase in peripheral pentosidine levels. This cohort study tested whether the accumulation of pentosidine was related to the disease severity or the treatment (routine administration of high antipsychotic doses). We followed up our original investigation using a new group of 137 patients with acute schizophrenia and 45 healthy subjects, and then pooled the two cohorts to conduct the following analysis on a total of 274 patients. The associations of serum pentosidine and pyridoxal levels with duration of education, estimated duration of medication, the severity of symptoms, and daily doses of antipsychotics, antiparkinsonian drugs, and anxiolytics were evaluated by multiple linear regression analysis. The combined cohort of 274 patients exhibited abnormally high serum levels of pentosidine, were associated with a higher daily dose of antipsychotic drugs and a longer estimated duration of medication without statistical significance of diagnosis. This was also observed in the patients treated with antipsychotic polypharmacy, but the serum pentosidine levels of patients treated with first- or second-generation antipsychotic monotherapy showed no relationship with these two variables. High levels of serum pentosidine were associated with high daily doses of antipsychotic drugs and a longer estimated duration of medication in patients treated with antipsychotic polypharmacy.


Clinical review and treatment of select adverse effects of dopamine receptor agonists in Parkinson's disease.
Dopamine receptor agonists provide a viable alternative or adjunct to levodopa therapy in Parkinson's disease and are associated with fewer motor complications and dyskinesia. However, all available dopamine agonists may cause profound adverse effects in some patients. In many cases, these adverse effects amplify non-motor symptoms that people with Parkinson's disease may already be experiencing. Nausea from dopamine agonists generally lessens with time and may be responsive to both antiemetic therapy and complementary remedies, such as ginger, peppermint and chamomile. Unfortunately, compulsive behaviours, as well as peripheral oedema caused by dopamine agonists, are poorly responsive to pharmacological therapy and require a reduction or discontinuation of agonist therapy. Somnolence and associated sleep attacks generally require elimination of the agonist or the use of a stimulating agent. The necessity of treatment for hallucinations and psychosis associated with dopamine agonists must be thoroughly evaluated prior to initiating therapy. If a medication is initiated for hallucinations or psychosis, quetiapine or clozapine are agents of choice. Orthostatic hypotension, though not always symptomatic, responds well to nonpharmacological strategies and medications, including indometacin, midodrine and fludrocortisone. Care must be taken to educate patients with Parkinson's disease about the common adverse effects of dopamine agonists and what can be done to lessen them.


Quantifying the economic impact of a digital self-care behavioral health platform on Missouri Medicaid expenditures.
The primary objective of this study is to estimate the economic benefits relative to return on investment (ROI) of a state-wide initiative to integrate digital behavioral health (BH) self-care into the community BH system. The observational study reviewed claims data of 799 people who registered with the digital tool (myStrength) and 715 matched control study participants. The control group was formed via coarsened exact match with blocking variables, including presence on the claims file, volume of health care utilization, participation in a medical health home, BH diagnosis and volume of psychotherapy claims. The primary study analysis of cost differences for the BH self-care tool group versus the control group were calculated by cost setting and the ROI of the BH self-care tool was estimated. Cost settings assessed include inpatient, emergency services, general and psychiatric outpatient, and outpatient psychotherapy. An incremental annual difference in difference reduction of $382 per user was observed over the 11 month study period in the self-care tool group. Sensitivity analysis indicated an ROI of between 142% and 695%. Augmenting BH offerings to include digital BH self-care tools appears to generate positive ROI via reduced total cost of care.


Contrast Bolus Interference in a Multimodal CT Stroke Protocol.
Whether CTP is performed before or after CTA varies within multimodal CT stroke protocols. CTA after CTP might show venous filling, and CTP metrics might be disturbed by prior CTA. Therefore, we compared CTP metrics conducted before and after CTA in a large cohort of patients with stroke and analyzed interferences of the CTA bolus with the CTP measurement. We analyzed 1980 patients (368 patients with CTP performed before CTA [group A] versus 1612 patients with CTP performed after [group B]) in a retrospective study. Mean curves, histograms of CTP baseline Hounsfield units, CBF, CBV, time-to-maximum, hypoperfusion, and core volumes were calculated using the software VEOcore. CTA and CTP interferences were analyzed, and a detection and correction method was proposed. Mean CTP baseline values were significantly different in both groups (41 versus 45 HU within the groups A and B, respectively). However, perfusion metrics, hypoperfusion, and core volumes yielded no significant differences. In 49 patients, the descending flank of the CTA bolus interfered with the baseline of the CTP measurement, leading to erroneously low CBV values. These errors vanished when a correction method was applied. CTP can be reliably performed after CTA without a relevant net effect on perfusion metrics. However, when measuring CTP after CTA, either a short pause on the order of 30 seconds should be observed or an appropriate correction method should be applied. It may help to avoid excluding patients from mechanical thrombectomy by overestimating infarct cores.


Regional Homogeneity Abnormalities and Its Correlation With Impulsivity in Male Abstinent Methamphetamine Dependent Individuals.
Methamphetamine (MA) use affects the brain structure and function. However, no studies have investigated the relationship between changes in regional homogeneity (ReHo) and impulsivity in MA dependent individuals (MADs). The aim of this study was to investigate the changes of brain activity under resting state in MADs and their relationship to impulsivity using ReHo method. Functional magnetic resonance imaging (fMRI) was performed to collect data from 46 MADs and 44 healthy controls (HCs) under resting state. ReHo method was used to investigate the differences in average ReHo values between the two groups. The ReHo values abnormalities of the brain regions found in inter-group comparisons were extracted and correlated with impulsivity. Compared to the HCs, MADs showed significant increased ReHo values in the bilateral striatum, while the ReHo values of the bilateral precentral gyrus and the bilateral postcentral gyrus decreased significantly. The ReHo values of the left precentral gyrus were negatively correlated with the BIS-attention, BIS-motor, and BIS-nonplanning subscale scores, while the ReHo values of the postcentral gyrus were only negatively correlated with the BIS-motor subscale scores in MADs. The abnormal spontaneous brain activity in the resting state of MADs revealed in this study may further improve our understanding of the neuro-matrix of MADs impulse control dysfunction and may help us to explore the neuropathological mechanism of MADs related dysfunction and rehabilitation.


Blood function in the hydrothermal vent vestimentiferan tube worm.
Extracellular hemoglobin in the whole blood of Riftia pachyptila has a high oxygen affinity (P50 = 1.8 millimeters of mercury at 3 degrees C), a moderate decrease in oxygen affinity at higher temperatures (P50 = 2.7 millimeters of mercury at 14 degrees C), a small effect of carbon dioxide on oxygen affinity (Delta log P50/Delta pH =-0.12), and a high oxygen carrying capacity (up to 11 milliliters of oxygen per 100 milliliters of blood). These characteristics are compatible with the high oxygen demand of chemoautotrophic metabolism in the variable vent environment.


Comparison of different methods for nutrition assessment in patients with tumors.
Nutrition screening to identify patients at risk of malnutrition is vital for cancer patients because of the high prevalence of malnutrition in this population. The aim of the present study was to compare different methods of nutrition assessment in patients with tumors. From June 2013 to June 2014, we conducted an observational multicenter study to compare the assessment of nutritional status in patients with tumors by anthropometry, biochemical indicators, nutritional risk screening (NRS-2002) and patient-generated subjective global assessment (PG-SGA). Mann-Whitney test and Kruskal-Wallis H non-parametric test were used for intergroup comparisons. Spearmans rank correlation coefficients were calculated to evaluate the association between different methods of nutritional assessment. The κ statistic was used to evaluate the agreement between two assessment methods. A total of 927 oncology inpatients underwent full nutritional assessment and nutrition screening. The PG-SGA tool determined that 13.7% of patients were well-nourished (PG-SGA from 0-1) and the rest (86.3%) were malnourished. Among the malnourished patients, 57.8% were moderately malnourished (PG-SGA from 2-8) and 28.5% were severely malnourished (PG-SGA ≥9). According to NRS-2002, 30.7% of patients were at nutritional risk (NRS-2002 ≥3). There was a significant positive correlation between PG-SGA scores and NRS-2002 scores in both men and women. Compared to albumin, the PG-SGA had a sensitivity of 93.78% and specificity of 21.80%. In comparison, NRS-2002 had a low sensitivity of 43.13% and relatively higher specificity of 82.16%. In conclusion, the relationship between PG-SGA, NRS-2002 and nutritional status is statistically significant. Compared with NRS-2002, PG-SGA is a suitable screening tool for detecting the risk of malnutrition in patients with cancer.


Vertebral body reshaping after fractures: an important index of recovery in glucocorticoid-treated children.
In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome. Subjects were 79 children (mean age 7.4 years) who had VF evaluation on lateral spine radiographs at least one year after VF detection. VF were graded using the modified Genant semi-quantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4). Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region versus 70.7% in the lumbar region (p=0.004). Cox models showed that: (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping (hazard ratio [HR]=0.81; 95% confidence interval [CI]=0.71, 0.92; p=0.001); (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR=0.75; 95% CI=0.62, 0.90; p=0.002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR=0.35; 95% CI=0.21, 0.57; p<0.001). After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity.


Relationship between serologic markers of periodontal bacteria and metabolic syndrome and its components.
Periodontitis is a result of a complex biologic alteration of the periodontal microenvironment and a distributional shift of key periodontal pathogens. Metabolic syndrome (MetS), a complex cluster of cardiovascular risk factors, has been linked to periodontal diseases; however, the contribution of periodontal bacteria to systemic conditions remains unclear. The study population comprised 7,848 United States adults who participated in an interview, underwent a clinical oral-health examination, and had serum immunoglobulin G titers measured against 19 periodontal bacteria as part of the third National Health and Nutritional Examination Survey. The z-score antibody titers were clustered into four mutually exclusive groups and named after Socransky's classification of periodontal bacteria (Orange-Red, Red-Green, Yellow-Orange, and Orange-Blue). Survey logistic regression was used to investigate the independent associations between the cluster scores, and MetS and each component, including hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, central obesity, and elevated fasting glucose. The Orange-Red cluster score (that included Porphyromonas gingivalis and Prevotella spp.) was positively associated (odds ratio [OR] = 1.067, 95% confidence interval [CI] = 1.02 to 1.12) and the Orange-Blue cluster score (which included Actinomyces naeslundii and Eubacterium nodatum) was inversely associated (OR = 0.93, 95% CI = 0.88 to 0.97) with elevated fasting glucose (≥ 110 mg/dL) after adjustment for clusters and potential confounders. Neither MetS nor its other remaining MetS components were associated with a particular cluster score. The associations between specific antibody clusters (Orange-Red and Orange-Blue) against periodontal bacteria and elevated plasma glucose were in qualitatively opposite directions after multivariable adjustment in a large, adult population. The periodontal bacterial profile was not found to be associated with metabolic control other than a very moderate association with elevated plasma glucose.


Construction and Cloning of Reporter-Tagged Replicon cDNA for an In Vitro Replication Study of Murine Norovirus-1 (MNV-1).
A norovirus maintains its viability, infectivity and virulence by its ability to replicate. However, the biological mechanisms of the process remain to be explored. In this work, the NanoLuc™ Luciferase gene was used to develop a reporter-tagged replicon system to study norovirus replication. The NanoLuc™ Luciferase reporter protein was engineered to be expressed as a fusion protein for MNV-1 minor capsid protein, VP2. The foot-and-mouth disease virus 2A (FMDV2A) sequence was inserted between the 3'end of the reporter gene and the VP2 start sequence to allow co-translational 'cleavage' of fusion proteins during intracellular transcript expression. Amplification of the fusion gene was performed using a series of standard and overlapping polymerase chain reactions. The resulting amplicon was then cloned into three readily available backbones of MNV-1 cDNA clones. Restriction enzyme analysis indicated that the NanoLucTM Luciferase gene was successfully inserted into the parental MNV-1 cDNA clone. The insertion was further confirmed by using DNA sequencing. NanoLuc™ Luciferase-tagged MNV-1 cDNA clones were successfully engineered. Such clones can be exploited to develop robust experimental assays for in vitro assessments of viral RNA replication.


Semi-continuous anaerobic digestion of food waste using a hybrid anaerobic solid-liquid bioreactor.
A hybrid anaerobic solid-liquid (HASL) bioreactor was developed to enhance food waste conversion. The HASL bioreactor is a modified two-phase anaerobic digestion system with a solid waste reactor and a high-rate anaerobic wastewater reactor, which was a UASB reactor. In this study, the methanogenesis in the UASB reactor was investigated under a semi-continuous operation of the food waste digestion system. The HASL process, including 7 days of start-up and 23 days of semi-continuous operation followed by 6 days of batch operation, was commenced by loading 2.8 kg of shredded food waste. During the semi-continuous operation, 0.2 kg of the same waste was loaded daily. The leachate from acidification phase, i.e., solid waste reactor, remained acidic (pH 4.9-5.5) and high in total VFA (TVFA), 9,500-11,500 mg/L, and COD (8,000-11,800 mg/L) levels. In the methanogenesis phase, i.e., UASB reactor, effective TVFA and COD removals (88 +/- 5% and 85 +/- 7%, respectively) were obtained, while the methane content was 71%. At the end of operation, about 78% of VS added in the HASL bioreactor was removed, while TOC and total COD reductions were 78% and 79%, respectively. The results showed that the use of UASB reactor in the semi-continuous HASL system can enhance the methanogenesis process and increase the methane content in biogas production.


MEMO: an mHealth intervention to prevent the onset of depression in adolescents: a double-blind, randomised, placebo-controlled trial.
Depression often starts in adolescence making it an ideal time to intervene. We developed a universal cognitive behavioural therapy-based programme (MEMO CBT) to be delivered via multimedia mobile phone messages for teens. We conducted a prospective multicentre, randomised, placebo-controlled superiority trial in 15 high schools in Auckland, New Zealand, comparing MEMO CBT with a control programme [MEMO control] matched for intensity and type of message but with alternative content not targeting depression. The primary outcome was the change in score on the Children's Depression Rating Scale-Revised from baseline to 12 months. Secondary outcomes included the change in scores in the self-reported Reynold's Adolescent Depression Rating Scale-Second Edition, the Moods and Feelings Questionnaire, suicidal ideation using selected items from the Youth Risk Behaviour Survey, the Pediatric Quality of Life questionnaire, 12-month period prevalence of the diagnosis of depressive disorder using the Kiddie-Schedule for Affective Disorders and Schizophrenia, and students' ratings of their satisfaction with the programme. Eight hundred and fifty-five students (13-17 years old, mean 14.3 years) were randomly assigned to MEMO CBT (426) or to MEMO Control (429). Participants (68% female) had a mean CDRS-R at baseline of 21.5 (SD: 5). Overall 394 (93%) from the intervention group and 392 (91%) from the control group were followed up at 12 months. At the end of the intervention (approximately 9 weeks) the mean CDRS-R scores were 20.8 in the intervention group versus 20.4 in the control group, and at 12 months they were 22.4 versus 22.4 (p value for difference in change from baseline = 0.3). There was no obvious association between the amount of the intervention viewed by participants and outcomes. There was no evidence of benefit from the mobile phone CBT intervention compared with a control programme. Universal depression prevention remains a challenge.


Hepatitis B virus reactivation associated with antirheumatic therapy: Risk and prophylaxis recommendations.
Accompanying the increased use of biological and non-biological antirheumatic drugs, a greater number of cases of hepatitis B virus (HBV) reactivation have been reported in inactive hepatitis B surface antigen (HBsAg) carriers and also in HBsAg-negative patients who have resolved HBV infection. The prevalence of resolved infection varies in rheumatic disease patients, ranging from 7.3% to 66%. Through an electronic search of the PubMed database, we found that among 712 patients with resolved infection in 17 observational cohort studies, 12 experienced HBV reactivation (1.7%) during biological antirheumatic therapy. Reactivation rates were 2.4% for etanercept therapy, 0.6% for adalimumab, 0% for infliximab, 8.6% for tocilizumab, and 3.3% for rituximab. Regarding non-biological antirheumatic drugs, HBV reactivation was observed in 10 out of 327 patients with resolved infection from five cohort studies (3.2%). Most of these patients received steroids concomitantly. Outcomes were favorable in rheumatic disease patients. A number of recommendations have been established, but most of the supporting evidence was derived from the oncology and transplantation fields. Compared with patients in these fields, rheumatic disease patients continue treatment with multiple immunosuppressants for longer periods. Optimal frequency and duration of HBV-DNA monitoring and reliable markers for discontinuation of nucleoside analogues should be clarified for rheumatic disease patients with resolved HBV infection.


Modulation of the actomyosin interaction during fatigue of skeletal muscle.
Fatigue of skeletal muscle involves many systems beginning with the central nervous system and ending with the contractile machinery. This review concentrates on those factors that directly affect the actomyosin interaction: the build-up of metabolites; myosin phosphorylation; and oxidation of the myofibrillar proteins by free radicals. The decrease in [ATP] and increase in [ADP] appear to play little role in modulating function. The increase in phosphate inhibits tension. The decrease in pH, long thought to be a major factor, is now known to play a more minor role. Myosin phosphorylation potentiates the force achieved in a twitch, and a further role in inhibiting velocity is proposed. Protein oxidation can both potentiate and inhibit the actomyosin interaction. It is concluded that these factors, taken together, do not fully explain the inhibition of the actomyosin interaction observed in living fibers, and thus additional modulators of this interaction remain to be discovered.


The isolation and characterization of colorectal epithelial cell lines at different stages in malignant transformation from familial polyposis coli patients.
The genetic disease familial polyposis coli (hereditary adenomatosis of the colon and rectum) provides an excellent model for the study of tumour progression in the large bowel. We have isolated and characterized four epithelial cell lines from colorectal tumours from polyposis coli patients. These cell lines are grown on collagen-coated Petri dishes in the presence of mouse 3T3 feeder cells in medium containing 20% foetal bovine serum. Of these cell lines three were isolated from premalignant adenomas and one from an adenocarcinoma. All four lines have a characteristic cuboidal epithelial morphology, and their epithelial origin was confirmed by positive staining with a monoclonal antibody which reacts specifically with the keratin filaments of simple epithelia. The adenoma-derived lines display ultrastructural features characteristic of colonic epithelium including desmosomes, microvilli and mucin droplets. One of the adenoma-derived cell lines, designated PC/AA, has retained differentiated functions in culture, namely mucin production, after 21 in vitro passages. PC/AA has a karyotype of 46, XY with no detectable chromosome rearrangements. The adenoma-derived lines could be passaged from clumps of cells but not from single cells even in the presence of 3T3 feeder cells. The carcinoma-derived line, designated PC/JW, could however grow from single cells in the presence of a feeder layer. The one premalignant adenoma-derived line tested so far, PC/AA, did not produce tumours in athymic nude mice. In contrast, the carcinoma-derived line, PC/JW was tumorigenic in athymic nude mice. PC/JW produced moderately well-differentiated tumours which were histologically similar to the adenocarcinoma from which the cell line was isolated. PC/JW has a near-diploid chromosome number with an isochromosome (1q), an isochromosome (14q) and an (Xp; 17q) translocation. Unidentified marker chromosomes were present in a few cells. The features at present which distinguish the carcinoma-derived line from the adenoma-derived lines are tumorigenicity, growth from single cells and chromosomal abnormalities. The isolation and characterization of differentiating human epithelial cell lines at different stages in malignant transformation provide an opportunity to examine the cellular and molecular mechanisms controlling tumour progression in the large intestine, and to obtain an insight into the multistep process of human epithelial carcinogenesis.


The determination and application of (87) Sr/(86) Sr ratio in verifying geographical origin of wheat.
As 87 Sr/86 Sr ratio plays a significant role in authenticating the geographical origin of foodstuff, it is important to identify where the 87 Sr/86 Sr signature in food comes from, and the methods of 87 Sr/86 Sr ratio analysis in food and environmental samples. Wheat with three genotypes, soil and groundwater samples were collected from three regions of China during harvest time of 2014. The 87 Sr/86 Sr ratios in the samples were determined by thermal ionization mass spectrometer in order to investigate the possible source of 87 Sr/86 Sr in wheat, and the concentrations of Rb and Sr in wheat and soils were also detected by inductively coupled plasma mass spectrometry and combined with 87 Sr/86 Sr ratio in order to trace the geographical origin of wheat. The 87 Sr/86 Sr ratio, the contents Rb and Sr, and Rb/Sr ratio of wheat and soil samples showed significant differences among three regions. The 87 Sr/86 Sr ratios and the concentrations of Rb and Sr in soils were higher than those in corresponding wheat. The 87 Sr/86 Sr ratio in wheat was identical to that corresponding soil NH4 NO3 extracts (labile fraction of soil) and groundwater. Wheat uptake more Rb than Sr. 3D distribution of 87 Sr/86 Sr, Rb and Sr could identify wheat samples from different regions clearly. The 87 Sr/86 Sr ratio of wheat reflects the 87 Sr/86 Sr ratio of the associated environment including soil and groundwater. It is expected that the use the parameters of 87 Sr/86 Sr ratio, the contents of Rb and Sr will allow to trace geographical origin of wheat. Copyright © 2017 John Wiley & Sons, Ltd.


The Effect of the Family-Centered Empowerment Model (FCEM) on the Care Burden of the Parents of Children Diagnosed with Cancer.
Background: Families face multiple problems after their children are diagnosed with cancer. This study aims to determine the effect of the Family-Centered Empowerment Model (FCEM) on the care burden of the parents of children, diagnosed with cancer. Methods: This quasi-experimental study was conducted with 78 parents, having children with cancer. The FCEM was implemented in the intervention group in four stages, namely perceived a threat, self-efficacy, educational participation, and evaluation during four sessions of 20-40 minutes. The control group only received the usual care. The burden of care of the control and intervention groups were measured one month after filling out the initial questionnaire, and one month after the end of the intervention, respectively. Results: The two groups were similar in terms of demographic variables and level of burden of care. However, a statistically significant difference was observed between the two groups, in terms of the level of burden (p<0.001). Conclusion: The results of this study showed that the empowerment of parents of children with cancer has an impact on reducing their care burden, and using this empowerment model is recommended to the treatment team, especially nurses.


[Diagnosis of stromal hyperplasia of the endometrium (author's transl)].
In three cases of endometrial stromal hyperplasia, nuclear DNA-content was determined by Feulgen microspectrophotometry. In two cases DNA-content exhibited the diploid pattern. In the third case values ranged from diploid to tetraploid, also showing an additional peak for hypotetraploid values. The two cases with diploid DNA patterns are considered to have less malignant potential. This corresponds well to clinical follow-up examinations performed three and nine years later, where no progression to malignant growth was established. The pronounced proliferative tendency observed in the third case would make progression to malignancy appear highly probable.


Clathrin-Independent Killing of Intracellular Mycobacteria and Biofilm Disruptions Using Synthetic Antimicrobial Polymers.
Current membrane targeting antimicrobials fail to target mycobacteria due to their hydrophobic membrane structure, ability to form drug-resistant biofilms, and their natural intracellular habitat within the confines of macrophages. In this work, we describe engineering of synthetic antimicrobial polymers (SAMPs) derived from biocompatible polyamides that can target drug-sensitive and drug-resistant mycobacteria with high selectivity. Structure-activity relationship studies revealed that reduced hydrophobicity of cationic pendants induces enhanced and selective permeabilization of mycobacterial membranes. The least hydrophobic SAMP (TAC1) was found to be the most active with maximum specificity toward mycobacteria over E. coli, S. aureus, and mammalian cells. Membrane perturbation studies, scanning electron microscopy, and colony PCR confirmed the ability of TAC1 to induce membrane lysis and to bind to the genomic material of mycobacteria, thereby inducing mycobacterial cell death. TAC1 was most effective in perfusing and disrupting the mycobacterial biofilms and was also able to kill the intracellular mycobacteria effectively without inducing any toxicity to mammalian cells. Cellular uptake studies revealed clathrin independent uptake of TAC1, thereby allowing it to escape hydrolytic lysosomal degradation and effectively kill the intracellular bacteria. Therefore, this manuscript presents the design and selective antimycobacterial nature of polyamide polymers with charged hydrophobic pendants that have ability to disrupt the biofilms and kill intracellular mycobacteria.


Alcohol neurolysis of genicular nerve for chronic knee pain.
Radiofrequency neurolysis (RFN) of the genicular nerves has recently become accepted as an effective technique to alleviate knee pain particularly in patients with knee osteoarthritis (OA) or postoperative pain. However, genicular nerve RFN can produce high procedure and equipment costs, longer procedural times, procedure-related pain, and failure rate of over 25%. We are presenting two cases of alcohol neurolysis of the genicular nerve using fluoroscopy and ultrasonography in patients with knee OA or persistent postsurgical pain of the knee. Alcohol neurolysis of the genicular nerve with dual imaging modality can be a cheap, safe and effective method in patients with chronic knee pain.


Splenic Artery Pseudoaneurysm Masquerading as a Pancreatic Cyst-A Diagnostic Challenge.
Splenic artery pseudoaneurysm is a rare entity. Clinical diagnosis is challenging because presentation is often varied. It can range from an incidental finding to hemodynamic collapse from sudden rupture and bleeding. The most common cause of this condition is pancreatitis. We report an unusual case of a young man not known to have pancreatitis who presented with hematemesis with normal esophagogastroduodenoscopy. Imaging modalities did not lead to a definitive diagnosis, and he underwent emergency laparotomy with surgical ligation of splenic artery pseudoaneurysm for hemodynamic instability, without a definitive preoperative diagnosis.


Mycobacterium fortuitum infection in continuous ambulatory peritoneal dialysis.
Mycobacterium fortuitum group species is an atypical rapidly growing nontuberculous mycobacterium. It has been increasingly recognized as a potential pathogen mostly encountered in skin and soft tissue infections. Rarely, however, it has been associated with catheter-related infections, either central venous lines or peritoneal dialysis catheters. In this report we describe 2 patients maintained on continuous ambulatory peritoneal dialysis who developed Mycobacterium fortuitum peritonitis and a catheter tunnel abscess, respectively. Molecular biology identification of the isolates was performed in both cases. The literature is reviewed regarding all similar cases.


Transforming growth factor-beta1 reduces megalin- and cubilin-mediated endocytosis of albumin in proximal-tubule-derived opossum kidney cells.
Transforming growth factor (TGF)-beta1 is a member of a superfamily of multifunctional cytokines involved in several pathological processes of the kidney, including fibrogenesis, apoptosis and epithelial-mesenchymal transition. These events lead to tubulointerstitial fibrosis and glomerulosclerosis. Less is known about TGF-beta1-induced alterations of cell function. An important function of proximal tubular cells is reabsorption of filtered proteins, including albumin, via megalin-cubilin-dependent receptor-mediated endocytosis. In this study we used a well established cell culture model (proximal-tubule-derived opossum kidney (OK) cells) in order to test the hypothesis that TGF-beta1 reduces megalin-cubilin-mediated endocytosis. Previously we have shown that albumin endocytosis in OK cells is mediated by megalin/cubulin. TGF-beta1 led to a time- and dose-dependent downregulation of megalin-cubilin-mediated endocytosis without affecting two other transport systems tested. Binding, internalization and intracellular trafficking of the ligand albumin were affected. Decreased binding resulted from reduced cubilin and megalin expression in the 200 000 g membrane fraction. The underlying mechanism of TGF-beta1 action does not involve mitogen-activated protein kinases, protein kinase C or A, or reactive oxygen species. In contrast, TGF-beta1-induced downregulation of megalin-cubilin-mediated endocytosis was sensitive to inhibition of translation and transcription and was preceded by Smad2 and 3 phosphorylation. Dominant negative Smad2/3 constructs prevented the effect of TGF-beta1. In conclusion our data indicate that enhanced levels of TGF-beta1 occurring in various nephropathies can lead to downregulation of megalin-cubilin-dependent endocytosis. Probably, TGF-beta1 leads to Smad2- and Smad3-dependent expression of negative regulators of receptor-mediated endocytosis.


The sphincteric and sensory components of preserved continence after ileoanal reservoir.
Sphincteric and sensory components of anal continence were investigated before and after restorative proctocolectomy and three loop ileal reservoir. Bowel habit, appearance of small intestinal mucosa, resting tone, squeeze pressure, anal canal length, pouch capacity and ileal sensation were investigated in 50 patients. The physiologic, endoscopic and histologic patterns were related to the occurrence of functional disturbances. The pressures in the anal canal as measured by manometry were found to be within the range of normality. The length of the sphincter was 3.4 +/- 0.6 centimeters; the maximal capacity of the reservoir was 450 +/- 204 milliliters of air. An ileorectoanal inhibitory reflex was recorded postoperatively in 52 per cent of the patients and normal postoperative continence was observed in 86 per cent of the patients, with no instances of gross incontinence. According to the results of the present study, the anatomic rearrangement that occurs after this surgical procedure preserved a satisfactory continence due to the integrity of the anal sphincters; minor leakage rarely occurred and was mainly related to a long inflamed distal portion of the ileum requiring self catheterization after operations for colitis. The best results were obtained in patients with polyposis who neither had staged procedures nor preoperative steroids.


[Comparison of the effectiveness of prostaglandin E2 gel in evening and morning induction of labor].
100 women participated in an open randomised study. 50 of them received 0.5 mg PGE2 in 2.5 ml Triacetin gel (Prepidil) intracervically in the morning (6.00 a.m.) and 50 at night (10.00 p.m.). The success rate was 74% (37 of 50) in the treatment group of the night compared with 52 (26 of 50) in the group of morning labor induction. A second dose after 8 hours was necessary in 26% (13 of 50) in the night group and in 48% (24 of 50) of the morning labor induction. Labor induction failed completely in 32% of the morning and in 12% of the night group. The induction time for contractions was 2 hours shorter after night labor induction, in primiparae the duration of first stage was 2 hours shorter but in multiparae there was no difference between the groups. There was also no difference in intrapartum and postpartum complications between the groups. In conclusion the induction of labor with intracervical PGE2 at night seems to be more effective without increasing the rate of complications.


[Post marketing surveillance study with an analgesic (transdermal buprenorphine patch) in patients with moderate to severe chronic pain].
To obtain information on the efficacy, tolerability and safetyofa transdermal buprenorphine patch (Transtec PRO) in patients with moderate to severe chronic pain. In addition it should be evaluated to what extent the two fixed patch change days per weekare simplifyingthe therapy. In this prospective multi-center post marketing surveillance study patients with chronic cancer and non-cancer pain were treated with transdermal buprenorphine for up to eight weeks. The evaluation included pain intensity, the dosage of the applied analgesics and additional therapies, the renal function (by serum creatinine) and adverse events. 3654 patients were treated for a mean of 50.4 days. Using the NRS-11 the mean pain intensity decreased from 6.3 at the time when patients were switched to the transdermal buprenorphine patch to 2.6 at the last treatment evaluation. The matrix patch was safe and well tolerated also in patients with advanced renal insufficiency. Adverse events were reported in 6.7% of the patients. 89.3% of the physicians quoted to prefer transdermal buprenorphine with the two fixed patch change days per week compared to the pre-treatment. The buprenorphine-containing matrix patch was effective and well tolerated in patients with moderate to severe chronic cancer and noncancer pain. From the physicians view the two fixed patch change days per week facilitate the guidance of therapy. In patients with advanced renal insufficiency a dose adjustment is not necessary.


Systematic review on the evaluation criteria of orphan medicines in Central and Eastern European countries.
In case of orphan drugs applicability of the standard health technology assessment (HTA) process is limited due to scarcity of good clinical and health economic evidence. Financing these premium priced drugs is more controversial in the Central and Eastern European (CEE) region where the public funding resources are more restricted, and health economic justification should be an even more important aspect of policy decisions than in higher income European countries. To explore and summarize the recent scientific evidence on value drivers related to the health technology assessment of ODs with a special focus on the perspective of third party payers in CEE countries. The review aims to list all potentially relevant value drivers in the reimbursement process of orphan drugs. A systematic literature review was performed; PubMed and Scopus databases were systematically searched for relevant publications until April 2015. Extracted data were summarized along key HTA elements. From the 2664 identified publications, 87 contained relevant information on the evaluation criteria of orphan drugs, but only 5 had direct information from the CEE region. The presentation of good clinical evidence seems to play a key role especially since this should be the basis of cost-effectiveness analyses, which have more importance in resource-constrained economies. Due to external price referencing of pharmaceuticals, the relative budget impact of orphan drugs is expected to be higher in CEE than in Western European (WE) countries unless accessibility of patients remains more limited in poorer European regions. Equity principles based on disease prevalence and non-availability of alternative treatment options may increase the price premium, however, societies must have some control on prices and a rationale based on multiple criteria in reimbursement decisions. The evaluation of orphan medicines should include multiple criteria to appropriately measure the clinical added value of orphan drugs. The search found only a small number of studies coming from CEE, therefore European policies on orphan drugs may be based largely on experiences in WE countries. More research should be done in the future in CEE because financing high-priced orphan drugs involves a greater burden for these countries.


Illicit drug initiation among institutionalized drug users in China.
To examine the circumstances and correlates associated with initiation of illicit drug use among institutionalized drug users in China. Cross-sectional, retrospective study. Six compulsory drug cessation programs in Yunnan Province and Gunagxi Zhuang Autonomous Region of China. A gender-stratified random sample of 833 drug users (88% males and 12% females) enrolled in compulsory drug cessation programs in November 1996. Circumstances of illicit drug initiation (age, type of drugs, routes of drug administration, social setting, source of drugs, reasons for drug use), the risk behaviors and risk perceptions prior to drug initiation. The majority of participants initiated drug use with heroin (90%). Initial drugs were frequently administered through sniffing/snorting (55%) and smoking cigarettes mixed with a drug (38%). First drug use occurred most commonly at a friend's home (65%) and in the company of other drug users (83%). Drugs were generally provided free for first-time use by other drug users (72%). Reasons for first drug use included experimentation (90%), being lured into drugs by other people (44%) and relaxation (42%). Most drug users had a history of regular cigarette smoking (89%), alcohol consumption (49%) and deviant behaviors (51%) prior to their drug initiation. The majority perceived that their friends (90%) and neighbors (88%) used illicit drugs. The findings are similar to studies in western countries with respect to the pattern and correlates of illicit drug initiation, and underscore the need for drug prevention efforts in China.


Reinfection of dogs with fish-borne zoonotic trematodes in northern Vietnam following a single treatment with praziquantel.
Fish-borne zoonotic trematodes (FZT) infections including liver- and minute intestinal flukes are common in Southeast Asia in both humans and domestic animals eating raw fish and since 2010, the liver flukes are recognised as neglected tropical diseases by WHO. Mass drug treatment with praziquantel is advised for humans, but no recommendations for control of the FZT in the reservoir hosts exist. A study was conducted to assess the ability of praziquantel treatment for control of FZT in farm dogs in an endemic area in Northern Vietnam. Initially, 101 dogs from 73 households were examined for small trematode eggs in their faeces. Forty seven copro-positive dogs were included in the study. Thirty eight dogs received treatment with a single dose of 40 mg/kg of praziquantel. A group of nine dogs were left untreated. Coprological examination for small trematode eggs was performed on day 0, 3, 10, 30, 60, 90 and 120 post treatment. Farmers were questioned about dog keeping practises. All dogs were copro-negative for small trematode eggs on both day 3 and 10 post treatment. From day 30 onwards previously negative dogs became positive again. The reinfection rates were 26.3% (day 30), 45.5% (day 60), 53.1% (day 90), 61.3% (day 120).The nine untreated dogs remained positive throughout the study period. There was no difference in the intensity of infection at day 0 and 120 neither in the treated or untreated group. Dogs had easy access to raw fish and did not receive treatment against flukes by their owner. More than 50% of the dogs were reinfected 3 months post treatment. We do not recommend controlling FZT infections in dogs by anthelmintic treatment alone since reinfection occurs fast under the existing farm management systems.


HGV&TB: a comprehensive online resource on human genes and genetic variants associated with tuberculosis.
Tuberculosis (TB) is an infectious disease caused by fastidious pathogen Mycobacterium tuberculosis. TB has emerged as one of the major causes of mortality in the developing world. Role of host genetic factors that modulate disease susceptibility have not been studied widely. Recent studies have reported few genetic loci that provide impetus to this area of research. The availability of tools has enabled genome-wide scans for disease susceptibility loci associated with infectious diseases. Till now, information on human genetic variations and their associated genes that modulate TB susceptibility have not been systematically compiled. In this work, we have created a resource: HGV&TB, which hosts genetic variations reported to be associated with TB susceptibility in humans. It currently houses information on 307 variations in 98 genes. In total, 101 of these variations are exonic, whereas 78 fall in intronic regions. We also analysed the pathogenicity of the genetic variations, their phenotypic consequences and ethnic origin. Using various computational analyses, 30 variations of the 101 exonic variations were predicted to be pathogenic. The resource is freely available at http://genome.igib.res.in/hgvtb/index.html. Using integrative analysis, we have shown that the disease associated variants are selectively enriched in the immune signalling pathways which are crucial in the pathophysiology of TB. Database URL: http://genome.igib.res.in/hgvtb/index.html


Morphodynamics of non-canonical autophagic structures in Neurospora crassa.
Autophagy is a major pathway for unspooling cytoplasmic constituents and recycling them. Here, we investigate autophagy in Neurospora crassa, a close ascomycete relative to the model yeast Saccharomyces cerevisiae. High-pressure-freeze and freeze-substitution techniques proved keys to preservation of the surprising autophagic structures observed in Neurospora by transmission electron microscopy and electron tomography. Depriving Neurospora of carbon triggers two parallel processes at the plasma membrane: formation of vacuoles, initially along the plasma membrane but stuffing 70%-80% of cytoplasmic volume after several hours. The vacuoles contain material left over from digested proteins, disrupted ribosomes or glycogen clumps, plus other discrete organelle-like objects. Also, they accumulate the canonical autophagy marker Atg8, appear to be lytic from the start, and probably grow from lysosomes. Formation of diverse phagophores and autophagosomes, multi-membrane organelles manufactured de novo by the plasma membrane-a feature so far unique to Neurospora. These autophagic structures can be observed attached either to the cell membrane, to the cell wall, or free in the cytoplasm, viz. as mature organelles after detachment from the cell membrane. Although phagophores are clearly observed in carbon-replete cells, their production increases with carbon starvation-and these, too, often appear lytic. ATG1, the canonical initiator of phagophore formation in yeast, is not required for the formation of phagophores in Neurospora. This work provides clear structural and functional evidence that Neurospora's autophagic organelles differ from those observed by others in yeast.IMPORTANCENeurospora is a quintessential tip-growing organism, which is well known for packaging and longitudinal transport of tip-building blocks. Thus far, however, little attention has been paid to the co-essential process of reclamation, that is-taking apart of upstream, older structural elements, otherwise known as "autophagy". We are not yet prepared to set out the chemistry of that elaborate process, but its morphological start alone is worthy of attention. Carbon starvation triggers significant autophagic changes, beginning with prolific vacuolation along the plasma membrane, and eventual filling of 70% (or more) of cytoplasmic volume. Additionally, the Neurospora plasma membrane elaborates a variety of phagophores which themselves often look lytic. These have either dual enclosing membranes, like the familiar autophagosomes, can be doubled and have four wrapping membranes, or can be compounded with multiple membrane layers. These reclamation processes must be accommodated by the mechanism of tip growth.


Control of insect vectors and plant viruses in protected crops by novel pyrethroid-treated nets.
Long-lasting insecticide-treated nets (LLITNs) constitute a novel alternative that combines physical and chemical tactics to prevent insect access and the spread of insect-transmitted plant viruses in protected enclosures. This approach is based on a slow-release insecticide-treated net with large hole sizes that allow improved ventilation of greenhouses. The efficacy of a wide range of LLITNs was tested under laboratory conditions against Myzus persicae, Aphis gossypii and Bemisia tabaci. Two nets were selected for field tests under a high insect infestation pressure in the presence of plants infected with Cucumber mosaic virus and Cucurbit aphid-borne yellows virus. The efficacy of Aphidius colemani, a parasitoid commonly used for biological control of aphids, was studied in parallel field experiments. LLITNs produced high mortality of aphids, although their efficacy decreased over time with sun exposure. Certain nets excluded whiteflies under laboratory conditions; however, they failed in the field. Nets effectively blocked the invasion of aphids and reduced the incidence of viruses in the field. The parasitoid A. colemani was compatible with LLITNs. LLITNs of appropriate mesh size can become a very valuable tool in combination with biocontrol agents for additional protection against insect vectors of plant viruses under IPM programmes.


Bioluminescence imaging on-chip platforms for non-invasive high-content bioimaging.
Incorporating non-invasive biosensing features in organ-on-chip models is of paramount importance for a wider implementation of these advanced in vitro microfluidic platforms. Optical biosensors, based on Bioluminescence Imaging (BLI), enable continuous, non-invasive, and in-situ imaging of cells, tissues or miniaturized organs without the drawbacks of conventional fluorescence imaging. Here, we report the first-of-its-kind integration and optimization of BLI in microfluidic chips, for non-invasive imaging of multiple biological readouts. The cell line HEK293T-GFP was engineered to express NanoLuc® luciferase under the control of a constitutive promoter and were cultured on-chip in 3D, in standard ECM-like hydrogels, to assess optimal cell detection conditions. Using real-time in-vitro dual-color microscopy, Bioluminescence (BL) and fluorescence (FL) were detectable using distinct imaging setups. Detection of the bioluminescent signals were observed at single cell resolution on-chip 20 min post-addition of Furimazine substrate and under perfusion. All hydrogels enabled BLI with higher signal-to-noise ratios as compared to fluorescence. For instance, agarose gels showed a ∼5-fold greater BL signal over background after injection of the substrate as compared to the FL signal. The use of BLI with microfluidic chip technologies opens up the potential for simultaneous in situ detection with continuous monitoring of multicolor cell reporters. Moreover, this can be achieved in a non-invasive manner. BL has great promise as a highly desirable biosensor for studying organ-on-chip platforms.


In Situ Growth of Nano-MoS2 on Graphite Substrates as Catalysts for Hydrogen Evolution Reaction.
In order to synthesize a high-efficiency catalytic electrode for hydrogen evolution reactions, nano-MoS2 was deposited in situ on the surface of graphite substrates via a one-step hydrothermal method. The effects of the reactant concentration on the microstructure and the electrocatalytic characteristics of the nano-MoS2 catalyst layers were investigated in detail. The study results showed that nano-MoS2 sheets with a thickness of about 10 nm were successfully deposited on the surface of the graphite substrates. The reactant concentration had an important effect on uniform distribution of the catalyst layers. A higher or lower reactant concentration was disadvantageous for the electrochemical performance of the nano-MoS2 catalyst layers. The prepared electrode had the best electrocatalytic activity when the thiourea concentration was 0.10 mol·L-1. The minimum hydrogen evolution reaction overpotential was 196 mV (j = 10 mV·cm-2) and the corresponding Tafel slope was calculated to be 54.1 mV·dec-1. Moreover, the prepared electrode had an excellent cycling stability, and the microstructure and the electrocatalytic properties of the electrode had almost no change after 2000 cycles. The results of the present study are helpful for developing low-cost and efficient electrode material for hydrogen evolution reactions.


MMPI adolescent norms: patterns and trends across 4 decades.
This article examines central issues involving the accuracy of Minnesota Multiphasic Personality Inventory (MMPI) adolescent norms through examination of findings from eight investigations (n = 17,286), reporting MMPI mean values for samples of normal adolescents conducted between 1949 and 1964, and four studies (n = 1,758), based on adolescent samples collected since 1975. Issues related to sex and racial differences in adolescent samples are also examined. In addition, MMPI data from 1,315 normal adolescents, collected at the Mayo Foundation, and from 217 normal adolescents, collected in Norfolk, Virginia, are evaluated in relation to adult normative values on the Harris-Lingoes (Harris & Lingoes, 1955) content subscales to identify unique characteristics of adolescents' response patterns. Results support the adequacy of the adolescent norms, developed by Marks, Seeman, and Haller (1974), for evaluation of samples of normal adolescents collected between 1947 and 1965. MMPI patterns, produced by contemporary samples of adolescents collected since 1975, are elevated above the Marks et al. norms on most clinical scales. This latter finding indicated the need for the development of new adolescent norms that more precisely reflect current adolescent response frequencies and patterns. Finally, results from Harris-Lingoes subscales are reviewed to highlight unique aspects of adolescent developmental experience and to underscore the necessity of development of age appropriate adolescent norms for MMPI special scales.


Halide-propene complexes: validated DSD-PBEP86-D3BJ calculations and photoelectron spectroscopy.
Anion photoelectron spectroscopy has been used to determine the electron binding energies of the X-⋯C3H6 (X = Cl, Br, I) complexes. To complement the experimental spectra the DSD-PBEP86-D3BJ functional has been employed, following comparison with previously calculated halide/halogen-molecule van der Waals complexes. To validate the functional, comparison between the complex geometries and vertical detachment energies with both experimental and CCSD(T)/CBS data for a suite of halide-molecule complexes is also made. PES spectra determine the electron binding energies as 3.89 eV and 4.00 eV, 3.59 eV and 4.01 eV, and 3.26 eV and 4.20 eV for transitions to perturbed 2P states of the chlorine, bromine and iodine complexes respectively. Two contributing structures resulting in the photoelectron spectrum are those where the halide is coordinated by two hydrogens, each from a terminal carbon in C3H6, and when bifurcating the CC bond. These complexes are distinct from the corresponding halide-ethene complexes and represent potential entry pathways to haloakyl radical formation in atmospheric and extraterrestrial environments.


An Outlook on the European and Italian Rules to Guarantee Magistral Formulas.
Pharmaceutical compounded medicinal preparations are aimed to fulfill the special needs of a subpopulation of patients for whom a medicinal product is not commercially available. Nowadays, this activity remains an important component of pharmacy practice and an integral part of the modern healthcare system. In 2011, the Committee of Ministers of the Council of Europe adopted a resolution to harmonize quality assurance and safety standards for medicinal products prepared in pharmacies for the special needs of patients in European countries. This article discusses the actual rules and technical norms that regulate the compounding activity in Italy in the light of the new European laws.


Photoinhibition in marine picocyanobacteria.
Marine Synechococcus and Prochlorococcus cyanobacteria have different antenna compositions although they are genetically near to each other, and different strains thrive in very different illumination conditions. We measured growth and photoinhibition of PSII in two low-light and one high-light Prochlorococcus strains and in one Synechococcus strain. All strains were found to be able to shortly utilize moderate or even high light, but the low-light strains bleached rapidly in moderate light. Measurements of photoinhibition in the presence of the antibiotic lincomycin showed that a low-light Prochlorococcus strain was more sensitive than a high-light strain and both were more sensitive than the marine Synechococcus. The action spectrum of photoinhibition showed an increase from blue to ultraviolet wavelengths in all strains, suggesting contribution of manganese absorption to photoinhibition, but blue light caused less photoinhibition in marine cyanobacteria than expected on the basis of earlier results from plants and cyanobacteria. The visible-light part of the action spectrum resembled the absorption spectrum of the organism, suggesting that photosynthetic antenna pigments, especially divinyl chlorophylls, have a more important role as photoreceptors of visible-light photoinhibition in marine cyanobacteria than in other photoautotrophs.


Chemical interrogation of mismatches in DNA-DNA and DNA-RNA duplexes under nonstringent conditions by selective 2'-amine acylation.
2'-Amine-substituted nucleotides in hybridized duplexes can be chemically tagged in an acylation reaction that is faster for mismatched or flexible nucleotides than for residues constrained by base pairing. Here we explore mismatch and hybridization detection using probe oligodeoxynucleotides containing single 2'-aminocytidine or -uridine nucleotides annealed to DNA or RNA targets under nonstringent conditions, below T(m). Consistent with a mechanism in which 2'-amine acylation is gated by local nucleotide flexibility, we find that efficient acylation is correlated with formation of weaker or fewer hydrogen bonds in base pair mismatches. Using 2'-aminocytidine-containing probes annealed to both DNA and RNA targets, mismatches are reliably detected as rapid selective acylation of the 2'-amine group in two sequence contexts. For probe oligonucleotides containing 2'-aminouridine residues, good discrimination between U-A base pairs and U-G mismatches could be obtained for DNA-DNA but not for DNA-RNA duplexes upon the introduction of a single 2'-O-Me group 5' to the 2'-amino nucleotide. The 2'-O-Me group introduces a structural perturbation, presumably to a more A-form-like structure, that exaggerates local flexibility at mismatches in DNA strands. Thus, 2'-amine acylation can be used to interrogate all possible mismatches in DNA-DNA duplexes and mismatches involving 2'-amine-substituted cytidine nucleotides in DNA-RNA heteroduplexes. Applications of this chemistry include detecting and chemically proofreading single nucleotide polymorphisms in both DNA and RNA targets and quantifying absolute amounts of RNA.


Lattice Boltzmann method for the compressible Euler equations.
The lattice Boltzmann model for the compressible Euler equations is proposed together with its rigorous theoretical background. The proposed model has completely overcome the defects of the previous model that the specific-heat ratio cannot be chosen freely. The macroscopic variables obtained from the solution are shown to satisfy, in the limit of the small Knudsen number, the compressible Euler equations if the variation of the solution is moderate. This is the case where no shock waves or contact discontinuities appear. In contrast, when the solution makes steep variation at several localized regions due to the appearance of shock waves and contact discontinuities, the corresponding macroscopic variables satisfy the weak form of the Euler equations. Their derivation is carried out rigorously by taking into account the scale of variation of the solution correctly. This is the first study that has laid the theoretical foundation of the lattice Boltzmann model for the simulation of flows with shock waves and contact discontinuities. Numerical examples and the error estimates are also given, which are consistent with the above theoretical arguments.


[Case of oral lichen planus due to dental metal allergy].
This clinical report describes the treatment of a patient who experienced a hypersensitivity reaction associated with prosthetic restorations fabricated with a silver-palladium-copper-gold alloy. Patch testing revealed an allergy to the palladium substrate. Allergic symptoms disappeared from the patient's mucous membrane after all the prosthetic restorations in the patient were replaced with those fabricated using some alternative alloys. The case presented indicates that the release of palladium from prosthesis fabricated with dental metal alloys is able to induce hypersensitivity reactions resulting in soft-tissue changes in the buccal mucosa. Dental procedures as a multidisciplinary approach to the care taking of patient are presented.


[Incorporation of H3 uridine in chick embryo skin cultured in media containing histones].
In this paper the authors have carried out further research on the differentiation of six-day limb skin from chick embryos cultured in vitro in mediam containing histones. When 3H-uridine is added to this modified medium, a decrease of 3H-uridine uptake and incorporation is observed. The authors conclude that in their system the histones not only interfere with the regulation of genetic transcription by inhibiting DNA-dependent RNA synthesis, but they also change cellular permeability.


Bilayer ambipolar organic thin-film transistors and inverters prepared by the contact-film-transfer method.
Ambipolar organic thin-film transistors with a bilayer structure of poly(3-hexylthiophene) and [6,6]phenyl C(61) butyric acid methyl ester were fabricated using a simple solution-based, contact-film-transfer method. The transistors exhibited balanced electron and hole mobilities of 2.1 x 10(-2) and 1.1 x 10(-2) cm(2) V(-1) s(-1), respectively. Complementary inverters based on two identical ambipolar transistors showed good performance with a gain of 14.


Prenatal detection and outcome of congenital diaphragmatic hernia: a French registry-based study.
To describe the true incidence, prenatal detection rate and fetal outcome of congenital diaphragmatic hernia (CDH) in a systematically registered population over an 18-year period and to determine any change in trends over time. This was a retrospective study of all cases of CDH registered in the Central-Eastern France Birth Defects Registry from 1986 to 2003. All fetuses and infants up to 1 year of age diagnosed with CDH were registered, including miscarriages later than 22 weeks of gestation, stillbirths and terminations of pregnancy (TOP). Routine prenatal screening consisted of three ultrasound examinations and there was no upper limit of gestational age for TOP. Five hundred and one cases of CDH were identified from a total of 1 835 022 live births (2.7 cases per 10 000 live births). The overall prenatal detection rate was 54%. There was a significant increase over time in the detection rate mainly for associated CDH and left-sided CDH (P < 0.0001), and in the proportion of neonates delivered in tertiary centers (P < 0.0001). The overall survival rate at discharge was 47% and this increased significantly over time for isolated CDH (P = 0.04), whereas it was lower and remained stable for associated CDH (P = 0.64). The TOP rate for isolated CDH did not vary significantly in contrast to that for associated CDH cases in which the TOP rate increased over time, progressively replacing the neonatal death rate (P = 0.01). Over an 18-year period, this large population-based study demonstrated increasing prenatal detection rates for associated CDH and left-sided CDH and confirmed an increasing survival rate mainly for isolated CDH.


Computer-assisted navigation increases precision of component placement in total knee arthroplasty.
In our clinical study, 200 total knee arthroplasties were evaluated to compare the use of the OrthoPilot system with conventional mechanical instrumentation. Long-term outcome of total knee replacement depends mainly on the accuracy of implant positioning and restoration of the mechanical leg axis. Our experience was that navigation could achieve a greater degree of accuracy concerning the aforementioned aspects. Among 513 primary-inserted total knee replacements, 100 navigated knees were compared with 100 conventionally implanted knees after matching the two groups of patients by gender, body mass index, age, preoperative deformities, radiographic findings, and operating time. Three weeks after surgery, the radiographic results were significantly better in the computer-assisted group compared with the results in the conventional group when we assessed component positioning in four axes. Only the sagittal tibial component angle was not significantly different. Total knee arthroplasty using the OrthoPilot system led to increased precision of tibial and femoral component positioning in comparison with hand-guided replacement surgery. An additional 10 minutes of operating time was acceptable. Navigation-specific complications were not seen, and the number of outliers decreased. Because computer navigation in orthopaedics is a new technology, data regarding long-term outcomes are not available. Diagnostic study, Level II-1 (retrospective study). See the Guidelines for Authors for a complete description of levels of evidence.


Mapping the genes for susceptibility and response to Leishmania tropica in mouse.
L. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the recombinant congenic strain CcS-16 carrying 12.5% genes from the resistant parental strain STS/A and 87.5% genes from the susceptible strain BALB/c is more susceptible to L. tropica than BALB/c. We used these strains to map and functionally characterize the gene-loci regulating the immune responses and pathology. We analyzed genetics of response to L. tropica in infected F2 hybrids between BALB/c×CcS-16. CcS-16 strain carries STS-derived segments on nine chromosomes. We genotyped these segments in the F2 hybrid mice and tested their linkage with pathological changes and systemic immune responses. We mapped 8 Ltr (Leishmania tropica response) loci. Four loci (Ltr2, Ltr3, Ltr6 and Ltr8) exhibit independent responses to L. tropica, while Ltr1, Ltr4, Ltr5 and Ltr7 were detected only in gene-gene interactions with other Ltr loci. Ltr3 exhibits the recently discovered phenomenon of transgenerational parental effect on parasite numbers in spleen. The most precise mapping (4.07 Mb) was achieved for Ltr1 (chr.2), which controls parasite numbers in lymph nodes. Five Ltr loci co-localize with loci controlling susceptibility to L. major, three are likely L. tropica specific. Individual Ltr loci affect different subsets of responses, exhibit organ specific effects and a separate control of parasite load and organ pathology. We present the first identification of genetic loci controlling susceptibility to L. tropica. The different combinations of alleles controlling various symptoms of the disease likely co-determine different manifestations of disease induced by the same pathogen in individual mice.


[Successful full-term pregnancy in the Herlyn-Werner-Wunderlich syndrome: a case report and review of literature].
Herlyn-Werner-Wunderlich Syndrome results in a doubling of the internal genitalia accompanied by unilateral gynatresia (with hemi-hematokolpos, hemi-hematometra and/or hemi-hematosalpings) and ipsilateral renal agenesis. The authors considered the case of a successful full-term pregnancy in one uterus after pregnancy failure in the other imposed surgical removal of the same.


Effect of extracorporeal shock wave therapy on fracture healing in rat femural fractures with intact and excised periosteum.
The aim of this study is to compare the effect of extracorporeal shock wave therapy (ESWT) on fractures with intact periosteum and excised periosteum. Thirty-seven Wistar albino rats were randomized into four groups. Osteotomy and intramedullary Kirschner wire fixation were performed on all right femurs under ketamin anesthesia. The first group (n=10) was identified as control group. In the second group (n=10), periosteum located at the osteotomy site was excised circumferentially during surgery. In the third group (n=9), periosteum was left intact and ESWT was applied. In the forth group (n=8), periosteums of all rats were excised and ESWT was applied. All fracture lines were evaluated radiographically each two weeks and histologically at the sixth week. Results were evaluated statistically. In periosteum excised group which represents a model of open fractures with soft tissue defect, ESWT application had a significantly positive histologic effect on bone healing. However, radiological evaluation did not reveal any statistically significant difference between groups with intact and excised periosteums. According to our findings, ESWT can be used to improve fracture healing and prevent pseudoarthrosis in the treatment of open fractures with accompanying soft tissue and periosteum damage. However, further clinical studies are required to include ESWT in routine practice.


[Therapy with vasopressin receptor antagonists: the aquaretics].
Aquaretic drugs, by definition, can induce an increase in urinary volume and urinary free water associated with a decreased urinary osmolarity with a consequent increase in plasma sodium. This enhanced diuresis is not accompanied by an increased loss of electrolytes, whereas traditional diuretics have the opposite, so-called saluretic effect. Aquaretics belong to a family of vasopressin receptor antagonists, V2 in particular, that regulate tubular water reabsorption. Several studies have confirmed their utility in the treatment of hyponatremic states associated with water retention such as heart failure, cirrhosis related ascites and SIADH. Furthermore, new applications may include the treatment of arterial hypertension, polycystic kidney disease, glaucoma and Meniere's syndrome.


Plasma renin activity (PRA) and aldosterone (PA) in patients with chronic glomerulonephritis (GN) and hypertension.
Patients with chronic glomerulonephritis and mild hypertension show a consistent behaviour in their renin-aldosterone-system. There is a close correlation between the elevation of mean blood pressure and destruction of glomeruli. No correlation has been found between renin values and the degree of hypertension. Thus the cuase of mild hypertension occurring in the early stages of chronic GN remains to be elucidated. Normal PRA values in spite of hypertension and expansion of ECFV accompaning progression of chronic glomerulonephritis could be a sign of "relative hyperreninemia". Apparently various mechanisms are involved in the pathogenesis of renal hypertension. These include sodium retention, increased cardiac output. anemia, renin, aldosterone, prostaglandins, expanded plasma volume and peripheral vasoconstriction. These factors are more or less active in the different stages of hypertension and renal failure.


A putative role of micro RNA in regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes.
Cholesterol 7alpha-hydroxylase (CYP7A1) plays a critical role in regulation of bile acid synthesis in the liver. CYP7A1 mRNAs have very short half-lives, and bile acids destabilize CYP7A1 mRNA via the 3'-untranslated region (3'-UTR). However, the underlying mechanism of translational regulation of CYP7A1 mRNA remains unknown. Screening of a human micro RNA (miRNA) microarray has identified five differentially expressed miRNAs in human primary hepatocytes treated with chenodeoxycholic acid, GW4064, or fibroblast growth factor (FGF)19. These compounds also significantly induced the expression of miR-122a, a liver-specific and the predominant miRNA in human hepatocytes. The putative recognition sequences for miR-122a and miR-422a were localized in the 3'-UTR of human CYP7A1 mRNA. The miR-122a and miR-422a mimics inhibited, whereas their inhibitors stimulated CYP7A1 mRNA expression. These miRNAs specifically inhibited the activity of the CYP7A1-3'-UTR reporter plasmids, and mutations of miRNA binding sites in 3'-UTR abrogated miRNA inhibition of reporter activity. These results suggest that miR-122a and miR-422a may destabilize CYP7A1 mRNA to inhibit CYP7A1 expression. However, these miRNAs did not play a role in mediating FGF19 inhibition of CYP7A1 transcription. Under certain conditions, miRNA may reduce CYP7A1 mRNA stability to inhibit bile acid synthesis, and the miR-122a antagomirs may stimulate bile acid synthesis to reduce serum cholesterol and triglycerides.


Mental disorders, quality of care, and outcomes among older patients hospitalized with heart failure: an analysis of the national heart failure project.
To evaluate the effect of a mental illness diagnosis on quality of care and outcomes among patients with heart failure. Retrospective, national, population-based sample of patients with heart failure hospitalized from April 1, 1998, through March 31, 1999, and July 1, 2000, through June 30, 2001. Nonfederal US acute care hospitals. A total of 53 314 Medicare beneficiaries. Quality of care measures, including left ventricular ejection fraction (LVEF) assessment, prescription of an angiotensin-converting enzyme (ACE) inhibitor at discharge among patients without treatment contraindications, and 1-year readmission and 1-year mortality. Of the patients included in the study, 17.0% had a mental illness diagnosis. Compared with patients without mental illness diagnoses, eligible patients with mental illness diagnoses had lower rates of LVEF evaluation (53.0% vs 47.3%; P < .001) but comparable rates of ACE inhibitor prescription (71.3% vs 69.7%; P = .40). Findings were unchanged after multivariate adjustment: patients with mental illness had lower odds of LVEF evaluation (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.76-0.87) but comparable rates of ACE inhibitor prescription (0.96; 0.80-1.14). Patients with mental illness diagnoses had higher crude rates of 1-year all-cause readmission (73.7% vs 68.5%; P < .001), which persisted after multivariate adjustment (OR, 1.30; 95% CI, 1.21-1.39). Crude 1-year mortality was higher among patients with a mental illness diagnosis (41.0% vs 36.2%; P < .001). Presence of a comorbid mental illness diagnosis was associated with 1-year mortality after multivariate adjustment (OR, 1.20; 95% CI, 1.12-1.28). Mental illness is commonly diagnosed among elderly patients hospitalized with heart failure. This subgroup receives somewhat poorer care during hospitalization and has a greater risk of death and readmission to the hospital.


Air exchange rates and advection-diffusion of CO2 and aerosols in a route bus for evaluation of infection risk.
As COVID-19 continues to spread, infection risk on public transport is concerning. Air exchange rates (ACH) and advection-diffusion of CO2 and particles were determined in a route bus to evaluate the infection risk. ACH increased with bus speed whether windows were open or closed, and ACH were greater when more windows were open. With two open windows, ACH was greater when a front and rear window were open than when two rear windows were open. With both front and rear ventilation fans set to exhaust, ACH was more than double that when both were set to supply. With air conditioning (AC) off, CO2 and particles spread proportionally at the same rate from a source, whereas with the AC on, the spread rate of particles was about half that of CO2 , because particles might be trapped by a prefilter on the AC unit. Infection risk can be reduced by equipping AC unit with an appropriate filter. Calculations with a modified Wells-Riley equation showed that average infection risk was reduced by 92% in the moving bus with windows open comparing to with windows closed. When the bus was moving with windows closed, exhaust fan operation reduced the average risk by 35%.


Amino acid sequence of the small cyanogen bromide peptide of thermitase, a thermostable serine proteinase from Thermoactinomyces vulgaris. Relation to the subtilisins.
The following amino acid sequence of the small cyanogen bromide peptide (mol. wt. 5399) of thermitase from Thermoactinomyces vulgaris has been determined: Ala-Thr-Pro-His-Val-Ala-Gly-Val-Ala-Gly-Leu-Leu-Ala-Ser-Gln-Gly-Arg-Ser-Ala-Ser -Asn-Ile-Arg-Ala-Ala-Ile-Glu-Asn-Thr-Ala-Asp-Lys-Ile-Ser-Gly-Thr-Gly-Thr-Tyr-Trp-Ala-Lys-Gly-Arg-Val-Asn-Ala-Tyr-Lys-Ala-Val-Gln-Tyr. The results obtained support the classification of the enzyme as a serine proteinase of the subtilisin type as proposed in a previous paper (1). This partial sequence extending from the serine residue involved in the active site to the C-terminal amino acid of the enzyme shows a 40% homology with the corresponding part of the subtilisin BPN' or subtilisin Carlsberg molecule but a 56% homology as regards conservative amino acid replacements. The secondary structure of this polypeptide fragment, predicted from the data obtained by the method of Chou & Fasman (2) agrees fairly well, within the limit or error of the method, with the structure of the corresponding part of the subtilisin BPN' molecule. Therefore, as expected, no dramatic changes in the spatial structure appear to account for the higher thermostability of thermitase, at least in this area of the polypeptide chain.


[Outpatient or short-stay videothoracoscopy-assisted thoracic sympathectomy: anesthesia in 445 cases].
To demonstrate the safety of outpatient or short-stay bilateral videothoracoscopy-assisted thoracic sympathectomy. The medical records of 445 who underwent bilateral videothoracoscopy-assisted thoracic sympathectomy were reviewed; the same protocols were used to guide these outpatient or short-stay procedures in all cases. Intravenous anesthesia was provided. An orotracheal tube allowed for carrying out the sympathectomy procedure during short periods of apnea. A 2% lidocaine solution was infused through the thoracic drains, which were removed soon after surgery. Data on intraoperative respiratory variables, pain, and intra- and postoperative complications were gathered. The data for patients undergoing the procedure on an outpatient or short-stay basis were compared. No significant differences in demographic or perioperative variables were found between the 2 groups. In 3.6% of the patients in the series, there was a record of a postoperative pulmonary complication: 4 therapeutic minithoracotomies; 1 subcutaneous emphysema without radiologic changes; 9 residual pneumothoraces, 2 requiring pleural drainage; 1 chylothorax; and 1 delayed hemothorax. With the exception of the late-developing hemothorax, all complications were diagnosed and treated in the immediate postoperative period. In the outpatient surgery group, unplanned admissions because of patient refusal to leave occurred in 6.5% of the cases. The low incidence of complications, and especially the finding that complications are detected in the early recovery period, indicate that this procedure can be performed on an outpatient basis.