Naso- and oropharyngeal potential respiratory pathogens in adults with nonpneumonic lower respiratory tract infection.
The objective of this prospective study was to determine positive isolation rates for potential respiratory pathogens (PRPs) in the naso- and oropharynx of adults hospitalized for nonpneumonic lower respiratory tract infection (NPLRTI), compared with patients with community-acquired pneumonia (CAP) and healthy controls. The study population was 315 non-chronic obstructive pulmonary disease adults hospitalized with febrile lower respiratory tract infection (158 NPLRTI and 157 CAP) and 450 control subjects. Each participant was sampled by oropharyngeal swab, nasopharyngeal swab, and nasopharyngeal washings that were tested by conventional bacteriologic methods to identify PRP. At least 1 of the samples was positive for at least 1 of the 3 PRP bacteria in 55 NPLRTI patients (35%) compared with 51 CAP patients (33%) (NS) and 100 controls (22%) (P = 0.003 compared with NPLRTI and P = 0.02 compared with CAP). Samples were positive for Streptococcus pneumoniae in 14 NPLRTI patients (9%) compared with 29 CAP patients (19%) (P = 0.02) and 16 controls (4%) (NPLRTI P = 0.015, CAP P < 0.0001). The corresponding rates for Haemophilus influenzae were 23 (15%), 16 (10%), and 60 (13%) (NS for all 3 comparisons), and for Moraxella catarrhalis, 28 (18%), 25 (16%), and 48 (11%), respectively (NPLRTI versus controls, P = 0.03, NS other comparisons). We conclude that the rate of positive naso/oropharyngeal isolates for at least 1 of the 3 PRP bacteria in NPLRTI patients is similar to the corresponding rates for CAP patients and is higher in both groups than in controls.


Dechlorination of DDT by Aerobacter aerogenes.
Dechlorination of DDT to DDD in higher animals requires the presence of molecular oxygen, but in microorganisms the presence of oxygen hinders dechlorination. In cell-free preparations of Aerobacter aerogenes, the use of selected metabolic inhibitors indicated that reduced Fe(II) cytochrome oxidase was responsible for DDT dechlorination. This finding may possibly explain. the persistence of DDT residues in soils and sediments.


Evaluation of the WATCHMAN left atrial appendage closure device.
Left atrial appendage device occlusion for the preventions of systemic thromboembolism and stroke represents a major breakthrough in the field of cardiovascular disease. The wide prevalence of atrial fibrillation with devastating consequences of thromboembolic stroke as a result of thrombus arising from the left atrial appendage has led to the development of transcatheter and surgical based occlusion devices. Though this device is yet to be formally approved for a clinical indication in the USA, the WATCHMAN appendage occlusion device remains the most rigorously examined and studied of all transcatheter-based devices in this space. This review will focus on the needs assessment in this space, the technology of the current WATCHMAN device, trials and studies looking at safety and efficacy, specific patient populations who might benefit as well as future perspectives.


Medical Student Debt Reform: a Proposed Value-Based Loan Repayment Policy.
The call for value-based medicine has augmented the role of primary care physicians, potentially exacerbating the already-acknowledged shortage of primary care physicians in the current delivery landscape. Lifetime earnings for primary care physicians are millions lower than those for other specialties, and the burden of medical school debt is increasing at a rate that outpaces inflation. Given the societal value of primary care entry for newly minted physicians, one option is a loan repayment program that shares some of that societal value with the physicians themselves, essentially a subsidy that is continuous and tied to present-day specialty choice. While income-based options exist currently, these are merely a proxy for specialty, and other service-driven options are finite and may impose undue burden on physicians at an early and pressure-laden time in their careers. Value-based repayment reflects the graduate's benefit from physician training while also rewarding the real-time societal value of specialties such as primary care, allowing doctors to put their talents to their best uses while advancing the transformation of the physician workforce necessary to realize value-based, patient-centered, population-oriented care.


Representation-mediated Aversion as a Model to Study Psychotic-like States in Mice.
Several paradigms for rodent models of the cognitive and negative endophenotypes found in schizophrenic patients have been proposed. However, significant efforts are needed in order to study the pathophysiology of schizophrenia-related positive symptoms. Recently, it has been shown that these positive symptoms can be studied in rats by using representation-mediated learning. This learning measure the accuracy of mental representations of reality, also called 'reality testing'. Alterations in 'reality testing' performance can be an indication of an impairment in perception which is a clear hallmark of positive psychotic-like states. Thus, we describe here a mouse task adapted from previous findings based on a sensory preconditioning task. With this task, associations made between different neutral stimuli (e.g., an odor and a taste) and subsequent selective devaluation of one of these stimuli have allowed us to study mental sensory representations. Thus, the interest of this task is that it can be used to model positive psychotic-like states in mice, as recently described.


Meat and colo-rectal cancer.
In early epidemiological studies of diet and cancer the stress was on the search for causal factors. Population (ecological) studies tended to show a strong correlation between meat intake, particularly red meat, and the risk of colo-rectal cancer. They also tended to show meat to be strongly inversely correlated with cancers of the stomach and oesophagus and liver. Early case-control studies tended to support the postulated role for red meat in colo-rectal carcinogenesis, although more recent case-control studies, particularly those from Europe, have tended to show no relationship. The cohort studies in general failed to detect any relationship between meat intake and colo-rectal cancer risk. The available evidence points to the intake of protective factors such as vegetables and whole-grain cereals being the main determinants of colo-rectal cancer risk, with meat intake only coincidentally related.


The effects of lovastatin on neointimal hyperplasia following injury in a porcine coronary artery model.
To assess the effectiveness of lovastatin, an HMGCoA reductase inhibitor, in the inhibition of coronary arterial restenosis post-balloon angioplasty. Randomized single-blind study comparing the degree of restenosis in a control and lovastatin group of animals with similar degree of arterial injury. Seventeen domestic cross-bred pigs received either oral lovastatin (11 animals) or no lovastatin (six animals). The pigs received 20 mg of oral lovastatin twice daily or no drug. All pigs received acetylsalicylic acid and verapamil preprocedure. One or more coronary arteries were injured by deployment of tantalum wire stents delivered on oversized percutaneous transluminal coronary angioplasty balloons. The balloons were intentionally overexpanded to create arterial injury. The animals were sacrificed at 28 days. The arteries were cross-sectioned and evaluated blindly by quantitative histomorphometry. The amounts of arterial injury and neointimal thickening were quantitated. A series of linear regression models was used to control for the degree of injury. The reduction of neointimal thickness for the lovastatin group compared with the control animals was 0.08 mm, a statistically significant result (P < 0.05). Although lovastatin produced a statistically significant decrease in neointimal thickness post-balloon angioplasty, when extrapolated to angiographical end-points, the differences would not be clinically significant. These data suggest that lovastatin may be of marginal use in humans for limiting restenosis.


Role of glucose in cloned mouse embryo development.
Cloned mouse embryos display a marked preference for glucose-containing culture medium, with enhanced development to the blastocyst stage in glucose-containing medium attributable mainly to an early beneficial effect during the first cell cycle. This early beneficial effect of glucose is not displayed by parthenogenetic, fertilized, or tetraploid nuclear transfer control embryos, indicating that it is specific to diploid clones. Precocious localization of the glucose transporter SLC2A1 to the cell surface, as well as increased expression of glucose transporters and increased uptake of glucose at the one- and two-cell stages, is also seen in cloned embryos. To examine the role of glucose in early cloned embryo development, we examined glucose metabolism and associated metabolites, as well as mitochondrial ultrastructure, distribution, and number. Clones prepared with cumulus cell nuclei displayed significantly enhanced glucose metabolism at the two-cell stage relative to parthenogenetic controls. Despite the increase in metabolism, ATP content was reduced in clones relative to parthenotes and fertilized controls. Clones at both stages displayed elevated concentrations of glycogen compared with parthenogenetic controls. There was no difference in the number of mitochondria, but clone mitochondria displayed ultrastructural alterations. Interestingly, glucose availability positively affected mitochondrial structure and localization. We conclude that cloned embryos may be severely compromised in terms of ATP-dependent processes during the first two cell cycles and that glucose may exert its early beneficial effects via positive effects on the mitochondria.


Genetic components of heat stress in finishing pigs: development of a heat load function.
The objective of this study was to quantify the effect of heat stress during the life of a pig on its final weight, as a first step toward a genetic evaluation for heat tolerance. Data included carcass weights of 23,556 crossbred pigs [Duroc x (Landrace x Large White)] raised on 2 farms in North Carolina and slaughtered from May 2005 through December 2006. Weather data were available from a nearby weather station. Lifetime of a pig was assumed to be partitioned into 2 periods. During an initial period, the effect of heat stress was assumed to be negligible or compensated for later. During the second period ending in slaughtering, the ADG was assumed to be affected linearly by heat load. Weekly heat load was calculated as degrees of average temperature-humidity index in excess of a threshold (18 degrees C). The total heat load (H) was the sum of weekly heat loads during the second period. During the months of January to May H was 0; H reached a peak in September. The final BW during the peak of heat stress decreased about 6 kg compared with BW during months of non-heat stress. Weekly and monthly averages of carcass weight generally moved similarly to H. However, there were large fluctuations unrelated to H; the fluctuations were different on the 2 farms. The model included the effects of farm-year of slaughter, sex, age at slaughter, and H, where age at slaughter and H were linear regressions. In analyses, the threshold was varied from 16 to 20 degrees C, and the second period was varied from 8 to 16 wk. The greatest R(2) (10.4%) was at the threshold of temperature-humidity index = 18 degrees C for a period of 10 wk. Varying the threshold and the length of time reduced R(2) less than 1%. Least squares means of year-month and year-week of carcass weight were calculated using a model with the fixed effects farm-year-month or farm-year-week of slaughter, sex, and age at slaughter (linear covariate), and the random effect of birth litter. Changes in BW of finisher pigs due to heat stress can be quantified by H during the last 10 wk of the life of the pig.


Fully automated deep learning models with smartphone applicability for prediction of pain using the Feline Grimace Scale.
This study used deep neural networks and machine learning models to predict facial landmark positions and pain scores using the Feline Grimace Scale© (FGS). A total of 3447 face images of cats were annotated with 37 landmarks. Convolutional neural networks (CNN) were trained and selected according to size, prediction time, predictive performance (normalized root mean squared error, NRMSE) and suitability for smartphone technology. Geometric descriptors (n = 35) were computed. XGBoost models were trained and selected according to predictive performance (accuracy; mean square error, MSE). For prediction of facial landmarks, the best CNN model had NRMSE of 16.76% (ShuffleNetV2). For prediction of FGS scores, the best XGBoost model had accuracy of 95.5% and MSE of 0.0096. Models showed excellent predictive performance and accuracy to discriminate painful and non-painful cats. This technology can now be used for the development of an automated, smartphone application for acute pain assessment in cats.


Radiocarbon-based chronology for dynastic Egypt.
The historical chronologies for dynastic Egypt are based on reign lengths inferred from written and archaeological evidence. These floating chronologies are linked to the absolute calendar by a few ancient astronomical observations, which remain a source of debate. We used 211 radiocarbon measurements made on samples from short-lived plants, together with a Bayesian model incorporating historical information on reign lengths, to produce a chronology for dynastic Egypt. A small offset (19 radiocarbon years older) in radiocarbon levels in the Nile Valley is probably a growing-season effect. Our radiocarbon data indicate that the New Kingdom started between 1570 and 1544 B.C.E., and the reign of Djoser in the Old Kingdom started between 2691 and 2625 B.C.E.; both cases are earlier than some previous historical estimates.


Body mass index as a predictor of healthy and disease-free life expectancy between ages 50 and 75: a multicohort study.
While many studies have shown associations between obesity and increased risk of morbidity and mortality, little comparable information is available on how body mass index (BMI) impacts health expectancy. We examined associations of BMI with healthy and chronic disease-free life expectancy in four European cohort studies. Data were drawn from repeated waves of cohort studies in England, Finland, France and Sweden. BMI was categorized into four groups from normal weight (18.5-24.9 kg m-2) to obesity class II (⩾35 kg m-2). Health expectancy was estimated with two health indicators: sub-optimal self-rated health and having a chronic disease (cardiovascular disease, cancer, respiratory disease and diabetes). Multistate life table models were used to estimate sex-specific healthy life expectancy and chronic disease-free life expectancy from ages 50 to 75 years for each BMI category. The proportion of life spent in good perceived health between ages 50 and 75 progressively decreased with increasing BMI from 81% in normal weight men and women to 53% in men and women with class II obesity which corresponds to an average 7-year difference in absolute terms. The proportion of life between ages 50 and 75 years without chronic diseases decreased from 62 and 65% in normal weight men and women and to 29 and 36% in men and women with class II obesity, respectively. This corresponds to an average 9 more years without chronic diseases in normal weight men and 7 more years in normal weight women between ages 50 and 75 years compared to class II obese men and women. No consistent differences were observed between cohorts. Excess BMI is associated with substantially shorter healthy and chronic disease-free life expectancy, suggesting that tackling obesity would increase years lived in good health in populations.


High throughput analysis of neural progenitor cell proliferation in adult rodent hippocampus.
Extensive efforts have been made to determine the status on neural progenitor cell proliferation in specific pathological conditions and to evaluate the therapeutic efficacy of drugs for preventing neurogenic deficits in neurodegenerative diseases. However, the most commonly used stereological analysis using 5-bromo-2'-deoxyuridine (BrdU) immuno-positive sections is a time consuming and labor intensive process and is often a bottle neck in neurogenic drug development, particularly when large sample sizes are needed. In addition, BrdU is toxic to new born neurons and also labels DNA damage in old cells. In this study, we established a method that quantitatively measures the number of Ki-67, an endogenous cell proliferation marker, positive cells by flow cytometry which analyzes extracted cell nuclei from rodent hippocampi in suspension. Our results demonstrate that this approach can be applied to a large number of rodent samples, can be accomplished in a short period of time (1-3 days), and can be completed in a more accurately objective manner than by using 3-D cell counting with immunohistochemically processed sections.


Glycans function as a Golgi export signal to promote the constitutive exocytic trafficking.
Most proteins in the secretory pathway are glycosylated. However, the role of glycans in membrane trafficking is still unclear. Here, we discovered that transmembrane secretory cargos, such as interleukin 2 receptor α subunit or Tac, transferrin receptor, and cluster of differentiation 8a, unexpectedly displayed substantial Golgi localization when their O-glycosylation was compromised. By quantitatively measuring their Golgi residence times, we found that the observed Golgi localization of O-glycan-deficient cargos is due to their slow Golgi export. Using a superresolution microscopy method that we previously developed, we revealed that O-glycan-deficient Tac chimeras localize at the interior of the trans-Golgi cisternae. O-Glycans were observed to be both necessary and sufficient for the efficient Golgi export of Tac chimeras. By sequentially introducing O-glycosylation sites to ST6GAL1, we demonstrated that O-glycan's effect on Golgi export is probably additive. Finally, the finding that N-glycosylated GFP substantially reduces the Golgi residence time of a Tac chimera suggests that N-glycans might have a similar effect. Therefore, both O- and N-glycans might function as a generic Golgi export signal at the trans-Golgi to promote the constitutive exocytic trafficking.


Regulation of nuclear and mitochondrial gene expression by contractile activity in skeletal muscle.
Increased contractile activity of skeletal muscle augments the volume fraction and enzymatic capacity of mitochondria and suppresses the enzymatic capacity of several cytoplasmic enzymes of glycolysis. To examine the biochemical mechanisms underlying these effects, we measured the concentrations of cytochrome b mRNA and aldolase A mRNA in tibialis anterior muscles of adult rabbits that had been stimulated via the motor nerve to contract continuously at 10 Hz for 5 or 21 days; these were compared with the corresponding levels in the unstimulated limbs of the same animals. After 21 days of stimulation aldolase mRNA had fallen to one-fourth of control levels, while cytochrome b mRNA had increased by 5-fold. A reduction in aldolase mRNA was already evident after only 5 days of stimulation, whereas the level of cytochrome b mRNA was not elevated at this stage. Mitochondrial DNA was unchanged after 5 days but had increased by 4-fold after 21 days. We conclude that contractile activity in skeletal muscle produces reciprocal changes in the expression of these two genes at a transcriptional level but via different regulatory mechanisms. Enhancement of the expression of the mitochondrial cytochrome b gene appears to be proportional to the increase in its copy number and may not, therefore, depend upon changes in transcriptional or translational efficiency. The reduction in aldolase A mRNA occurs at an earlier stage in the response to contractile activity and is probably mediated by a reduced transcriptional efficiency.


Dietary acrylamide and risk of prostate cancer.
Acrylamide has been designated by IARC as a "probable human carcinogen." High levels are formed during cooking of many commonly consumed foods including French fries, potato chips, breakfast cereal and coffee. Two prospective cohort studies and two case-control studies in Europe found no association between acrylamide intake and prostate cancer. We examined this association in a large prospective cohort of 47,896 US men in the Health Professionals' Follow-up Study, using updated dietary acrylamide intake from food frequency questionnaires in 1986, 1990, 1994, 1998 and 2002. From 1986 through 2006, we documented 5025 cases of prostate cancer, and 642 lethal cancers. We used Cox proportional hazards models to assess the association between acrylamide intake from diet and prostate cancer risk overall as well as risk of advanced or lethal cancer. Acrylamide intake ranged from a mean of 10.5 mcg/day in the lowest quintile to 40.1 mcg/day in the highest quintile; coffee and potato products were largest contributors to intake. The multivariate-adjusted relative risk of prostate cancer was 1.02 (95% confidence interval: 0.92-1.13) for the highest versus lowest quintile of acrylamide intake (p-value for trend = 0.90). Results were similar when restricted to never smokers and to men who had prostate-specific antigen (PSA) tests. There was no significant association for dietary acrylamide and risk of lethal, advanced or high-grade disease, or for different latency periods ranging from 0-4 years to 12-16 years. We found no evidence that acrylamide intake, within the range of US diets, is associated with increased risk of prostate cancer.


Diagnosis and management of anal cancer.
During the past three decades, anal cancer has served as a paradigm for the successful application of chemoradiation to solid tumors. Since the early 1990s, the increasing incidence of anal cancer in homosexual men has highlighted the causative role of oncogenic human papilloma-virus infection. This review focuses on significant trends and developments in the management of patients with squamous cell carcinoma of the anal canal, emphasizing three major aspects of diagnosis and treatment: routine screening and eradication of premalignant lesions in high-risk individuals; outcome of chemoradiation therapy in HIV-positive individuals in the era of highly active antiretroviral therapy; and potential improvements in chemoradiation protocols through improved radiation delivery technique and the combination of mitomycin with cisplatin in current prospective randomized trials.


[Criteria for social isolation based on associations with health indicators among older people. A 10-year follow-up of the Aichi Gerontological Evaluation Study].
No clear evidence for a cut-off point for social isolation has been established so far. The purpose of this study was to evaluate the criteria for social isolation based on associations with objective health outcomes in a 10-year follow-up study. We performed a prospective study of functionally independent residents aged 65 years or older who lived in six municipalities as part of the Aichi Gerontological Evaluation Study (response rate: 50.4%) that began in 2003. Data on the onset of functional disability, dementia, and death were obtained from municipal databases of the public long-term care insurance system. A total of 12,085 participants were followed up for up to 10 years. We used frequencies of face-to-face and non-face-to-face contact with non-resident children, relatives and friends, or neighbors as indicators of social isolation. The overall frequency of contact with others was categorized from "less than once a month" to "frequently, every day." Cox's proportional hazard model revealed that, after controlling for sex, age, education level, marital status, equivalent household income, need for medical care, self-recognition of forgetfulness, and residential area, the hazard ratios for functional disability (over long-term care level 2), dementia, and premature death increase in those with contact frequency of "less than once a month" were 1.37 (95% confidence interval [CI]: 1.16-1.61), 1.45 (95% CI: 1.21-1.74), and 1.34 (95% CI: 1.16-1.55), respectively. The "from once a month to once a week" frequency was also associated with these health indicators, although the "more than once a week" frequency was not significantly associated with any measured outcome. The prevalence of "less than once a month" contact was 7.4% (men=10.2%, women=4.7%), and this was 15.8% (men=21.2%, women=10.6%) when including those with "less than once a week" contact. These findings suggest that "less than once a week" or "less than once a month" contact with non-cohabitant others are valid operational definitions of social isolation that are closely associated with premature death and other health indicators.


Dirofilaria repens as a cause of subconjunctival infection in a 77-years old female patient from Croatia--a case report.
The zoonotic parasites of the genus Dirofilaria are on the increase as an accidental finding or as a cause of disease in humans worldwide. Human dirofilariasis usually manifests as either subcutaneous infiltrates or lung parenchymal disease, in many cases asymptomatically. We report the case of a 77-year old female patient presenting with irritation and pain in her left eye. Ophthalmologic examination of the temporal part of her left eye revealed motile and threadlike organism, which was surgically extracted and morphologically identified as Dirofilaria. Further molecular diagnostics with polymerase chain reaction (PCR) confirmed that the isolated organism is Dirofilaria repens. Due to already recognized autochthonous occurrence of human dirofilariasis in Croatia, human dirofilariasis must be included in the differential diagnosis of patients presenting with subcutaneous nodules, eye affection and other potential manifestations of this disease.


Genome-wide analysis of polymorphism × sodium interaction effect on blood pressure identifies a novel 3'-BCL11B gene desert locus.
Excessive sodium intake is a global risk factor for hypertension. Sodium effects on blood pressure vary from person to person; hence, high-risk group targeting based on personal genetic information can play a complementary role to ongoing population preventive approaches to reduce sodium consumption. To identify genetic factors that modulate sodium effects on blood pressure, we conducted a population-based genome-wide interaction analysis in 8,768 Japanese subjects, which was >3 times larger than a similar previous study. We tested 7,135,436 polymorphisms in the discovery cohort, and loci that met suggestive significance were further examined in an independent replication cohort. We found that an interaction between a novel 3'-BCL11B gene desert locus and daily sodium consumption was significantly associated with systolic blood pressure in both discovery and replication cohorts under the recessive model. Further statistical analysis of rs8022678, the sentinel variant of the 3'-BCL11B gene desert locus, showed that differences in mean systolic blood pressure between high and low sodium consumption subgroups were 5.9 mm Hg (P = 8.8 × 10-12) in rs8022678 A carriers and -0.3 mm Hg (P = 0.27) in rs8022678 A non-carriers, suggesting that the rs8022678 genotype can classify persons into sodium-sensitive (A carriers) and sodium-insensitive (A non-carriers) subgroups. Our results implied that rs8022678 A carriers may receive a greater benefit from sodium-lowering interventions than non-carriers.


Interventions for treating proximal humeral fractures in adults.
Fractures of the proximal humerus are common injuries. The management, including surgical intervention, of these fractures varies widely. This is an update of a Cochrane review first published in 2001 and last updated in 2010. To review the evidence supporting the various treatment and rehabilitation interventions for proximal humeral fractures. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and other databases, and bibliographies of trial reports. The full search ended in January 2012. All randomised controlled trials pertinent to the management of proximal humeral fractures in adults were selected. Two people performed independent study selection, risk of bias assessment and data extraction. Only limited meta-analysis was performed. Twenty-three small randomised trials with a total of 1238 participants were included. Bias in these trials could not be ruled out. Additionally there is a need for caution in interpreting the results of these small trials, which generally do not provide sufficient evidence to conclude that any non-statistically significant finding is 'evidence of no effect'.Eight trials evaluated conservative treatment. One trial found an arm sling was generally more comfortable than a less commonly used body bandage. There was some evidence that 'immediate' physiotherapy compared with that delayed until after three weeks of immobilisation resulted in less pain and potentially better recovery in people with undisplaced or other stable fractures. Similarly, there was evidence that mobilisation at one week instead of three weeks alleviated short term pain without compromising long term outcome. Two trials provided some evidence that unsupervised patients could generally achieve a satisfactory outcome when given sufficient instruction for an adequate self-directed exercise programme.Six heterogeneous trials, involving a total of 270 participants with displaced and/or complex fractures, compared surgical versus conservative treatment. Pooled results of patient-reported functional scores at one year from three trials (153 participants) showed no statistically significant difference between the two groups (standardised mean difference -0.10, 95% CI -0.42 to 0.22; negative results favour surgery). Quality of life based on the EuroQol results scores from three trials (153 participants) showed non-statistically significant differences between the two groups at three time points up to 12 months. However, the pooled EuroQol results at two years (101 participants) from two trials run concurrently from the same centre were significantly in favour of the surgical group. There was no significant difference between the two groups in mortality (8/98 versus 5/98; RR 1.55, 95% CI 0.55 to 4.36; 4 trials). Significantly more surgical group patients had additional or secondary surgery (18/112 versus 5/111; RR 3.36, 95% CI 1.33 to 8.49; 5 trials). This is equivalent to an extra operation in one of every nine surgically treated patients.Different methods of surgical management were tested in seven small trials. One trial comparing two types of locking plate versus a locking nail for treating two-part surgical neck fractures found some evidence of better function after plate fixation but also of a higher rate of surgically-related complications. One trial comparing a locking plate versus minimally invasive fixation with distally inserted intramedullary nails found some evidence of a short-term benefit for the nailing group. Compared with hemiarthroplasty, tension-band fixation of severe injuries using wires was associated with a higher re-operation rate in one trial. Two trials found no important differences between 'polyaxial' and 'monaxial' screws combined with locking plate fixation. One trial produced some preliminary evidence that tended to support the use of medial support locking screws in locking plate fixation. One trial found better functional results for one of two types of hemiarthroplasty.Very limited evidence suggested similar outcomes from early versus later mobilisation after either surgical fixation (one trial) or hemiarthroplasty (one trial). There is insufficient evidence to inform the management of these fractures. Early physiotherapy, without immobilisation, may be sufficient for some types of undisplaced fractures. It remains unclear whether surgery, even for specific fracture types, will produce consistently better long term outcomes but it is likely to be associated with a higher risk of surgery-related complications and requirement for further surgery.There is insufficient evidence to establish what is the best method of surgical treatment, either in terms of the use of different categories of surgical intervention (such as plate versus nail fixation, or hemiarthroplasty versus tension-wire fixation) or different methods of performing an intervention in the same category (such as different methods of plate fixation). There is insufficient evidence to say when to start mobilisation after either surgical fixation or hemiarthroplasty.


[Infection diagnostics in pneumology. Part 1. Survey and methods].
Lower respiratory tract infections rank among the most important illnesses in medicine. However, the identification of a causative microbiological agent is often difficult. Pulmonary infections must be differentiated from non-infectious causes of pulmonary diseases with similar symptoms and infiltrates on chest imaging. Among the important novel developments ranks the analysis of serum procalcitonin for a better identification and treatment monitoring of bacterial pneumonias compared to conventional tests and a simple scoring system, like the CRB-65/CURB score, for a rapid risk stratification. A rational diagnostic approach is necessary to identify causative microorganisms of pulmonary infectious diseases depending on the severity of the illness, the exposition and predisposition of the patient. In addition to the classical microbiological methods, rapid test systems for the identification of microorganisms are becoming increasingly important. The first part of this review gives a detailed survey of the methods for the diagnosis of pulmonary infectious diseases. In the second part of the manuscript, we will focus on special pulmonary infectious diseases.


Training and Evaluation of Residents to Ensure Competent Physician Metrics to Recognize Struggling Residents.
Assessing competency across domains of knowledge, skills, and behavior is critical to ensure that graduating orthopaedic residents possess the requisite skills and attributes to enter independent orthopaedic practice. Of the domains, knowledge is most easily assessed. In addition to the AAOS Orthopaedic In-Training Examination®, which provides a yearly gauge of residents' orthopaedic knowledge relative to their peers, there are several online platforms such as Orthobullets, the American Academy of Orthopaedic Surgeons ResStudy program, and the Journal of Bone and Joint Surgery Clinical Classroom that offer online learning resources and question banks. Clinical skills are best assessed through a combination of observation tools, including live or video assessments, 360° evaluations, and objective structured clinical examinations. Surgical skills can be evaluated in two domains: live surgical cases or simulations. The American Board of Orthopaedic Surgery is attempting to standardize live surgical evaluations through the use of the O-P tool. Although most available models feature only arthroscopic procedures, surgical simulators provide for opportunity to objectively evaluate resident performance. Behavior and professionalism has traditionally been the most challenging domain to assess. The American Board of Orthopaedic Surgery's Behavior Assessment Tool has demonstrated success in pilot testing and is being introduced as the standard for measuring behavior and professionalism in orthopaedic training. Although no single assessment tool can accurately gauge a resident's overall performance, a combination of readily available tools should be used to assess competence across domains.


B-mode sonography wall thickness assessment of the temporal and axillary arteries for the diagnosis of giant cell arteritis: a cohort study.
We aimed to determine the diagnostic accuracy of B-mode compression sonography of the temporal arteries (tempCS) and B-mode sonographic measurement of the axillary artery intima media thickness (axIMT) for the diagnosis of giant cell arteritis (GCA). After having established measurement of tempCS and axIMT in our routine diagnostic workup, 92 consecutive patients with a suspected diagnosis of GCA were investigated. Clinical characteristics were recorded and wall thickening of the temporal arteries (tempCS) and axillary arteries (axIMT) was measured (mm). Using the final clinical diagnosis as the reference standard, receiver operator characteristics (ROC) analysis was performed. In a subgroup of 26 patients interobserver agreement was assessed using Spearman's rank correlation. Cranial GCA, extracranial GCA, and combined cranial/extracranial GCA were diagnosed in 18, 7, and 9 individuals, respectively. For the diagnosis of cranial GCA, tempCS had an excellent area under the curve (AUC) of 0.95, with a cut-off of ≥0.7 mm offering a sensitivity and specificity of 85% and 95%. The AUC of axIMT for the diagnosis of extracranial GCA was 0.91 (cut-off ≥1.2 mm: sensitivity and specificity 81.3 and 96.1%). Applying a combined tempCS/axIMT cut-off of ≥0.7mm/1.2 mm, we calculated an overall sensitivity and specificity for the final clinical diagnosis of cranial and/or extracranial GCA of 85.3% and 91.4%. Interobserver agreement was strong for both parameters assessed (Spearman's rho 0.72 and 0.77, respectively). The combination of tempCS/axIMT allows objective sonographic assessment in suspected GCA with promising diagnostic accuracy.


Computer-Assisted 3-Dimensional Reconstructions of Scaphoid Fractures and Nonunions With and Without the Use of Patient-Specific Guides: Early Clinical Outcomes and Postoperative Assessments of Reconstruction Accuracy.
To present results regarding the accuracy of the reduction of surgically reconstructed scaphoid nonunions or fractures using 3-dimensional computer-based planning with and without patient-specific guides. Computer-based surgical planning was performed with computed tomography (CT) data on 22 patients comparing models of the pathological and the opposite uninjured scaphoid in 3 dimensions. For group 1 (9 patients), patient-specific guides were designed and manufactured using additive manufacturing technology. During surgery, the guides were used to define the orientation of the reduced fragments. The scaphoids in group 2 (13 patients) were reduced with the conventional freehand technique. All scaphoids in both groups were fixed with a headless compression screw or K-wires, and all bone defects (except one) were filled with autologous bone grafts or vascularized grafts. Postoperative CT scans were acquired 2 or more months after the operations to monitor consolidation and compare the final result with the preoperative plan. The clinical results and accuracy of the reconstructions were compared. In group 1, 8 of 9 scaphoids healed after 2 to 6 months, and partial nonunion after 9 months was observed in one patient. In group 2, 11 of 13 scaphoids healed between 2 and 34 months whereas 2 scaphoids did not consolidate. Comparison of the preoperative and postoperative 3-dimensional data revealed an average residual displacement of 7° (4° in flexion-extension, 4° in ulnar-radial deviation, and 3° in pronation-supination) in group 1. In group 2, residual displacement after surgery was 26° (22° in flexion-extension, 12° in ulnar-radial deviation, and 7° in pronation-supination). The difference in the accuracy of reconstruction was significant. Although the scaphoid is small, patient-specific guides can be used to perform scaphoid reconstructions. When the guides were used, the reconstructions were significantly more anatomic compared with those resulting from the freehand technique. Therapeutic III.


Functional analyses of miRNA-146b-5p during myogenic proliferation and differentiation in chicken myoblasts.
In the poultry and livestock industries, precise genetic information is crucial for improving economic traits. Thus, functional genomic studies help to generate faster, healthier, and more efficient animal production. Chicken myoblast cells, which are required for muscle development and regeneration, are particularly important because chicken growth is closely related to muscle mass. In this study, we induced expression of microRNA-146b-5p mediated by the piggyBac transposon system in primary chicken myoblast (pCM) cells. Subsequently, we analyzed and compared the proliferation and differentiation capacity and also examined the expression of related genes in regular pCM (rpCM) cells and pCM cells overexpressing miRNA-146b-5p (pCM-146b OE cells). pCM-146b OE cells showed increased proliferation and upregulated gene expression related to cell proliferation. In addition, next-generation sequencing analyses were performed to compare global gene expression patterns between rpCM cells and pCM-146b OE cells. We found that the higher proliferation in pCM-146b OE cells was the result of upregulation of gene sets related to the cell cycle. Moreover, miRNA-146b-5p overexpression had inhibitory effects on myotube differentiation in pCM cells. Collectively these results demonstrate that miR-146b-5p is closely related to the proliferation and differentiation of chicken myogenic cells as a modulator of post-transcription.


Rapid molecular tests for tuberculosis and tuberculosis drug resistance: a qualitative evidence synthesis of recipient and provider views.
Programmes that introduce rapid molecular tests for tuberculosis and tuberculosis drug resistance aim to bring tests closer to the community, and thereby cut delay in diagnosis, ensure early treatment, and improve health outcomes, as well as overcome problems with poor laboratory infrastructure and inadequately trained personnel. Yet, diagnostic technologies only have an impact if they are put to use in a correct and timely manner. Views of the intended beneficiaries are important in uptake of diagnostics, and their effective use also depends on those implementing testing programmes, including providers, laboratory professionals, and staff in health ministries. Otherwise, there is a risk these technologies will not fit their intended use and setting, cannot be made to work and scale up, and are not used by, or not accessible to, those in need. To synthesize end-user and professional user perspectives and experiences with low-complexity nucleic acid amplification tests (NAATs) for detection of tuberculosis and tuberculosis drug resistance; and to identify implications for effective implementation and health equity. We searched MEDLINE, Embase, CINAHL, PsycInfo and Science Citation Index Expanded databases for eligible studies from 1 January 2007 up to 20 October 2021. We limited all searches to 2007 onward because the development of Xpert MTB/RIF, the first rapid molecular test in this review, was completed in 2009. We included studies that used qualitative methods for data collection and analysis, and were focused on perspectives and experiences of users and potential users of low-complexity NAATs to diagnose tuberculosis and drug-resistant tuberculosis. NAATs included Xpert MTB/RIF, Xpert MTB/RIF Ultra, Xpert MTB/XDR, and the Truenat assays. Users were people with presumptive or confirmed tuberculosis and drug-resistant tuberculosis (including multidrug-resistant (MDR-TB)) and their caregivers, healthcare providers, laboratory technicians and managers, and programme officers and staff; and were from any type of health facility and setting globally. MDR-TB is tuberculosis caused by resistance to at least rifampicin and isoniazid, the two most effective first-line drugs used to treat tuberculosis. We used a thematic analysis approach for data extraction and synthesis, and assessed confidence in the findings using GRADE CERQual approach. We developed a conceptual framework to illustrate how the findings relate. We found 32 studies. All studies were conducted in low- and middle-income countries. Twenty-seven studies were conducted in high-tuberculosis burden countries and 21 studies in high-MDR-TB burden countries. Only one study was from an Eastern European country. While the studies covered a diverse use of low-complexity NAATs, in only a minority of studies was it used as the initial diagnostic test for all people with presumptive tuberculosis. We identified 18 review findings and grouped them into three overarching categories. Critical aspects users value People with tuberculosis valued reaching diagnostic closure with an accurate diagnosis, avoiding diagnostic delays, and keeping diagnostic-associated cost low. Similarly, healthcare providers valued aspects of accuracy and the resulting confidence in low-complexity NAAT results, rapid turnaround times, and keeping cost to people seeking a diagnosis low. In addition, providers valued diversity of sample types (for example, gastric aspirate specimens and stool in children) and drug resistance information. Laboratory professionals appreciated the improved ease of use, ergonomics, and biosafety of low-complexity NAATs compared to sputum microscopy, and increased staff satisfaction. Challenges reported to realizing those values People with tuberculosis and healthcare workers were reluctant to test for tuberculosis (including MDR-TB) due to fears, stigma, or cost concerns. Thus, low-complexity NAAT testing is not implemented with sufficient support or discretion to overcome barriers that are common to other approaches to testing for tuberculosis. Delays were reported at many steps of the diagnostic pathway owing to poor sample quality; difficulties with transporting specimens; lack of sufficient resources; maintenance of low-complexity NAATs; increased workload; inefficient work and patient flows; over-reliance on low-complexity NAAT results in lieu of clinical judgement; and lack of data-driven and inclusive implementation processes. These challenges were reported to lead to underutilization. Concerns for access and equity The reported concerns included sustainable funding and maintenance and equitable use of resources to access low-complexity NAATs, as well as conflicts of interest between donors and people implementing the tests. Also, lengthy diagnostic delays, underutilization of low-complexity NAATs, lack of tuberculosis diagnostic facilities in the community, and too many eligibility restrictions hampered access to prompt and accurate testing and treatment. This was particularly the case for vulnerable groups, such as children, people with MDR-TB, or people with limited ability to pay. We had high confidence in most of our findings. Low-complexity diagnostics have been presented as a solution to overcome deficiencies in laboratory infrastructure and lack of skilled professionals. This review indicates this is misleading. The lack of infrastructure and human resources undermine the added value new diagnostics of low complexity have for recipients and providers. We had high confidence in the evidence contributing to these review findings. Implementation of new diagnostic technologies, like those considered in this review, will need to tackle the challenges identified in this review including weak infrastructure and systems, and insufficient data on ground level realities prior and during implementation, as well as problems of conflicts of interest in order to ensure equitable use of resources.


Emerging therapies in the pharmacological treatment of Parkinson's disease.
The pharmacological management of Parkinson's disease is a complex and dynamic task; there is no one 'right' strategy indicating which drugs should be used at a particular stage of the disease. There are now many different drugs belonging to several classes that may be effective, and there are still differences of opinion among leading clinicians about the best course of treatment. This review focuses on drug therapy for the motor impairment in Parkinson's disease. Current and future research directions are summarised by taking inventory of recent and innovative areas of development in the field, representing each category with at least one of its featured treatments. The main research efforts are being directed towards delaying the use of levodopa or finding therapies to be used as adjunct to it, in order to postpone motor complications and, in particular, dyskinesias. One of the recent trends is early employment of dopamine agonists. Additional efforts are being directed towards protecting and restoring dopamine neurons. Novel therapies acting on non-dopaminergic systems are also being researched.


Health Effects of the Asthma Care Program under the Universal Coverage Scheme in Children and Young Adults in Thailand.
This study aimed to evaluate the effect of the asthma care program available under the Universal Coverage Scheme (UCS) in Thailand on hospital admissions per 100,000 population, its regional and seasonal variation, readmission within 28 days, and the asthma-specific fatality rate of patients aged 0-29 years in 2009-2016 compared with those in 2007-2008. A retrospective study was conducted using data sources from the UCS register and in-patient databases from the National Health Security Office (NHSO), Thailand. Hospital admissions per 100,000 population was the highest among those aged 0-4 years, but the trends decreased from 470.8 to 288.1 per 100,000 population in 2010-2014. The hospital admission rates were high in Southern Thailand and common in rainy seasons. The readmission rates within 28 days slightly decreased in all age groups in 2016 compared to those in 2007. The case fatality rate of patients aged 20-29 years decreased from 0.40% in 2007 to 0.34% in 2016. The readmission rate within 28 days and case fatality rate were the highest in patients aged 20-29 years. In conclusion, the asthma hospital admission, readmission, and case fatality rates declined over time along with the investment in the asthma care program under the UCS in Thailand. The highest hospital admission rates in patients aged 0-4 years and the readmission and case fatality rates in patients aged 20-29 years should be given more attention. Recordings of individual service utilization data in asthma patients, including quality of care provided, should be monitored to improve the asthma care system.


Immediate Effects of Repetitive Magnetic Stimulation on Single Cortical Pyramidal Neurons.
Repetitive Transcranial Magnetic Stimulation (rTMS) has been successfully used as a non-invasive therapeutic intervention for several neurological disorders in the clinic as well as an investigative tool for basic neuroscience. rTMS has been shown to induce long-term changes in neuronal circuits in vivo. Such long-term effects of rTMS have been investigated using behavioral, imaging, electrophysiological, and molecular approaches, but there is limited understanding of the immediate effects of TMS on neurons. We investigated the immediate effects of high frequency (20 Hz) rTMS on the activity of cortical neurons in an effort to understand the underlying cellular mechanisms activated by rTMS. We used whole-cell patch-clamp recordings in acute rat brain slices and calcium imaging of cultured primary neurons to examine changes in neuronal activity and intracellular calcium respectively. Our results indicate that each TMS pulse caused an immediate and transient activation of voltage gated sodium channels (9.6 ± 1.8 nA at -45 mV, p value < 0.01) in neurons. Short 500 ms 20 Hz rTMS stimulation induced action potentials in a subpopulation of neurons, and significantly increased the steady state current of the neurons at near threshold voltages (at -45 mV: before TMS: I = 130 ± 17 pA, during TMS: I = 215 ± 23 pA, p value = 0.001). rTMS stimulation also led to a delayed increase in intracellular calcium (153.88 ± 61.94% increase from baseline). These results show that rTMS has an immediate and cumulative effect on neuronal activity and intracellular calcium levels, and suggest that rTMS may enhance neuronal responses when combined with an additional motor, sensory or cognitive stimulus. Thus, these results could be translated to optimize rTMS protocols for clinical as well as basic science applications.


[Surgical repair for ascending aortic pseudoaneurysm derived from the proximal anastomotic site of saphenous vein graft after coronary artery bypass grafting; report of a case].
A 61-year-old male had undergone coronary artery bypass grafting (CABG) using a saphenous vein. Postoperative angiography represented an ascending aortic pseudoaneurysm derived from the proximal anastomotic site of the saphenous vein graft( SVG) which was connected to the obtuse marginal branch and left posterior descending branch sequentially. We performed the closure of tear and the plication of pseudoaneurysmal wall through median sternotomy on the 56th postoperative day. A 7mm length longitudinal tear in the ascending aorta close to the proximal anastomotic site of the SVG was observed. This tear was considered to be caused by the intimal injury during the anastomosis of SVG to ascending aorta. Aortic pseudoaneurysm formation close to the proximal anastomotic site of SVG is a rare and potentially lethal complication requiring urgent operation. Postoperative angiography or enhanced 3 dimensional computed tomography after CABG should be performed before hospital discharge.


Is the matched extreme case-control design more powerful than the nested case-control design?
For time-to-event data, the study sample is commonly selected using the nested case-control design in which controls are selected at the event time of each case. An alternative sampling strategy is to sample all controls at the same (pre-specified) time, which can either be at the last event time or further out in time. Such controls are the long-term survivors and may therefore constitute a more 'extreme' comparison group and be more informative than controls from the nested case-control design. We investigate this potential information gain by comparing the power of various 'extreme' case-control designs with that of the nested case-control design using simulation studies. We derive an expression for the theoretical average information in a nested and extreme case-control pair for the situation of a single binary exposure. Comparisons reveal that the efficiency of the extreme case-control design increases when the controls are sampled further out in time. In an application to a study of dementia, we identified Apolipoprotein E as a risk factor using a 1:1 extreme case-control design, which provided a hazard ratio estimate with a smaller standard error than that of a 2:1 nested case-control design.


miRNA-132/212 Deficiency Disrupts Selective Corticosterone Modulation of Dorsal vs. Ventral Hippocampal Metaplasticity.
Cortisol is a potent human steroid hormone that plays key roles in the central nervous system, influencing processes such as brain neuronal synaptic plasticity and regulating the expression of emotional and behavioral responses. The relevance of cortisol stands out in the disease, as its dysregulation is associated with debilitating conditions such as Alzheimer's Disease, chronic stress, anxiety and depression. Among other brain regions, cortisol importantly influences the function of the hippocampus, a structure central for memory and emotional information processing. The mechanisms fine-tuning the different synaptic responses of the hippocampus to steroid hormone signaling remain, however, poorly understood. Using ex vivo electrophysiology and wild type (WT) and miR-132/miR-212 microRNAs knockout (miRNA-132/212-/-) mice, we examined the effects of corticosterone (the rodent's equivalent to cortisol in humans) on the synaptic properties of the dorsal and ventral hippocampus. In WT mice, corticosterone predominantly inhibited metaplasticity in the dorsal WT hippocampi, whereas it significantly dysregulated both synaptic transmission and metaplasticity at dorsal and ventral regions of miR-132/212-/- hippocampi. Western blotting further revealed significantly augmented levels of endogenous CREB and a significant CREB reduction in response to corticosterone only in miR-132/212-/- hippocampi. Sirt1 levels were also endogenously enhanced in the miR-132/212-/- hippocampi but unaltered by corticosterone, whereas the levels of phospo-MSK1 were only reduced by corticosterone in WT, not in miR-132/212-/- hippocampi. In behavioral studies using the elevated plus maze, miRNA-132/212-/- mice further showed reduced anxiety-like behavior. These observations propose miRNA-132/212 as potential region-selective regulators of the effects of steroid hormones on hippocampal functions, thus likely fine-tuning hippocampus-dependent memory and emotional processing.


Cutaneous manifestations of diabetes mellitus.
Of 100 cases of diabetes mellitus examined for cutaneous findings 82% showed cutaneous lesions. Infection (49%) was the most common finding followed by involvement of foot (30%). High incidence of vitiligo (10%) and localized anogenital pruritus (19%) was an unusual feature. Some of the cutaneous markers of diabetes mellitus like necrobiosis lipoidica diabeticorum, diabetic bullae, acquired perforating dermatoses and scleredema were not seen in this study.


Halosarcina limi sp. nov., a halophilic archaeon from a marine solar saltern, and emended description of the genus Halosarcina.
A halophilic archaeon, strain RO1-6(T), was isolated from a marine solar saltern in eastern China. Cells of strain RO1-6(T) were pleomorphic and motile and stained Gram-negative. Strain RO1-6(T) grew well on complex medium and colonies were red-pigmented. It was able to grow at 20-50°C (optimum 37°C), in 2.1-5.1M NaCl (optimum 3.9 M NaCl), in 0.05-0.70 M MgCl₂ (optimum 0.30 M MgCl₂) and at pH 6.5-8.0 (optimum pH 7.0). Cells lysed in distilled water and the minimal NaCl concentration to prevent cell lysis was 12 % (w/v). The major polar lipids of strain RO1-6(T) were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and two glycolipids that were chromatographically identical to S-DGD-1 and S₂-DGD. The 16S rRNA gene sequence of strain RO1-6(T) showed similarities of 96.9 and 96.4 % to those of the type strains of Halosarcina pallida and Halogeometricum borinquense, respectively, members of the most closely related recognized genera within the family Halobacteriaceae. The DNA G+C content of strain RO1-6(T) was 61.2 mol%. Phenotypic characterization and phylogenetic analysis revealed that strain RO1-6(T) is related to Halosarcina pallida and represents a novel species of the genus Halosarcina, for which the name Halosarcina limi sp. nov. is proposed; the type strain is RO1-6(T) (=CGMCC 1.8711(T) =JCM 16054(T)).


[Preinvasive lesions in gynaecology - uterine cervix].
Preinvasive lesion of the uterine cervix can give rise to cervical cancer. High-risk human papillomaviruses with high oncogenic potential are considered to be the main etiopathological factors with interaction of other risk factors (recurrent inflammation of the cervix, injury of the cervix, immunosuppressive conditions, sexual promiscuity, etc.). Early dia-gnosis of these changes at regular gynecological examinations and adequate treatment can prevent of malignant transformation. Organized cervical screening and implementation of nationwide vaccination against human papillomavirus promises to reduce the incidence of cervical cancer.


[Seroepidemiology of human parvovirus B19 using recombinant VP1 + VP2 particle antigen].
Antibody prevalence to B19 virus in Japan was previously reported with 1973 and 1984 serum collections. Since then we have had two big epidemics of erythema infectiosum in Japan: 1986-87 and 1991-92. In an attempt to estimate how much those epidemics have affected seroprevalence to B19 virus infection, we studied seroepidemiology in three separate areas using a newly developed ELISA system consisting of recombinant VP1 + VP2 particle antigen. Total of 900 sera obtained in 1993 from healthy individuals living in northern, central and southwest parts of Japan were assayed for the presence of anti B19 IgG antibody. In the first, the new assay system was compared with our conventional assay system in which native B19 virus particles were used as antigen. Of 220 serum samples tested, 212 (96.4%) gave same results in both assays. Remaining 8 samples which gave variable results were those of near cut off values. We concluded that this new ELISA system can be recommended for seroepidemiological use. Antibody prevalence rates were 10% (0-4 y), 54% (5-9 y), 59% (10-14 y), 46% (15-19 Y), 38% (20-29 y), 48% (30-39 y), 64% (40-49y) and 76% (50 y-). No gender difference was observed. Comparison of antibody prevalences in 1973, 1984 and 1993 suggested that approximately 10% (about 8 million people) of the total population under 40 years of age acquired immunity to B19 virus during one epidemic period.


Body hydration and haemolymph osmolality affect feeding and its neural correlate in the terrestrial gastropod, Limax maximus.
When terrestrial slugs (Limax maximus) are dehydrated to 65-70% of their initial body weight (IBW) their feeding responsiveness is greatly decreased. There is a 90% decrease in feeding responsiveness when slugs are injected with hyperosmotic mannitol solution that raises the haemolymph osmolality to that of slugs dehydrated to 65-70% IBW (i.e. 200 mosmol kg-1 H2O). The duration of the Feeding Motor Programme (FMP) that can be recorded from an isolated CNS-lip preparation is reduced by increasing the osmolality of the saline bathing the preparation. The osmolality of the saline that can modify the FMP corresponds to that of the haemolymph of a slug dehydrated to 65-70% IBW. The pattern of the motor programme is not affected. A gradual increase in saline osmolality which temporally mimics the progressive increase in haemolymph osmolality of a dehydrating slug also causes a decrease in the duration of the FMP. The neural network underlying the FMP appears to adapt to hyperosmotic saline since the duration of FMP bouts gradually returns to normal levels after long-term exposure (6-8 h).


Bilateral presumed astrocytic hamartomas in a patient with retinitis pigmentosa.
Retinal astrocytic hamartomas are benign intraocular tumors classically associated with phacomatoses. Their appearance in isolation is rare. An association between astrocytic hamartomas and retinitis pigmentosa (RP) has been described previously, but controversy still exists regarding the precise nature of these lesions in RP patients. The authors present a case report of a 24-year-old male with RP and multiple bilateral lesions clinically consistent with retinal astrocytic hamartomas. Optical coherence tomography revealed multiple bilateral hyper-reflective intraretinal masses, loss of retinal architecture, intralesional calcifications, and prominent optical posterior shadowing. Comprehensive systemic evaluation was negative for phacomatoses. However, given that a biopsy was not performed, the diagnosis of optic nerve head drusen could not be excluded.


Switching catalysis from hydrolysis to perhydrolysis in Pseudomonas fluorescens esterase.
Many serine hydrolases catalyze perhydrolysis, the reversible formation of peracids from carboxylic acids and hydrogen peroxide. Recently, we showed that a single amino acid substitution in the alcohol binding pocket, L29P, in Pseudomonas fluorescens (SIK WI) aryl esterase (PFE) increased the specificity constant of PFE for peracetic acid formation >100-fold [Bernhardt et al. (2005) Angew. Chem., Int. Ed. 44, 2742]. In this paper, we extend this work to address the three following questions. First, what is the molecular basis of the increase in perhydrolysis activity? We previously proposed that the L29P substitution creates a hydrogen bond between the enzyme and hydrogen peroxide in the transition state. Here we report two X-ray structures of L29P PFE that support this proposal. Both structures show a main chain carbonyl oxygen closer to the active site serine as expected. One structure further shows acetate in the active site in an orientation consistent with reaction by an acyl-enzyme mechanism. We also detected an acyl-enzyme intermediate in the hydrolysis of epsilon-caprolactone by mass spectrometry. Second, can we further increase perhydrolysis activity? We discovered that the reverse reaction, hydrolysis of peracetic acid to acetic acid and hydrogen peroxide, occurs at nearly the diffusion limited rate. Since the reverse reaction cannot increase further, neither can the forward reaction. Consistent with this prediction, two variants with additional amino acid substitutions showed 2-fold higher k(cat), but K(m) also increased so the specificity constant, k(cat)/K(m), remained similar. Third, how does the L29P substitution change the esterase activity? Ester hydrolysis decreased for most esters (75-fold for ethyl acetate) but not for methyl esters. In contrast, L29P PFE catalyzed hydrolysis of epsilon-caprolactone five times more efficiently than wild-type PFE. Molecular modeling suggests that moving the carbonyl group closer to the active site blocks access for larger alcohol moieties but binds epsilon-caprolactone more tightly. These results are consistent with the natural function of perhydrolases being either hydrolysis of peroxycarboxylic acids or hydrolysis of lactones.


BMP3 is a novel locus involved in the causality of ocular coloboma.
Coloboma, a congenital disorder characterized by gaps in ocular tissues, is caused when the choroid fissure fails to close during embryonic development. Several loci have been associated with coloboma, but these represent less than 40% of those that are involved with this disease. Here, we describe a novel coloboma-causing locus, BMP3. Whole exome sequencing and Sanger sequencing of patients with coloboma identified three variants in BMP3, two of which are predicted to be disease causing. Consistent with this, bmp3 mutant zebrafish have aberrant fissure closure. bmp3 is expressed in the ventral head mesenchyme and regulates phosphorylated Smad3 in a population of cells adjacent to the choroid fissure. Furthermore, mutations in bmp3 sensitize embryos to Smad3 inhibitor treatment resulting in open choroid fissures. Micro CT scans and Alcian blue staining of zebrafish demonstrate that mutations in bmp3 cause midface hypoplasia, suggesting that bmp3 regulates cranial neural crest cells. Consistent with this, we see active Smad3 in a population of periocular neural crest cells, and bmp3 mutant zebrafish have reduced neural crest cells in the choroid fissure. Taken together, these data suggest that Bmp3 controls Smad3 phosphorylation in neural crest cells to regulate early craniofacial and ocular development.


Microdeletion 9q22.3 syndrome includes metopic craniosynostosis, hydrocephalus, macrosomia, and developmental delay.
Basal cell nevus syndrome (BCNS), also known as Gorlin syndrome (OMIM #109400) is a well-described rare autosomal dominant condition due to haploinsufficiency of PTCH1. With the availability of comparative genomic hybridization arrays, increasing numbers of individuals with microdeletions involving this locus are being identified. We present 10 previously unreported individuals with 9q22.3 deletions that include PTCH1. While 7 of the 10 patients (7 females, 3 males) did not meet strict clinical criteria for BCNS at the time of molecular diagnosis, almost all of the patients were too young to exhibit many of the diagnostic features. A number of the patients exhibited metopic craniosynostosis, severe obstructive hydrocephalus, and macrosomia, which are not typically observed in BCNS. All individuals older than a few months of age also had developmental delays and/or intellectual disability. Only facial features typical of BCNS, except in those with prominent midforeheads secondary to metopic craniosynostosis, were shared among the 10 patients. The deletions in these individuals ranged from 352 kb to 20.5 Mb in size, the largest spanning 9q21.33 through 9q31.2. There was significant overlap of the deleted segments among most of the patients. The smallest common regions shared among the deletions were identified in order to localize putative candidate genes that are potentially responsible for each of the non-BCNS features. These were a 929 kb region for metopic craniosynostosis, a 1.08 Mb region for obstructive hydrocephalus, and a 1.84 Mb region for macrosomia. Additional studies are needed to further characterize the candidate genes within these regions.


Associations between quality of life, physical activity, worry, depression and insomnia: A cross-sectional designed study in healthy pregnant women.
Health-related quality of life (QOL) is reported to be reduced during pregnancy. Associations between QOL, physical activity (PA), insomnia, depression and worry are insufficiently investigated among pregnant women. The aim of this study was to evaluate QOL and PA patterns among healthy pregnant women, and to examine how QOL might correlate to PA, sleep, worry and depression. This is an observational cross-sectional study, conducted among a convenient sample of 141 healthy pregnant women using five questionnaires: WHOQOL-brief (WHO quality of life questionnaire, brief version, ISI (Insomnia Severity Index), PSWQ (Penn State Worry Questionnaire), ZSRDS (Zung Self-Rating Depression Scale), and Pregnancy Physical Activity Questionnaire (PPAQ). Pre-gestational BMI was inversely correlated to overall health while education was positively correlated to psychological health, social relationships and environment domains. Smoking before and during pregnancy significantly impacted the general health and psychological health. Total and light PA were positively correlated to psychological health and social relationships. Sports/exercise showed positive correlations with several QOL domains. Insomnia and depression were significantly associated with a decrease in all domains of QOL, while worries were associated with a decrease in physical, psychological and environmental domains. There were significant negative correlations between ZSRDS scores and total activity. PA, worries, depression and insomnia affected QOL during pregnancy. Furthermore, pregnant women presenting depression had a reduced total PA. Sleep and mental health as well as encouraging PA during pregnancy are necessary to improve the quality of life of pregnant women.


Long-term effect of 2-hydroxyethyl retinamide on urinary bladder carcinogenesis and tumor transplantation in Fischer 344 rats.
The effects of HER upon early and late stages of BBN-induced bladder cancer in rats were examined. Female Fischer 344 rats were administered HER in the diet either before and during or continuously after BBN administration and were monitored periodically for up to 2 years. The total dose of BBN was 600 mg administered over a 6-week period. In a separate experiment, the effects of HER administration to syngeneic recipients of a transplanted primary bladder cancer were examined. No effects on neoplastic development were observed as the result of HER treatment before and during carcinogen administration. However, at the 1-year sacrifice, there was a significant increase in bladder tumor incidence in the animals receiving BBN followed by continuous retinoid treatment versus animals receiving BBN only. At the 2-year sacrifice, there was a significant increase in tumor progression in the continuous retinoid group versus the animals receiving BBN alone, based upon grading and staging of tumors, although tumor incidences were not significantly different. In the transplantation experiment, more recipients (9/20 versus 2/20) receiving continuous HER had large, anaplastic tumors following 9 months of observation than did control animals. This study supports the view that retinoids should not be considered as only inhibitors of carcinogenesis, but rather as modifiers which vary in their effects depending upon factors yet to be understood.


Classification of periodic activities using the Wasserstein distance.
In this paper, we introduce a novel nonparametric classification technique based on the use of the Wasserstein distance. The proposed scheme is applied in a biomedical context for the analysis of recorded accelerometer data: the aim is to retrieve three types of periodic activities (walking, biking, and running) from a time-frequency representation of the data. The main interest of the use of the Wasserstein distance lies in the fact that it is less sensitive to the location of the frequency peaks than to the global structure of the frequency pattern, allowing us to detect activities almost independently of their speed or incline. Our system is tested on a 24-subject corpus: results show that the use of Wasserstein distance combined with some supervised learning techniques allows us to compare with some more complex classification systems.


Scoring Algorithm-Based Genomic Testing in Dystonia: A Prospective Validation Study.
Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications. We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity). We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses. Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81. The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.


Modulation of active site electronic structure by the protein matrix to control [NiFe] hydrogenase reactivity.
Control of the reactivity of the nickel center of the [NiFe] hydrogenase and other metalloproteins commonly involves outer coordination sphere ligands that act to modify the geometry and physical properties of the active site metal centers. We carried out a combined set of classical molecular dynamics and quantum/classical mechanics calculations to provide quantitative estimates of how dynamic fluctuations of the active site within the protein matrix modulate the electronic structure at the catalytic center. Specifically we focused on the dynamics of the inner and outer coordination spheres of the cysteinate-bound Ni-Fe cluster in the catalytically active Ni-C state. There are correlated movements of the cysteinate ligands and the surrounding hydrogen-bonding network, which modulate the electron affinity at the active site and the proton affinity of a terminal cysteinate. On the basis of these findings, we hypothesize a coupling between protein dynamics and electron and proton transfer reactions critical to dihydrogen production.


Efficient CO2-reducing activity of NAD-dependent formate dehydrogenase from Thiobacillus sp. KNK65MA for formate production from CO2 gas.
NAD-dependent formate dehydrogenase (FDH) from Candida boidinii (CbFDH) has been widely used in various CO2-reduction systems but its practical applications are often impeded due to low CO2-reducing activity. In this study, we demonstrated superior CO2-reducing properties of FDH from Thiobacillus sp. KNK65MA (TsFDH) for production of formate from CO2 gas. To discover more efficient CO2-reducing FDHs than a reference enzyme, i.e. CbFDH, five FDHs were selected with biochemical properties and then, their CO2-reducing activities were evaluated. All FDHs including CbFDH showed better CO2-reducing activities at acidic pHs than at neutral pHs and four FDHs were more active than CbFDH in the CO2 reduction reaction. In particular, the FDH from Thiobacillus sp. KNK65MA (TsFDH) exhibited the highest CO2-reducing activity and had a dramatic preference for the reduction reaction, i.e., a 84.2-fold higher ratio of CO2 reduction to formate oxidation in catalytic efficiency (kcat/KB) compared to CbFDH. Formate was produced from CO2 gas using TsFDH and CbFDH, and TsFDH showed a 5.8-fold higher formate production rate than CbFDH. A sequence and structural comparison showed that FDHs with relatively high CO2-reducing activities had elongated N- and C-terminal loops. The experimental results demonstrate that TsFDH can be an alternative to CbFDH as a biocatalyst in CO2 reduction systems.


[Volvulus of the colon. Presentation of 22 cases].
A study was made of patients hospitalized with the diagnosis of colonic volvulus in two provincial hospitals of Camagüey during two different time periods (1979-1986 in the Amalia Simoni and 1978-1983 in the Manuel A. Domenech), for a total of 22 cases that represent 4.49% of the 489 patients admitted with a diagnosis of intestinal occlusion. We present 17 volvuli of the sigmoid, 4 ceco-ascendant and 1 transverse. Male sex and age over 70 years were strongly predominant. The principal symptoms were pain (90.9%) and abdominal distension (81.82%). Diagnosis was not reached in one patient who died in the preoperative period. Seventy-five percent of deaths had more than 72 hours of evolution. Several therapeutic procedures were used in this study, but all were considered emergency surgery according to our norms. Fifty percent of patients suffered complications, 38.46% of them wound infection. The mortality was 18.18%. A comparative study was made with other national and international series.


Electromagnetic energy within single-resonance chiral metamaterial spheres.
We derive an exact expression for the time-averaged electromagnetic (EM) energy inside a chiral dispersive sphere irradiated by a plane wave. The dispersion relations correspond to a chiral metamaterial consisting of uncoupled single-resonance helical resonators. Using a field decomposition scheme and a general expression for the EM energy density in bianisotropic media, we calculate the Lorenz-Mie solution for the internal fields in a medium that is simultaneously magnetic and chiral. We also obtain an explicit analytical relation between the internal EM energy and the absorption cross section. This result is applied to demonstrate that strong chirality leads to an off-resonance field enhancement within weakly absorbing spheres.


Hierarchy of sorting signals in chimeras of intestinal lactase-phlorizin hydrolase and the influenza virus hemagglutinin.
Lactase-phlorizin hydrolase (LPH) is an apical protein in intestinal cells. The location of sorting signals in LPH was investigated by preparing a series of mutants that lacked the LPH cytoplasmic domain or had the cytoplasmic domain of LPH replaced by sequences that comprised basolateral targeting signals and overlapping internalization signals of various potency. These signals are mutants of the cytoplasmic domain of the influenza hemagglutinin (HA), which have been shown to be dominant in targeting HA to the basolateral membrane. The LPH-HA chimeras were expressed in Madin-Darby canine kidney (MDCK) and colon carcinoma (Caco-2) cells, and their transport to the cell surface was analyzed. All of the LPH mutants were targeted correctly to the apical membrane. Furthermore, the LPH-HA chimeras were internalized, indicating that the HA tails were available to interact with the cytoplasmic components of clathrin-coated pits. The introduction of a strong basolateral sorting signal into LPH was not sufficient to override the strong apical signals of the LPH external domain or transmembrane domains. These results show that basolateral sorting signals are not always dominant over apical sorting signals in proteins that contain each and suggest that sorting of basolateral from apical proteins occurs within a common compartment where competition for sorting signals can occur.


Comparison of Serological Biomarkers in Rheumatoid Arthritis and Their Combination to Improve Diagnostic Performance.
The diagnosis of rheumatoid arthritis (RA) is based on a combined approach that includes serological markers such as rheumatoid factor (RF) and anti-citrullinated peptide/protein antibodies (ACPA). The goal of this study was to evaluate the clinical performance of several RF and ACPA immunoassays for the diagnosis of RA, as well as the diagnostic value of a combinatory approach with these markers. The study cohort included 1,655 patients from the Swiss Clinical Quality Management registry with sera from 968 patients with RA and 687 disease controls, including patients with axial spondyloarthritis (n = 450) and psoriatic arthritis (n = 237). ACPA were determined by anti-CCP2 IgG enzyme-linked immunosorbent assay (ELISA), QUANTA Flash® CCP3 IgG [chemiluminescent immunoassay (CIA)], and QUANTA Lite® CCP3 IgG ELISA. RF was determined by ELISA (QUANTA Lite® RF IgM, RF IgA, and RF IgG) and with two research use only CIAs (QUANTA Flash® RF IgM and RF IgA). All three ACPA assays showed good discrimination between RA patients and controls and good clinical performance. Overall, CCP3 performed better than CCP2. More pronounced differences were observed between the RF assays. We observed that CIA platforms for both RF IgM and RF IgA showed better performance than the ELISA platforms. Excellent and good total agreements were found between ELISA and CIA for CCP3 (total agreement 95.3%, kappa = 0.90), and between CCP2 and CCP3 ELISA (total agreement 86.6%, kappa = 0.73), respectively. RF IgM CIA and ELISA had a good qualitative agreement (86.5%, kappa = 0.73); RF IgA CIA and ELISA showed a moderate total agreement (78.5%, kappa = 0.53). When combinatory analyses were performed, the likelihood of RA increased with dual positivity and triple positivity and combining different markers resulted in higher odds ratio than the individual markers in all cases. ACPA and RF showed good clinical performance in this large Swiss cohort of RA patients and controls. Overall, the performance of CCP3 was superior to CCP2. The combination of these biomarkers in an interval model represents a potential tool for the diagnosis of RA patients.


[Acute dyspnoea following transfusion of plasma-containing blood products].
A 35-year-old male patient who was given chemotherapy because of chronic myeloid leukaemia became dyspnoeic after transfusion of thrombocytes; initially, no explanation could be found for this dyspnoea. He went home before all diagnostic procedures were evaluated. Chest X-ray revealed bilateral pulmonary oedema, which could be due to transfusion-related acute lung injury (TRALI), especially since there were no indications for a cardiac aetiology. The patient was sent to the nearest hospital where he was treated with diuretics and observed for 24 hours. There were no complications. The pathogenesis of TRALI has been attributed to an interaction between anti-granulocyte antibodies and granulocytes. In addition, bioactive compounds produced during the storage of blood products have been implicated. It is important to recognize TRALI as the cause of dyspnoea when cardiac or pulmonary causes are excluded. The overall prognosis is good when treatment is started in time. The management of TRALI is supportive, with mechanical ventilation when necessary. After excluding donors with proven anti-granulocyte antibodies from further donation, there is no increased risk for recurrent episodes after future transfusion of plasma-containing blood products.


Alkylglycerol opening of the blood-brain barrier to small and large fluorescence markers in normal and C6 glioma-bearing rats and isolated rat brain capillaries.
1. The blood-brain barrier (BBB) represents the major impediment to successful delivery of therapeutic agents to target tissue within the central nervous system. Intracarotid alkylglycerols have been shown to increase the transfer of chemotherapeutics across the BBB. 2. We investigated the spatial distribution of intracarotid fluorescein sodium and intravenous lissamine-rhodamine B200 (RB 200)-albumin in the brain of normal and C6 glioma-bearing rats after intracarotid co-administration of 1-O-pentylglycerol (200 mm). To elucidate the mechanisms involved in the alkylglycerol-mediated BBB opening, intraluminal accumulation of fluorescein isothiocyanate (FITC)-dextran 40,000 was studied in freshly isolated rat brain capillaries using confocal microscopy during incubation with different alkylglycerols. Furthermore, 1-O-pentylglycerol-induced increase in delivery of methotrexate (MTX) to the brain was evaluated in nude mice. 3. Microscopic evaluation showed a marked 1-O-pentylglycerol-induced extravasation of fluorescein and RB 200-albumin in the ipsilateral normal brain. In glioma-bearing rats, increased tissue fluorescence was found in both tumor tissue and brain surrounding tumor. Confocal microscopy revealed a time- and concentration-dependent accumulation of FITC-dextran 40,000 within the lumina of isolated rat brain capillaries during incubation with 1-O-pentylglycerol and 2-O-hexyldiglycerol, indicating enhanced paracellular transfer via tight junctions. Intracarotid co-administration of MTX and 1-O-pentylglycerol (200 mm) in nude mice resulted in a significant increase in MTX concentrations in the ipsilateral brain as compared to controls without 1-O-pentylglycerol (P<0.005). 4. In conclusion, 1-O-pentylglycerol increases delivery of small and large compounds to normal brain and brain tumors and this effect is mediated at least in part by enhanced permeability of tight junctions.


Effective equilibrium states in mixtures of active particles driven by colored noise.
We consider the steady-state behavior of pairs of active particles having different persistence times and diffusivities. To this purpose we employ the active Ornstein-Uhlenbeck model, where the particles are driven by colored noises with exponential correlation functions whose intensities and correlation times vary from species to species. By extending Fox's theory to many components, we derive by functional calculus an approximate Fokker-Planck equation for the configurational distribution function of the system. After illustrating the predicted distribution in the solvable case of two particles interacting via a harmonic potential, we consider systems of particles repelling through inverse power-law potentials. We compare the analytic predictions to computer simulations for such soft-repulsive interactions in one dimension and show that at linear order in the persistence times the theory is satisfactory. This work provides the toolbox to qualitatively describe many-body phenomena, such as demixing and depletion, by means of effective pair potentials.


The clinical use of angiotensin converting enzyme inhibitors in hypertension and cardiac failure.
The renin-angiotensin system has a range of physiological actions concerned with the control of the circulation. Angiotensin II has both an immediate and a delayed pressor effect, it stimulates the secretion of aldosterone and antidiuretic hormone, promotes thirst, stimulates the sympathetic nervous system at various sites while inhibiting vagal tone, and has a range of direct effects on the kidney. Several aspects of this range of actions can become deranged in a number of forms of hypertension as well as in congestive cardiac failure. Hence much effort has been directed in recent years to the development of agents designed to interfere with the renin-angiotensin system and to apply these clinically in the treatment of hypertension and congestive cardiac failure. Orally active converting enzyme inhibitors are of proven benefit not only in renovascular hypertension, but also, when combined with loop diuretics, in the treatment of intractable hypertension as well as, both alone and in combination with thiazide diuretics, in the treatment of essential hypertension. In congestive cardiac failure controlled trials have shown that converting enzyme inhibitors can improve exercise tolerance while diminishing lassitude, correct potassium deficiency and limit ventricular arrhythmias. Energetic efforts are being made to develop orally active inhibitors of the enzyme renin itself, since these would be more specific in action than the presently available and very successful converting enzyme inhibitors.


Reduction of Secondhand Smoke Exposure in the Cars of Children With Cancer.
This study examined whether an intervention designed to reduce secondhand smoke exposure (SHSe) among children being treated for cancer had effects in the specific setting of a motor vehicle. The parents or guardians (n = 71) of children being treated for cancer were randomized to either a behavioral secondhand smoke (SHS) reduction program or a standard care control group. Parental reports of SHSe were collected over the course of 12 months. Younger children were exposed at baseline more than their older counterparts. The greatest initial declines in car exposure were observed among children ≤5 years old in the intervention group compared with same-aged peers in the control group. After the 3-month time point, the control group showed greater reductions in car exposure in comparison with the intervention group. Interventions that teach parents strategies to manage their smoking while driving in their personal vehicles may produce even greater reductions in child exposure and should be developed. Based on the age-specific results reported here, future studies should account for effects of child age and use setting-specific measures of SHS.


Designing superior solid electrolyte interfaces on silicon anodes for high-performance lithium-ion batteries.
The solid electrolyte interface (SEI) is a passivation layer formed on the surface of lithium-ion battery (LIB) anode materials produced by electrolyte decomposition. The quality of the SEI plays a critical role in the cyclability, rate capacity, irreversible capacity loss and safety of lithium-ion batteries (LIBs). The stability of the SEI is especially important for Si anodes which experience tremendous volume changes during cycling. Therefore, in this review we discuss the effect of the SEI on Si anodes. Firstly, the mechanism of formation, composition, and component properties of solid electrolyte interfaces (SEIs) are introduced, and the SEI of native-oxide-terminated Si is emphasized. Then the growth model and mechanical failure of SEIs are analyzed in detail, and the challenges facing SEIs of Si anodes are proposed. Moreover, we highlight several modification methods for SEIs on Si anodes, including electrolyte additives, surface-functionalization of Si, coating artificial SEIs or protective layers, and the structural design of Si-based composites. We believe that designing a high-quality SEI is of great significance and is beneficial for the improved electrochemical performance of Si anodes.


Identification of genes in the VirR regulon of Pectobacterium atrosepticum and characterization of their roles in quorum sensing-dependent virulence.
In the economically important phytopathogen, Pectobacterium atrosepticum, expression of plant cell wall degrading enzymes and other virulence determinants is controlled in a cell density-dependent fashion, termed quorum sensing (QS). Canonical QS systems in Gram-negative bacteria contain a LuxI-type protein, synthesizing a signalling molecule, and a LuxR-type regulator, responding to the signalling molecule above threshold concentrations. In P. atrosepticum, the central LuxR-type repressor of virulence, VirR, has been identified and its impacts on virulence characterized. Here we define the broader VirR regulon using chromatin immunoprecipitation (ChIP) and in planta microarrays. Ninety-four direct VirR targets were identified by ChIP microarrays and a consensus VirR binding site was determined. Purified VirR was used in DNA gel shift assays on target promoters and VirR : promoter binding was disrupted by exogenous addition of the signalling molecule, N-(3-oxohexanoyl)-l-homoserine lactone (OHHL). VirR autorepressed, and directly activated the transcription of rsmA in the absence of OHHL. Finally, we showed that VirR directly regulated the production of siderophores and controlled swimming motility. This is the first report characterizing the direct targets of VirR and provides clear evidence that this LuxR-type protein can act in vivo as both an activator and repressor of transcription in the absence of its cognate signalling molecule.


Effects of feeding intensity during the dry period. 1. Feed intake, body weight, and milk production.
The objective of this experiment was to study dry matter intake (DMI), body condition, milk yield, and milk composition in cows with different body condition at the time of parturition. Twenty four multiparous cows with genetic merit for high or low milk fat content were assigned to one of three diets during the dry period. The treatments consisted of 6, 9, or 14.5 kg dry matter of a total mixed ration providing 71, 106, or 177 MJ/d of metabolizable energy and are referred to as low (L), medium (M), and high (H) dry period rations, respectively. These diets were introduced when the cows were dried off from the previous lactation, at least 8 wk before expected parturition. After parturition all cows were fed another total mixed ration ad libitum. The dietary treatments generated differences between the groups in body weight as well as in body condition score at parturition. There were no differences in DMI in early lactation, but during wk 6 to 12 DMI was lower among H cows, which was linked to a prolonged negative energy balance in this group. The milk yield was 38.5 +/- 0.8 kg of energy-corrected milk the first 4 wk postpartum and did not differ between treatments or selection lines. Body weight loss mainly occurred in lactation wk 1 to 4 and was greatest in H cows. The mobilization of body tissues was reflected in a higher milk fat content of C18:0 for the H cows during wk 1 to 4. There were no marked effects of treatments on milk fat content or milk protein content, which indicates that cows in early lactation have a potential to compensate for low nutrient intake during the dry period if they are offered a high-quality diet. The observed differences between treatments in DMI wk 6 to 12 could not be explained by differences in milk yield or mobilization of body tissues. Milk fat content was 4.7% in cows with genetic merit for high milk fat content and 4.2% in cows with genetic merit for low milk fat content. There was a tendency for higher body weight in cows with genetic merit for low milk fat content throughout the experiment.


[Isoproterenol-induced, lymphocyte-dependent hyperplasia of mouse salivary glands--a possible analog of a syngeneic mixed lymphocyte culture in vivo].
T-cell phenotype that regulates isoproterenol-induced lymphocyte-dependent hyperplasia of mouse salivary glands and conditions of its activation has been investigated. Stimulated Thy-1 and Ly-1-positive cell populations proliferated in the medium supplemented with both interleukin-1 (IL-1) and interleukin-2 (IL-2). The inhibiting population was Thy-1 and Ly-2-positive, proliferating only in IL-2-containing medium. Both regulatory cell properties and the character of their activation are similar to those of lymphocytes that regulate syngeneic mixed lymphocyte culture. The regularities shown may reflect important processes of cell proliferation regulation in multicellular organisms.


A cross-sectional study of muscle strength and mass in 45- to 78-yr-old men and women.
The isokinetic strength of the elbow and knee extensors and flexors was measured in 200 healthy 45- to 78-yr-old men and women to examine the relationship between muscle strength, age, and body composition. Peak torque was measured at 60 and 240 degrees/s in the knee and at 60 and 180 degrees/s in the elbow by use of a Cybex II isokinetic dynamometer. Fat-free mass (FFM) was estimated by hydrostatic weighing in all subjects, and muscle mass (MM) was determined in 141 subjects from urinary creatinine excretion. FFM and MM were significantly lower (P less than 0.001) in the oldest group. Strength of all muscle groups at both testing speeds was significantly (P less than 0.006) lower (range 15.5-26.7%) in the 65- to 78- than in the 45- to 54-yr-old men and women. When strength was adjusted for FFM or MM, the age-related differences were not significant in all muscle groups except the knee extensors tested at 240 degrees/s. Absolute strength of the women ranged from 42.2 to 62.8% that of men. When strength was expressed per kilogram of MM, these gender differences were smaller and/or not present. These data suggest that MM is a major determinant of the age- and gender-related differences in skeletal muscle strength. Furthermore, this finding is, to a large extent, independent of muscle location (upper vs. lower extremities) and function (extension vs. flexion).


[Work and alcohol: considerations on a caseload of patients undergoing treatment].
An enquiry into alcohol dependent subjects admitted to the clinical wards of the first section of Occupational Medicine belonging to Medicina Preventiva Occupazionale e di Comunità of University of Pavia for an alcohol disaddiction treatment has been performed through a phone interview. 289 patients have been contacted and time elapsed from admission to interview was one to three years. The questions focused alcohol abstinence, occupational position before and after admission, any improvement in the work sphere (relationship with the collegues), any feeling of empowerment of the work abilities and any increase in the responsibilities load. From our results we can conclude that alcohol disaddiction carried on during admission has positively contributed to the reinstatement of alcoholics patients.