Locked down with my eating disorder: a retrospective study on the impact of COVID-19 lockdown on adolescents with eating disorders.
Negative effects of COVID-19 lockdowns have been reported in adult patients with feeding and eating disorders (FED) whereas evidence of its impact on young clinical populations is still limited and somewhat inconsistent. The present study aims to investigate the effect of the first COVID-19 lockdown on a range of FED symptoms in children and adolescents: (a) already receiving treatment in our specialist service for FED when the pandemic hit, and (b) prospectively evaluated in our service from October 2020 to July 2021. Out of sixty-one eligible patients with a broad spectrum of FED invited, forty-five young patients (aged 11-18) consented to participate and were included. An ad-hoc survey, consisting of open questions, multiple choice questions, yes/no questions, and a symptoms checklist, was administered online. About half of the participants (46.7%) reported a positive effect of lockdown on FED symptomatology. Patients with anorexia nervosa (AN) reported the highest rate of symptomatology worsening (58.6%). Younger patients (11-13 years) showed a greater improvement of symptoms compared to older ones (14-18 years of age). COVID-19 lockdown was identified as the precipitating factor for FED onset in 60.7% of newly evaluated patients. Evidence from our investigation points out that although the COVID-19 pandemic was a precipitating factor for a FED for many active and newly referred patients, it had a positive impact on youth who were already in treatment and younger participants.


Pathogenicity, infective dose and altered gut microbiota in piglets infected with porcine deltacoronavirus.
Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus that cause severe diarrhea, resulting in high mortality in neonatal piglets. Little is known regarding the pathogenicity of PDCoV in different infective dose and the dynamic changes in the composition of the gut microbiota in PDCoV-induced diarrhea piglets. In this study, 5-day-old piglets were experimentally infected with different dose of PDCoV. The challenged piglets developed typical symptoms, characterized by acute and severe watery diarrhea from 1 to 8 days post-inoculation (DPI), and viral shedding was detected in rectal swab until 11 DPI. Tissues of small intestines displayed significant macroscopic and microscopic lesions with clear viral antigen expression. However, no significant differences among groups were found in challenged piglets. Then alteration in gut microbiota in the jejunum and colon of PDCoV infected-piglets were analyzed using 16S rRNA sequencing. PDCoV infection reduced bacterial diversity and richness, and significantly altered the structure and abundance of the microbiota from the phylum to genus. Fusobacterium, and Proteobacteria was significantly increased (P < 0.05), while the abundance of Bacteroidota was markedly decreased in the infected-piglets. Furthermore, microbial function prediction indicated that the changes in intestinal bacterial also affected the immune system, excretory system, circulatory system, neurodegenerative disease, cardiovascular disease, xenobiotics biodegradation and metabolism, etc. These findings suggest that regulating gut microbiota community may be an effective approach for preventing PDCoV infection.


New tools for understanding coping and resilience.
In humans, many of the factors determining vulnerability and resilience to the impact of an adverse event revolve around coping factors. This mini-review focuses on the neural mechanisms by which coping reduces the impact of adverse events, as studied in an animal model, and discusses some of the challenges of linking neural circuit activity with stressor outcome. We highlight several approaches for probing circuit function with cell-type and pathway-specificity that overcome some of the limitations of traditional neuroscience techniques and will likely yield a more detailed and comprehensive understanding of how the brain regulates stress-responsive structures when coping behaviors are engaged.


Laparoscopic Reversal of the Biliopancreatic Diversion with Duodenal Switch: a Step by Step Video Case.
Despite the success of the Biliopancreatic Diversion with Duodenal Switch procedure (BPD-DS) in weight loss and comorbidities resolution, reversal of BPD-DS is necessary in 0.2-0.6% of BPD-DS cases for vitamin, protein, and other micronutrient deficiencies. Different techniques are available to reverse the malabsorptive component of the BPD-DS. A retrospective chart review for a 37-year-old female patient who presented with lower leg edema and signs of malnutrition 5 years after a BPD/DS. The patient was not compliant with the required daily vitamin and protein intake. Thus, after extensive discussion with the patient, a decision was made to reverse the malabsorptive component of the BPD-DS. A laparoscopic reversal of the malabsorptive component of the BPD-DS was concluded by transecting the roux limb distally at the ileo-ileal anastomosis and reconnecting it to the proximal jejunum thus substantially lengthening the common channel for absorption. At 6 months follow-up, the patient normalized her vitamin deficiency and had a normal level of serum protein. Her weight, BMI, EWL%, and TBWL% were 72 kg, 27.5 kg/m2, 90%, and 45%, respectively. Proper nutrition and vitamin supplementation is essential to avoid nutritional complications. Different techniques are available to reverse the malabsorptive component of the BPD-DS. However, no standard approach is adopted by the surgical community. We demonstrate our preferred technique in reversing the malabsorptive component of the BPD-DS.


The Home Observation of Periconceptional Exposures (HOPE) study, a prospective cohort: aims, design, recruitment and compliance.
To examine transient environmental exposures and their relationship with human fecundity, exposure assessment should occur optimally at the time of conception in both members of the couple. We performed an observational, prospective cohort study with biomonitoring in both members of a heterosexual couple trying to conceive. Couples collected urine, saliva, and semen specimens for up to two menstrual cycles on days corresponding to the time windows of fertilization, implantation, and early pregnancy, identified based on the woman's observations of her cervical fluid. Three hundred nine eligible couples were screened between 2011 and 2015, of which 183 enrolled. Eleven couples (6.0 %) withdrew or were lost to follow up. The most successful and cost effective recruiting strategies were word of mouth (40 % of participating couples), posters and flyers (37 %), and targeted Facebook advertising (13 %) with an overall investment of $37.35 spent on recruitment per couple. Both men and women collected ≥97.2 % of requested saliva samples, and men collected ≥89.9 % of requested semen samples. Within the periovulatory days (±3 days), there was at least one urine specimen collected by women in 97.1 % of cycles, and at least one by men in 91.7 % of cycles. Daily compliance with periovulatory urine specimens ranged from 66.5 to 92.4 % for women and from 55.7 to 75.0 % for men. Compliance was ≥88 % for questionnaire completion at specified time points. Couples planning to conceive can be recruited successfully for periconceptional monitoring, and will comply with intensive study protocols involving home collection of biospecimens and questionnaire data.


Are extreme halophiles actually "bacteria"?
Comparative cataloging of the 16SrRNA of Halobacterium halobium indicates that the organism did not arise, as a halophilic adaptation, from some typical bacterium. Rather, H. halobium is a member of the Archaebacteria, an ancient group of organisms that are no more related to typical bacteria than they are to eucaryotes.


Modelling the impact of school reopening and contact tracing strategies on Covid-19 dynamics in different epidemiologic settings in Brazil.
We simulate the impact of school reopening during the COVID-19 pandemic in three major urban centers in Brazil to identify the epidemiological indicators and the best timing for the return of in-school activities and the effect of contact tracing as a mitigation measure. Our goal is to offer guidelines for evidence-based policymaking. We implement an extended SEIR model stratified by age and considering contact networks in different settings - school, home, work, and community, in which the infection transmission rate is affected by various intervention measures. After fitting epidemiological and demographic data, we simulate scenarios with increasing school transmission due to school reopening, and also estimate the number of hospitalization and deaths averted by the implementation of contact tracing. Reopening schools results in a non-linear increase in reported COVID-19 cases and deaths, which is highly dependent on infection and disease incidence at the time of reopening. When contact tracing and quarantining are restricted to school and home settings, a large number of daily tests is required to produce significant effects in reducing the total number of hospitalizations and deaths. Policymakers should carefully consider the epidemiological context and timing regarding the implementation of school closure and return of in-person school activities. While contact tracing strategies prevent new infections within school environments, they alone are not sufficient to avoid significant impacts on community transmission.


Expected and observed in-hospital mortality in heart failure patients before and during the COVID-19 pandemic: Introduction of the machine learning-based standardized mortality ratio at Helios hospitals.
Reduced hospital admission rates for heart failure (HF) and evidence of increased in-hospital mortality were reported during the COVID-19 pandemic. The aim of this study was to apply a machine learning (ML)-based mortality prediction model to examine whether the latter is attributable to differing case mixes and exceeds expected mortality rates. Inpatient cases with a primary discharge diagnosis of HF non-electively admitted to 86 German Helios hospitals between 01/01/2016 and 08/31/2020 were identified. Patients with proven or suspected SARS-CoV-2 infection were excluded. ML-based models were developed, tuned, and tested using cases of 2016-2018 (n = 64,440; randomly split 75%/25%). Extreme gradient boosting showed the best model performance indicated by a receiver operating characteristic area under the curve of 0.882 (95% confidence interval [CI]: 0.872-0.893). The model was applied on data sets of 2019 and 2020 (n = 28,556 cases) and the hospital standardized mortality ratio (HSMR) was computed as the observed to expected death ratio. Observed mortality rates were 5.84% (2019) and 6.21% (2020), HSMRs based on an individual case-based mortality probability were 100.0 (95% CI: 93.3-107.2; p = 1.000) for 2019 and 99.3 (95% CI: 92.5-106.4; p = .850) for 2020. Within subgroups of age or hospital volume, there were no significant differences between observed and expected deaths. When stratified for pandemic phases, no excess death during the COVID-19 pandemic was observed. Applying an ML algorithm to calculate expected inpatient mortality based on administrative data, there was no excess death above expected event rates in HF patients during the COVID-19 pandemic.


Anaemia in patients with chronic kidney disease: management with epoetin beta in primary care setting in New Zealand.
Anaemia is a major complication of advancing chronic kidney disease (CKD) and is amenable to treatment with epoetin. In order to manage the large number of CKD patients, it is essential that much of the care take place in primary care practices. We describe a programme to treat anaemia with epoetin beta (EPO), using a simple referral and management protocol, by general practitioners remotely supported by a nephrologist and nurse coordinator team. Data for 79 patients treated between May 2005 and May 2007 was analysed. Patients were treated with stepwise alterations of EPO dose, beginning with 4000 units/week, and were followed up for a mean of 11 months (range 3-25). The mean age was 73 years and 91% were of Caucasian origin. Sixty-seven per cent had stage 4 CKD and 27% were at stage 3. Mean haemoglobin increased from 92.9 (standard deviation (SD) 7.1) to 118.5 (SD 11.7) g/L (P < 0.01). More than 75% achieved Hb of 110 g/L or more by the fifth month of therapy. Mean starting dose of EPO was 58.8 (SD 25.0) and increased to 79.9 (SD 55.6) units/kg/week (P < 0.01). Mean serum ferritin decreased (P = 0.05), but transferrin saturation was not significantly altered. Estimated glomerular filtration rate remained stable. There was non-significant elevation of systolic and diastolic blood pressure during treatment. The study demonstrates that treatment of anaemia with EPO can be successfully accomplished in primary care setting by general practitioners without the need for many patients to attend a nephrology clinic.


Oxidative-stress-induced T lymphocyte hyporesponsiveness is caused by structural modification rather than proteasomal degradation of crucial TCR signaling molecules.
In several human pathologies (e.g. cancer, rheumatoid arthritis, AIDS and leprosy) oxidative stress induces T cell hyporesponsiveness. Hyporesponsive T cells often appear to display impaired expression of some (e.g. TCR-zeta, p56(lck) and LAT) but not all (e.g. TCR-alphabeta and CD3-epsilon) crucial TCR-proximal signaling molecules but the underlying mechanisms have as yet not been identified. Using an in vitro system for oxidative-stress-induced T cell hyporesponsiveness we here report two sequential effects of oxidative stress on TCR signaling molecules: protein alterations and proteasomal degradation. We have identified the C-terminal part of TCR-zeta and the membrane-proximal domain of p56(lck) as potential targets for modifications induced by reactive oxygen species. Oxidative-stress-exposed proteins were differentially susceptible to proteasomal degradation: whereas modified TCR-zeta was relatively resistant, reactive oxygen species (ROS)-altered LAT and p56(lck) were much more susceptible. Importantly, we found that T cell hyporesponsiveness best correlated with ROS-dependent protein alteration since inhibition of proteasomal degradation did not restore function. Finally, our data provide an explanation for the paradox of reduced TCR-zeta signals combined with unaltered TCR-alphabeta and CD3-epsilon expression levels: the TCR-zeta chain in hyporesponsive T cells is still expressed but no longer detectable by certain mAb recognizing ROS-sensitive epitopes.


Simultaneous powerline interference and baseline wander removal from ECG and EMG signals by sinusoidal modeling.
We present a compact approach to joint modeling of powerline interference (PLI) and baseline wonder (BW) for denoising of biopotential signals. Both PLI and BW are modeled by a set of harmonically related sinusoids modulated by low-order time polynomials. The sinusoids account on the harmonicity and mean instantaneous frequency of the PLI in the analysis window, while the polynomials capture the frequency and amplitude deviations from their nominal values and characterize the BW at the same time. The resulting model is linear-in-parameters and the solution to the corresponding linear system is estimated in a simple and efficient way through linear least-squares. The proposed modeling method was evaluated on real electrocardiographic (ECG) and electromyographic (EMG) signals against three reference methods for different analysis scenarios. The comparative study suggests that the proposed method outperforms the reference methods in terms of residual interference energy in the denoised biopotential signals.


Infection in a complex network of apical ramifications as the cause of persistent apical periodontitis: a case report.
This article reports a case of persistent apical periodontitis lesion in a mesiobuccal root of a maxillary molar subjected to single-visit endodontic treatment. The treatment protocol followed endodontic standards including using nickel-titanium instruments with working length ending 0.5-mm short of the apex, establishment and maintenance of apical foramen patency, irrigation with 5% NaOCl, smear layer removal, a final rinse with and ultrasonic agitation of chlorhexidine, and filling by the vertical compaction technique. Even so, the lesion in the mesiobuccal root became larger in size after follow-up examination at 1 year 6 months, and periradicular surgery was performed. Radiographic control after 11 months showed that periradicular healing was almost complete. The root apex and the lesion were analyzed histologically and histobacteriologically. The lesion was diagnosed as a "pocket cyst," and no bacteria were noted extraradicularly. The cause of continued disease was a heavy bacterial biofilm infection located in an intricate network of apical ramifications. Bacteria were also observed on the walls of one of the mesiobuccal canals packed between the obturation material and the root canal wall. This case report reinforces the need for treating the infected root canal as a complex system that possesses anatomic intricacies in which bacteria can spread and remain unaffected by treatment procedures.


Clinical Impact of Pretransplantation Physical Function on Transplantation after Allogeneic Hematopoietic Cell Transplantation in Older Adults.
Clinical research regarding the impact of pretransplantation physical function on transplantation outcomes in older adults remains limited. We retrospectively reviewed the charts of 150 consecutive patients age >55 years who underwent their first allogeneic hematopoietic cell transplantation (HCT) at our center between 2010 and 2021. We evaluated the clinical impact of pretransplantation physical function, including hand grip strength (HGS), knee extension strength (KES), and distance covered in a 6-minute walk test (6MWT), along with other clinical factors, on transplantation outcomes such as overall survival (OS), nonrelapse mortality (NRM), and cumulative incidence of disease relapse (CIR). There was no difference in OS, NRM, or CIR among the 3 age groups studied (56 to 60 years, 61 to 65 years, and 66 to 70 years). With regard to physical function tests, we divided the study patients into 2 groups based on the median HGS, KES, and 6MWT values: higher physical function and lower physical function groups. Because there were significant differences in HGS and KES between male and female patients, sex-specific threshold values were used. In a univariate analysis, OS tended to be better in the higher physical function group compared with the lower physical function group (4-year OS, 42.0% versus 32.0% in HGS, P = .14; 44.8% versus 37.8% in KES, P = .17; 46.7% versus 30.5% in 6MWT, P = .099). NRM was significantly lower in the higher physical function group (4-year NRM, 25.5% versus 39.9% in HGS, P = .045; 17.7% versus 38.0% in KES, P = .005; 22.5% versus 43.4% in 6MWT, P = .033). There was no significant difference in CIR between the higher and lower physical function groups (4-year CIR, 34.6% versus 28.7% in HGS, P = .38; 38.5% versus 25.8% in KES, P = .20; 33.0% versus 27.0% in 6MWT, P = .42). In multivariate analysis, the higher KES group (hazard ratio [HR], .54; 95% confidence interval [CI], .32 to .90) was significantly associated with better OS, as were female sex (HR, .48; 95% CI, .26 to .89) and low/intermediate Disease Risk Index (HR, 3.59; 95% CI, 2.04 to 6.31). Higher KES (HR, .37; 95% CI, .17 to .83) and female sex (HR .36; 95% CI, .13 to .998) were significantly associated with a reduced risk of NRM. Higher HGS and higher 6MWT tended to be associated with a reduced risk of NRM, but this trend was not statistically significant. Pretransplantation physical function, particularly the strength of the lower extremities, but not chronological age, is associated with NRM and OS after allogeneic HCT in adults age >55 years.


Gender based differences, pharmacogenetics and adverse events in chronic pain management.
Safety data in chronic non-cancer pain (CNCP) with long-term opioid therapy has been poorly studied and can be differently influenced by gender. Furthermore, pharmacogenetics (PGx) could possibly be used to tailor pain medication based on the individual's genetic background. The aim was to assess whether PGx applied to a pharmacovigilance system could help to improve a patient's security profile. A pharmacovigilance data recording system was conducted over 24 months, including genotyping of OPRM1 variants (opioid receptor, A118G) and COMT (enzyme that degrades catecholamines such as norepinephrine, G1947A). Pain intensity (visual analogue scale, VAS), morphine equivalent daily dose (MEDD), adverse events (AEs) and suspected adverse drug reactions (ADRs) were recorded and analysed by gender. The Ethics Committee approved the study and data were analysed with R 3.6.0 software. A total of 748 patients were recruited in the study (67% female, VAS 62 ± 29 mm, MEDD 119 ± 114 mg/day) reporting a median of 6 (3.5-9) AEs/patient. Women presented more nausea, headaches, insomnia, loss of appetite, weight change, depression and dizziness than men. Analysis by genotype demonstrated that PGx influenced the prevalence of vomiting and depression in men, dizziness in women and sexual dysfunction in both. Physicians notified 150 ADRs mostly in females (79%) related to nervous system disorders. PGx applied to a pharmacovigilance recording system provides important information to achieve a better knowledge about AEs in CNCP pharmacological therapy. OPRM1 and COMT polymorphisms were associated with AEs in CNCP patients that differed according to gender.


Na+-dependent activation of NADH oxidase in membrane fractions from halophilic Vibrio alginolyticus and V. costicolus.
Membrane-bound NADH oxidase activities from slightly halophilic marine Vibrio alginolyticus and moderately halophilic V. costicolus required 0.3 and 0.5 M Na+, respectively, for maximum activity; other cations such as Li+,K+,Rb+,Cs+,Mg2+, and Ca2+ were relatively ineffective as replacements for Na+. The concentration of Na+ required to give half-maximum activity with the NADH oxidase from V. alginolyticus was 82 mN. This value was reduced to 6.4 and 13.8 mM in the presence of 400 mM K+ and 10 mM Mg2+, respectively, indicating that K+ and Mg2+ cooperated with Na+ for activation. The same pattern of cation dependence was observed with the NADH oxidase from V. costicolus. The NADH oxidase from nonhalophilic Escherichia coli, however, had no specific requirement for Na+. Thus, Na+-dependent activation of NADH oxidase appeared to be a characteristic feature of these halophilic bacteria. All NADH oxidases examined were influenced by the species of anion present and the order of activating effect followed the lyotropic series:SO4(2-), CH3COO- greater than Cl- greater than NO3- greater than SCN-. Chaotropic anions such as NO3- and SCN- were inhibitory to the NADH oxidases, irrespective of the halophilic nature of the bacterial source.


Analysis of Granulometric Composition of Algal Suspensions in Wastewater Treated with Hydroponic Method.
The aim of the study was to determine the changes in suspension particle size identified in biologically treated wastewater, which was then treated in hydroponic system with use of engineering lighting by the light-emitting diodes (LED). The study was subjected to wastewater purified under laboratory conditions, in a hydroponic system using the effect of macrophytes Pistia stratiotes and growing algae. Measurement of particle size was made using a laser granulometer. Analysis of the results showed that the additional lighting of the hydroponic system with LED can significantly influence the ability of the suspension particles to agglomerate and, consequently, determine their sedimentation properties. In hydroponic system supported by additional lighting, more particles were observed with equivalent diameter D(3.2) smaller than 10 μm than those in the tank without additional lighting, indicating a higher reactivity of the particles. Determining the size of equivalent diameters D(4.3) allowed us to observe that in hydroponic system, particles of relatively small size predominate, which negatively affects the sedimentation process of the suspensions. Determination of particle size of suspensions consisting mainly of algae and the dynamics of their changes are the basis for specification of an effective method of removing particles from the system to protect the receiver from excessive suspension concentrations.


[Effects of irradiated wheat flour in the AKR mouse. III. Effects of activity of hepatic and pancreatic enzymes].
The livers and the pancreas of AKR mice fed with irradiated or non-irradiated wheat flour were homogenized to measure the activities of the follow enzymes : alkaline phosphatase, acid phosphatase, glucose . 6 . phosphate dehydrogenase, amylase. No effect could be demonstrated.


Retrograde axonal transport of mercury in primary sensory neurons innervating the tooth pulp in the rat.
The pulp cavity of the first upper molar was exposed unilaterally in adult rats with a dental drill and about 1 microliter of mercuric chloride was injected into the coronal pulp. The rats were killed after 1-24 days and frozen sections from the trigeminal ganglia were subjected to silver acetate autometallography for demonstration of mercury. Mercury was found to have accumulated in neurons of the ipsilateral trigeminal ganglion by retrograde axonal transport. The possible implications of this finding are discussed.


Evaluating Sex Disparities in the Emergency Department Management of Patients With Suspected Acute Coronary Syndrome.
We compare clinical management and outcomes of emergency department (ED) encounters by sex after implementation of a clinical care pathway in 15 community EDs that standardized recommendations based on patient risk, using the History, ECG, Age, Risk Factors, and Troponin (HEART) score. This was a retrospective analysis of adult ED encounters evaluated for suspected acute coronary syndrome with a documented HEART score from May 20, 2016, to December 1, 2017. The primary outcomes were hospitalization or 30-day stress testing. Secondary outcomes included 30-day acute myocardial infarction or all-cause death (major adverse cardiac event). A generalized estimating equation regression model was used to compare the odds of hospitalization or stress testing by sex; we report HEART scores (0 to 10) stratified by sex and describing major adverse cardiac events. A total of 34,715 adult ED encounters met the inclusion criteria (56.0% women). A higher proportion of women were classified as low risk (60.5% versus 52.4%; odds ratio [OR] 1.39; 95% confidence interval [CI] 1.33 to 1.45). Women were hospitalized or received stress testing less frequently than men for low HEART scores (18.8% versus 22.8%; OR 0.79; 95% CI 0.73 to 0.84) and intermediate ones (46.7% versus 49.7%; OR 0.88; 95% CI 0.83 to 0.95), but similarly for high-risk ones (74.1% versus 74.4%; OR 0.99; 95% CI 0.77 to 1.28). Women had 18% lower odds of hospitalization or noninvasive cardiac testing (OR 0.82; 95% CI 0.78 to 0.86), even after adjusting for HEART score and comorbidities. Men had higher risks of major adverse cardiac events than women for all HEART score categories but the risk for men was significantly higher among low-risk HEART scores (0.4% versus 0.1%). Women with low-risk HEART scores are hospitalized or stress tested less than men, which is likely appropriate, and women have better outcomes than men. Use of the HEART score has the potential to reduce sex disparities in acute coronary syndrome care.


Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain.
Neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) is a novel hypnotic and voltage-dependent blocker of T-type calcium channels. Here, we examine its potential analgesic effects and adjuvant anaesthetic properties using a post-surgical pain model in rodents. Analgesic properties of 3β-OH were investigated in thermal and mechanical nociceptive tests in sham or surgically incised rats and mice, with drug injected either systemically (intraperitoneal) or locally via intrathecal or intraplantar routes. Hypnotic properties of 3β-OH and its use as an adjuvant anaesthetic in combination with isoflurane were investigated using behavioural experiments and in vivo EEG recordings in adolescent rats. A combination of 1% isoflurane with 3β-OH (60 mg·kg-1 , i.p.) induced suppression of cortical EEG and stronger thermal and mechanical anti-hyperalgesia during 3 days post-surgery, when compared to isoflurane alone and isoflurane with morphine. 3β-OH exerted prominent enantioselective thermal and mechanical antinociception in healthy rats and reduced T-channel-dependent excitability of primary sensory neurons. Intrathecal injection of 3β-OH alleviated mechanical hyperalgesia, while repeated intraplantar application alleviated both thermal and mechanical hyperalgesia in the rats after incision. Using mouse genetics, we found that CaV 3.2 T-calcium channels are important for anti-hyperalgesic effect of 3β-OH and are contributing to its hypnotic effect. Our study identifies 3β-OH as a novel analgesic for surgical procedures. 3β-OH can be used to reduce T-channel-dependent excitability of peripheral sensory neurons as an adjuvant for induction and maintenance of general anaesthesia while improving analgesia and lowering the amount of volatile anaesthetic needed for surgery.


The C677T mutation of the 5,10-methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy.
To estimate the risk for spina bifida associated with the common mutation C677T of the MTHFR gene in a country with a relatively low prevalence of NTDs. Case-control study. 203 living patients affected with spina bifida (173 myelomeningocele and 30 lipomeningocele); controls: 583 subjects (306 young adults and 277 unselected newborns) from northern and central-southern Italy. three spina bifida centres; young adult controls: DNA banks; newborn controls: regional neonatal screening centres. Prevalence of the C677T genotypes in cases and controls by place of birth; odds ratios for spina bifida and estimated attributable fraction. The prevalence of T/T, T/C, and C/C genotype was 16.6%, 53.7%, and 29.7% in controls and 25.6%, 43.8%, and 30.6% in cases, respectively. We found no differences between type of defect or place of birth. The odds ratio for spina bifida associated with the T/T genotype v C/C plus T/C was 1.73 (95% CI 1.15, 2.59) and the corresponding attributable fraction was 10.8%. No increased risk was found for heterozygous patients (OR=0.79, 95% CI 0.53-1.18). This study, as well as the meta-analysis we updated, shows that homozygosity for the MTHFR C677T mutation is a moderate risk factor in Europe, and even in Italy where there is a relatively low prevalence of spina bifida. The estimated attributable fraction associated with this risk factor explains only a small proportion of cases preventable by periconceptional folic acid supplementation. Thus, other genes involved in folate-homocysteine metabolism, their interaction, and the interaction between genetic and environmental factors should be investigated further.


Long-term evaluation of biological versus mechanical prosthesis use at reoperative aortic valve replacement.
Recent evidence indicated that the use of a bioprosthesis in young patients at first-time aortic valve replacement (AVR) is associated with an increased reoperation risk, but not with an increase in long-term mortality, when compared with the use of a mechanical valve. However, at reoperative AVR, follow-up data by prosthesis type have been lacking from the literature. Therefore, we examined long-term survival and valve-related complications according to the type of prosthesis used at reoperative AVR. We studied 437 patients who underwent reoperative AVR, at a mean age of 58.6 ± 14.2 years, for failure of a previously implanted aortic valve prosthesis. Thirty-day mortality at reoperative AVR was 6% (n = 27). A bioprosthesis was used in 135 (31%) patients. Patients were subsequently followed up for a mean of 7.6 ± 6.8 years after reoperative AVR. The use of a bioprosthesis at reoperative AVR was not associated with impaired survival on adjusted analysis (hazard ratio [HR], 0.8 ± 0.4; P = .6). Freedom from thromboembolism, and endocarditis were similar between valve types (both P > .05); however, late postoperative major hemorrhage occurred only in patients who received a mechanical prosthesis at reoperative AVR. Risk factors for third-time AVR included the use of a bioprosthesis (HR, 14.0) and younger age (HR, 1.05 per decreasing year) at reoperative AVR (both P < .001). Thirty-day mortality of third-time AVR was 4% (n = 1/27). At reoperative AVR, the use of a bioprosthesis is associated with equivalent long-term survival compared with a mechanical prosthesis. Patients who receive a bioprosthesis at reoperative AVR are less likely to experience major hemorrhage but more likely to require third-time AVR, albeit with an acceptable third-time perioperative mortality risk. Therefore, the patient's informed preferences regarding prosthesis choice should prevail, even in a reoperative context.


A preliminary coronary computed tomography angiography-based study of perivascular fat attenuation index: relation with epicardial adipose tissue and its distribution over the entire coronary vasculature.
To investigate the perivascular fat attenuation index (FAI) in association with epicardial adipose tissue (EAT) parameters and its distribution over the entire coronary vasculature in patients with known or suspected coronary artery disease (CAD). Patients with known or suspected CAD who underwent coronary computed tomography angiography from January 1, 2019, to June 1, 2019, were retrospectively included. The perivascular FAI was quantified on four main epicardial coronary arteries and seven coronary segments. Moreover, EAT density and volume were measured. We included 192 consecutive patients (55 without coronary plaque [mean age 46.4 ± 13.2 years, 69.1% male] and 137 with coronary plaque [mean age 57.9 ± 13.0 years, 84.7% male]). EAT density was lower than perivascular FAI in both groups, but they exhibited substantial correlation (- 83.33 ± 4.54 vs. - 78.22 ± 6.52 HU, p < 0.001; r = 0.667 in plaque- patients and - 83.11 ± 4.48 vs. - 77.81 ± 5.63 HU, p < 0.001; r = 0.778 in plaque+ patients). The left main coronary artery had the highest perivascular FAI, followed by the left circumflex artery. The perivascular FAI in proximal segments was significantly higher compared to that in distal segments (all p < 0.05). Furthermore, the presence of plaque did not alter perivascular FAI on the patient or segmental level. The perivascular FAI was significantly higher than EAT density and correlated substantially with EAT density. The perivascular FAI distribution over the entire coronary tree varied and prompted for vessel-specific or segment-specific thresholds to determine abnormal perivascular FAI in practice. • The perivascular FAI correlated well with EAT density and had higher values than EAT density. • The distributions of perivascular FAI differ between coronary vessels or segments; considering segment and vessel confounding factors while conducting a perivascular FAI study is necessary. • No significant difference of perivascular FAI was observed between patients without and with coronary plaque, nor between coronary segments without plaque and those with plaque.


Observation of ligand effects during alkene hydrogenation catalysed by supported metal clusters.
Homogeneous organometallic catalysts and many enzymes activate reactants through coordination to metal atoms; that is, the reactants are turned into ligands and their reactivity controlled through other ligands in the metal's coordination sphere. In the case of supported metal clusters, catalytic performance is influenced by the support and by adsorbed reactants, intermediates or products. The adsorbates are usually treated as ligands, whereas the influence of the supports is usually ascribed to electronic interactions, even though metal clusters supported on oxides and zeolites form chemical bonds to support oxygen atoms. Here we report direct observations of the structure of supported metal clusters consisting of four iridium atoms, and the identification of hydrocarbon ligands bound to them during propene hydrogenation. We find that propene and molecular hydrogen form propylidyne and hydride ligands, respectively, whereas simultaneous exposure of the reactants to the supported iridium cluster yields ligands that are reactive intermediates during the catalytic propane-formation reaction. These intermediates weaken the bonding within the tetrahedral iridium cluster and the interactions between the cluster and the support, while replacement of the MgO support with gamma-Al2O3 boosts the catalytic activity tenfold, by affecting the bonding between the reactant-derived ligands and the cluster and therefore also the abundance of individual ligands. This interplay between the support and the reactant-derived ligands, whereby each influences the interaction of the metal cluster with the other, shows that the catalytic properties of supported metal catalysts can be tuned by careful choice of their supports.


The C-terminal domain of A1/Bfl-1 regulates its anti-inflammatory function in human endothelial cells.
A1/Bfl-1 is a NF-κB dependent, anti-apoptotic Bcl-2 family member that contains four Bcl-2 homology domains (BH) and an amphipathic C-terminal domain, and is expressed in endothelial cells (EC). Based on NF-κB reporter assays in bovine aortic EC, we have previously demonstrated that A1, like Bcl-2 and Bcl-xL, inhibits NF-κB activation. These results, however, do not fully translate when evaluating the cell's own NF-κB machinery in human EC overexpressing A1 by means of recombinant adenovirus (rAd.) mediated gene transfer. Indeed, overexpression of full-length A1 in human umbilical vein EC (HUVEC), and human dermal microvascular EC (HDMEC) failed to inhibit NF-κB activation. However, overexpression of a mutant lacking the C-terminal domain of A1 (A1ΔC) demonstrated a potent NF-κB inhibitory effect in these cells. Disparate effects of A1 and A1ΔC on NF-κB inhibition in human EC correlated with mitochondrial (A1) versus non-mitochondrial (A1ΔC) localization. In contrast, both full-length A1 and A1ΔC protected EC from staurosporine (STS)-induced cell death, indicating that mitochondrial localization was not necessary for A1's cytoprotective function in human EC. In conclusion, our data uncover a regulatory role for the C-terminal domain of A1 in human EC: anchoring A1 to the mitochondrion, which conserves but is not necessary for its cytoprotective function, or by its absence freeing A1 from the mitochondrion and uncovering an additional anti-inflammatory effect.


Symptoms and cognitive dysfunction in patients with the late whiplash syndrome.
The aim of the study was to record the severity of symptoms in patients with the late whiplash syndrome and to assess how the symptom load affected the performance on a simple psychometric test. The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) with an additional question on neck pain, modified RPQ (mRPQ), and the Short Test of Mental Status (STMS) were applied on 40 chronic whiplash patients. Symptoms reported by the whiplash group were compared to those of 50 normal controls. The patients scored significantly higher than the controls on all symptoms listed in the mRPQ. The most frequent symptoms reported.


Ambulatory blood pressure correlates with renal volume and number of renal cysts in children with autosomal dominant polycystic kidney disease.
In adult patients with autosomal dominant polycystic kidney disease (ADPKD) renal volume was found to be significantly greater in hypertensive compared to normotensive patients. The purpose of this study was to find out if blood pressure (BP) is related to renal size also in children with ADPKD, for example, in an early stage of the disease. Sixty-two children with ADPKD and normal renal function (mean age 12.3+/-4.3 years) were examined by renal ultrasound and ambulatory BP monitoring (ABPM). Twenty-two children were hypertensive and 40 normotensive. Mean renal volume was significantly greater in hypertensive than in normotensive children (2.7+/-2.3 SDS versus 1.2+/-2.5 SDS, P<0.01) despite similar anthropometric data and renal function. Similarly the mean number of cysts was significantly higher in hypertensive patients than in normotensive (35+/-15 cysts versus 23+/-14 cysts, P<0.01). Renal volume correlated with daytime as well as with night-time systolic and diastolic BP (r=0.41-0.47, P<0.01). Correlations with renal length and the number of renal cysts were somewhat less (r=0.29-0.43, P<0.05 and 0.01, respectively). This study revealed a significant relationship between renal volume, renal length and number of renal cysts and BP. It is suggested that children with ADPKD should regularly be checked for BP changes by ABPM, especially those who show increased renal size or a high number of renal cysts on ultrasound. All these children are at high risk for development of hypertension.


Interactions between monogenean parasites and their fish hosts.
Parasite factors associated with recognition and selection of the host and the mechanisms in the host responsible for acceptance or rejection of the invading organism were evaluated. Sensory structures in parasites are able to detect differences between different fish species and this ability to discern between fishes may be based on both chemical and mechanical stimuli on the host surface. Complex glycoproteins, proteins, carbohydrates and simple molecules attract parasites or modify their behaviour. Furthermore, attachment of the monogenean parasite to a host is dependent on both mechanical structures and chemical factors in the parasite. These systems comprise anterior pads, posterior haptors, gland secretions, and muscular elements. The parasite needs access to appropriate nutrients which can be absorbed and used for reproduction and in this context signals from the host are needed for an optimal physiological response of the parasite. The innate and adaptive immune systems of the host are important elements in this question. Investigations have indicated that innate host factors (complement, lectins, acute phase reactants, macrophages) can bind to monogeneans and elicit severe damage to the parasites. The targets for these hostile products are not only the monogenean tegument, but may involve the gastrodermis and glands. However, the parasite's ability to avoid and even exploit the wide array of immunological elements of the host may be an important player in the dynamic interactions between host and monogenean determining host specificity. Even fish hosts susceptible to a certain parasite show an ability to mount a protective response at post-infection periods. Elevation of the host's production of adaptive and non-adaptive factors following monogenean infections of a certain duration may explain the acquired response.


Ultrasensitive tumour-penetrating nanosensors of protease activity.
The ability to identify cancer lesions with endogenous biomarkers is currently limited to tumours ~1 cm in diameter. We recently reported an exogenously administered tumour-penetrating nanosensor that sheds, in response to tumour-specific proteases, peptide fragments that can then be detected in the urine. Here, we report the optimization, informed by a pharmacokinetic mathematical model, of the surface presentation of the peptide substrates to both enhance on-target protease cleavage and minimize off-target cleavage, and of the functionalization of the nanosensors with tumour-penetrating ligands that engage active trafficking pathways to increase activation in the tumour microenvironment. The resulting nanosensor discriminated sub-5 mm lesions in human epithelial tumours and detected nodules with median diameters smaller than 2 mm in an orthotopic model of ovarian cancer. We also demonstrate enhanced receptor-dependent specificity of signal generation in the urine in an immunocompetent model of colorectal liver metastases, and in situ activation of the nanosensors in human tumour microarrays when re-engineered as fluorogenic zymography probes.


Effect of cardiac rehabilitation on postprandial response to a high fat meal in patients with coronary artery disease.
Past studies have shown decreased lipemic responses to a high fat meal in healthy trained vs. untrained subjects. The purpose of this study was to characterize fasting lipid profiles and lipemic responses in 13 male cardiac patients (6 in cardiac rehabilitation (CR) and 7 controls (NONCR]. Body composition and dietary composition were assessed. Plasma total cholesterol (TC), HDL-cholesterol (HDL-C) and triglyceride (TG) were determined after a 12-h fast. Subjects consumed a high fat meal (60% of calories) and the lipemic response to the meal was assessed by determining plasma TG hourly for 8 h following the meal. CR had a lower percent body fat than NONCR (26% vs. 34%, P less than 0.05). CR consumed fewer calories from fat than NONCR (28% vs. 41%, P less than 0.05). There were no significant differences between groups in TC, HDL-C or TG, although the differences approached significance (P less than 0.10). CR had a lower TC/HDL-C ratio than NONCR (5.0 vs. 7.7, P less than 0.05). Lipemic responses between groups were similar. There was no significant difference in peak TG, time to peak TG, or area under the TG curve between CR and NONCR groups. Thus, subjects undergoing cardiac rehabilitation appear to have both a more favorable diet and fasting lipid profile than NONCR; however, both groups had a similar response to a high fat meal.


BubR1 insufficiency impairs angiogenesis in aging and in experimental critical limb ischemic mice.
Budding uninhibited by benzimidazole-related 1 (BubR1), a cell cycle-related protein, is an essential component of the spindle checkpoint that regulates cell division. Mice in which BubR1 expression is reduced to 10% of the normal level display the phenotypic features of progeria. However, the role of BubR1 in vascular diseases and angiogenesis remains unknown. To investigate the influence of BubR1 on angiogenesis, we generated a low-null-BubR1-expressing (BubR1L/-) mouse strain with reduced BubR1 expression as low as 15% of the normal level without any abnormalities in appearance. To elucidate the role of BubR1 in angiogenesis, we used a hind limb ischemia model induced in BubR1L/- mice and age-matched wild-type (WT) littermates. To evaluate the pathologic influence of BubR1 on angiogenesis, we measured the blood flow before and after hind limb ischemia surgery, and the expression of typical angiogenic factors in vivo and in vitro. In WT mice, blood flow in the ischemic left limb gradually recovered to approximately 80%, 14 days after surgery. Conversely, in the BubR1L/- group, blood flow in the left ischemic limb recovered to at most 30% (14 days after surgery, P < .01; immediately after the operation, and 5 and 9 days after surgery, P < .05). In adductor and calf muscles from BubR1L/- mice, regenerated muscle bundles, granulation tissue, and inflammatory cell invasion were more evident than in calf muscles from WT mice at 14 days after surgery. All WT mice at 14 days after surgery had complete limb salvage, but loss of limbs was observed in approximately 70% of BubR1L/- mice (P < .05). The vascular endothelial growth factor protein increase in ischemic hind limb muscles was lower in BubR1L/- mice compared with WT mice (P < .05), and vascular endothelial growth factor levels in human aortic smooth muscle cells treated with BubR1 knockdown siRNA were lower compared with scramble siRNA under hypoxic conditions (P < .01). HIF1α protein levels in the muscles after hind limb ischemia surgery were also significantly lower in BubR1L/- mice compared with WT mice (P < .05). BubR1 insufficiency impairs angiogenesis and results in limb loss in ischemic hind limbs. BubR1 may be a crucial angiogenic factor and might be beneficial for the treatment of limb ischemia.


Diagnostic performance of screening mammography according to menstrual cycle among Asian women.
To investigate the performance metrics of screening mammography according to menstrual cycle week in premenopausal Asian women. This retrospective study included 69,556 premenopausal Asian women who underwent their first screening mammography between 2011 and 2019. The presence or absence of a breast cancer diagnosis within 12 months after the index screening mammography served as the reference standard, determined by linking the study data to the national cancer registry data. Menstrual cycles were calculated, and participants were assigned to groups according to weeks 1-4. The performance metrics included cancer detection rate (CDR), sensitivity, specificity, and positive predictive value (PPV), with comparisons across menstrual cycles. Among menstrual cycles, the lowest CDR at 4.7 per 1000 women (95% confidence interval [CI], 3.8-5.8 per 1000 women) was observed in week 4 (all P < 0.05). The highest sensitivity of 72.7% (95% CI, 61.4-82.3) was observed in week 1, although the results failed to reach statistical significance. The highest specificity of 80.4% (95% CI, 79.5-81.3%) was observed in week 1 (P = 0.01). The lowest PPV of 2.2% (95% CI, 1.8-2.7) was observed in week 4 (all P < 0.05). Screening mammography tended to show a higher performance during week 1 and a lower performance during week 4 of the menstrual cycle among Asian women. These results emphasize the importance of timing recommendations that consider menstrual cycles to optimize the effectiveness of screening mammography for breast cancer detection.


Lack of prognostic significance of conventional peritoneal cytology in colorectal and gastric cancers: results of EVOCAPE 2 multicentre prospective study.
In digestive cancers, the prognostic significance of intraperitoneal free cancer cells remains unclear (IPCC). The main objective of this study was to assess the prognostic significance of IPCC in colorectal and gastric adenocarcinoma. The secondary objectives were to evaluate the predictive significance of IPCC for the development of peritoneal carcinomatosis (PC) and to evaluate the prevalence of synchronous PC and IPCC. This was a prospective multicentre study. All patients undergoing surgery for a digestive tract cancer had peritoneal cytology taken. Patients with gastric and colorectal cancer with no residual tumour after surgery and no evidence of PC were followed-up for 2 years. The primary end point was overall survival. Between 2002 and 2007, 1364 patients were enrolled and 956 were followed-up over 2 years. Prevalence of IPCC was 5.7% in colon cancer, 0.6% in rectal cancer and 19.5% in gastric cancer. The overall 2-year survival rate for patients with IPCC was 34.7% versus 86.8% for patients with negative cytology (p<0.0001). By multivariate analysis, IPCC was not an independent prognostic factor. No relationship between cytology and recurrence was found. The presence of IPCC was not an independent prognostic and didn't add any additional prognostic information to the usual prognostic factors related to the tumour (pTNM and differentiation). Moreover the presence of IPCC detected with this method didn't appear to predict development of PC. Peritoneal cytology using conventional staining doesn't seem to be a useful tool for the staging of colorectal and gastric cancers.


Leopold Ordenstein: on paralysis agitans and multiple sclerosis.
In 1868 the German Leopold Ordenstein (1835-1902) published in Paris a doctoral thesis in French language under the patronage of Jean-Martin Charcot (1825-1893). For the first time, multiple sclerosis and Parkinson's disease were clearly recognized as different clinical entities, based on clinical and pathological data. Ordenstein's work represents today a fundamental and often credited, yet still widely unknown, contribution to the history of these two diseases. The present paper delivers a synopsis of this key document. In addition, the life and work of Leopold Ordenstein will be reviewed.


Mechanistic Investigation of Curcuma Protection against Oral Submucous Fibrosis.
Oral submucous fibrosis (OSMF) is a chronic, fibrotic disease that affects the oral cavity, showing a high rate of malignant transformation. Curcuma exerts therapeutic potentials in many diseases including OSMF. However, the potential targets and pathways to explain the therapeutic effects of curcuma on OSMF are outside the scope of present knowledge. Herein we intend to reveal the predictive targets and potential pathways of curcuma against OSMF by a network pharmacology-based approach followed by molecular docking technology. We searched the SymMap, GeneCards, and OMIM database to obtain curcuma and OSMF common targets. The protein-protein interaction (PPI) of curcuma and OSMF common targets were then analyzed, followed by functional enrichment analysis. The best binding mode of curcuma and target proteins was analyzed by molecular docking technology. We collected 290 putative targets of curcuma molecules and 600 known therapeutic targets of OSMF, with 64 curcuma and OSMF common targets sorted out. In the PPI network, there were 63 nodes with 922 edges. The node indicates protein and the line indicates PPI relation. The most enriched GO term in the BP level is "gland development", followed by "cellular response to chemical stress", and then "response to oxygen levels", while the most enriched GO term in CC and MF is "membrane raft" and "cytokine receptor binding", respectively. We also found 131 KEGG pathways significantly enriched by curcuma and OSMF common targets. The binding energy of curcuma to ALB, TNF, TP53, IL6, and VEGFA was -9.5 kcal/mol, -3.9 kcal/mol, -3.5 kcal/mol, -3.6 kcal/mol, and -8.9 kcal/mol, respectively, which suggested ALB and VEGFA were regarded as main targets involving in the potential mechanism of curcuma against OSMF. The present study illustrated that the therapeutic effects of curcuma on OSMF were achieved by targeting ALB and VEGFA, which giving reference to further drug design and development for OSMF.


Distribution patterns and community assembly processes of eukaryotic microorganisms along an altitudinal gradient in the middle reaches of the Yarlung Zangbo River.
Eukaryotic microorganisms play an important role in the biogeochemical cycles of rivers. Dynamic hydrological processes in rivers are thought to influence the assembly processes of eukaryotic microbes, as well as affecting local geomorphology. These processes have not been extensively studied for eukaryotic river microbes in extreme environments on the Tibetan Plateau. This study used 18S rDNA gene amplification sequencing, a neutral community model, and a null model to analyze the spatial and temporal dynamics and assembly processes of eukaryotic microbial communities in the middle reaches of the Yarlung Zangbo River. We conducted analyses across wet and dry seasons, as well as varying altitudinal gradients. Our results showed that the diversity, structure, and taxonomic composition of eukaryotic microbial communities varied more with altitude than season, and the diversity of the communities first increased, then decreased, with increasing elevation. Distance-decay analysis showed that the correlation between eukaryotic microbial communities and environmental distance was stronger than the correlation between the microbial communities and geographical distance. Deterministic processes (homogeneous selection) dominated the construction of eukaryotic microbial communities, and water temperature, pH, and total phosphorus were the primary environmental factors that influenced the construction of eukaryotic microbial communities. These results expand our understanding of the characteristics of eukaryotic microbial communities in rivers on the Tibetan Plateau and provide clues to understanding the mechanisms that maintain eukaryotic microbial diversity in extreme environments.


Allergic rhinitis: a growing primary care challenge.
To describe the growing problem of allergic rhinitis (AR) and the latest recommendations on its diagnosis and management for the nurse practitioner (NP) in primary care settings. Recent clinical research, review articles and consensus guidelines, and the author's clinical experience. The prevalence of AR is increasing, possibly due to increased airborne pollutants, poor ventilation, and rising levels of indoor allergens. Allergic disease is systemic and rarely involves a single symptom. Treatments include reducing exposure to allergens as well as pharmacotherapy. Patient education is crucial for successful management and includes understanding the allergic basis of symptoms, reducing allergen exposure, understanding proper use of medications, and reassessing the plan on a regular basis.


Our experience with the anterior interosseous artery fasciocutaneous flap for local and distant soft tissue reconstructions.
Martin and his colleagues in 1989 described for the first time a fasciocutaneous flap based on a posterior branch of the anterior interosseous artery (AIA). Despite its promising characteristics, this flap never achieved popularity and the literature about it is limited. The aim of the present study is to share our experience with the AIA flap both as a local and free flap in reconstructing defects of various body regions. A retrospective review of 26 consecutive patients operated between January2001 and August 2020 was conducted. Seventeen male and nine female patients, mean age 52 years, underwent reconstruction of local and distant soft tissue defects using the AIA flap. Fourteen flaps were raised as free flap and 12 as local flaps for a total of 26 flaps. The locations of the defects included the face, the lower limb, the hand dorsum, and fingers. Twenty-four out of 26 flaps survived completely, and two pedicled flaps presented partial necrosis, with one requiring a new free flap procedure. One free anterior interosseous flap required revision of the venous anastomosis. Two donor site dehiscence were observed, and they both healed by secondary intention healing. Follow-ups were conducted for a mean of 18 months. All patients showed good contour restoration of the affected body part. The AIA flap, either free or pedicled, represents a reliable tool to perform "like-with-like" reconstructions of hand defects. In some occasions, it is well suited for shallow defects in other body parts.


Small bowel capsule endoscopy in obscure gastrointestinal bleeding: A matched cohort comparison of patients with normal vs surgically altered gastric anatomy.
Little is known about small bowel capsule endoscopy (SBCE) outcomes in patients with surgically altered anatomy. To assess the feasibility and diagnostic yield of orally ingested SBCE to investigate obscure gastrointestinal bleeding (OGIB) in patients with surgically altered gastric anatomy, compared to native gastric anatomy. 207 patients with OGIB were selected from an open, multicenter, retrospective cohort (SAGA study) and match-paired according to age, gender and bleeding type (overt/occult) to 207 control patients from a randomized controlled trial (PREPINTEST). Primary outcomes were the diagnostic yield (P1 or P2 findings), completion rate, adverse events rate, and small bowel transit time (SBTT). The diagnostic yield was not statistically different between groups (44.9% in SAGA vs 42.5% in control patients). Inflammatory/ulcerated lesions were significantly more frequent in patients with SAGA (43.0% vs 29.3%). The median SBTT was significantly longer in the SAGA group than in control patients (283 vs 206 minutes), with a significantly lower completion rate (82.6% vs 89.9%); Adverse events were scarce (0.5% vs 0.0%). Patients with surgically altered gastric anatomy should benefit from SBCE investigation for OGIB as much as non-operated patients.


Specifying the effects of physician's communication on patients' outcomes: A randomised controlled trial.
To experimentally test the effects of physician's affect-oriented communication and inducing expectations on outcomes in patients with menstrual pain. Using a 2×2 RCT design, four videotaped simulated medical consultations were used, depicting a physician and a patient with menstrual pain. In the videos, two elements of physician's communication were manipulated: (1) affect-oriented communication (positive: warm, emphatic; versus negative: cold, formal), and (2) outcome expectation induction (positive versus uncertain). Participants (293 women with menstrual pain), acting as analogue patients, viewed one of the four videos. Pre- and post video participants' outcomes (anxiety, mood, self-efficacy, outcome expectations, and satisfaction) were assessed. Positive affect-oriented communication reduced anxiety (p<0.001), negative mood (p=0.001), and increased satisfaction (p<0.001) compared to negative affect-oriented communication. Positive expectations increased feelings of self-efficacy (p<0.001) and outcome expectancies (p<0.001), compared to uncertain expectations, but did not reduce anxiety. The combination of positive affect-oriented communication and a positive expectation reduced anxiety (p=0.02), increased outcome expectancies (p=0.01) and satisfaction (p=0.001). Being empathic and inducing positive expectations have distinct and combined effects, demonstrating that both are needed to influence patients' outcomes for the best. Continued medical training is needed to harness placebo-effects of medical communication into practice.


Application of ultrasonic inspection in monitoring dynamic healing of mandibular fracture in rabbit model.
To investigate the feasibility of ultrasonic diagnosis for monitoring fracture healing. Thirty rabbit models with fraction of mandible body were established by surgically removing partial lower jawbone. At the 1st, 2nd, 4th, 6th, 8th and 12th week after the operation, they were examined by X-ray and ultrasound, respectively. All detection results were scored according to a generally accepted standard. Spearman rank correlation analysis was conducted to explore the relationship between the results of the two inspection methods. In each healing stage, the results of the ultrasonic inspection were basically consistent with those of the X-ray examination, as supported by a Spearman rank correlation coefficient of 0.892 (P<0.001). Non-invasive ultrasonic inspection can be used instead of X-ray examination to monitor and diagnose fracture healing.


The effects of dietary mackerel oil on the recovery of cardiac function after acute ischaemic events in the pig.
To investigate the effects of fish oil nutrition on cardiac haemodynamics and the biochemical response to ischaemia-reperfusion, young pigs (5 weeks old) were fed a 9% lard fat diet or a mixed diet of 4.5% mackerel oil and 4.5% lard fat for 16 weeks. In the mackerel oil fed pigs plasma cholesterol and triglyceride levels decreased by 22% and 58% (both p less than 0.05), respectively, while levels in the animals which received only lard fat did not change. The n-6 fatty acids present in cardiac and platelet membrane phospholipids underwent a partial replacement by n-3 fatty acids in the mackerel oil fed pigs. Under anaesthesia, multiple coronary artery occlusions (5 min) were interrupted by 10 min of reperfusion. The extent of recovery of cardiac function and reduction of adenine nucleotide levels were similar for both dietary groups. The incidence of reperfusion arrhythmias was significantly lower and the reactive hyperaemic responses were of longer duration in the mackerel oil fed animals. These effects cannot be explained by diet-induced alterations in thromboxane B2/6-keto-PGF1 alpha ratio, although a marked reduction in absolute levels of both prostaglandins was seen in the mackerel oil fed pigs (p less than 0.05). In conclusion, dietary fish oil caused changes in membrane fatty acid composition and plasma prostaglandin levels, although these did not affect alterations of cardiac performance during and after short periods of ischaemia.


Pressure-induced enhancement of the superconducting transition temperature in La2O2Bi3AgS6.
Charge density wave (CDW) instability is often found in phase diagrams of superconductors such as cuprates and certain transition-metal dichalcogenides. This proximity to superconductivity triggers the question on whether CDW instability is responsible for the pairing of electrons in these superconductors. However, this issue remains unclear and new systems are desired to provide a better picture. Here, we report the temperature-pressure phase diagram of a recently discovered BiS2superconductor La2O2Bi3AgS6, which shows a possible CDW transition atT* ∼ 155 K and a superconducting transition atTc∼ 1.0 K at ambient pressure, via electrical resistivity measurements. Upon applying pressure,T* decreases linearly and extrapolates to 0 K at 3.9 GPa. Meanwhile,Tcis enhanced and reaches maximum value of 4.1 K at 3.1 GPa, forming a superconducting dome in the temperature-pressure phase diagram.


Efficient and exceptionally selective semireduction of alkynes using a supported gold catalyst under a CO atmosphere.
A new efficient method for chemo- and regio-selective semireduction of alkynes using CO/H2O as the hydrogen source catalyzed by gold supported on high surface area TiO2 was developed. A facile and practical synthesis of 1,2-dideuterioalkenes was also realized by using CO/D2O as the reducing agent.


Genetic engineering of Escherichia coli for the production of NI,NII-diacetylchitobiose (chitinbiose) and its utilization as a primer for the synthesis of complex carbohydrates.
Chitinbiose was produced at more than 4 g L-1 by a high cell density culture of an Escherichia coli strain that co-expressed the rhizobial chitinoligosaccharide synthase gene nodC and a truncated form of the chitinase gene chiA which has been designed to be functionally produced in the E. coli cytoplasm. Chitinpentaose, which has previously been shown to be produced by the nodC protein in growing E. coli, was formed as an intermediate that was subsequently hydrolyzed into chitinbiose by the chitinase encoded by chiA. Chitinbiose was mainly recovered in the extracellular medium and to prevent its catabolism, the genes for the chitinbiose PTS permease had to be disrupted. When the additional gene lgtB for beta1,4-galactosyltransferase was expressed, intracellular chitinbiose was converted into the trisaccharide Galbeta-4GlcNAcbeta-4GlcNAc which could serve as acceptor for glycosyltransferase that recognize the terminal N-acetyllactosamine structure.


Laboratory wash resistance of long-lasting insecticidal nets.
Long-lasting insecticidal nets (LLINs) may eliminate the need for retreatment of mosquito nets used for the control of malaria and other vector-borne diseases. The efficacy of LLINs after repeated washing under laboratory conditions has been used to predict long-lasting efficacy under field conditions. We evaluated under laboratory conditions the wash resistance of two LLINs (PermaNet 1.0, Vestergaard-Frandsen, Denmark; Olyset, Sumitomo Chemical Co., Japan), two candidate LLINs (Dawa, Siamdutch Mosquito Netting Co., Thailand; Insector, Athanor, France) and a net treated with a process designed to increase its wash resistance and compared them with conventionally treated nets (deltamethrin, 25 mg/m(2)). Nets of all six types were washed using a standard protocol and tested weekly using WHO cone bioassays with Anopheles gambiae (Kisumu strain). The PermaNet 1.0 was the most wash resistant with >50% mosquito mortality in WHO cone bioassays after as many as 20 washes. The Dawa net also retained some activity after repeated washing but exhibited wide variation in insecticide retention and biological activity. The remaining nets lost >90% of their biological activity after six washes as measured by 24-h mortality of A. gambiae in WHO cone tests. After 20 washes, all nets lost >50% of their initial insecticide concentrations except for the Olyset net. After 20 washes, nets were heated for 4 h at 60 degrees C to determine whether biological activity could be restored by heat-assisted regeneration. Only the Olyset net was regenerated by heating, with average mosquito mortality and knockdown in WHO cone tests rising to >90% after heating for 4 h at 60 degrees C. However, regeneration of the biological activity of Olyset nets that had been washed three times did not occur at 30 degrees C or 35 degrees C after 12 weeks. The wash resistance of these LLINs corresponded well to their retention of biological activity observed in a field trial, suggesting that wash resistance may be a good predictor of the longevity of insecticidal activity of LLINs under field conditions.


Metabolomic Profiling of Adherent Mammalian Cells In Situ by LAESI-MS with Ion Mobility Separation.
Ambient ionization-based mass spectrometry (MS) methods coupled with ion mobility separation (IMS) have emerged as promising approaches for high-throughput in situ analysis for biomedical to environmental applications. These methods are capable of direct profiling and molecular imaging of metabolites, lipids, peptides, and xenobiotics from biological tissues with minimal sample preparation. Furthermore, employing IMS within the workflow improves the molecular coverage, resolves isobaric species, and improves biomolecule identifications through accurate collision cross section measurements. Laser ablation electrospray ionization (LAESI)-MS coupled with IMS has been successful in profiling and molecular imaging of small biomolecules directly from biological tissues and single cells. Herein, we describe a protocol for the direct analysis of adherent mammalian cells with limited perturbations by LAESI-IMS-MS. A benefit of IMS is that within the same LAESI acquisition, the spectral features related to the ESI background, washing buffer, and cell signal can be extracted and isolated separately.


Detailed phylogenetic analysis tracks transmission of distinct SARS-COV-2 variants from China and Europe to West Africa.
SARS-CoV-2, the virus causing the COVID-19 pandemic emerged in December 2019 in China and raised fears it could overwhelm healthcare systems worldwide. Mutations of the virus are monitored by the GISAID database from which we downloaded sequences from four West African countries Ghana, Gambia, Senegal and Nigeria from February 2020 to April 2020. We subjected the sequences to phylogenetic analysis employing the nextstrain pipeline. We found country-specific patterns of viral variants and supplemented that with data on novel variants from June 2021. Until April 2020, variants carrying the crucial Europe-associated D614G amino acid change were predominantly found in Senegal and Gambia, and combinations of late variants with and early variants without D614G in Ghana and Nigeria. In June 2021 all variants carried the D614G amino acid substitution. Senegal and Gambia exhibited again variants transmitted from Europe (alpha or delta), Ghana a combination of several variants and in Nigeria the original Eta variant. Detailed analysis of distinct samples revealed that some might have circulated latently and some reflect migration routes. The distinct patterns of variants within the West African countries point at their global transmission via air traffic predominantly from Europe and only limited transmission between the West African countries.


The vulnerable versatility of Salmonella antibiotic persisters during infection.
Tolerance and persistence are superficially similar phenomena by which bacteria survive bactericidal antibiotics. It is assumed that the same physiology underlies survival of individual tolerant and persistent bacteria. However, by comparing tolerance and persistence during Salmonella Typhimurium infection, we reveal that these two phenomena are underpinned by different bacterial physiologies. Multidrug-tolerant mutant Salmonella enter a near-dormant state protected from immune-mediated genotoxic damages. However, the numerous tolerant cells, optimized for survival, lack the capabilities necessary to initiate infection relapse following antibiotic withdrawal. In contrast, persisters retain an active state. This leaves them vulnerable to accumulation of macrophage-induced dsDNA breaks but concurrently confers the versatility to initiate infection relapse if protected by RecA-mediated DNA repair. Accordingly, recurrent, invasive, non-typhoidal Salmonella clinical isolates display hallmarks of persistence rather than tolerance during antibiotic treatment. Our study highlights the complex trade-off that antibiotic-recalcitrant Salmonella balance to act as a reservoir for infection relapse.


Acute non-lymphocytic leukemia following FAM combination adjuvant chemotherapy for gastric and lung adenocarcinoma.
We report 2 cases of acute non-lymphocytic leukemia with distinct clinical and karyotypic features shared by therapy-related acute non-lymphocytic leukemia occurring after adjuvant chemotherapy including 5-fluorouracil, doxorubicin and mitomycin C. Our observation suggests a causal relationship between exposure to mitomycin C and the occurrence of acute non-lymphocytic leukemia.


Molecular analysis of ARF1 expression profiles during development of physic nut (Jatropha curcas L.).
A cDNA clone designated arf1 was isolated from a physic nut (Jatropha curcas L.) endosperm cDNA library which encodes a small GTP-binding protein and has significant homology to ADP-ribosylation factors (ARF) in plants, animals and microbes. The cDNA contains an open reading frame that encodes a polypeptide of 181 amino acids with a calculated molecular mass of 20.7 kDa. The deduced amino acid sequence showed high homology to known ARFs from other organisms. The products of the arf1 obtained by overexpression in E. coli revealed the specific binding activity toward GTP. The expression of arf1 was observed in flowers, roots, stems and leaves as analyzed by RT-PCR, and its transcriptional level was highest in flowers. In particular, the accumulation of arf1 transcripts was different under various environmental stresses in seedlings. The results suggest that arf1 plays distinct physiological roles in Jatropha curcas cells.


Rationale and design of the ARAMIS trial: Anakinra versus placebo, a double blind randomized controlled trial for the treatment of acute myocarditis.
Acute myocarditis is an inflammation of the myocardium that can cause life-threatening events. However, anti-inflammatory strategies did not reduce the risk of clinical outcomes in randomized trials. Recently, experimental studies have suggested that specific blockade of the interleukin-1β immune innate pathway could be effective in acute myocarditis. To test the hypothesis that inhibition of the interleukin-1β immune innate pathway can reduce the risk of clinical events in acute myocarditis. The "Anakinra versus placebo double blind Randomized controlled trial for the treatment of Acute MyocarditIS" (ARAMIS) trial (ClinicalTrials.gov identifier: NCT03018834) is a national multicentre randomized parallel-group double blind study among symptomatic patients with elevated cardiac troponin and cardiac magnetic resonance-proven acute myocarditis. Patients (n=120) are randomized within 72hours of hospital admission to receive a daily subcutaneous dose of anakinra 100mg or placebo during the hospitalization, in addition to standard of care, including an angiotensin-converting enzyme inhibitor and a beta-blocker. The primary endpoint is the number of days alive free from any myocarditis complication, including ventricular arrhythmias, heart failure, recurrent chest pain requiring medication and ventricular dysfunction (defined as left ventricular ejection fraction<50%), from randomization to 28 days after hospital discharge. At 28 days after discharge, patients with normal left ventricular ejection fraction are then randomized to angiotensin-converting enzyme inhibitor continuation or discontinuation and all patients are followed for 1 year, with regular left ventricular function evaluation. ARAMIS is the first trial evaluating inhibition of the interleukin-1β immune innate pathway in the setting of acute myocarditis. Although of small size, it will be the largest randomized trial in acute myocarditis, a serious and poorly studied cardiac condition.


Radiation-Sterilization of Food: Treating Scanty Data from Inoculated Packs 1.
This paper is about the mathematical methods used in calculating the 12D radiation-dose for a food which has been subjected to an inoculated pack. It concerns the case in which only one partial-spoilage data point is obtained from the experiment. A simple, partly graphical procedure is described. This method is based on binomial confidence limits and furnishes an estimate that lies above the (unknown) true 12D value with probability greater than 90%. The method is applied to an inoculated pack for low-level nitrite/nitrate ham described by Anellis et al. (2).


Natural Language Processing in Pathology: Current Trends and Future Insights.
Natural language processing (NLP) plays a key role in advancing health care, being key to extracting structured information from electronic health reports. In the last decade, several advances in the field of pathology have been derived from the application of NLP to pathology reports. Herein, a comprehensive review of the most used NLP methods for extracting, coding, and organizing information from pathology reports is presented, including how the development of tools is used to improve workflow. In addition, this article discusses, from a practical point of view, the steps necessary to extract data and encode natural language information for its analytical processing, ranging from preprocessing of text to its inclusion in complex algorithms. Finally, the potential of NLP-based automatic solutions for improving workflow in pathology and their further applications in the near future is highlighted.


Transsphenoidal surgery for Rathke's cleft cyst can reduce headache severity and frequency.
The purpose of this study was to determine the effect of transsphenoidal surgery for Rathke's cleft cyst(RCC) on headache frequency, severity, and duration. The medical records of 43 consecutive patients who underwent transsphenoidal resection of a pathologically-proven RCC at our institution by the senior author (E.R.L.) between April 2008 and April 2014 were reviewed. Patients were called by telephone and asked to answer questions about the severity, location, type, duration,and quality of their headaches, both pre- and postoperatively.This information was joined with detailed data collected directly from each patient's medical record regarding headaches upon presentation and at 1-week,6-week, 3-month, and annual post-operative appointments. Twenty-three patients (53 %) responded to our telephone survey after repeated attempts at contact. Median follow-up was 64 months (range 6–83 months). Of these patients, 19 (82.6 %) reported pre-operative headaches,compared to 12 (52.2 %) who reported post-operative headaches (OR = 1.75, p = 0.02). Average headache severity on a 1–10 scale decreased from 6.4 (SD = 2.0)pre-operatively to 3.4 (SD = 1.9) post-operatively (p = 0.006), while average maximum severity decreased from 8.6 (SD = 2.2) pre-operatively to 4.0 (SD = 3.3)post-operatively (p<0.001). The frequency of headaches also decreased, from 18.1 (SD = 12.6) per month pre-operatively to 3.7 (SD = 8.4) per month post-operatively(p<0.001). Overall, 14 patients (60.9 %) reported improvement in their headaches, and three patients(13.0 %) reported that their headaches had completely resolved. In a carefully selected patient population,transsphenoidal surgery for RCC can reduce headache monthly frequency, average typical severity, and average maximum severity with minimal risk of morbidity or mortality.


Sex without crossing over in the yeast Saccharomycodes ludwigii.
Intermixing of genomes through meiotic reassortment and recombination of homologous chromosomes is a unifying theme of sexual reproduction in eukaryotic organisms and is considered crucial for their adaptive evolution. Previous studies of the budding yeast species Saccharomycodes ludwigii suggested that meiotic crossing over might be absent from its sexual life cycle, which is predominated by fertilization within the meiotic tetrad. We demonstrate that recombination is extremely suppressed during meiosis in Sd. ludwigii. DNA double-strand break formation by the conserved transesterase Spo11, processing and repair involving interhomolog interactions are required for normal meiosis but do not lead to crossing over. Although the species has retained an intact meiotic gene repertoire, genetic and population analyses suggest the exceptionally rare occurrence of meiotic crossovers in its genome. A strong AT bias of spontaneous mutations and the absence of recombination are likely responsible for its unusually low genomic GC level. Sd. ludwigii has followed a unique evolutionary trajectory that possibly derives fitness benefits from the combination of frequent mating between products of the same meiotic event with the extreme suppression of meiotic recombination. This life style ensures preservation of heterozygosity throughout its genome and may enable the species to adapt to its environment and survive with only minimal levels of rare meiotic recombination. We propose Sd. ludwigii as an excellent natural forum for the study of genome evolution and recombination rates.


Interaction of vanadium(V) oxoanions with ovalbumin and transfusion gelatin.
Vanadate(V) anions have been found to modulate the activity of a large number of enzymes. To elucidate these interactions, a physico-chemical study of the binding of meta-vanadate(V) with two typical proteins ovalbumin and transfusion gelatin has been taken up. The binding has been investigated by polarographic method at pHs 7.5 and 9.3, and at 30 degrees C. Values of intrinsic association constant, standard Gibb's free energy change, and the number of amino acids involved in these bindings are reported. Analysis of the binding sites has been done.


Engulfment and cell motility 1 (ELMO1) and apolipoprotein A1 (APOA1) as candidate genes for sickle cell nephropathy.
Sickle cell disease (SCD) and apolipoprotein L1 (APOL1) G1/G2 variants increase chronic kidney disease (CKD) risk in African Americans by poorly understood mechanisms. We applied bioinformatics to identify new candidate genes associated with SCD-related CKD. An interaction network demonstrated APOA1 connecting haemoglobin subunit β (HBB) and APOL1 with 36 other candidate genes. Gene expression revealed upregulation of engulfment and cell motility 1 (ELMO1) and downregulation of APOA1 in the kidney cortex of SCD versus non-SCD mice. Analysis of candidate genes identified ELMO1 rs10951509 to be associated with albuminuria and APOA1 rs11216132 with haemoglobinuria in patients with SCD. A bioinformatic approach highlights ELMO1 and APOA1 as potentially associated with SCD nephropathy.


The influence of flunixin on the response to Salmonella typhimurium endotoxin in calves.
The effects of intravenous injection of 0.5 microgram/kg body weight of Salmonella typhimurium endotoxin were studied in calves. The injection was followed by ruminal stasis and general dullness. The clinical signs disappeared within 24 hours. The injection was followed by a tremendous increase in the plasma level of 15-ketodihydro-PGF2 alpha, the main metabolite of PGF2 alpha. The injection was also associated with a profound leukopenia and significant decreases in the serum levels of iron, zinc and calcium. In order to study the role of prostaglandin (PG) for the development of endotoxin-induced changes a group of calves was pretreated with flunixin, a potent cyclo-oxygenase inhibitor, at a dose of 2.2 mg/kg body weight. Flunixin inhibited the PG release completely, but did not influence the other responses to endotoxin. The pyrogenic response to endotoxin was very moderate and it was suggested that fever is not the most suitable parameter for monitoring endotoxin effects in calves. The studied blood parameters (15-ketodihydro-PGF2 alpha, iron, zinc, calcium and the number of leukocytes) appeared to be much more sensitive.


Ecological Effect of Arginine on Oral Microbiota.
Dental caries is closely associated with the microbial dybiosis between acidogenic/aciduric pathogens and alkali-generating commensal bacteria colonized in the oral cavity. Our recent studies have shown that arginine may represent a promising anti-caries agent by modulating microbial composition in an in vitro consortium. However, the effect of arginine on the oral microbiota has yet to be comprehensively delineated in either clinical cohort or in vitro biofilm models that better represent the microbial diversity of oral cavity. Here, by employing a clinical cohort and a saliva-derived biofilm model, we demonstrated that arginine treatment could favorably modulate the oral microbiota of caries-active individuals. Specifically, treatment with arginine-containing dentifrice normalized the oral microbiota of caries-active individuals similar to that of caries-free controls in terms of microbial structure, abundance of typical species, enzymatic activities of glycolysis and alkali-generation related enzymes and their corresponding transcripts. Moreover, we found that combinatory use of arginine with fluoride could better enrich alkali-generating Streptococcus sanguinis and suppress acidogenic/aciduric Streptococcus mutans, and thus significantly retard the demineralizing capability of saliva-derived oral biofilm. Hence, we propose that fluoride and arginine have a potential synergistic effect in maintaining an eco-friendly oral microbial equilibrium in favor of better caries management.


Evaluation of the anterior chamber angle in glaucoma: a report by the american academy of ophthalmology.
To assess the published literature pertaining to the association between anterior segment imaging and gonioscopy and to determine whether such imaging aids in the diagnosis of primary angle closure (PAC). Literature searches of the PubMed and Cochrane Library databases were last conducted on July 6, 2011. The searches yielded 371 unique citations. Members of the Ophthalmic Technology Assessment Committee Glaucoma Panel reviewed the titles and abstracts of these articles and selected 134 of possible clinical significance for further review. The panel reviewed the full text of these articles and identified 79 studies meeting the inclusion criteria, for which the panel methodologist assigned a level of evidence based on a standardized grading scheme adopted by the American Academy of Ophthalmology. Three, 70, and 6 studies were rated as providing level I, II, and III evidence, respectively. Quantitative and qualitative parameters defined from ultrasound biomicroscopy (UBM), anterior segment optical coherence tomography (OCT), Scheimpflug photography, and the scanning peripheral anterior chamber depth analyzer (SPAC) demonstrate a strong association with the results of gonioscopy. There is substantial variability in the type of information obtained from each imaging method. Imaging of structures posterior to the iris is possible only with UBM. Direct imaging of the anterior chamber angle (ACA) is possible using UBM and OCT. The ability to acquire OCT images in a completely dark environment allows greater sensitivity in detecting eyes with appositional angle closure. Noncontact imaging using OCT, Scheimpflug photography, or SPAC makes these methods more attractive for large-scale PAC screening than contact imaging using UBM. Although there is evidence suggesting that anterior segment imaging provides useful information in the evaluation of PAC, none of these imaging methods provides sufficient information about the ACA anatomy to be considered a substitute for gonioscopy. Longitudinal studies are needed to validate the diagnostic significance of the parameters measured by these instruments for prospectively identifying individuals at risk for PAC. Proprietary or commercial disclosure may be found after the references.


Silyl-substituted amino acids: new routes to the construction of selectively functionalized peptidomimetics.
[reaction: see text]. Silylated amino acids have been incorporated into peptides and then converted into N-acyliminium ions with the use of an anodic oxidation reaction. The result is a method for selectively incorporating conformational constraints or external nucleophiles within the peptide.


Prevalence of left main coronary artery disease, of three- or four-vessel coronary artery disease, and of obstructive coronary artery disease in patients with and without peripheral arterial disease undergoing coronary angiography for suspected coronary artery disease.
Data from the present investigation showed that the prevalence of current cigarette smoking, current or ex-cigarette smoking, systemic hypertension, diabetes mellitus, and dyslipidemia was significantly higher in patients with peripheral arterial disease (PAD) than in patients without PAD. The present report also showed that compared with patients without PAD undergoing coronary angiography for suspected coronary artery disease (CAD), patients with PAD undergoing coronary angiography for suspected CAD had a higher prevalence of left main CAD (18% vs <1%), a higher prevalence of 3- or 4-vessel CAD (63% vs 11%), and a higher prevalence of obstructive CAD (98% vs 81%).


Gene rational design: the dawn of crop breeding.
Limited natural genetic diversity restricts the creation of excellent crops. Modeling-guided rational design represents a promising protein engineering technology to optimize existing genes for desired agronomic traits. Rational design coupled with other engineering approaches could also be applied in artificial gene improvement for the creation of economically valuable crops.


Valence excitations in electron microscopy: resolved and unresolved issues.
Recent progress in the interpretation of spatially localized valence loss spectra is outlined. For a well-defined geometry of dielectric interfaces, detailed and quantitative analysis is now possible. In other cases, useful results may still be available although the common assumption that the spectrum at each point should be directly related to that from a uniform reference sample of appropriate composition may not always be valid.


A bacterial cysteine protease effector protein interferes with photosynthesis to suppress plant innate immune responses.
The bacterial pathogen Pseudomonas syringae pv tomato DC3000 suppresses plant innate immunity with effector proteins injected by a type III secretion system (T3SS). The cysteine protease effector HopN1, which reduces the ability of DC3000 to elicit programmed cell death in non-host tobacco, was found to also suppress the production of defence-associated reactive oxygen species (ROS) and callose when delivered by Pseudomonas fluorescens heterologously expressing a P. syringae T3SS. Purified His(6) -tagged HopN1 was used to identify tomato PsbQ, a member of the oxygen evolving complex of photosystem II (PSII), as an interacting protein. HopN1 localized to chloroplasts and both degraded PsbQ and inhibited PSII activity in chloroplast preparations, whereas a HopN1(D299A) non-catalytic mutant lost these abilities. Gene silencing of NtPsbQ in tobacco compromised ROS production and programmed cell death by DC3000. Our data reveal PsbQ as a contributor to plant immunity responses and a target for pathogen suppression.


Altered sensitivity of forebrain neurones to iontophoretically applied noradrenaline in aging rats.
Responses of unidentified neurones in the rostral cerebral cortex to iontophoretically applied noradrenaline and GABA were compared in young (3-4 months old) and old (22-24 months old) albino rats. Depressant responses to noradrenaline were smaller in the older animals and this was manifested particularly as a decrease in response duration. Depressant responses to GABA did not differ significantly in the two groups. The results indicate that neurones in the cerebral cortex, as in the cerebellum, exhibit a decrease in postsynaptic responsiveness to noradrenaline with advancing age.


Supernumerary small chromosomal anomaly: report of three cases including one with a familial inversion of chromosome 5.
Three cases of a small supernumerary chromosomal anomaly of essentially unknown origin associated with wide variability of clinical expression are reported. Case II has, in addition, a pericentric inversion of chromosome 5, which enables us to propose a mechanism, involving an unsuccessful crossing over, for the origin of the supernumerary chromosome.


Effects of different starch structures on energy metabolism in pigs.
Starch is a major component of carbohydrates and a major energy source for monogastric animals. Starch is composed of amylose and amylopectin and has different physiological functions due to its different structure. It has been shown that the energy supply efficiency of amylose is lower than that of amylopectin. However, there are few studies on the effect of starch structure on the available energy of pigs. The purpose of this study was to measure the effect of different structures of starch in the diet on the net energy (NE) of pigs using a comparative slaughter method and to establish a prediction equation to estimate the NE of starch with different structures. Fifty-six barrows (initial BW 10.18 ± 0.11 kg) were used, and they were housed and fed individually. Pigs were divided into 7 treatments, with 8 replicates for each treatment and 1 pig for each replicate. One of the treatments was randomly selected as the initial slaughter group (ISG). Pigs in the remaining treatments were assigned to 6 diets, fed with basic diet and semi-pure diets with amylose/amylopectin ratio (AR) of 3.09, 1.47, 0.25, 0.15 and 0.12, respectively. The experiment lasted for 28 d. Results showed that compared with the high amylose (AM) groups (AR 3.09 and 1.47), the high amylopectin (AP) group (AR 0.15) significantly increased the final BW, average daily weight gain and average daily feed intake of pigs (P < 0.05), but the F:G of the AM group was lower (P < 0.01). In addition, AR 0.15 and 0.12 groups have higher (P < 0.01) nutrient digestibility of dry matter, crude protein, gross energy and crude ash. Meanwhile, compared with other groups, AR 0.15 group has a higher (P < 0.05) NE intake and energy retention (RE). The regressive equation for predicting with starch structures was established as RE = 1,235.243 - 48.298AM/AP (R2 = 0.657, P = 0.05). In conclusion, NE intake and RE of pigs augmented with the increase of dietary amylopectin content, indicating that diets high in amylopectin were more conducive to promoting the growth of pigs in the late conservation period.


American Brachytherapy Society radiation oncology alternative payment model task force: Quality measures and metrics for brachytherapy.
Brachytherapy is an essential technique to deliver radiation therapy and is involved in the treatment of multiple disease sites as monotherapy or as an adjunct to external beam radiation therapy. With a growing focus on the cost and value of cancer treatments as well as new payment models, it is essential that standardized quality measures and metrics exist to allow for straightforward assessment of brachytherapy quality and for the development of clinically significant and relevant clinical data elements. We present the American Brachytherapy Society consensus statement on quality measures and metrics for brachytherapy as well as suggested clinical data elements. Members of the American Brachytherapy Society with expertise in disease site specific brachytherapy created a consensus statement based on a literature review and clinical experience. Key quality measures (ex. workup, clinical indications), dosimetric metrics, and clinical data elements for brachytherapy were evaluated for each modality including breast cancer, cervical cancer, endometrial cancer, prostate cancer, keratinocyte carcinoma, soft tissue sarcoma, and uveal melanoma. This consensus statement provides standardized quality measures and dosimetric quality metrics as well as clinical data elements for each disease site to allow for standardized assessments of brachytherapy quality. Moving forward, a similar paradigm can be considered for external beam radiation therapy as well, providing comprehensive radiation therapy quality measures, metrics, and clinical data elements that can be incorporated into new payment models.


Rhegmatogenous retinal detachment after YAG laser posterior capsulotomy.
Twenty-five eyes in 24 patients with rhegmatogenous retinal detachment (RD) after YAG laser posterior capsulotomy were treated during 1984 and 1985. The average time from extracapsular cataract surgery to YAG capsulotomy was 15 months. The average interval from capsulotomy to RD was 6 months (median time, 3 1/2 months). In 8 of the 25 eyes, a risk factor for RD (i.e., high myopia, lattice degeneration, or a history of RD in the fellow eye) was present. All but one of the detachments was successfully repaired.