Meta-analysis of the effectiveness of psychological and medical treatments for binge-eating disorder (MetaBED): study protocol.
Binge-eating disorder (BED) was included as its own diagnostic entity in the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). An increasing number of treatment studies have been published, but an up-to-date comprehensive meta-analysis on diverse treatment approaches for BED is lacking. In an updated and extension of a previous meta-analysis, the goals of this study are to assess the short-term and long-term effectiveness of psychological and medical treatments for BED. We will search bibliographic databases and study registries, including manual searches for studies published before January 2016. The search strategy will include terms relating to binge eating and diverse forms of psychological and medical interventions. Language will be restricted to English. The studies included will be treatment studies, that is, randomised-controlled trials, and non-randomised and non-controlled studies, for individuals with BED (DSM-IV or DSM-5), and studies that provided a pre-treatment and at least one post-treatment or follow-up assessment of binge eating. The primary outcomes will be the number of binge-eating episodes, abstinence from binge eating and diagnosis of BED at post-treatment and/or follow-up(s), and changes from pre-treatment to post-treatment and/or follow-up(s). Likewise, as secondary outcomes, eating disorder and general psychopathology, quality of life, and body weight will be analysed and adverse events and treatment drop-out will be examined. Study search, selection and data extraction, including risk of bias assessment, will be independently performed by 2 reviewers and consensus will be sought. Moderator analyses will be conducted, and equity aspects will be considered. Sensitivity analyses will be conducted to determine the robustness of the results. Ethical approval is not required for this meta-analysis. Published in a peer-reviewed journal and disseminated electronically and in print, this meta-analysis will form the basis of the renewal of the German evidence-based S3 Guidelines of Diagnosis and Treatment of Eating Disorders, specifically BED. CRD42016043604.


Patterns and drivers of global gross nitrogen mineralization in soils.
Soil gross nitrogen (N) mineralization (GNM), a key microbial process in the global N cycle, is mainly controlled by climate and soil properties. This study provides for the first time a comprehensive analysis of the role of soil physicochemical properties and climate and their interactions with soil microbial biomass (MB) in controlling GNM globally. Through a meta-analysis of 970 observations from 337 published papers from various ecosystems, we found that GNM was positively correlated with MB, total carbon, total N and precipitation, and negatively correlated with bulk density (BD) and soil pH. Our multivariate analysis and structural equation modeling revealed that GNM is driven by MB and dominantly influenced by BD and precipitation. The higher total N accelerates GNM via increasing MB. The decrease in BD stimulates GNM via increasing total N and MB, whereas higher precipitation stimulates GNM via increasing total N. Moreover, the GNM varies with ecosystem type, being greater in forests and grasslands with high total carbon and MB contents and low BD and pH compared to croplands. The highest GNM was observed in tropical wet soils that receive high precipitation, which increases the supply of soil substrate (total N) to microbes. Our findings suggest that anthropogenic activities that affect soil microbial population size, BD, soil substrate availability, or soil pH may interact with changes in precipitation regime and land use to influence GNM, which may ultimately affect ecosystem productivity and N loss to the environment.


Characterization of Adults With Type 1 Diabetes Not Attending Self-Management Education Courses: The Barriers to Uptake of Type 1 Diabetes Education (BUD1E) Study.
People with type 1 diabetes mellitus (T1DM) are offered attendance at diabetes self-management education courses to provide them with skills for self-management of flexible insulin dose adjustment. Attendance is poor, even when courses are evidence-based and nationally available. To understand barriers to attendance, we sought common characteristics of nonattenders from adults with T1DM living in south London. Twenty-five in person semistructured interviews were carried out until thematic saturation occurred. Thematic framework analysis identified six themes: psychological capability, numerical capability, internal/external judgment, confidence in self, thirst for knowledge, and barriers to attendance. Characterization of response profiles according to the themes identified four different typologies. These identified typologies and themes for barriers to attending diabetes self-management courses suggest strategies to improve attendance and extend the benefit of such courses more widely.


Advocacy for children's mental health: a personal journey.
This article describes the ways in which I have tried, primarily as a policy researcher, to bring an advocacy perspective to my own work and, in collaboration with others, engage in efforts to improve the lives of children experiencing emotional and behavioral challenges as well as the lives of their families. It is organized in 3 sections. The 1st section highlights my early career path and its relation to advocacy. The 2nd section summarizes the policy research I have conducted that has given me a broad understanding of children's mental health. The 3rd highlights lessons for advocates and my view of critical recommendations for the future.


Cage-Walking: Vertex Differentiation by Palladium-Catalyzed Isomerization of B(9)-Bromo-meta-Carborane.
We report the first observed Pd-catalyzed isomerization ("cage-walking") of B(9)-bromo-meta-carborane during Pd-catalyzed cross-coupling, which enables the formation of B-O and B-N bonds at all boron vertices (B(2), B(4), B(5), and B(9)) of meta-carborane. Experimental and theoretical studies suggest this isomerization mechanism is strongly influenced by the steric crowding at the Pd catalyst by either a biaryl phosphine ligand and/or substrate. Ultimately, this "cage-walking" process provides a unique pathway to preferentially introduce functional groups at the B(2) vertex using B(9)-bromo-meta-carborane as the sole starting material through substrate control.


Beneficial effects of penicillamine treatment on hereditary avian muscular dystrophy.
Hereditary muscular dystrophy in chickens of the New Hampshire strain was treated with penicillamine from the 9th day after hatching to the 425th day. The adult maintenance dose for males was 50 mg/kg per day and for females, 13-65 mg/kg per day. In avian dystrophy, deterioration of the muscle fibers is evidenced in the 2nd mo by an inability of the birds to rise after falling on their backs and by a progressive rigidity of the wings. The drug delayed the onset of symptoms and partially alleviated the debilitating aspects of the disease. Penicillamine produced three major improvements: (a) better righting ability when birds were placed on their backs; (b) greater wing flexibility; (c) and suppression of plasma creatine phosphokinase activity. The results are statistically analyzed and discussed in relationship to Duchenne dystrophy. Normal birds were not affected by penicillamine as judged by these parameters. The rationale for using penicillamine, a sulfhydryl compound with reducing properties, was (a) to attempt to protect essential thiol enzymes in the anabolic and glycolytic pathways against inactivation and (b) to prevent collagen cross-linking and deposition in muscle. Although the precise mechanism of drug action has not been determined. the possible role of penicillamine in mitigating the symptoms of genetic dystrophy in man is under consideration. Further, penicillamine may have a more generalized application i the prevention of contractures in a variety of neuromuscular disorders.


Globus pallidus/putamen T1WI signal intensity ratio in grading and predicting prognosis of neonatal acute bilirubin encephalopathy.
This study sought to investigate the relationship between the globus pallidus/putamen T1 weighted image (T1WI) signal intensity ratio (G/P ratio) and the acute bilirubin encephalopathy (ABE) in neonates, and to develop a new strategy for the grading and prognosis of ABE based on the G/P ratio. A total of 77 full-term neonates with ABE were scored according to bilirubin-induced neurological dysfunction and divided into mild, moderate, and severe groups. Cranial magnetic resonance imaging examinations were performed and the G/P ratio was recorded. The follow-up reexaminations were carried out at 6 months, 1 year, and 2 years after the initial examination. The neonates were then divided into two groups, the good prognosis group and the kernicterus spectrum disorder (KSD) group, according to the evaluation of Gesell Developmental Schedules and Brainstem Audio Electric Potential at 6 months. The differences of G/P ratios were statistically significant, not only among the mild, moderate, and severe ABE groups for the initial examinations but also between the KSD and the good prognosis groups for the follow-up reexaminations. Therefore, the ABE grading model and prognosis predicting model could be established based on the G/P ratio. In the KSD group, the area under the receiver operating characteristic curve of the G/P ratio-based predicting model was 93.5%, the optimal critical point was 1.29, the sensitivity was 88.2%, and the specificity was 93.3%. The G/P ratio can be used as an indicating parameter for both the clinical grading of neonatal ABE and the assessment of neonatal ABE prognosis. Specifically, the G/P ratio greater than 1.29 indicates a KSD of neonatal ABE.


Serial extraction protocol: transitioning a hopeless dentition to a full-arch reconstruction.
Conversion of a hopeless dentition to a full-arch reconstruction can be a difficult period for patients if they have to wear a denture. A serial extraction protocol can help to avoid this dilemma. Protocols for serial extraction of teeth are presented. This methodology avoids having patients wear a denture while converting from a hopeless dentition to a full-arch reconstruction supported by dental implants. Treatment planning with regard to placing all implants in one round of implantation vs two or more rounds of implantation is reviewed. In addition, strategies to simplify treatment regimens are discussed. The presented protocols facilitate transitioning patients from a destroyed dentition to a full-arch reconstruction. These protocols also can be used for a segment of an arch.


The Symptoms Targeted for Monitoring in a Web-Based Tracking Tool by Caregivers of People With Dementia and Agitation: Cross-Sectional Study.
In people with dementia, neuropsychiatric symptoms (NPSs), especially agitation, are associated with worse quality of life and caregiver burden. As NPSs may vary with illness severity, knowledge of how people with dementia and their caregivers describe and rate the importance of agitation symptoms can improve the understanding of the clinical meaningfulness of the manifestations of agitation. The internet provides new opportunities to better understand patient experiences, as patients and caregivers increasingly look to Web-based platforms as a means of managing symptoms. The aim of this study was to examine Web-based reports from a dementia symptom website to better understand the symptoms of agitation and explore how they are being targeted for monitoring by caregivers of people with dementia. The Dementia Guide website hosts a Web-based database used by caregivers (97%) and people with dementia (3%). From its 61 dementia symptoms, users can select relevant symptoms that they deem important to monitor or track the effects of treatment. We employed a staging algorithm to determine if individuals had mild cognitive impairment (MCI) or mild, moderate, or severe dementia. Agitation was defined using terms consistent with the International Psychogeriatrics Association's provisional consensus definition. We compared the proportion of people with NPSs and agitation across stages of dementia severity and studied how many agitation-defining descriptors were selected, and how often they occurred, by stage. As of March 2017, 4121 people had used the tracking tool, of whom 2577 provided sufficient data to allow disease severity staging. NPSs were tracked by 2127/2577 (82.54%) and agitation by 1898/2577 (73.65%). The proportion in whom agitation was tracked increased with increasing cognitive impairment: 68.5% (491/717) in people with MCI, and 72.50% (754/1040), 73.3% (378/516), and 90.5% (275/304) in mild, moderate, and severe dementia, respectively (χ23=54.9; P<.001). The number of NPS and agitation descriptors selected also increased with severity (median number of NPSs=1, 2, 2, and 3 for MCI, mild, moderate, and severe dementia, respectively, Kruskal-Wallis H Test H3=250.47; P<.001; median number of agitation descriptors=1, 2, 3, and 4, H3=146.11; P<.001). NPSs and agitation are common targets for tracking over the course of dementia and appear more frequently with increasing disease severity. These common and distressing symptoms represent clinically meaningful targets in treating people with dementia.


Ultrasonography of intrascrotal torsed appendages: size and interval between symptom onset and the ultrasonographic examination according to echogenicity.
This study investigated the size of torsed appendages and the interval between symptom onset and the ultrasonographic examination according to the echogenicity of the torsed appendages. This was a retrospective analysis of 54 cases in 46 patients with torsion of the testicular appendages between December 2008 and July 2021. Eight patients received follow-up ultrasonography 7-48 days after initial ultrasonography. The echogenicity of torsed appendages was classified into three groups: hypoechoic, hyperechoic, or isoechoic. The 54 torsed appendages were hypoechoic (n=40), hyperechoic (n=9), or isoechoic (n=5). The size of the torsed appendages ranged from 4 to 14 mm (8.0±3.1 mm) in hypoechoic torsed appendages and from 2.6 to 5.0 mm (3.7±0.9 mm) in hyperechoic torsed appendages. The interval between symptom onset and the ultrasonographic examination ranged from 0 to 17 days (4.2±4.4 days) in hypoechoic torsed appendages and from 8 to 48 days (29.8±16.0 days) in hyperechoic torsed appendages. The hyperechoic torsed appendages were smaller and had longer intervals between symptom onset and the ultrasonographic examination than the hypoechoic torsed appendages (P<0.05). Three hypoechoic torsed appendages and a single isoechoic torsed appendage on initial ultrasonography became hyperechoic on follow-up ultrasonography. The size of the torsed appendages and the interval between symptom onset and the ultrasonographic examination varied according to the echogenicity of the torsed appendages. The hyperechoic torsed appendages were smaller and had longer intervals until the examination than the hypoechoic torsed appendages.


New insight into the electronic shell of Au(38)(SR)(24): a superatomic molecule.
Based on the recently proposed super valence bond model, in which superatoms can compose superatomic molecules by sharing valence pairs and nuclei for shell closure, the 23c-14e bi-icosahedral Au(23)((+9)) core of Au(38)(SR)(24) is proved to be a superatomic molecule. Molecular orbital analysis reveals that the Au(23)((+9)) core is an exact analogue of the F(2) molecule in electronic configuration. Chemical bonding analysis by the adaptive natural density partitioning method confirms the superatomic molecule bonding framework of Au(38)(SR)(24) in a straightforward manner.


Synchronization engineering: theoretical framework and application to dynamical clustering.
A method for engineering the global behavior of populations of rhythmic elements is presented. The framework, which is based on phase models, allows a nonlinear time-delayed global feedback signal to be constructed which produces an interaction function corresponding to the desired behavior of the system. It is shown theoretically and confirmed in numerical simulations that a polynomial, delayed feedback is a versatile tool to tune synchronization patterns. Dynamical states consisting of one to four clusters were engineered to demonstrate the application of synchronization engineering in an experimental electrochemical system.


Medical Incidents and Evacuations on Wilderness Expeditions for the Northwest Outward Bound School.
Outdoor education (OE) expeditions travel far from definitive care and have unique epidemiology. Most OE expedition studies have examined a single organization and results may not generalize. This study examines the injuries, illnesses, medical evacuations, and nonmedical incidents of the Northwest Outward Bound School (NWOBS) to broaden our understanding and demonstrate commonalities within the field. This retrospective database review examined incidents and evacuations on NWOBS expeditions from June 1, 2014 through October 31, 2016. Incident rates, evacuation rates, and incident type frequencies were calculated. Frequencies of incidents during different expedition time periods were compared with a 1-sample χ2 test. The odds ratio that each type of incident would require evacuation was calculated and compared with other incident types using Fisher exact test. The study period included 59,058 program days, 277 incidents, 143 medical incidents, 75 medical evacuations, and no fatalities. Injuries occurred at a rate of 1.64 per 1000 program days and illnesses at a rate of 0.78 per 1000 program days. The most common injuries were strains, sprains, and trauma or infection of the skin and soft tissue. Most injuries occurred while backpacking, hiking, or moving around camp. The most common illnesses were nausea, vomiting, diarrhea, abdominal pain, asthma, respiratory infections, and urinary tract infections. The medical incidents with the highest odds of evacuation were fractures, urinary tract infections, abdominal pain, and asthma. Results from the NWOBS database are consistent with those from other expeditionary OE programs. These findings should guide risk-management strategies and staff medical training.


Synergism between a serotonin 5-HT2A receptor (5-HT2AR) antagonist and 5-HT2CR agonist suggests new pharmacotherapeutics for cocaine addiction.
Relapse to cocaine dependence, even after extended abstinence, involves a number of liability factors including impulsivity (predisposition toward rapid, unplanned reactions to stimuli without regard to negative consequences) and cue reactivity (sensitivity to cues associated with cocaine-taking which can promote cocaine-seeking). These factors have been mechanistically linked to serotonin (5-hydroxytryptamine, 5-HT) signaling through the 5-HT(2A) receptor (5-HT(2A)R) and 5-HT(2C)R; either a selective 5-HT(2A)R antagonist or a 5-HT(2C)R agonist suppresses impulsivity and cocaine-seeking in preclinical models. We conducted proof-of-concept analyses to evaluate whether a combination of 5-HT(2A)R antagonist plus 5-HT(2C)R agonist would have synergistic effects over these liability factors for relapse as measured in a 1-choice serial reaction time task and cocaine self-administration/reinstatement assay. Combined administration of a dose of the selective 5-HT(2A)R antagonist M100907 plus the 5-HT(2C)R agonist WAY163909, each ineffective alone, synergistically suppressed cocaine-induced hyperactivity, inherent and cocaine-evoked impulsive action, as well as cue- and cocaine-primed reinstatement of cocaine-seeking behavior. The identification of synergism between a 5-HT(2A)R antagonist plus a 5-HT(2C)R agonist to attenuate these factors important in relapse indicates the promise of a bifunctional ligand as an anti-addiction pharmacotherapeutic, setting the stage to develop new ligands with improved efficacy, potency, selectivity, and in vivo profiles over the individual molecules.


Prevailing genotypes of hepatitis C virus in Saudi Arabia: a systematic analysis of evidence.
Although hepatitis C virus (HCV) genotype 4 has been reported to be prevalent in some countries of the Middle East, the genotype distribution in some geographical areas is not conclusive. We aimed to perform a meta-analysis on available literature on this issue in an attempt to identify or confirm the prevailing HCV genotypes in Saudi Arabia. We searched for reports describing genotypes in Saudi Arabia. A meta-analysis was performed on the samples in 18 studies, published between 1995 and 2011, in which HCV genotypes were identified. A total of 2277 specimens from 18 studies showed that 617, 82, 119 and 1198 subjects were HCV-positive for genotypes 1, 2, 3 and 4, respectively. The meta-analyses showed that there is a great deal of heterogeneity in estimated prevalence among the studies. The highest prevalence was found in genotype HCV-4, followed by HCV-1, HCV-3, and HCV-2. Our meta-analysei emphasizes that HCV genotype 4 is the most prevalent, followed by genotype 1. Further studies on genotype determination and subtype distribution are warranted.


Androgen replacement in the treatment of Klinefelter's syndrome: efficacy and safety of a nonscrotal permeation-enhanced testosterone transdermal system.
To report the efficacy and safety of a permeation-enhanced nonscrotal testosterone transdermal (TTD) system for the treatment of Klinefelter's syndrome. Fifteen male patients with Klinefelter's syndrome, including 12 patients who received previous intramuscular (IM) treatment with testosterone esters, were part of the study population from three phase III clinical studies; 13 completed the studies. Patients applied two TTD systems nightly for 6 months or more. Nocturnal erections were assessed by RigiScan monitoring; sexual function was evaluated by using the Watts and Davidson questionnaires. Hypogonadal symptoms were determined by direct patient questioning. Mean morning serum testosterone levels increased to within normal range in all 13 patients (from 5.9 +/- 3.2 nmol/L at hypogonadal baseline to 22.3 +/- 5.6 nmol/L at 6 months). Luteinizing hormone levels decreased to within normal range in six patients and showed clinically significant decreases in four of the other seven patients (from 25 +/- 12 IU/L at hypogonadal baseline to 17 +/- 11 IU/L at 6 months). Nocturnal erections improved significantly during TTD system therapy in comparison with the hypogonadal state. Patient self-reported measures of sexual functioning were comparable to those during prior IM testosterone treatment and better than during the hypogonadal state. Hypogonadal symptoms decreased during TTD therapy in comparison with hypogonadal baseline. No clinically significant changes were noted in prostate volume, prostate-specific antigen, or lipid values. Three patients experienced anxiety or depression during TTD treatment, requiring discontinuation of therapy in one case and use of antidepressants in the other two. The testosterone patches were generally well tolerated in all patients. The nonscrotal TTD system for testosterone replacement is a safe and effective treatment for patients with Klinefelter's syndrome.


Evaluation of Sensibility Threshold for Interocclusal Thickness of Patients Wearing Complete Dentures.
The aim of this study was to evaluate sensibility threshold for interocclusal thickness in experienced and nonexperienced denture wearers after the insertion of new complete dentures. A total of 88 patients with complete dentures have participated in this study. The research was divided into two experimental groups, compared with the previous experience prosthetic dental treatment. The sensibility threshold for interocclusal thickness was measured with metal foil with 8 μm thickness and width of 8 mm, placed between the upper and lower incisor region. Statistical analysis was performed using standard software package BMDP (biomedical statistical package). Results suggest that time of measurement affects the average values of the sensibility threshold for interocclusal thickness (F = 242.68, p = 0.0000). Gender appeared to be a significant factor when it interacted with time measurement resulting in differences in sensibility threshold for interocclusal thickness (gender: F = 9.84, p = 0.018; F = 4.83, p = 0.0003). The sensibility threshold for interocclusal thickness was the most important functional adaptation in patient with complete dentures. A unique trait of this indicator is the progressive reduction of initial values and a tendency to reestablish the stationary state in the fifteenth week after dentures is taken off.


Automatic Measurement of the Total Visceral Adipose Tissue From Computed Tomography Images by Using a Multi-Atlas Segmentation Method.
The visceral adipose tissue (VAT) volume is a predictive and/or prognostic factor for many cancers. The objective of our study was to develop an automatic measurement of the whole VAT volume using a multi-atlas segmentation (MAS) method from a computed tomography. A total of 31 sets of whole-body computed tomography volume data were used. The reference VAT volume was defined on the basis of manual segmentation (VATMANUAL). We developed an algorithm, which measured automatically the VAT volumes using a MAS based on a nonrigid volume registration algorithm coupled with a selective and iterative method for performance level estimation (SIMPLE), called VATMAS_SIMPLE. The results were evaluated using intraclass correlation coefficient and dice similarity coefficients. The intraclass correlation coefficient of VATMAS_SIMPLE was excellent, at 0.976 (confidence interval, 0.943-0.989) (P < 0.001). The dice similarity coefficient of VATMAS_SIMPLE was also good, at 0.905 (SD, 0.076). This newly developed algorithm based on a MAS can measure accurately the whole abdominopelvic VAT.


Treatment of heroin dependence with buprenorphine in primary care.
Buprenorphine is an effective treatment for heroin dependence. The feasibility and potential efficacy of buprenorphine with brief counseling in primary care is unknown. We enrolled 14 heroin dependent patients in a 13-week clinical trial using thrice weekly buprenorphine along with brief counseling in the primary care center of an urban medical center. Primary outcomes included urine toxicology and treatment retention. Opioid-positive urine toxicology tests reduced over the 13-week period from 95 to 25% (p < 0.05). Eleven patients (79%) had greater than or equal to one week of opioid-free urine toxicologies. Nine patients (64%) had greater than or equal to three weeks of opioid-free urine toxicologies. Eleven patients (79%) were retained through the maintenance phase. We conclude that buprenorphine maintenance is feasible in a primary care setting.


Electrophysiological analysis of the mutated Na,K-ATPase cation binding pocket.
Na,K-ATPase mediates net electrogenic transport by extruding three Na+ ions and importing two K+ ions across the plasma membrane during each reaction cycle. We mutated putative cation coordinating amino acids in transmembrane hairpin M5-M6 of rat Na,K-ATPase: Asp776 (Gln, Asp, Ala), Glu779 (Asp, Gln, Ala), Asp804 (Glu, Asn, Ala), and Asp808 (Glu, Asn, Ala). Electrogenic cation transport properties of these 12 mutants were analyzed in two-electrode voltage-clamp experiments on Xenopus laevis oocytes by measuring the voltage dependence of K+-stimulated stationary currents and pre-steady-state currents under electrogenic Na+/Na+ exchange conditions. Whereas mutants D804N, D804A, and D808A hardly showed any Na+/K+ pump currents, the other constructs could be classified according to the [K+] and voltage dependence of their stationary currents; mutants N776A and E779Q behaved similarly to the wild-type enzyme. Mutants E779D, E779A, D808E, and D808N had in common a decreased apparent affinity for extracellular K+. Mutants N776Q, N776D, and D804E showed large deviations from the wild-type behavior; the currents generated by mutant N776D showed weaker voltage dependence, and the current-voltage curves of mutants N776Q and D804E exhibited a negative slope. The apparent rate constants determined from transient Na+/Na+ exchange currents are rather voltage-independent and at potentials above -60 mV faster than the wild type. Thus, the characteristic voltage-dependent increase of the rate constants at hyperpolarizing potentials is almost absent in these mutants. Accordingly, dislocating the carboxamide or carboxyl group of Asn776 and Asp804, respectively, decreases the extracellular Na+ affinity.


In-person, Hybrid, and Virtual Grand Rounds in Plastic Surgery: Impact and Participant Perceptions.
Many plastic surgery residency programs adapted to the COVID-19 pandemic by implementing virtual grand rounds. This study aimed to assess the impact of virtual grand rounds and how attendees perceived virtual grand rounds to inform future programmatic planning. This was a quality improvement initiative involving a cross-sectional survey and retrospective review of administrative records for the 2017-2018 (in-person) and 2021-2022 (virtual) academic years for two academic plastic surgery training programs in Boston, MA. Respondents were residents, fellows, and faculty within the two multisite plastic surgery residency training programs. There were 39 respondents (51% faculty, 41% residents, and 8% fellows). There was no evidence of different preferences for the format of future grand rounds (P = 0.08), with most preferring hybrid, defined as in person for speakers and others who could attend. Most respondents indicated a more accessible learning environment (86.8%) and lack of in-person interaction (82.1%) as reasons for liking and not liking virtual grand rounds, respectively. Excluding outliers, attendance in 2021-2022 was on average 7.4% points greater than that in 2017-2018 (P < 0.001), or six to seven more individuals at each session. There were significantly more out-of-state speakers in 2021-2022 (84%) as compared to 2017-2018 (28%) (P = 0.0008). Virtual grand rounds improved attendance and the geographic diversity of speakers. Attendees preferred a hybrid format for future grand rounds, citing advantages and disadvantages to both in-person and virtual formats.


Theoretical Studies on the Electronic Structure Parameters and Reactive Activity of Neu5Gc and Neu5Ac under Food Processing Solvent Environment.
The animal product hazard factor N-glycolylneuraminic (Neu5Gc) and brain nutrient substance N-acetylneuraminic acid (Neu5Ac) were studied at the M062X/6-311 + G(d,p) geometry optimization level. We considered the electronic structure parameters with different solvents: (benzene ε = 2.27, acetic acid ε = 6.25, ethanol ε = 24.85, lactic acid ε = 22.00, formic acid ε = 51.1, water ε = 78.35). The maximum molecular surface electrostatic potentials, which were 62.77 for Neu5Gc and 60.90 kcal/mol for Neu5Ac, are both located on the carboxyl group hydrogen. The orbital analysis showed that the amide group and carboxyl group confer the sites with susceptibility to nucleophilic and electrophilic attack, respectively. The solvent effect showed that polar solvents, such as formic acid and water, can enhance the two molecules' nucleophilic activity. To better understand the roles of the hydroxyl group in the two molecules, the independent gradient model theory confirmed the four intramolecular hydrogen bonds of Neu5Gc at gas phase, whereas Neu5Ac only has two. The lowest bond dissociation energy in solvent occurs at O7-H, which is 104.03 kcal/mol in water for Neu5Gc and 104.57 kcal/mol in lactic acid for Neu5Ac. The lowest proton affinity value for Neu5Gc (20.34 kcal/mol) and Neu5Ac (20.76 kcal/mol) was both occur at the carboxyl group O6-H under ethanol. The antioxidant mechanisms of the two sialic acid are prone to sequential proton-loss electron transfer under polar or non-polar solvents.


[Bladder lavage cytology in the diagnosis and follow-up of superficial bladder cancer].
Classical mictional cytology (MC) has a series of widely recognized limitations for the diagnosis and follow-up of surface vesical carcinoma (SVC). A prospective study was conducted in 171 patients with suspected signs and symptoms or a background of SVC using cystoscopy, MC and vesical lavage cytology (LC). Overall sensitivity was 98.8%, 45.4% and 66.6% respectively. LC showed a significant difference (p < 0.05) when compared to MC in suspected disease with no SVC background, and follow-up with endovesical prophylaxis.


Protein quality & amino acid requirements in relation to needs in India.
The relevance of protein and its constituent amino acids (AAs) in the structure and function of the human body is well known. Accumulating evidence has conferred specific functional and regulatory roles for individual AAs, adding relevance to their requirements across different age groups. The methods for measuring AA requirements have progressed from the classical nitrogen balance to the current stable isotope-based AA balance methods. Requirements of most of the indispensable AA (IAA) have been estimated in healthy Indian population by the best available balance method and has shown to be higher than earlier 1985 WHO/FAO/UNU (World Health Organization/Food and Agriculture Organization/United Nations University) recommendations. In addition, potential changes in the requirement, through adaptation to chronic undernutrition or to infection, have also been evaluated. In 2007, the WHO/FAO/UNU released a recommendation that increased the daily IAA requirement, based on primary evidence from Indian balance studies. This meant that to ensure that the new IAA requirements were met, individual foods or mixed diets needed to be assessed for their protein quality, or their ability to deliver the required amount of IAA. The recent FAO report on protein quality evaluation recommends the use of a new chemical AA score, the digestible IAA score (DIAAS), to replace the earlier protein digestibility corrected AA score. The DIAAS requires the determination of individual AA digestibility at the ileal level. A minimally invasive dual stable isotope tracer-based approach has been developed in India and has been used to determine digestibility of various foods in Indian adults and children. The increase in IAA requirements and subsequent protein quality requirements have implications for national regulatory frameworks, growth and development, and in turn, for economic and agricultural policy.


Analysis of DNS cache effects on query distribution.
This paper studies the DNS cache effects that occur on query distribution at the CN top-level domain (TLD) server. We first filter out the malformed DNS queries to purify the log data pollution according to six categories. A model for DNS resolution, more specifically DNS caching, is presented. We demonstrate the presence and magnitude of DNS cache effects and the cache sharing effects on the request distribution through analytic model and simulation. CN TLD log data results are provided and analyzed based on the cache model. The approximate TTL distribution for domain name is inferred quantificationally.


Social support and the quality of parenting under economic pressure and workload in Finland: the role of family structure and parental gender.
This study focused on how factors outside the home affect the quality of mothering and fathering. Economic pressure and workload were evaluated along with the compensating role of social support on parenting. Information was gathered from 842 mothers and 573 fathers including 139 single-mother and 21 single-father families. The results showed that the nature of the strains, together with parental gender and family structure, influenced their effects on parenting. The results further revealed some gender- and strain-specific protective functions of social support on parenting. For example, economic pressure was related to increased punitive parenting, which was compensated by instrumental and emotional support among the mothers. Workload was related to less authoritative single fathering, which was compensated by instrumental support.


[Experimental study of non-invasive percutaneous electrical stimulator for treatment of obstructive sleep apnea syndrome and its clinical effect].
To study the stimulation of the genioglossus with percutaneous biphasic current pulses as a new therapeutical method to treat the obstructive sleep apnea syndrome (OSAS), polysomnography (PSG) was used to synchronously monitor the patient. When OSAS was occurring, the stimulation with the optimal parameter was given in time to make the tongue move forward, the glossopharyngeal airway dilated, the resistance of the upper respiratory tract reduced, the hypoxia at night to be improved and the sleeping structure to be ameliorated because of the function of the dilated muscle of the upper airway. The results of the clinical therapeutic effect indicated that 17 of 22 patients with OSAS had cured effects, 2 of whom improved and 3 of whom were without effect. The effective rate was 77.27%. It is preliminarily proved that this is a new method in the treatment of patients suffered from OSAS.


Relaxation times measurement in single and multiply excited xenon clusters.
Direct measurement of the rates of nonradiative relaxation processes in electronically excited xenon clusters was carried out. The clusters were created in a pulsed supersonic beam and two-photon excited by femtosecond laser pulses with a wavelength of 263 nm. The measurements were performed using the pump-probe method and electron spectroscopy. It is shown that relaxation of light clusters XeN (N < 15) predominantly occurs by desorption of excited xenon atoms with a characteristic time constant of 3 ps. Heavier electronically excited clusters (N > 10) vibrationally relax to the lowest electronically excited state at a rate of about 0.075 eV/ps. Multiply excited clusters are deactivated via energy exchange between excited centers with the ionization of one of them. The production of electrons in this process occurs with a delay of ∼4 ps from the pump pulse, and the process is completed in 10 ps.


SrrB, a Pseudo-Receptor Protein, Acts as a Negative Regulator for Lankacidin and Lankamycin Production in Streptomyces rochei.
Streptomyces rochei 7434AN4, a producer of lankacidin (LC) and lankamycin (LM), carries many regulatory genes including a biosynthesis gene for signaling molecules SRBs (srrX), an SRB receptor gene (srrA), and a SARP (Streptomyces antibiotic regulatory protein) family activator gene (srrY). Our previous study revealed that the main regulatory cascade goes from srrX through srrA to srrY, leading to LC production, whereas srrY further regulates a second SARP gene srrZ to synthesize LM. In this study we extensively investigated the function of srrB, a pseudo-receptor gene, by analyzing antibiotic production and transcription. Metabolite analysis showed that the srrB mutation increased both LC and LM production over four-folds. Transcription, gel shift, and DNase I footprinting experiments revealed that srrB and srrY are expressed under the SRB/SrrA regulatory system, and at the later stage, SrrB represses srrY expression by binding to the promoter region of srrY. These findings confirmed that SrrB acts as a negative regulator of the activator gene srrY to control LC and LM production at the later stage of fermentation in S. rochei.


Male breast carcinoma: a clinicopathological and immunohistochemical characterization study.
Male breast carcinoma is a relatively rare disease. This study retrospectively investigated the clinicopathological features of 73 cases of male breast carcinoma in Chinese population, and classified the molecular subtype based on surrogate immunohistochemical definitions. The expression of GCDFP15, MGB, AR and FOXP1 were evaluated. Invasive carcinoma of no special type was the most common histological type in the study group (71.2%, 52/73). The luminal A and B subtypes were the major types of male breast carcinoma (60.9%, 34.8% respectively). AR and FOXP1 are expressed in 84.2% (48/57) and 71.9% (41/57) of the studied cases. Carcinoma of the luminal A subtype expressed GCDFP15 (73.5%, 25/34) and MGB (58.8%, 20/34) more frequently than cases of the luminal B subtypes (34.8%, 8/23 and 43.5%, 10/23, respectively; P = 0.004, P = 0.255, respectively). In conclusion, invasive carcinoma of no special type was the most common histological type in male breast carcinoma among Chinese population. Our study revealed that the luminal A and B subtypes were the major types of male breast carcinoma. AR and FOXP1 are highly expressed in male breast cancer. The luminal A subtype tends to express GCDFP15 and MGB more frequently than the luminal B subtype.


Asbestos exposure, cigarette smoking, and airflow limitation in long-term Canadian chrysotile miners and millers.
To investigate further the relationships of asbestos exposure, cigarette smoking, and airflow limitation, we have obtained detailed pulmonary function tests (PFT) in 331 long-term Canadian chrysotile workers, 34 of whom were lifetime nonsmokers. Three disease categories were defined on the bases of standard diagnostic criteria, gallium-67 lung uptake, and the lung pressure-volume curve. Category A was composed of workers without changes suggestive of alveolitis or asbestosis. There were eight nonsmokers (ns), among whom we found a statistically significant 30% reduction in airflow conductance (Gus) at low lung volume, which is consistent with the concept of an asbestos airway lesion. The 85 smokers (sm) of category A had reduction of Gus at both high and low lung volumes. Category B was composed of workers without asbestosis but with evidence of asbestos alveolitis. In the six ns, Gus was significantly reduced to 50% normal at low lung volume. The 59 sm had reduction of Gus at both high and low lung volumes but less severely than sm in category A. Category C was composed of workers with asbestosis. The 20 ns had restrictive pattern of lung function, and Gus was decreased to 39% normal at 50% TLC. The 153 sm in C had airflow reduction comparable to sm in B. We concluded that asbestos exposure, which leads to asbestos airway disease, asbestos peribronchiolar alveolitis, and asbestosis, causes airflow limitation at low lung volume but does not reduce the expiratory flow rates on the flow-volume curve in lifetime nonsmokers. In the smoking asbestos workers with alveolitis or asbestosis, the major component of airflow limitation is a smoking effect. In these smoking workers, rigidity of the lung lessens airflow obstruction associated with smoking at the expense of increased work of breathing.


Mannose 6-phosphate/insulin-like growth factor-II receptor targets the urokinase receptor to lysosomes via a novel binding interaction.
The urokinase-type plasminogen activator receptor (uPAR) plays an important role on the cell surface in mediating extracellular degradative processes and formation of active TGF-beta, and in nonproteolytic events such as cell adhesion, migration, and transmembrane signaling. We have searched for mechanisms that determine the cellular location of uPAR and may participate in its disposal. When using purified receptor preparations, we find that uPAR binds to the cation-independent, mannose 6-phosphate/insulin-like growth factor-II (IGF-II) receptor (CIMPR) with an affinity in the low micromolar range, but not to the 46-kD, cation-dependent, mannose 6-phosphate receptor (CDMPR). The binding is not perturbed by uPA and appears to involve domains DII + DIII of the uPAR protein moiety, but not the glycosylphosphatidylinositol anchor. The binding occurs at site(s) on the CIMPR different from those engaged in binding of mannose 6-phosphate epitopes or IGF-II. To evaluate the significance of the binding, immunofluorescence and immunoelectron microscopy studies were performed in transfected cells, and the results show that wild-type CIMPR, but not CIMPR lacking an intact sorting signal, modulates the subcellular distribution of uPAR and is capable of directing it to lysosomes. We conclude that a site within CIMPR, distinct from its previously known ligand binding sites, binds uPAR and modulates its subcellular distribution.


Cytoreductive nephrectomy in the age of immunotherapy-based combination treatment.
Renal cell carcinoma (RCC) displays a wide spectrum of oncological prognosis and clinical behavior, and is noted for its generally poor outcome in metastatic settings. However, the introduction of immunotherapy after the cytokine era has changed the landscape of treatment for metastatic RCC, outperforming previous targeted therapy and providing new hope for patients with advanced disease. Cytoreductive nephrectomy (CN) has been the center of controversy, with questionable survival benefit when compared to systemic therapy. Despite discouraging results from the two randomized clinical trials (CARMENA & SURTIME), interest into the role of CN is being rekindled, and contemporary real-world studies provide supporting evidence to suggest that CN may still have a role in well-selected patients treated or expecting treatment with immunotherapy, not only for symptomatic control but also for oncological benefit. In this review article, we attempt to review the modern insight into the role of CN for metastatic RCC in contemporary medicine, with a focus on treatment with immune checkpoint inhibitor combination-based immunotherapy.


[Histocompatibility HLA system of man. Considerations in the light of current concepts. VII. Nonclassical HLA- E, F, and H loci].
Current opinions connected with HLA-E and HLA-F genes determining "nonclassical" (HLA-Ib) class I antigens of the Main Histocompatibility Complex MHC, and formed in the consequence of mutation or partial deletion of HLA-H pseudogene loci were presented. The expression of protein products of HLA-E and -F genes on some cells and tissues, their polymorphism, and also their biological functions in organisms were qualified by the use of molecular technics. The kind and frequency of occurrence of mutations 845 A (C282Y) and 187 G (H63D) in gene HLA-H were analysed, and in this context some genetic aspects of hereditary hemochromatozy (HH) were discussed.


Cognitive Attributes of Adequate and Inadequate Responders to Reading Intervention in Middle School.
No studies have investigated the cognitive attributes of middle school students who are adequate and inadequate responders to Tier 2 reading intervention. We compared students in Grades 6 and 7 representing groups of adequate responders (n = 77) and inadequate responders who fell below criteria in (a) comprehension (n = 54); (b) fluency (n = 45); and (c) decoding, fluency, and comprehension (DFC; n = 45). These students received measures of phonological awareness, listening comprehension, rapid naming, processing speed, verbal knowledge, and nonverbal reasoning. Multivariate comparisons showed a significant Group-by-Task interaction: the comprehension-impaired group demonstrated primary difficulties with verbal knowledge and listening comprehension, the DFC group with phonological awareness, and the fluency-impaired group with phonological awareness and rapid naming. A series of regression models investigating whether responder status explained unique variation in cognitive skills yielded largely null results consistent with a continuum of severity associated with level of reading impairment, with no evidence for qualitative differences in the cognitive attributes of adequate and inadequate responders.


A comprehensive screening program for β-thalassemia and other hemoglobinopathies in the Hooghly District of West Bengal, India, dealing with 21 137 cases.
We here present a report of population screening programs (January 2012-December 2015) conducted by the Thalassemia Control Unit, Imambara Sadar Hospital, Chinsurah, Hooghly in the Hooghly District of West Bengal, India for prevention of thalassemia. We screened β-thalassemia (β-thal) heterozygotes and homozygotes, and Hb E (HBB: c.79G > A)-β-thal compound heterozygotes. Among 21 137 cases, we found 1968 heterozygotes and 192 homozygotes or compound heterozygotes. Results were evaluated with standard hematological analyses including red cell indices, hemoglobin (Hb) typing and quantification. The participants of the screening program were divided into six groups (children, pre-marriage cases, post-marital cases, family members of affected individuals, family members of carriers and pregnant women). While considering the average frequency of carriers, many reports recorded both related individuals (family members of trait and affected individuals) as well as unrelated individuals such as school children and pregnant women. These would have to be considered separately and only the unrelated individuals taken to estimate carrier frequencies in this article that would give more realistic data on carrier frequency of unrelated individuals.


Systematic Review With Meta-Analysis: Chronic Opioid Use Is Associated With Esophageal Dysmotility in Symptomatic Patients.
We aimed to conduct a systematic review and meta-analysis to assess the impact of chronic opioid exposure on esophageal motility in patients undergoing manometric evaluation. Multiple databases were searched through October 2022 for original studies comparing the manometric results of patients who have used chronic opioids (for >90 days) with those who do not. The primary outcomes were esophageal dysmotility disorders. Three high-resolution manometry parameters were conducted as secondary outcomes. A random-effects model was applied to calculate the odds ratio (OR) and means difference (MD) along with a 95% confidence interval (CI). Nine studies were included in this meta-analysis. Opioid use was associated with higher esophageal dysmotility disorders, including distal esophageal spasm (pooled OR 4.84, 95% CI 1.60-14.63, P = 0.005, I 2 = 96%), esophagogastric junction outflow obstruction (pooled OR 5.13, 95% CI 2.11-12.43, P = 0.0003, I 2 = 93%), and type III achalasia (pooled OR 4.15, 95% CI 2.15-8.03, P < 0.0001, I 2 = 64%). No significant differences were observed for hypercontractile esophagus, type I achalasia, or type II achalasia. The basal lower esophageal sphincter pressure (MD 3.02, 95% CI 1.55-4.50, P < 0.0001, I 2 = 90%), integrated relaxation pressure (MD 2.51, 95% CI 1.56-3.46, P < 0.00001, I 2 = 99%), and distal contractile integral (MD 640.29, 95% CI 469.56-811.03, P < 0.00001, I 2 = 91%) significantly differed between the opioid use and nonopioid use group. However, opioid use was associated with a lower risk of ineffective esophageal motility (pooled OR 0.68, 95% CI 0.49-0.95, P = 0.02, I 2 = 53%). Chronic opioid exposure is associated with an increased frequency esophageal dysmotility disorders. Our results revealed that opioid use is significantly associated with type III achalasia but not with type I and II achalasia. Therefore, opioid treatment should be taken into account as a potential underlying risk factor when diagnosing these major esophageal motor abnormalities.


WHO strategy for collecting safety data in public health programmes: complementing spontaneous reporting systems.
Globally, national pharmacovigilance systems rely on spontaneous reporting in which suspected adverse drug reactions (ADRs) are reported to a national coordinating centre by health professionals, manufacturers or patients. Spontaneous reporting systems are the easiest to establish and the cheapest to run but suffer from poor-quality reports and underreporting. It is difficult to estimate rates and frequencies of ADRs through spontaneous reporting. Public health programmes need to quantify and characterize risks to individuals and communities from their medicines, to minimize harm and improve use, to sustain public confidence in the programmes, and to track problems due to medication errors and poor quality medicines. Additional methods are therefore needed to monitor the quantitative aspects of medicine safety, to better identify specific risk factors and high-risk groups, and to characterize ADRs associated with specific medicines and in specific populations. The present paper introduces two methods, cohort event monitoring and targeted spontaneous reporting, that are being implemented by the WHO, in its public health programmes, to complement spontaneous reporting. The advantages and disadvantages of these methods and how each can be applied in clinical practice are discussed.


Inhibition of rat renin by antibody elicited against pure mouse renin and the effect on blood pressure.
Antibodies raised against mouse submaxillary renin showed affinity for rat renal renin. The affinity was characterized by enzyme kinetics in vitro. The antibodies and the purified Fab fragments showed total inhibition of rat renin, with a Ki of 6.5 +/- 0.7 x 10(-8)mol/l for the Fab fragments. The effect of enzymatic inhibition on blood pressure in anaesthetized rats was compared with converting enzyme inhibition. The antibodies showed a significant effect on blood pressure, with a depressor effect corresponding to that of the converting enzyme inhibitor [SQ 20 881]. The reduction of mean arterial pressure was from 116 +/- 3 to 108 +/- 3 mmHg for the antibodies and to 107 +/- 4 mmHg for the converting enzyme inhibitor. The pressor response of infused rat renal renin was totally blocked by the antibodies while pressor responses of angiotensin II were unchanged.


Constitutional partial 1q trisomy mosaicism and Wilms tumor.
We report on a female patient with severe-profound mental retardation, multiple congenital anomalies, as well as a history of mosaicism for partial 1q trisomy in the amniotic fluid and a previous Wilms tumor specimen. Peripheral blood and fibroblasts were studied and did not demonstrate the mosaicism initially detected for 1q. Array comparative genomic hybridization yielded negative results. Additional cytogenetic studies helped clarify the previous findings and revealed evidence of partial 1q trisomy mosaicism in normal kidney tissue and in a kidney lesion. GTG-banded results showing low-percentage mosaicism for the structural rearrangement der(1)t(1;1)(p36.1;q23) in both tissues were corroborated by fluorescence in situ hybridization studies. We hypothesize that the partial 1q trisomy predisposed the target tissue (in this case kidney) to neoplasia. This study provides further support for the hypothesis that certain constitutional chromosomal abnormalities can predispose to cancer. As detection of a low-percentage mosaicism may be hampered by the limits imposed by currently available technology and the constraint of a finite sample size, extra vigilance in monitoring other somatic tissues will be needed throughout the patient's lifetime. Anticipatory clinical guidance and prognostication are meaningful only if given accurate cytogenetic diagnoses. To the best of our knowledge, this is the first reported case of Wilms tumor associated with constitutional partial 1q trisomy, either in pure or mosaic form, with the particular 1q23 breakpoint in conjunction with a break on 1p36.1.


Genetic analysis of litter size in mice.
We performed quantitative trait locus (QTL) mapping analysis for litter size (total number of pups born and/or number of pups born alive) in 255 backcross mice derived from C57BL/6J and RR/Sgn inbred mice. We identified one significant QTL on chromosome 7 and 4 suggestive QTLs on chromosomes 3, 5, 10 and 13. In addition, two suggestive QTLs were identified on chromosomes 1 and 4 for the number of stillbirth. These results suggested that both litter size and number of stillbirth were heritable traits, although they were controlled by distinct genes. The RR allele was associated with reduced litter size and increased stillbirth at all QTLs. Therefore, RR mothers were observed to have reduced prolificacy in this particular genetic cross.


Variables correlated with early relapses after external electrical cardioversion of persistent atrial fibrillation.
The aim of this study was to identify the clinical and echocardiographic variables possibly correlated with the early relapses of atrial fibrillation (AF) after external electrical cardioversion (EC) in a large cohort of patients with persistent AF. Two hundred patients (117 males, 83 females, mean age 67.9 +/- 8.7 years) with successful EC of persistent AF (> 72 hours) were included in the present study. In order to identify the predictors of early relapses (within 7 days) of AF, 16 clinical and echocardiographic variables were compared at univariate analysis. The variables with a p value < 0.10 at univariate analysis were subsequently analyzed at multivariate analysis. Seventy-five patients (37.5%) had relapses of AF within 7 days of EC. By univariate analysis only a younger age (65.9 +/- 8.9 vs 69.0 +/- 8.3 years, p = 0.01) was found to be significantly correlated with a higher incidence of early relapses of AF. At multivariate analysis no variable was found to be significantly correlated with early relapses of AF. In patients with persistent AF, recurrences of this arrhythmia within 7 days of EC occur frequently (37.5%). Multivariate analysis did not reveal any clinical or echocardiographic variable significantly correlated with the early recurrence of AF.


Computational design strategy: an approach to enhancing the transdermal delivery of optimal capsaicin-loaded transinvasomes.
The aim of this study was to design and develop simultaneous optimal transinvasome formulations (OTV) to enhance the transdermal delivery of capsaicin. Using a central composite experimental design with duplicate centroids, 10 model formulations of transinvasomes (TVs) were demonstrated. The lipid compositions of the TV formulations were determined as formulation factors (Xn) and response variables (Yn), respectively. TV formulations containing a constant concentration of phosphatidylcholine, cholesterol, 0.15% capsaicin, and various percentages of d-limonene (X1) and cocamide diethanolamine (X2) were prepared. The physicochemical characteristics, e.g. the vesicle size, size distribution, zeta potential, entrapment efficiency, and skin permeability, of the TV formulations were experimentally investigated. The relationship among the formulation factor, the response variables, and the OTV was predicted using Design Expert® software. The accuracy and reliability of the OTV predicted using computer software were experimentally confirmed and investigated as an experimental transinvasome formulation (ETV). The results indicated that the skin permeability of the ETV was close to the OTV and was significantly higher than that of conventional liposomes and commercial products. The response surfaces estimated by the computer software were helpful in understanding the complicated relationship among the formulation factor, the response variables, and the stability of the TV formulation.


Genetic and Molecular Mechanisms in Brugada Syndrome.
Brugada syndrome is a rare hereditary arrhythmia disorder characterized by a distinctive electrocardiogram pattern and an elevated risk of ventricular arrhythmias and sudden cardiac death in young adults. Despite recent advances, it remains a complex condition, encompassing mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The underlying electrophysiological mechanism of Brugada syndrome requires further investigation, with current theories focusing on abnormalities in repolarization, depolarization, and current-load match. The genetic basis of the syndrome is strong, with mutations found in genes encoding subunits of cardiac sodium, potassium, and calcium channels, as well as genes involved in channel trafficking and regulation. While the initial discovery of mutations in the SCN5A gene provided valuable insights, Brugada syndrome is now recognized as a multifactorial disease influenced by several loci and environmental factors, challenging the traditional autosomal dominant inheritance model. This comprehensive review aims to provide a current understanding of Brugada syndrome, focusing on its pathophysiology, genetic mechanisms, and novel models of risk stratification. Advancements in these areas hold the potential to facilitate earlier diagnosis, improve risk assessments, and enable more targeted therapeutic interventions.


Room temperature synthesis of a luminescent crystalline Cu-BTC coordination polymer and metal-organic framework.
Synthesis of crystalline materials is elemental in the field of coordination chemistry towards optical applications. In the present work, coordination between copper and benzene-1,3,5-tricarboxylic acid (BTC) is controlled by adjusting the pH scale of the reaction mixture at room temperature to synthesize two crystalline structures: metal-organic framework HKUST-1 and coordination polymer Cu(BTC)·3H2O. The post-synthesis transformation of HKUST-1 into Cu(BTC)·3H2O is further demonstrated. Single crystals of both structures are studied by multi-laser Raman and luminescence spectroscopy. It is found that both crystals exhibit photoluminescence in the range of 700-900 cm-1 within the optical gap of the bulk materials, which can be associated with crystallographic defects. This work gives impetus for the synthesis of large metal-organic crystals based on which optical properties can be studied in depth.


Chemical Proteomic Profiling of Bromodomains Enables the Wide-Spectrum Evaluation of Bromodomain Inhibitors in Living Cells.
Bromodomains, epigenetic "readers" of lysine acetylation marks, exist in different nuclear proteins with diverse biological functions in chromatin biology. Malfunctions of bromodomains are associated with the pathogenesis of human diseases, such as cancer. Bromodomains have therefore emerged as therapeutic targets for drug discovery. Given the high structural similarity of bromodomains, a critical step in the development of bromodomain inhibitors is the evaluation of their selectivity to avoid off-target effects. While numerous bromodomain inhibitors have been identified, new methods to evaluate the inhibitor selectivity toward endogenous bromodomains in living cells remain needed. Here we report the development of a photoaffinity probe, photo-bromosporine (photo-BS), that enables the wide-spectrum profiling of bromodomain inhibitors in living cells. Photo-BS allowed light-induced cross-linking of recombinant bromodomains and endogenous bromodomain-containing proteins (BCPs) both in vitro and in living cells. The photo-BS-induced labeling of the bromodomains was selectively competed by the corresponding bromodomain inhibitors. Proteomics analysis revealed that photo-BS captured 28 out of the 42 known BCPs from the living cells. Assessment of the two bromodomain inhibitors, bromosporine and GSK6853, resulted in the identification of known as well as previously uncharacterized bromodomain targets. Collectively, we established a chemical proteomics platform to comprehensively evaluate bromodomain inhibitors in terms of their selectivity against endogenous BCPs in living cells.


Neuronal DAF-16-to-intestinal DAF-16 communication underlies organismal lifespan extension in C. elegans.
Previous studies have revealed the importance of inter-tissue communications for lifespan regulation. However, the inter-tissue network responsible for lifespan regulation is not well understood, even in a simple organism Caenorhabditis elegans. To understand the mechanisms underlying systemic lifespan regulation, we focused on lifespan regulation by the insulin/insulin-like growth factor-1 signaling (IIS) pathway; IIS reduction activates the DAF-16/FOXO transcription factor, which results in lifespan extension. Our tissue-specific knockdown and knockout analyses demonstrated that IIS reduction in neurons and the intestine markedly extended lifespan. DAF-16 activation in neurons resulted in DAF-16 activation in the intestine and vice versa. Our dual gene manipulation method revealed that intestinal and neuronal DAF-16 mediate longevity induced by daf-2 knockout in neurons and the intestine, respectively. In addition, the systemic regulation of intestinal DAF-16 required the IIS pathway in intestinal and neurons. Collectively, these results highlight the importance of the neuronal DAF-16-to-intestinal DAF-16 communication for organismal lifespan regulation.


Predictive value of pre-procedural N-terminal pro-B-type natriuretic peptide level for atrial fibrillation recurrence after radiofrequency catheter ablation.
N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been demonstrated as a valuable risk marker for mortality and morbidity of cardiovascular disease. Recurrence after atrial fibrillation (AF) radiofrequency catheter ablation remains common. We investigated the predictive value of the pre-procedural level of NT-proBNP to differentiate high-risk patients for post-ablation AF recurrence. 326 individuals with nonvalvular AF and preserved systolic function after enduring an initial radiofrequency catheter ablation (RFCA) between March 2018 and December 2019 were categorized into a recurrent group and a non-AF recurrent group. The serum NT-proBNP levels were examined before the ablation procedure. The researchers used multivariate logistic regression to find the determinants of AF recurrence. During a 14-month (interquartile range (IQR): 12-16) median follow-up, AF recurred in 84 (25.8%) patients. Patients in the recurrence group had considerably greater pre-ablation NT-proBNP levels (389.4 vs. 141.7 pg/ml, p < 0.001 in non-paroxysmal AF and 348.0 vs. 99.4 pg/ml, p < 0.001 in paroxysmal AF) as well as a greater left atrium (40 vs. 36 mm, p = 0.01 in non-paroxysmal AF and 38 vs. 36 mm, p = 0.01 in paroxysmal AF) than the non-AF recurrence group. A cut-off value of NT-proBNP ≥ 168.05 pg/ml identified AF recurrence with a sensitivity of 78.6% and specificity of 53.7% (area under ROC curve 0.68, 95% confidence interval (CI) 0.62-0.74, p < 0.001). Kaplan-Meier examination revealed that the elevated NT-proBNP (≥ 168.05 pg/ml) group presented a considerably shorter period without an occurrence compared to the low-NT-proBNP group (18.4 vs. 22.2 months, log-rank p = 0.001). Multivariate cox regression investigation showed that a level of NT-proBNP ≥ 168.05 pg/ml (hazard ratio (HR): 2.89, 95% CI: 1.71-4.903, p < 0.001) was a reliable predictor of AF recurrence after RFCA. A high pre-ablation NT-proBNP level was associated with AF recurrence, and it was also discovered to be a prognostic factor of recurrence of AF following RFCA.


Kinetics and New Mechanism of Azoxystrobin Biodegradation by an Ochrobactrum anthropi Strain SH14.
Azoxystrobin is one of the most popular strobilurin fungicides, widely used in agricultural fields for decades.Extensive use of azoxystrobin poses a major threat to ecosystems. However, little is known about the kinetics and mechanism of azoxystrobin biodegradation. The present study reports a newly isolated bacterial strain, Ochrobactrum anthropi SH14, utilizing azoxystrobin as a sole carbon source, was isolated from contaminated soils. Strain SH14 degraded 86.3% of azoxystrobin (50 μg·mL-1) in a mineral salt medium within five days. Maximum specific degradation rate (qmax), half-saturation constant (Ks), and inhibition constant (Ki) were noted as 0.6122 d-1, 6.8291 μg·mL-1, and 188.4680 μg·mL-1, respectively.Conditions for strain SH14 based azoxystrobin degradation were optimized by response surface methodology. Optimum degradation was determined to be 30.2 °C, pH 7.9, and 1.1 × 107 CFU·mL-1 of inoculum. Strain SH14 degraded azoxystrobin via a novel metabolic pathway with the formation of N-(4,6-dimethoxypyrimidin-2-yl)-acetamide,2-amino-4-(4-chlorophenyl)-3-cyano-5,6-dimethyl-pyridine, and 3-quinolinecarboxylic acid,6,8-difluoro-4-hydroxy-ethyl ester as the main intermediate products, which were further transformed without any persistent accumulative product. This is the first report of azoxystrobin degradation pathway in a microorganism. Strain SH14 also degraded other strobilurin fungicides, including kresoxim-methyl (89.4%), pyraclostrobin (88.5%), trifloxystrobin (78.7%), picoxystrobin (76.6%), and fluoxastrobin (57.2%) by following first-order kinetic model. Bioaugmentation of azoxystrobin-contaminated soils with strain SH14 remarkably enhanced the degradation of azoxystrobin, and its half-life was substantially reduced by 95.7 and 65.6 days in sterile and non-sterile soils, respectively, in comparison with the controls without strain SH14. The study presents O. anthropi SH14 for enhanced biodegradation of azoxystrobin and elaborates on the metabolic pathways to eliminate its residual toxicity from the environment.


Enhancing transplant patients' adherence to medication therapy.
Despite the importance of proper medication use, many transplant patients do not take their medications correctly. Non-adherence to medication therapy leads to adverse consequences, and practitioners should encourage adherence by transplant patients. This manuscript discusses several aspects of medication taking behavior including: (1) methods of identifying medication non-adherence; (2) models used to identify possible determinants of medication taking behavior; (3) strategies to educate patients concerning their therapy; (4) factors promoting adherence and non-adherence; and (5) practical interventions that we, as practitioners, can employ to enhance adult and pediatric transplant patients' adherence to therapy. By using the strategies suggested, transplant patients' adherence to medication therapy may be enhanced and patients' quality of life improved.


Changing EMS dispatcher CPR instructions to 400 compressions before mouth-to-mouth improved bystander CPR rates.
To examine the impact of changing dispatcher CPR instructions (400 compressions: 2 breaths, followed by 100:2 ratio) on rates of bystander CPR and survival in adults with presumed cardiac out-of-hospital arrest (OHCA) in Melbourne, Australia. The Victorian Ambulance Cardiac Arrest Registry (VACAR) was searched for OHCA where Emergency Medical Services (EMS) attempted CPR between August 2006 and August 2009. OHCA included were: (1) patients aged ≥18 years old; (2) presumed cardiac etiology; and (3) not witnessed by EMS. For the pre- and post-study periods, 1021 and 2101 OHCAs met inclusion criteria, respectively. Rates of bystander CPR increased overall (45-55%, p<0.001) and by initial rhythm (shockable 55-70%, p<0.001 and non-shockable 40-46%, p=0.01). In VF/VT OHCA, there were improvements in the number of patients arriving at hospital with a return of spontaneous circulation (ROSC) (48-56%, p=0.02) and in survival to hospital discharge (21-29%, p=0.002), with improved outcomes restricted to patients receiving bystander CPR. After adjusting for factors associated with survival, the period of time following the change in CPR instructions was a significant predictor of survival to hospital discharge in VF/VT patients (OR 1.57, 95% CI: 1.15-2.20, p=0.005). Following changes to dispatcher CPR instructions, significant increases were seen in rates of bystander CPR and improvements were seen in survival in VF/VT patients who received bystander CPR, after adjusting for factors associated with survival.


Encoding folding paths of RNA switches.
RNA co-transcriptional folding has long been suspected to play an active role in helping proper native folding of ribozymes and structured regulatory motifs in mRNA untranslated regions (UTRs). Yet, the underlying mechanisms and coding requirements for efficient co-transcriptional folding remain unclear. Traditional approaches have intrinsic limitations to dissect RNA folding paths, as they rely on sequence mutations or circular permutations that typically perturb both RNA folding paths and equilibrium structures. Here, we show that exploiting sequence symmetries instead of mutations can circumvent this problem by essentially decoupling folding paths from equilibrium structures of designed RNA sequences. Using bistable RNA switches with symmetrical helices conserved under sequence reversal, we demonstrate experimentally that native and transiently formed helices can guide efficient co-transcriptional folding into either long-lived structure of these RNA switches. Their folding path is controlled by the order of helix nucleations and subsequent exchanges during transcription, and may also be redirected by transient antisense interactions. Hence, transient intra- and inter-molecular base pair interactions can effectively regulate the folding of nascent RNA molecules into different native structures, provided limited coding requirements, as discussed from an information theory perspective. This constitutive coupling between RNA synthesis and RNA folding regulation may have enabled the early emergence of autonomous RNA-based regulation networks.


Glycosylation modulates TRAIL-R1/death receptor 4 protein: different regulations of two pro-apoptotic receptors for TRAIL by tunicamycin.
Death receptor 4 (DR4) is a receptor of the antitumor death ligand, TNF-related apoptosis-inducing ligand (TRAIL), and is considered a promising molecular target for cancer therapy. Here, we show a novel regulation of DR4 protein. Tunicamycin treatment, which is an inducer of endoplasmic reticulum (ER)-stress, generated a lower molecular-weight pattern of DR4, but not DR5 protein in prostate cancer DU145 and PC3 cells. Thus, we termed the small form of DR4 protein, DR4-Small (DR4-S) and the large form, DR4-Large (DR4-L). Using DR4 siRNA, we confirmed that DR4-S also stands for DR4 protein. Other ER-stress inducers, brefeldin A and thapsigargin did not generate DR4-S. On the other hand, these ER-stress inducers increased DR5 protein. Tunicamycin induces ER-stress following the inhibition of N-linked glycosylation. Thus, we examined DR4 protein in cell lysates treated with glycosydase. Glycosydase treatments generated DR4-S protein, similar to tunicamycin. These results indicate that tunicamycin regulates DR4 protein size via inhibition of glycosylation.


Surface/interface electronic structure in C(60) anchored aminothiolate self-assembled monolayer: an approach to molecular electronics.
Electronic structure in self-assembled monolayers (SAMs) of C(60) anchored 11-amino-1-undecane thiol (C(60)-11-AUT) on Au(111) was studied by means of ultraviolet photoelectron spectroscopy and hybrid density functional theory calculations. Valence band features of the molecular conformation revealed the interface electronic structure to be dominated by sigma(S-Au), localized at the thiolate anchor to Au. Formation of a localized covalent bond as a result of hybridization between N P(z) orbital of -NH(2) group of the thiolate SAM and the pi level of C(60) resulted in a symmetry change from I(h) in C(60) to C1 in C(60)-11-AUT SAM. Appearance of low, but finite amplitude surface electronic states of bonded C(60), much beyond the Fermi level, ruled out Au-C(60) end group contact. The band gap E(g) of the SAM, determined to be 2.7 eV, was drastically reduced from the insulating alkanethiol SAMs ( approximately 8.0 eV) and fell intermediate between the C(60) ground state (N electrons, 1.6 eV) and C(60) solid (N+/-1 electrons, 3.7 eV).


Lipid II-independent trans editing of mischarged tRNAs by the penicillin resistance factor MurM.
Streptococcus pneumoniae is a causative agent of nosocomial infections such as pneumonia, meningitis, and septicemia. Penicillin resistance in S. pneumoniae depends in part upon MurM, an aminoacyl-tRNA ligase that attaches L-serine or L-alanine to the stem peptide lysine of Lipid II in cell wall peptidoglycan. To investigate the exact substrates the translation machinery provides MurM, quality control by alanyl-tRNA synthetase (AlaRS) was investigated. AlaRS mischarged serine and glycine to tRNA(Ala), as observed in other bacteria, and also transferred alanine, serine, and glycine to tRNA(Phe). S. pneumoniae tRNA(Phe) has an unusual U4:C69 mismatch in its acceptor stem that prevents editing by phenylalanyl-tRNA synthetase (PheRS), leading to the accumulation of misaminoacylated tRNAs that could serve as substrates for translation or for MurM. Although the peptidoglycan layer of S. pneumoniae tolerates a combination of both branched and linear muropeptides, deletion of MurM results in a reversion to penicillin sensitivity in strains that were previously resistant. However, because MurM is not required for cell viability, the reason for its functional conservation across all strains of S. pneumoniae has remained elusive. We now show that MurM can directly function in translation quality control by acting as a broad specificity lipid-independent trans editing factor that deacylates tRNA. This activity of MurM does not require the presence of its second substrate, Lipid II, and can functionally substitute for the activity of widely conserved editing domain homologues of AlaRS, termed AlaXPs proteins, which are themselves absent from S. pneumoniae.


Auditory nerve fibre responses in the ferret.
The ferret (Mustela putorius) is a medium-sized, carnivorous mammal with good low-frequency hearing; it is relatively easy to train, and there is therefore a good body of behavioural data detailing its detection thresholds and localization abilities. However, despite extensive studies of the physiology of the central nervous system of the ferret, even extending to the prefrontal cortex, little is known of the functioning of the auditory periphery. Here, we provide an insight into this peripheral function by detailing responses of single auditory nerve fibres. Our expectation was that the ferret auditory nerve responsiveness would be similar that of its near relative, the cat. However, by comparing a range of variables (the frequency tuning, the variation of rate-level functions with spontaneous rate, and the high-frequency cut-off of phase locking) across several species, we show that the auditory nerve (and hence cochlea) in the ferret is more similar to that of the guinea-pig and chinchilla than to that of the cat. Animal models of hearing are often chosen on the basis of the similarity of their audiogram to that of the human, particularly in the low-frequency region. We show here that whereas the ferret hears well at low frequencies, this is likely to occur via fibres with higher characteristic frequencies. These qualitative differences in response characteristics in auditory nerve fibres are important in interpreting data across all of auditory science, as it has been argued recently that tuning in animals is broader than in humans.


Phosphorylation-independent binding of 14-3-3 to NtCDPK1 by a new mode.
14-3-3 pproteins play essential roles in diverse cellular processes through the direct binding to target proteins. REPRESSION OF SHOOT GROWTH (RSG) is a tobacco (Nicotiana tabacum) transcription factor that is involved in gibberellin (GA) feedback regulation. The 14-3-3 proteins bind to RSG depending on the RSG phosphorylation of Ser-114 and negatively regulate RSG by sequestering it in the cytoplasm in response to GAs. The Ca(2+)-dependent protein kinase NtCDPK1 was identified as an RSG kinase that promotes 14-3-3 binding of RSG by phosphorylation of RSG. 14-3-3 weakly binds to NtCDPK1 by a new mode. The autophosphorylation of NtCDPK1 was necessary for the formation of the binding between NtCDPK1 and 14-3-3 but not for its maintenance. In this study, we showed that 14-3-3 binding to NtCDPK1 does not require the autophosphorylation when RSG was bound to NtCDPK1. These data suggest that 14-3-3 binds to an unphosphorylated motif in NtCDPK1 exposed by a conformational change in NtCDPK1 but not to a phosphate group generated by autophosphorylation of NtCDPK1.


Further evidence for a reversed crossing of foveal projections in schizophrenic vulnerability.
Further evidence in support of the thesis developed in a previous article published in Medical Hypotheses (Sept. 2000) proposing that schizophrenic vulnerability might consist of the temporal instead of the nasal foveal projections crossing over in the chiasma opticum has been provided by an experiment in which pinholes are used to isolate foveally stimulated from peripherally stimulated vergence. By shifting the pinholes inwards or outwards a dilemma is created regarding the fusion of the edges of the two pinholes or of a single diode light seen at the inner or outer edges of the pinholes. It was revealed that schizophrenic patients never solved the dilemma in favour of what was represented on the temporal foveal halves while this was always the case in the control group. At best, the patients fusioned neither the diode light nor the pinhole edges but saw both double. An explanation is given as to how this disturbance might be based on the interchange of nasal and temporal foveal projections and might lead to the dissociation of the visual goals of the two eyes, as shown in a previous test. The cause of markers of schizophrenic vulnerability mentioned in literature, in particular saccaded SPEM, P50 response and hyperdopaminergia, is related to such an interchange and suggestions are made for further experiments. Finally, the difficulty of schizophrenic patients to distinguish between reality and illusion is attributed to a disconnection of spatial and object perception.


Antioxidant activity and cytotoxicity of exopolysaccharide from mushroom Hericium coralloides in submerged fermentation.
Mushrooms of the genus Hericium spp. represent a series of delicious edible mushrooms with medicinal value. Here, for the first time, the species native to Iran, the mushroom Hericium coralloides, was collected in Mazandaran province, identified, and registered with the NCBI under accession number MW136052. The production of exopolysaccharides (EPS) in submerged culture was optimized using the response surface method. Among the physicochemical and culture medium conditions tested, rotation speed and concentration of maltose and peptone of soybean significantly affected the production of EPS. The proposed model predicts maximum EPS production (0.13 g/L) at 50 g/L maltose, 3 g/L soy peptone, and 1 g/L yeast extract, pH = 6.5, 200 rpm, inoculum at 5% v/v, and 22 °C. The molecular weight of the EPS chains was 413 and 1578 Da. EPS has antioxidant action (EC50 = 6.59 mg/mL) and cytotoxic activity against cancer cells. The viability of AGS and MKN-45 cancer cell lines declined to 20 and 30% after 48 h of the EPS treatment. H. coralloides EPS could be considered a natural dietary anti-cancer supplement. Further studies are necessary to understand the mechanism of the H. coralloides EPS activity on the cell cycle of cancer cells and to prove its action in vivo. The online version contains supplementary material available at 10.1007/s13399-022-03386-0.


Leaky RyR2 channels unleash a brainstem spreading depolarization mechanism of sudden cardiac death.
Cardiorespiratory failure is the most common cause of sudden unexplained death in epilepsy (SUDEP). Genetic autopsies have detected "leaky" gain-of-function mutations in the ryanodine receptor-2 (RyR2) gene in both SUDEP and sudden cardiac death cases linked to catecholaminergic polymorphic ventricular tachycardia that feature lethal cardiac arrhythmias without structural abnormality. Here we find that a human leaky RyR2 mutation, R176Q (RQ), alters neurotransmitter release probability in mice and significantly lowers the threshold for spreading depolarization (SD) in dorsal medulla, leading to cardiorespiratory collapse. Rare episodes of sinus bradycardia, spontaneous seizure, and sudden death were detected in RQ/+ mutant mice in vivo; however, when provoked, cortical seizures frequently led to apneas, brainstem SD, cardiorespiratory failure, and death. In vitro studies revealed that the RQ mutation selectively strengthened excitatory, but not inhibitory, synapses and facilitated SD in both the neocortex as well as brainstem dorsal medulla autonomic microcircuits. These data link defects in neuronal intracellular calcium homeostasis to the vulnerability of central autonomic brainstem pathways to hypoxic stress and implicate brainstem SD as a previously unrecognized site and mechanism contributing to premature death in individuals with leaky RYR2 mutations.


Thoracic Epidural Catheter Placement in a Preoperative Block Area Improves Operating Room Efficiency and Decreases Epidural Failure Rate.
The primary aim of this study was to review the impact of inserting thoracic epidural catheters in a preoperative block room setting on operating room efficiency. We conducted a retrospective preintervention/postintervention review of thoracic epidurals inserted over a 12-month period. The review included 6 months of data prior to implementation of the regional anesthesia block room and 6 months of data following implementation. The primary outcome measure was anesthesia-controlled operating room time, defined as time from patient arrival to the operating room to time of surgical site sterile preparation. Secondary measures included operating room waiting time for the patient arrival, thoracic epidural failure rate, and number of epidural insertion attempts. Data from thoracic epidurals for 112 patients of preblock room and 142 patients of postblock room implementation were collected. Anesthesia-controlled operating room time was reduced by an average of 22.9 minutes per patient (95% confidence interval, 19.3-26.3 minutes; P < 0.01). Average operating room waiting time for patient arrival increased by 3.8 minutes (95% confidence interval, 1.0-6.5 minutes; P < 0.01), resulting in net operating room time savings of 19.1 minutes per epidural. The epidural failure rate decreased from 16.0% to 5.6% (P < 0.01). There was no difference in the number of epidural insertion attempts made per patient. Insertion of thoracic epidural analgesia in a preoperative block room setting can significantly reduce anesthesia-controlled operating room time and epidural failure rates.


Proteomic analysis of differentially expressed whey proteins in Saanen goat milk from different provinces in China using a data-independent acquisition technique.
Whey proteins of Saanen goat milk samples from 3 provinces in China (Guangdong, GD; Inner Mongolia, IM; Shaanxi, SX) were characterized and compared using data-independent acquisition quantitative proteomics technique. A total of 550 proteins were quantified in all 3 samples. There were 44, 44, and 33 differentially expressed proteins (DEP) for GD versus IM, GD versus SX, and IM versus SX, respectively. Gene ontology annotation analysis showed that the largest number of DEP for the 3 comparisons were as follows: for biological processes: response to progesterone, glyceraldehyde-3-phosphate metabolic process, and negative regulation of megakaryocyte differentiation; for molecular functions: antioxidant activity, binding, and peroxiredoxin activity; and for cellular components: the same category of extracellular regions for the 3 comparisons, respectively. Pathways for the DEP of 3 comparisons were (1) disease; (2) synthesis and metabolism; and (3) synthesis, degradation, and metabolism. Protein-protein interaction network analysis showed that DEP for GD versus SX had the most interactions.


Applicability of the ReproQ client experiences questionnaire for quality improvement in maternity care.
Background. The ReproQuestionnaire (ReproQ) measures the client's experience with maternity care, following the WHO responsiveness model. In 2015, the ReproQ was appointed as national client experience questionnaire and will be added to the national list of indicators in maternity care. For using the ReproQ in quality improvement, the questionnaire should be able to identify best and worst practices. To achieve this, ReproQ should be reliable and able to identify relevant differences. Methods and Findings. We sent questionnaires to 17,867 women six weeks after labor (response 32%). Additionally, we invited 915 women for the retest (response 29%). Next we determined the test-retest reliability, the Minimally Important Difference (MID) and six known group comparisons, using two scorings methods: the percentage women with at least one negative experience and the mean score. The reliability for the percentage negative experience and mean score was both 'good' (Absolute agreement = 79%; intraclass correlation coefficient = 0.78). The MID was 11% for the percentage negative and 0.15 for the mean score. Application of the MIDs revealed relevant differences in women's experience with regard to professional continuity, setting continuity and having travel time. Conclusions. The measurement characteristics of the ReproQ support its use in quality improvement cycle. Test-retest reliability was good, and the observed minimal important difference allows for discrimination of good and poor performers, also at the level of specific features of performance.


Intracorporeal needle breakage as an unusual complication of intracavernous self-injection.
Intracorporeal needle breakage during intracavernous self-injection of vasoactive drugs in the treatment of erection disorders represents an unusual complication. This article presents a case of intracorporeal needle breakage during self-injection in a 50-year-old man. Our case allowed an immediate removal of the needle by manipulation, without resorting to surgery or delayed retrieval.


Molecular classification of scrapie strains in mice using gene expression profiling.
Transmissible spongiform encephalopathy strains demonstrate specific prion characteristics, each with specific incubation times, and strain-specific patterns of deposition of the misfolded isoform of prion, PrPSc, in the brains of infected individuals. Different biochemical properties, including glycosylation profiles and the degree of proteinase resistance, have been shown to be strain-specific. However, no relationship between these properties and the phenotypic differences in the subsequent diseases has as yet been determined. Here we explore the utility of gene expression profiles to identify differences in the host response to different strains of prion agent. We identify 114 genes that exhibit significantly different levels of expression in mice infected with three strains of scrapie. These genes represent a pool of genes involved in a strain-specific response to prion disease. We have identified the most discriminatory genes from this list utilizing a wrapper-based feature selection algorithm with external cross-validation.


Phylogenetic and codon usage analysis of atypical porcine pestivirus (APPV).
Atypical porcine pestivirus (APPV) has been identified as the main causative agent for congenital tremor (CT) type A-II in piglets, which is threatening the health of the global swine herd. However, the evolution of APPV remains largely unknown. In this study, phylogenetic analysis showed that APPV could be divided into three phylogroups (I, II, and III). Phylogroups I and II included viral strains from China, while phylogroup III contained strains from Europe, North America, and Asia. Phylogroups I and II are tentatively thought to be of Chinese origin. Next, compositional property analysis revealed that a high frequency of nucleotide A and A-end codons was used in the APPV genome. Intriguingly, the analysis of preferred codons revealed that the AGA[Arg] and AGG[Arg] were overrepresented. Dinucleotide CC was found to be overrepresented, and dinucleotide CG was underrepresented. Furthermore, it was found that the weak codon usage bias of APPV was mainly dominated by selection pressures versus mutational forces. The codon adaptation index (CAI), relative codon deoptimization index (RCDI), and similarity index (SiD) analyses showed that the codon usage patterns of phylogroup II and III were more similar to the one of a pig than phylogroup I, suggesting that phylogroup II and III may be more adaptive to pigs. Overall, this study provides insights into APPV evolution through phylogeny and codon usage pattern analysis.


Bronchiolar disorders: a clinical-radiological diagnostic algorithm.
Bronchiolar disorders are generally difficult to diagnose because most patients present with nonspecific respiratory symptoms of variable duration and severity. A detailed clinical history may point toward a specific diagnosis. Pertinent clinical questions include history of smoking, collagen vascular disease, inhalational injury, medication usage, and organ transplant. It is important also to evaluate possible systemic and pulmonary signs of infection, evidence of air trapping, and high-pitched expiratory wheezing, which may suggest small airways involvement. In this context, pulmonary function tests and plain chest radiographs may demonstrate abnormalities; however, they rarely prove sufficiently specific to obviate bronchoscopic or surgical biopsy. Given these limitations, in our experience, high-resolution CT (HRCT) scanning of the chest often proves to be the most important diagnostic tool to guide diagnosis in these difficult cases, because different subtypes of bronchiolar disorders may present with characteristic image findings. Three distinct HRCT patterns in particular are of value in assisting differential diagnosis. A tree-in-bud pattern of well-defined nodules is seen primarily as a result of infectious processes. Ill-defined centrilobular ground-glass nodules point toward respiratory bronchiolitis when localized in upper lobes in smokers or subacute hypersensitivity pneumonitis when more diffuse. Finally, a pattern of mosaic attenuation, especially when seen on expiratory images, is consistent with air-trapping characteristic of bronchiolitis obliterans or constrictive bronchiolitis. Based on an appreciation of the critical role played by HRCT scanning, this article provides clinicians with a practical algorithmic approach to the diagnosis of bronchiolar disorders.


Copper (II)-doped semiconducting polymer dots for nitroxyl imaging in live cells.
The first nanoparticle-based fluorescent probe for the specific detection of nitroxyl (HNO) was designed and constructed by doping copper(II) into semiconducting polymer dots (Pdots). The probe turns on and fluoresces in the presence of HNO. We used the new sensor to monitor changes of HNO levels in live cells.


[Establishment and validation of a new predictive equation with multiple risk factors for the development of cardiorenal syndrome type 1 in patients with acute myocardial infarction].
Objective: To investigate the independent risk factors of cardiorenal syndrome type 1 (CRS1) in patients with acute myocardial infarction (AMI) and to build a predictive equation for the development of CRS1 in these patients. Method: Consecutive inpatients with AMI, who hospitalized from January 2017 to December 2018 in the Hunan Provincial People's Hospital, were enrolled in this case-control study. Patients were divided into CRS1 group and non-CRS1 group according to the presence or absence of CRS1.The clinical data were collected through the electronic medical record system of Hunan Provincial People's Hospital. The matching process was conducted with a minimum-distance scoring method and a 1∶1 match between the CRS1 group and the no-CRS1 group, the propensity score was calculated through the logistic regression model. Factors with statistically significant differences in univariate analysis were included in the multivariate logistic regression model to analyze the risk factors of AMI patients with CRS1, then the independent risk factors were used to establish a predicting equation for CRS1 by logistic regression function for model building. Area under the curve (AUC) value and the best cut-off value of the combined predictors was determined according to the ROC curve. Python 3.8 software was used to perform 10-fold cross-validation on modeling samples. Results: A total of 942 patients were included, there were 113 cases in CRS1 group and 829 cases in non-CRS1 group. Ultimately, 99 CRS1 patients were successfully matched to 99 non-CRS1 patient using 1∶1 matching. After propensity score matching, the baseline age and sex along with heart rate, mean arterial pressure, percentage of people with a history of diabetes, hypertension, ST-segment elevation myocardial infarction, myocardial ischemia time, angiotensin converting enzyme inhibitors or angiotensin Ⅱ receptor blockers use, and β receptor blocker use were similar between the two groups(all P>0.05). The contrast agent dosage was also similar between the two groups (P=0.266). The peak cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide(NT-proBNP), white blood cell count, base estimated glomerular filtration rate (eGFR), albumin and hemoglobin levels were statistically significant between the two groups (all P<0.05). Multivariate logistic regression analysis showed that decreased baseline eGFR, increased NT-proBNP, peak cTnI concentrations and white blood cell count were independent risk factors of CRS1 in AMI patients (all P<0.01).The predicting equation of the combined predictor was established by transforming the logistic model equation, L=0.031×cTnI+0.000 2×NT-proBNP-0.024×eGFR+0.254×white blood cell count, where L represented the combined predictor. ROC curve analysis indicated that the AUC of the peak cTnI, NT-proBNP, baseline eGFR, white blood cell count, and combined predictor were 0.76, 0.85, 0.79, 0.81, and 0.92 respectively (all P<0.05), and the cutoff value of combined predictor was 2.6. The AUC of ROC curve after the model's ten-fold cross validation was 0.89. Conclusions: Decreased baseline eGFR, increased NT-proBNP, peak cTnI concentrations and white blood cell count are the independent risk factors for CRS1 in AMI patients. The combined predictor equation based on the above 4 biomarkers presents a good predictive value for CRS1 in AMI patients.


Pilot study: does the Five Shot Questionnaire give an indication of the severity of alcohol use-related problems?
This study explores whether the Five Shot Questionnaire reflects the severity of alcoholic inpatients' problems, such as assessed clinically by means of the EuropASI. Data were collected from 101 patients admitted to a psychiatric hospital in Belgium for alcohol use-related problems between September 2003 and December 2004. To investigate the research question, regression analyses--linear, ordinal, and binary logistic regression--have been performed. We conclude that the Five Shot Questionnaire gives an indication of the severity of alcohol use-related problems. As such, it can be recommended in general practice and emergency departments for further evaluation and treatment planning. The article ends with a discussion of its limitations and some suggestions for future research.