Prospective validation study of Cernea classification for predicting EMG alterations of the external branch of the superior laryngeal nerve.
Cernea classification is applied to describe the external branch of the superior laryngeal nerve (EBSLN). Using intraoperative neural monitoring we evaluated whether or not this classification is useful for predicting which EBSLN subtype has an increased risk of injury. An analysis of 400 EBSLN. The identification of EBSLN was achieved with both cricothyroid muscle twitch and the glottis evoked electromyography response. We defined S1 initial EBSLN stimulation at identification and S2 final nerve stimulation achieved in the most cranial aspect of the nerve exposed above the area of surgical dissection after superior artery ligation. The mean S1 amplitude acquired was 259+/67 (180-421), 321 +/79 (192-391), 371 +/38 (200-551) μV, respectively, for type 1, 2A, 2B (p = 0.08). The S1 and S2 amplitudes were similar in type 1 (p = 0.3). The S1 and S2 determinations changed significantly in type 2A and 2B (p = 0.04 and 0.03). EBSLN which demonstrated a >25 % decreased amplitude in S2 increased significantly from Type 1 (4.9 %) to Type 2A (11.2 %) and 2B (18 %) (p = 0.01). None of type 1, 2.8 % type 2A and 3 % type 2B showed a loss of EBSLN conductivity. The latency determinations did not vary significantly for any parameter compared. The Cernea classification was, therefore, found to predict the risk of EBSLN stress. We identified amplitude differences between S1 and S2 determinations in type 2A and 2B, thus confirming that surgical dissection in these subtypes is, therefore, extremely difficult to perform.


Primary afferent nociceptor mechanisms mediating NGF-induced mechanical hyperalgesia.
The underlying mechanism for nerve growth factor (NGF) evoked pain and long-lasting mechanical hyperalgesia remains poorly understood. Using intrathecal antisense against the NGF receptor, receptor tyrosine kinase (TrkA), we found NGF to act at the primary afferent nociceptor directly in the Sprague-Dawley rat. Inhibitors of the three major pathways for TrkA receptor signalling, extracellular signal-related kinase (ERK)/mitogen-activated protein kinase kinase (MEK) (ERK/MEK), phosphatidylinositol 3-kinase (PI3K), and phospholipase Cgamma (PLCgamma) all attenuate NGF-induced hyperalgesia. Although inhibitors of kinases downstream of PI3K and PLCgamma[glycogen synthetase kinase 3 (GSK3), calmodulin-dependent protein kinase II (CAMII-K) or protein kinase C (PKC)] do not reduce mechanical hyperalgesia, hyperalgesia induced by activation of PI3K was blocked by ERK/MEK inhibitors, suggesting cross-talk from the PI3K to the ERK/MEK signalling pathway. As integrins have been shown to modulate epinephrine and prostaglandin E(2)-induced hyperalgesia, we also evaluated a role for integrins in NGF-induced mechanical hyperalgesia using beta(1)-integrin-specific antisense or antibodies.


Effects of drought during grain filling on PS II activity in rice.
The Rice varieties Araure 4 (A4) and Fonaiap 2000 (F2000) were grown in the glasshouse under natural sunlight and subjected to drought at heading. The drought induced changes in chlorophyll a fluorescence parameters, pigment composition, D1 contents and carbohydrate accumulation were investigated. Drought decreased phiPS II, FV'/FM' and qP, and increased qN in both varieties. F2000 had larger values of phiPS II and FV'/FM' at a lower RWC than A4. With the onset of drought only A4 increased the xanthophyll cycle pool, F2000 remaining constant throughout the drought cycle. Irrigated plants of A4 had a Larger de-epoxidation state (DEPS) of the xanthophyll cycle than F2000. A 40% increase in DEPS was induced by drought in both varieties but in A4 it was attained at a larger RWC than in F2000. Drought increased glucose and fructose contents of leaves 8-fold in A4 and 3-fold in F2000. Contrarily, sucrose contents decreased with drought but the effects were larger in A4 than in F2000. Sugars accumulation preceded and was proportional to the decrease in PS II activity elicited by drought in both varieties. In F2000 a decrease in D1 content smaller than 20% occurred at 70% of RWC, whereas droughted plants of A4 had lost 80% of D1 protein at 77% of RWC. Our data show that drought severely affected PS II activity and its main regulatory mechanisms in rice. There are genotypic differences in the response of PS II activity to drought that could be exploited as traits for selection to drought tolerance. There is a possible link between the drought-induced sugars accumulation in the flag leaf and the response of PS II to water deficit.


Specific early maladaptive schemas differentially mediate the relations of emotional and sexual maltreatment to recent life events in youth with depression.
The current study provided a novel investigation of relations among particular types of childhood maltreatment (emotional vs. physical vs. sexual maltreatment), specific cognitive schema themes and the generation of dependent versus independent life events. Participants included 227 adolescents and emerging adults (74% female; aged 12-29) in a current episode of a unipolar depressive disorder drawn from three archival cross-sectional studies. Childhood maltreatment and life events from the past 6 months were assessed using detailed contextual interviews with independent, standardized ratings. Emotional maltreatment was uniquely associated with schema themes of emotional deprivation and subjugation, and sexual maltreatment was uniquely associated with schema themes of abandonment, vulnerability and dependence/incompetence. Further, subjugation and abandonment cross-sectionally mediated the relations of emotional and sexual maltreatment, respectively, to greater dependent, but not independent, life events. Physical maltreatment was not associated with cognitive schemas or recent life events after accounting for its overlap with emotional and sexual maltreatment. Results suggest targets for cognitive intervention that may improve outcomes for youth with specific histories of emotional and sexual maltreatment.


Acute deafness as an extraintestinal manifestation of ulcerative colitis.
Autoimmune sensorineural hearing loss is a syndrome with an immunological mechanism occasionally associated with diverse autoimmune diseases. We describe a case of sensorineural hearing loss in a patient with ulcerative colitis. Several pathogenic mechanisms have been invoked. Treatment is steroid therapy and should be initiated when symptoms appear to restore hearing.


Evaluation of four tenofovir-containing regimens as first-line treatments in Cameroon and Senegal: the ANRS 12115 DAYANA Trial.
The aim of the present study was to determine appropriate tenofovir-based regimens meriting evaluation in large-scale randomized trials among sub-Saharan African patients. This was a randomized open-label 96-week prospective pilot study evaluating four first-line regimens: tenofovir/emtricitabine/nevirapine (group 1), tenofovir/lopinavir/ritonavir (group 2), tenofovir/emtricitabine/zidovudine (group 3) and tenofovir/emtricitabine/efavirenz (group 4) in antiretroviral-naive, HIV-1-infected patients in Senegal and Cameroon. The primary end point was defined as an HIV-1 RNA viral load <50 copies/ml (study detection limit) at week 16 in ≥50% of patients using intention-to-treat analysis. At baseline, 119 patients included were 34% male, had a median plasma viral load of 5.4 log10 copies/ml and median CD4(+) T-cell count of 200 cells/mm(3) (range 53-358). The primary end point was achieved for groups 1, 3 and 4 (58% [n=31], 62% [n=29] and 53% [n=30], respectively), but not for group 2 (38% [n=29]). At week 96, undetectable HIV-1 RNA had been achieved in 74% of patients in group 1, 38% in group 2, 72% in group 3 and 73% in group 4. Patients with detectable HIV-1 RNA at week 16 were more likely to have baseline HIV-1 RNA≥100,000 copies/ml (adjusted OR 5.56, 95% CI 1.72, 16.67). HIV mutations associated with protease inhibitor resistance emerged in three patients, all of whom were in group 2. Anaemia occurred in two group 3 patients and was the only serious treatment-related adverse event. Three efficient and safe tenofovir-based triple regimens were identified; the two-drug regimen (tenofovir/lopinavir/ritonavir) did not achieve the protocol-defined virological threshold of efficacy.


Cinchona alkaloids - acid, anion-driven fluorescent INHIBIT logic gates with a receptor1-fluorophore-spacer-receptor2 format and PET and ICT mechanisms.
The fluorescent natural products, quinine, quinidine, cinchonine and cinchonidine are demonstrated as H+-enabled, halide-disabled (Cl-, Br- or I-) INHIBIT and INHIBIT-OR combinatorial logic gates in water. More fluorescent natural products with intrinsic logic properties await to be discovered.


[Viral hepatitis A in lower Old World monkeys (possibility of use as a model for vaccine testing)].
Morphological, virological and serological data characteristic of spontaneous hepatitis A in macaques and green monkeys have been presented. The disease similar to human hepatitis A was induced in M. iris macaques, with the virus isolated from spontaneously infected rhesus monkeys. Experimental model of hepatitis A in macaques is likely to be used for the testing of vaccines and antiviral preparations.


The road not taken: transferability issues in multinational trials.
National regulatory agencies often have to use cost-effectiveness (CE) data from multinational randomized controlled trials (RCTs) for national decision making on reimbursement of new drugs. We need to make the best use of these patient-level data to obtain estimates of country-specific CE. Several methods, ranging from simple to statistically complex, have existed for years. We investigated which of these methods are used to estimate CE ratios in economic evaluations performed alongside recent, multinational RCTs that enrolled at least 500 patients. In this systematic literature review, studies were classified based on whether resource use, unit costs, health outcomes and utility value sets were obtained from all countries, a subset of countries or one country. We recorded if the study presented trial-wide and country-specific CE results and reported the statistical analyses that were used to estimate them. We included 21 studies, of which the majority used measurements of health care utilization and health outcomes from all countries to estimate CE. Thirteen studies used a one-country valuation of health care utilization; six used a multi-country valuation. Despite the availability of country-specific utility value sets, none of the studies that presented quality-adjusted life-years (QALYs) used multi-country valuation. Valuation of health care utilization and health outcomes was not always consistent within a study: three studies combined a multi-country valuation of health care utilization, with a one-country valuation of health outcomes. Most studies calculated trial-wide CE estimates, while 11 studies calculated country- or region-specific estimates. Thirteen studies used relatively simple methods, which do not take the possible interaction between the country and treatment effect on health care utilization and health outcomes into account. Eight studies used more advanced statistical methods. Three of them used a fixed-effects modeling approach. Five studies explicitly took the hierarchical structure of the data into account, which leads to more appropriate estimates of population average results and associated standard errors. In this way, they help improve transferability of the published results. Based on this systematic review, we concluded that the uptake of more advanced statistical methods has been relatively slow, while simpler naïve methods are still routinely employed.


Laparoscopic sentinel node procedure using a combination of patent blue and radiocolloid in women with endometrial cancer.
We assessed the feasibility of a laparoscopic sentinel node (SN) procedure based on the combined use of radiocolloid and patent blue labeling in patients with endometrial cancer. Seventeen patients (median age, 69 years) with endometrial cancer of stage I (16 patients) or stage II (1 patient) underwent a laparoscopic SN procedure based on combined radiocolloid and patent blue injected pericervically. After the SN procedure, all patients underwent complete laparoscopic pelvic lymphadenectomy and either laparoscopically assisted vaginal hysterectomy (16 patients) or laparoscopic radical hysterectomy (1 patient). SNs (mean number per patient, 2.6; range, 1-4) were identified in 16 (94.1%) of the 17 patients. Macrometastases were detected in three SNs from two patients by hematoxylin and eosin staining. In three other patients, immunohistochemical analysis identified six micrometastatic SNs and one SN containing isolated tumor cells. No false-negative SN results were observed. An SN procedure based on a combination of radiocolloid and patent blue is feasible in patients with early endometrial cancer. Combined use of laparoscopy and this SN procedure permits minimally invasive management of endometrial cancer.


Impact of behavioral and psychological symptoms of Alzheimer's disease on caregiver outcomes.
This study was to determine the prevalence of behavioral and psychological symptoms of dementia (BPSD) and its association with dementia severity and to explore the association between specific BPSD and caregiver stress, burden, and depression. A cross-sectional study involving the interviewing of the primary caregivers of patients with Alzheimer's disease (AD) was conducted. Multivariable analysis was used to analyze the associations between specific symptoms of BPSD and caregiver outcomes. A total of 102 AD patients (age 79.4 ± 7.9 years, 70.6% female) and their caregivers were included. Nearly 46% had moderate-to-severe AD. Nearly all patients (99.0%) had at least one BPSD. Apathy was among the most common symptoms (74.5%), and hallucination was the only symptom associated with severity of AD (p = 0.017). After adjustment, agitation was associated with Patient Health Questionnaire-9 (PHQ-9) and Zarit Burden Interview (ZBI-22) (p = 0.021 and 0.007, respectively); sleep disorders were associated with only PHQ-9 (p = 0.049). In conclusion, the BPSD, especially agitation and sleep disorders, can give rise to difficulties for both patients and their caregivers. The prevalence of BPSD is high (99.0%), and the symptoms can start early. Routine screening of BPSD in all AD patients is advocated.


Novel potential mechanism-based inhibitors of human leukocyte elastase and cathepsin G: derivatives of isothiazolidin-3-one.
A series of heterocyclic compounds designed to function as mechanism-based inhibitors of human leukocyte elastase and cathepsin G has been synthesized and their inhibitory activity was investigated. These isothiazolidin-3-one derivatives were found to be effective inhibitors of cathepsin G.


The timing of visual speech modulates auditory neural processing.
In face-to-face communication, visual information from a speaker's face and time-varying kinematics of articulatory movements have been shown to fine-tune auditory neural processing and improve speech recognition. To further determine whether the timing of visual gestures modulates auditory cortical processing, three sets of syllables only differing in the onset and duration of silent prephonatory movements, before the acoustic speech signal, were contrasted using EEG. Despite similar visual recognition rates, an increase in the amplitude of P2 auditory evoked responses was observed from the longest to the shortest movements. Taken together, these results clarify how audiovisual speech perception partly operates through visually-based predictions and related processing time, with acoustic-phonetic neural processing paralleling the timing of visual prephonatory gestures.


Regulator of calmodulin signaling knockout mice display anxiety-like behavior and motivational deficits.
Regulator of calmodulin (CaM) signaling (RCS), when phosphorylated by protein kinase A (PKA) on Ser55, binds to CaM and inhibits CaM-dependent signaling. RCS expression is high in the dorsal striatum, nucleus accumbens and amygdala, suggesting that the protein is involved in limbic-striatal function. To test this hypothesis, we examined RCS knockout (KO) mice in behavioral models dependent on these brain areas. Mice were tested for food-reinforced instrumental conditioning and responding under a progressive ratio (PR) schedule of reinforcement and in models of anxiety (elevated plus maze and open field). While RCS KO mice showed normal acquisition of a food-motivated instrumental response, they exhibited a lower breakpoint value when tested on responding under a PR schedule of reinforcement. RCS KO mice also displayed decreased exploration in both the open arms of an elevated plus maze and in the center region of an open field, suggesting an enhanced anxiety response. Biochemical studies revealed a reduction in the levels of dopamine and cAMP-regulated phosphoprotein (DARPP-32) in the striatum of RCS KO mice. DARPP-32 is important in reward-mediated behavior, suggestive of a possible role for DARPP-32 in mediating some of the effects of RCS. Together these results implicate a novel PKA-regulated phosphoprotein, RCS, in the etiology of motivational deficits and anxiety.


Type IV pilus gene homologs pilABCD are required for natural transformation in Actinobacillus actinomycetemcomitans.
Some clinical isolates of the gram-negative periodontal pathogen Actinobacillus actinomycetemcomitans are naturally competent for DNA uptake. In this study, we examined the sequence and the function of a type IV pilus-like pilABCD gene cluster and its downstream region in a naturally transformable A. actinomycetemcomitans strain D7S. Specific knockout mutants of pilABCD of strain D7S were constructed by replacing individual genes with an antibiotic resistance cassette. The transformation frequency of chromosome markers in the wildtype strain D7S was approximately 10(-3) per CFU. In contrast, the delta pilA, delta pilB, delta pilC, delta pilBC or delta pilD mutants were non-transformable (transformation frequency <10(-8)). Disruption of an ORF downstream of pilD had no apparent effect on the transformability of this bacterium. The pilA or pilBC deletion did not seem to affect fimbria expression or cell surface structure in either rough or smooth strains as determined by scanning and transmission electron microscopy examinations. RT-PCR analysis showed that pilA was expressed in strain D7S under a competence-inducing growth condition. The expression of pilA was barely detectable in strain D7S cultured under a non-competence-inducing condition or in the non-transformable strain JP-2. The results indicate that pilABCD are required for competence but are apparently not involved in fimbria expression of A. actinomycetemcomitans.


Ultrasound scoring system for prenatal diagnosis of placenta accreta spectrum.
To develop an ultrasound scoring system for placenta accreta spectrum (PAS), evaluate its diagnostic value, and provide a practical approach to prenatal diagnosis of PAS. A total of 532 pregnant women (n = 184 no PAS, n = 120 placenta accreta, n = 189 placenta increta, n = 39 placenta percreta) at high-risk for placenta accreta who delivered in the Third Affiliated Hospital of Zhengzhou University between January 2021 and December 2022 underwent prenatal ultrasound to evaluate placental invasion. An ultrasound scoring system that included placental and cervical morphology and history of cesarean section was created. Each feature was assigned a score of 0 ~ 2, according to severity. Thresholds for the total ultrasound score that discriminated between no PAS, placenta accreta, placenta increta, and placenta percreta were calculated. Univariate and multivariate regression analysis identified seven indicators of PAS that were included in the ultrasound scoring system, including placental location, placental thickness, presence/absence of the retroplacental space, thickness of the retroplacental myometrium, presence/absence of placental lacunae, retroplacental myometrial blood flow and history of cesarean section. Using the final ultrasound scoring system, no PAS is diagnosed at a total score < 5, placenta accreta or placenta increta is diagnosed at a total score 5-10, and placenta percreta is diagnosed at a total score ≥ 10. This study identified seven indicators of PAS and included them in an ultrasound scoring system that has good diagnostic efficacy and clinical utility. ChiCTR2300069261 (retrospectively registered on 10/03/2023).


Intersectoral collaboration at a decentralized level: information flows in child welfare and healthcare networks.
As needs of families with social and behavioral health problems often exceed the expertise and possibilities of a single professional, service or organization, cross-service collaboration is indispensable to adequately meeting those needs. Despite the progressive focus on organizing integrated care, service fragmentation and service duplication remain persistent problems in child welfare and healthcare service delivery systems. A crucial factor to overcome these problems is information exchange between organizations. This study explores and compares the development over time of structures of information exchange in networks, concerning both material and knowledge-based information. A comparative case study and social network analysis of three inter-organizational networks of child welfare and healthcare services in different-sized municipalities in the Netherlands. The research population consisted of organizations from various sectors participating in the networks. Data were collected at two moments in time with a mixed method: semi-structured interviews with network managers and an online questionnaire for all network members. Density and degree centralization were used to examine the information exchange structures. Ucinet was used to analyze the data, with use of the statistical tests: Compare Density Procedure and Quadratic Assignment Procedure. This study shows that different structures of information exchange can be distinguished, concerning both material and knowledge-based information. The overall connectedness of the studied structures of the networks are quite similar, but the way in which the involvement is structured turns out to be different between the networks. Over time, the overall connectedness of those structures appears to be stable, but the internal dynamics reveals a major change in relationships between organizations in the networks. Our study yields empirical evidence for the existence of and the differences between structures and dynamics of both material and knowledge-based information exchange relationships. With a loss of more than a half of the relations in a year, the relationships between the organizations in the network are not very stable over time. The contrast between major internal dynamics and the stable overall connectedness is an important point of concern for network managers and public officials, since this impermanence of relations means that long-term integrated care cannot be guaranteed.


Community Composition and Diversity of Coastal Bacterioplankton Assemblages in Lakes Michigan, Erie, and Huron.
The Laurentian Great Lakes, including Lakes Superior, Michigan, Huron, Erie, and Ontario, located in the eastern part of North America are considered the largest of freshwater lakes in the world; however, very little is known about the diversity and distribution of indigenous microbial assemblages within these vast bodies of freshwater systems. Therefore, to delineate the microbial structure and community composition in these aquatic environments, combinations of high-throughput sequencing and fluorescent in situ hybridization (FISH) approaches were utilized to quantitatively characterize the occurrence, diversity, and distribution of bacterioplankton assemblages in six different sites located along the coastal regions of Lakes Michigan, Huron, and Erie. Phylogenetic examination showed a diverse bacterial community belonging to 11 different taxonomic groups. Pyrosequencing results revealed that the majority of the sequences were clustered into four main groups, i.e., Proteobacteria, Bacteriodetes, Actinobacteria, and Cyanobacteria, while fluorescent in situ hybridization also showed the numerical dominance of members of the Gammaproteobacteria and the Cytophaga-Flavobacterium in the six lake sites examined. Overall, the assemblages were shown to be quite diverse in distribution among the lake sites examined, comprising mostly of various heterotrophic populations, with the exception of the Lake Erie-Sandusky Bay site with more than 50% domination by autotrophic Cyanobacteria. This indicates that combinations of factors including water chemistry and various anthropogenic disturbances as well as the lake morphometric characteristics are probably influencing the community structure and diversity of the bacterial assemblages within the systems.


Gold nanoparticles/horseradish peroxidase encapsulated polyelectrolyte nanocapsule for signal amplification in Listeria monocytogenes detection.
Bioconjugate nanocapsules were fabricated by using polystyrene sulfonate (PSS) to encapsulate gold nanoparticles (AuNPs) bearing adsorbed horseradish peroxidase (HRP). The average size of nanocapsule was in a range 150-400 nm. The efficiency of the capsules to enhance signals in an immunoassay was demonstrated by using an enzyme linked immunosorbent assay (ELISA) to detect the food-borne pathogen -Listeria monocytogenes. The antibody adsorbed onto the PSS shell of the nanocapsules provided the recognition molecule. For a given quantity of antibody, the bioconjugate nanocapsules showed 30 times greater sensitivity and a shorter assay time (5 min) when compared to conventional ELISA using an HRP labelled antibody. This proof-of-concept encapsulation of HRP through PSS nanocapsules may pave the way for alternative signal enhancement strategies where sensitivity is a priority.


Evolving treatment strategies in thin cutaneous head and neck melanoma: 1 institution's experience.
Although existing melanoma literature provides recommendations for thinner lesions (≤1 mm) within a heterogeneous population, a focus on the head and neck group is less pervasive. The records of 49 node-negative individuals with thin head and neck melanoma that underwent surgical intervention ± sentinel lymph node (SLN) biopsy were reviewed. A significant increased Breslow thickness and mitotic rate, and a trend toward significance in Clark level ≥ IV were shown in patients that underwent an SLN biopsy versus those that did not. The total number of positive biopsies was 2 (5%). In our subset analysis using the modified American Joint Committee on Cancer recommendations by Wong and colleagues, the incidence of positive SLN biopsy would have increased to 11%. We advocate performing an SLN biopsy in thin head and neck melanomas for primary tumors > 0.75 mm, regardless of "high-risk" features as described by Wong and colleagues.


Trajectories and individual determinants of regular cancer screening use over a long period based on data from the French E3N cohort.
Despite several incentive policies for cancer screenings over the last two decades, the overall and regular use of cancer screenings remains insufficient in France. While the individual determinants of cancer screening uptake have been fairly well studied, the literature has rarely focused on the regularity of screening uptake, which is key to early cancer detection. We aimed to address this issue by studying cancer screening behaviors over 15 years, emphasizing the regularity and diversity of use. Using data from 40,021 women in the French E3N cohort, we studied the individual trajectories of screenings for breast, colorectal and cervical cancer between 2000 and 2014. We employed optimal matching methods to identify typical behaviors of use for each cancer screening. Then, we determined the associations between the identified behavior screening patterns for the different cancer screenings and, finally, assessed the associated individual determinants with logistical and multinomial models. We found that screening behaviors were fairly stable over time, with few typical screening patterns for each cancer. Overall, once a woman starts screening, she continues, and once she stops, she no longer returns. Cancer screening behaviors appear consistent; in particular, insufficient use of mammography appears to be associated with long-term nonuse of other cancer screenings. Factors associated with low or nonuse of screening are overall common between cancer screenings and are similar to those identified in the literature of screening use at a single point in time. Ultimately, these barriers prevent some women from entering a screening process in the long run, ultimately reinforcing social inequalities in health. Targeting women with insufficient mammography uptake may reach women outside of cancer screening settings more generally and, thus, both increase the overall uptake of cancer screening and reduce social inequalities in cancer screening.


Retracted: Study on the Mental Health Service Behavior of Medical Staff Based on Electrocardiogram.
[This retracts the article DOI: 10.1155/2022/7580008.].


Ber-H2 (anti-CD30)-saporin immunotoxin: a new tool for the treatment of Hodgkin's disease and CD30+ lymphoma: in vitro evaluation.
An immunotoxin containing an anti-CD30 monoclonal antibody (Ber-H2) and saporin, a ribosome-inactivating protein type 1, is described. It specifically inhibits protein synthesis by Hodgkin derived target cell lines with a very high efficiency (IC50 ranging from 5 x 10(-12) M to 5 x 10(-14) M, as saporin), while irrelevant immunotoxins do not. Present results suggest that this immunotoxin could be used for in vivo therapy as well as for ex vivo bone marrow purging in Hodgkin's disease and CD30+ lymphomas.


Bilateral calcified ureteral stenosis in eosinophilic granulomatosis with polyangitis.
Ureteral calcification is a rare complication of systemic vasculitis. Bilateral ureteral calcification in a patient with eosinophilic granulomatosis with polyangitis led to obstructive uropathy. A combination of immunosuppressive therapy and ureteral reconstruction successfully restored kidney function.


Changing trends in the epidemiology of pediatric lead exposure: interrelationship of blood lead and ZPP concentrations and a comparison to the US population.
To determine blood lead and zinc protoporphyrin (ZPP) concentrations in a pediatric population, confirm their interrelationship at low blood lead concentrations, and assess changing trends through comparison of these data with those found in a similar population 10 years earlier and to US national values. The study was conducted in a large pediatric hospital in the Washington DC area (CNMC) on patient whole blood specimens (n = 4908) (0-17 years) accrued from January 2001 to June 2002. Pediatric blood lead concentrations were determined by atomic absorption spectrophotometry, and ZPP by hematofluorometry. The data were analyzed using a computer adaptation of the Hoffmann approach. Blood lead level (BLL) means ranged between 2.2 and 3.3 micro g/dL, and the median BLL was 3 micro g/dL throughout. Mean ZPP concentrations ranged between 21.1 and 26.6 micro g/dL and the median concentrations between 21 and 27 micro g/dL. In comparison to data obtained from a similar pediatric population at CNMC between 1991 and 1992, pediatric BLLs have significantly declined in the Washington DC area. The current data are also compared with data obtained from the National Health and Nutrition Examination Survey (NHANES III) of the US population. The interrelationship between ZPP and BLLs is examined.


Are people with disabilities at higher risk of COVID-19-related mortality?: a systematic review and meta-analysis.
To undertake a systematic review and meta-analysis to estimate the relative risk of COVID-19-related mortality among people with disabilities compared to people without disabilities. Systematic review and meta-analysis. We systematically searched four databases from March 1, 2020, to August 15, 2022. We included prospective studies with a baseline assessment of disability and a longitudinal assessment of the COVID-19-related mortality. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. We undertook random-effects meta-analyses to calculate pooled adjusted hazard ratios for COVID-19-related mortality for people with disabilities, also disaggregated by disability type and study setting. We identified 2596 articles throughout the electronic data search, and 56 studies were included in the review. Most (73%) had a moderate risk of bias. The pooled adjusted effect estimate for COVID-19-related mortality in people with disabilities compared to those without was 2.7 (95% confidence interval [CI]: 2.4-3.2). Heterogeneity between the studies was high (τ2 = 0.28, I2 = 97%). Effect estimates were highest for population-based samples (3.3, 95% CI: 2.7-3.9), compared to hospital settings (2.1, 95% CI: 1.7-2.7). Risk was not elevated among people with disabilities in care home settings (1.6, 95% CI: 0.7-3.5). Disaggregation by disability type showed that people with intellectual disabilities were at the highest relative risk of COVID-19 mortality. Risk of COVID-19 mortality is elevated among people with disabilities, especially people with intellectual disabilities. Efforts are needed to collect better routine data on disability and to include people with disabilities in the pandemic response for COVID-19.


[Male non-neurogenic overactive bladder].
Male lower urinary tract symptoms (LUTS) and in particular overactive bladder (OAB) are a frequent reason for consultation in urology and have a significant functional impact in patients. To synthesize current knowledge on non-neurogenic OAB in male patients. A systematic literature review based on Pubmed, Embase, Google Scholar was conducted in June 2020. The prevalence of OAB and benign prostatic hyperplasia increases with age. Symptoms of OAB, on the one hand, and symptoms of prostatic bladder outlet obstruction, on the other hand, can be concomitant and the causal link between the two types of symptoms is difficult to establish. In case of mixed symptoms, it is recommended to treat the most troublesome type of symptoms first and to inform the patient of the risks of failure or deterioration. Indeed, many patients remain symptomatic after prostate surgery and the predictive factors for failure remain to be defined. Thus, preoperative urodynamics is not routinely performed even in case of OAB. De novo detrusor overactivity after radical prostatectomy can reach 77% and persists in the majority of cases. The overall relative risk of storage symptoms after radiotherapy and brachytherapy is higher than that after prostatectomy. The etiology of OAB after prostate surgery is multifactorial. While drug treatments have proven to be effective, little data exists on second-line treatments for OAB after prostate surgery. OAB in men is often linked to a prostatic bladder outlet obstruction. It is essential to inform patients about the possibility of persistence, deterioration, or occurrence of OAB after prostate surgery while the predictors of surgical failure are not clearly defined.


Extracellular loop 3 substitutions K589N and A590S in FSH receptor increase FSH-induced receptor internalization and along with S588T substitution exhibit impaired ERK1/2 phosphorylation.
The interaction of follicle stimulating hormone with its specific GPCR, the follicle stimulating hormone receptor (FSHR) is facilitated by the extracellular loops (ELs) which contact the transmembrane domain and relay the signal downstream. In order to determine the contribution of non conserved residues from the EL3 of FSHR in conferring specificity to FSH-FSHR interaction, they were swapped with respective residues from luteinizing hormone/choriogonadotropin receptor. The triple mutant EL3M exhibited increased internalization of FSH-FSHR complexes without affecting the cAMP signaling response. Here, substitution point mutants S588T, K589N and A590S of the EL3 of FSHR were generated and characterized. None of these substitutions affected FSHR expression, FSH binding ability and cAMP production as compared to wild type FSHR. However, the high internalization of EL3M was observed to be due to the K589N and A590S substitutions. Further, all the mutants showed an impaired FSH mediated ERK phosphorylation response and the extent of impairment was most striking in case of the A590S substitution. Interestingly, S588T mutant exhibited impaired ERK phosphorylation, without change in receptor internalization, indicating that these processes can be dissociated. Thus, the FSHR specific residues K589 and A590 in the EL3 of FSHR seem to be crucial for FSH-induced internalization and ERK phosphorylation.


Evaluation of perfluorooctanoate for potential genotoxicity.
Perfluorooctanoate (PFOA) is a fully fluorinated eight-carbon fatty acid analog with exceptional stability toward degradation that has been used as an industrial surfactant and has been detected in environmental and biological matrices. Exposures to PFOA in the workplace and in the environment have continuously stimulated investigations into its potential human health hazards. In this article, the results of fifteen unpublished genotoxicity assays conducted with perfluorooctanoate (as either the linear or linear/branched ammonium salt (APFO) or the linear/branched sodium salt) are reported and include: seven mutation assays (three in vitro reverse mutation assays with histidine auxotrophic strains of Salmonella typhimurium, two in vitro reverse mutation assays with the tryptophan auxotrophic Escherichia coli WP2uvr strain, one in vitro mitotic recombination (gene conversion) assay with Saccharomyces cerevisiae D4, and an in vitro Chinese hamster ovary (CHO) HGPRT forward mutation assay); seven studies to assess potential for chromosomal damage (three in vitro CHO chromosomal aberration studies, an in vitro human whole blood lymphocyte chromosomal aberration study, and three in vivo mouse micronucleus assays); and an in vitro C3H 10T1/2 cell transformation assay. Although PFOA has not been demonstrated to be metabolized, all in vitro assays were conducted both in the presence and in the absence of a mammalian hepatic microsomal activation system. These assays were originally described in twelve contract laboratory reports which have been available via the United States Environmental Protection Agency public docket (Administrative Record 226) for over a decade; however, the details of these assays have not been published previously in the open scientific literature. With the exception of limited positive findings at high and cytotoxic concentrations in some assay trials which reflected the likely consequence of cytotoxic disruption of normal cellular processes and not a specific genotoxic effect, the results of the studies presented in this paper and other published results clearly demonstrate the absence of direct mutagenic or genotoxic risk associated with PFOA. This finding is consistent with the physical/chemical characteristics of PFOA and is supported by other published genotoxicity studies.


Improved control over spontaneously formed GaN nanowires in molecular beam epitaxy using a two-step growth process.
We investigate the influence of modified growth conditions during the spontaneous formation of GaN nanowires (NWs) on Si(111) in plasma-assisted molecular beam epitaxy. We find that a two-step growth approach, where the substrate temperature is increased during the nucleation stage, is an efficient method to gain control over the area coverage, average diameter, and coalescence degree of GaN NW ensembles. Furthermore, we also demonstrate that the growth conditions employed during the incubation time that precedes nanowire nucleation do not influence the properties of the final nanowire ensemble. Therefore, when growing GaN NWs at elevated temperatures or with low Ga/N ratios, the total growth time can be reduced significantly by using more favorable growth conditions for nanowire nucleation during the incubation time.


Histological, molecular, clinical and outcomes characteristics of Multiple Lesion Glioblastoma. A retrospective monocentric study and review of literature.
Multiple lesion glioblastoma (M-GBM) represent a group of GBM patients in which there exist multiple foci of tumor enhancement. The prognosis is poorer than that of single-lesion GBM patients, but this actually is a controversial data. Is unknown whether multifocality has a genetic and molecular basis. Our specific aim is to identify the molecular characteristics of M-GBM by performing a comprehensive multidimensional analysis. The surgical, radiological and clinical outcomes of patients that underwent surgery for GBM at our institution for 2 years have been retrospectively reviewed. We compared the overall survival (OS), progression free survival and extent of resection (EOR) between M-GBM tumors (type I) and S-GBM (single contrast-enhancing lesion, type II). A total of 177 patients were included in the final cohort, 12 patients had M-GBM and 165 patients had S-GBM. Although patients with M-GBM had higher tumor volumes and midline location, the EOR was not different between both type of lesions. Higher percentage of tumors with EGFR overexpression was detected in M-GBM. PFS and OS was significantly shorter in M-GBM. Considering no differences in EOR, patients with M-GBM showed shorter PFS and OS in comparison with S-GBM. Evidences about the M-GBM origin as a multifocal lesion because its molecular profile are suggested.


Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 2: SAR of the amine tether.
A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin-dependant kinase. Inhibitory activities against the enzyme ranged from 34nM to >20microM and were dependant upon both the nature of the aryl group and the tether joining the basic amine to the indolyl maleimide core. Key interactions with the kinase ATP site and hinge region, predicted by homology modeling, were confirmed.


Hyperacusis-associated pathological resting-state brain oscillations in the tinnitus brain: a hyperresponsiveness network with paradoxically inactive auditory cortex.
Although hyperacusis, a hyperresponsiveness to non-noxious auditory stimuli, is a sound-evoked symptom, possible resting-state pathologic oscillations in hyperacusis brain have never been explored. By comparing 17 tinnitus participants with hyperacusis (T+H+) and 17 without hyperacusis (T+H-), we aimed to explore characteristic resting-state cortical activity of hyperacusis. The T+H+ and T+H- groups, strictly matched for all tinnitus sound characteristics to exclude tinnitus-related cortical changes, were compared using resting-state electroencephalography source-localized activity complemented by functional connectivity analyses. Correlation analysis revealed that hyperacusis questionnaire score was positively correlated with the orbitofrontal cortex (OFC) beta power, the right auditory cortex (AC) alpha1 power, and the dorsal anterior cingulate cortex (dACC) beta1 power. Compared to the T+H- group, the T+H+ group demonstrated increased beta power in the dACC and OFC, and increased alpha power in the right AC. Region of interest analyses including 17 normal controls further confirmed that these differences originated solely from relatively increased power of the T+H+ group, not from a relative power decrease of the T+H- group. Also, the T+H+ group showed increased connectivity between the OFC/dACC and the AC as compared to the T+H- group. The beta power increase in the OFC/dACC may indicate increased resting-state vigilance in tinnitus patients with hyperacusis. In addition, increased alpha power in the AC may reflect an adaptive top-down inhibition against sound stimuli probably mediated by the increased beta power of the OFC. The OFC/dACC, also frequently found to be activated in analogous diseases such as allodynia/hyperalgesia, may compose a hyperresponsiveness network.


Constant enthalpy change value during pyrophosphate hydrolysis within the physiological limits of NaCl.
A decrease in water activity was thought to result in smaller enthalpy change values during PPi hydrolysis, indicating the importance of solvation for the reaction. However, the physiological significance of this phenomenon is unknown. Here, we combined biochemistry and calorimetry to solve this problem using NaCl, a physiologically occurring water activity-reducing reagent. The pyrophosphatase activities of extremely halophilic Haloarcula japonica, which can grow at ∼4 M NaCl, and non-halophilic Escherichia coli and Saccharomyces cerevisiae were maximal at 2.0 and 0.1 M NaCl, respectively. Thus, halophilic and non-halophilic pyrophosphatases exhibit distinct maximal activities at different NaCl concentration ranges. Upon calorimetry, the same exothermic enthalpy change of -35 kJ/mol was obtained for the halophile and non-halophiles at 1.5-4.0 and 0.1-2.0 M NaCl, respectively. These results show that solvation changes caused by up to 4.0 M NaCl (water activity of ∼0.84) do not affect the enthalpy change in PPi hydrolysis. It has been postulated that PPi is an ATP analog, having a so-called high energy phosphate bond, and that the hydrolysis of both compounds is enthalpically driven. Therefore, our results indicate that the hydrolysis of high energy phosphate compounds, which are responsible for biological energy conversion, is enthalpically driven within the physiological limits of NaCl.


Failure of second-trimester measurement of soluble endoglin and other angiogenic factors to predict placental abruption.
High level of soluble endoglin (sEng), a potent antiangiogenic factor, predicts pre-eclampsia. We compared the serum levels of sEng in early second trimester in women with and without subsequent placental abruption. Proangiogenic placental growth factor (PlGF) and antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt-1) were also studied. Serum samples of 42 women with placental abruption and 50 control women, collected at 15 to 16 gestational weeks were analyzed for sEng, sFlt-1 and PlGF by immunoassays. The levels of sEng showed no difference between the cases and controls, but parous or smoking women with abruption had lower levels of sEng. Similarly, sFlt-1, PlGF, or sFlt-1/PlGF ratio showed no difference between the cases and the controls. Our data suggest that sEng, PlGF and sFlt-1 levels in early second trimester fail to predict placental abruption.


Neopterin and hsCRP are not correlated in gestational diabetes mellitus.
To determine serum neopterin and high sensitive C-reactive protein (hsCRP) levels in patients with and without gestational diabetes mellitus (GDM). Neopterin and hsCRP levels were quantified in 28 women with GDM and 20 pregnant women with normal glucose tolerance (NGT). Postpartum neopterin and hsCRP levels were measured in a follow-up study. Neopterin levels were significantly higher in women with GDM than in women with NGT (15.89 ± 8.19 nmol/L versus 10.4 ± 3.8 nmol/L, p < 0.008, respectively), however the levels significantly decreased after delivery in GDM group (15.89 ± 8.19 nmol/L versus 11.63 ± 5.96 nmol/L, p < 0.001). hsCRP levels were not different between women with and without GDM (5.74 ± 3.91 versus 5.73 ± 3.34, p = 0.9, respectively). In contrast, hsCRP levels decreased after delivery in patients with GDM (5.74 ± 3.91 versus 3.78 ± 2.78, p < 0.01). Neopterin levels were correlated with maternal age (r = 0.3, p = 0.02) and fasting glucose (r = 0.4, p = 0.004), postprandial glucose (r = 0.3, p = 0.01), HbA1c (r = 0.3, p = 0.02), whereas hsCRP levels were correlated with pre-pregnancy (r = 0.3, p = 0.04) and pregnancy body mass index (r = 0.4, p = 0.008). No correlation between serum neopterin and hsCRP levels was found (p = 0.9). Neopterin levels increased in patients with GDM; hence, it may be related to inflammation. However, the lack of correlation between neopterin and hsCRP suggests the role of different attitudes of these two parameters in the course of pregnancy and GDM.


Examining the variations in the implementation of interventions to address stillbirth from the national to subnational levels: experiences from Uganda.
The current global burden of stillbirth disproportionately affects regions such as sub-Saharan Africa, where Uganda is located. To respond to this burden, policies made at the national level were diffused from the centre and translated into service delivery at the district level, which is charged with implementation under the decentralization of health services arrangement. Variations emerge whenever policy recommendations are moved from national to subnational levels, with some aspects often lost along the way. Tools are available to facilitate knowledge of determinants of policy and innovation implementation within the healthcare system. However, the extent to which these have been applied to explain variations in implementation of interventions to address stillbirth reduction in Uganda remains scant. The aim of this article was to examine the variations in the implementation of interventions to address stillbirth from the national to the subnational levels in Uganda using the Consolidated Framework for Implementation Research (CFIR). The study adopted a qualitative case study design. Data were collected from a purposively selected sample of key informants drawn from both the national and subnational levels. All interviews were conducted in English and transcribed verbatim. ATLAS.ti was used to guide the coding process, which used a codebook developed following the CFIR domains as codes and constructs as sub-codes. Analysis followed a content analysis technique. National-level factors that favoured implementation of interventions to address stillbirth included the desire to comply with global norms, incentives to improve performance for stillbirth reduction indicators for better comparison with global peers, and clear policy alternatives as process implementation advanced by champions. Variations at the subnational level revealed aspirations to address service delivery gaps which fell within maternal health routine standard of care and ongoing health systems strengthening initiatives. Coalescing existing networks around maternal and child health was a key mobilization factor for advocacy and programming, with a promise that the set targets would be operationalized at the subnational level. The key champions were defined by their official roles within the district health systems, which enhanced accountability. Feedback and reflection were distinguished from the national to subnational through joint assemblies and formal audit reviews, respectively. A heavy influence of the global events directed national-level adaptation of interventions to address stillbirth. Implementation context at the subnational level led to local adaptation and translation of policy provisions from the national level to suit the context, which to a greater extent explains the variations in the final content of policy provisions delivered.


One-Dimensional Magnetic FeCoNi Alloy Toward Low-Frequency Electromagnetic Wave Absorption.
Rational designing of one-dimensional (1D) magnetic alloy to facilitate electromagnetic (EM) wave attenuation capability in low-frequency (2-6 GHz) microwave absorption field is highly desired but remains a significant challenge. In this study, a composite EM wave absorber made of a FeCoNi medium-entropy alloy embedded in a 1D carbon matrix framework is rationally designed through an improved electrospinning method. The 1D-shaped FeCoNi alloy embedded composite demonstrates the high-density and continuous magnetic network using off-axis electronic holography technique, indicating the excellent magnetic loss ability under an external EM field. Then, the in-depth analysis shows that many factors, including 1D anisotropy and intrinsic physical features of the magnetic medium-entropy alloy, primarily contribute to the enhanced EM wave absorption performance. Therefore, the fabricated EM wave absorber shows an increasing effective absorption band of 1.3 GHz in the low-frequency electromagnetic field at an ultrathin thickness of 2 mm. Thus, this study opens up a new method for the design and preparation of high-performance 1D magnetic EM absorbers.


Left-handedness: differences between student artists and scientists.
Majors in music and the visual arts had more left-handers among them than majors in the sciences. Handedness was determined by the self-reported hand used to perform a simple drawing task. Unexpectedly, a high proportion of left-handed females were in the sample.


Sealing ability in vitro study and biocompatibility in vivo animal study of different bioceramic based sealers.
The effectiveness of root canal therapy in endodontic practice is largely determined by providing a compact fluid-tight closure at the apex of the root canal, which inhibits irritant entry and buildup, which leads to a biological breakdown of the attachment mechanism and failure. During obturation, along with gutta-percha, root canal sealers are employed to fill voids and seal root canals. Root canal sealers come in a variety of shapes and sizes, each with its own set. Evaluation of sealing ability in vitro study by using scanning electron microscopy (SEM) and biocompatibility in vivo animals study of BioRoot RCS and meta Biomed bio_ceramic sealer (CeraSeal RCS) and compared the findings with that of Zinc oxide eugenol (ZOE) sealer as control. This study utilized two bio_ceramic sealers (BioRoot RCS and meta Biomed bio_ceramic sealer (CeraSeal RCS) and compared the findings with that of ZOE sealer as control. Biocompatibility was determined by examining histopathological biopsy specimens collected from rabbits. Each rabbit had four dentin tubes implanted into the subcutaneous tissues, one for BioRoot RCS, one for CeraSeal RCS, and one for ZOE RCS, with the fourth tube being empty haematoxylin and eosin were used to stain histological sections, and a light microscope was used to evaluate them. Extracted human single canal premolars were used to evaluate the sealing ability. The root canals were divided into three sections (coronal, middle, and apical). SEM was used to assess the adhesion quality at the sealer-dentin interface. BioRoot and CeraSeal sealers have excellent sealing adaptation and biocompatibility, as well as rapid tissue recovery, while ZOE sealers have a slower recovery of inflammatory reaction results when compared to bio_root and ceraSeal sealers, as well as a less sealing adaptation than the two other bio_ceramic sealers. In general, the two bioceramic sealers tested were biocompatible and capable of sealing or adhesion. While ZOE had less adherence ability and less biocompatibility.


Inhibition of caspase-3-like activity prevents apoptosis while retaining functionality of human chondrocytes in vitro.
Apoptosis was induced in a human chondrocyte cell line, T/C 28a4, by treatment with various stimuli, including camptothecin, tumor necrosis factor-alpha, staurosporine, okadaic acid, and reduced serum conditions. All stimuli induced a cytosolic DEVDase activity, coincident with apoptosis. Caspase activities in the lysates were characterized and quantitated with peptide cleavage profiles. To confirm that the results were not related to the immortalized nature of the cell line, primary human chondrocytes also were shown to undergo apoptosis under similar conditions, which resulted in increased cytosolic DEVDase activity. There was little or no caspase-1 (interleukin-1beta-converting enzyme) or caspase-8-like activity in the apoptotic cells. In all cases, the irreversible nonselective caspase inhibitor, Z-VAD-FMK, and the caspase-3-selective inhibitor, Ac-DMQD-CHO, inhibited DEVDase activity and apoptosis, whereas the caspase-1-selective inhibitor, Ac-YVAD-CHO, had no effect. Human chondrocytes were stably and transiently transfected with a type-II collagen gene (COL2A1) regulatory sequence driving a luciferase reporter as a specific marker of chondrocyte gene expression. Treatment of the cells with camptothecin or tumor necrosis factor-alpha plus cycloheximide significantly inhibited COL2A1 transcriptional activity. Significantly, cotreatment with Z-VAD-FMK or Ac-DMQD-CHO maintained COL2A1-reporter gene activity, indicating that the prevention of apoptosis by caspase-3 inhibition was sufficient to maintain cell functionality as assessed by the retention of type-II collagen promoter activity.


The Impacts of Drought on the Health and Demography of Eastern Grey Kangaroos.
Extreme climatic events such as droughts and floods are expected to become more intense and severe under climate change, especially in the southern and eastern parts of Australia. We aimed to quantify the relationship between body condition scores (BCS), demography, activity rate, and parasitic infections of eastern grey kangaroos on a large conservation property under different climate extremes by employing camera traps established at artificial water points (AWPs). The survey period included a severe drought, broken by a significant flooding event. Climatic and environmental conditions were documented using remotely sensed indices of moisture availability and vegetation productivity. These conditions were found to affect all health and population parameters measured. BCS, juvenile proportions, and sex ratios were most correlated with 6-month lags in climatic conditions, while the activity rate of kangaroos at AWPs was most correlated with vegetation productivity. Ticks were mostly found on individuals with a poorer BCS, while the concentration of parasitic eggs in feces was higher in autumn than in spring. Our study offers a glimpse into some of the environmental drivers of eastern grey kangaroo populations and their health, information that may become increasingly important in today's climate. It further emphasizes the importance of this knowledge for wildlife conservation efforts appropriate to managing the impact of climate change alongside other threats.


The Endo-lysosomal System in Parkinson's Disease: Expanding the Horizon.
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, and its prevalence is increasing with age. A wealth of genetic evidence indicates that the endo-lysosomal system is a major pathway driving PD pathogenesis with a growing number of genes encoding endo-lysosomal proteins identified as risk factors for PD, making it a promising target for therapeutic intervention. However, detailed knowledge and understanding of the molecular mechanisms linking these genes to the disease are available for only a handful of them (e.g. LRRK2, GBA1, VPS35). Taking on the challenge of studying poorly characterized genes and proteins can be daunting, due to the limited availability of tools and knowledge from previous literature. This review aims at providing a valuable source of molecular and cellular insights into the biology of lesser-studied PD-linked endo-lysosomal genes, to help and encourage researchers in filling the knowledge gap around these less popular genetic players. Specific endo-lysosomal pathways discussed range from endocytosis, sorting, and vesicular trafficking to the regulation of membrane lipids of these membrane-bound organelles and the specific enzymatic activities they contain. We also provide perspectives on future challenges that the community needs to tackle and propose approaches to move forward in our understanding of these poorly studied endo-lysosomal genes. This will help harness their potential in designing innovative and efficient treatments to ultimately re-establish neuronal homeostasis in PD but also other diseases involving endo-lysosomal dysfunction.


Value of washed sputum gram stain smear and culture for management of lower respiratory tract infections in children.
To date, the technique of washed sputum examinations has not been widely used in the clinical management of lower respiratory tract infections in children. A total of 224 sputum samples from 125 pediatric patients with lower respiratory tract infections were collected for washed sputum Gram stain smears and cultures. The results with these methods were compared to find correlation rates. The value of washed sputum cultures was assessed by examining the clinical responses of the patients who received antibiotic therapies instituted on the basis of the sputum culture results. Isolation rates of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus were 22.4%, 9.4%, 4.9%, and 0.4%, respectively. For the prediction of H. influenzae, S. pneumoniae, and M. catarrhalis, the sensitivities of the washed sputum Gram stain smears compared with the culture method were 86.0%, 81.0%, and 90.9%, respectively. The specificities of the washed sputum Gram stain smear technique were 94.8%, 97.5%, and 98.1%, respectively. Overall, the sensitivity and specificity of the washed sputum Gram stain smear method were 85.5% and 87.2%, respectively. S. aureus was isolated from only one specimen; and washed sputum Gram stain smear estimation was correlated with the culture result. On the basis of the washed sputum culture results, appropriate antibiotic therapies were instituted for 93.3% of the patients with acute lower respiratory tract infections. This study suggests that the techniques of washed sputum Gram stain smear and culture are valuable and should be encouraged in clinical practice for the management of lower respiratory tract infections in children.


Targeted and Intracellular Antibacterial Activity against S. agalactiae of the Chimeric Peptides Based on Pheromone and Cell-Penetrating Peptides.
The significance of the complex bacterial ecosystem in the human body and the impediment of the mammalian membrane against many antibiotics together emphasize the necessity to develop antimicrobial agents with precise antimicrobial and cell-penetrating activities. A simple and feasible method for generating dual-function antimicrobial peptides inspired by highly hydrophobic peptide pheromone and cationic cell-penetrating peptides is presented. Furthermore, the extension of the peptide candidate library is achieved by modifying the charged domain. The bacteria-selective peptides L1, L2, L10, and L11 kill Streptococcus agalactiae by disrupting the membrane structure, and the targeted mechanism is suggested where the peptides offset the entrapment of S. agalactiae rather than of other bacteria. Moreover, L2 and L10 possess intracellular antibacterial activity and carrier property, which is mainly dependent on endocytosis. Given their suitable biocompatibility, high tolerance, no drug resistance, and effective antimicrobial capacity in a mouse mastitis model, L2 and L10 can be powerful weapons against S. agalactiae pathogen infection.


Changes of skin temperature of parts of the body and serum asymmetric dimethylarginine (ADMA) in type-2 diabetes mellitus Indian patients.
In India, number of people with type 2 Diabetes Mellitus (DM) would be 87 million by the year 2030. DM disturbs autonomic regulation of skin micro-circulation, and causes decrease in resting blood flows through the skin. The skin blood flow has a major effect on its temperature. The aim of the study was to evaluate changes of skin temperature of all parts of the body and serum asymmetric dimethylarginine, ADMA (μmol/L) in type-2 DM Indian patients. Group-I: Normal (n = 17; M/F: 10/15, mean ± SD = 43.2 ± 9.4 years); Group-II: Type-2 DM without cardiovascular (CV) complications (n = 15; M/F: 10/7, mean ± SD = 46.3 ± 14.0 years); Thermograms of all parts of the body were acquired using a non-contact infrared (IR) thermography camera (ThermaCAM T400, FLIR Systems, Sweden). Blood parameters and thyroid hormone were measured biochemically. Indian diabetic risk score (IDRS) was calculated for each subject. In type-2 DM patients without CV group (n = 15), there was a statistically significant (p = 0.01) negative correlations between HbA(1c) and skin temperature of eye and nose (r = -0.57 and r = -0.55 respectively). ADMA was correlated significantly (p = 0.01) with HbA(1c) (r = 0.65) and estimated average glucose, eAG (r = 0.63). In normal subjects, mean minimum and maximum values of skin temperatures were observed at posterior side of sole (26.89 °C) and ear (36.85 °C) respectively. In type-2 DM without CV, mean values of skin temperature in different parts of the body from head to toe were lesser than those values in control group; but this decreases were statistically significant in nose (32.66 Vs 33.99 °C, p = 0.024) as well as in tibia (32.78 Vs 33.13 °C, p = 0.036) regions.


Using web-based video to enhance physical examination skills in medical students.
Physical examination (PE) skills among U.S. medical students have been shown to be deficient. This study examines the effect of a Web-based physical examination curriculum on first-year medical student PE skills. Web-based video clips, consisting of instruction in 77 elements of the physical examination, were created using Microsoft Windows Moviemaker software. Medical students' PE skills were evaluated by standardized patients before and after implementation of the Internet-based video. Following implementation of this curriculum, there was a higher level of competency (from 87% in 2002-2003 to 91% in 2004-2005), and poor performances on standardized patient PE exams substantially diminished (from a 14%-22%failure rate in 2002-2003, to 4% in 2004-2005. A significant improvement in first-year medical student performance on the adult PE occurred after implementing Web-based instructional video.


[Results of arthroscopic treatment of rotator cuff rupture in patients over 60 years of age].
Increasing life expectancies in population increase the number of patients with rotator cuff tears. The purpose of this study was to evaluate clinical outcomes after arthroscopy rotator cuff repair in patients over 60 years old. We hypothesized that shoulder arthroscopy would allow significant improvements in clinical outcomes without serious complications. We screened from our shoulder arthroscopy database patients older than 60 years old, with rotator cuff tear, and minimun 2-year follow-up. The patients were evaluated using Constant scores for clinical outcomes and Quick-DASH score for quality of life. In total, 42 patients were enrolled in the study with a mean age of 66.7 years old (range 60 to 83). A double-row repair was indicated in 25 patients (59.5%), and single-row repair in 17 patients (40.5%). As associated injuries we found proximal biceps pathology in 31 patients (48.4%), subscapularis tears in 24 patients (37.5%), and SLAP tears in 3 patients (7.1%). Mean follow-up was 32.4 months. Constant scores improved from 48.3 preoperatively to 87.2 at final follow-up. Quick-DASH decreased from 52.5 preoperatively to 11.0 at final follow-up. Arthroscopy cuff repair in patients older than 60 years old provides satisfactory clinical outcomes without morbidity at medium follow-up.


Intensity-dependent modulatory effects of vagus nerve stimulation on cortical excitability.
Vagus nerve stimulation (VNS) is an effective treatment for refractory epilepsy. It remains unknown whether VNS efficacy is dependent on output current intensity. The present study investigated the effect of various VNS output current intensities on cortical excitability in the motor cortex stimulation rat model. The hypothesis was that output current intensities in the lower range are sufficient to significantly affect cortical excitability. VNS at four output current intensities (0 mA, 0.25 mA, 0.5 mA and 1 mA) was randomly administered in rats (n = 15) on four consecutive days. Per output current intensity, the animals underwent five-one-hour periods: (i) baseline, (ii) VNS1, (iii) wash-out1, (iv) VNS2 and (v) wash-out2. After each one-hour period, the motor seizure threshold (MST) was measured and compared to baseline (i.e. ∆MSTbaseline , ∆MSTVNS 1 , ∆MSTwash-out1 , ∆MSTVNS 2 and ∆MSTwash-out2 ). Finally, the mean ∆MSTbaseline , mean ∆MSTwash-out1 , mean ∆MSTwash-out2 and mean ∆MSTVNS per VNS output current intensity were calculated. No differences were found between the mean ∆MSTbaseline , mean ∆MSTwash-out1 and mean ∆MSTwash-out2 within each VNS output current intensity. The mean ∆MSTVNS at 0 mA, 0.25 mA, 0.5 mA and 1 mA was 15.3 ± 14.6 μA, 101.8 ± 23.5 μA, 108.1 ± 24.4 μA and 85.7 ± 18.1 μA respectively. The mean ∆MSTVNS at 0.25 mA, 0.5 mA and 1 mA were significantly larger compared to the mean ∆MSTVNS at 0 mA (P = 0.002 for 0.25 mA; P = 0.001 for 0.5 mA; P = 0.011 for 1 mA). This study confirms efficacy of VNS in the motor cortex stimulation rat model and indicates that, of the output current intensities tested, 0.25 mA is sufficient to decrease cortical excitability and higher output current intensities may not be required.


[Predictive factors of spontaneous pregnancies among women with diminished ovarian reserve patients treated with DHEA].
Diminished ovarian reserve remains a challenge in the reproductive medicine field. Treatment options for these patients are limited and there is no consensus to make any recommendations. Regarding adjuvant supplements, DHEA could play a role in follicular recruitment and, therefore, may increase spontaneous pregnancy rate. This study was a monocentric historical and observational cohort study carried out in the reproductive medicine department at the University Hospital, Femme-Mère-Enfant in Lyon. All women presenting with a diminished ovarian reserve treated with 75mg/day of DHEA were consecutively included. The main objective was to evaluate the spontaneous pregnancy rate. The secondary objectives were to identify predictive factors for pregnancy and the evaluation of treatment side effects. Four hundred and thirty-nine women were included. In all, 277 were analyzed, 59 had a spontaneous pregnancy (21.3%). The probability of being pregnant was respectively 13.2% (IC95 9-17.2%), 21.3% (IC95 15.1-27%) and 38.8% (IC95 29.3-48.4%) at 6, 12 and 24 months. Only 20.6% of patients complained of side effects. DHEA may improve spontaneous pregnancies in women with diminished ovarian reserve without any stimulation.


Thermal decomposition hazard evaluation of hydroxylamine nitrate.
Hydroxylamine nitrate (HAN) is an important member of the hydroxylamine family and it is a liquid propellant when combined with alkylammonium nitrate fuel in an aqueous solution. Low concentrations of HAN are used primarily in the nuclear industry as a reductant in nuclear material processing and for decontamination of equipment. Also, HAN has been involved in several incidents because of its instability and autocatalytic decomposition behavior. This paper presents calorimetric measurement for the thermal decomposition of 24 mass% HAN/water. Gas phase enthalpy of formation of HAN is calculated using both semi-empirical methods with MOPAC and high-level quantum chemical methods of Gaussian 03. CHETAH is used to estimate the energy release potential of HAN. A Reactive System Screening Tool (RSST) and an Automatic Pressure Tracking Adiabatic Calorimeter (APTAC) are used to characterize thermal decomposition of HAN and to provide guidance about safe conditions for handling and storing of HAN.


Coxiella burnetii outbreak, Northern Italy 2021.
We report an outbreak of 14 cases of Q fever among tourists caused by an infected calf and characterized by respiratory transmission and a high attack rate in humans. Following the identification of an index case of Q fever in September 2021, an epidemiological investigation was conducted in collaboration with local Health and Veterinary authorities and an unknown outbreak was discovered and terminated. The outbreak originated from the delivery by an infected cow, with spread of C. burnetii by air and infection via the respiratory route. The transmission period was calculated, and 25 potentially exposed tourists were identified: 14 were infected (56%) based on serological investigations, four were hospitalized, there were no deaths. All the 22 cows were tested by PCR for C. burnetii: 3 cows (14%) were positive on milk samples and one, the index animal, was also positive on blood. Timely diagnosis in a human patient was pivotal to identify the outbreak since involved animals were asymptomatic. The close collaboration between veterinary and human Public Health services in six different geographical areas of two countries was crucial for the rapid termination of the outbreak.


Efficacy of intravenous alendronate for the treatment of glucocorticoid-induced osteoporosis in children with autoimmune diseases.
Our objective was to investigate the efficacy of intravenous alendronate for the treatment of glucocorticoid-induced osteoporosis (GIOP) in children with autoimmune diseases. Five children with autoimmune disease and GIOP were treated with 5 mg intravenous alendronate once every 3 months. After 1 and 2 years, we evaluated the changes in the Z score of the femoral neck bone mineral density (BMD), serum bone alkaline phosphatase, and urinary deoxypyridinoline. Six patients with GIOP, whose BMD could be observed over a 1-year period without alendronate treatment, were defined as controls. After 1 and 2 years of treatment, intravenous treatment significantly inhibited bone loss. The efficacy of alendronate demonstrated a significant correlation with a high level of bone turnover markers before alendronate treatment. Intravenous alendronate is considered to be a good choice for the treatment of GIOP because of its excellent efficacy. In addition, our study suggests that the efficacy of alendronate depends on the bone turnover of patients before treatment. Intervention with bisphosphonates during periods of high bone turnover may be recommended.


Effects of subunit types of the recombinant GABAA receptor on the response to a neurosteroid.
When vertebrate brain poly(A)+ RNA is expressed in Xenopus oocytes the response of the GABA receptors formed is found to be inhibited allosterically by a neurosteroid, pregnenolone sulphate (PS). This negative modulation was reproduced after expressing RNAs encoding bovine GABAA receptor subunits in the combinations alpha i + beta 1, or alpha i + beta 1 + gamma 2 (where i = 1, 2 or 3). The characteristics of this inhibition vary significantly with the type of the alpha subunit (alpha 1, alpha 2, or alpha 3) used. When the bovine gamma 2L alternate form of the gamma 2 subunit was replaced by the human gamma 2S subunit, the behaviour was unchanged: the human gamma 2S subunit used is a newly-cloned form, which encodes a polypeptide with two amino acid differences from the human gamma 2 subunit previously described. The results of co-application of PS and 3 alpha-hydroxy-5 alpha-pregnan-ol-20-one, a neurosteroid which is a positive modulator of the GABAA receptor, indicate that these act at different sites on the receptor. PS also increases the desensitisation of the receptor by GABA. This effect, also, is alpha-subunit-type dependent and occurs by an acceleration of the fast phase of desensitisation.


Unravelling the Interaction of Piperlongumine with the Nucleotide-Binding Domain of HSP70: A Spectroscopic and In Silico Study.
Piperlongumine (PPL) is an alkaloid extracted from several pepper species that exhibits anti-inflammatory and anti-carcinogenic properties. Nevertheless, the molecular mode of action of PPL that confers such powerful pharmacological properties remains unknown. From this perspective, spectroscopic methods aided by computational modeling were employed to characterize the interaction between PPL and nucleotide-binding domain of heat shock protein 70 (NBD/HSP70), which is involved in the pathogenesis of several diseases. Steady-state fluorescence spectroscopy along with time-resolved fluorescence revealed the complex formation based on a static quenching mechanism. Van't Hoff analyses showed that the binding of PPL toward NBD is driven by equivalent contributions of entropic and enthalpic factors. Furthermore, IDF and Scatchard methods applied to fluorescence intensities determined two cooperative binding sites with Kb of (6.3 ± 0.2) × 104 M-1. Circular dichroism determined the thermal stability of the NBD domain and showed that PPL caused minor changes in the protein secondary structure. Computational simulations elucidated the microenvironment of these interactions, showing that the binding sites are composed mainly of polar amino acids and the predominant interaction of PPL with NBD is Van der Waals in nature.


Ultrastructure of pinealocytes of the cotton rat, Sigmodon hispidus.
Fine structural features of pinealocytes of cotton rats (Sigmodon hispidus) were examined. Golgi complexes, mitochondria, endoplasmic reticulum and polysomes are usual organelles seen in the perikaryonal cytoplasm of pinealocytes. Many non-granulated vesicles (40 to 80 nm in diameter) and a few granulated vesicles (about 100 nm in diameter) are associated with the Golgi cisternae. Occasionally, the cisternae contain granular materials. The perikaryonal cytoplasm of pinealocytes is characterized by the presence of inclusion bodies. These bodies are usually round in shape, not bounded by a limiting membrane and composed of fine granular or filamentous materials of high electron-opacity, which are similar in appearance to the substance seen in the nucleolonema. Pinealocyte processes, filled with abundant non-granulated vesicles and some granulated vesicles, are mainly found within the parenchyma and occasionally in perivascular spaces.


Relationship between insecticide resistance profiles in Anopheles gambiae sensu lato and agricultural practices in Côte d'Ivoire.
Insecticide-based malaria vector control is increasingly undermined due to the development of insecticide resistance in mosquitoes. Insecticide resistance may partially be related to the use of pesticides in agriculture, while the level and mechanisms of resistance might differ between agricultural practices. The current study aimed to assess whether phenotypic insecticide resistance and associated molecular resistance mechanisms in Anopheles gambiae sensu lato differ between agricultural practices. We collected An. gambiae s.l. larvae in six sites with three different agricultural practices, including rice, vegetable and cocoa cultivation. We then exposed the emerging adult females to discriminating concentrations of bendiocarb (0.1%), deltamethrin (0.05%), DDT (4%) and malathion (5%) using the standard World Health Organization insecticide susceptibility test. To investigate underlying molecular mechanisms of resistance, we used multiplex TaqMan qPCR assays. We determined the frequency of target-site mutations, including Vgsc-L995F/S and Vgsc-N1570Y, and Ace1-G280S. In addition, we measured the expression levels of genes previously associated with insecticide resistance in An. gambiae s.l., including the cytochrome P450-dependent monooxygenases CYP4G16, CYP6M2, CYP6P1, CYP6P3, CYP6P4, CYP6Z1 and CYP9K1, and the glutathione S-transferase GSTe2. The An. gambiae s.l. populations from all six agricultural sites were resistant to bendiocarb, deltamethrin and DDT, while the populations from the two vegetable cultivation sites were additionally resistant to malathion. Most tested mosquitoes carried at least one mutant Vgsc-L995F allele that is associated with pyrethroid and DDT resistance. In the cocoa cultivation sites, we observed the highest 995F frequencies (80-87%), including a majority of homozygous mutants and several in co-occurrence with the Vgsc-N1570Y mutation. We detected the Ace1 mutation most frequently in vegetable-growing sites (51-60%), at a moderate frequency in rice (20-22%) and rarely in cocoa-growing sites (3-4%). In contrast, CYP6M2, CYP6P3, CYP6P4, CYP6Z1 and CYP9K1, previously associated with metabolic insecticide resistance, showed the highest expression levels in the populations from rice-growing sites compared to the susceptible Kisumu reference strain. In our study, we observed intriguing associations between the type of agricultural practices and certain insecticide resistance profiles in the malaria vector An. gambiae s.l. which might arise from the use of pesticides deployed for protecting crops.


Dextromethorphan: polymorphic serum pattern of the O-demethylated and didemethylated metabolites in man.
1. The interindividual differences in serum concentrations of dextromethorphan (DM) and its metabolites were studied in 29 healthy subjects given 120 mg orally. They were also phenotyped according to the urinary ratio of debrisoquine and 4-hydroxy-debrisoquine. 2. Four (14%) subjects were found to be poor metabolizers (PM) with a dextromethorphan/dextrorphan metabolite ratio in plasma of 3.6 or more compared with extensive metabolizers (EM) with a ratio of 0.11 or less. Significant levels of 3-hydroxymorphinan were measurable in all individuals except two, both of whom were PMs. This subdivision corresponded to the phenotype determined by the metabolic ratio of debrisoquine (r = 0.92). 3. Twelve of the 29 subjects reported adverse drug reactions after dextromethorphan administration compared with none after placebo.


A ternary logic model for recurrent neuromime networks with delay.
In contrast to popular recurrent artificial neural network (RANN) models, biological neural networks have unsymmetric structures and incorporate significant delays as a result of axonal propagation. Consequently, biologically inspired neural network models are more accurately described by nonlinear differential-delay equations rather than nonlinear ordinary differential equations (ODEs), and the standard techniques for studying the dynamics of RANNs are wholly inadequate for these models. This paper develops a ternary-logic based method for analyzing these networks. Key to the technique is the realization that a nonzero delay produces a bounded stability region. This result significantly simplifies the construction of sufficient conditions for characterizing the network equilibria. If the network gain is large enough, each equilibrium can be classified as either asymptotically stable or unstable. To illustrate the analysis technique, the swim central pattern generator (CPG) of the sea slug Tritonia diomedea is examined. For wide range of reasonable parameter values, the ternary analysis shows that none of the network equilibria are stable, and thus the network must oscillate. The results show that complex synaptic dynamics are not necessary for pattern generation.


T2-weighted cardiac MR assessment of the myocardial area-at-risk and salvage area in acute reperfused myocardial infarction: comparison of state-of-the-art dark blood and bright blood T2-weighted sequences.
To compare different state-of-the-art T2-weighted (T2w) imaging sequences combined with late gadolinium enhancement (LGE) for myocardial salvage area (MSA) assessment by cardiac magnetic resonance (CMR). T2w imaging has been used to assess the myocardial area at risk (AAR) in acute myocardial infarction (AMI) patients, but its clinical application is challenging due to technical and physical limitations. Thirty patients with reperfused AMI underwent complete CMR imaging 2-5 days after hospital admission. Myocardial AAR and MSA were quantified on four different T2w sequences: (a) free-breathing T2-prepared single-shot balanced steady-state free precession (T2p_ssbSSFP); (b) breathhold T2-weighted acquisition for cardiac unified T2 edema (ACUTE); (c) breathhold T2w dark-blood inversion recovery turbo-spin echo (IR-TSE) (short-term inversion recovery: STIR); and (d) free-breathing high-resolution T2 dark-blood navigated BLADE. The diagnostic performance of each technique was also assessed. Quantitative analysis showed significant differences in myocardial AAR extent as quantified by the four T2w sequences (P < 0.05). There were also significant differences in sensitivity, specificity and overall diagnostic performance. Detection and quantification of AAR, and thus of MSA, by T2wCMR in reperfused AMI patients varied significantly between different T2w sequences in the same clinical setting.


Differential Diagnosis of a Case of Dercum's Disease with Possible Familial Involvement and Review of Literature.
Dercum's disease (DD), also described as adiposis dolorosa, is a poorly understood and rare adipose tissue disorder involving obesity and painful adipose tissue masses. Patients may have associated bruising and constitutional symptoms such as fatigue, difficulty concentrating, and sleep disturbance. DD was initially described in 1888 by Francis Xavier Dercum, and was classified into four subtypes, including generalized diffuse, generalized nodular, localized nodular, and juxta-articular subtypes. While this disease has been described for more than 130 years, its etiology and treatment remain elusive. We describe a case of a patient with DD who presented to Ochsner Medical Center, New Orleans, LA, for evaluation of treatment options. We review current knowledge on this rare disease and data on modern treatment methods.


Two-stage ECG signal denoising based on deep convolutional network.
Background.An electrocardiogram (ECG) is an effective and non-invasive indicator for the detection and prevention of arrhythmia. ECG signals are susceptible to noise contamination, which can lead to errors in ECG interpretation. Therefore, ECG pretreatment is important for accurate analysis.Methods.The ECG data used are from CPSC2018, and the noise signal is from MIT-BIH Noise Stress Test Database. In the experiment, the signal-to-noise ratio (SNR), the root mean square error (RMSE), and the correlation coefficientPare used to evaluate the performance of the network. The method proposed is divided into two stages. In the first stage, a Ude-net model is designed for ECG signal denoising to eliminate noise. The DR-net model in the second stage is used to reconstruct the ECG signal and to correct the waveform distortion caused by noise removal in the first stage. In this paper, the Ude-net and the DR-net are constructed by the convolution method to achieve end-to-end mapping from noisy ECG signals to clean ECG signals.Result.In SNR, RMSE andPindicators, Ude-net + DR-net proposed in this paper can achieve the best performance compared with the other five schemes (FCN, U-net etc). In the three data sets, SNR can be increased by 11.61 dB, 13.71 dB and 14.40 dB and RMSE can be reduced by 10.46 × 10-2, 21.55 × 10-2and 15.98 × 10-2.Conclusions.Despite the contradictory results, the proposed two-stages method can achieve both the elimination of noise and the preservation of effective details to a large extent of the signals. The proposed method has good application prospects in clinical practice.


Conformational changes during in vitro balloon fracture of internal aortic annuloplasty ring.
HAART 300 300 (BioStable Science and Engineering, Inc) aortic annuloplasty rings restore physiologic annular geometry during aortic valve repair. Transcatheter valve-in-ring implantation is appealing for recurrent valve dysfunction but may necessitate balloon fracture of downsized annuloplasty rings. We characterized the feasibility of ring fracture and changes in ring geometry preceding fracture. The 19-mm, 21-mm, and 23-mm HAART 300 annuloplasty rings were obtained, and 23-mm, 24-mm, 25-mm, and 26-mm valvuloplasty balloons were obtained. Under continuous fluoroscopy and video recording, a 23-mm balloon was inflated within a 19-mm ring at 1 atm/s until ring fracture or balloon failure occurred. If balloon failure occurred, experiments were sequentially repeated with 1-mm upsized balloons until ring fracture occurred or no larger-sized balloons were available. Upon balloon inflation, all rings exhibited an irreversible conformational change from an elliptical, annular geometry to a circular shape with ring posts flaring outward. A 23-mm balloon burst at 21 atm without fracturing the 19-mm ring. The 24-mm balloon fractured the 19-mm ring at 15 atm. Likewise, a 24-mm balloon ruptured at 18 atm without fracturing the 21-mm annuloplasty ring. A 25-mm balloon fractured the 21-mm ring at 18 atm. Finally, a 26-mm balloon burst at 20 atm without fracturing a 23-mm annuloplasty ring, but it did elicit the confirmational changes described. All fractures occurred along the upslope of a ring post. The exposed metal frame was visible after the 21-mm ring fracture. Fracture of HAART 300 aortic annuloplasty rings is possible with an oversized, high-pressure balloon. However, the geometrical changes in the ring and subsequent rupture of its fabric covering may be obstacles to safe, in vivo ring fracture.


Functional characterization of a KCNAB3 genetic epilepsy with febrile seizures plus adult mouse model.
Genetic epilepsy with febrile seizures plus (GEFS+) is a type of epileptic syndrome closely related to heredity factors, which can be caused by gene mutations. However, it still remains unclear how these mutations result in seizures. Previously, we identified a new heterozygous missense mutation of the KCNAB3 gene, H258R, in the GEFS+ family; the electric currents of the human embryonic kidney 293 (HEK293) cells co-expressing Kvβ3 (H258R) and Kv1.1 showed obvious inactivation. This study sought to examine the effects of this mutation on the potassium channels in the mammalian brain. Mutant mice were generated by introducing the human H258R missense mutation within exon 10 at an equivalent position in the mouse KCNAB3 gene via CRISPR/Cas9 and homologous recombination. A patch clamp was used to detect the potassium currents in the pyramidal cells of the hippocampal CA1 region of the mutant mice. The total potassium currents of the pyramidal cells in the hippocampal CA1 region of KCNAB3 [wild-type (WT)] and KCNAB3 (H258R) adult mice were recorded with increased voltage. We found a decreased total potassium current in the H258R group but no significant differences at a maximum voltage (+80 mV; P>0.05). These results suggest that the KCNAB3 mutation reduced hippocampal potassium currents in this mouse model.


[When was the Royal Academy of Surgery founded? What were its statutes?].
The Royal Academy of Surgery was generally thought to have been created in 1731. In reality, it was a group called "the Academy Society of Surgery" which met at this time. The true date for the foundation of the Royal Academy of Surgery was in July 1748.


How do narratives relate to heuristics?
Narratives and heuristics are both tools for dealing with uncertainty, intractability, and incommensurability, that is, for all real-world situations outside the domain of Bayesian decision theory. But how do narratives and heuristics relate? I suggest two links: Heuristics select narratives to explain events, and "big" narratives select the heuristics that people live by, to execute their values and moral principles.


ZNF521/EBF1 axis regulates AKR1B1 to promote the proliferation, migration, and invasion of gastric cancer cells.
Although the incidence and death rates of gastric cancer (GC) are decreasing, approximately one million new cases and 800,000 GC-related deaths were reported worldwide in 2018. Currently, the oncogenesis of GC remains unclear, and the demand for novel treatment options are unmet. Here, we explored the role of aldo-keto reductase family 1 member B (AKR1B1) in the progression of GC. The proliferation, migration, and invasion of GC cells were evaluated by CCK-8 assay, wound healing assay, and transwell assay, respectively. The interaction between EBF transcription factor 1 (EBF1) and the promoter region of AKR1B1 was determined by luciferase reporter assay and chromatin immunoprecipitation (ChIP). Gene expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting assay. The expression of AKR1B1 was elevated in GC cells, resulting in increased cell proliferation, migration, and invasion. Meanwhile, EBF1 was a negative regulator of AKR1B1; its overexpression suppressed AKR1B1 expression and GC progression. Furthermore, knockdown of ZNF521 induced EBF1 expression, thus suppressing AKR1B1 expression and resulting in attenuated GC growth and invasiveness. Notably, knockdown of ZNF521 attenuated GC progression and was rescued by overexpression of AKR1B1. Our current study revealed a novel ZNF521/EBF1/AKR1B1 axis in GC and elaborated its important role in promoting GC progression, providing potential therapeutic targets for anti-GC treatments.


Design and application of near-infrared fluorophore based on a novel thiazolidinedione-functionalized dicyanoisophorone.
A novel dicyanoisophorone (DCI)-based NIR fluorophore employing 2, 4-thiazolidinediones as the modification site was designed for fluorescence imaging. The fluorophore was assessed as a switchable reporter for H2O2 and the probe exhibited lysosomes-targeted, a large turn-on fluorescence signal at 720 nm with a large stokes shift (150 nm) and can be used in biological systems. The ability of the novel fluorophore to emit NIR fluorescence through a "turn-on" activation mechanism makes it a promising fluorophore for in vivo imaging applications. The strategy of introducing the thiazolidinediones with the easy modification site into the fluorophore has a good application prospect to expand the application of the NIR fluorophore.


Glomerular filtration and volume regulation in gravid animal models.
The gestational increase in glomerular filtration rate (GFR) that occurs in the normal rat is the result exclusively of an increase in plasma flow rate, and there is no sustained increase in glomerular capillary blood pressure during a normal pregnancy. The factor or factors that initiate the gestational renal vasodilatation (and plasma volume expansion) are maternal, not fetoplacental in origin. Apart from ruling out prostaglandins as an initiating agent, animal studies have not yet defined the precise nature of the initiating factors; it is unlikely that the gestational plasma volume expansion can be the sole cause of the increased GFR seen in pregnancy. The normal kidney in pregnancy exhibits substantial renal reserve to amino acid infusion, despite being already vasodilated by the gestational stimulus. The renal volume-sensing and control system of tubuloglomerular feedback is fully operative in pregnancy, and appears to be 'reset' to perceive the expanded plasma volume of pregnancy as normal. This observation agrees with many other indications that the sensors perceiving and controlling intravascular volume are reset during a normal pregnancy to enable the mother to accommodate the increased plasma volume without provoking a natriuretic response. Multiple pregnancies do not have any cumulative, long-term deleterious effects on renal function, either when the underlying function is normal or when it has been compromised by removal of renal mass plus high-protein feeding. In the short-term, pregnancy does not worsen kidney function when underlying glomerulonephritis is present. Therefore, the hyperfiltration of pregnancy does not appear to be a damaging entity, unlike other hyperfiltration states studied in the male rat. Still unknown is the mechanism by which pregnancy does worsen underlying glomerular disease in some women. The preliminary data in the rat, presented above, suggest that the exacerbating influence may be something other than the glomerular haemodynamic changes of pregnancy.