Auditory and visual neurons in the cat's superior colliculus selective for the direction of apparent motion stimuli.
In the cat, cells of the superior colliculus (SC) and the tectofugal pathways of the visual system are highly selective for the direction of a moving visual stimulus. Deep layer units of SC in addition respond to auditory and somatosensory stimuli, but the proportion of such non-visual cells is usually found to be much lower than that of visual cells. We recorded the responses of 174 cells in the SC to sequentially presented, localized visual and/or auditory stimuli that produced the sensation of apparent motion to human observers. Controls using single LED flashes or tone pips or clicks at very long intervals that did not produce apparent motion were also used. We found both visual and auditory units that responded vigorously to the apparent motion stimuli and showed pronounced directional selectivity. However, in the auditory domain such units were rare and thus did not increase the proportion of auditory responses in SC substantially. Varying the interstimulus interval (ISI) of these stimuli, both visual and auditory, indicated that the mechanism of direction selectivity in these cells was suppression of the response in the 'non-preferred' direction rather than facilitation in the 'preferred' direction. With long ISI's of 200 ms or more, every single stimulus gave a discrete response peak of constant amplitude. For ISI's of 50 ms or less the discrete peaks merged to a continuous response. Maximal firing rate in the preferred direction remained the same as for longer ISI's, but was decreased for movement in the non-preferred directions. Very short ISI's (10 ms) produced little response in any direction.(ABSTRACT TRUNCATED AT 250 WORDS)


Akimba Proliferative Diabetic Retinopathy Model: Understanding Molecular Mechanism and Drug Screening for the Progression of Diabetic Retinopathy.
As the prevalence of diabetes has reached epidemic proportions worldwide, diabetic retinopathy incidence is increasing rapidly. An advanced diabetic retinopathy (DR) stage can lead to a sight-threatening form. There is growing evidence showing diabetes causes a range of metabolic changes that subsequently lead to pathological modifications in the retina and retinal blood vessels. To understand the complex mechanism of the pathophysiology of DR, a precise model is not readily available. By crossbreeding the Akita and Kimba strains, a suitable proliferative DR model was acquired. This new Akimba strain manifests marked hyperglycemia and vascular changes, which resemble the early and advanced stage of DR.Here, we describe the breeding method, colony screening for experiments, and imaging techniques widely used to investigate the DR progression in this model. We elaborate step-by-step protocols to set up and perform fundus, fluorescein angiography, optical coherence tomography, and optical coherence tomography-angiogram to study retinal structural changes and vascular abnormalities. In addition, we show a method to label the leukocytes with fluorescence and laser speckle flowgraphy to examine the inflammation in the retina and retinal vessel blood flow speed, respectively. Lastly, we describe electroretinogram to evaluate the functional aspect of the DR transformations.


[Vascular endothelial growth factor in benign and malignant pleural effusions].
Vascular endothelial growth factor (VEGF) is a potent inducer of capillary permeability and its role as a crucial mediator in pleural fluid formation has been established. This study was conducted to assess the usefulness of VEGF for diagnosing malignant and non-malignant pleural effusions of various causes. VEGF levels in pleural effusions collected from 52 patients (20 with malignant effusion, 12 with tuberculous effusion, 10 with transudative effusion, and 10 with parapneumonic effusion) were assessed by enzyme-linked immunosorbent assay. The median level of VEGF was significantly higher (P = .001) in exudative effusions (10.16 pg/mL) than in the transudative effusions (3.82 pg/mL). Although malignant pleural fluids tended to have higher median and mean levels of VEGF compared to tuberculous effusions, the difference was not statistically significant. Pleural VEGF levels in subtypes of lung cancer and in malignant effusions of different origins were not significantly different. In conclusion, although VEGF levels in pleural effusions of different origins vary, they were only able to discriminate exudates from transudates significantly in this study. Further studies in larger groups of patients are needed to establish the role of VEGF in diagnosing malignant and/or tuberculous effusions.


Poor prognostic value of lymphovascular invasion for pT1 urothelial carcinoma with squamous differentiation in bladder cancer.
Lymphovascular invasion (LVI) is the primary and essential step in the systemic dissemination of cancer cells. The aim of our study was to assess the independent prognostic role of LVI for pT1 urothelial carcinoma with squamous differentiation in bladder cancer. We retrospectively analyzed the clinical and pathological information of 206 patients diagnosed pT1 urothelial carcinoma with squamous differentiation. Of the 206 patients, LVI was detected in 57 (27.6%) patients. The 5 year cancer specific survival (CSS) rates were 87.2% in LVI (-) and 52.4% in LVI (+) (p < 0.001). According to univariate analysis, tumor multiplicity, tumor size, recurrence and LVI were the prognostic factors associated with CSS. Additionally, tumor size and LVI significantly influenced the CSS in multivariate analysis. TURBT had shorter median CSS than RC in recurred patients with LVI (+). Our study suggested that LVI is an important predictor for survival of pT1 urothelial carcinoma with squamous differentiation. LVI positive status and tumor size ≥3 cm led to a higher risk of death. RC should be routinely performed in recurred LVI (+) bladder cancer patients of pT1 urothelial carcinoma with squamous differentiation.


Multicenter randomized, and blinded European field study evaluating the efficacy and safety of Felpreva®, a novel spot-on formulation containing tigolaner, emodepside and praziquantel, in treating cats with mixed infection with intestinal nematodes, cestodes and/or lungworms.
This paper describes a multicentric field study which has evaluated the safety and efficacy of a novel spot on formulation containing emodepside 2.04% w/v, praziquantel 8.14% w/v and tigolaner 9.79% w/v (Felpreva®, Vetoquinol) when administered at the intended commercial dose of 0.15 ml/kg body weight to privately owned cats infected with major intestinal nematodes (Toxocara cati, Toxascaris leonina, Ancylostoma tubaeforme, Uncinaria stenocephala) and/or cestodes (Dipylidium caninum, Taenia taeniaeformis) and/or lungworms (Aelurostrongylus abstrusus, Troglostrongylus brevior). A total of 219 cats from 26 veterinary clinics located in Albania, Greece, Hungary, Italy and Portugal were included in the study. Feces from the cats were examined on a single occasion between Study Day -7 and Day 0 (baseline) and post-treatment (i) twice between Day 7 and Day 14 (± 2) (for intestinal helminths) or (ii) twice between Day 21 (± 2) and Day 28 (± 2) (for lungworms). Cats were allocated into two groups at a ratio of 2:1 (Felpreva®: Profender®, i.e. a commercial control product containing emodepside and praziquantel). Cats infected with intestinal helminths were treated once on Day 0 (i) with Felpreva® (Group 1) or (ii) with Profender® (Group 2). Animals infected with lungworms received a second treatment with Profender® on Day 14 (± 2) regardless of group allocation. Faecal egg or larval count reduction for Felpreva® was 97.47% for intestinal nematodes and 96.80% for lungworms. No cats infected with cestodes at baseline resulted positive after treatment with Felpreva®. However, the low number of cats (n = 10) did not allow for a statistical analysis to be performed. Non-inferiority of Felpreva® compared to Profender® was statistically demonstrated for all target intestinal and respiratory parasites. No adverse events nor application site reactions were observed. These results show that the new topical combination product Felpreva® is highly safe and efficacious in treating infections caused by major species of feline intestinal nematodes, cestodes and lungworms under field conditions.


Depression with psychotic features is influenced by the polymorphism of the serotonin transporter gene.
Current diagnostic classifications regard psychotic symptoms during depressive episodes as indicators of depression severity. However, growing evidence suggests that depression with psychotic symptoms (MDP) may represent a distinct subtype of depression. In the course of the search for discriminating factors we tested the hypothesis that the serotonin transporter gene (5-HTTLPR) may interact with the manifestation of psychotic symptoms in acute depression. 112 inpatients (61 female) with a depressive episode (16 bipolar, 86 unipolar) at admission were genotyped for 5-HTTLPR variants. Psychotic symptoms und general psychopathology were evaluated comprehensively using the Manual of the Association for Methodology and Documentation in Psychiatry (Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie, 1981). For statistical analysis a chi-square test and a logistic regression model was used. 16 (14.3%) out of 112 patients were currently presenting with psychotic symptoms. The primary finding of our study was the higher prevalence of the s-allele of the 5-HTTLPR within the group of MDP patients (Pearson χ²=7.87; df=2; p<0.03). Secondly, in a logistic regression model, 5-HTTLPR was found to significantly contribute to the diagnosis of MDP (χ²=6.5; df=1; p=0.01). This effect was even more pronounced upon comparing only severely depressed patients with MDP patients. From a psychopathological perspective, MDP patients showed higher AMDP hostility and apathy scores but equal AMDP depression scores. This is the first study to show an influence of 5-HTTLPR on psychotic symptoms in acutely depressed patients. The lack of a control group and the relatively small sample size limits the present study's findings, thus replication in a larger sample is necessary.


The impact of neighborhood social disadvantage on presentation and management of first-time hemodialysis access surgery patients.
The impact of social determinants of health on the presentation, management, and outcomes of patients requiring hemodialysis (HD) arteriovenous (AV) access creation have not been well-characterized. The Area Deprivation Index (ADI) is a validated measure of aggregate community-level social determinants of health disparities experienced by members living within a community. Our goal was to examine the effect of ADI on health outcomes for first-time AV access patients. We identified patients who underwent first-time HD access surgery in the Vascular Quality Initiative between July 2011 to May 2022. Patient zip codes were correlated with an ADI quintile, defined as quintile 1 (Q1) to quintile 5 (Q5) from least to most disadvantaged. Patients without ADI were excluded. Preoperative, perioperative, and postoperative outcomes considering ADI were analyzed. There were 43,292 patients analyzed. The average age was 63 years, 43% were female, 60% were of White race, 34% were of Black race, 10% were of Hispanic ethnicity, and 85% received autogenous AV access. Patient distribution by ADI quintile was as follows: Q1 (16%), Q2 (18%), Q3 (21%), Q4 (23%), and Q5 (22%). On multivariable analysis, the most disadvantaged quintile (Q5) was associated with lower rates of autogenous AV access creation (OR, 0.82; 95% confidence interval [CI], 0.74-0.90; P < .001), preoperative vein mapping (OR, 0.57; 95% CI, 0.45-0.71; P < .001), access maturation (OR, 0.82; 95% CI, 0.71-0.95; P = .007), and 1-year survival (OR, 0.81; 95% CI, 0.71-0.91; P = .001) compared with Q1. Q5 was associated with higher 1-year intervention rates than Q1 on univariable analysis, but not on multivariable analysis. The patients undergoing AV access creation who were most socially disadvantaged (Q5) were more likely to experience lower rates of autogenous access creation, obtaining vein mapping, access maturation, and 1-year survival compared with the most socially advantaged (Q1). Improvement in preoperative planning and long-term follow-up may be an opportunity for advancing health equity in this population.


Natural enamel caries, dentine reactions, dentinal fluid and biofilm.
It is believed that penetration of dentinal fluid into natural enamel caries (NEC) is negligible because of the barrier created by underlying sclerotic dentine, but there are conflicting evidences on whether dentine subjacent to NEC is sclerotic or demineralized. This study aimed at investigating the relationship between NEC, subjacent dentine reactions, modification of dentinal fluid, and composition of cariogenic biofilm formed on the NEC surface. Proximal NEC (PNEC) lesions of human permanent posterior teeth were included in five experiments. Histologically, microradiographic analysis with contrast solution (MRC) in dentine revealed a decreased proportion of sclerotic dentine and an increased proportion of deep dentine demineralization compared to the classical stereomicroscopic histological analysis based on dentin color and translucency. Real-time MRC and 3D optical profilometry, and 3D microtomographic analysis evidenced a facilitated transport of modified dentinal fluid towards PNEC lesions. Cariogenic biofilm formed in vitro on the PNEC surface presented lower amounts of insoluble and soluble matrix polysaccharides when 2% chlorexidine was inserted in the pulp chamber. In conclusion, this study evidenced that dentine subjacent to PNEC is mostly demineralized, providing facilitated pathway for dentinal fluid to penetrate into PNEC and alter the composition of the biofilm formed on the PNEC surface.


Randomized clinical trial of BioFoam® Surgical Matrix to achieve hemostasis after liver resection.
Topical agents were designed to facilitate hemostasis during hepatic resection. The aim of this prospective randomized controlled clinical trial was to evaluate the effectiveness and safety of BioFoam® Surgical Matrix for achieving hemostasis after open hepatic resection. This was a prospective, randomized controlled monocentric trial of patients undergoing elective open liver resection between December 2015 and September 2017. The primary endpoint was time-to-complete hemostasis. A total of 101 patients were enrolled in this trial, giving 51 patients in the BioFoam® group and 50 patients in the control group (without use of BioFoam®). Time-to-complete hemostasis was significantly reduced in the BioFoam® group (156 ± 129 versus 307 ± 264 s; P = 0.001). There were no significant differences in postoperative bile leaks (n = 6 (12%) vs. n = 5 (10%); P = 0.776), postoperative morbidity (n = 37 (73%) vs. n = 40 (80%); P = 0.482) or mortality (n = 3 (6%) vs. n = 1 (2%); P = 0.618) between groups. BioFoam® is a safe topical agent for achieving faster hemostasis during hepatic resection, however, the true clinical relevance of this finding needs to be further evaluated. ClinicalTrials.gov ID NCT02612220.


U.S., European researchers face monkey shortage crisis.
Two new reports highlight growing demand and shrinking availability of nonhuman primates for biomedical studies.


Cytohistology of papillary carcinoid and emerging concept of pulmonary neuroendocrine neoplasms.
This timely review starts by reporting the clinical, cytologic and histologic features of a morphologic variant of pulmonary carcinoid tumor forming exclusively of papillae. This growth pattern is so rare that it was not included in 2014 WHO classification of pulmonary neuroendocrine neoplasms. The current concept is reviewed, and example of spindle cell carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma are illustrated with fine needle aspiration cytology, surgical and clinical follow-up. Finally, the new findings in cell biology and molecular biology that led to the emerging concept that carcinoids and high-grade neuroendocrine lung carcinomas are separate biological entities are reviewed and summarized in a tumorigenic module.


Effect of kangai injection combined with platinum-based chemotherapy on the immune function of patients with advanced non-small-cell lung cancer: A meta-analysis.
Kangai injection (KAI) is a well-known Chinese patent medicine applied for several different types of cancers in the clinic as an auxiliary therapeutic approach, which is refined from three herbal extracts (Astragalus, Ginseng and Matrine). To systematically evaluate the effect of combination treatment of platinum-based chemotherapy and KAI on patients with advanced non-small-cell lung cancer (NSCLC). A meta-analysis of randomized clinical trials. The randomized controlled trials (RCTs) about stage Ⅲ-Ⅳ NSCLC using KAI combined platinum-based chemotherapy were electronically retrieved from eight electronic databases up to July 2021. We applied RevMan 5.4, Stata 16.0, TSA 0.9.5.10 Beta and GRADE Pro-GDT to evaluate the quality of the included RCTs and perform the meta-analysis. 19 RCTs were included, consisting a total sample size of 1,389 cases. Meta-analysis revealed that compared with chemotherapy alone, KAI combined with platinum-based chemotherapy was associated with significantly higher objective response rate (ORR) [RR = 1.36, 95%CI (1.21,1.54), p< 0.00001], higher disease control rate (DCR) [RR = 1.15, 95%CI (1.09,1.21), p< 0.00001], greater Karnofsky performance status (KPS) [RR = 1.75, 95%CI (1.41,2.18), p< 0.00001], lower white blood cell toxicity [RR = 0.67, 95%CI (0.55,0.82), p = 0.0001], lower platelet toxicity [RR = 0.60, 95%CI (0.47,0.75), P < 0.0001], and lower incidence of vomiting [RR = 0.66, 95%CI (0.57,0.76), p< 0.00001]. In terms of the immune function, KAI united with chemotherapy significantly raised the ratio of CD3+ cells [MD = 10.65, 95%CI (8.21,13.09), p< 0.00001], CD4+ cells [MD = 7.67, 95%CI (6.31,9.03), p< 0.00001], NK cells [MD = 4.97, 95%CI (3.03,6.92), p< 0.00001], and CD4+/ CD8+ [MD = 0.32, 95%CI (0.19,0.45), p< 0.00001], and decreased the percentage of CD8+ cells [MD = -5.56, 95%CI (-7.51,-3.61), p< 0.00001]. This meta-analysis identified that the combination treatment of KAI and platinum-based chemotherapy was more beneficial to patients with advanced NSCLC when compared to chemotherapy alone, which could significantly improve the clinical efficacy, enhance the immune function, and reduce chemotherapy toxicity. Our study provides a theoretical basis and treatment guidance for patients with NSCLC.


BMP4 promotes oxaliplatin resistance by an induction of epithelial-mesenchymal transition via MEK1/ERK/ELK1 signaling in hepatocellular carcinoma.
Bone morphogenetic protein-4 (BMP4) is a key regulator of epithelial-mesenchymal transition (EMT), which is crucial for cancer cells to acquire chemoresistance. The effects of BMP4 on OXA sensitivity in HCC need to be elucidated. Functional analysis of BMP4 on EMT-regulated OXA sensitivity was performed in human HCC specimens, in the HCC cell lines HepG2 and HCCLM3, and in a subcutaneous tumor model receiving OXA treatment. The downstream signaling targets of BMP4 in HCC were profiled and confirmed. BMP4 expression was significantly increased in HCC tissue, and was correlated with tumor de-differentiation and unfavorable prognosis. BMP4 promoted HCC EMT and was correlated with OXA resistance. Blocking of BMP4 reversed EMT and increased OXA chemosensitivity in vitro and in vivo. ELK1, a transcription factor involved in EMT, was an important mediator of BMP4-induced OXA resistance in HCC. Blocking of MEK/ERK/ELK1 attenuated BMP4-induced EMT and enhanced OXA sensitivity. BMP4 induces EMT and OXA chemoresistance via MEK/ERK/ELK1 signaling pathway in HCC. BMP4 may be a valuable therapeutic target for HCC patients receiving OXA-based chemotherapy.


Use of real-time three-dimensional echocardiography to measure left atrial volume: comparison with other echocardiographic techniques.
Left atrial (LA) volume (LAV) is a prognostically important biomarker for diastolic dysfunction, but its reproducibility on repeated testing is not well defined. LA assessment with 3-dimensional (3D) echocardiography (3DE) has been validated against magnetic resonance imaging, and we sought to assess whether this was superior to existing measurements for sequential echocardiographic follow-up. Patients (n = 100; 81 men; age 56 +/- 14 years) presenting for LA evaluation were studied with M-mode (MM) echocardiography, 2-dimensional (2D) echocardiography, and 3DE. Test-retest variation was performed by a complete restudy by a separate sonographer within 1 hour without alteration of hemodynamics or therapy. In all, 20 patients were studied for interobserver and intraobserver variation. LAVs were calculated by using M-mode diameter and planimetered atrial area in the apical 4-chamber view to calculate an assumed sphere, as were prolate ellipsoid, Simpson's biplane, and biplane area-length methods. All were compared with 3DE. The average LAV was 72 +/- 27 mL by 3DE. There was significant underestimation of LAV by M-mode (35 +/- 20 mL, r = 0.66, P < .01). The 3DE and various 2D echocardiographic techniques were well correlated: LA planimetry (85 +/- 38 mL, r = 0.77, P < .01), prolate ellipsoid (73 +/- 36 mL, r = 0.73, P = .04), area-length (64 +/- 30 mL, r = 0.74, P < .01), and Simpson's biplane (69 +/- 31 mL, r = 0.78, P = .06). Test-retest variation for 3DE was most favorable (r = 0.98, P < .01), with the prolate ellipsoid method showing most variation. Interobserver agreement between measurements was best for 3DE (r = 0.99, P < .01), with M-mode the worst (r = 0.89, P < .01). Intraobserver results were similar to interobserver, the best correlation for 3DE (r = 0.99, P < .01), with LA planimetry the worst (r = 0.91, P < .01). The 2D measurements correlate closely with 3DE. Follow-up assessment in daily practice appears feasible and reliable with both 2D and 3D approaches.


[Interaction of quartz with human erythrocyte membrane--major protein changes and the effect of aluminium citrate].
The changes of the major proteins of human erythrocyte membrane by quartz were analysed by SDS-polyacrylamide gel electrophoresis. The relative mobility of proteins remained unchanged, whilst the relative abundance of Band 3 and PAS-1 proteins decreased (stained with Coomassie blue and PAS). The adsorption of Band 3 on to quartz were dose- and time-dependent. Aluminium citrate can inhibit the quartz adsorptive activity. The results support that the membrane damage of quartz is related to interacting with Band 3 proteins.


Model investigations of the temperature dependence of demyelinated and reorganized axonal membrane.
The temperature dependence (from 10 degrees to 50 degrees C) of the intracellular action potentials' parameters in a fiber with a simulated reorganization of the axonal membrane against the background of a systematic paranodal demyelination of the fiber was investigated. The temporal and spatial distribution of the potential as well as the ionic currents' kinetics have been represented. The reorganization of the axonal membrane was achieved by means of potassium channels blocking and increase of the sodium-channel permeability, while the demyelination was achieved by means of elongation of the nodes of Ranvier. In order to account for the temperature dependence of the rate constants and of the maximal sodium and potassium permeabilities, the temperature coefficients (Q10) have been used. It has been shown for the demyelinated and reorganized membrane that increased temperature blocks the conduction at temperatures much higher than the blocking temperature for the demyelinated fiber only. When temperature increases the amplitude of the potential decreases while the velocity increases up to temperatures approaching the blocking temperature after which it abruptly drops. The dependence of the asymmetry and the wavelength of the potential on temperature is complex and nonmonotonic. For the reorganized membrane at the background of a given degree of demyelination with increasing temperature the ionic currents' flow and the membrane conduction respectively increase, but, at lower temperatures, when the temperature increase is combined with the increased degree of the fiber demyelination, the conduction is blocked.


Lifetime risk of cardiovascular disease among individuals with and without diabetes stratified by obesity status in the Framingham heart study.
We assessed the lifetime risk of cardiovascular disease (CVD) among individuals with and without obesity and diabetes. Participants were drawn from the original and offspring cohorts of the Framingham Heart Study. Lifetime (30-year) risk of CVD was assessed using a modified Kaplan-Meier approach adjusting for the competing risk of death, beginning from age 50 years. Over 30 years, the lifetime risk of CVD among women with diabetes was 54.8% among normal-weight women and 78.8% among obese women. Among normal-weight men with diabetes, the lifetime risk of CVD was 78.6%, whereas it was 86.9% among obese men. The lifetime risk of CVD among individuals with diabetes is high, and this relationship is further accentuated with increasing adiposity.


Off-label and unlicensed drug use in neonatal intensive care units in Turkey: the old-inn study.
Recently several developed countries have improved the safety and efficacy of drugs used in infants and pediatric patients. Most drugs administered to adults have licensed approvals outlining indications, doses, and the recommended route of administration. However, many drugs that are given to children are unlicensed or used off-label. To assess the extent and nature of unregistered and off-label drug use in neonatal intensive care units (NICUs) in Turkey, and to explore awareness and views of the general public on the unlicensed use of medicine in preterm and term infants in developing countries. A prospective observational study of a dynamic cohort of 464 neonates from 17 NICUs in Turkey. All medications administered to neonates who were hospitalized and admitted to the NICU over a 24-h period were recorded. The prescriptions were analyzed to determine whether the medicines were used in a licensed or unlicensed manner. In total, 1,315 prescriptions comprising 93 different medicines were written. We found that 62.3% of the drugs prescribed to the neonates over the 24-h period were unlicensed or off-labeled. The present study indicates that unlicensed and off-label medicines are frequently used in preterm and term infants in Turkish NICUs. This finding is consistent and reported in other countries. We believe that the needs of the neonatal population must be a priority and access to safe and appropriate medicines requires urgent attention.


Human cathepsin D.
Cathepsin D was purified from human liver by a procedure involving autolysis, acetone fractionation, and chromatography on ion-exchange media and organomercurial-sepharose. Multiple forms of the enzyme were then separated by preparative isoelectric focusing. The molecular weight of the protein was found to be 43,000. Its amino acid composition was determined and it was shown to be a glycoprotein. When treated with sodium dodecyl sulphate or chaotropic agents (without reduction) all forms of the enzyme tested gave components of about 28,000 and 14,000 molecular weight. Specific antisera were raised against the enzyme, and the characteristics of immunoinhibition were investigated. Immuno-inhibition of rabbit cathepsin D within living macrophages was shown to interfere with degradation of some proteins endocytosed by the cells. The antisera against human and rabbit cathepsin D were used in immunofluorescent localization of the enzyme in sites of tissue damage in which cathepsin D might be implicated. The characteristics of inhibition of human cathepsin D by pepstatin were established. At pH values below 5, KD values of 5 x 10(-10)M were determined and pepstatin was shown to be an excellent titrant for cathepsin D. In the range pH 5-6.4 DK increased steeply and it was concluded that the binding site for substrate and inhibitor was abolished by a conformational change in the enzyme molecule in which three protons are lost.


Single-incision laparoscopic total abdominal colectomy for refractory ulcerative colitis.
A three-stage restorative proctocolectomy with ileal pouch-anal anastomosis is the treatment of choice for the particularly debilitated patient with medically refractory ulcerative colitis (UC). Laparoscopic surgery has been shown to offer several advantages over the open approach in this setting. Single-incision laparoscopic surgery is an emerging minimally invasive strategy representing a truly scarless procedure for the first surgical step, namely, the total abdominal colectomy (TAC). Nine consecutive patients with medically refractory UC underwent a single-incision laparoscopic TAC between May and October 2010. All patients were on aggressive medical therapy with corticosteroids or immunosuppressors and were selected for this approach on the basis of their body habitus and the absence of relevant comorbidities. The whole operation was performed through a single access to the abdominal cavity, placed at the ostomy site marked preoperatively. Mean operating time was 142 ± 23 min, with an estimate blood loss of 108 ± 125 ml. No intraoperative complications or conversions to conventional laparoscopy or open surgery occurred. In all cases the postoperative course was uneventful. The return of bowel function was observed on postoperative day 1.7 ± 0.7, and patients could tolerate a solid diet on postoperative day 3 ± 0.5. The mean postoperative length of stay was 5.2 ± 1.3 days. In our experience, a single-incision laparoscopic approach to total abdominal colectomy for refractory ulcerative colitis has been shown to be safe and feasible. Initial results suggest that this technique can lead to improvements in short-term outcomes in selected patients.


CsPbI3/N-GQDs dual layer phosphor-converted white-LEDs with ultrahigh luminous efficiency and color rendering index.
Phosphor-converted LEDs or pc-LEDs, as a solid-state lighting source, are attractive for next-generation display technologies because of their energy savings, and green environmentally friendly nature. Recently, white LEDs are being produced commercially by coating blue LED (440-470 nm) chips with various yellow-emitting phosphors. However, the LEDs produced by this technique often exhibit high correlated color temperature (CCT) and low color rendering index (CRI) values, due to sufficient red spectral components not being present, and thus aren't suitable for commercial grade white illumination. To circumvent this drawback, our work reports for the first time the use of blue and green-emitting nitrogen-functionalized graphene quantum dots (GQDs) coupled with red-emitting CsPbI3NCs for phosphor-based LED applications. We deployed near-UV to visible excitable red-emitting perovskite CsPbI3nanocrystals which contribute toward the red spectral component, thus greatly improving the CRI of the LEDs. CsPbI3nanocrystals are optically excited by nitrogen-functionalized GQD with blue and green emissions in a remote double-layer phosphor stack technique. This double phosphor layer stacking greatly improves both the CRI and luminous efficiency of radiation (LER), which usually has a trade-off in previously reported phosphor stacks. A CCT of ∼5182 K providing daylight white tonality, with superior CRI (∼90%) and ultrahigh LER (∼250 lumens/watt) are reported, which are significantly higher than the established benchmarks.


Interaction of ionic biomolecular building blocks with nonpolar solvents: acidity of the imidazole cation (Im+) probed by IR spectra of Im+-Ln complexes (L = Ar, N2; n < or = 3).
The intermolecular interaction between the imidazole cation (Im+ = C3N2H4+) and nonpolar ligands is characterized in the ground electronic state by infrared photodissociation (IRPD) spectroscopy of size-selected Im+-Ln complexes (L = Ar, N2) and quantum chemical calculations performed at the UMP2/6-311G(2df,2pd) and UB3LYP/6-311G(2df,2pd) levels of theory. The complexes are created in an electron impact cluster ion source, which predominantly produces the most stable isomers of a given cluster ion. The analysis of the size-dependent frequency shifts of both the N-H and the C-H stretch vibrations and the photofragmentation branching ratios provides valuable information about the stepwise microsolvation of Im+ in a nonpolar hydrophobic environment, including the formation of structural isomers, the competition between various intermolecular binding motifs (H-bonding and pi-bonding) and their interaction energies, and the acidity of both the CH and NH protons. In line with the calculations, the IRPD spectra show that the most stable Im+-L dimers feature planar H-bound equilibrium structures with nearly linear H-bonds of L to the acidic NH group of Im+. Further solvation occurs at the aromatic ring of Im+ via the formation of intermolecular pi-bonds. Comparison with neutral Im-Ar demonstrates the drastic effect of ionization on the topology of the intermolecular potential, in particular in the preferred aromatic substrate-nonpolar recognition motif, which changes from pi-bonding to H-bonding. .


Crystal Structure Formation of CH₃NH₃PbI3-xClx Perovskite.
Inorganic-organic hydride perovskites bring the hope for fabricating low-cost and large-scale solar cells. At the beginning of the research, two open questions were raised: the hysteresis effect and the role of chloride. The presence of chloride significantly improves the crystallization and charge transfer property of the perovskite. However, though the long held debate over of the existence of chloride in the perovskite seems to have now come to a conclusion, no prior work has been carried out focusing on the role of chloride on the electronic performance and the crystallization of the perovskite. Furthermore, current reports on the crystal structure of the perovskite are rather confusing. This article analyzes the role of chloride in CH₃NH₃PbI3-xClx on the crystal orientation and provides a new explanation about the (110)-oriented growth of CH₃NH₃PbI₃ and CH₃NH₃PbI3-xClx.


Plasma and erythrocyte zinc concentrations in pre-eclampsia.
Plasma and erythrocyte zinc concentrations were measured in 28 Chinese pre-eclamptic women and 28 controls matched for parity, race and gestation. There were no differences in either the plasma or erythrocyte zinc concentrations between pre-eclamptic and control groups, although the mean birth weight (p less than 0.001) and period of gestation (p less than 0.001) at delivery in the control group were significantly higher. In the pre-eclamptic patients, those delivering before 37 weeks or those who gave birth to low birth weight (less than 2500 g), babies had a significantly higher plasma urate concentration (p less than 0.02) compared to the pre-eclamptic patients with better fetal outcome. However, the plasma and erythrocyte zinc concentrations between these subgroups were not significantly different. Our results suggest that zinc deficiency is unlikely to play a significant role in pre-eclampsia in our patients, and that measurement of plasma and erythrocyte zinc concentrations is of doubtful clinical value in the management of pre-eclampsia.


A novel method for identifying geomechanical parameters of rock masses based on a PSO and improved GPR hybrid algorithm.
In view of the shortcomings of existing artificial neural network (ANN) and support vector regression (SVR) in the application of three-dimensional displacement back analysis, Gaussian process regression (GPR) algorithm is introduced to make up for the shortcomings of existing intelligent inversion methods. In order to improve the generality of the standard GPR algorithm with single kernel function, an improved Gaussian process regression (IGPR) algorithm with combined kernel function is proposed by adding two single kernel functions. In addition, in the training process of IGPR model, the particle swarm optimization (PSO) is combined with the IGPR model (PSO-IGPR) to optimize the parameters of the IGPR model. After the IGPR model can accurately map the relationship between geomechanical parameters and rock mass deformation, the PSO algorithm is directly used to search the best geomechanical parameters to match the deformation calculated by igpr model with the measured deformation of rock mass. The application case of Beikou tunnel shows that the combined kernel function GPR has higher identification accuracy than the single kernel function GPR and SVR model, the IGPR model with automatic correlation determination (ARD) kernel function can obtain higher identification accuracy than the IGPR model with isotropic (ISO) kernel function, and the PSO-IGPR hybrid model based on ARD kernel function has the highest identification accuracy. Therefore, this paper proposes a displacement back analysis method of the PSO-IGPR hybrid algorithm based on ARD kernel function, which can be used to identify the geomechanical parameters of rock mass and solve other engineering problems.


Contrast-enhanced ultrasound (CEUS) in the diagnostic evaluation of popliteal artery aneurysms, a single-center study.
Popliteal artery aneurysms (PAA) are the most common peripheral artery aneurysms. Most common cause is arteriosclerosis. Acute thromboembolic limb ischemia and rupture of the PAA depict severe complications. Diagnostic tools for identifying PAAs are (Doppler) ultrasound, CT/MR angiography and DSA. The aim of the present retrospective single-center study is to assess the application and safety of CEUS for assessing untreated and treated PAAs. 13 patients were included in this study on whom CEUS was performed between 2007-2016. CEUS examinations were performed and interpreted by an experienced single radiologist (EFSUMB Level 3). CEUS allowed for the detection of PAAs in all cases. CEUS allowed for detection of partial thrombosis of PAA in 7/8 of untreated patients, proper exclusion of PAA upon femoro-popliteal bypass in 3 patients, incomplete exclusion of PAA upon femoro-popliteal bypass in 1 patient and ruling out of in-stent stenosis in 1 patient. CEUS is a useful and safe tool for in real-time evaluation of PAAs in the pre-/post-treatment status. In addition to conventional (Doppler) ultrasound and as an alternative tool to more elaborate imaging modalities, CEUS might be integrated in the future diagnostic work-up and follow-up of PAA patients.


On the occasion of world kidney day 2017; obesity and its relationship with chronic kidney disease.
Numerous studies have reported the impact of obesity in the incidence of chronic kidney disease (CKD). Some studies have suggested the direct role of obesity in the incidence of CKD, while some other studies suggest an indirect effect caused by the effects of obesity on blood pressure and diabetes. PubMed, EBSCO, Web of Science, directory of open access journals (DOAJ), EMBASE, and Google Scholar have been searched. Recent studies have presented more strong evidences on the role of obesity on the incidence of CKD. The double role of obesity in the incidence of CKD has also been mentioned in some studies. Such an additional effect arises from the impact of obesity on the incidence of some conditions and diseases such as cardiovascular disease, hypertension, and diabetes, which in turn are involved in the incidence of CKD and are considered as its risk factors.


Incidence of human immunodeficiency virus antibody in a prenatal population at a community hospital.
Prenatal human immunodeficiency virus (HIV) screening may reduce vertical HIV transmission. We screened 4,419 prenatal sera and found 38 repeatedly reactive specimens with an HIV-1-HIV-2 enzyme-linked immunosorbent assay. Western blot analysis confirmed four of these specimens as positive for HIV-1 antibodies. Screening detects previously unidentified HIV infections, but false-positive results may also occur.


Detection of stenoses in the internal carotid artery by waveform analysis of continuous wave ultrasound signals (II).
Analysis of the morphological aspects of continuous-wave Doppler examination is a reliable means of detecting carotid stenosis involving 50% or more of the diameter of the arterial lumen. This study was undertaken to evaluate the indexes likely to increase the diagnostic accuracy of this noninvasive investigation method. The indexes studied were the variations of the maximal frequency and the systolic peak frequencies, measured proximal to and at the level of stenosis, and the ratio of the systolic peak frequency measured in the internal carotid artery and in the common carotid artery. After obtaining data on an experimental model, the study was conducted in healthy volunteers (n = 24) and in patients with carotid atherosclerotic disease (n = 23). The experimental study confirmed that stenosis greater than 50% leads to a reduction of blood flow and that there is a mathematical relationship between the frequency measured proximal to and at the level of the stenosis and the degree of stenosis. Clinical data showed that there was a significant decrease in the frequency of the systolic peak in elderly "healthy" subjects as compared with younger subjects. However there was no difference between patients with and without stenosis. The index was 0.8 in young subjects, 1.3 in healthy elderly subjects, and greater than 1.3 in subjects who had a stenosis. There was no statistically significant difference between these two last groups. At the threshold value of 2.3, the sensitivity of the FI index was 22% and the specificity was 94% in the detection of carotid artery stenosis. In the assessment of the tight stenosis, sensitivity was 44%.


Prevalence and characteristics of a feline parvovirus-like virus in dogs in China.
In this study, 192 diarrheal fecal samples were collected from 2019 to 2021 for monitoring the molecular prevalence of canine parvovirus 2 (CPV-2) among dogs in Southwest China, and 113 samples were detected as Carnivore protoparvovirus 1-positive. Surprisingly, 28/113 (24.8%) strains were identified as feline parvovirus (FPV)-like viruses based on the key amino acid (aa) residues in VP2. Further, 6 FPV-like strains were successfully isolated and genome sequenced, and phylogenetic trees based on the genome, VP2 and NS1 sequences showed that the 6 FPV-like strains were most genetically related with FPV instead of CPV-2. Interestingly, the VP2 proteins of the FPV-like virus contained all key aa residues typical for FPV and can be 100% identical to that of FPV, but the VP1 intron and NS1 aa sequences exhibited some unique molecular characteristics. The FPV-like isolate could hemagglutinate swine erythrocyte at pH values between 6 and 8, and replicated efficiently in MDCK cell line; moreover, the virus could cause canine systemic infection via oral administration. Further analysis based on VP2 sequences of FPV and CPV-2 in GenBank revealed that the FPV-like virus had already existed among dogs in 4 Asian countries, and have circulated widely in China. This study first confirmed that the FPV-like isolates could efficiently infect dogs, and has been prevalent among dogs in China. Moreover, this study first reported the genome characteristics of the FPV-like virus in dogs, which may represent a novel evolution pattern involving in the cross-species transmission of the virus from cats to dogs.


Electrophysiologic effects and clinical efficacy of oral propafenone therapy in patients with ventricular tachycardia.
The effects of the antiarrhythmic agent propafenone were evaluated in 25 patients with recurrent symptomatic ventricular tachycardia. Oral propafenone was given to a maximal dose of 300 mg every 8 hours. Ten of the 25 patients developed side effects or had inadequate suppression of spontaneous ventricular arrhythmias during propafenone therapy. Electrophysiologic studies were performed before and during drug therapy on the 15 patients who had a satisfactory clinical response. Propafenone increased the PR interval from 168 +/- 46 to 188 +/- 25 ms (p less than 0.007), the HV interval from 47 +/- 10 to 65 +/- 13 ms (p less than 0.005), the shortest atrial pacing cycle length to maintain 1:1 atrioventricular (AV) nodal conduction from 385 +/- 44 to 436 +/- 42 ms (p less than 0.005), the ventricular effective refractory period from 231 +/- 17 to 255 +/- 19 ms (p less than 0.001) and the ventricular functional refractory period from 260 +/- 15 to 278 +/- 17 ms (p less than 0.002). Before propafenone therapy, all 15 patients had ventricular tachycardia induced by programmed ventricular stimulation. During propafenone treatment, 12 patients still had ventricular tachycardia induced, and the tachycardia cycle length significantly increased from 236 +/- 44 to 374 +/- 103 ms (p less than 0.001). Ten patients were considered to have satisfactory electrophysiologic response to propafenone on the basis of either the inability to initiate ventricular tachycardia or a marked increase in ventricular tachycardia cycle length associated with lack of symptoms during the induced tachycardia. These patients were discharged receiving propafenone.(ABSTRACT TRUNCATED AT 250 WORDS)


Twenty-four-hour variations in ornithine decarboxylase and acid phosphatase in mice.
Polyamines are essential for cell growth and differentiation. Ornithine decarboxylase (ODC) is the rate-limiting enzyme in polyamine biosynthesis. Acid phosphatases (AP) are lysosomal enzymes that are important in normal intracellular metabolism. Twenty-four-hour variations in these enzymes may be important in understanding the temporal responses of different tissues to various stimuli. The purpose of this study was to examine a variety of tissues for fluctuations in the levels of ODC and AP over a 24-hr period. Significant circadian variations in the amount of ODC activity were observed in all tissues examined. Activity of AP varied with time of day in the liver, kidney, and heart. The highest and lowest measurements of ODC activity were as follows: liver, 81.5 +/- 7.0, 47.9 +/- 4.4; colon, 11.7 +/- 1.2, 3.1 +/- 0.7; stomach 3.1 +/- 0.4, 0.9 +/- 0.1; kidney, 420.9 +/- 0.9, 67.5 +/- 0.8; and heart, 4.7 +/- 1.0, 2.5 +/- 0.2. The highest and lowest measurements of AP activity were as follows: liver 3.8 +/- 0.1, 2.8 +/- 0.1; kidney, 3.4 +/- 0.1, 1.9 +/- 0.1; and heart, 2.6 +/- 0.1, 2.0 +/- 0.1. These findings suggest that rhythmic fluctuations in polyamine biosynthesis and lysosomal enzymes may influence other metabolic pathways differentially throughout 24 hr.


Estimation of differential occupational risk of COVID-19 by comparing risk factors with case data by occupational group.
The disease burden of coronavirus disease 2019 (COVID-19) is not uniform across occupations. Although healthcare workers are well-known to be at increased risk, data for other occupations are lacking. In lieu of this, models have been used to forecast occupational risk using various predictors, but no model heretofore has used data from actual case numbers. This study assesses the differential risk of COVID-19 by occupation using predictors from the Occupational Information Network (O*NET) database and correlating them with case counts published by the Washington State Department of Health to identify workers in individual occupations at highest risk of COVID-19 infection. The O*NET database was screened for potential predictors of differential COVID-19 risk by occupation. Case counts delineated by occupational group were obtained from public sources. Prevalence by occupation was estimated and correlated with O*NET data to build a regression model to predict individual occupations at greatest risk. Two variables correlate with case prevalence: disease exposure (r = 0.66; p = 0.001) and physical proximity (r = 0.64; p = 0.002), and predict 47.5% of prevalence variance (p = 0.003) on multiple linear regression analysis. The highest risk occupations are in healthcare, particularly dental, but many nonhealthcare occupations are also vulnerable. Models can be used to identify workers vulnerable to COVID-19, but predictions are tempered by methodological limitations. Comprehensive data across many states must be collected to adequately guide implementation of occupation-specific interventions in the battle against COVID-19.


Molecular cloning of cDNA for human von Willebrand factor: authentication by a new method.
We have identified a 2.4 kb partial cDNA clone (pDL34) for human von Willebrand factor (vWf) mRNA. pDL34 was selected by screening an endothelial cell cDNA library with a radiolabeled reverse transcript of mRNA obtained by specific immunoisolation of vWf polysomes from endothelial cells. pDL34 selectively hybridized to an endothelial cell-associated 9.5 kb mRNA. To confirm its identity, SP6 RNA polymerase was used to generate in vitro transcripts of the cDNA. This synthetic RNA, truncated at its 5' end, directed the synthesis of several unique polypeptides in rabbit reticulocyte lysates. These polypeptides were immunoprecipitated by polyclonal and monoclonal anti-vWf antibodies. These results indicate that pDL34 contains an authentic partial copy of vWf mRNA. In vitro transcription of partial cDNA clones and translation of the resulting RNAs may be a useful general method of verifying the identity of various cDNA clones in circumstances where antibodies are available and protein sequence is not.


Peritonsillar abscess with parapharyngeal and retropharyngeal involvement: incidence and intraoral approach.
This study illustrates common sites of infection seen in peritonsillar abscesses with involvement of the pharyngeal space and retropharyngeal space. Abscesses behind and/or inferior to the tonsil were encountered more frequently than expected. In these cases, the drainage had to be placed in the inferior pole of the tonsil and these types were frequently seen in older patients. The aim of this study was to assess to what extent abscesses spread in patients with peritonsillar abscess and to determine to what extent pus can be drained intraorally. The clinical charts of 45 patients with peritonsillar abscess involvement of the parapharyngeal space and/or retropharyngeal space were retrospectively reviewed. In 45 cases, 21 patients were diagnosed with the superior type, and we could drain the pus intraorally in 90% of the patients. On the other hand, 24 cases were diagnosed with the inferior type and they were drained intraorally in 58% of the cases.


Retracted: The Protection for Personal Information Based on IoT Network Management and Data Sharing in Big Data Era.
[This retracts the article DOI: 10.1155/2022/5143396.].


Data quality from a longitudinal study of adolescent health at schools near industrial livestock facilities.
Longitudinal designs enable examination of temporal relationships between exposures and health outcomes, but extended participation can cause study fatigue. We present an approach for analyzing data quality and study fatigue in a participatory, longitudinal study of adolescents. Participants (n = 340) in the Rural Air Pollutants and Children's Health study completed daily diaries for 3 to 5 weeks in 2009 while we monitored outdoor pollutant concentrations. We used regression models to examine established associations between disease, symptoms, anthropometrics, and lung function as indicators of internal consistency and external validity. We modeled temporal trends in data completeness, lung function, environmental odors, and symptoms to assess study fatigue. Of 5728 records, 94.2% were complete. Asthma and allergy status were associated with asthma-related symptoms at baseline and during follow-up, for example, prevalence ratio = 8.77 (95% confidence interval: 4.33-17.80) for awakening with wheeze among diagnosed asthmatics versus nonasthmatics. Sex, height, and age predicted mean lung function. Plots depicting outcome reporting over time and associated linear trends showed time-dependent declines for most outcomes. We achieved data completeness, internal consistency, and external validity, yet still observed study fatigue, despite efforts to maintain participant engagement. Future investigators should model time trends in reporting to monitor longitudinal data quality.


Hemodynamic benefits of atrial ventricular sequential pacing in complete heart block and left ventricular failure: case study.
The authors describe 2 cases of insertion of atrial ventricular (AV) sequential pacemakers and their hemodynamic benefits.


Urinary thiosulphate as an indicator of exposure to hydrogen sulphide vapour.
Urinary thiosulphate analysed as its bromobimane complex by liquid chromatography revealed quantitatively a preceding hydrogen sulphide gas exposure. The highest thiosulphate concentrations were detected 15 h after the exposure. Controls without a contact to sulphides showed low excretion rates of thiosulphate so that exposures clearly below the fatal hydrogen sulphide gas concentrations could be detected. The urinalysis can therefore be used in the occupational health care as well as for forensic ends.


Matrix metalloproteinase-9 as new biomarkers of severity in multiple organ dysfunction syndrome caused by trauma and infection.
Multiple organ dysfunction syndrome (MODS) is an important cause of morbidity and mortality in intensive care unit. A severe insult in the form of infection or trauma primes the host immune system so that a subsequent, relatively trivial insult produces systemic inflammation response syndrome, which can lead to MODS and death. Matrix metalloproteinase-9 (MMP-9) is stored in the tertiary granules of polymorphonuclear leukocytes. These cells are key effectors in acute inflammatory diseases, such as sepsis and MODS. Endotoxin leads to rapid release of MMP-9 from these granules in vitro and in vivo. However, the role of this enzyme in MODS, and whether it is associated with organ injury at the early stage of MODS remains unclear. This present work may study role of MMP-9 with the MODS rats that caused by trauma and infection and investigate the mechanism of organ injury at the early stage of MODS. Here, we developed a rat model for MODS caused by trauma and infection and analyzed the dynamic level of MMP-9 and determined the relationship between MMP-9 level and early phase of organ injury in MODS rat. The histological changes in pulmonary, renal, and hepatic tissue were observed by light microscope. The expressions of plasma MMP-9 proteins were detected by an enzyme linked immunosorbent assay and its levels in the pulmonary, renal, and hepatic tissue were detected by using immunohistochemistry, respectively. The results indicated that there were no significant improvements in histopathology of rats in control group. However, the pulmonary, renal, and hepatic damage were serious in MODS groups. The concentration of MMP-9 in plasma and tissues of MODS rats increased markedly at the early stage and were higher than that of the control group. Moreover, the MMP-9 level in plasma positively correlated with the levels of pulmonary, renal, and hepatic tissue. This study clearly shows that MMP-9 is good biomarker to predict the severity of injury organ at the early phase of MODS.


Lumbar artery compression by the diaphragmatic crus: a new etiology for spinal cord ischemia.
We describe a new cause of spinal cord ischemia illustrated by two cases--compression by the diaphragmatic crus of a lumbar artery giving rise to a spinal artery. The diagnosis has been established by dynamic spinal angiography, showing complete occlusion of the lumbar artery. Surgical section of the diaphragmatic crus prevents irreversible infarction.


FISHing for Chromosome Instability and Aneuploidy in the Alzheimer's Disease Brain.
Fluorescence in situ hybridization (FISH) is the method of choice for visualizing chromosomal DNA in post-mitotic cells. The availability of chromosome-enumeration (centromeric), site-specific, and multicolor-banding DNA probes offers opportunities to uncover genomic changes, at the chromosomal level, in single interphase nuclei. Alzheimer's disease (AD) has been associated repeatedly with (sub)chromosome instability and aneuploidy, likely affecting the brain. Although the types and rates of chromosome instability in the AD brain remain a matter of debate, molecular cytogenetic analysis of brain cells appears to be important for uncovering mechanisms of neurodegeneration. Here, we describe a FISH protocol for studying chromosome instability and aneuploidy in the AD brain.


Soft rot of postharvest pepper: bacterial pathogen, pathogenicity and its biological control using Lactobacillus farciminis LJLAB1.
Soft rot is the most important bacterial disease of postharvest pepper during storage and transportation. The main objectives of this study were to investigate the bacterial pathogen species causing pepper soft rot and seek for an antagonistic bacterium to control this disease. Pathogens Pectobacterium carotovorum, Enterobacter sp., Klebsiella sp., Pseudomonas sp. and Bacillus sp. were verified to be the causes of soft rot which were isolated from rotten peppers. Among them, P. carotovorum had the highest prevalence, including P. carotovorum subsp. carotovorum (Pcc) and P. carotovorum subsp. brasilisesis (Pcb). The result of pathogenicity analysis showed that Pcb Jm2 had strong pathogenicity at 25 °C even at a cell concentration of 103 CFU mL-1 . Its pathogenicity decreased at 4 °C. Multiple pathogenic factors were identified in the draft genome of Pcb Jm2, including cellulase, pectinase, pectin methylesterase, pectinesterase, pectin lyase, polygalacturonase and so forth. Further, the disease control ability of Lactobacillus farciminis LJLAB1 was investigated. The cell-free supernatant (CFS) and crude bacteriocin of L. farciminis LJLAB1 had good antibacterial activities to Pcb Jm2 in vitro, but CFS exhibited a better disease control effect in vivo. CFS treatment prevented the damage of pepper epidermal structure caused by Pcb Jm2, and 99.26% of pathogen cells on pepper were killed by it. Moreover, CFS treatment delayed firmness decrease, soluble solid content loss, weight loss, yellowing and malonaldehyde accumulation of pepper during storage after pathogen infection. L. farciminis LJLAB1 can be an effective biological control agent to control pepper soft rot caused by Pcb. © 2023 Society of Chemical Industry.


Improved Gate Dielectric Deposition and Enhanced Electrical Stability for Single-Layer MoS2 MOSFET with an AlN Interfacial Layer.
Transistors based on MoS2 and other TMDs have been widely studied. The dangling-bond free surface of MoS2 has made the deposition of high-quality high-k dielectrics on MoS2 a challenge. The resulted transistors often suffer from the threshold voltage instability induced by the high density traps near MoS2/dielectric interface or inside the gate dielectric, which is detrimental for the practical applications of MoS2 metal-oxide-semiconductor field-effect transistor (MOSFET). In this work, by using AlN deposited by plasma enhanced atomic layer deposition (PEALD) as an interfacial layer, top-gate dielectrics as thin as 6 nm for single-layer MoS2 transistors are demonstrated. The AlN interfacial layer not only promotes the conformal deposition of high-quality Al2O3 on the dangling-bond free MoS2, but also greatly enhances the electrical stability of the MoS2 transistors. Very small hysteresis (ΔVth) is observed even at large gate biases and high temperatures. The transistor also exhibits a low level of flicker noise, which clearly originates from the Hooge mobility fluctuation instead of the carrier number fluctuation. The observed superior electrical stability of MoS2 transistor is attributed to the low border trap density of the AlN interfacial layer, as well as the small gate leakage and high dielectric strength of AlN/Al2O3 dielectric stack.


Ultrasound-guided femoral nerve block using a ventral suprainguinal approach in healthy dogs.
To determine whether an ultrasound (US)-guided femoral nerve block using a ventral suprainguinal approach could be successfully achieved in sedated dogs; to measure the time to execute the nerve block, onset time, duration, and complete block rate in sensory and motor nerves; and to examine any differences between two volumes for injection. Blinded crossover experimental study. A total of 10 clinically healthy adult Beagle dogs. The femoral nerve of the right pelvic limb was infiltrated with 0.5% bupivacaine at 0.4 (treatment 0.4B) or 0.2 mL kg-1 (treatment 0.2B), or saline at 0.4 mL kg-1 (control) in sedated dogs. The sensory and motor nerve functions were scored on a scale of 0 (complete blockade) to 2 (normal). The onset time and duration of the sensory and motor nerve blockade were compared between treatments 0.4B and 0.2B using a Wilcoxon signed rank test. Sensory and motor nerve function scores for each of the three treatments were compared at multiple time points using a nonparametric multiple comparisons test. The time to execute the nerve block was 2.5 ± 0.9 minutes (n = 30). For both 0.4B and 0.2B treatments, the onset times of both the sensory and motor nerve blockades were 15 minutes. The durations of the sensory nerve blockade for 0.4B and 0.2B were 9.9 ± 1.4 and 10.0 ± 1.2 hours, respectively, and those of the motor nerve blockades were 10.5 ± 1.3 and 10.2 ± 1.3 hours, respectively. No adverse effects were noted. No significant difference was observed between 0.4B and 0.2B. A US-guided femoral nerve block using a ventral suprainguinal approach demonstrated a short onset and long duration with 0.5% bupivacaine 0.2 mL kg-1 and can be performed under sedation in dogs.


[Art therapy in treatment, rehabilitation, micro- and macrosocial adaptation of children with autism spectrum disorders by means of a special rehabilitation and adaptation program "Art therapy (drama therapy): 'Because You are Needed…' for children with general disorders of psychological development and other mental disorders"].
For the first time, the effectiveness of art therapy (drama therapy) in children with mental disorders has been studied on substantial clinical data. Psychotherapeutic work involved certain form of drama therapy that included patients watching Moscow theaters performances and then discussing them with family and in group therapy sessions with psychologists. Researchers have developed drama therapy methods for children with mental disorders, determined indications and contraindications for this treatment. The study shows effects of art therapy on the child adaptation to the conditions of the micro-social environment, particularly on his family adaptation, formation of harmonious, supportive, rehabilitative family relations. It is noted that art therapy influences adolescent's adaptation to the conditions of the macrosocial environment, particularly his adaptation in a peer group, behavior in various situations and formation of normal behavioral patterns in different environmental conditions.


Comparison of abo antibody levels in apheresis platelets suspended in platelet additive solution and plasma.
Transfusion of platelets (PLTs) with high ABO antibody titres can pose a risk of hemolysis if the unit crosses the ABO type. The PLTs stored in the platelet additive solution (PAS) remove asubstantial fraction of plasma and replace it with an isotonicbuffered solution.We aimed to assess the difference in anti-A/B antibody levels in Groups O, A and B apheresis platelets (APs) suspended in plasma and PAS. Apheresis donors are categorized into two groups, Plasma (Group I) and PAS (Group II), each blood group (A, B and O) had 20 samples. The anti-A/B(IgM)antibody levels were recorded from the AP donor (Group II) and from the AP units for both groups. The reduction in the anti-A/B(IgM) antibody levels in the APs suspended in the PAS for each blood group was determined. The median anti-A titres in blood Groups B (p = 0.009) and O (p = 0.005) was significantly lower in Group II. However, the difference in anti-B levels was not significant in the blood groups A (p = 0.057) and O (p = 0.205). The median level of reduction in IgM antibody titres across donor samples and the PAS-stored platelets was two-fold. The regression showed a level of reduction in antibody titres which can be explained by baseline donor antibody titres in blood groups A and B compared to blood group O. The medianABO antibody titres were lower in APs suspended in PAS than in plasma. Addition of the PAS significantly lowered the IgM antibody titres by twofold, compared to plasma.


Performance of bioelectrode based on different carbon materials in bioelectrochemical anaerobic digestion for methanation of maize straw.
The performance of the bioelectrochemical anaerobic digestion (BEAD) reactor was investigated with different carbon material-modified electrodes for the methanation of maize straw. The carbon material-modified electrodes used titanium (Ti) mesh modified with carbon nanotube (CNT), carbon black (CB), and activated carbon (AC). The maximum cumulative methane production obtained in the Ti-CNT reactor was (616.4 ± 9.3) mL/g VS, while the maximum methane production rate in the Ti-AC reactor was (61.9 ± 1.0) mL/g VS.d.The electroactive bacteria were well enriched by the different electrodes, and the enriched electroactive bacteria further facilitate the direct interspecies electron transfer (DIET) for methane production. Additionally, we found the phylum Firmicutes showed a linear relationship to methanogenic performance, as well as the Genus Proteiniborus. The Ti-CNT electrode shows better performance by the electrochemical analysis. These findings provide critical knowledge for the large-scale use of the BEAD process and the treatment of maize straw.


Structural and Dynamic Disorder, Not Ionic Trapping, Controls Charge Transport in Highly Doped Conducting Polymers.
Doped organic semiconductors are critical to emerging device applications, including thermoelectrics, bioelectronics, and neuromorphic computing devices. It is commonly assumed that low conductivities in these materials result primarily from charge trapping by the Coulomb potentials of the dopant counterions. Here, we present a combined experimental and theoretical study rebutting this belief. Using a newly developed doping technique based on ion exchange, we prepare highly doped films with several counterions of varying size and shape and characterize their carrier density, electrical conductivity, and paracrystalline disorder. In this uniquely large data set composed of several classes of high-mobility conjugated polymers, each doped with at least five different ions, we find electrical conductivity to be strongly correlated with paracrystalline disorder but poorly correlated with ionic size, suggesting that Coulomb traps do not limit transport. A general model for interacting electrons in highly doped polymers is proposed and carefully parametrized against atomistic calculations, enabling the calculation of electrical conductivity within the framework of transient localization theory. Theoretical calculations are in excellent agreement with experimental data, providing insights into the disorder-limited nature of charge transport and suggesting new strategies to further improve conductivities.


Extensive cortico-subcortical lesions in Wilson's disease: clinico-pathological study of two cases.
Wilson's disease (WD) with extensive cortico-subcortical lesions represents a rare neuropathological subgroup, the pathogenesis of which is not clearly determined. We report two new cases with identical lesions. In the families of each of the patient, there were mutations in the ATPase7B gene, especially in the family of proband 1, and in the first cousin of proband 2. These cases included massive destruction of the white matter in superior gyri, mostly frontal, extending to the deep cortex with neuronal loss and capillary proliferation. Astrocytes were of Alzheimer type 1 and 2; and type 1 were labeled by anti-metallothionein. Opalski cells were abundant and their macrophagic lineage was confirmed by immunostaining. Among the possible mechanisms proposed, the role of vascular factors and penicillamine treatment could be excluded. Cerebral copper content in white matter and putamen of case 1 was at the same level as in common WD but accumulation of unbound copper in the white matter was a distinctive feature, which suggested a pathological neurotoxic effect.


Metastatic transitional cell carcinoma of the bladder causing Addison's disease.
Addison's disease is rarely caused by metastatic cancer. We report a unique case of hypoadrenalism owing to metastatic transitional cell carcinoma of the bladder. The relevant literature is reviewed.


Mid-infrared multi-mode absorption spectroscopy using interband cascade lasers for multi-species sensing.
An interband cascade laser (ICL) operating at 3.7 μm has been used to perform multimode absorption spectroscopy, MUMAS, at scan rates up to 10 kHz. Line widths of individual modes in the range 10-80 MHz were derived from isolated lines in the MUMAS signatures of HCl. MUMAS data for methane covering a spectral range of 30 nm yielded a detection level of 30 μbar·m for 1 s measurement time at 100 Hz. Simultaneous detection of methane, acetylene, and formaldehyde in a gas mixture containing all three species is reported.


Building a Self-Management Toolkit for Patients with Pediatric Inflammatory Bowel Disease: Introducing the resilience 5.
Transition from pediatric to adult health care is a complex process that calls for complex interventions and collaboration between health care teams and families. However, many inflammatory bowel disease (IBD) clinical care teams do not have the resources to implement rigorous transition programs for youth. This review provides a description of the Resilience5: self-efficacy, disease acceptance, self-regulation, optimism, and social support. The Resilience5 represents teachable skills to support IBD self-management, offset disease interfering behaviors, and build resilience in adolescents and young adults transitioning to adult health care systems. These skills can also be encouraged and reinforced during routine IBD clinical care.


Immune mediators of postoperative ileus.
CLINICAL BACKGROUND: In all patients undergoing abdominal surgery, a transient phase of interruption of bowel motility, named postoperative ileus (POI) occurs. POI is often accepted as an unavoidable "physiological" response and a self-limiting complication after surgery although it has a significant impact on patient morbidity with prolonged hospitalization and increased costs. Annual economic burden has been estimated as much as US $1.47 billion in the USA (Iyer et al. in J Manag Care Pharm 15(6):485-494, 2009). The pathophysiology has been elucidated within the last decades, demonstrating that both, neurogenic and inflammatory mechanisms are involved in response to the surgical trauma. It is now generally accepted that POI pathogenesis processes in two phases: a first neurogenic phase is accountable for the immediate postoperative impairment of bowel motility. This is followed by a second immunological phase that can last for days and mainly affects strength and length of POI. More recent findings demonstrate a bidirectional interaction between the nervous and the immune system, and this interaction significantly contributed to our present understanding of POI pathophysiology. Although nerval mechanisms have a significant impact in the early phase of POI, the contribution of the immune system and subsequently its manipulation has risen as the most promising strategy in prevention or treatment of the clinically relevant prolonged form of POI. The present manuscript will give an update on the inflammatory responses, the involved cell types, and participating immune mediators in POI.


The effect of intravenous administration of fat emulsion on the flow rate and composition of thoracic duct lymph in the dog.
In seven dogs weighing 17-25 kg, the terminal segment of the thoracic duct was isolated, under total pentobarbital anesthesia, so as to collect lymph continuously before, during and after infusion of a 20% fat emulsion Intralipid (Vitrum). Arterial blood and lymph were withdrawn simultaneously for analysis of total protein, amylase, cholesterol, triglycerides, urea and AST. The lymph flow rate was calculated in ml/min. Compared with the control period, during which a 5% glucose solution was administered, a two-hour infusion of the fat emulsion did not change the lymph flow rate nor the levels of biochemical parameters monitored in lymph. These results distinguish intravenous administration of a fat emulsion from a situation, in which fat is administered orally. The unchanged lymph amylase levels following fat administration suggest that no significant stimulation of external pancreatic secretion occurs after this route of fat administration.


Seasonal variation of aerosol fungal community structure in reed constructed wetlands.
In recent years, the impact of biological aerosols produced by sewage treatment plants on air quality and human health has become a hot spot of concern. Airborne fungi were characterized via KC-1000 large-flow air sampler and Anderson-type six-stage sampler, at free surface flowing reed constructed wetland located in Qingdao City, Shandong Province. The high-throughput sequencing technology and fungal culture-dependent method were selected to analyze the composition and dynamic changes of the fungal community attached to the atmospheric particulate matter in the free surface flow constructed wetland. The results showed that the aerosol concentration of fungi in the constructed wetlands varied from 587 to approximately 3382 CFU m-3, with a peak at the range of 1.10 to 2.10 μm particle size, and the particles (< 4.70 μm) that easily entered the lungs accounted for 57.03 ~ 96.03%. Significant seasonal differences in fungal richness and community diversity were found. The particle size distribution of fungi in atmospheric particles was not obvious. Fungal genera in the atmospheric particulate matter were mainly driven by humidity. However, other factors, i.e., temperature, NO2, SO2, and PM10 contents, also contributed.


Avanafil: a review of its use in patients with erectile dysfunction.
Avanafil (STENDRA™, SPEDRA™, Zepeeed™) is an oral phosphodiesterase type 5 inhibitor indicated for the treatment of erectile dysfunction. Avanafil is rapidly absorbed after oral administration, with a median time to maximum plasma concentration of 30 to 45 min. In a 12-week, randomized, double-blind, placebo-controlled, multicentre trial in patients with erectile dysfunction, avanafil 50, 100 and 200 mg recipients had significantly greater improvements from baseline than placebo recipients in mean international index of erectile dysfunction-erectile function domain scores and in successful vaginal penetration and sexual intercourse attempts (coprimary endpoints). Treatment effects were significantly larger in avanafil 100 and 200 mg recipients than 50 mg recipients. For avanafil recipients, approximately two-thirds of attempts at sexual intercourse that were made prior to 15 min, or more than 6 h, after drug administration were successful, compared with approximately one-quarter of attempts made during these time periods by placebo recipients. In trials in patients with erectile dysfunction in association with diabetes mellitus, and after nerve-sparing radical prostatectomy, avanafil 100 or 200 mg was significantly more efficacious than placebo for primary and most secondary endpoints. Avanafil was generally well tolerated in the above-mentioned studies. In a pooled analysis of three clinical trials, ≤2 % of avanafil and placebo recipients discontinued treatment because of adverse events. During extended treatment with avanafil for >52 weeks, 2.8 % of patients discontinued treatment because of adverse reactions and there were no drug-related serious adverse events.


Treatment of acute lymphoblastic leukemia with an rGel/BLyS fusion toxin.
Acute lymphoblastic leukemia (ALL) is the most common malignancy affecting children and a major cause of mortality from hematopoietic malignancies in adults. A substantial number of patients become drug resistant during chemotherapy, necessitating the development of alternative modes of treatment. rGel (recombinant Gelonin)/BlyS (B-lymphocyte stimulator) is a toxin-cytokine fusion protein used for selective killing of malignant B-cells expressing receptors for B-cell-activating factor (BAFF/BLyS) by receptor-targeted delivery of the toxin, Gelonin. Here, we demonstrate that rGel/BLyS binds to ALL cells expressing BAFF receptor (BAFF-R) and upon internalization, it induces apoptosis of these cells and causes downregulation of survival genes even in the presence of stromal protection. Using an immunodeficient transplant model for human ALL, we show that rGel/BLyS prolongs survival of both Philadelphia chromosome-positive and negative ALL-bearing mice. Furthermore, we used AMD3100, a CXCR4 antagonist, to mobilize the leukemic cells protected in the bone marrow (BM) microenvironment and the combination with rGel/BLyS resulted in a significant reduction of the tumor load in the BM and complete eradication of ALL cells from the circulation. Thus, a combination treatment with the B-cell-specific fusion toxin rGel/BLyS and the mobilizing agent AMD3100 could be an effective alternative approach to chemotherapy for the treatment of primary and relapsed ALL.


Atmospheric-pressure ionization studies and field dependence of ion mobilities of isomeric hydrocarbons using a miniature differential mobility spectrometer.
The ionization pathways and ion mobility were determined for sets of structural isomeric and stereoisomeric non-polar hydrocarbons (saturated and unsaturated cyclic hydrocarbons and aromatic hydrocarbons) using a novel miniature differential mobility spectrometer with atmospheric-pressure photoionization (APPI) to assess how structural and stereochemical differences influence ion formation and ion mobility. The analytical results obtained using the differential mobility spectrometry (DMS) were compared with the reduced mobility values measured using conventional time-of-flight ion mobility spectrometry (IMS) with the same ionization technique. The majority of differences in DMS ion mobility spectra observed among isomeric cyclic hydrocarbons can be explained by the formation of different product ions. Comparable differences in ion formation were also observed using conventional IMS and by investigations using the coupling of ion mobility spectrometry with mass spectrometry (APPI-IMS-MS) and APPI-MS. Using DMS, isomeric aromatic hydrocarbons can in the majority of cases be distinguished by the different behavior of product ions in the strong asymmetric radio frequency (rf) electric field of the drift channel. The different peak position of product ions depending on the electric field amplitude permits the differentiation between most of the investigated isomeric aromatics with a different constitution; this stands in contrast to conventional IMS in which comparable reduced mobility values were detected for the isomeric aromatic compounds.


Parafunctional habits, nightguards, and root form implants.
Occlusal schemes and designs of fixed and removable implant prostheses must satisfy requirements for the innocuous vertical loading of root form implants. Parafunctional habits (clenching, bruxing, or engaging) can transmit forces to the supporting bone that may result in destructive lateral stresses and overloading. Most nocturnal parafunctional habits can be ameliorated by acrylic resin nightguards.


Epigenetic priming improves salvage chemotherapy in diffuse large B-cell lymphoma via endogenous retrovirus-induced cGAS-STING activation.
Although most patients with diffuse large B-cell lymphoma (DLBCL) achieve complete remission after first-line rituximab-containing immunochemotherapy, up to 40% of patients relapse and require salvage therapy. Among those patients, a substantial proportion remain refractory to salvage therapy due to insufficient efficacy or intolerance of toxicities. A hypomethylating agent, 5-azacytidine, showed a chemosensitizing effect when primed before chemotherapy in lymphoma cell lines and newly diagnosed DLBCL patients. However, its potential to improve outcomes of salvage chemotherapy in DLBCL has not been investigated. In this study, we demonstrated the mechanism of 5-azacytidine priming as a chemosensitizer in a platinum-based salvage regimen. This chemosensitizing effect was associated with endogenous retrovirus (ERV)-induced viral mimicry responses via the cGAS-STING axis. We found deficiency of cGAS impaired the chemosensitizing effect of 5-azacytidine. Furthermore, combining vitamin C and 5-azacytidine to synergistically activate STING could be a potential remedy for insufficient priming induced by 5-azacytidine alone. Taken together, the chemosensitizing effect of 5-azacytidine could be exploited to overcome the limitations of the current platinum-containing salvage chemotherapy in DLBCL and the status of cGAS-STING has the potential to predict the efficacy of 5-azacytidine priming.


Regulation of trypsin-like esteroprotease synthesis by 5 alpha-dihydrotestosterone and triiodothyronine in mouse submandibular gland.
The hormonal regulation of trypsin-like esteroprotease synthesis in mouse submandibular gland was studied at the isozyme level. Antiserum to a mixture of two purified esteroproteases precipitated all the esteroproteases in a crude extract of this gland. Measurement of incorporation of [3H]leucine showed that total esteroprotease synthesis was stimulated by both 5 alpha-dihydrotestosterone and triiodothyronine and that the two hormones had synergistic effects. The observed correlation between the increases of synthetic rate and specific activity of this enzyme suggests that the enzyme level is regulated mainly by the rate of enzyme synthesis. Newly synthesized esteroprotease-antibody complexes gave four peaks of radioactivity with esteroprotease activity and one peak without enzyme activity on isoelectric focusing in acrylamide gel containing 8 M urea. The radioactivities of these five peaks were increased similarly by the two hormones separately or in a combination. These results suggest that the actions of androgens and thyroid homrones in esteroprotease synthesis are indistinguishable at the isozyme level.


Current modifications to totally laparoscopic "apron technique".
Since our original description in 1997 of a totally laparoscopic technique for treatment of aortoiliac disease, this type of minimally invasive procedure has been used both in the United States and abroad. We describe improvements that should make this technique more easily reproducible. This modified procedure was offered to six patients, one of whom received a tube graft for treatment of aneurysm disease.


On computational predictions of fluid flow and its effects on bone healing in dental implant treatments: an investigation of spatiotemporal fluid flow in cyclic loading.
Fluid flow in (porous) bone plays an important role in its maintenance, adaptation, and healing after an injury. Experimental and computational studies apply mechanical loading on bone to predict fluid flow development and/or to find its material properties. In most cases, mechanical loading is applied as a linear function in time. Multiple loading functions-with identical peak load and loading frequency-were used to investigate load-induced fluid flow and predict bone healing surrounding a dental implant. Implementing an instantaneous healing stimulus led to major differences in healing predictions for slightly different loading functions. Load-induced fluid flow was found to be displacement-rate dependent with complex spatial-temporal variations and not necessarily symmetrical during loading and unloading phases. Haversine loading resulted in more numerical stability compared to ramped/triangular loading, providing the opportunity for further investigation of the effects of various physiological masticatory loadings. It was concluded that using the average healing stimulus during cyclic loading gives the most robust bone healing predictions.


Role of two operators in regulating the plasmid-borne raf operon of Escherichia coli.
The plasmid-borne raf operon encodes functions required for the inducible uptake and utilization of raffinose in Escherichia coli K12. The expression of three structural genes for alpha-galactosidase (rafA), Raf permease (rafB) and sucrose hydrolase (rafD) is negatively controlled by the binding of RafR repressor (rafR) to two operator sites, O1 and O2, that flank the -35 sequence of the raf promoter, PA. In vitro, O1 and O2 are occupied on increasing the concentration of RafR, without detectable preference for one site or the other or any indication of cooperative binding. Nucleotide substitutions at positions 3, 4 or 5 in an operator half-site prevented repressor binding, supporting a model that postulates specific interactions of these base pairs with the recognition helix of RafR. To study the role of each operator site, we have compared by gel shift analysis the binding of purified RafR repressor to DNA fragments containing the original O1O2 configuration or mutant O1 or O2. When either one of the two operators was inactivated by site-directed mutagenesis, both O1 and O2 exhibited the same affinity for repressor and the same sensitivity to arrest of repressor binding by the natural inducer, melibiose. However, in the native O1O2 configuration, simultaneous binding of RafR to both operators was sterically hindered, leading to a 13-fold decrease in the intrinsic affinity of an operator site for repressor, once the other site had been occupied. To assess the role of each operator in vivo, rafA was used as a reporter gene. A 1200-fold repression (100%) was exerted by RafR binding to the native O1O2 configuration, whereas O2 alone exerted 45% and O1 alone 6% repression of rafA transcription. The differential effects of O1 versus O2 on transcription (despite matching affinities of O1 and O2 for repressor) suggest that positioning of the O2-repressor complex between the -35 and -10 signals is crucial for transcription control and that repressor binding to the upstream O1 serves to enhance this effect.


The action of peptides on the mudpuppy electroretinogram (ERG).
Two neuropeptide substances were applied to the mudpuppy retina while the electroretinogram (ERG) was recorded. A low concentration of somatostatin (10(-9)M) was found to be a potent agent in increasing the amplitudes of all the oscillatory potentials (OPs) of the ERG. There was no appreciable change of the threshold sensitivity or the stimulus response curve of the b-wave. The highest concentration tested (10(-6)M) reduced the first OP to about the same amplitude as at the start of the experiment and attenuated the later OPs. A decrease of the suprathreshold b-wave was induced by the highest concentrations (10(-7), 10(-6)M) of somatostatin. A low concentration of substance P (10(-11)M) selectively and differentially decreased the earlier OPs (O1O2). Higher concentrations (10(-10), 10(-9)M) diminished the earlier OPs further, reduced the later OPs and decreased the supra-threshold a- and b-waves. The results support previous suggestions that the OPs reflect activities in feedback circuits initiated by the amacrines and indicate that somatostatin and substance P through separate mechanisms seem to interact with the inhibitory neuronal circuits which have been suggested to give rise to the OPs. Secondly, in agreement with previous work, the OPs appear to have a different origin from the b-wave. Thirdly, two separate classes of amacrines, each with a different transmitter, seem to be associated with different physiological roles.


Tissue vs Liquid Biopsies for Cancer Detection: Ethical Issues.
Cancer is the second leading cause of death in developed countries, making it a global public health problem. In this scenario, early detection is the key to successful treatment. Tissue biopsy, the current gold standard for cancer diagnosis, offers reliable results, but it is feasible only when the mass becomes detectable. On the other hand liquid biopsy, a promising experimental system, not yet implemented within clinical practice, allows early detection as its functioning relies on the analysis of body fluids. Yet, its results are less reliable if compared to those of tissue biopsy as, for instance, false positives and false negatives might occur. Despite technical features, the tradeoff between a reliable diagnosis available at a later time and a potentially less reliable diagnosis available at an early stage poses significant ethical challenges in the clinical scenario which involve, among other aspects, informed consent, communication, and patient-physician encounter.


Recessive dystrophic epidermolysis bullosa caused by a de novo interstitial deletion spanning COL7A1 and a hemizygous splicing mutation in trans.
Recessive dystrophic epidermolysis bullosa (RDEB) is a rare heritable blistering skin condition caused by loss-of-function mutations in the COL7A1 gene. Incongruent gene transmission is occasionally reported in recessive diseases, and its underlying mechanism is often uniparental disomy (UPD). To understand the genetic basis of incongruent gene transmission in a Chinese family with RDEB, in which a discrepancy of COL7A1 genotyping was encountered during our mutation analysis. We used a pCAS2 minigene-based in vitro splicing assay to confirm the pathogenicity of the splicing variant we identified in the proband. Next, a combination of genetic tools, including whole-genome SNP array analysis and multiplex ligation-dependent probe amplification copy number analysis, was used to unravel the cause of the discrepancy in the COL7A1 genotyping. Sanger sequencing identified a novel, single-peak mutation, c.4980+5G>C, in COL7A1 in the proband, which was heterozygous in his father and wild type in his mother. In vitro splicing assay showed that c.4980+5G>C was pathogenic and led to skipping of COL7A1 exon 53. SNP array analysis and multiplex ligation-dependent probe amplification of the proband's DNA revealed a maternally derived, de novo, interstitial deletion on chromosome 3p21.31, which removed COL7A1 and 15 flanking genes, excluding the possibility of UPD. Our findings favour an exceptionally rare event, namely a de novo COL7A1 microdeletion in concurrence with an inherited mutation in trans. This study should aid molecular diagnosis and genetic counselling of RDEB and possibly other recessive diseases in which genotyping discrepancy is encountered.


GPCR agonist binding revealed by modeling and crystallography.
Despite recent progress in structural coverage of the G-protein-coupled receptor (GPCR) family, high plasticity of these membrane proteins poses additional challenges for crystallographic studies of their complexes with different classes of ligands, especially agonists. The ability to predict computationally the binding of natural and clinically relevant agonists and corresponding changes in the receptor pocket, starting from inactive GPCR structures, is therefore of great interest for understanding GPCR biology and drug action. Comparison of computational models published in 2009 and 2010 with recently determined agonist-bound structures of β-adrenergic and adenosine A(2A) receptors reveals high accuracy of the predicted agonist binding poses (0.8 Å and 1.7 Å respectively) and receptor interactions. In the case of the β(2)AR, energy-based models with limited backbone flexibility have also allowed characterization of side-chain rotations and a finite backbone shift in the pocket region as determinants of full, partial or inverse agonism. Development of accurate models of agonist binding for other GPCRs will be instrumental for functional and pharmacological studies, complementing biochemical and crystallographic techniques.


Resolution of a Focal Pruritic Rash Following Neurosurgical Decompression in an Adolescent With Chiari I and Syringomyelia.
Chiari I malformation (Chiari I) is defined by the downward displacement of one or both cerebellar tonsils below the foramen magnum of the skull with crowding altering cerebrospinal fluid flow. It can be associated with the development of a fluid-filled cavity within the spinal cord, syringomyelia. Neurological deficits or symptoms can occur at the level of anatomic involvement of syringomyelia. A young man presented to dermatology clinic for evaluation of a pruritic rash. Recognizing a unique left "cape-like" distribution of neuropathic itch leading to prurigo nodularis, he was referred for further evaluation by neurology in the local emergency department. After additional history and neurological exam, a magnetic resonance imaging confirmed Chiari I with an associated syringobulbia and a syrinx extending to T10/11 of the spinal cord. Anteriorly the syrinx extended into the left parenchyma of his spinal cord involving the dorsal horn, a lesion explaining his neuropathic itch. The sensation of itch and rash resolved after posterior fossa craniectomy and C1 laminectomy with duraplasty. Neuropathic itch, in addition to pain, can be a symptom of Chiari I with syringomyelia. Focal pruritus without an obvious cutaneous trigger should prompt providers to consider a central neurological pathology. While many patients with Chiari I are asymptomatic, the presence of neurological deficits and syringomyelia, are indications for neurosurgical evaluation.


[Emotional status, cognitive performance and quality of life in HIV-infected patients. Results of an exploratory study].
Due to the change of HIV disease from an acute life-threatening disease to a chronic infection, it is more psychosocial rather than therapeutic aspects that have become of interest in scientific investigations. The purpose of this exploratory study was to evaluate emotional distress, health-related quality of life (HRQoL) and cognitive performance. The diagnosis of HIV was considered a life event that may lead to post-traumatic stress syndrome. We recruited 37 HIV-positive outpatients and assessed the frequency of depressive (BDI) and post-traumatic stress symptoms (PTSS) due to the diagnosis of HIV (IES), HRQoL (SF-36) and cognitive performance (SKT). Further, the new diagnostic concept of adjustment disorder as a stress response syndrome according to Maercker was considered. Of the 37 Patients, 67.6% (n=25) of the sample had a post-traumatic stress syndrome. The HIV-related PTSS was considered adjustment disorder using the concept proposed by Maercker. Fourteen patients (37.8%) suffered from a depressive syndrome, and 27% (n=10) showed cognitive deficits (minimal: n=8; mild: n=1; moderate: n =1). HIV-positive patients with PTSS had significantly unfavourable values in the SF-36 domains general health (p=0.003), vitality (p=0.007), social functioning (p=0.000), role-emotional (p=0.016) and mental health (p=0.000). HIV-infected patients may face a major risk of HIV-related PTSS in the sense of adjustment disorder according to Maercker, depression and cognitive dysfunction. The presence of emotional distress is associated with impairments in quality of life. We therefore suggest an early and comprehensive bio-psycho-social assessment and therapy of HIV-infected patients.


Hammock mitral valve in an adult patient.
We describe a case of hammock mitral valve in an adult. A 38-year-old woman presented with recently acquired dyspnea. Echocardiography showed severe mitral stenosis related to a hammock mitral valve characterized by the presence of an overdeveloped papillary muscle that gives short chordae to both mitral leaflets. No other valve insufficiency was noted. At operation, we observed direct continuity accompanying several fenestrations between both leaflets and the huge abnormal muscular band just underneath the mural leaflet. Resection of the anterior leaflet and was successfully replaced with a bioprosthetic valve. Her postoperative course was unremarkable.


A machine-learning approach to discerning prevalence and causes of myopia among elementary students in Hubei.
Our aim is to establish a machine-learning model that will enable us to investigate the key factors influencing the prevalence of myopia in students. We performed a cross-sectional study that included 16,653 students from grades 1-3 across 17 cities in Hubei Province. We used questionnaires to discern levels of participation in potential factors contributing to the development of myopia. The relative importance of potential contributors was ranked using machine-learning methods. The students' visual acuity (VA) was measured and those with logMAR VA of > 0.0 underwent a autorefraction test to determine students' refraction status. The prevalence of myopia in grades 1, 2, and 3 was 14.70%, 20.54% and 28.93%, respectively. Myopia rates among primary school students in provincial capital city (32.35%) were higher than those in other urban (23.03%) and rural (14.82%) areas. Children with non-myopic parents, only one myopic parent, or both parents having myopia exhibited myopic rates of 16.36%, 25.18%, and 41.37%, respectively. Myopia prevalence was higher in the students who continued to use their eyes at close range for a long time and lower in those engaged longer in outdoor activities. The machine-learning model determined that the top three contributing factors were the students' age (0.36), followed by place of residence (0.34), starting age of education (0.21). The overall prevalence of myopia was 21.52%. Children's age and place of residence were the important influencing factors, but genetics and environmental were also played key roles in myopia development.


Ethical issues in the use of genetic information.
Advances in molecular genetics promise to deepen our understanding of the biological basis of human behavior and shed light on the pathophysiology of mental illness. Genetic research is likely to improve our ability to develop somatic treatments for psychiatric syndromes as well as to identify targets for environmental intervention. However, population-screening tests for disorders with multifactorial inheritance may offer little clinical benefit to outweigh their potential for misuse. Relevant legal issues surrounding the use of genetic information in psychiatry include the perceived need for laws to prevent insurance and employment discrimination, and concerns about genetic status as a possible excuse for criminal behavior. Relevant ethical issues include threats to patient privacy and confidentiality and the importance of fairly distributing the benefits and burdens of genetic advances.