Effects of selective inhibition of cyclooxygenase and lipooxygenase pathways in follicle rupture and ovulation in the rat.
Treatment with non-steroidal anti-inflammatory drugs, either non-selective or selective cyclooxygenase-2 (COX-2) inhibitors, consistently impairs ovulation, indicating the essential role of COX-2/prostaglandins in the ovulatory process. Indomethacin, a potent inhibitor of both COX-1 and COX-2, induced several ovulatory alterations, consisting of a decrease in the number of oocytes effectively ovulated, trapping of oocytes inside the luteinized follicle, as well as abnormal follicle rupture at the basolateral sides, with release of the oocyte and follicular fluid to the interstitium. Yet, the precise role of prostaglandins in ovulation and whether some of the ovulatory defects induced by indomethacin are due to interference with additional components of the ovulatory cascade, beyond prostaglandin synthesis, are not completely understood. We have used gonadotrophin-primed immature rats to analyse whether, compared to indomethacin, selective inhibition of COX-2, with or without concomitant inhibition of COX-1, or selective inhibition of the lipooxygenase (LOX) pathway, induce similar ovulatory alterations. Immature rats (27 days of age) were injected PMSG (10 IU), and 48 h later hCG (10 IU) subcutaneously, and different anti-inflammatory drugs. Animals were killed at 21 h after hCG injection. Rats treated with the selective COX-2 inhibitor NS398 (10 mg/kg body weight, (bw)) showed alterations in follicle rupture as those treated with indomethacin (0.5 mg/rat), albeit affecting a lower number of follicles, irrespective of the concomitant inhibition of COX-1 with the selective inhibitor SC560 (10 mg/kg bw). Rats treated with the LOX inhibitor NDGA (300 mg/kg bw) did not show ovulatory alterations. These data indicate that the characteristic alterations of follicle rupture induced by indomethacin, are also induced by selective COX-2 inhibitors, strengthening the contention that prostaglandins play a crucial role in the spatial targeting of follicle rupture at the apex.


Quantifying the roles of random motility and directed motility using advection-diffusion theory for a 3T3 fibroblast cell migration assay stimulated with an electric field.
Directed cell migration can be driven by a range of external stimuli, such as spatial gradients of: chemical signals (chemotaxis); adhesion sites (haptotaxis); or temperature (thermotaxis). Continuum models of cell migration typically include a diffusion term to capture the undirected component of cell motility and an advection term to capture the directed component of cell motility. However, there is no consensus in the literature about the form that the advection term takes. Some theoretical studies suggest that the advection term ought to include receptor saturation effects. However, others adopt a much simpler constant coefficient. One of the limitations of including receptor saturation effects is that it introduces several additional unknown parameters into the model. Therefore, a relevant research question is to investigate whether directed cell migration is best described by a simple constant tactic coefficient or a more complicated model incorporating saturation effects. We study directed cell migration using an experimental device in which the directed component of the cell motility is driven by a spatial gradient of electric potential, which is known as electrotaxis. The electric field (EF) is proportional to the spatial gradient of the electric potential. The spatial variation of electric potential across the experimental device varies in such a way that there are several subregions on the device in which the EF takes on different values that are approximately constant within those subregions. We use cell trajectory data to quantify the motion of 3T3 fibroblast cells at different locations on the device to examine how different values of the EF influences cell motility. The undirected (random) motility of the cells is quantified in terms of the cell diffusivity, D, and the directed motility is quantified in terms of a cell drift velocity, v. Estimates D and v are obtained under a range of four different EF conditions, which correspond to normal physiological conditions. Our results suggest that there is no anisotropy in D, and that D appears to be approximately independent of the EF and the electric potential. The drift velocity increases approximately linearly with the EF, suggesting that the simplest linear advection term, with no additional saturation parameters, provides a good explanation of these physiologically relevant data. We find that the simplest linear advection term in a continuum model of directed cell motility is sufficient to describe a range of different electrotaxis experiments for 3T3 fibroblast cells subject to normal physiological values of the electric field. This is useful information because alternative models that include saturation effects involve additional parameters that need to be estimated before a partial differential equation model can be applied to interpret or predict a cell migration experiment.


A Data-Driven Assessment of the U.S. Health Informatics Programs and Job Market.
Health Informatics (HI) is an interdisciplinary field, integrating health sciences, computer science, information science, and cognitive science to assist health information management, analysis, and utilization. As the HI field is broad, it is impossible that a student will be able to master all the diverse HI topics. Thus, it is important to train the HI students based on the offering of the various HI programs and needs of the current market. This project will study the U.S. HI programs, training materials, HI job market, the skillset required by the employers, competencies taught in HI programs, and comparisons between them. We collected the training information for the 238 U.S. universities that offered MS, PhD, or postbaccalaureate certificate programs in HI or related professions. Next, we explored the HI job market by randomly checking 200 jobs and their required skillsets and domain knowledge. Then, we compared these skillsets with those offered by the HI programs and identified the gaps and overlaps for program enhancements. Among the 238 U.S. universities, 94 universities offer HI programs: 92 universities with MS (Master of Science), 43 with doctoral, 42 with both MS and doctoral, and 54 with certificate programs. The most offered HI courses are related to practicum, data analytics, research, and ethics. For the HI job postings, the three most technical skillsets required in HI job posting are data analysis, database management, and knowledge of electronic health records. However, only 58% of HI programs offer courses in database management and analytics. Compared with American Medical Informatics Association's recommended 10 fundamental domains, the HI curriculum generally lacks training in socio-technical systems, social-behavioral aspects of health, and interprofessional collaborative practice. There are gaps between the industry expectations of HI and the training received in HI programs. Advance level technical courses are needed in HI programs to meet industry expectations.


Activity-dependent regulation of the dopamine transporter is mediated by Ca(2+)/calmodulin-dependent protein kinase signaling.
The mechanisms regulating expression of the dopamine transporter are poorly understood. We tested the hypothesis that neuronal activity is one of the non-genetic determinants of dopamine transporter abundance. Sustained changes in neuronal activity caused by tetrodotoxin and 4-aminopyridine altered the dopamine uptake and abundance of dopamine transporter and its mRNA in rat mesencephalic cultures. The altered neuronal activity caused by these two drugs is accompanied by changes in intracellular calcium concentrations and Ca(2+)/calmodulin-dependent protein (CaM) kinase II activity in dopamine neurons. Chronic treatment with an L-type calcium channel blocker (nifedipine) or CaM kinase inhibitor (KN93) decreased dopamine transporter-mediated uptake and occluded the effects of tetrodotoxin and 4-aminopyridine. These data suggest that neuronal activity can regulate dopamine transporter function and abundance via calcium/CaM kinase II signaling.


Artificial Intelligence Technology Driven Environmental Factors Extraction and Analysis Method in Traditional Clothing Handicraft.
The application of artificial intelligence (AI) technology in the field of clothes can provide a good development mode and system under the social context of AI technology development. AI provides help for the development of intelligent clothing. Intelligent clothing is a high-tech product that integrates intelligent technology and clothing. It combines cutting-edge technologies in electronic information technology, sensor technology, textile science, and material science. In the extraction and analysis of environmental factors in clothing handicraft, AI technology has a considerable application prospect and a certain development potential. In order to improve the accuracy of environmental factors extraction in clothing handicraft, this paper uses convolutional neural network (CNN) to extract and analyze environmental factors in traditional clothing handicraft. We carried out experiments on the extraction of environmental factors in clothing handicrafts with pure color, few patterns, patterns, and complex background. The experimental results show that the CNN has a good effect on the extraction of environmental factors in clothing handicraft under different backgrounds. In addition, the model in this paper has good stability, accuracy, and feature extraction speed, which has high practical value and research significance.


[The effect of endotoxin on the expression of tissue factor in the CCl4-treated rat liver].
Endotoxemia is known to cause hepatic microcirculation disturbance and hepatic injury through blood coagulation and thrombosis in the cirrhotic patients. This study was to investigate the effect of endotoxin on the expression of tissue factor in rat liver with persistent injury. Male Sprague-Dawley rats were used for this experiment. Persistent hepatic injury was induced by injecting 0.1 mL of CCl4 and 0.1 mL of mineral oil per 100 grams of body weight, intraperitoneally. Twenty-four rats were divided into 4 groups and lipopolysaccharide (LPS, E. coli O111:B4) was injected intraperitoneally in 3 groups in a dose of 200 microgram/kg, 400 microgram/kg, and 800 microgram/kg, respectively. Expression of tissue factor was evaluated by real time PCR method. SYBR Green I, a DNA binding fluorophore was used for the detection of PCR product. Expression of hepatic tissue factor tended to increase according to the amounts of LPS. Specially, the expression of tissue factor was significantly increased in the group into which 400 microgram/kg of LPS was injected, compared with control group (p<0.05). Expression of tissue factor tends to increase according to the amounts of LPS in the persistent hepatic injury. LPS may play an important role in the expression of tissue factor in the CCl4-treated rat liver.


Reflections on the idea of personal fate and its psychopathology: Helene Deutsch's "Hysterical Fate Neurosis" revisited.
The idea of a psychopathology of fate or what had come to be called a fate neurosis has failed to retain any established place in the structure of psychoanalytic thought. The clinical observations and theoretical formulations, to which the idea of a fate neurosis answered, have been subsumed in the course of things by more fundamental and systematic conceptualizations. A review of Helene Deutsch's (1930) paper, "Hysterical Fate Neurosis," is therefore bound to be largely an excursion into an area of intellectual history. However, such history never fails to shed light on certain ongoing clinical and theoretical problems that may have lost too much to current developments in psychoanalytic thought. It is with this historical purpose that the present study of Deutsch's classic paper on a fate neurosis is undertaken.


Optimization of Agrobacterium-Mediated Transformation in Soybean.
High transformation efficiency is a prerequisite for study of gene function and molecular breeding. Agrobacterium tumefaciens-mediated transformation is a preferred method in many plants. However, the transformation efficiency in soybean is still low. The objective of this study is to optimize Agrobacterium-mediated transformation in soybean by improving the infection efficiency of Agrobacterium and regeneration efficiency of explants. Firstly, four factors affecting Agrobacterium infection efficiency were investigated by estimation of the rate of GUS transient expression in soybean cotyledonary explants, including Agrobacterium concentrations, soybean explants, Agrobacterium suspension medium, and co-cultivation time. The results showed that an infection efficiency of over 96% was achieved by collecting the Agrobacterium at a concentration of OD650 = 0.6, then using an Agrobacterium suspension medium containing 154.2 mg/L dithiothreitol to infect the half-seed cotyledonary explants (from mature seeds imbibed for 1 day), and co-cultured them for 5 days. The Agrobacterium infection efficiencies for soybean varieties Jack Purple and Tianlong 1 were higher than the other six varieties. Secondly, the rates of shoot elongation were compared among six different concentration combinations of gibberellic acid (GA3) and indole-3-acetic acid (IAA). The shoot elongation rate of 34 and 26% was achieved when using the combination of 1.0 mg/L GA3 and 0.1 mg/L IAA for Jack Purple and Tianlong 1, respectively. This rate was higher than the other five concentration combinations of GA3 and IAA, with an 18 and 11% increase over the original laboratory protocol (a combination of 0.5 mg/L GA3 and 0.1 mg/L IAA), respectively. The transformation efficiency was 7 and 10% for Jack Purple and Tianlong 1 at this optimized hormone concentration combination, respectively, which was 2 and 6% higher than the original protocol, respectively. Finally, GUS histochemical staining, PCR, herbicide (glufosinate) painting, and QuickStix Kit for Liberty Link (bar) were used to verify the positive transgenic plants, and absolute quantification PCR confirmed the exogenous gene existed as one to three copies in the soybean genome. This study provides an improved protocol for Agrobacterium-mediated transformation in soybean and a useful reference to improve the transformation efficiency in other plant species.


Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease.
Enzyme replacement therapy (ERT) became a reality for patients with Pompe disease, a fatal cardiomyopathy and skeletal muscle myopathy caused by a deficiency of glycogen-degrading lysosomal enzyme acid alpha-glucosidase (GAA). The therapy, which relies on receptor-mediated endocytosis of recombinant human GAA (rhGAA), appears to be effective in cardiac muscle, but less so in skeletal muscle. We have previously shown a profound disturbance of the lysosomal degradative pathway (autophagy) in therapy-resistant muscle of GAA knockout mice (KO). Our findings here demonstrate a progressive age-dependent autophagic buildup in addition to enlargement of glycogen-filled lysosomes in multiple muscle groups in the KO. Trafficking and processing of the therapeutic enzyme along the endocytic pathway appear to be affected by the autophagy. Confocal microscopy of live single muscle fibers exposed to fluorescently labeled rhGAA indicates that a significant portion of the endocytosed enzyme in the KO was trapped as a partially processed form in the autophagic areas instead of reaching its target--the lysosomes. A fluid-phase endocytic marker was similarly mistargeted and accumulated in vesicular structures within the autophagic areas. These findings may explain why ERT often falls short of reversing the disease process and point toward new avenues for the development of pharmacological intervention.


Detecting Sugarcane yellow leaf virus infection in asymptomatic leaves with hyperspectral remote sensing and associated leaf pigment changes.
Sugarcane infected with Sugarcane yellow leaf virus (SCYLV) rarely produces visual symptoms until late in the growing season. High-resolution, hyperspectral reflectance data from SCYLV-infected and non-infected leaves of two cultivars, LCP 85-384 and Ho 95-988, were measured and analyzed on 13 July, 12 October, and 4 November 2005. All plants were asymptomatic. Infection was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Results from discriminant analysis showed that leaf reflectance was effective at predicting SCYLV infection in 73% of the cases in both cultivars using resubstitution and 63% and 62% in LCP 85-384 and Ho 95-988, respectively, using cross-validation. Predictive equations were improved when data from sampling dates were analyzed individually. SCYLV infection influenced the concentration of several leaf pigments including violaxanthin, beta-carotene, neoxanthin, and chlorophyll a. Pigment data were effective at predicting SCYLV infection in 80% of the samples in the combined data set using the derived discriminant function with resubstitution, and 71% with cross-validation. Although further research is needed to improve the accuracy of the predictive equations, the results of this study demonstrate the potential application of hyperspectral remote sensing as a rapid, field-based method of identifying SCYLV-infected sugarcane plants prior to symptom expression.


[Bilateral quadriceps rupture in a patient with osteogenesis imperfecta. A case report].
We present the case of a 24-year-old patient with bilateral quadriceps rupture and history of type I congenital osteogenesis imperfecta diagnosed clinically and with ultrasound. Bilateral quadriceps tenoplasty was performed with an anterior approach and without any complications. The patient was discharged with bilateral neoprene knee-guards. The sutures were removed at the 21-day follow-up visit, rehabilitation was started at six weeks and the patient was doing well at the 2- and 3-month follow-up visits. Timely management and early rehabilitation contribute to decrease the risk of sequelae despite the poor functional prognosis.


Forced withdrawal from methadone maintenance therapy in criminal justice settings: a critical treatment barrier in the United States.
The World Health Organization classifies methadone as an essential medicine, yet methadone maintenance therapy remains widely unavailable in criminal justice settings throughout the United States. Methadone maintenance therapy is often terminated at the time of incarceration, with inmates forced to withdraw from this evidence-based therapy. We assessed whether these forced withdrawal policies deter opioid-dependent individuals in the community from engaging methadone maintenance therapy in two states that routinely force inmates to withdraw from methadone (N = 205). Nearly half of all participants reported that concern regarding forced methadone withdrawal during incarceration deterred them engaging methadone maintenance therapy in the community. Participants in the state where more severe methadone withdrawal procedures are used during incarceration were more likely to report concern regarding forced withdrawal as a treatment deterrent. Methadone withdrawal policies in the criminal justice system may be a broader treatment deterrent for opioid-dependent individuals than previously realized. Redressing this treatment barrier is both a health and human rights imperative.


Relative clause reading in hearing impairment: different profiles of syntactic impairment.
Children with hearing impairment show difficulties in sentences derived by Wh-movement, such as relative clauses and Wh-questions. This study examines the nature of this deficit in 48 hearing impaired children aged 9-12 years and 38 hearing controls. The task involved reading aloud and paraphrasing of object relatives that include a noun-verb heterophonic homograph. The correct pronunciation of the homograph in these sentences depended upon the correct construction of the syntactic structure of the sentence. An analysis of the reading and paraphrasing of each participant exposed two different patterns of syntactic impairment. Some hearing-impaired children paraphrased the object relatives incorrectly but could still read the homograph, indicating impaired assignment of thematic roles alongside good syntactic structure building; other hearing-impaired children could neither read the homograph nor paraphrase the sentence, indicating a structural deficit in the syntactic tree. Further testing of these children confirmed the different impairments: some are impaired only in Wh-movement, whereas others have CP impairment. The syntactic impairment correlated with whether or not a hearing device was fitted by the age of 1 year, but not with the type of hearing device or the depth of hearing loss: children who had a hearing device fitted during the first year of life had better syntactic abilities than children whose hearing devices were fitted later.


Diploid hybrid speciation in Penstemon (Scrophulariaceae).
Hybrid speciation has played a significant role in the evolution of angiosperms at the polyploid level. However, relatively little is known about the importance of hybrid speciation at the diploid level. Two species of Penstemon have been proposed as diploid hybrid derivatives based on morphological data, artificial crossing studies, and pollinator behavior observations: Penstemon spectabilis (derived from hybridization between Penstemon centranthifolius and Penstemon grinnellii) and Penstemon clevelandii (derived from hybridization between P. centranthifolius and P. spectabilis). Previous studies were inconclusive regarding the purported hybrid nature of these species because of a lack of molecular markers sufficient to differentiate the parental taxa in the hybrid complex. We developed hypervariable nuclear markers using inter-simple sequence repeat banding patterns to test these classic hypotheses of diploid hybrid speciation in Penstemon. Each species in the hybrid complex was genetically distinct, separated by 10-42 species-specific inter-simple sequence repeat markers. Our data do not support the hybrid origin of P. spectabilis but clearly support the diploid hybrid origin of P. clevelandii. Our results further suggest that the primary reason diploid hybrid speciation is so difficult to detect is the lack of molecular markers able to differentiate parental taxa from one another, particularly with recently diverged species.


Impact of Percutaneous Endoscopic Gastrostomy Tube Feeding on Nutritional Status in Patients Undergoing Chemoradiotherapy for Oesophageal Cancer.
Oesophageal cancer causes dysphagia and weight loss. Malnutrition further worsens with multimodal treatment. The aim of the study was to evaluate the impact of percutaneous endoscopic gastrostomy (PEG) placement in the nutritional status of patients with oesophageal cancer requiring chemoradiotherapy (CRT). A comparative study with a prospective arm and a historical cohort was conducted. Oesophageal cancer patients undergoing CRT with dysphagia grade >2 and/or weight loss >10% were submitted to PEG-tube placement (pull method) before CRT. Stoma seeding was evaluated through a swab obtained after placement and, in surgical patients, the resected stoma. A matched historical cohort without PEG placement was used as control (trial ACTRN12616000697482). Twenty-nine patients (intervention group, IG) were compared to 30 patients (control group, CG). Main outcomes did not differ in the IG and CG: weight loss during CRT 8.1 ± 5.5 kg versus 9.1 ± 4.2 kg (p = 0.503); 6-month mortality after CRT or surgery 17.2% versus 26.7% (p = 0.383); perioperative complication rate 54.5% versus 55.6% (p = 1.000); unplanned hospital admissions 34.5% versus 40.0% (p = 0.661). In the CG, during CRT, 14 (46.7%) patients presented with dysphagia grade 3-4, of whom 12 required nasogastric tube feeding (n = 10), surgical gastrostomy (n = 1), and oesophageal dilation (n = 1). In the IG, 89.7% used the PEG tube during CRT, sometimes exclusively in 51.7%. Adverse events were mainly minor (n = 12, 41.4%), mostly late peristomal infections, 1 major complication (exploratory laparotomy due to suspected colonic interposition, not confirmed). There was no cytological or histological evidence of stomal tumour seeding. Weight loss, hospital admissions, surgical complications, and mortality were identical in oesophageal cancer patients referred for CRT, regardless of prophylactic PEG. However, half of the patients required exclusive enteral nutritional support, making PEG-tube placement an alternative to consider.


Impact of switching from zidovudine to tenofovir disoproxil fumarate on bone mineral density and markers of bone metabolism in virologically suppressed HIV-1 infected patients; a substudy of the PREPARE study.
In virologically suppressed, antiretroviral-treated patients, the effect of switching to tenofovir (TDF) on bone biomarkers compared to patients remaining on stable antiretroviral therapy is unknown. We examined bone biomarkers (osteocalcin [OC], procollagen type 1 amino-terminal propeptide, and C-terminal cross-linking telopeptide of type 1 collagen) and bone mineral density (BMD) over 48 weeks in virologically suppressed patients (HIV RNA < 50 copies/ml) randomized to switch to TDF/emtricitabine (FTC) or remain on first-line zidovudine (AZT)/lamivudine (3TC). PTH was also measured. Between-group differences in bone biomarkers and associations between change in bone biomarkers and BMD measures were assessed by Student's t tests, Pearson correlation, and multivariable linear regression, respectively. All data are expressed as mean (SD), unless otherwise specified. Of 53 subjects (aged 46.0 y; 84.9% male; 75.5% Caucasian), 29 switched to TDF/FTC. There were reductions in total hip and lumbar spine BMD in those switching to TDF/FTC (total hip, TDF/FTC, -1.73 (2.76)% vs AZT/3TC, -0.39 (2.41)%; between-group P = .07; lumbar spine, TDF/FTC, -1.50 (3.49)% vs AZT/3TC, +0.25 (2.82)%; between-group P = .06), but they did not reach statistical significance. Greater declines in lumbar spine BMD correlated with greater increases in OC (r = -0.28; P = .05). The effect of TDF/FTC on bone biomarkers remained significant when adjusted for baseline biomarker levels, gender, and ethnicity. There was no difference in change in PTH levels over 48 weeks between treatment groups (between-group P = .23). All biomarkers increased significantly from weeks 0 to 48 in the switch group, with no significant change in those remaining on AZT/3TC (between-group, all biomarkers, P < .0001). A switch to TDF/FTC compared to remaining on a stable regimen is associated with increases in bone turnover that correlate with reductions in BMD, suggesting that TDF exposure directly affects bone metabolism in vivo.


Downregulation of NPM reverses multidrug resistance in human hepatoma cells via inhibition of P-glycoprotein expression.
Multidrug resistance (MDR) is an important issue in current cancer treatments. In human cancer, drug resistance is primarily associated with the overexpression of multidrug resistance gene 1 (MDR1). Therefore, the human MDR1 gene promoter may be a target for anti‑MDR drug screening. Numerous methods to prevent MDR have been investigated. However, they have been proven to be clinically ineffective. Therefore, the aim of the present study was to investigate whether downregulation of nucleophosmin (NPM) demonstrates any effects on the reversal of MDR in hepatocellular carcinoma (HCC) cells. In the present study, two in vitro MDR HCC cell lines, HepG2/Adriamycin (ADM) and SMMC7721/ADM, were established and the level of MDR was measured. The results demonstrated that NPM downregulation markedly reversed the effects of MDR in the model used. In addition, NPM downregulation reduced P-glycoprotein expression, as well as MDR1 expression. These results suggested that downregulation of NPM may be a novel and effective method of reversing the effects of MDR, and may be a potential adjuvant for tumor chemotherapy.


Prospective evaluation of the clinical profile and referral pattern differences of vestibular schwannomas and other cerebellopontine angle tumors.
To evaluate the clinical profile, referral pattern, delay in diagnosis, and impact of tumor size of cases involving vestibular schwannomas (VS) versus other cerebellopontine angle (CPA) tumors in an Egyptian population. Case series study. Tertiary referral center. A prospective study of possible retrocochlear lesions was conducted from 2008 to 2010. Patients were subjected to a full clinical history, complete otorhinolaryngological examination, a basic audiologic evaluation, auditory brainstem response assay, and gadolinium-enhanced magnetic resonance imaging. According to the findings of magnetic resonance imaging, patients with retrocochlear lesions were divided into 2 groups: those with VS (n = 17) and those with other CPA lesions (n = 14). Diagnostic delay and criteria of VS and CPA tumors. Unilateral hearing loss and tinnitus were presented in 52.9% of VS cases with a diagnostic delay of 15.5 months. For cases involving other CPA lesions, a combination of otologic symptoms was observed in 9 (64%) of 14 cases, and a diagnostic delay of 47.5 months was experienced. An absence of auditory brainstem response waves was identified significantly (p < 0.05) for the affected ears of both groups. Only differences in Wave V latency were significant between the 2 groups (p < 0.05). A longer diagnostic delay was associated with cases involving other types of CPA lesions versus cases of VS, and tumor size and volume did not affect the diagnostic delay of the former. Moreover, the only significant difference in clinical presentation for these 2 groups of intracranial tumor involved Wave V latency.


Seeking Relevant Biomarkers in Common Variable Immunodeficiency.
Common variable immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiency. More than 50% of patients in some series suffer from autoimmune or inflammatory complications (the "CVID+" phenotype), and these are not adequately addressed by current treatments. Despite major advancements in genetics, the pathogenesis of the CVID+ phenotype has remained unexplained for most patients, necessitating the need for relevant biomarkers in both the clinic and research settings. In the clinics, reduced isotype-switched memory B cells (≤ 0.55% of B cells) and reduced T cells (CD4) can be utilized to identify those with increased complication risks. Additionally, condition-specific markers have also been suggested for lymphoma (normal or elevated IgM) and progressive interstitial lung disease (increased BAFF, normal or elevated IgM). Additional biomarkers have provided insights into disease pathogenesis, demonstrating wider systemic inflammation (increased LBP, sCD14, and sCD25; expanded ILC3), mucosal defects (increased zonulin, I-FABP), and perhaps reduced anti-inflammatory capability (reduced HDL) in CVID. Most recently, efforts have revealed elevated circulating bioactive bacterial DNA levels - marking microbial translocation and potentially linking the causation of multiple inflammatory changes previously observed in CVID. The implementation of high throughput profiling techniques may accelerate the search of relevant biomarker profiles in CVID and lead to better clinical risk stratification, revealing disease insights, and identifying potential therapeutic targets.


Visible-Light-Promoted Regioselective Hydroborylation of Ketene Dithioacetals with NHC-Boranes.
NHC-boranes have been treated as a reliable source of boryl radicals. In this study, regioselective hydroborylation of ketene dithioacetals with NHC-borane was achieved under mild conditions via a visible-light-promoted radical chain process using thiophenol as a proton donor and hydrogen atom transfer. This protocol features a low-cost catalyst, good functional group tolerance, a relatively broad range of substrate scope, and good to excellent yields. Moreover, mechanism of this hydroborylation reaction was preliminarily studied.


Structure of the variant glycoproteins and surface coat of Trypanosoma brucei.
The pathogenic African trypanosomes have a unique mechanism for antigenic variation. Each cell is covered by a surface coat consisting of about seven million essentially identical glycoprotein molecules drawn from a large repertoire of variants, each encoded by an individual gene. Amino acid sequence variation extends throughout the molecule but reduces from the amino terminus to the carboxy terminus, where certain features, especially the grouping of cysteine residues, are quite conserved. The range of diversity within the thousand or so variant glycoprotein genes that exist in each cell is large. New variants may arise instantaneously by segmental gene conversion. Variant surface glycoproteins are synthesized with amino terminal signal sequences and hydrophobic carboxy terminal tails. The tails are extraordinarily conserved. After synthesis, they are replaced by a complex glycolipid structure in which myristic (dodecanoic) acid serves to anchor the polypeptide to the surface membrane. Enzymic cleavage of myristic acid releases variant glycoproteins from the surface coat.


Association between subcutaneous steroid injection for extravasation of vesicant anticancer drugs and skin ulcers requiring surgery.
Although subcutaneous steroid injections are conventionally used to treat extravasation of vesicant anticancer drugs, their effects on the extravasation site remain unclear. We investigated the association between subcutaneous steroid injection in patients with extravasation of vesicant anticancer drugs and incidence of skin ulcers requiring surgery. We performed a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database. We identified patients with extravasation of vesicant anticancer drugs who were prescribed steroid ointment or cream on the same day as vesicant drug use between July 2010 and March 2019. The exposure group consisted of patients who had received subcutaneous steroid injections and local anesthetic in addition to topical steroids, whereas the control group had received topical steroids alone. The outcome was the incidence of skin surgical procedures during hospitalization. We performed a mixed-effect logistic regression analysis with random intercept for each hospital to compare outcomes between the groups. We identified 7284 patients from 704 hospitals, including 3713 patients who had received topical steroids alone and 3571 who had received subcutaneous steroid injection in addition to topical steroids. According to mixed-effect logistic regression analysis, subcutaneous steroid injection was significantly associated with a higher incidence of skin surgery (odds ratio, 1.61; 95% confidence interval, 1.14-2.26; P = 0.007). Barthel Index, type of cancer, and type of vesicant drugs were also associated with surgery. Subcutaneous steroid injections after extravasation of vesicant anticancer drugs are associated with more frequent skin surgery. Randomized controlled trials are required to evaluate the safety and effectiveness of steroid injection.


Extinction learning in childhood anxiety disorders, obsessive compulsive disorder and post-traumatic stress disorder: implications for treatment.
Threat conditioning and extinction play an important role in anxiety disorders, obsessive compulsive disorder (OCD), and post-traumatic stress disorder (PTSD). Although these conditions commonly affect children, threat conditioning and extinction have been primarily studied in adults. However, differences in phenomenology and neural architecture prohibit the generalization of adult findings to youth. A comprehensive literature search using PubMed and PsycInfo was conducted to identify studies that have used differential conditioning tasks to examine threat acquisition and extinction in youth. The information obtained from this review helps to clarify the influence of these processes on the etiology and treatment of youth with OCD, PTSD and other anxiety disorders. Thirty studies of threat conditioning and extinction were identified Expert commentary: Youth with anxiety disorders, OCD, and PTSD have largely comparable threat acquisition relative to unaffected controls, with some distinctions noted for youth with PTSD or youth who have suffered maltreatment. However, impaired extinction was consistently observed across youth with these disorders and appears to be consistent with deficiencies in inhibitory learning. Incorporating strategies to improve inhibitory learning may improve extinction learning within extinction-based treatments like cognitive behavioral therapy (CBT). Strategies to improve inhibitory learning in CBT are discussed.


Eccentric hamstring strength in young athletes is best documented when normalised to body mass: A cross-sectional study with normative data of 590 athletes from different age categories.
Despite its widespread use in adults, the Nordic hamstring exercise remains underexplored in athletic youth populations. Further, given the dynamic nature of growth and maturation, comparisons with elite adult populations may be inaccurate. Here we describe absolute and body mass-normalised eccentric hamstring normative values for football, athletics and multi-sport youth populations. 676 routine standardised tests were conducted, including 244 U12-U18 student-athletes (football, athletics, multi-sport) and 346 Qatar Stars League (QSL) football players using the NordBord. The average maximum values for the left and right leg from 3 repetitions were recorded. Significant increases in absolute strength were seen across chronological (e.g., 150 N ± 15 for U12 to 330 N ± 40 for U18) and skeletal (142.9 N ± 13.9 for skeletal age of 12 compared to 336.2 N ± 71.2 for skeletal age of 18) age groups. The differences in values normalised to body mass were smaller at 3.6 N/kg ± 0.25 for the U-13 group, but similar for the U14 to U18 groups (4.5 N/kg ± 0.16, 4.6 N/kg ± 0.11, 4.6 N/kg ± 0.27, 4.7 N/kg ± 0.14, 4.5 N/kg ± 0.18). Students displayed lower absolute strength than the professional football players (272.1 N compared to 297.3 N, p < 0.0001) but higher relative strength (4.7 N/kg compared to 4.2 N/kg, p < 0.0001). Comparing Nordic hamstring strength values between athletes, and between skeletal and chronological age groups can be done when values are normalised to the athlete's body mass. For the U14s and onwards age categories, body mass normalised values are comparable to professional football players.


Practice and Impact of Multidisciplinary Tumor Boards on Patient Management: A Prospective Study.
Multidisciplinary tumor boards (MTBs) have become commonplace. The use, attendance, and function of MTBs need continued assessment and improvement. We prospectively recorded and assessed all cases presented at MTBs between October 2013 and December 2014. Data were collected before and during each MTB. Data were analyzed using SPSS for Windows version 23 (SPSS, Chicago, IL). Five hundred three cases were presented: 234 cases (46%) at GI cancer MTBs, 149 cases (29.6%) at breast cancer MTBs, 69 cases (13.7%) at thoracic/head and neck cancer MTBs, and 51 cases (10.7%) at neuro-oncology MTBs. A total of 86.7% of MTB cases were presented to make plans for management. Plans for upfront management were made in 67% of the breast cancer cases, 63% of GI cases, 59% of thoracic/head and neck cases, and 49% of neuro-oncology cases. Three hundred ninety-four cases (78.3%) were presented by medical oncologists, whereas only 74 cases (14.7%) were presented by surgeons, and 10 cases (2%) were presented by radiation oncologists. The majority of MTBs, with the exception of the neurosurgery MTBs, were led by medical oncologists. Surgeons presented the least number of cases but attended the most, and their contributions to discussions and decision making were essential. MTBs enhance the multidisciplinary management of patients with cancer. Upfront multidisciplinary decision making should be considered as an indicator of benefit from MTBs, in addition to changes in management plans made at MTBs. Increasing the contributions of surgeons to MTBs should include bringing more of their own cases for discussion.


An approach to the prevention of blindness in diabetes.
Diabetic eye disease is the leading cause of new cases of legal blindness in American adults under the age of 65 yr. Diabetic persons are at risk for visual loss due to diabetic retinopathy, glaucoma, and cataracts. Better understanding of the natural histories of these complications and recent advances in treatment have provided a rationale for developing an approach to prevent visual loss. This approach requires that diabetic patients who are at high risk for visual loss, and not under the care of ophthalmologists, be systematically screened, referred, and treated.


Rickets in the 17th century.
Rickets was first documented as a cause of death in the Bills of Mortality for The City of London in 1634, but detailed descriptions were only published between 1645 and 1668. It was thought at the time that this was a new disease in England, but there was no indication as to the cause of the condition. However, air pollution from smoke produced by burning coal caused serious problems at that time, and so it can be suggested that vitamin D deficiency was responsible.


Hospitalization-Associated Disability After Cardiac Surgery in Elderly Patients - Exploring the Risk Factors Using Machine Learning Algorithms.
Background: Hospitalization-associated disability (HAD) is associated with prolonged functional decline and increased mortality after discharge. Therefore, we examined the incidence and risk factors associated with HAD in elderly patients undergoing cardiac surgery in Japan. Methods and Results: We retrospectively examined 2,262 elderly patients who underwent elective cardiac surgery at Sakakibara Heart Institute. HAD was defined as a functional decline between time of admission and discharge measured by the Barthel Index. We analyzed clinical characteristics using machine learning algorithms to identify the risk factors associated with HAD. After excluding 203 patients, 2,059 patients remained, of whom 108 (5.2%) developed HAD after cardiac surgery. The risk factors identified were age, serum albumin concentration, estimated glomerular filtration rate, Revised Hasegawa's Dementia Scale, N-terminal pro B-type natriuretic peptide, vital capacity, preoperative Short Physical Performance Battery (SPPB) score, operation times, cardiopulmonary bypass times, ventilator times, length of postoperative intensive care unit stay, and postoperative ambulation start day. The highest incidence of HAD was found in patients with an SPPB score ≤9 and in those who started ambulation >6 days after surgery (76.9%). Conclusions: Several risk factors for HAD are components of frailty, suggesting that preoperative rehabilitation to reduce the risk of HAD is feasible. Furthermore, the association between HAD and a delayed start of ambulation reaffirms the importance of early mobilization and rehabilitation.


Local proteolytic activity in tumor cell invasion and metastasis.
Proteolytic cleavage of extracellular matrix (ECM) is a critical regulator of many physiological and pathological events. It affects fundamental processes such as cell growth, differentiation, apoptosis and migration. Most proteases are produced as inactive proenzymes that undergo proteolytic cleavage for activation. Proteolytic activity is additionally modified by endogenous inhibitors. Mechanisms that localize and concentrate protease activity in the pericellular microenvironment of cells are prerequisites for processes like angiogenesis, bone development, inflammation and tumor cell invasion. Methods that enable real-time, high-resolution imaging and precise quantification of local proteolytic activity in vitro and in vivo remain major challenges. These methods will play an important role in the understanding of basic principles e.g. in cancer cell invasion, the identification of new therapeutical targets and hence drug design. This review highlights mechanisms and functions of local proteolytic activity with special emphasis on tumor cell invasion and metastasis, and focuses on techniques for the investigation of this process.


Escape trajectories are deflected when fish larvae intercept their own C-start wake.
Fish larvae may intercept their own wake during sharp turns, which might affect their escape performance. We analysed C-starts of larval zebrafish (Danio rerio, Hamilton, 1822) using a computational fluid dynamics approach that simulates free swimming (swimming trajectory is determined by fluid forces) by coupling hydrodynamics and body dynamics. The simulations show that fish may intercept their own wake when they turn by 100-180°. During stage 1 of a C-start, the fish generates a strong jet at the tail that is shed into the wake. During stage 2, the fish intercepts this wake. Counterfactual simulations showed that wake interception increased the lateral force on the fish and reduced the fish's turning angle by more than 5°. Wake interception caused no significant acceleration tangential to the trajectory of the fish and did not affect total power output. While experimental and simulation evidence suggests that fish larvae can either undershoot or intercept but not overshoot their wake, our simulations show that larger fish might be able to avoid intercepting their wake by either under- or overshooting. As intercepting its own wake modifies the fish's escape trajectory, fish should account for this effect when planning their escape route.


CIEL*a*b* parameters of white dehydrated grapes as quality markers according to chemical composition, volatile profile and mechanical properties.
In the oenological sector, the withering process is of particular importance in the production of dry and sweet dessert wines due to the total or partial use of overripe and/or dehydrated grapes. This complex process leads to several changes in the chemical-physical characteristics of white grape berries affecting the wine quality and, at the end of the dehydration period, different visual attributes are usually present in the berry skins. The aim of this work, therefore, was to study the properties of Erbaluce dried grapes of varying external colors, classified into three groups based on reflectance colorimetry (green, gold and blue). The chemical composition, volatile profile and mechanical attributes were investigated, focusing on establishing relationships between CIEL*a*b* parameters of dehydrated grapes and their chemical-physical characteristics. The higher values of the glucose-fructose ratio, together with the higher content of sugars, gluconic acid and glycerol, but lower titratable acidity, suggests the presence of Botrytis cinerea Pers. infection in blue withered berries, which has been microbiologically confirmed. Regarding the instrumental mechanical properties, blue dehydrated grapes were characterized by a lower skin hardness and higher skin thickness in agreement with the higher weight loss experienced. Finally, the determination of free and bound volatile compounds showed that some of them were only found in blue withered berries, δ-lactones being considered the main chemical markers of the noble rot infection that are important for the odor character. C-10 alkyl massoia lactone was the most abundant volatile compound in blue botrytized grapes.


Mobilizing for a war on the home front against sugar-related morbidity and mortality.
In Israel today, there are 420,200 Israelis diagnosed with diabetes, and every year, Israelis sustain thousands of diabetes-related deaths and tens of thousands of diabetes-related amputations. As such, in Israel, as in much of the world, there is a silent and deadly public health war against obesity and diabetes taking place on the home front -- one in which clinicians, patients, and families fight thousands of life- and limb-threatening battles daily, involving preventable heart disease, diabetes, strokes and amputations. Yet the global clinical and scientific communities, indeed society at large, have barely begun to mobilize. Fighting this war requires confronting and altering "obesogenic" and "diabetogenic" economic and social factors, including food and beverage marketing and pricing that push diets engorged with processed sugars. Ginsberg, in a study recently published in IJHPR, contributes to our understanding of the combined sugar-related health burdens in Israel, producing an epidemiology and health economics study that estimates the health burdens of obesity, overweight, and dental caries in Israel today. He projects the reductions resulting from that portion of disease burden and associated costs if sugar consumption declined to 10 or 5% of daily caloric consumption as a result of multifaceted public health interventions. Projected over 70 years, these reductions in sugar consumption would prevent 16,590 and 34,580 deaths, respectively. These numbers of Israeli deaths averted are similar to, or exceed, the total resulting from armed conflict or terrorism over the past 70 years. While overconsumption of sugar is only one of many factors that drive cardio-metabolic disease, the study by Ginsberg suggests a path through which we can overcome the numerous internal and external obstacles that societies face in making a public policy commitment to fight the warm on the home front: promoting health by reducing added sugar exposure.


Management and treatment of Magnusiomyces capitatus (Geotrichum capitatum) pleural infection in a non-neutropenic patient with posaconazole. A new therapeutic opportunity?
Magnusiomyces capitatus may cause uncommon yet severe infections, especially in patients with haematologic disorders. Diagnosis may be difficult and time-consuming and newer approaches are required including the MALDI-TOF technique implemented with the detection of fungal antigens in the body fluids. The recommended treatment includes amphotericin B alone or in combination with flucytosine. We describe a case of a non-neutropenic patient with M. capitatus pleural infection, as identified by MALDI-TOF, positivity for galactomannan antigen in the BAL fluid, and successfully treated with oral posaconazole in single therapy.


Topical treatment of contact dermatitis by pine processionary caterpillar.
Skin contact dermatitis by pine processionary (Thaumetopoea pityocampa) is a public health problem of increasing significance. The authors present here the case of a 65-year-old man who was diagnosed with processionary caterpillar dermatitis. Patient was treated with topical potassium dobesilate 5% cream twice a day for 2 days. An improvement occurred soon after treatment.


Influence of human jaw movement on cerebral blood flow.
Temporal changes in cerebral blood flow induced by jaw movement have yet to be investigated. To assess the influence of pattern and intensity of muscle contraction during jaw movement on task-induced change in cerebral blood flow, we performed bilateral transcranial Doppler ultrasound examination during clenching, gum chewing, and tooth tapping in healthy volunteers. A random-effects model analysis revealed a significant increase in middle cerebral artery blood flow velocity during clenching (high muscle activity) and gum chewing (moderate muscle activity), compared with the preceding rest period; however, such an increase was not detected during tooth tapping (low muscle activity). Cerebral blood flow was greater on the working side during the intensive isometric contraction of the masseter muscle in clenching. These results suggest that task-induced change in cerebral blood flow during jaw movement is influenced by the change in peripheral circulation evoked by muscle contraction.


Changes in the use of hematopoietic stem cell transplantation: a model for diffusion of medical technology.
Innovations in hematology spread rapidly. Factors affecting the speed of introduction, international diffusion, and durability of use of innovations are, however, poorly understood. We used data on 251,106 hematopoietic stem cell transplants from 591 teams in 36 European countries to analyze the increase and decrease in such transplants for breast cancer and chronic myeloid leukemia and the replacement of bone marrow by peripheral blood as the source of stem cells as processes of diffusion. Regression analyses were used to measure the quantitative impact of defined macro- and microeconomic factors, to look for significant associations (t-test), and to describe the coefficient of determination or explanatory content (R(2)). Gross national income per capita, World Bank category, team density, team distribution, team size, team experience and, team innovator status were all significantly associated with some or all of the changes. The analyses revealed different patterns of associations and a wide range of explanatory content. Macro- and micro-economic factors were sufficient to explain the increase of allogeneic hematopoietic stem cell transplants in general (R(2) = 78.41%) and for chronic myeloid leukemia in particular (R(2) = 79.39%). They were insufficient to explain the changes in stem cell source (R(2) =26.79% autologous hematopoietic stem cell transplants; R(2) = 9.67% allogeneic hematopoietic stem cell transplants) or the decreases in hematopoietic stem cell transplants (R(2) =10.22% breast cancer; R(2)=33.17% chronic myeloid leukemia). The diffusion of hematopoietic stem cell transplants is more complex than previously thought. Availability of resources, evidence, external regulations and, expectations were identified as key determinants. These data might serve as a model for diffusion of medical technology in general.


Longitudinal study of adiposity in chickens selected for high or low abdominal fat content: further evidence of a glucose-insulin imbalance in the fat line.
Selected fat (FL) or lean (LL) lines of chickens have been further studied. Total lipid and abdominal fat content and size of adipocytes isolated from the gizzard were significantly increased in both sexes of the fat line from 2 to 4 weeks of age onwards. The divergence in abdominal fat content was maximum at 9 weeks of age. Both in the fed and the fasted state, the plasma glucose level was lower in FL than in LL chickens, at hatching and shortly after. This was not, however, associated with higher plasma insulin levels in FL chickens. At 2 weeks of age, insulin content of the pancreas did not differ. From 5-8 weeks of age after ad libitum refeeding or forced-feeding following a fast, plasma glucose increased to similar levels in both lines but in contrast, plasma insulin levels were largely enhanced in FL chickens. At 17 weeks of age, glucose clearance was faster in FL chickens and associated with a slightly (although nonsignificant) higher insulin release. In eggs laid by FL hens, yolk weight was disproportionately increased and albumen glucose content was decreased. During the last third of embryonic development, plasma glucose levels were similar in both lines at the F4 generation and in contrast lower in the FL embryos at the F5 generation. The physiological situation of FL chickens appears therefore very similar to short-lived preobese state observed in mammals.


Brown Carbon Production in Ammonium- or Amine-Containing Aerosol Particles by Reactive Uptake of Methylglyoxal and Photolytic Cloud Cycling.
The effects of methylglyoxal uptake on the physical and optical properties of aerosol containing amines or ammonium sulfate were determined before and after cloud processing in a temperature- and RH-controlled chamber. The formation of brown carbon was observed upon methylglyoxal addition, detected as an increase in water-soluble organic carbon mass absorption coefficients below 370 nm and as a drop in single-scattering albedo at 450 nm. The imaginary refractive index component k450 reached a maximum value of 0.03 ± 0.009 with aqueous glycine aerosol particles. Browning of solid particles occurred at rates limited by chamber mixing (<1 min), and in liquid particles occurred more gradually, but in all cases occurred much more rapidly than in bulk aqueous studies. Further browning in AS and methylammonium sulfate seeds was triggered by cloud events with chamber lights on, suggesting photosensitized brown carbon formation. Despite these changes in optical aerosol characteristics, increases in dried aerosol mass were rarely observed (<1 μg/m3 in all cases), consistent with previous experiments on methylglyoxal. Under dry, particle-free conditions, methylglyoxal reacted (presumably on chamber walls) with methylamine with a rate constant k = (9 ± 2) × 10-17 cm3 molecule-1 s-1 at 294 K and activation energy Ea = 64 ± 37 kJ/mol.


Straw Return and Nitrogen Fertilization to Maize Regulate Soil Properties, Microbial Community, and Enzyme Activities Under a Dual Cropping System.
Soil sustainability is based on soil microbial communities' abundance and composition. Straw returning (SR) and nitrogen (N) fertilization influence soil fertility, enzyme activities, and the soil microbial community and structure. However, it remains unclear due to heterogeneous composition and varying decomposition rates of added straw. Therefore, the current study aimed to determine the effect of SR and N fertilizer application on soil organic carbon (SOC), total nitrogen (TN), urease (S-UE) activity, sucrase (S-SC) activity, cellulose (S-CL) activity, and bacterial, fungal, and nematode community composition from March to December 2020 at Guangxi University, China. Treatments included two planting patterns, that is, SR and traditional planting (TP) and six N fertilizer with 0, 100, 150, 200, 250, and 300 kg N ha-1. Straw returning significantly increased soil fertility, enzymatic activities, community diversity, and composition of bacterial and fungal communities compared to TP. Nitrogen fertilizer application increased soil fertility and enzymes and decreased the richness of bacterial and fungal communities. In SR added plots, the dominated bacterial phyla were Proteobacteria, Acidobacterioia, Nitrospirae, Chloroflexi, and Actinobacteriota; whereas fungal phyla were Ascomycota and Mortierellomycota and nematode genera were Pratylenchus and Acrobeloides. Co-occurrence network and redundancy analysis (RDA) showed that TN, SOC, and S-SC were closely correlated with bacterial community composition. It was concluded that the continuous SR and N fertilizer improved soil fertility and improved soil bacterial, fungal, and nematode community composition.


Substitution of isoleucine-31 by helical-breaking proline abolishes oxidative stress and neurotoxic properties of Alzheimer's amyloid beta-peptide.
Alzheimer's disease (AD) brain is characterized by excess deposition of the 42-amino acid amyloid beta-peptide [A(beta)(1-42)]. AD brain is under intense oxidative stress, and we have previously suggested that A(beta)(1-42) was associated with this increased oxidative stress. In addition, we previously demonstrated that the single methionine residue of A(beta)(1-42), residue 35, was critical for the oxidative stress and neurotoxic properties of this peptide. Others have shown that the C-terminal region of A(beta)(1-42) is helical in aqueous micellar solutions, including that part of the protein containing Met35. Importantly, Cu(II)-binding induces alpha-helicity in A(beta) in aqueous solution. Invoking the i + 4 rule of helices, we hypothesized that the carbonyl oxygen of Ile31 would interact with the S atom of Met35 to change the electronic environment of the sulfur such that molecular oxygen could lead to the production of a sulfuramyl free radical on Met35. If this hypothesis is correct, a prediction would be that breaking the helical interaction of Ile31 and Met35 would abrogate the oxidative stress and neurotoxic properties of A(beta)(1-42). Accordingly, we investigated A(beta)(1-42) in which the Ile31 residue was replaced with the helix-breaking amino acid, proline. The alpha-helical environment around Met35 was completely abolished as indicated by circular dichroism (CD)-spectroscopy. As a consequence, the aggregation, oxidative stress, Cu(II) reduction, and neurotoxic properties of A(beta)(1-42)I31P were completely altered compared to native A(beta)(1-42). The results presented here are consistent with the notion that interaction of Ile31 with Met35 may play an important role in the oxidative processes of Met35 contributing to the toxicity of the peptide.


Effects of exogenous porcine somatotropin on the carcass composition, hormonal and metabolic profiles, lipogenic capacity, and binding of insulin to erythrocyte receptors of fast- versus slow-growing swine.
Twenty barrows were designated as fast-growing (FG) and their littermates designated as slow-growing (SG) based on birth, weaning, and 56-d weight. Half of each group received 70 micrograms of porcine somatotropin (pST)/kg BW daily beginning at 40 kg BW. At 60 and 105 kg BW, blood was collected every .5 h for 12 h beginning 1 h before pST injection, fat biopsies were taken for in vitro lipogenic activity, and insulin erythrocytes were isolated for receptor binding. Swine treated with pST had elevated ADG (.95 vs .88 kg/d; P < .1) and reduced days to slaughter (61 vs 67; P < .1). The pST-treated pigs had less average backfat (2.73 vs 3.96 cm; P < .01), larger longissimus muscle areas (32.3 vs 28.2 cm2; P < .05), and a higher percentage of muscle (56.3 vs 50.3%; P < .01) than control pigs. Exogenous pST increased protein (17.4 vs 13.2%; P < .05) and decreased fat (22.9 vs 37.1%; P < .05). The FG pigs had higher ADG (.98 vs .86 kg/d; P < .01) and required fewer days to slaughter (57 vs 71; P < .01) than SG pigs. Administration of pST increased (P < .01) average pST levels (1.7 vs 14.0 ng/mL) in FG and SG pigs at 60 kg BW. At 105 kg BW, pST was higher (P < .01) in pST-FG than in pST-SG swine (46.0 vs 19.3 ng/mL) but was not different between FG and SG control swine (1.9 vs 1.8 ng/mL). Administration of pST increased concentrations of IGF-I (510.0 vs 160.0 ng/mL) and nonesterified fatty acids (182 vs 109 muEq/L, P < .01) in FG and SG swine. Over sample periods and growth rates, pST reduced (P < .05) CO2 production and lipid synthesis (.345 and 1.85 vs .575 and 2.71 mumol of glucose incorporated.g-1.2 h-1). At 60 kg BW, FG swine had less (P < .01) CO2 production and lipid synthesis (.299 and 1.83 vs .921 and 3.61 mumol.g-1.2 h-1) than did SG swine. Exogenous pST increased (P < .05) binding to insulin erythrocyte receptors (7.25 vs 6.34%).


Epidemiological Evaluation of Bacillus cereus-Induced Foodborne Outbreaks - China, 2010-2020.
Bacillus cereus (B. cereus) is a common gram-positive bacterium that contaminates starch-rich food and can cause outbreaks of foodborne diseases. This study describes the characteristics of outbreaks caused by B. cereus in China during 2010-2020 and explore the possible reasons for changes in the number of outbreaks over time. Results of this analysis can efficiently help guide and allocate public resources to prevent B. cereus-caused foodborne diseases. Descriptive statistical methods were used to analyze the data on B. cereus outbreaks in China during this period. The data were identified and reported at all levels in China through National Foodborne Disease Outbreak Surveillance System. From 2010 to 2020, a total of 419 foodborne outbreaks prompted by B. cereus were reported in China, leading to 7,892 cases, 2,786 hospital admissions, and 5 fatalities. The bulk of the outbreaks were recorded in the summer, primarily between May and September. The most recurrent food vehicle was linked with rice or flour-based products, notably those made with rice or fried rice. School canteens bore the brunt of the B. cereus outbreaks. In multifactor outbreaks, food contamination was identified as the most common culprit; while in instances where only one factor contributed, improper storage was most frequently implicated. The prevalence of B. cereus outbreaks remained relatively consistent throughout the studied period. Understanding the types of foods, causative factors, and contributing elements leading to B. cereus outbreaks can help inform prevention strategies for foodborne illnesses. The majority of outbreaks were associated with rice- or flour-based foods in school canteens, suggesting contamination and improper storage during food preparation. Consequently, it is essential to prioritize continuous education for canteen staff on food safety, efficacious management, and proper practices. The implementation of comprehensive guidelines, encompassing multiple critical aspects, can potentially reduce the occurrence of B. cereus outbreaks.


Phylogeny and geographical distribution of the genus Boettcherisca Rohdendorf (Diptera: Sarcophagidae).
The phylogeny of the genus Boettcherisca Rohdendorf was investigated by numerical techniques. The phenetic and phyletic dendrograms were obtained by mean character difference (MCD) and Russell and Rao's coefficient (SRR) proximity analyses and unweighted pair-group (UPGA) cluster analysis, and then related to the classification of the species group and the geographical distribution of the group. Two monophyletic and one paraphyletic groups were recognized: peregrina-group, septentrionalis-group and karnyi-group, respectively. A biological evolution was postulated commencing with a hypothetical ancestor having occurred in Sundaland and involving two lines of specialization, the peregrina-group found in and around Sundaland and the septentrionalis-group in Far East, Walacea and Papualand. On the basis of the cladogram and the present geographical distribution, a Sundaland origin was postulated for the genus.


Excitatory amino acid antagonists inhibit synaptic responses in the guinea pig hypothalamic paraventricular nucleus.
1. The effects of specific excitatory amino acid (EAA) antagonists on evoked excitatory synaptic responses were studied in the hypothalamic paraventricular nucleus (PVN) of the guinea pig, by the use of the in vitro slice preparation. Intracellular recordings were obtained from paraventricular neurons, and excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) were induced by perifornical electrical stimulation. To reduce the influence of a potential gamma-aminobutyric acidA (GABAA) inhibitory component on the synaptic responses, all experiments were performed in the presence of 50 microM picrotoxin. 2. Of 20 cells tested, 13 had electrophysiological characteristics similar to magnocellular neuropeptidergic cells (MNCs) and 7 displayed low-threshold Ca2+ spikes (LTSs). No difference was detected in the effect of the antagonists on the synaptic responses of cells with or without LTS potentials. 3. The broad-spectrum EAA antagonist kynurenic acid decreased the amplitude of the EPSPs and EPSCs in a dose-dependent manner: the mean decrease was 5% for 100 microM, 43% for 300 microM, and 70% for 1 mM. 4. The quisqualate/kainate-receptor-selective antagonist 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) induced a dose-dependent decrease of the EPSPs and EPSCs: 1 microM had no detectable effect, 3 and 10 microM caused 30 and 70% decreases, respectively, and 30 microM blocked the response almost completely. This effect was not accompanied by a change in resting membrane potential or input resistance and was slowly reversible. 5. The N-methyl-D-aspartate (NMDA)-receptor-selective antagonist DL-2-amino-5-phosphonopentanoic acid (AP5), applied at 30 and 300 microM, reduced slightly the amplitude of the decay phase of the EPSP but did not significantly affect the peak amplitude. In some cells, the current-voltage relationship of the decay phase of the EPSC revealed a region of negative slope conductance between -70 and -40 mV. 6. These results suggest that 1) glutamate or a related EAA is responsible for the fast excitatory input to magnocellular and parvocellular neurons in the PVN and probably also for cells around PVN, 2) a quisqualate/kainate receptor type is responsible for the rising phase and peak amplitude of the synaptic current, and 3) an NMDA receptor contributes to the late part of the synaptic response.


Detection of growth hormone-producing cells in human thymus by immunohistochemistry and non-radioactive in situ hybridization.
It is well recognized that growth hormone (GH) may act as a growth and differentiation factor for the thymus gland. Recently, it has been reported that Pit-1/GHF-1 transcription factor, which controls the expression of both GH and prolactin, is expressed in stromal (not lymphoid) cells of human thymus. Here, we demonstrated by immunohistochemistry and in situ hybridization the presence of distinct GH-producing epithelial cell subsets in human thymus. The cells positive for GH mRNA and GH-immunoreactive substance are both located in the same thymus compartments, i.e., along the thymus capsule, in the subcapsular cortex, and within the septa. Local concentration of GH higher than systemic ones, in combination with other factors, may be important in regulating the thymic microenvironment necessary for T-lymphocyte differentiation.


I'm hot, so i'd say you're not: the influence of objective physical attractiveness on mate selection.
Four studies investigated the importance of objective and subjective attributes to mate selection. This research tested whether perceivers' objective physical attractiveness influenced how they evaluated the physical attractiveness of others and, if considered, may provide a parsimonious account for matching in mate selection. Study 1 (N = 102) demonstrated that ratings of targets' attractiveness decreased as perceivers' objective physical attractiveness increased. Studies 2 (N = 89) and 3 (N = 68) revealed that as perceivers' objective physical attractiveness increased, reductions in expected satisfaction and rejection were mediated by perceivers' reduced assessments of targets' attractiveness. Study 4 (N = 114) produced patterns of matching by finding that attractive perceivers expected to date more attractive targets while unattractive perceivers expected to date less attractive targets. This research emphasizes the importance of objective physical attractiveness to target evaluations and describes how matching results from the combined influence of objective and subjective attributes.


Safety and prognostic value of regadenoson stress cardiovascular magnetic resonance imaging in heart transplant recipients.
There is a critical need for non-invasive methods to detect coronary allograft vasculopathy and to risk stratify heart transplant recipients. Vasodilator stress testing using cardiovascular magnetic resonance imaging (CMR) is a promising technique for this purpose. We aimed to evaluate the safety and the prognostic value of regadenoson stress CMR in heart transplant recipients. To evaluate the safety, we assessed adverse effects in a retrospective matched cohort study of consecutive heart transplant recipients who underwent regadenoson stress CMR matched in a 2:1 ratio to age- and gender-matched non-heart transplant patients. To evaluate the prognostic value, we compared the outcomes of patients with abnormal vs. normal regadenoson stress CMRs using a composite endpoint of myocardial infarction, percutaneous intervention, cardiac hospitalization, retransplantation or death. For the safety analysis, 234 regadenoson stress CMR studies were included - 78 performed in 57 heart transplant recipients and 156 performed in non-heart transplant patients. Those in heart transplant recipients were performed at a median of 2.74 years after transplantation. Thirty-four (44%) CMR studies were performed in the first two years after heart transplantation. There were no differences in the rates of adverse effects between heart transplant recipients and non-heart transplant patients. To study the prognostic value of regadenoson stress CMRs, 20 heart transplant recipients with abnormal regadenoson stress CMRs were compared to 37 with normal regadenoson stress CMRs. An abnormal regadenoson stress CMR was associated with a significantly higher incidence of the composite endpoint compared with a normal regadenoson stress CMR (3-year cumulative incidence estimates of 32.1% vs. 12.7%, p = 0.034). Regadenoson stress CMR is safe and well tolerated in heart transplant recipients, with no incidence of sinus node dysfunction or high-degree atrioventricular block, including in the first two years after heart transplantation. An abnormal regadenoson stress CMR identifies heart transplant recipients at a higher risk for major adverse cardiovascular events.


Pathogenicity of Fumonisin-producing and Nonproducing Strains of Aspergillus Species in Section Nigri to Maize Ears and Seedlings.
Species of Aspergillus section Nigri are commonly associated with maize kernels, and some strains can produce fumonisin mycotoxins. However, there is little information about the extent to which these fungi contribute to fumonisin contamination in grain, the damage they cause to maize ears, or their effects on maize seed germination and seedling health. We compared fumonisin-producing and nonproducing strains of A. niger, A. welwitschiae, A. phoenicis, A. tubingensis, and A. carbonarius from the United States and Italy in laboratory and field studies to assess their ability to contribute to fumonisin contamination, to cause maize ear rot, and to affect seed germination and seedling growth. In laboratory experiments, some strains of each Aspergillus species reduced germination or seedling growth, but there was high variability among strains within species. There were no consistent differences between fumonisin-producing and nonproducing strains. In field studies in Iowa and Illinois, strains were variable in their ability to cause ear rot symptoms, but this was independent of the ability of the Aspergillus strains to produce fumonisins. Contamination of grain with fumonisins was not consistently increased by inoculation with Aspergillus strains compared with the control, and was much greater in F. verticillioides-inoculated treatments than in Aspergillus-inoculated treatments. However, the ratio of the FB analogs FB2 and FB1 was altered by inoculation with some Aspergillus strains, indicating that FB2 production by Aspergillus strains occurred in the field. These results demonstrate the pathogenic capabilities of strains of Aspergillus in section Nigri, but suggest that their effects on maize ears and seedlings are not related to their ability to produce fumonisins, and that fumonisin contamination of grain caused by Aspergillus spp. is not as significant as that caused by Fusarium spp.


Rhinoorbitocerebral mucormycosis: a case report and literature review.
Mucormycosis is a rare oportunistic infection typically described in diabetic patients with a ketoacidotic status, as well as neutropenic patients. The infection is caused by a group of saprophytic fungi of the class Phycomicetes, being the most frequent ones the Rhizomucor, Rhizopus and Mucor. Its hystological findings include vascular trombosis and tissue necrosis, predominantly in the rino-orbito-cerebral area. Even though the frequency of presentation is very low, given its rapid evolution and severe consequences which include a high mortality rate, it is very important to be aware of the main features of the disease and treat it promptly. Although the diagnosis is based on the high clinical suspect, the computed tomography (CT) and the magnetic resonance image (MRI) plays an important role in determining the extension. The patients should receive treatment in a reference hospital so that a multidisciplinary approach is ensured. In this sense, we present a case of rhino-orbito-cerebralmucormycosis in a diabetic patient, recently treated in our Department. A comprehensive review of the literature has been performed to update the physiopathology and diagnosis. Finally, we describe the different treatment options focusing in the surgical approach, as well as the medical treatment with amphotericine and posaconzole.


Oral cancer in Australia: 1983-1996.
The aims of this study were to identify differences in oral cancer incidence and mortality between sexes, age groups, oral sites and Australian States and Territories and recent trends in oral cancer incidence, mortality and age-profile over time. Data were obtained from the Australian Institute for Health and Welfare and were age-standardized to the Australian 1991 Population Standard. Differences and trends were assessed with the Wilcoxon matched-pairs signed-ranks test and the Spearman correlation test, respectively. In Australia in 1996, there were 2173 new oral cancers and 400 deaths due to oral cancer, the majority of oral cancers were in the 60+ age group, oral cancer affected men more than women (>2:1), lip cancer accounted for more than 50 per cent of oral cancers and the oral cancer mortality-to-incidence (M:I) ratio was greatest in ACT and NSW and least in QLD and SA. From 1983 to 1996, the annual incidence of lip cancer increased while the M:I ratio of lip cancer decreased. The annual incidence of cervical cancer decreased whereas the annual incidence of intra-oral cancer remained constant. The M:I ratio of cervical cancer was consistently lower than the M:I ratio of intra-oral cancer. Reducing exposure to environmental carcinogens, increasing public awareness and population screening may reduce the incidence and mortality of oral cancer in Australia.


[Growth hormone enhances regeneration of cavernous nerves after their transplantation in rats].
To investigate the effect of growth hormone (GH) on penile erection after reconstruction of cavernous nerves using sural nerve as an interposition nerve graft in rats. Twenty-four male Sprague-Dawley rats (3-4 ms of age and 300-400 g in weight) were randomly divided into 2 groups: nerve graft group and GH group, each electrostimulated to determine the erectile potency 2 and 4 months after nerve graft (followed by hypodermic GH injection). The nNOS-positive nerve fibers in the corpora cavemosa were examined by streptavidin-peroxidase immunohistochemistry technique (SP method). Image analysis was used to calculate the area stained in pixel. Electrostimulation at 2 months produced 31.25% of erections in the GH group but none in the grafted rats. There was a significant difference in the erection rate produced by electrostimulation between the two groups at 2 months (P < 0.05). The pixel of the expression of nNOS-positive nerve fibers in the GH group (38971 +/- 7692) was also greater than that of the graft group (16538 +/- 3179, P < 0.05). At 4 months, 43.75% of the graft group and 75% of the GH group produced erections upon electrostimulation, with no significant difference between the two groups (P > 0.05). The pixels of the expression of nNOS-positive nerve fibers were 79276 +/- 12,021 and 91348 +/- 18965, respectively (P > 0.05). GH can accelerate the regeneration of cavernous nerves after bilateral nerve grafting, and GH administration may present a new physiological approach to the treatment of erectile dysfunction after radical pelvic surgery.


Systems biological approach of molecular descriptors connectivity: optimal descriptors for oral bioavailability prediction.
Poor oral bioavailability is an important parameter accounting for the failure of the drug candidates. Approximately, 50% of developing drugs fail because of unfavorable oral bioavailability. In silico prediction of oral bioavailability (%F) based on physiochemical properties are highly needed. Although many computational models have been developed to predict oral bioavailability, their accuracy remains low with a significant number of false positives. In this study, we present an oral bioavailability model based on systems biological approach, using a machine learning algorithm coupled with an optimal discriminative set of physiochemical properties. The models were developed based on computationally derived 247 physicochemical descriptors from 2279 molecules, among which 969, 605 and 705 molecules were corresponds to oral bioavailability, intestinal absorption (HIA) and caco-2 permeability data set, respectively. The partial least squares discriminate analysis showed 49 descriptors of HIA and 50 descriptors of caco-2 are the major contributing descriptors in classifying into groups. Of these descriptors, 47 descriptors were commonly associated to HIA and caco-2, which suggests to play a vital role in classifying oral bioavailability. To determine the best machine learning algorithm, 21 classifiers were compared using a bioavailability data set of 969 molecules with 47 descriptors. Each molecule in the data set was represented by a set of 47 physiochemical properties with the functional relevance labeled as (+bioavailability/-bioavailability) to indicate good-bioavailability/poor-bioavailability molecules. The best-performing algorithm was the logistic algorithm. The correlation based feature selection (CFS) algorithm was implemented, which confirms that these 47 descriptors are the fundamental descriptors for oral bioavailability prediction. The logistic algorithm with 47 selected descriptors correctly predicted the oral bioavailability, with a predictive accuracy of more than 71%. Overall, the method captures the fundamental molecular descriptors, that can be used as an entity to facilitate prediction of oral bioavailability.


Tight junction in blood-brain barrier: an overview of structure, regulation, and regulator substances.
Blood-brain barrier (BBB) is a dynamic interference that regulates the nutrition and toxic substance in and out of the central nervous system (CNS), and plays a crucial role in maintaining a stable circumstance of the CNS. Tight junctions among adjacent cells form the basic structure of BBB to limiting paracellular permeability. In the present review, the constituents of tight junction proteins are depicted in detail, together with the regulation of tight junction under stimulation and in pathological conditions. Tight junction modulators are also discussed.


Sexual assault in the lives of urban sex workers: a descriptive and comparative analysis.
This exploratory study contributes to the sparse literature on sexually assaulted sex workers. We examined 462 sexual assault cases seen at an emergency department-based sexual assault service and reported to the police between 1993 and 1997. More than one fifth of victims were sex workers. We compared them to other victims on victim characteristics, assault characteristics, and medical-legal findings. Relative to other victims, sex workers were younger, had lower incomes, and were more likely to be heroin and/or cocaine users. They suffered a greater number of injuries and forensic samples collected from their bodies were more likely to test positive for sperm and/or semen. These victims were also less likely to have been using alcohol and/or marijuana prior to the assault and to be emotionally expressed during the medical- legal examination. The substantial proportion of sex workers in the study population suggests that attention to their particular needs should be an important part of hospital-based sexual assault services. Clinical implications and directions for future research are discussed.


Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement.
New U.S. Preventive Services Task Force (USPSTF) recommendation statement on vitamin D and calcium supplementation to prevent fractures in adults. The USPSTF commissioned 2 systematic evidence reviews and a meta-analysis on vitamin D supplementation with or without calcium to assess the effects of supplementation on bone health outcomes in community-dwelling adults, the association of vitamin D and calcium levels with bone health outcomes, and the adverse effects of supplementation. These recommendations apply to noninstitutionalized or community-dwelling asymptomatic adults without a history of fractures. This recommendation does not apply to the treatment of persons with osteoporosis or vitamin D deficiency. The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of combined vitamin D and calcium supplementation for the primary prevention of fractures in premenopausal women or in men. (I statement)The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of daily supplementation with greater than 400 IU of vitamin D3 and greater than 1000 mg of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women. (I statement)The USPSTF recommends against daily supplementation with 400 IU or less of vitamin D3 and 1000 mg or less of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women. (D recommendation).


Determination of amine and aldehyde surface densities: application to the study of aged plasma treated polyethylene films.
The aim of this work was to test and to compare different methods reported in the literature to quantify amine and aldehyde functions on the surface of polyethylene (PE) films treated by ammonia plasma and to specify their stability against time. A low pressure ammonia plasma reactor was used to functionalize PE films with amine groups, which could be subsequently used for further immobilization of biomolecules. In order to determine the density of amine groups on the surface of treated films, various molecule probes and spectrophotometric analytical methods have been investigated. Two methods using (i) sulfosuccinimidyl 6-[3'-(2-pyridyldithio)-propionamido] hexanoate (sulfo-LC-SPDP) and (ii) 2-iminothiolane (ITL) associated with bicinchoninic acid (BCA) have been proved to be reliable and sensitive enough to estimate the surface concentration of primary amine functions. The amount of primary amino groups on the functionalized polyethylene films was found to be between 1.2 and 1.4 molecules/nm2. In a second step, the surface concentration of glutaraldehyde (GA), which is currently used as a spacer arm before immobilization of biomolecules, has been assessed: two methods were used to determine the surface density of available aldehyde functions, after the reaction of GA with the aminated polyethylene film. The concentration of GA was found to be in the same range as primary amine concentration. The influence of aging time on the density of available amino and aldehyde groups on the surfaces were evaluated under different storage conditions. The results showed that 50% of the initial density of primary amine functions remained available after storage during 6 days of the PE samples in PBS (pH 7.6) at 4 degrees C. In the case of aldehyde groups, the same percentage of the initial density (50%) remained active after storage in air at RT over a longer period, i.e., 15 days.


Effects of ice and floods on vegetation in streams in cold regions: implications for climate change.
Riparian zones support some of the most dynamic and species-rich plant communities in cold regions. A common conception among plant ecologists is that flooding during the season when plants are dormant generally has little effect on the survival and production of riparian vegetation. We show that winter floods may also be of fundamental importance for the composition of riverine vegetation. We investigated the effects of ice formation on riparian and in-stream vegetation in northern Sweden using a combination of experiments and observations in 25 reaches, spanning a gradient from ice-free to ice-rich reaches. The ice-rich reaches were characterized by high production of frazil and anchor ice. In a couple of experiments, we exposed riparian vegetation to experimentally induced winter flooding, which reduced the dominant dwarf-shrub cover and led to colonization of a species-rich forb-dominated vegetation. In another experiment, natural winter floods caused by anchor-ice formation removed plant mimics both in the in-stream and in the riparian zone, further supporting the result that anchor ice maintains dynamic plant communities. With a warmer winter climate, ice-induced winter floods may first increase in frequency because of more frequent shifts between freezing and thawing during winter, but further warming and shortening of the winter might make them less common than today. If ice-induced winter floods become reduced in number because of a warming climate, an important disturbance agent for riparian and in-stream vegetation will be removed, leading to reduced species richness in streams and rivers in cold regions. Given that such regions are expected to have more plant species in the future because of immigration from the south, the distribution of species richness among habitats can be expected to show novel patterns.


Autosomal dominant retinitis pigmentosa caused by the threonine-17-methionine rhodopsin mutation: retinal histopathology and immunocytochemistry.
The retinas from a 68-year-old man with autosomal dominant retinitis pigmentosa caused by the threonine-17-methionine rhodopsin mutation were studied. Patients with this mutation have a characteristic clinical phenotype that shows intra- and interfamilial consistency. The retinas were examined by light and electron microscopy, including immunocytochemistry with markers for rods, cones, the retinal pigment epithelium, the interphotoreceptor matrix and Müller cells, and the results were correlated with those from visual function tests performed fourteen months before death. Grossly, both retinas had heavy deposits of bone spicule-like pigmentation inferiorly, but the superior retinas showed much less pigmentation. The maculas contained no rods and an incomplete monolayer of cone somata, consistent with the patient's severely reduced central vision. The inferior retinas contained no rods and rare cone somata, correlating with an absolute scotoma in the superior field. The superior retinas had near-normal-appearing rods and cones in the far periphery and a gradient from the midperipheral to central retina of progressively shortened outer segments and loss of photoreceptors, consistent with the patient's reduced rod and cone electroretinograms and retained rod and cone sensitivities in the inferior peripheral field by perimetry. Immunocytochemistry with rod-specific markers was qualitatively normal in the superior mid to far peripheral retina. Electron microscopic immunogold labeling with anti-rhodopsin revealed similar densities of gold particles over rod outer segments of the RP and a normal donor retina. Degenerate photoreceptors in the superior equatorial region of the RP retina had short outer segments, and some rods had surface labeling with anti-rhodopsin of the inner segments, somata and synapses. The results indicate regional retinal differences of disease severity in this genotype and that rods in the superior peripheral retina have normal morphology despite the presence of the mutant allele. To the authors' knowledge, this is the first detailed study of rod photoreceptors in the retina of an RP patient with a rhodopsin mutation.


Effect of pH and ATP on the equilibrium density of lysosomes.
Lysosomes are membrane bound structures that accumulate and hydrolyze material internalized by the endocytic pathway. A very conspicuous property of this subcellular compartment is its relatively high equilibrium density. The actual mechanism that regulates lysosomal density is poorly understood. In an attempt to gain knowledge on the factors that regulate lysosomal density we have assessed the equilibrium density of lysosomal markers after in vitro incubation of a lysosome-enriched subcellular fraction. Incubation at pH 6 for 10 min at 37 degrees C causes a density shift of several lysosomal markers to light density regions of Percoll gradients. Addition of ATP was able to prevent the acid-induced density shift. Pretreatment of the vesicles with N-ethylmaleimide (NEM) or trypsin inhibited the effect of ATP. Working in intact cells, ATP depletion, a condition that causes cytoplasmic acidification, also decreases lysosomal density. The results indicate that at low pH lysosomal density is preserved by an active process that requires ATP and membrane associated proteins.


Mitochondrial response to calcium in the developing brain.
Developmental differences in mitochondrial content and metabolic enzyme activities have been defined, but less is understood about the responses of brain mitochondria to stressful stimuli during development. Cerebral mitochondrial response to high Ca(2+) loads after brain injury is a critical determinant of neuronal outcome. Brain mitochondria isolated from 16-18-day-old rats had lower maximal, respiration-dependent Ca(2+) uptake capacity than brain mitochondria isolated from adult rats in the presence of ATP at both a pH of 7.0 and 6.5. However, in the absence of ATP, immature brain mitochondria exhibited greater Ca(2+) uptake capacity at pH 7.0 and 6.5, indicating a greater resistance of immature brain mitochondria to Ca(2+)-induced dysfunction under conditions relevant to those that exist during acute ischemic and traumatic brain injury. Acidosis reduced the maximal Ca(2+) uptake capacity in both immature and adult brain mitochondria. Cytochrome c was released from both immature and adult brain mitochondria in response to Ca(2+) exposure, but was not affected by cyclosporin A, an inhibitor of the mitochondrial membrane permeability transition. Developmental changes in mitochondrial response to Ca(2+) loads may have important implications in the pathobiology of brain injury to the developing brain.


First-pass radionuclide angiocardiography with single-crystal gamma cameras.
Both multicrystal and single-crystal detectors have been in use for more than 25 years for measurement of ejection fraction by analysis of images collected during the first-pass transit of radionuclides through the heart. Originally, multicrystal cameras were preferred, because they provided higher count rates than Anger cameras; however, over the years improvements in count rate capability and collimator design have enabled Anger cameras to perform equally well. This has become an important issue now that readily available 99mTc agents, such as sestamibi, enable evaluation of both myocardial function and perfusion from a single injection. The technical abilities of a particular camera determine which acquisition protocols are most likely to provide clinically useable images for the widest spectrum of patients. Electrocardiographic-gated list mode collection is highly desirable for first-pass imaging, providing the greatest flexibility of data review, rebinning, and analysis. Attention to quality control issues of data characterization and processing is important to ensure accuracy and precision of all measurements. Accurate determinations of ejection fraction of the left ventricle are possible routinely and, under favorable circumstances, of the right ventricle as well.


Dot immunobinding assay method with chlorophyll removal for the detection of southern rice black-streaked dwarf virus.
Southern rice black-streaked dwarf virus (SRBSDV), a new virus from Fiji, has seriously damaged rice crops in southern China and northern Vietnam in recent years. This virus is difficult to diagnose in the early stages of infection, and is very destructive at the late stage. In the present study, a dot immunobinding assay (DIBA) that has a high sensitivity for diagnosing SRBSDV was developed. Two kinds of treatment for the DIBA were evaluated to determine the most effective one for removing chlorophyll interferences via rice extraction. The first included several reagents to remove chlorophyll, namely, the alkaline reagents like magnesium oxide and alumina oxide, the adsorbent reagents like activated carbon and bentonite, as well as the extraction agent acetone. The second and third treatments, which were used to remove chlorophyll in blot membrane-nitrocellulose and polyvinylidene fluoride (PVDF), included several organic solvents containing methanol, ethanol, acetone, ethyl acetate, and diethyl ether. The results showed that activated carbon and methanol yielded the best contrasting purple color for the infected samples by decreasing the chlorophyll content.


Rising serum digoxin without further dosage in acute renal failure.
A 73-year-old man was given a total of 1 mg of digoxin intravenously over 3 days, close to the time that he developed acute renal failure with oligo-anuria. He received no cardiac glycosides before or after this 3-day period. 2 days after the last dose, the serum digoxin concentration (SDC) was 2.9 ng/ml, yet a peak value of 4.2 ng/ml was reached only 11 days later. The SDC remained above 2 ng/ml for another week, until urine output began to increase appreciably. As renal function improved, the SDC gradually fell to become undetectable 32 days after the last dose. Values for apparent volume of distribution calculated from the total dose, and also determined after injection of tritiated digoxin, suggest that the rise in SDC in the absence of additional doses was due in large part to a decrease in the apparent volume of distribution. Dosage and parameters of toxicity should be carefully monitored in patients receiving digoxin who develop acute renal failure.