Development of comorbidities in type 2 diabetes between 2005 and 2017 using German claims data.
Against the background of increasing life expectancy over time, several hypotheses have been proposed on the way morbidity has been developing. In type 2 diabetes (T2D), previous research suggests that morbidity compression could be ruled out due to increasing prevalence and life expectancy with T2D over time. Understanding how the health state in individuals with T2D is developing would help identify whether morbidity expansion or a dynamic equilibrium pattern applies for this disease. This study aims to answer the following questions: (1) How do the number and the prevalence of T2D concordant comorbidities develop over time? (2) What does this imply in terms of morbidity development in T2D in Germany? The study used claims data from a statutory health insurance provider in Lower Saxony, Germany. Period prevalence of T2D concordant comorbidities was examined for the periods 2005-2007, 2010-2012 and 2015-2017 in 240,241, 295,868 and 308,134 individuals with T2D respectively. The effect of time period on the number and prevalence of comorbidities was examined by means of (ordered) logistic regression. The age-adjusted predicted probabilities of more severe cardiovascular diseases (CVDs) decreased over the three periods while those of less severe CVDs and other vascular diseases increased significantly in men and women and among all examined age-groups. Predicted probability of having at least one more comorbidity over time also increased significantly among all examined groups. While less and more severe CVDs exhibited different developmental patterns, the results of the study point towards morbidity expansion in T2D. Future studies should focus on mechanisms that contribute to these trends.


Changes in granulosa cells gene expression associated with growth, plateau and atretic phases in medium bovine follicles.
The objective of this study was to build the transcriptomic profile of granulosa cells originating from follicles 6 to 9 mm in diameter in dairy cattle using microarrays. Granulosa cells originating from three different phases of antral follicle growth were compared: growing (G), plateau (P) and atresia (A), as categorized by flow cytometry profiles of DNA. The growing and atretic conditions were each hybridized against the plateau condition as a reference in order to understand the specific biological mechanisms modulated in this class of follicles. 2,942 genes were differentially expressed (P < 0.05) in P vs. G and 1,974 in A vs. P. A clear segregation of the 3 phases was confirmed by between group analysis (BGA). The first characteristic of the plateau phase is the activation of the upstream regulators TP53 and PTEN which participate in the reduction of cell growth through MYC, FOS and E2F1-2-3. We also observed the down-regulation of steroidogenesis genes: CYP11A1 and CYP19A1, in the granulosa cells of the plateau phase relative to the growth phase. On the other hand, the A vs. P contrast showed up-regulation of multiple transcripts associated to apoptosis: CCT2, DAB2, DSG2 and TGM2. This study offers multiple candidate genes to be further studied in order to elucidate their role in the modulation of follicular development and, ultimately, of oocyte quality.


Inadequate treatment for elderly patients: professional norms and tight budgets could cause "ageism" in hospitals.
We have studied ethical considerations of care among health professionals when treating and setting priorities for elderly patients in Norway. The views of medical doctors and nurses were analysed using qualitative methods. We conducted 21 in depth interviews and 3 focus group interviews in hospitals and general practices. Both doctors and nurses said they treated elderly patients different from younger patients, and often they were given lower priorities. Too little or too much treatment, in the sense of too many interventions and too much drugs, combined with too little care and comfort, was admitted as a relatively frequent yet unwanted consequence of the way clinical priorities were set for elderly patients. This was explained in terms of elderly patients not tolerating the same treatment as younger patients, and questions were raised about the quality of life of many elderly patients after treatment. These explanations were frequently referred to as medically sound decision making. Other explanations had little to do with medically sound decisions. These often included deep frustration with executive guidelines and budget constraints.


The microRNA cluster miR-30b/-30d prevents tumor cell switch from an epithelial to a mesenchymal-like phenotype in GBC.
As a malignancy of the gastrointestinal tract, gallbladder cancer (GBC) continues to exhibit notable rates of mortality. The current study aimed at investigating the effects associated with miR-30b and miR-30d (miR-30b/-30d) patterns in tumor cells undergoing epithelial-to-mesenchymal transition (EMT) in GBC. It identified that miR-30b and miR-30d, composed as a miRNA cluster, exhibited lower levels in the cancerous tissues from 50 patients with GBC relative to the gallbladder tissues from 35 patients with chronic cholecystitis. As expected, elevated expression of miR-30b/-30d was found to inhibit the EMT process, as evidenced by enhanced E-cadherin and reduced N-cadherin and vimentin in human GBC cells treated with miR-30b mimic, miR-30d mimic, and miR-30b/-30d mimic. Semaphorin-6B (SEMA6B) was identified as a target gene of miR-30b/-30d. Silencing of SEMA6B by its specific small interfering RNA (siRNA) mimicked the effect of miR-30b/-30d upregulation on the GBC cell EMT. Consistently, SEMA6B overexpression promoted this phenotypic switch even in the presence of miR-30b/-30d mimic. The tumorigenicity assay data obtained from nude mice also further supported the notion that miR-30b/-30d inhibited EMT of GBC cells. Thus, based on the key findings of the current study, we concluded that the miR-30b/-30d cluster may provide a potential avenue for targeting mesenchymal-like, invasive tumor cells in GBC.


Optimising the use of computed radiography in pediatric chest imaging.
The objective of this study was to analyze image quality of chest examinations in pediatric patients using computed radiography (CR) obtained with a wide range of doses to suggest the appropriate parameters for optimal image quality. A sample of 240 chest images in four age ranges was randomly selected from the examinations performed during 2004. Images were obtained using a CR system and were evaluated independently by three radiologists. Each image was scored using criteria proposed by the European Guidelines on Quality Criteria in Pediatrics. Mean global scoring and scoring of individual criteria more sensitive to noise were used to evaluate image quality. Agfa dose level (DL) was in the range 1.20 to 2.85. It was found that there was not significant correlation (R < 0.5) between image quality and DL for any of the age ranges for either global score or for individual criteria more related to noise. The mean value of DL was in the ranges 1.9-2.1 for the four age bands. From this study, a DL value of 1.6 is proposed for pediatric CR chest imaging. This could yield a reduction of approximately a factor of 2.5 in mean patient entrance surface doses.


Nephrogenic Adenoma Intermixed With Urothelial Carcinoma.
Nephrogenic adenoma (NA) is a common urinary tract lesion typically associated with urothelial disruption, leading to implantation of shed renal tubular cells. NA may demonstrate a spectrum of architectural and cytologic features mimicking urothelial carcinoma (UC), adenocarcinoma (including clear cell adenocarcinoma and prostatic adenocarcinoma), and invasion. However, admixed UC and NA has not been described. To describe cases where the NA was intimately intermixed with UC, potentially mimicking variant differentiation or invasion. In 3 health care systems we identified specimens of NA and UC intimately intermixed with each other to the extent that they could mimic a spectrum of one lesion. We assessed patterns of NA and clinical implications of misdiagnosing NA as glandular differentiation of UC. There were 4 women and 29 men (median age, 72 years; range, 31-89 years). Twenty-four patients had transurethral resections, 3 had biopsies, and 6 had major resections. Fourteen had noninvasive high-grade papillary UC, 6 had carcinoma in situ, and 11 had invasive high-grade UC. In 2 patients, NA developed in a papillary urothelial neoplasm with extensive denudation. Three patients had fibromyxoid NA infiltrated by invasive UC. Classical NA (n = 30) had tubulopapillary (n = 18), pure tubular (n = 7), or pure papillary architecture (n = 5). In 1 lesion, NA was present in muscularis propria, and 2 lesions involved adventitia. NA could have been misdiagnosed as invasion in 17 of 22 (77%) noninvasive tumors or higher stage in 19 of 33 (58%). NA can be intermingled with high-grade UC, expanding the spectrum of entities that must be considered in the differential diagnosis, as it may mimic glandular or tubular differentiation, invasion, and a higher stage of disease. Misinterpretation of NA in such a setting may incorrectly convey a more aggressive biological potential of cancer to clinicians.


Manganese oxide increases bleaching efficacy and reduces the cytotoxicity of a 10% hydrogen peroxide bleaching gel.
The study aims to assess the effects of a 10% H2O2 bleaching gel with different MnO2 concentrations on the bleaching efficacy (BE), degradation kinetics (DK) of H2O2, and trans-amelodentinal cytotoxicity (TC). Standardized bovine enamel/dentin disks (n = 96) were placed in artificial pulp chambers, and the bleaching gels were applied for 45 min. Thus, the following groups were established: (G1) no treatment (negative control/NC); (G2) 35% H2O2 (positive control/PC); (G3) 10% H2O2; (G4) 10% H2O2 + 2 mg/mL MnO2; (G5) 10% H2O2 + 6 mg/mL MnO2; and (G6) 10% H2O2 + 10 mg/mL MnO2. After analyzing bleaching efficacy (ΔE00 and ΔWI), the degradation kinetics of H2O2 and trans-amelodentinal cytotoxicity were determined (n = 8, ANOVA/Tukey; p < 0.05). G6 presented BE (ΔE00 and ΔWI) statistically similar to G2, which represented conventional in-office bleaching (p = 0.6795; p > 0.9999). A significant reduction in the diffusion of H2O2 occurred in G3, G4, G5, and G6 compared to G2 (p < 0.0001). The highest DK of H2O2 occurred in G6 (p < 0.0001), which had the lowest TC in comparison with all other bleached groups (p ≤ 0.0186). The addition of 10 mg/mL of MnO2 in a 10% H2O2 bleaching gel potentiates the degradation of this reactive molecule, which increases the BE of the product and decreases TC. Replacing a 35% H2O2 gel commonly used for conventional in-office dental bleaching by a 10% H2O2 gel containing 10 mg/mL of MnO2 reduces the cytotoxicity of this professional therapy, maintaining its excellent esthetic efficacy.


Insulin-like growth factor binding protein-3 and -5 are regulated by transforming growth factor-beta and retinoic acid in the human prostate adenocarcinoma cell line PC-3.
The family of insulin-like growth factor binding proteins (IGFBPs) can affect cell proliferation by modulating the availability and bioactivity of insulin-like growth factors (IGFs), or by mechanisms independent of IGFs. To understand better the role(s) of IGFBPs in prostate growth and malignancy, we examined the regulation of IGFBPs in PC-3 cells, a human prostatic adenocarcinoma epithelial cell line that is androgen-insensitive. Both transforming growth factor-beta (TGF-beta) and retinoic acid (RA), known inhibitors of cellular proliferation, significantly changed the IGFBP profile in PC-3 cells. In cells that were treated with transforming growth factor beta-2 (TGF-beta 2) (0.5-10 ng/mL), IGFBP-3, and IGFBP-5 protein and mRNA increased in a time- and dose-dependent manner. At 10 ng/mL TGF-beta, IGFBP-3, and IGFBP-5 protein concentrations were 14- and 9-fold, respectively, over that of controls. Cells treated with RA (0-1 microM) also showed a time- and dose-dependent increase in IGFBP-3 protein and mRNA levels. However, in contrast to TGF-beta 2, high concentrations of RA (1 microM) negatively regulated IGFBP-5 expression, with IGFBP-5 mRNA levels downregulated to 20% of that of the control, and protein levels were decreased by 50%. Since both TGF-beta and RA increased IGFBP-3 expression and both are known to inhibit prostate cell growth, we speculate that the inhibition of growth is mediated, at least in part, by IGFBP-3.


The lineage commitment of haemopoietic progenitor cells.
Multipotent haemopoietic progenitor cells appear to be 'primed' for commitment by co-expression of a multiplicity of genes characteristic of different lineages. Lineage commitment proceeds as the consolidation of a distinct pattern of gene expression out of this milieu.


Jejunal mucosal DNA content and maturation. Inverse relation to serum gastrin levels in suckling and weanling rats.
Although pentagastrin has a tropic action on intestinal mucosa in suckling rat pups, and at weaning a rise in gastrin levels coincides with maturation of the intestinal mucosa, direct correlations of serum gastrin levels and intestinal maturation have yet to be made. Ten-day-old rats were subjected either to antrectomy to produce a 43% decrease in serum gastrin levels or to fundectomy to produce a 319% increase over gastrin levels in rumenectomized or normal animals. These changes were not associated with tropic or adaptive changes in jejunal or colonic mucosa as determined by jejunal and colonic DNA content, jejunal sucrase activity, jejunal villous height, or crypt depths in jejunum and colon at the beginning (day 15), middle (day 21), or end (day 27) of the weaning period. To the contrary, an inverse relation was found between serum gastrin levels and both jejunal mucosal DNA content and sucrase activity as an index of maturation.


Results in fifty cases of advanced squamous cell carcinoma of the head and neck treated by intravenous chemotherapy.
The results of intravenous chemotherapy for advanced squamous cell carcinoma of the head and neck in 50 patients are presented. Forty patients were treated with methotrexate alone-3 patients showed partial regression of disease and a further 7 were controlled for periods of up to 4 months. Of those patients who failed to respond, or who relapsed on methotrexate, 16 were treated with combination chemotherapy. One patient showed complete regression of disease, 2 partial regression and in 2 others control was achieved for up to 4 months. A further 10 patients were treated with combination chemotherapy only, with no previous methotrexate. In this group no objective regressions were noted and only one patient was controlled for a period of 14 months. It is suggested that intravenous chemotherapy in advanced squamous cell carcinoma of the head and neck is of doubtful value.


Pyogenic abscess from Providencia stuartii mimicking necrotic tumour at perfusion-weighted imaging.
The purpose of this case report is to increase the knowledge about magnetic resonance spectrum of pyogenic abscesses of the brain. A 74-year-old woman presented with a left frontal lobe cystic mass, developed in the site of post-traumatic contusions after surgical evacuation of a subdural hematoma. MR imaging showed an ipsilateral mass lesion with a thin, regular rim of T1 high-intensity signal, T2 low-intensity signal, and gadolinium-enhancement. Diffusion-weighted imaging with measure of apparent diffusion coefficient value showed inhomogenous diffusion restriction in the lesion core. Perfusion-weighted imaging (PWI) demonstrated high relative cerebral blood volume (rCBV) in both the lesion wall and perilesional area, with a maximal rCBV ratio (rCBV of the lesion/rCBV of the normal contralateral white matter) of 5.65 and 0.58, respectively. As a result, surgery and pathology showed a pyogenic abscess. Cultures grew were Providencia stuartii species. In conclusion, a pyogenic brain abscess from P. stuartii may show high rCBV at PWI, thus mimicking a necrotic tumour.


Following cancer viruses through the laboratory, clinic, and society.
These essays in this special issue follow cancer viruses as a means of better understanding the history of biomedicine. Spanning the worlds of chronic and infectious disease research, the history of cancer viruses touches upon an enormous diversity of settings and scientific disciplines. Cancer viruses appeared during the twentieth century as vaccine targets, vaccine contaminants, laboratory anomalies, and tools for molecular biology. Rather than picking one discipline or setting to privilege above others, this issue suggests what can be learned, not only about cancer viruses but also about the character of modern biomedicine, from following these viruses through their different historical trajectories.


1H and 31P NMR measurement of cerebral lactate, high-energy phosphate levels, and pH in humans during voluntary hyperventilation: associated EEG, capnographic, and Doppler findings.
In order to explore the sensitivity of spatially resolved 1H and 31P NMR spectroscopy on a whole-body NMR instrument, cerebral metabolic changes in human volunteers were measured during hyperventilation provocation. During hyperventilation the flow velocity in the middle cerebral artery decreased significantly and the EEG showed a marked increase in slow activity. 1H NMR spectra revealed an increase in cerebral lactate concentration. 31P NMR spectra showed no changes in ATP or PCr peak heights, but a shift toward tissue alkalosis was derived from changes in Pi chemical shift. During subsequent recovery, lactate concentration decreased and a slight intracellular acidosis was detected. In three experiments broadening of the lactate resonance peak resulted in separation into two components at 1.32 and 1.48 ppm, in which the latter signal possibly arose from alanine.


Structural factors influencing energy carbon emissions in China's service industry: an input-output perspective.
Existing literatures on energy carbon emissions mainly focus on high-energy industries such as electricity, transportation, and construction, while there are few researches on energy carbon emissions of relatively low-carbon industries such as the service industry. But with the service sector accounting for more than one-half of China's national economy, its carbon emissions are increasingly not negligible. Based on this, we use the structural decomposition model, input-output analysis method, and energy consumption method to study the structural factors influencing energy carbon emissions in China's service industry from 2007 to 2017. The results show that (1) the pressure and space of energy carbon emission reduction of the service industry are still huge in the future. Specifically, in the sample range, although the excessive growth of the energy carbon emissions of the service industry has been alleviated, the proportion of high-carbon energy in the energy carbon emissions of the service industry is still high, and the optimization of the energy consumption structure has not been significantly improved. (2) During the sample period, the energy utilization efficiency of the service industry has been significantly optimized and improved, which leads to the inhibition of the energy intensity effect on the growth of carbon emissions of the service industry. However, it should be noted that the emission reduction effect exerted by the energy intensity effect over time shows a tired trend. Therefore, in the future, the control of energy carbon emissions in the service industry needs to take multiple approaches to work together. (3) Input structure effect, energy structure effect, and final demand effect promote the growth of service industry energy carbon emissions. This also indicates that in the sample range, the service industry as the final demand product has the characteristics of high carbonization, the generalized technological progress of the input structure effect has not been improved, and the energy consumption structure on the supply side of the service industry has not been optimized. Therefore, China's service industry still has great potential for emission reduction from the above three aspects in the future. The research results provide a theoretical analysis basis and practical guidance for more accurate and efficient emission reduction in the service industry from the input-output perspective.


Editorial Commentary: Hip Arthroscopy Evolution and Causes of Failure.
Hip arthroscopy use has grown as a result of expanding indications; improved imaging including higher resolution magnetic resonance imaging with stronger magnetic fields and the advent of 3-dimensional computed tomography revealing the nuances of hip joint morphology; increased specialized training; improvements in instruments and implants; a record of successful outcomes; and increased understanding of microinstability, focal acetabular undercoverage or occult dysplasia, indications for labral reconstruction and capsular plication, and, most of all, femoroacetabular impingement syndrome, the leading diagnosis for which hip arthroscopy is performed, in the orthopaedic community as well as the general medical and athletic communities. We now know that labral repair results in better outcomes than labral debridement, and evidence suggests that capsule closure leads to better long-term success. Osteoarthritis and its correlate, advanced age, result in inferior survivorship after hip arthroscopy, which is unsurprising; hip preservation surgery is not designed to treat irreparable cartilage damage. Association of female sex with hip arthroscopy failure requires additional investigation. More females undergo hip arthroscopy than males, and females initially present with greater disability. Females tend to have smaller alpha angles, greater femoral and acetabular anteversion, and lower center edge angles than males, consistent with increased prevalence of hip dysplasia. Thus surgeons indicating females for hip arthroscopy should be aware of atypical locations of cam lesions, borderline dysplasia, or ligamentous laxity, all of which must be appropriately respected at the time of surgery. With all of the improvements we have made in techniques, patient diagnosis and surgical indications, and our overall understanding of complex anatomy and a technically challenging surgery, we can speculate that our long-term survivorship will only improve. I await with interest the long-term outcomes we will see 10 years from today, with the addition of insight from patient-reported outcome measures to answer these questions with greater certainty.


Combined cranio-facial fractures.
Clinically, fronto-maxillary injuries may constitute a diagnostic problem, as their severity need not correlate with the patient's general condition. To establish a definitive radiological diagnosis, both normal standard films and tomographs are required. These will help to identify fracture lines involving the base of the skull. Most serious among the complications which may be associated with fronto-maxillary injuries is the occurrence of cerebrospinal rhinorrhoea with potential ascending infection. Other complications include oculomotor dysfunction, obstruction of lacrimal drainage and nasal airways as well as dental malocclusion. Primary surgical management is indicated in compound fractures, suspected intracranial haemorrhage and compression of the optic nerve, while fractures with associated dural injuries and involvement of orbital roofs as well as all other combined maxillo-facial fractures with functional impairment require early secondary management. Open exposure of the fracture site is best obtained through a coronal hair-line incision. Dural injuries are preferentially approached through craniotomies.


A prognostic nomogram for predicting the long-term survival outcome of hypopharyngeal squamous cell carcinoma patients after tumour resection to assist the decision-making of postoperative adjuvant treatment.
Surgery remains the most common therapeutic strategy for Chinese patients with hypopharyngeal squamous cell carcinoma (HSCC), yet the indications for postoperative adjuvant treatment (POAT) remain unclear. We retrospectively analysed 385 patients with primary HSCC in our hospital between 2003 and 2014. Patients that received pharyngectomy without POAT were enrolled in this study for developing a nomogram that predicts their survival outcome. Multivariate analyses showed that the tumour size, oesophagal invasion, extracapsular spread or internal jugular vein adhesion, thyroid gland invasion, and the number of lymph node metastases (≤3 or >3) were significantly correlated to the overall survival (OS) of the patient and were included as risk factors in the nomogram. The C-index was 0.768 (95% CI, 0.719-0.817) in development cohort and 0.767 (95% CI, 0.753-0.781) in validation cohort. A calibration curve was also conducted and was found favourable. The patients were stratified into three groups based on their nomogram scores. In the high-risk group, patients that received POAT had a better OS than those that received only surgery. In the moderate-risk group, POAT did not show any significant association with the OS. However, patients in the low-risk group that received POAT showed a worse OS than those without. The newly-developed nomogram can effectively predict the survival outcome of patients with HSCC. According to the novel stratification criteria created, patients stratified as high-risk could benefit from POAT, while those in the low-risk group are advised not to receive POAT as this correlates with a worse OS.


Estimating survival probability using the terrestrial extinction history for the search for extraterrestrial life.
Several exoplanets have been discovered to date, and the next step is the search for extraterrestrial life. However, it is difficult to estimate the number of life-bearing exoplanets because our only template is based on life on Earth. In this paper, a new approach is introduced to estimate the probability that life on Earth has survived from birth to the present based on its terrestrial extinction history. A histogram of the extinction intensity during the Phanerozoic Eon is modeled effectively with a log-normal function, supporting the idea that terrestrial extinction is a random multiplicative process. Assuming that the fitted function is a probability density function of extinction intensity per unit time, the estimated survival probability of life on Earth is [Formula: see text] from the beginning of life to the present. This value can be a constraint on [Formula: see text] in the Drake equation, which contributes to estimating the number of life-bearing exoplanets.


Encephalitis and meningitis in Western Africa: a scoping review of pathogens.
To give an overview of the recently reported literature on the aetiologies of meningitis and encephalitis in western sub-Saharan Africa. We conducted a scoping review following PRISMA guidance on published meningitis and encephalitis cases in the 16 countries of the United Nations-defined western sub-Saharan African region as identified in cohort studies, case series, and case reports, published 01/01/2000-08/01/2020, and available in four databases in August 2020 with an abstract in English, French or Italian. There were 38 distinct pathogens identified from 91 cohort studies' data and 48 case reports or case series' data. In cohort-level data, the majority of cases were caused by Neisseria meningitidis (71.5%), Streptococcus pneumoniae (17.6%) and Haemophilus influenzae (7.3%). In case report- and case series-level data, 40.5% of patients were <18 years old, 28.6% were female, and 28.6% were known to be immunocompromised. The case fatality rate was 39.3%. The most commonly reported pathogens among immunocompetent patients were Salmonella species (13 cases) and Ebola virus (9 cases), and the most commonly reported pathogen among immunocompromised patients was Cryptococcus neoformans (18 cases). Most cohort cases (52.3%) derived from Niger followed by Burkina Faso (28.6%). Most cases from single reports or series were reported from Nigeria (21.4%), Mali (20.2%) and Burkina Faso (19.0%). Given the small number of pathogens reported, our findings underscore the need to better screen, diagnose and monitor populations in western sub-Saharan Africa for additional CNS pathogens, including those posing significant outbreak risks.


Myths and media in oral collagen supplementation for the skin, nails, and hair: A review.
As a key component of the hair, skin, and nails, there is strong consumer interest in the dermatologic efficacy of oral collagen supplementation. Oral supplementation with collagen peptides has increased in popularity in recent years. There are relatively few studies investigating the dermatologic effects of ingested collagen peptides, many of which are limited by sample size and variability of results. The question remains whether there is sufficient evidence to support companies' promises and consumers' goals. In this review, we investigate and compare the claims surrounding collagen supplementation on Instagram and YouTube, made by collagen companies, and established in the literature. Although some studies have demonstrated that collagen supplementation can enhance skin qualities such as elasticity and hydration, dermatologic claims in the media surpass any evidence currently supported by the literature. More research is needed to establish knowledge of the effects and physiologic mechanism of collagen supplementation. Dermatologists should be aware of the unsubstantiated proclamations of collagen made by companies and in social media, as well as what evidence is established thus far, to be equipped to discuss collagen supplementation with patients.


Influence of misonidazole on survival of wild-type and radiosensitive mutants of yeast.
Survival curves were obtained for haploid and diploid yeasts, Saccharomyces cerevisiae, of a wild-type strain and radiosensitive mutants exposed to gamma-rays in oxygenated and hypoxic conditions both in the absence and in the presence of misonidazole. Misonidazole enhanced the radiosensitivity only of hypoxic cells. A correlation between oxygen and misonidazole sensitization was observed. The data confirm that misonidazole mimics the sensitizing effect of oxygen. The degree of liquid-holding recovery of yeast cells was greater when the cells were irradiated in hypoxic conditions with than without misonidazole. Possible reasons for the observed radiation responses are discussed.


Uterine papillary serous carcinoma.
Reviewed are 37 patients with the diagnosis of uterine papillary serous carcinoma. Clinically, 19 patients presented as stage I, 9 as stage II, 1 as stage III, and 8 as stage IV. Four of 18 patients with clinical stage I disease who underwent surgery had pelvic metastases and five had disease spread beyond the pelvis. Three of nine clinical stage II patients had intraabdominal metastases. At least 50% myometrial invasion was found in 43% of the 30 hysterectomy specimens, and lymphatic invasion in the myometrium was demonstrated in 78% of the specimens. Each of the 15 patients with surgical stage I or II disease received local radiation therapy: 10 are alive and of these 9 are disease-free. Each of nine clinical stage II patients received intense radiation therapy and hysterectomy; seven are alive and of these four are disease free. The five-year survival for combined surgical stages I and II patients was 45%. The three-year survival for combined surgical stages III and IV was 11%. Thirteen patients have been treated with combination chemotherapy, 11 with cis-platinum-based combinations. Nine of these patients are dead; four are alive, with three of these having progressive disease.


Effect of thiazolidinediones on glucose and fatty acid metabolism in patients with type 2 diabetes.
The current study aimed to compare the effects of treatment (2 months) with thiazolidinediones (TZDs) and placebo on glucose and fat metabolism in patients with type 2 diabetes (T2DM) in a crossover design. Eight patients received placebo (2 months) followed by TZD (2 months). Two-stage (1.5 and 6.0 pmol/kg min) hyperinsulinemic-euglycemic clamps were performed in all 8 patients pre- and post-placebo and post-TZD (post-placebo = pre-TZD). We determined rates of glucose disappearance (G(Rd)), glycolysis (GLS), glycogen synthesis (GS) (all with 3-(3)H glucose), carbohydrate (CHO) oxidation (indirect calorimetry), endogenous glucose production (EGP), free fatty acid (FFA) release ((2)H(5) glycerol), and oxidation (indirect calorimetry) and re-esterification, as well as plasma adiponectin and leptin concentrations, and fat cell size and number (determined in upper thigh biopsy samples). Placebo treatment had no effects on any of the measured parameters. TZD treatment improved insulin-stimulated glucose uptake (ISGU) from 17.1 to 26.4 micromol/kg min (P <.01) and insulin-stimulated GS from 4.8 to 13.4 micromol/kg min (P < 0.03), potentiated insulin-induced suppression of lipolysis from 4.3 to 2.3 micromol/kg min (P <.03) and FFA re-esterification from 1.9 to 1.0 micromol/kg min (P <.02), increased plasma adiponectin levels from 2.7 to 7.2 microg/mL (P <.05), and decreased plasma leptin levels from 30.8 to 23.4 ng/mL (P <.02). In addition, TZD tended to increase the number of small adipocytes (<50 microm) in subcutaneous adipose tissue. We conclude that TZDs have multiple actions and that many, but perhaps not all, can be accounted for by their action on adipose tissue.


Increasing availability of lower energy meals vs. energy labelling in virtual full-service restaurants: two randomized controlled trials in participants of higher and lower socioeconomic position.
There are a range of interventions designed to promote healthier food choices in full-service restaurants. However, it is unclear how these interventions affect dietary choices in people of lower and higher socioeconomic position (SEP). A total of 2091 US participants recruited online completed Study 1 (n = 1001) and Study 2 (n = 1090). Recruitment was stratified by participant highest education level, resulting in higher SEP and lower SEP groups. In a between-subjects design, participants made hypothetical food choices (main dish, plus optional sides and desserts) from six restaurants menus in the absence vs. presence of menu energy labelling and from menus with baseline (10%) vs. increased availability (50%) of lower energy main dishes. Data were collected and analysed in 2019. Two studies were conducted in order to examine replicability and generalisability of findings across different restaurant menu types. Across both studies, increasing the availability of lower energy main menu options decreased the average energy content of the ordered main dish (- 129 kcal, 95% CI [- 139; - 119]) and total energy ordered (- 117 kcal, 95% CI [- 138; - 95]) in both higher and lower SEP participants. Energy labelling significantly reduced the energy content of ordered main dishes in higher SEP participants (- 41 kcal, 95% CI [- 54; - 29]), but not lower SEP participants (- 5 kcal, 95% CI [- 22; 11]). However, energy labelling reduced total energy ordered (- 83 kcal, 95% CI [- 105; - 60]) irrespective of SEP. In two virtual experiments, increasing the availability of lower energy restaurant main menu options impacted on main menu dish choice and decreased total energy ordered irrespective of SEP. Energy labelling had a less pronounced effect on total energy ordered and had a larger impact on the energy content of main menu dish choice in higher as opposed to lower SEP participants. Clinicaltrials.gov NCT04336540 retrospectively registered (7 April, 2020).


Theory of optimal balance predicts and explains the amplitude and decay time of synaptic inhibition.
Synaptic inhibition counterbalances excitation, but it is not known what constitutes optimal inhibition. We previously proposed that perfect balance is achieved when the peak of an excitatory postsynaptic potential (EPSP) is exactly at spike threshold, so that the slightest variation in excitation determines whether a spike is generated. Using simulations, we show that the optimal inhibitory postsynaptic conductance (IPSG) increases in amplitude and decay rate as synaptic excitation increases from 1 to 800 Hz. As further proposed by theory, we show that optimal IPSG parameters can be learned through anti-Hebbian rules. Finally, we compare our theoretical optima to published experimental data from 21 types of neurons, in which rates of synaptic excitation and IPSG decay times vary by factors of about 100 (5-600 Hz) and 50 (1-50 ms), respectively. From an infinite range of possible decay times, theory predicted experimental decay times within less than a factor of 2. Across a distinct set of 15 types of neuron recorded in vivo, theory predicted the amplitude of synaptic inhibition within a factor of 1.7. Thus, the theory can explain biophysical quantities from first principles.


Cytokine induced 3-D organotypic psoriasis skin model demonstrates distinct roles for NF-κB and JAK pathways in disease pathophysiology.
Psoriasis vulgaris is an inflammatory skin disease that affects 2%-3% of the population worldwide. One of the major challenges in discovering novel therapies is the poor translatability of animal models to human disease. Therefore, it is imperative to develop human preclinical models of psoriasis that are amenable to pharmacological intervention. Here, we report a 3-D reconstituted human epidermis (RHE) culture system treated with cytokines commonly associated with psoriasis (TNFα, IL-17A and IL-22) that reproduced some key features of the human disease. The effects on epidermal morphology, gene transcription and cytokine production, which are dysregulated in psoriasis were assessed. Certain morphological features of psoriatic epidermis were evident in cytokine-stimulated RHEs, including hypogranulosis and parakeratosis. In addition, RHEs responded to a cytokine mix in a dose-dependent manner by expressing genes and proteins associated with impaired keratinocyte differentiation (keratin 10/K10, loricrin), innate immune responses (S100A7, DEFB4, elafin) and inflammation (IL-1α, IL-6, IL-8, IL-10, IL-12/23p40, IL-36γ, GM-CSF and IFNγ) typical of psoriasis. These disease-relevant changes in morphology, gene transcription and cytokine production were robustly attenuated by pharmacologically blocking TNFα/IL-17A-induced NF-κB activation with IKK-2 inhibitor IV. Conversely, inhibition of IL-22-induced JAK1 signalling with ABT-317 strongly attenuated morphological features of the disease but had no effect on NFκB-dependent cytokine production, suggesting distinct mechanisms of action by the cytokines driving psoriasis. These data support the use of cytokine-induced RHE models for identifying and targeting keratinocyte signalling pathways important for disease progression and may provide translational insights into novel keratinocyte mechanisms for novel psoriasis therapies.


Nuclear imaging of the liver: is there a diagnostic role of HIDA in posttransplantation?
Biliary complications are common after liver transplantation. This study sought to assess the value of hepatic iminodiacetic acid (HIDA) scans (hepatobiliary iminodiacetic acid scan) to detect early posttransplantation biliary complications. From April 2003 to June 2006, 34 liver transplantations (recipients of mean +/- SD age of 43.0 +/- 15.7 years) were performed in 25 (73.5%) males from 20 (58.8%) cadaveric donors and 14 (41.2%) living-related donors. The subjects underwent HIDA scans using a single head gamma camera Meridian (Philips) after intravenous (IV) administration of 185 MBq Tc-99m Disofenin. The mean time +/- SD posttransplantation to HIDA scan was 14.6 +/- 18.2 days (range, 0-74). The results were compared with endoscopic retrograde cholangio pancreatography, magnetic resonant cholangiopancreatography, percutaneous cholangiograhy, and/or liver biopsy. Twenty-four abnormalities were detected by HIDA scan in 16 patients (47.1%): 10 (29.4%) biliary leaks; 4 (11.4%) biliary obstruction or cholestasis; 1 (2.9%) delayed uptake; 5 (14.7%) delayed blood pool clearance; and 8 (23.5%) delayed transit to the bowel. The complications were more common among living-donor compared with deceased-donor graft recipients, albeit a not statistically significant difference (P = .066). Total and direct bilirubin levels were significantly higher in patients with abnormal than normal HIDA scans (P = .011 and P = .040, respectively). The sensitivity and specificity of HIDA scans to detect overall postoperative complications were 100% and 66.7%, respectively. Biliary leak results were false positives in 7/10 patients, and true in 3. Detection of obstruction was 75% sensitive by HIDA. HIDA scans are a noninvasive, reliable modality for early exclusion of posttransplantation biliary complications. However, correlation with clinical status and imaging modalities is essential to confirm detected abnormalities.


The oral health knowledge and oral hygiene practices among primary school children age 5-17 years in a rural area of Uasin Gishu district, Kenya.
To determine the oral health knowledge and oral hygiene practices among school children in the study region This was a descriptive cross-sectional study carried out among primary school going children in Kapsaret Educational division, Uasin-Gishu District, Kenya. A researcher administered questionnaire was used to determine the oral health knowledge and practices in a random sample of 401 students in the period March to June 2002. 92% of the students claimed they brushed their teeth. About 48% brushed at least twice daily. More students (59.1%) reported using the chewing stick compared to those using commercial toothbrushes (p = 0.000).Female students brushed more frequently than their male counterparts (p = 0.000, chi2 = 24.65). 39.9% of the students knew the cause of tooth decay, 48.2% could state at least one method of prevention, while 16.5% knew the importance of teeth. Use of toothpaste was reported by 38.9% of the students. Less than half of the students knew the causes of tooth decay and how to prevent it. Only about half of the students brushed their teeth twice daily with the chewing stick being more frequently used. There is need to increase the oral health knowledge through well Planned school based oral health education programmes in the primary schools. This would hopefully lead to improvement on the oral hygiene practices.


A prospective controlled randomized multicenter study to evaluate the severity of compensatory sweating after one-stage bilateral thoracic sympathectomy versus unilateral thoracic sympathectomy in the dominant side.
To evaluate the contribution that unilateral thoracic sympathectomy in dominant side or two-stage bilateral thoracic sympathectomy can have as strategies to reduce the incidence of compensatory sweating after sympathectomy for palmar hyperhidrosis. This is a prospective, controlled, randomized multicenter trial of 200 participants with palmar hyperhidrosis, which will be randomized into two arms: (a) one-stage bilateral thoracic sympathectomy (control arm); or (b) unilateral thoracic sympathectomy in dominant side (intervention arm). At six months the participants submitted to unilateral procedure can make the contralateral surgery if they wanted it, creating a third group called two-stage bilateral sympathectomy. Participants will be evaluated for the degree of sweating by the Hyperhidrosis Disease Severity Scale (HDSS) and of quality of life questionnaires. 96 participants out of the 200 proposed have been included so far, with 48 participants randomized to each arm. From the sample 61 (63.5%) are female, with a mean age of 24 (20-32) years. There were exclusive palmar hiperhydrosis in 14 cases (14.5%), palmar and plantar hyperhidrosis in 36 (37.5%) cases, palmar and axillar hyperhidrosis in 12 (12,5%) cases and palmar-axillary-plantar hyperhidrosis in 34 (35,4%) cases. The age at the beginning of the disease was childhood (78%), with mean of time of disease 15 (11-22) years. If one or both hypothesis: (a) unilateral sympathectomy in dominant hand is a satisfactory treatment; b) two-stage bilateral sympathectomy causes less compensatory sweating than in one stage are confirmed there is a chance that surgical therapy for palmar hyperhidrosis can be changed for better.


Anti-inflammatory activity of Jasminum grandiflorum L. subsp. floribundum (Oleaceae) in inflammatory bowel disease and arthritis models.
Our study has renewed interest in the genus Jasmine for the treatment of chronic inflammatory conditions. Aerial parts of Jasminum grandiflorum L. subsp. floribundum total methanolic extract (JTME) were tested for its therapeutic potential as an anti-inflammatory agent using two experimental models in rats; acetic acid (AA) induced ulcerative colitis and adjuvant induced arthritis. The administration of JTME showed anti-inflammatory activity in a dose dependent manner. JTME, 400 mg/kg was like prednisolone, 2 mg/kg p.o. (the reference drug), since it improved the tissues of the colon clinically, macro and microscopically (ulcer index), and histopathological (scoring). It reduced the intestinal expression of pro-inflammatory cytokines in the colonic mucosa; IFNγ, TNFα, IL-6, IL-1, and MPO. It also preserved tight junctions in intestinal epithelial cells by counter-regulating claudin-5 and occludin levels additionally, it had a potent antioxidant activity. The expressions of NF-κB p65, TNF-α and caspase-3 in rats administered AA (2 mL of 4% solution, once, intrarectally) were significantly increased, where the lowest expression was scored in JTME, 400 mg/kg group. In the adjuvant induced model of rheumatoid arthritis, the TJME, 400 mg/kg reduced the levels of cathepsin D, iNOS, NO, RF, CRP, CPP and elevated the total antioxidant capacity of tissues. Additionally, it maintained bones without histopathological lesions, articular cartilage damage, and inflammation of the synovial membrane and periarticular tissues, in contrast to arthritic rats. Finally, we report a new detailed study to validate the medicinal importance of Jasminum for the chronic inflammatory disorders with immune dysfunction with anti-inflammatory and antioxidant effects.


Novel insights into RB1 mutation.
Since the discovery of the retinoblastoma susceptibility gene (RB1) decades ago, RB1 has been regarded as a prototype tumor suppressor gene providing a paradigm for tumor genetic research. Constant research has updated the understanding of RB1-related pathways and their impact on tumor and nontumor diseases. Mutation of RB1 gene has been observed in multiple types of malignant tumors including prostate cancer, lung cancer, breast cancer, and almost every familial and sporadic case of retinoblastoma. Even if well-known and long-investigated, the application potential of RB1 mutation has not been fully tapped. In this review, we focus on the mechanism underlying RB1 mutation during oncogenesis. Therapeutically, we have further discussed potential clinical strategies by targeting RB1-mutated cancers. The unsolved problems and prospects of RB1 mutation are also discussed.


Expanding the Molecular Diversity of CIC-Rearranged Sarcomas With Novel and Very Rare Partners.
Capicua transcriptional repressor (CIC)-rearranged sarcoma represents a distinct pathologic entity and constitutes the second most prevalent category of undifferentiated round cell sarcomas (URCSs) after Ewing sarcoma. The 2 most common translocations are t(4;19) and t(10;19), resulting in CIC fusions with either DUX4 and DUX4L paralog, respectively; however, other rare variant fusions have also been reported. In this study, we expand the molecular spectrum of CIC-gene partners, reporting on 5 cases of URCSs showing CIC fusions with AXL, CITED1, SYK, and LEUTX by targeted RNA or DNA sequencing. There were 4 female patients and 1 male patient with a wide age range (12-70 years; median, 36 years). Four cases occurred in the deep soft tissues (lower extremity, 3; neck, 1) and 1 case in the central nervous system (midbrain/thalamus). All cases showed similar histologic findings within the spectrum of URCSs. Immunohistochemistry, showed variable positivity for ETV4 in 4 of the 4 cases and positive results for ERG in 3 of the 4 cases and for WT1 in 1 of the 4 cases. CD31 showed positivity in 2 of the 3 cases, including one coexpressing ERG. Unsupervised clustering of methylation profiles by T-distributed stochastic neighborhood embedding performed in 4 cases showed that all clustered tightly together and along the CIC sarcoma methylation class. RNA-sequencing data showed consistent upregulation of ETV1 and ETV4 mRNA in all cases examined, at similar levels to CIC::DUX4 URCSs. Our study expands the molecular diversity of CIC-rearranged URCSs to include novel and rare partners, providing morphologic, immunohistochemical, gene expression, and methylation evidence supporting their classification within the family of tumors harboring the more common DUX4/DUX4L partner genes.


Longitudinal study of 18 children with perinatal LAV/HTLV III infection: attempt at prognostic evaluation.
We performed a longitudinal study (mean follow-up 19.5 months, range 3 to 42 months) in 18 consecutive children with clinical symptoms of LAV/HTLV III infection. Twelve patients were born to mothers infected with LAV/HTLV III, and six were infected by blood products administered during the first weeks of life. Immunologic studies included lymphocyte markers, in vitro responses to mitogens and antigens with corresponding skin tests, and antibody response with isoagglutinins, post-vaccination antibodies, and Candida. A serologic profile of antibody to GP110, P18, and P25 LAV/HTLV III antigens by radioimmunoprecipitation assay was also performed. The antigen-induced proliferative responses were normal in 10 patients who had a stable course, but were profoundly impaired in eight others who died or had poor condition with opportunistic infections. These in vitro measurements were well correlated with antigen skin tests. An abnormal antibody response to antigens, a low level of isoagglutinins, and a peculiar profile of LAV/HTLV III antibodies were also frequently observed in these eight patients. These measurements appear to be of prognostic value because they were noticed soon after onset of clinical symptoms.


Direct detection of brown adipose tissue thermogenesis in UCP1-/- mice by hyperpolarized 129Xe MR thermometry.
Brown adipose tissue (BAT) is a type of fat specialized in non-shivering thermogenesis. While non-shivering thermogenesis is mediated primarily by uncoupling protein 1 (UCP1), the development of the UCP1 knockout mouse has enabled the study of possible UCP1-independent non-shivering thermogenic mechanisms, whose existence has been shown so far only indirectly in white adipose tissue and still continues to be a matter of debate in BAT. In this study, by using magnetic resonance thermometry with hyperpolarized xenon, we produce the first direct evidence of UCP1-independent BAT thermogenesis in knockout mice. We found that, following adrenergic stimulation, the BAT temperature of knockout mice increases more and faster than rectal temperature. While with this study we cannot exclude or separate the physiological effect of norepinephrine on core body temperature, the fast increase of iBAT temperature seems to suggest the existence of a possible UCP1-independent thermogenic mechanism responsible for this temperature increase.


Is a grandmal seizure necessary and sufficient for the efficacy of electro convulsive therapy?
This paper highlights the recent research findings which suggest that the old teaching that a grandma! seizure is both necessary and sufficient for the efficacy of electroconvulsive therapy (ECT) is not correct. It is necessary; but not sufficient. The stimulus intensity should be adjusted so that it is far above the seizure threshold in order to get maximum efficacy of ECT.


Tandem intercostal thoracic schwannomas resected using a thoracoscopic nerve-sparing technique: case report.
To describe a novel nerve-sparing technique for the resection of intercostal nerve schwannomas. This case demonstrates that intercostal neuralgia can be caused by intercostal schwannomas and that it can be relieved by their removal. A young woman with schwannomatosis had progressively worsening intercostal neuralgia caused by compression of the intercostal nerve against the rib by tandem intercostal schwannomas. After the tumors were removed, her symptoms were completely relieved. A thoracoscopic technique was used to define the involved fascicles and to facilitate removal of the tumors while sparing the uninvolved nerve. The patient's radicular pain was relieved completely by the tumor resection. Thoracoscopic surgery offers a safe and minimally invasive technique for removal of intercostal schwannomas and is a valid alternative to open thoracotomy. Removal of thoracic schwannomas can relieve intercostal neuralgia.


Toward synthetic life: Biomimetic synthetic cell communication.
Engineering synthetic minimal cells provide a controllable chassis for studying the biochemical principles of natural life, increasing our understanding of complex biological processes. Recently, synthetic cell engineering has enabled communication between both natural live cells and other synthetic cells. A system such as these enable studying interactions between populations of cells, both natural and artificial, and engineering small molecule cell communication protocols for a variety of basic research and practical applications. In this review, we summarize recent progress in engineering communication between synthetic and natural cells, and we speculate about the possible future directions of this work.


Economic impact of low-osmolality contrast agents on radiology procedures and departments.
The financial impact at one institution of the use of low-osmolality contrast agents was analyzed. The impact is major, and several proposals for action are discussed.


Memory-efficient iterative process on a two-dimensional first-order regular graph.
We present a parallel and memory-efficient iterative algorithm based on 2D first-order regular graphs. For an M x N regular graph with L iterations, a carefully chosen computation order can reduce the memory resources from O(MN) to O(ML). This scheme can achieve a memory reduction of 4 to 27 times in typical computation-intensive problems such as stereo and motion.


Human milk oligosaccharides alleviate stress-induced visceral hypersensitivity and associated microbiota dysbiosis.
Pain-related functional gastrointestinal disorders (FGIDs) are characterized by visceral hypersensitivity (VHS) associated with alterations in the microbiota-gut-brain axis. Since human milk oligosaccharides (HMOs) modulate microbiota, gut and brain, we investigated whether HMOs impact VHS, and explored the role of gut microbiota. To induce VHS, C57BL/6JRj mice received hourly water avoidance stress (WAS) sessions for 10 d, or antibiotics (ATB) for 12 d. Challenged and unchallenged (Sham) animals were fed AIN93M diet (Cont) or AIN93M containing 1% of a 6-HMO mix (HMO6). VHS was assessed by monitoring the visceromotor response to colorectal distension. Fecal microbiome was analyzed by shotgun metagenomics. The effect of HMO6 sub-blends on VHS and nociceptive pathways was further tested using the WAS model. In mice fed Cont, WAS and ATB increased the visceromotor response to distension. HMO6 decreased WAS-mediated electromyographic rise at most distension volumes and overall Area Under Curve (AUC=6.12±0.50 in WAS/HMO6 vs. 9.46±0.50 in WAS/Cont; P<.0001). In contrast, VHS in ATB animals was not improved by HMO6. In WAS, HMO6 promoted most microbiota taxa and several functional pathways associated with low VHS and decreased those associated with high VHS. Among the sub-blends, 2'FL+DFL and LNT+6'SL reduced visceromotor response close to Sham/Cont values and modulated serotoninergic and CGRPα-related pathways. This research further substantiates the capacity of HMOs to modulate the microbiota-gut-brain communication and identifies mitigation of abdominal pain as a new HMO benefit. Ultimately, our findings suggest the value of specific HMO blends to alleviate pain associated FGIDs such as infantile colic or Irritable Bowel Syndrome.


The suppression of the μ rhythm during the creation of imagery representation of movement.
The aim of this study was to answer the following question: are there differences between the attenuation of μ rhythms, recorded with EEG in the parietal area during observation of movement and the creation of its imaginative representation? In addition, we checked the extent to which the μ rhythm suppression depends on whether the observed and the imagined movement is performed by a human or is artificial. As a result of the experiment a significant difference in μ rhythm suppression between the conditions "Observation," "Imagery," and "White noise" was recorded. It did not matter whether the motion was carried out by a human being or performed by a machine. The results are discussed in the light of findings which relate to the mirror neuron system.


Evaluation of different hydrocolloids to improve dough rheological properties and bread quality of potato-wheat flour.
The aim of study was to investigate the effect of hydroxylpropylmethylcellulose (HPMC), arabic gum (AG), konjac glucomannan (KG) and apple pectin (AP) at 2% (w/w, potato-wheat flour basis) on the potato-wheat dough (the mass ratio was 1:1) rheological, fermentation and bread making properties. The tan δ of potato-wheat dough was significantly increased upon addition of adding HPMC which was close to wheat dough (0.531). Moreover, dough height during fermentation process was significantly improved on addition of hydrocolloids, with the order of HPMC (23.1 mm) > AP (19.3 mm) > AG (18.6 mm) > KG (13.6 mm). Protein bands of potato-wheat dough were pale in the presence of hydrocolloids, suggesting the formation of higher molecular weight aggregates formed between proteins-hydrocolloids or proteins-proteins after fermentation process. Furthermore, HPMC significantly increased specific volume (from 1.45 to 2.22 ml/g), and hydrocolloids restricted the retrogradation of starch in potato-wheat breads.


Does a history of trauma contribute to HIV risk for women of color? Implications for prevention and policy.
We investigated history of abuse and other HIV-related risk factors in a community sample of 490 HIV-positive and HIV-negative African American, European American, and Latina women. Baseline interviews were analyzed, and logistic regressions were used to identify predictors of risk for positive HIV serostatus overall and by racial/ethnic group. Race/ethnicity was not an independent predictor of HIV-related risk, and few racial/ethnic differences in risk factors for HIV were seen. Regardless of race/ethnicity, HIV-positive women had more sexual partners, more sexually transmitted diseases, and more severe histories of abuse than did HIV-negative women. Trauma history was a general risk factor for women, irrespective of race/ethnicity. Limited material resources, exposure to violence, and high-risk sexual behaviors were the best predictors of HIV risk.


Genetic characterization of an alloalbumin, albumin Kashmir, using gene amplification and allele-specific oligonucleotides.
The molecular basis for albumin Kashmir was studied using the polymerase chain reaction to amplify a DNA fragment containing codon 501 in exon 12 of the human albumin gene. Southern blots of the amplified DNA were hybridized to oligonucleotide probes specific either for the normal allele of albumin or for albumin Kashmir. The results provide strong evidence that codon 501 in albumin Kashmir is AAG (lysine) instead of GAG (glutamic acid), thus confirming the protein sequences reported. This approach was used to characterize a bisalbuminaemic individual as a carrier for albumin Kashmir. Similar strategies may be devised to study the molecular basis and to identify carriers of other alloalbumins.


Programmed Cell Death Ligand 1 Expression on Immune Cells and Survival in Patients With Nonmetastatic Head and Neck Cancer: A Systematic Review and Meta-analysis.
The failure or success of radical treatment in patients with head and neck squamous cell carcinoma (HNSCC) is associated with many known and unknown factors; hence, there is a search for further prognostic markers to help optimize therapeutic strategy and improve treatment outcomes. To assess the association of programmed cell death ligand 1 (PD-L1) expression on immune or tumor cells, including its composite expression on both cell types, with overall survival (OS) or specific survival. MEDLINE, Embase, PQSciTech, and HCAPlus databases were systematically searched for cohort studies focused on the prognostic role of PD-L1 expression in patients with HNSCC in curative stages of the disease. Search results generated publications from January 1, 2010, to January 6, 2023. Of 3825 publications identified, a total of 17 cohort studies in the English language met inclusion criteria of this systematic review and meta-analysis. Eligible studies reported adjusted hazard ratios (aHRs) with 95% CIs for the association of PD-L1 expression levels with OS and arbitrary specific survival. Data from studies were extracted independently by 2 researchers strictly adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines and recommendations. The risk of bias was assessed using the Quality in Prognosis Studies tool and Newcastle-Ottawa Scale. Pooled effect estimates were obtained using a random-effect or fixed-effect model based on homogeneity of studies. The primary outcome was to investigate whether there was an association between PD-L1 expression on immune or tumor cells and OS. In 17 cohort studies of the association of PD-L1 expression with survival in 3190 patients with HNSCC, high PD-L1 expression on immune cells was associated with a favorable OS (pooled aHR, 0.39; 95% CI, 0.25-0.59). There was no association between composite PD-L1 expression on immune and tumor cells and OS (pooled aHR, 0.79; 95% CI, 0.55-1.14) or between PD-L1 expressed only on tumor cells and OS (pooled aHR, 1.22; 95% CI, 0.87-1.70). A high level of PD-L1 expression on immune cells was associated with favorable specific survival (pooled aHR, 0.52; 95% CI, 0.38-0.72). There were no interactions between tumor location or type of primary treatment (ie, surgery vs radiotherapy or radiochemotherapy) and the association between PD-L1 expression and OS. This study's findings suggest that PD-L1 expression on immune cells may serve as a new prognostic biomarker in patients with HNSCC. However, future studies may be warranted to verify this potential role given the limited number of studies on this topic conducted and published to date.


Influence of structure of human, rat, and bovine serum albumins on binding properties of photoactive drug hypericin.
Fluorescence binding measurements and molecular modeling were employed to study the interaction of hypericin (Hyp) with human (HSA), rat (RSA), and bovine (BSA) serum albumins. Fluorescence emission data show the solubility of Hyp increasing in the order BSA, HSA, and RSA. Molecular modeling was used to construct the detailed structural models of the complexes and to explain the differences in the binding properties of Hyp. It was shown that the structures of Hyp/HSA and Hyp/RSA complexes are more similar and in some aspects different from those found for the Hyp/BSA complex. The role of the amino acid sequence in the IIA subdomains of HSA, RSA, and BSA is discussed to explain the observed differences.


MicroRNA-23b alleviates neuroinflammation and brain injury in intracerebral hemorrhage by targeting inositol polyphosphate multikinase.
Neuroinflammation plays a critical role in the pathogenesis of intracerebral hemorrhage (ICH), contributing to detrimental brain injury and neurological function deficits. MicroRNA-23b (miR-23b) exerts anti-inflammatory effects in many diseases and is downregulated in patients with ICH. This study aimed to evaluate the involvement of miR-23b in ICH models in vivo and in vitro, using basal ganglia injection of collagenase type VII in rats and hemin stimulation for cells, respectively. Exogenous overexpression of miR-23b by transfection with lentivirus-miR-23b (LV-miR-23b) or miR-23b mimics was evaluated by RT-qPCR. In this study, we found miR-23b was downregulated in the ICH models and its overexpression effectively alleviated neurological deficits, brain edema, hematoma area, and neuronal apoptosis in ICH rats. Western blotting for neuroinflammation markers and immunofluorescence staining for microglial activation demonstrated that miR-23b could alleviate neuroinflammation in ICH in vivo. We also performed an in vitro mechanism study using BV2 microglial cells and HT22 neuronal cell lines to explore how miR-23b modulates neuroinflammation and neuronal protection after ICH. We found that miR-23b significantly decreased hemin-stimulated inflammation response in BV2 cells and attenuated co-cultured HT22 neuronal cell death. Additionally, we verified that miR-23b suppressed inflammation in BV2 cells by targeting inositol polyphosphate multikinase (IPMK) and that autophagy regulation through the Akt/mTOR pathway was involved in miR-23b-regulated inflammation after ICH. Our study illustrated that miR-23b played a protective role in ICH through inhibiting neuroinflammation by targeting IPMK; this mechanism may be related to the regulation of the Akt/mTOR autophagy pathway, making it a potential target for ICH treatment.


Effects of activators and inhibitors of protein kinase C on two-stage transformation in BALB/3T3 cells.
To determine the relationship between protein kinase C and the promotion of carcinogenesis, we investigated the effects of activators and inhibitors of protein kinase C on two-stage transformation in BALB/3T3 cells. Diacylglycerols, which are activators, and specific inhibitors, such as palmitoyl-DL-carnitine chloride (PC), 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), and staurosporine (ST) were used. Treatment with diacylglycerols enhanced focus formation in 3-methylcholanthrene (3-MC)-initiated cells, but not as much as 12-O-tetradecanoylphorbol-13-acetate (TPA). PC and H-7 inhibited TPA-enhanced transformation by 76 and 79%, respectively. ST, the most potent inhibitor of protein kinase C, had a low inhibitory effect on transformation at non-toxic doses (33% inhibition). The results suggest that protein kinase C may play an important role in the process by which transformation is promoted in BALB/3T3 cells.


Papillary thyroid carcinoma with distant metastases: survival predictors and the importance of local control.
The presence of distant metastases is the most important predictive factor of poor outcomes in patients with papillary thyroid carcinoma (PTC). Some patients have very slow-growing distant metastases with relatively favorable outcomes, so predicting prognosis is not easy. Furthermore, many patients with distant metastases show locally advanced disease, and no consensus is available for operative control of cervical tumor in this situation. Among 1023 patients with PTC who underwent primary thyroidectomy from 1976 to 2002, 42 patients displayed distant metastases at initial presentation and 44 patients developed distant metastases during follow-up. We reviewed the records retrospectively of these 86 patients. Mean duration of follow-up after detection of distant metastases was 7 years. Our treatment approach for patients with locally advanced neoplasms was radical resection including extensive neck dissection and extended resection of the involved organs, even when distant metastases were present. Disease-specific survival of the 86 patients with distant metastases at 5 and 10 years was 65% and 45%, respectively. Using multivariate analysis, older age at time of distant metastases detection, distant metastases involving sites other than the lung, distant metastases diameter > or = 2 cm, presence of large nodal metastases (> or = 3 cm), and a primary neoplasm with poorly differentiated components were all predictive of worse prognosis. Our aggressive approach allowed curative resection in all but 1 patient, and only 5 patients (6%) succumbed to local disease. Patients with cervical recurrences displayed worse prognosis than those without. Although the currently employed modalities of therapy for distant metastases do not have definitive impact on survival, some PTC patients with distant metastases, including younger patients with well-differentiated, small lung metastases appear to have relatively favorable outcomes. Local operative control of PTC is important even in patients with distant metastases, particularly when the distant metastases appear to be slow-growing.


An improved incubation apparatus for Western blots used for the detection of antinuclear antibodies.
To facilitate the use of Western blots for the detection of antibodies, we have developed an incubation apparatus. The use of this apparatus simplifies the incubation of blots with antisera, permits the testing of large numbers of sera and eliminates artefacts caused by the use of loose strips. The introduction of a pressure bag in the lower lid of the apparatus secures a steady pressure over the entire blot, a feature lacking in currently available commercial equipment. The detection of antinuclear antibodies is presented as an example of the use of this incubator.


Nondegradable Collagen Increases Liver Fibrosis but Not Hepatocellular Carcinoma in Mice.
Although hepatocellular cancer (HCC) usually occurs in the setting of liver fibrosis, the causal relationship between liver fibrosis and HCC is unclear. in vivo and in vitro models of HCC involving Colr/r mice (that produce a collagenase-resistant type I collagen) or wild-type (WT) mice were used to assess the relationship between type I collagen, liver fibrosis, and experimental HCC. HCC was either chemically induced in WT and Colr/r mice or Hepa 1-6 cells were engrafted into WT and Colr/r livers. The effect of hepatic stellate cells (HSCs) from WT and Colr/r mice on the growth of Hepa 1-6 cells was studied by using multicellular tumor spheroids and xenografts. Collagen type I deposition and fibrosis were increased in Colr/r mice, but they developed fewer and smaller tumors. Hepa 1-6 cells had reduced tumor growth in the livers of Colr/r mice. Although Colr/r HSCs exhibited a more activated phenotype, Hepa 1-6 growth and malignancy were suppressed in multicellular tumor spheroids and in xenografts containing Colr/r HSCs. Treatment with vitronectin, which mimics the presence of degraded collagen fragments, converted the Colr/r phenotype into a WT phenotype. Although Colr/r mice have increased liver fibrosis, they exhibited decreased HCC in several models. Thus, increased liver type I collagen does not produce increased experimental HCC.


Use of the abrasion technique in minimal processing as an alternative to increase purchase acceptability and minimize browning in yam.
The present study investigated the sensory acceptance, oxidative damage and protection, and possible anatomical-structural damage of cells from the surface of shapes of minimally processed yam. The tubers were minimally processed into the peeled rondelle, dice and 'chateau cut' (chateau) shapes, the latter of which was obtained after performing the abrasion technique. Control treatment corresponded to the rondelle shape with the periderm. The pieces were kept packed at 5 ± 2 °C for 14 days. Peeled rondelle and chateau were sensorially the most well-accepted yam shapes and achieved the highest purchase intention. The enzymes were partially modulated by the detected H2 O2 levels. Oxidative burst lasted longer in the minimally processed tissues than in the control. Polyphenol oxidase activity showed a clear difference in behavior between the minimally processed pieces and the control. Minimal processing induced transient increases in phenolic compounds, for which the expression was lowest in the abraded pieces. On the other hand, these pieces exhibited greater cell collapse on the surface of the amyliferous parenchyma. Based on the results of the trained panel, the abrasion technique is an alternative to provide shapes that are better accepted and marketable, more resistant to browning, and can be stored for up to 12 days. Resistance to browning may be related to a more efficient modulation of enzymatic antioxidant systems and intense deposition of cell debris on the surface of the amyliferous parenchyma. © 2021 Society of Chemical Industry.


Variations in inflammation and nerve fiber loss reflect different subsets of achalasia patients.
Achalasia is a debilitating motility disorder with an unknown etiology. Past research has demonstrated a spectrum of histological findings. The objective of this study was to further characterize the histopathology of achalasia, with attention to subsets of findings that may exist, possibly reflecting different pathogeneses. Lower esophageal muscle was obtained during surgery for achalasia (n = 12) or cancer (n = 9). Immunohistochemistry was performed to identify various inflammatory cells and nerve fibers, and grading was done by an expert pathologist. Clinical data were taken from medical records. There were two subsets of achalasia specimens with different histological findings. Group A (7/12; 58%) had an inflammatory infiltrate in the myenteric plexus consisting primarily of T-lymphocytes. Group B (5/12; 42%) had no such infiltrate and had less myenteric plexus macrophages versus Group A (P = 0.03). The loss of nerve fibers was most evident in the muscularis propria in achalasia as compared to controls (P = 0.01), and this loss was more striking in Group B versus A (P = 0.04). The mean duration of symptoms was 16.6 (A) versus 6.4 years (B) (P = NS). Two subsets of achalasia patients exist with different histological findings. Group A had T-cell-rich inflammation present with associated macrophages. Group B, with no inflammation, had greater loss of nerve fibers in the muscularis propria versus Group A, and therefore, may represent more aggressive disease with shorter duration of symptoms. These results suggest that various pathogeneses of achalasia may exist that share a common pathway of aganglionosis.


Percutaneous Techniques for the Treatment of Patients with Functional Mitral Valve Regurgitation.
Percutaneous approaches to mitral regurgitation remain largely investigational. In the last decade, novel percutaneous strategies have opened new options in the treatment of valvular heart disease. Several studies are currently underway to determine the benefits of transcatheter mitral valve repair therapy. Transcatheter chordal procedures are being developed, including chordal cutting and chordal implantation. Transcatheter valve implantation in the mitral position might offer a desirable alternative in selected patients and has been accomplished in a compassionate fashion on rare occasions in patients who are not candidates for surgical valve repair or replacement.


Relationship between size of distal accessory tubercles and hypocones in permanent maxillary molar crowns of southern Africans.
The relationships between total occlusal crown area and the basal cusp areas of the accessory distal tubercle (C5) and the hypocone were analysed in molars of complete upper tooth rows of a southern African sample. While non-parametric tests between hypocone and C5 sizes did not yield statistically significant results, analyses of metrical data revealed a trend towards compensatory interaction between both cusps. Contrary to previous reports the size of C5 was found to be independent of total crown area. As enamel is thickest on cusp tips there may be a functional reason for the frequency of occurrence of the distal accessory tubercle. The pattern of distribution of the hypocone and C5 within a tooth row may be related to the occlusal wear pattern in Homo, which exhibits a marked lingual slope of wear in anterior molars and a horizontal or even buccal slope in posterior teeth.


The myoglobin of primates. VIII. Nycticebus coucang (slow loris).
To the analysis of three prosimian myoglobins reported previously [1, 2] that of the slow loris (Nycticebus coucang) has been added. A cladogram has been constructed utilising the new information to arrive at a possible ancestral prosimian myoglobin. Within the primates only the four prosimians share residues of threonine at position 34 and of isoleucine at position 142. During tryptic digestion of the loris myoglobin, some hydrolysis was observed at bonds not usually considered to be susceptible to the action of this enzyme: 52 Pro-53 Asp, and 120 Pro-121 Gly.


Synthesis, Crystal Structures and Catalytic Property of Dioxomolybdenum(VI) and Nickel(II) Complexes Derived from bis-Schiff Bases.
A new mononuclear dioxomolybdenum(VI) complex, [MoO2L1], and a new linear trinuclear nickel(II) complex, [NiNiL2(?1-?1:?0-OAc)(?2-?1:?1-OAc)2]·H2O, where L1 is the dianionic form of N,N'-bis(5-fluorosalicylidene)-1,3-propanediamine (H2L1), L2 is the dianionic form of N,N'-bis(5-fluoro-2-hydroxybenzylidene)-2-hydroxy-1,3-propanediamine (H2L2), have been synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single-crystal X-ray determination. The Mo atom in the molybdenum complex is coordinated by four donor atoms of the Schiff base ligand, and two oxo groups, forming an octahedral coordination. In the nickel complex, there are three bridges across the Ni-Ni atom pairs, involving two phenolate O atoms of a Schiff base ligand, and an O-C-O moiety of a ?2-?1:?1-OAc group. The central Ni atom is located on an inversion center and has octahedral coordination involving four bridging O atoms from two Schiff base ligands in the equatorial plane and two O atoms from two ?2-?1:?1-OAc ligands in the axial positions. The coordination around the terminal Ni atoms is also octahedral, with two imino N and two phenolate O atoms from a Schiff base ligand defining the equatorial plane, and with two O atoms respectively from a ?1-?1:?0-OAc and a ?2-?1:?1-OAc ligands occupying the axial positions. The molybdenum complex has excellent catalytic property for sulfoxidation reactions.


Comparison between red nucleus and precentral neurons during learned movements in the monkey.
Monkeys were trained to depress a hold key for a period of 2 sec. After this hold period, either a red or a green cue lamp appeared in random sequence. The red lamp required the monkey to move his hand from the hold key to a target button within 1 sec of the cue presentation. The green lamp required continued depression of the hold key for 1 sec following presentation of the cue. Correct performance was reinforced with fruit juice. In comparing poststimulus and peri-response latencies of 48 red nucleus (RN) and 46 percentral gyrus (PG) units related to the arm movement triggered by the red lamp, the onset of activity in most RN units occurred after the onset of activity in most PG neurons. For 48 RN neurons, the peak of the distribution of onset times was shifted 120 msec later than for 46 neurons. This delay between PG and RN is even greater than the delay between PG and postcentral gyrus. It is known that RN receives powerful inputs both from the sensorimotor cortex and from cerebellum--and it seems possible that the activity in RN was dependent on the combined action of these two inputs, with sensory feedback from movement (relayed via postcentral gyrus and/or cerebellum) being one input, and a central program from cerebellum and/or precentral gyrus being the other input.


Chromate and selenate hydrocalumite solid solutions and their applications in waste treatment.
Hydrocalumite, a calcium aluminate hydrate phase, consists of positively-charged structure units, and is therefore an ideal candidate for accommodating anionic contaminants. In this study, a series of batch experiments was carried out to examine the uptake of chromate and selenate by hydrocalumite. To determine the uptake capacity and long-term stability, hydrocalumite solid solutions between chromate/selenate and hydroxyl were synthesized over a reaction time of more than one year. At a ratio of water to initial solids added (CaAl2O4+CaO) of 75:1, the maximum uptake capacities were over 77 and 114 g/kg for Cr and Se, respectively. These values are very close to the theoretical uptake capacities of chromate and selenate hydrocalumite end-members (81 and 118 g/kg, respectively). The oxyanion removal efficiency from solution was above 95%. Due to the high uptake capacity and anion removal efficiency of hydrocalumites, their application in wastewater treatment is promising. Hydrocalumites are also important hydration products of cementitious materials and the long-term stability of these phases is of significance for application in solidification/stabilization technology.


Primary spinal hydatid cyst in a patient with acquired immunodeficiency syndrome.
Spinal hydatid cyst is a serious and unusual infectious disease. There is little information on infections caused by cestodes in patients with human immunodeficiency virus (HIV) infection. Although infrequent, infections by cestodes constitute a cause of disease in HIV-infected patients, especially in endemic areas. This report presents, for the first time in the literature, primary spinal cyst hydatid in a patient with acquired immunodeficiency syndrome.


Teaching functional reading in context to severely retarded and severely retarded autistic adolescents of limited English proficiency.
Practical information on how to teach severely retarded and severely retarded autistic students of limited English proficiency is presented. Specific information is given on developing a functional word list for these students that utilizes both Spanish and English. Other helpful techniques for teaching students in both languages are offered.


Rhabdomyolysis in a patient with McArdle's disease.
McArdle's disease or glycogenosis type V is a rare disease due to deficiency of muscle myophosphorylase leading to inability to degrade glycogen at this level. Patients have fatigue, pain, and cramps on a regular basis. In addition, after intense exercise or stressful situation, they are exposed to cellular lysis. This can occur in the form of rhabdomyolysis and myoglobinuria, a potentially serious clinical syndrome if not treated quickly. We present the care plan of a 38-year-old man with McArdle's disease and secondary rhabdomyolysis on physical exercise, which required attention in the Emergency Department for 24 hours, as well as his subsequent admission to the ward. A nursing evaluation was performed following the care model of Virginia Henderson. Priority was given to nurse diagnoses: (00016) deterioration of urinary elimination, (00092) activity intolerance, (00093) fatigue and (00132) acute pain; and potential complication: risk of acute renal failure. The Care Plan is developed following the NANDA-NIC-NOC methodology, with special attention to alterations in the elimination and musculoskeletal system. The diuresis is monitored. Fluid replenishment is performed, and analgesic medication is given. There is little literature on the nursing care of patients with McArdle's disease, which has limited the comparison of our results with those of other authors. However, given the good response of the subject through fluid replacement, optimal pain control and rest, they made a rapid recovery.


Study of a new device for washing and concentrating cryopreserved hematopoietic stem cells and mononuclear cells: a single center experience.
Cryopreserved cellular products, as parts of hematopoietic progenitor cell (HPC) transplants, mononuclear cell reinjections for donor lymphocyte infusion or extracorporeal photopheresis, can be washed before being reinjected into the patient or infused directly, depending on local practices. The aim of washing is to reduce the incidence and severity of adverse reactions (ARs) due to the dimethyl sulfoxide (DMSO) used as a cryoprotective agent and other factors, such as dead cell debris. At the authors' cell therapy laboratory (CTL) in Poitiers, France, as in 76% of Etablissement Français du Sang (EFS) CTLs, all cryopreserved products undergo thawing in a water bath followed by washing with the COBE 2991. As this device will soon cease to be available, an alternative process needs to be assessed. The authors compared two closed systems: the authors' semi-automatic system using the traditional centrifugation method (COBE 2991) and an automated device using spinning membrane filtration (Lovo). A total of 72 HPC bags available for research were used. The authors first performed a paired comparison, processing one or two HPC bags washed by each device. A second study was carried out to compare two different washing solutions generally used by EFS CTLs along with variable storage conditions. Finally, the authors studied the efficiency of the Lovo with three or four thawed bags. The main parameters studied were viable CD34+ cell recovery and viability, CD3+ cell recovery, stability up to 6 h after washing, DMSO elimination and center feasibility. The Lovo device showed better CD34+ cell recovery compared with the COBE 2991 while maintaining CD34+ viability and stability over 6 h. Moreover, Lovo efficiency seemed to be independent of the number of thawed bags processed and washing solution used in the authors' study. CD3+ cell recovery met the authors' internal specifications (cell recovery >50%), with similar results seen when processing with either the COBE 2991 or Lovo. Additionally, on average, 97% of DMSO was removed after washing with Lovo, minimizing the risk of ARs. The storage conditions post-processing indicated preferred storage conditions of 7 ± 3°C. Finally, if processing time seemed shorter using COBE 2991 for one bag washed, the Lovo device required only one staff member regardless of the number of HPC bags processed. The Lovo device seems to provide an opportunity to standardize HPC processing, ensuring patient safety, with, on average, 97% of DMSO removed, while improving recovery of cells of interest and maintaining viability over time in case of delayed transplant. The Lovo device consequently seems to be a serious alternative to the COBE 2991.


Molecular cloning of the replication terminus of the plasmid R6K.
Analyses of the intermediates of DNA replication of the R6K plasmid derivatives, RSF1040, RJHC12 and RJHC26 demonstrate the transient accumulation of open circular DNA molecules with a discontinuity in either the plus or the minus strand of the DNA. The location of this discontinuity is nonrandom and is near the terminus of DNA replication. The discontinuity is not due to the activation of a relaxation complex since neither RJHC12 nor RJHC26 are relaxable. The replication terminus is functional in a clone containing approx. a 2000 bp sub-fragment of the HindIII-2 fragment of R6K. The replication terminus temporarily arrests the progression of replication fork of the unidirectionally replicating plasmid pBR313 at a region approx. 800 bp from HindIII site located nearest to the BamHI site of the vector. Subcloning experiments reveal that the upper limit of the replication termination sequence is 216 bp in length.


Nasal tactile sensitivity in allergic rhinitis.
These preliminary data show a decrease in nasal tactile sensitivity and point out interesting aspects of the nasal chronic inflammatory condition in allergic rhinitis. The aim of this study was to evaluate the effects of allergic rhinitis on nasal tactile sensitivity during the intercritical period. A total of 70 patients aged between 18 and 67 years (average 42 years), with a positive history of allergy caused by seasonal outdoor allergens, were included (group A). Patient outcome was assessed by the nasal monofilament test: a set of 20 Semmes-Weinstein monofilaments was used to detect nasal sensitivity for both nasal cavities. The sensitivity threshold was recorded as the minimum monofilament size with which patients could detect at least two of three stimuli. When compared to the control group (group B), subjects in group A required a significantly (p < 0.05) higher stimulus to trigger a touch response in the monofilament test, for both the inferior (195.1 ± 0.39 mg vs 67.7 ± 0.19 mg) and middle turbinate (108.7 ± 0.23 mg vs 67.7 ± 0.19 mg).


The impact of maturation of brainstem inhibition on enuresis: a startle eye blink modification study with 2-year followup.
Previous research reveals that children with enuresis show reduced prepulse inhibition, which is supposed to reflect dysfunction in a brainstem nucleus involved in the voiding circuitry cyclus. The main aim of this study was to investigate whether maturation of the brainstem, indexed by a marked increase in percent prepulse inhibition during a period of 2 years, co-occurs with children becoming dry at night. Electromyography recorded startle eye blink during modified Ornitz automatic attention task was used to measure brainstem function. For this followup study we randomly contacted 60 children with enuresis (30 with and 30 without attention deficit-hyperactivity disorder) and 25 normally developing controls from a baseline sample. Performance at baseline and at 2-year followup in 25 children with enuresis and attention deficit-hyperactivity disorder and 24 children with enuresis without attention deficit-hyperactivity disorder was compared to 25 controls. At short lead intervals a significant difference between enuresis groups and the control group was found at baseline, whereas no significant differences were found at 2-year followup. In the enuresis groups there was a significant increase in percent prepulse inhibition between baseline and 2-year followup. Percent prepulse inhibition increase did not differ between children with different 2-year followup enuresis status, or baseline incontinence or attention deficit-hyperactivity disorder symptoms. Brainstem maturation was detected in children with enuresis but was not associated with children becoming dry. Patients with and without enuresis at followup did not demonstrate a significant difference in percent prepulse inhibition increase. These data suggest that immaturity of the brainstem may be a mechanism involved in the pathogenesis of enuresis but not in its persistence.


Capnographic monitoring of ventilatory status during moderate (conscious) sedation.
Moderate (conscious) sedation is required to perform endoscopic procedures. Capnography provides a means for continuous, real-time monitoring of ventilation and may also decrease the incidence of oversedation. A retrospective examination of all endoscopic procedures performed from January through December 2001 at our institution was undertaken to determine the potential benefits of capnographic monitoring. In 4,846 endoscopic procedures performed without capnography, adverse outcomes related to moderate sedation were noted in 14 cases (0.29%). A subset of patients at higher risk for moderate sedation was identified. There were no cases of oversedation in 600 cases monitored with capnography. The complication rates were not significantly different for the two groups ( p = 0.30, NS). The addition of capnography during moderate sedation endoscopy does not appear to significantly lower anesthesia-related morbidity. However, in cases requiring moderate sedation for prolonged procedures, in older patients with comorbidities, or in instances where respiratory excursion of the patient is obscured from view, practitioners should nonetheless consider capnography.


Thermal and acute-phase protein responses of guinea pigs to intrapreoptic injections of leukotrienes.
Although it seems probable that intrahypothalamic prostaglandin (PG) E2, a cyclooxygenase metabolite of arachidonic acid, modulates interleukin-1 (IL1)-induced fever, the evidence that it plays such a role is still only circumstantial; PGE2 does not, however, centrally mediate the fever-associated, acute-phase glycoprotein response. In this study, we investigated whether lipoxygenase products of arachidonic acid, viz. leukotriene (LT) B4, C4, D4 OR E4, injected intrapreoptically (2 ng/microliter, 1 microliter bilaterally) induces, like IL1, febrile and acute-phase glycoprotein responses in guinea pigs; controls received pyrogen-free saline, IL1 or PGE2. Measurements were: core temperature (Tco) and, as indices of acute-phase glycoproteins, plasma levels of copper (Cu) and protein-bound N-acetylneuraminic acid (NANA). Unlike IL1 or PGE2, no LT caused a febrile rise in Tco. Similar to PGE2 but unlike IL1, no LT produced increases in the plasma levels of Cu and NANA. These results indicate that intrapreoptic LTs probably are not involved in initiating the febrile or acute-phase glycoprotein responses characteristics of IL1.


Major amputation rates and outcomes for Aboriginal and Torres Strait Islander and non-Indigenous people in North Queensland Australia between 2000 and 2015.
This study estimated the incidence of major amputation for people in North Queensland, Australia, examined changes in amputation rates over time and investigated survival after major amputation. This was a retrospective study of patients who underwent a major amputation above the ankle between 2000 and 2015. Major amputation rates and incidence rate ratios (IRR) were calculated using census data to define the at-risk population. Associations between risk factors and calendar year with major amputation were assessed using quasipoisson regression. Kaplan-Meier survival and Cox-proportional hazard analyses estimated the incidence of and risk factors for all-cause mortality. The annual incidence of major amputation was estimated to be greater in Aboriginal and Torres Strait Islanders than non-Indigenous people (IRR 2.75, 95 % CI 1.92 to 3.84). After adjusting for population growth, the annual incidence of major amputations did not change significantly over time for either groups. Aboriginal and Torres Strait Islander people were at greater risk of all-cause mortality after major amputation compared to non-Indigenous people, although this association was not significant after adjusting for other risk factors (hazard ratio 1.24, 95 % CI 0.82 to 1.90). The incidence of major amputation in North Queensland has not reduced over time, indicating the need for better preventative treatments, particularly in Aboriginal and Torres Strait Islander people.


Structural basis for Sarbecovirus ORF6 mediated blockage of nucleocytoplasmic transport.
The emergence of heavily mutated SARS-CoV-2 variants of concern (VOCs) place the international community on high alert. In addition to numerous mutations that map in the spike protein of VOCs, expression of the viral accessory proteins ORF6 and ORF9b also elevate; both are potent interferon antagonists. Here, we present the crystal structures of Rae1-Nup98 in complex with the C-terminal tails (CTT) of SARS-CoV-2 and SARS-CoV ORF6 to 2.85 Å and 2.39 Å resolution, respectively. An invariant methionine (M) 58 residue of ORF6 CTT extends its side chain into a hydrophobic cavity in the Rae1 mRNA binding groove, resembling a bolt-fitting-hole; acidic residues flanking M58 form salt-bridges with Rae1. Our mutagenesis studies identify key residues of ORF6 important for its interaction with Rae1-Nup98 in vitro and in cells, of which M58 is irreplaceable. Furthermore, we show that ORF6-mediated blockade of mRNA and STAT1 nucleocytoplasmic transport correlate with the binding affinity between ORF6 and Rae1-Nup98. Finally, binding of ORF6 to Rae1-Nup98 is linked to ORF6-induced interferon antagonism. Taken together, this study reveals the molecular basis for the antagonistic function of Sarbecovirus ORF6, and implies a strategy of using ORF6 CTT-derived peptides for immunosuppressive drug development.


Does routine postoperative contrast radiography improve outcomes for patients with perforated peptic ulcer? A multicenter retrospective cohort study.
Perforated peptic ulcer is a morbid emergency general surgery condition. Best practices for postoperative care remain undefined. Surgical dogma preaches practices such as peritoneal drain placement, prolonged nil per os, and routine postoperative enteral contrast imaging despite a lack of evidence. We aimed to evaluate the role of postoperative enteral contrast imaging in postoperative perforated peptic ulcer care. Our primary objective was to assess effects of routine postoperative enteral contrast imaging on early detection of clinically significant leaks. We conducted a multicenter retrospective cohort study of patients who underwent repair of perforated peptic ulcer between July 2016 and June 2018. We compared outcomes between those who underwent routine postoperative enteral contrast imaging and those who did not. Our analysis included 95 patients who underwent primary/omental patch repair. The mean age was 60 years, and 54% were male. Thirteen (14%) had a leak. Eighty percent of patients had a drain placed. Nine patients had leaks diagnosed based on bilious drain output without routine postoperative enteral contrast imaging. Use of routine postoperative enteral contrast imaging varied significantly between institutions (30%-87%). Two late leaks after initial normal postoperative enteral contrast imaging were confirmed by imaging after a clinical change triggered the second study. Two patients had contained leaks identified by routine postoperative enteral contrast imaging but remained clinically well. Duration of hospital stay was longer in those who received routine postoperative enteral contrast imaging (12 vs 6 days, median; P = .000). Routine postoperative enteral contrast imaging after perforated peptic ulcer repair likely does not improve the detection of clinically significant leaks and is associated with increased duration of hospital stay.


Representation of the path of a non-disintegrating capsule in the gastrointestinal tract using external scintigraphy and computer graphics.
The intestinal transit rate of a single non-disintegrating object has been measured using gamma scintigraphy. Using computer graphics, a three-dimensional visualization of the data has been developed. The display enables viewing from any angle and should be of value in assessing the effect of variables on the transit of pharmaceuticals and other materials.