Binding of common organic UV-filters to the thyroid hormone transport protein transthyretin using in vitro and in silico studies: Potential implications in health.
Several anthropogenic contaminants have been identified as competing with the thyroid hormone thyroxine (T4) for binding to transport proteins as transthyretin (TTR). This binding can potentially create toxicity mechanisms posing a threat to human health. Many organic UV filters (UVFs) and paraben preservatives (PBs), widely used in personal care products, are chemicals of emerging concern due to their adverse effects as potential thyroid-disrupting compounds. Recently, organic UVFs have been found in paired maternal and fetal samples and PBs have been detected in placenta, which opens the possibility of the involvement of TTR in the transfer of these chemicals across physiological barriers. We aimed to investigate a discrete set of organic UVFs and PBs to identify novel TTR binders. The binding affinities of target UVFs towards TTR were evaluated using in vitro T4 competitive binding assays. The ligand-TTR affinities were determined by isothermal titration calorimetry (ITC) and compared with known TTR ligands. In parallel, computational studies were used to predict the 3-D structures of the binding modes of these chemicals to TTR. Some organic UVFs, compounds 2,2',4,4'-tetrahydroxybenzophenone (BP2, Kd = 0.43 μM); 2,4-dihydroxybenzophenone (BP1, Kd = 0.60 μM); 4,4'-dihydroxybenzophenone (4DHB, Kd = 0.83 μM), and 4-hydroxybenzophenone (4HB, Kd = 0.93 μM), were found to display a high affinity to TTR, being BP2 the strongest TTR binder (ΔH = -14.93 Kcal/mol). Finally, a correlation was found between the experimental ITC data and the TTR-ligand docking scores obtained by computational studies. The approach integrating in vitro assays and in silico methods constituted a useful tool to find TTR binders among common organic UVFs. Further studies on the involvement of the transporter protein TTR in assisting the transplacental transfer of these chemicals across physiological barriers and the long-term consequences of prenatal exposure to them should be pursued.


PCBP2 promotes the development of glioma by regulating FHL3/TGF-β/Smad signaling pathway.
The purpose of this study was to investigate the role of Poly (C)-binding protein 2 (PCBP2) and the related signaling pathway in glioma progression. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were performed to measure PCBP2 messenger RNA and protein expression in glioma tissues or cells. Cell transfection was completed using Lipofectamine 2000. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Transwell assay and flow cytometry assay were used to explore the effects of PCBP2 expression on biological behaviors of glioma cells. Western blot assay was used for the detection of pathway related proteins. Expression of PCBP2 in glioma tissues and cells were higher than that in paracancerous tissues and normal cells (both p < .01). Moreover, the elevated expression of PCBP2 was significantly correlated with tumor size (p = .001) and WHO stage (p = .010). Knockdown of PCBP2 could suppress proliferation, migration and invasion of glioma cells and promote apoptosis. Besides, the expression of transforming growth factor-β (TGF-β) pathway related proteins TGF-β1, p-Smad2 and p-Smad7 were decreased following the downregulation of PCBP2. PCBP2 also inhibited FHL3 expression by binding to FHL3-3'UTR. The inhibition of FHL3 could reverse the antitumor action caused by PCBP2 silencing. In vivo assay, PCBP2 was also found to inhibit the tumor growth of glioma. PCBP2 activates TGF-β/Smad signaling pathway by inhibiting FHL3 expression, thus promoting the development and progression of glioma.


Effect of a glassy gellan/polydextrose matrix on the activity of α-D-glucosidase.
An investigation of the ability of the enzyme α-D-glucosidase to act on the substrate 4-nitrophenyl α-D-glucopyranoside (pNPG) while embedded in glassy carbohydrate matrices (deacylated gellan with polydextrose and polydextrose alone) is presented. Physicochemical characterisation of the matrices was achieved using the techniques of modulated differential scanning calorimetry, small deformation dynamic oscillation on shear, Fourier transform infra-red spectroscopy, wide angle X-ray diffraction and scanning electron microscopy. A UV-vis spectrophotometric procedure was adapted for the analysis of the activity of α-D-glucosidase in hydrolysing pNPG in the condensed carbohydrate systems. In order to derive a relationship between the structural properties of the matrix and the enzymatic activity, mechanical spectra were recorded using the combined framework of the Williams, Landel and Ferry equation with the time-temperature superposition principle. Theoretical modelling and experimental observations strongly argue for a pronounced effect of the gelling polysaccharide/co-solute mixture on enzymatic activity near the mechanical Tg of the matrix.


Effects of tissue outside of arterial blood vessels in pulse oximetry: a model of two-dimensional pulsation.
We describe a new model of pulse oximetry that addresses the disagreement between theoretical calibration curves based on Beer-Lambert's Law and test results based on human test subjects. Sources of this discrepancy include variability among human subjects, experimental conditions and the effect of optical radiation propagating in tissue surrounding arteries. Unlike the conventional model, our model considers the change in the relative proportion of light that does or does not pass through blood in pulsating vessels in addition to the change in the path length of optical radiation through the blood. Theoretical calibration curves based on this model agree with human test results and help to explain the variability between in vitro and in vivo test conditions.


Predictors of children's self-care performance: testing the theory of self-care deficit.
Orem's theory of self-care deficit proposes relationships between self-care performance and (a) basic conditioning factors, (b) self-care agency, and (c) dependent-care agent performance. The purpose of this study was to examine these proposed relationships in children. The study sample was composed of 414 students in grades 4 through 12, ages 9 through 18 years. Using regression analyses, study findings were that the variables chosen to represent the basic conditioning factors together accounted for 19% of the variance in children's self-care performance. Separately, both age and health state were significant predictors. Additionally, when self-care agency was added to the regression model, the combination accounted for 36% of the variance. A correlational analysis showed a moderate relationship between a child's self-care performance and her or his mothers' dependent-care agent performance. Future research should continue to investigate Orem's theories and the operationalization of the concepts.


The effects of Glivec on the urinary bladder excitation of rats with suprasacral or sacral spinal cord transection.
To investigate the effects of the c-kit blocker imatinib mesylate (Glivec) on the bladders of animals with suprasacral cord injury (SSCI) and sacral cord injury (SCI). We randomized 60 female Sprague-Dawley rats into control, sham, SSCI (T8/9 transection), and SCI (S1-3 transection) groups. Six weeks later, we evaluated the effects of stepwise Glivec administrations on urinary bladder contraction using cystometry and the detrusor strip stretch-test. We investigated spontaneous calcium transients of kit-positive interstitial cells of Cajal (ICCs) with the preloaded Ca(2+) indicator fluo-3AM. The expression levels of c-kit and the number of ICCs in those bladders were determined using Western blot and fluorescence staining analyses, respectively. Bladder capacity and compliance were decreased in SSCI bladders and increased in SCI bladders (P<0.05). The amplitude and frequency of spontaneous contractions of detrusor strips, the frequency and relative fluorescence intensity of the spontaneous Ca(2+) waves, and c-kit expression in the bladder were significantly increased in the SSCI group and decreased in the SCI group compared with the control and sham groups (P<0.05). The dose-dependent effects of Glivec also confirmed consistent functional variations in bladder activity. The expressions and effects of Glivec were enhanced in SSCI bladders and inhibited in SCI bladders, which may indicate potential roles of ICCs for the c-kit signaling pathway in the pathogenesis of SSCI and SCI bladder.


Immune response to COVID-19 vaccination in a population with a history of elevated exposure to per- and polyfluoroalkyl substances (PFAS) through drinking water.
Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to lower vaccine-induced antibody concentrations in children, while data from adults remains limited and equivocal. Characteristics of PFAS exposure and age at vaccination may modify such effects. We used the mass administration of novel COVID-19 vaccines to test the hypothesis that prior exposure to environmentally-relevant concentrations of PFAS affect antibody response to vaccines in adolescents and adults. Between April and June 2021, 226 participants aged 12-90 years with a history of exposure to PFAS in drinking water and who received an mRNA COVID-19 vaccine participated in our prospective cohort study. SARS-CoV-2 anti-spike and anti-nucleocapsid antibodies (IgG) were quantified before the first and second vaccine doses and again at two follow-ups in the following months (up to 103 days post dose 1). Serum PFAS concentrations (n = 39 individual PFAS) were measured once for each participant during baseline, before their first vaccination. The association between PFAS exposure and immune response to vaccination was investigated using linear regression and generalized estimating equation (GEE) models with adjustment for covariates that affect antibody response. PFAS mixture effects were assessed using weighted quantile sum and Bayesian kernel machine regression methods. The geometric mean (standard deviation) of perfluorooctane sulfonate and perfluorooctanoic acid serum concentrations in this population was 10.49 (3.22) and 3.90 (4.90) µg/L, respectively. PFAS concentrations were not associated with peak anti-spike antibody response, the initial increase in anti-spike antibody response following vaccination, or the waning over time of the anti-spike antibody response. Neither individual PFAS concentrations nor their evaluation as a mixture was associated with antibody response to mRNA vaccination against COVID-19. Given the importance of understanding vaccine response among populations exposed to environmental contaminants and the current gaps in understanding this relationship outside of early life/childhood vaccinations, our manuscript contributes meaningful data from an adolescent and adult population receiving a novel vaccination.


VOT and dysarthria: a descriptive study.
The purpose of this paper was to investigate whether voice onset time differences occurred among speakers exhibiting four different types of dysarthria. Twenty dysarthric speakers were used as subjects: five spastic, five flaccid, five ataxic, and five hypokinetic. Repeated utterance tasks using /p lambda/, /t lambda/ and /k lambda/ were analyzed using spectrography. All the speakers exhibited phonetic errors in their voice onset time productions, with voice onset times occurring in the range of values between voiced and voiceless stops. The spastic speakers exhibited shortest voice onset times while the flaccid and ataxic speakers exhibited significantly more voice onset time variability than the spastic and hypokinetic speakers. The short voice onset times exhibited by these speakers were related to the physiologic demands of voiceless stop productions.


Safety evaluation of a natural eggshell membrane-derived product.
Natural Eggshell Membrane (NEM®) is a novel dietary ingredient that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy joint and connective tissues. NEM® was evaluated for safety via in vitro and in vivo toxicological studies. This included testing for cytotoxicity, genotoxicity, acute oral toxicity, and 90-day repeated-dose oral toxicity. NEM® did not exhibit any cytotoxic effects at a dose of 100 μg in an in vitro human cell viability assay after incubation for up to 20 h. NEM® did not exhibit any genotoxic effects in an in vitro assay of four strains of histidine-dependent Salmonella typhimurium and one strain of tryptophan-dependent Escherichia coli at a dose of up to 5000 μg/plate. NEM® did not exhibit any signs of acute toxicity in rats at a single oral dose of up to 2000 mg/kg body weight, nor signs of toxicity (via urinalysis, hematology, clinical chemistry, or histopathological evaluation) in rats at a repeated oral dose of up to 2000 mg/kg body weight per day for 90 days. The results of these studies suggest that NEM® may be safe for human consumption.


Video-assisted thoracoscopic surgery in the paediatric population.
Video-assisted thoracoscopic surgery (VATS) is now widely practised in adults but there are few publications on its application in the paediatric population. Retrospective review of the authors' experience with VATS in children under 16 years old during an 18 month period in a university teaching hospital. From September 1993 to March 1994, VATS was attempted in 14 patients. Five were unsuccessful because of pleural symphysis or inability to collapse the upper lung. Ten cases of VATS were successfully performed in the remaining nine patients (eight males, one female; age range from 22 days to 15 years old). These included two drainages and limited decortications for loculated pleural effusion, one guided drainage of pericardial effusion, one thymectomy for thymic hyperplasia, three wedge resections for metastatic pulmonary osteosarcoma and three bleb excisions and pleurodesis for primary spontaneous pneumothoraces. There were no intra-operative complications. There was one death from dysrhythmia following an uneventful wedge resection. The mean duration of chest tube drainage was 1.4 days and postoperative hospital stay 2.6 days excluding two patients who stayed for further medical treatment. VATS is a useful approach in selected cases but further development of this approach awaits refinement of anaesthetic technique and endoscopic instrumentation.


Next-generation des-r-carboxy prothrombin for immunohistochemical assessment of vascular invasion by hepatocellular carcinoma.
We have previously shown the value of next-generation des-r-carboxy prothrombin (NX-DCP) for predicting vascular invasion in hepatocellular carcinoma (HCC). Since conventional DCP is inaccurate under some conditions, this study aimed to assess whether NX-DCP immunohistochemical staining was related to vascular invasion in HCC. Fifty-six patients scheduled to undergo resection for single HCC were divided into two groups, with and without pathological portal vein invasion. Immunohistochemical features of HCC and sites of vascular invasion were assessed using alpha-fetoprotein (AFP), conventional DCP, and NX-DCP. Pathological portal vein invasion was absent in 43 patients and present in 13 patients. Patient characteristics, pathological background of the liver parenchyma, and tumor-related factors did not differ significantly between the groups. There was no significant difference in the serum AFP level between the groups, whereas levels of conventional DCP (p < 0.0001) and NX-DCP (p < 0.0001) were significantly higher in the vascular invasion group. Immunohistochemical staining showed no significant difference in the staining rate of tumor (67.9% vs. 80.7%, p = 0.08), but NX-DCP stained significantly more at the sites of vascular invasion (15.4% vs. 46.2%, p = 0.01) than conventional DCP. No vascular invasion was stained by AFP. NX-DCP offers better sensitivity for detecting sites of vascular invasion than AFP and conventional DCP.


Plant dermatitis.
This review summarizes the major categories of plant dermatitis: (1) mechanical injury, (2) pharmacologic injury, (3) primary irritant phytodermatitis, (4) allergic phytodermatitis, (5) pseudophytodermatitis, (6) phytophotodermatitis, and (7) pseudophytophotodermatitis. Representative species from this classification are considered. Field characteristics, dermatitis produced, chemical constituents, and diagnosis are discussed.


Multifaceted Effects and Mechanisms of N-Acetylcysteine on Intestinal Injury in a Porcine Epidemic Diarrhea Virus-Infected Porcine Model.
This study investigates the potential effects of N-acetylcysteine (NAC) on intestinal injury in a porcine epidemic diarrhea virus (PEDV)-infected porcine model. Thirty-two piglets are randomly assigned to one of four groups: the control, PEDV, NAC, and NAC+PEDV. Piglets in the NAC+PEDV group are orally administrated with NAC (100 mg (kg·BW)-1 day-1 ) for 4 consecutive days after 2 days of PEDV infection. The results show that NAC administration decreases the diarrhea rate and improves intestinal morphology. The concentration of diamine oxidase and intestinal fatty-acid binding protein, as well as IL-1β, IL-8, and TNF-α in the plasma, is decreased by NAC. Intriguingly, NAC administration significantly increases the viral load in the jejunum and ileum and down-regulates the expression of interferon-related genes. Microarray and proteomic analyses show that the differentially expressed genes/proteins between NAC+PEDV and PEDV groups are highly enriched in substance transport. Furthermore, aquaporin 8/10 expression is significantly increased by NAC upon PEDV infection. NAC administration alleviates PEDV-induced intestinal injury by inhibiting inflammatory responses and improving substance transport, but promotes viral replication by inhibiting interferon signaling. These results suggest NAC exhibits multifaceted effects upon PEDV infection, and thus caution is required when using NAC as a dietary supplement to prevent viral infection.


Dose-dependent efficacy and safety of licogliflozin on obese adults: A systematic review and meta-analysis of randomized controlled trials.
Licogliflozin is a dual SGLT1/2 inhibitor acting on the intestine and kidney by reducing glycemic and calorie content. We aimed to determine the efficacy and safety of licogliflozin on Anthropometric measurements and cardiometabolic parameters in obese participants. We systematically searched the PubMed, Cochrane Library, Scopus, and Web of Science databases for randomized controlled trials (RCTs) relevant to our eligibility criteria. We performed a subgroup analysis based on licogliflozin doses and the diabetic state of participants. This meta-analysis was registered on PROSPERO (CRD42021286936). We identified five RCTs with a total of 905 obese and overweight participants. All participants had a weight reduction of 2.43 kg (95% CI: -3.17 to -1.69, p < 0.00001) compared with placebo. The mean difference in HbA1c of obese diabetic patients was (MD: -0.30%; 95% CI: -0.45, -0.16); I2 = 46% in favor of licogliflozin. The incidence of serious adverse events, all-cause mortality, headache, nausea, and vomiting were similar between licogliflozin and placebo (p = 0.72, 0.97, 0.09, 0.53, and 0.89, respectively). However, there was a higher incidence of diarrhea in the licogliflozin group. We found that licogliflozin was safe and tolerable. It reduces body weight significantly. Moreover, it improves glycemic control and other cardiometabolic parameters.


PREVALENCE AND PREDICTORS OF POSTTRAUMATIC STRESS DISORDER, DEPRESSION, AND ANXIETY IN PERSONNEL WORKING IN EMERGENCY DEPARTMENT SETTINGS: A SYSTEMATIC REVIEW.
Professionals working in the emergency department (ED) are regularly exposed to traumatic events. Rates of posttraumatic mental health conditions vary widely in the literature and there is no agreement that rates in ED staff are elevated relative to other populations. We conducted a systematic review of international literature reporting prevalence of posttraumatic stress disorder (PTSD), depression, and anxiety in ED personnel to determine whether prevalence is elevated compared to the general community, and to evaluate convergent evidence across the literature for predictive factors. To our knowledge, there is no comprehensive review on this topic in the literature at this time. Seven databases were searched for studies reporting rates of PTSD, depression, and anxiety in ED personnel. Two independent researchers screened studies and assessed quality using Munn's Prevalence Critical Appraisal Instrument. Best-evidence synthesis determined whether conditions demonstrated elevated prevalence compared to the general population of Canada, a conservative benchmark. Twenty-four studies from 12 countries and a combined sample size of 4768 were included. PTSD rates ranged from 0% to 23.6% (mean 10.47%), depression ranged from 0.7% to 77.1% (mean 24.8%), and anxiety rates ranged from 2.4% to 14.6% (mean 9.29%). Each condition was elevated compared to the general population. Sociodemographic variables were not consistent predictors. Elevated PTSD seemed most strongly related to workplace exposure and maladaptive coping. ED professionals have an elevated risk of experiencing PTSD, depression, and anxiety. Identification of organizational and workplace predictors are needed to inform interventions that will reduce risk and provide optimal treatment and management of PTSD, depression, and anxiety in ED settings.


The urinary bladder: An extremely rare location of pediatric neuroblastoma.
Pediatric malignant tumors in the urinary bladder are rare with a high prevalence of rhabdomyosarcomas. A 15-month-old patient was referred to the authors' center because of a urinary bladder tumor. Imaging studies disclosed a solid pelvic mass in the dome of the bladder confirmed by a cystoscopy. Surprisingly, the biopsy done during this procedure confirmed a neuroblastoma with a favorable Shimada classification. This tumor had no bad prognostic factors. But, vessel compression and local infiltration led to delayed surgery, and neoadjuvant chemotherapy was initiated. After chemotherapy, a complete surgical resection was accomplished. Currently, this patient is in complete continuous remission. Only 5 other cases have been reported. Thus, urinary neuroblastoma seems to be a very rare pediatric tumor, but it should be considered in the differential diagnoses of urinary bladder tumor.


Psychological and traumatic stress and the risk of developing diabetes and psychiatric disorders after a disaster-relief mission: An eight-year longitudinal study of Japan Maritime Self-Defense Force personnel dispatched for the 2011 Great East Japan Earthquake disaster-relief mission.
The Great East Japan Earthquake caused triple disasters-the earthquake itself, tsunamis, and nuclear leakage. Japan Maritime Self-Defense Force (JMSDF) personnel engaged in disaster-relief suffered various degrees of psychological stress, which is associated with psychiatric as well as physical disorders, such as diabetes. This study aimed to assess the effect of mission-related stress on the development of diabetes and psychiatric disorders in these personnel using JMSDF annual physical check-up data from 2010 to 2018 and Impact of Events Scale-Revised (IES-R) and Kessler Psychological Distress Scale (K-10) questionnaire data. Cox proportional hazard models were used to assess the hazard ratios (HRs) of developing diabetes and psychiatric disorders in the dispatched (N = 3686) vs. non-dispatched (N = 13,953) groups and high IES-R (score ≥25) vs. low IES-R score and high K-10 (score ≥25) vs. low K-10 score subgroups. We found a significantly higher HR of developing diabetes in the high IES-R score subgroup (2.02; 95% confidence interval [CI], 1.08-3.80). However, the HRs were not significant when comparing dispatched vs. non-dispatched groups and high vs. low K-10 score subgroups. Although the HR of developing psychiatric disorders was significantly lower in the dispatched group (0.64; 95% CI, 0.48-0.84), it was significantly higher in the high IES-R (7.95; 95% CI, 3.38-18.74) and high K-10 (8.76; 95% CI, 4.34-17.68) score subgroups. Thus, this study indicates the importance of paying closer attention to the risk of diabetes and psychiatric disorders in individuals with high IES-R or K-10 scores after disaster-relief activities.


Kinetics of antipyrine and sulfamethazine in patients recovered from dihydralazine-hepatitis.
Pharmacokinetic studies with sulfamethazine (500 mg) and antipyrine (15 mg/kg) were performed in 27 hypertonic patients (16 females, 11 males, 37-78 years) who had recovered from a dihydralazine-induced hepatitis, and 21 patients with essential hypertension (13 females, 8 males, 18-74 years) treated with antihypertonics excluding dihydralazine. 20 patients of the hepatitis group (74%) and 12 patients of the control group (57%) were slow acetylators. With regard to the pharmacokinetic parameters no differences were found in both slow and rapid acetylators between the sulfamethazine group and the antipyrine group.


Dietary diversity: case study of fruit and vegetable consumption by chiropractic patients.
A distinct health advantage has been linked with eating a wide variety of fresh fruit and vegetables. This study explores the diversity of fruits and vegetables consumed by chiropractic patients and inquires into their preferred purchasing patterns. A case study that included patients attending 24 chiropractic practices in 5 states and the Australian Capital Territory was undertaken. Seven hundred eighty-two patients were asked to complete a questionnaire providing general information about their life-style and particular information about the number of servings of fruits and vegetables that they usually consumed. Although overall chiropractic patients reported adhering to a number of healthy life-style behaviors, participants in this study would benefit from eating a greater diversity of fruits and vegetables. In view of the substantial health benefits associated with eating a wide variety of fruits and vegetables, it is suggested that chiropractic patients be encouraged to follow a color code system for purchasing their fresh produce.


Infinite cis influx of cyclic AMP into human erythrocyte ghosts.
Infinite cis uptake of cyclic AMP into red blood cell ghosts has been measured. The Koiic is calculated from two different integrated rate equations that are applicable when the substrate concentration is unsufficient to cause volume changes. Values of 0.69 mM and 0.66 mM are obtained for the infinite cis Km at 30 degrees C using these procedures. These values are only slightly higher than that predicted from zero trans net flux experiments. Lowering the temperature reduces Koiic from 0.69 mM at 30 degrees C to 0.478 mM at 20 degrees C, 0.108 mM at 10 degrees C and 0.072 mM at 4 degrees C (Q10 = 2.4). The Q10 for activation of influx permeability of 10(-5) M cyclic AMP is 1.55.


A proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes.
The incidence of bone metastasis in advanced breast cancer (BrCa) exceeds 70%. Bortezomib, a proteasome inhibitor used for the treatment of multiple myeloma, also promotes bone formation. We tested the hypothesis that proteasome inhibitors can ameliorate BrCa osteolytic disease. To address the potentially beneficial effect of bortezomib in reducing tumor growth in the skeleton and counteracting bone osteolysis, human MDA-MB-231 BrCa cells were injected into the tibia of mice to model bone tumor growth for in vivo assessment of treatment regimens before and after tumor growth. Controls exhibited tumor growth, destroying trabecular and cortical bone and invading muscle. Bortezomib treatment initiated following inoculation of tumor cells strikingly reduced tumor growth, restricted tumor cells mainly to the marrow cavity, and almost completely inhibited osteolysis in the bone microenvironment over a 3- to 4-week period as shown by [(18)F]fluorodeoxyglucose positron emission tomography, micro-computed tomography scanning, radiography, and histology. Thus, proteasome inhibition is effective in killing tumor cells within the bone. Pretreatment with bortezomib for 3 weeks before inoculation of tumor cells was also effective in reducing osteolysis. Our in vitro and in vivo studies indicate that mechanisms by which bortezomib inhibits tumor growth and reduces osteolysis result from inhibited cell proliferation, necrosis, and decreased expression of factors that promote BrCa tumor progression in bone. These findings provide a basis for a novel strategy to treat patients with BrCa osteolytic lesions, and represent an approach for protecting the entire skeleton from metastatic bone disease.


Changes in hormonal profiles during the estrous cycle in old lactating beef cows.
Patterns of concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), progesterone (P4) and estradiol-17 beta (E2) during an estrous cycle were compared between 15 lactating beef cows 5 to 7 years of age (young) and 15 cows greater than or equal to 12 years of age (old). Length of estrous cycle did not differ between young and old cows (P = .06). No differences due to age were found for LH. Patterns of concentrations of P4 during the first 15 days of the cycle, of FSH during days 6 through 12 and of E2 during the follicular phase differed with age (P less than .05). An earlier (P less than .025) midcycle elevation of FSH was associated with an earlier rise and greater concentration of E2 (P less than .05) during the follicular phase in old than in young cows. Differences in FSH and P4, although subtle, were consistent with an earlier or more advanced follicular development in old cows, leading to greater secretion of E2 from the preovulatory follicle.


Evaluation of cardioprotective effects of carvedilol in dogs receiving doxorubicin chemotherapy: A prospective, randomized, double-blind, placebo controlled pilot study.
The aim of this pilot study was to evaluate the cardioprotective effects of carvedilol in dogs receiving doxorubicin chemotherapy and provide suggestions to future studies based on results and limitations of our study. Thirteen dogs were randomized into two experimental groups: 6 dogs in carvedilol group and 7 dogs in placebo group. In carvedilol group, 0.39 mg/kg ± 0.04 twice-daily oral carvedilol was started on the day of the first doxorubicin treatment and continued throughout the chemotherapy protocol until the final cardiological evaluation. Cardiological evaluations were performed before the first doxorubicin administration and then 10 to 15 days after each subsequent dose. Troponin I and oxidative stress tests were performed with serum collected from dogs at the initial and final cardiological evaluation. Carvedilol produced some echocardiographic and electrocardiographic changes (reduced E velocity and E/IVRT ratio, as well reduced heart rate and increased PR and QT interval) due to its beta-block effect. In placebo group Doppler study showed a significant increase in mitral flow deceleration time (EDT), as well increased amplitude of the S wave in the right, and R wave in the left, precordial chest leads. There were significant difference in the EDT, E/IVRT and A' velocity, as well heart rate, PR interval and R wave in V4/CV6LU precordial chest lead between groups. In conclusion, some indexes of diastolic function and in precordial chest leads were less affected by doxorubicin in carvedilol than in control group. This suggests that carvedilol may have a beneficial effect in canine cancer patients receiving doxorubicin.


Breast-conserving therapy in breast cancer patients--a 12-year experience.
Twenty years ago prospective randomised controlled trials were initiated to compare conservative breast surgery plus radiation with radical mastectomy in the treatment of early-stage breast cancer. The results have shown no survival advantage for mastectomy over breast-conserving therapy (BCT). However, local recurrence of cancer after BCT has been reported to be as high as 14%, necessitating salvage mastectomy. This retrospective study was performed on 165 breast cancer patients undergoing BCT in the 12 years up to August 2002. Resection and intraoperative cytological assessment were used to achieve clear excision margins. Adjuvant therapy (hormones, chemotherapy) was undertaken, and the incidence and times of local recurrence and distant metastases were recorded. Ninety-four per cent of patients had clear margins at the initial operation. This was achieved irrespective of ductal carcinoma in situ alone or surrounding the cancer in 62% of cases. At a median follow-up of 65 months one patient developed local recurrence (LR) in the breast synchronously with distant relapse. Two patients had non-nodal axillary recurrences but no patient suffered LR in isolation in the treated breast. BCT is a safe alternative to mastectomy provided that the tumour is completely excised. The segment containing the cancer should be resected from the nipple to the periphery of the breast. Intraoperative cytological assessment helps to ensure clear margins. Reexcision is recommended for patients with close/involved margins.


Malacoplakia of the gallbladder.
A case of malacoplakia of the gallbladder is described. The cytoplasm of histiocytes in the gallbladder wall was filled with granules positive for periodic acid-Schiff, von Kossa's, and Perls' stains, which is highly suggestive of malacoplakia. Both local inflammation and recent neoplasia could have played a role in the histogenesis of the malacoplakia.


A novel ATPase in the chromaffin granule membrane.
The ATPase activity of the chromaffin granule membrane was found to differ profoundly from that of the mitochondrial inner membrane. First, mitochondrial ATPase is much more sensitive to low concentrations of dicyclohexylcarbodiimide than the chromaffin granule ATPase. Second, analysis of chromaffin granule preparations by immune replication revealed that mitochondrial contamination (as measured with an antibody against cytochrome c oxidase) could account for the presence of mitochondrial-type ATPase. Third, exposure of chromaffin granule preparation to sodium bromide removed the mitochondrial-type ATPase, but left over 70% of the total ATPase activity of the chromaffin granules intact. Finally, after solubilization of the chromaffin granule membranes with detergents, a novel ATPase could be separated from the mitochondrial-type ATPase. It is proposed that this novel ATPase represents most of the ATPase activity of the chromaffin granules and that the mitochondrial-type ATPase reflects contamination by mitochondria.


Abundance and diaspore weight in rare and common prairie grasses.
Abundance (g/m2) and diaspore weight are positively correlated in seven species of perennial grasses that occur in prairies. The rare grasses (<10.0 g/m2) have light dispersal units (0.06 to 1.76 mg); the common grasses (>10.0 g/m2) have heavy dispersal units (2.23 to 2.80 mg). This result is the first reported differentiating trait between related rare and common organisms occurring in same habitat.Three hypotheses that explain this phenomenon are compared; the third most likely holds. First, rare grasses may be rare because their small seeds are less successful in establishment than those of common grasses. Second, if the persistence of small populations is marginal, rare grasses may devote less energy (or other currency) to seed production. Third, rare grasses may be colonizers of spatially and temporally rare microsites appropriate for growth and thus have seeds adapted for longer distance dispersal than those of common grasses. This last hypothesis suggests a new pathway for the evolution of weeds.


Differential expression of transcripts for the autoimmunity-related human dendritic cell immunoreceptor.
Dendritic cell immunoreceptor (DCIR) deficiency is related to development of autoimmune disorders and DCIR gene polymorphisms are associated with rheumatoid arthritis (RA). We analyzed the mRNA expression from the four known transcripts of DCIR in IFN-gamma-treated human leukocytes together with fine mapping across the locus. RA patients and healthy controls were genotyped for several single nucleotide polymorphisms (SNPs) in DCIR and flanking regions. mRNA expression in peripheral blood mononuclear cells (PBMCs), stimulated with gamma-interferon (IFN-gamma) in vitro, was determined by transcript-specific PCR. Our data reveal that IFN-gamma significantly downregulates the average expression of transcripts DCIR_v1, DCIR_v2, DCIR_v3 and DCIR_v4 (P<0.0001 for v1, P<0.02 for v2, P<0.0001 for v3, P<0.001 for _v4, patients and controls, Wilcoxon signed-rank). The expression of DCIR showed significant association with variations in the gene. Cells with the RA-associated allele rs2024301 exhibit a significant increase in the expression of DCIR_v4. We also present a new fifth isoform lacking exons 2, 3 and 4. This data illustrate that common genetic variations may influence DCIR mRNA expression. We also show that the expression is regulated by the inflammatory mediator IFN-gamma, affecting all four transcripts and that this was independent of genotype.


Outcome of singleton infants delivered vaginally or by caesarean section at 23 to 28 weeks' gestation.
The survival and impairment rates of 276 inborn singleton infants of 23-28 weeks' gestation were reported according to route of delivery and mode of presentation. The Caesarean section rate was 29% overall, ranging from 13% at 25 weeks to 46% at 28 weeks. In the vertex group, no significant difference in survival or impairment rate was found between Caesarean and vaginal births. In the non-vertex group, Caesarean births had a similar survival rate but a significantly lower impairment rate compared to vaginal births. For Caesarean births, no significant difference in survival or impairment rate was found between vertex and non-vertex groups. In contrast, for vaginal births, the mode of presentation was important: the non-vertex group had a significantly lower survival rate and higher impairment rate compared to the vertex group. We found no evidence to support the use of Caesarean section in extremely preterm infants with vertex presentation, except for recognized maternal or fetal indications. The findings in the non-vertex group indicated that there is a definite need for a randomized clinical trial to investigate the possible benefits of Caesarean section in extremely preterm infants with non-vertex presentation.


Fungal Extracellular Vesicles in Interkingdom Communication.
Extracellular vesicles (EVs) have recently emerged as a key method of communication between cells. In this chapter, we examine the evidence for their role in inter-kingdom communication, in particular in the context of pathogenic fungi and their hosts. We detail what is known about modes of EV-driven communication, the consequences for host-pathogen interactions and the compositional and physical properties of the vesicles themselves. Looking forward, we point to the growing need for a detailed understanding of the heterogeneity of EV populations. This heterogeneity is likely to be key in understanding the diversity of responses to fungal infection in humans.


Complex karyotype in a low grade phyllodes tumor of the breast.
Cytogenetic analysis of a phyllodes tumor of low grade malignancy disclosed the karyotype 52-55,XX, -1,+5,+7,+9,+10,+11,-15,+18,-19,+20,der(21)t(1;21)(p13;q22),+mar1x 2-4,+mar2[cp18]/46,XX. This study shows that a complex chromosome karyotype can be found in low-grade phyllodes tumors and is not necessarily a sign of extreme malignancy of these neoplasms.


Unburned carbon as a low-cost adsorbent for treatment of methylene blue-containing wastewater.
Fly ash, natural zeolite, and unburned carbon separated from fly ash have been employed as low-cost adsorbents for dye adsorption in methylene blue-containing wastewater. It is found that the unburned carbon exhibits a much higher adsorption capacity than raw fly ash and natural zeolite. The adsorption capacities of fly ash, natural zeolite, and unburned carbon for methylene blue are 2 x 10(-5), 5 x 10(-5), and 2.5 x 10(-4) mol/g, respectively. Investigation also indicates that adsorption is influenced by initial dye concentration, particle size, dye solution pH, and adsorption temperature. Adsorption on unburned carbon increases with the initial dye concentration, solution pH, and temperature, but reduces with the increasing particle size. Kinetic studies show that adsorption of methylene blue on fly ash, natural zeolite, and unburned carbon can be best described by the pseudo-second-order adsorption model and that adsorption is a two-step diffusion process. The apparent activation energies for methylene blue adsorption on unburned carbon in the first and second diffusion processes are 12.4 and 39.3 kJ/mol, respectively.


Comparative mapping of DNA sequences in rye (Secale cereale L.) in relation to the rice genome.
The rice genome has proven a valuable resource for comparative approaches to address individual genomic regions in Triticeae species at the molecular level. To exploit this resource for rye genetics and breeding, an inventory was made of EST-derived markers with known genomic positions in rye, which were related with those in rice. As a first inventory set, 92 EST-SSR markers were mapped which had been drawn from a non-redundant rye EST collection representing 5,423 unigenes and 2.2 Mb of DNA. Using a BC1 mapping population which involved an exotic rye accession as donor parent, these EST-SSR markers were arranged in a linkage map together with 25 genomic SSR markers as well as 131 AFLP and four STS markers. This map comprises seven linkage groups corresponding to the seven rye chromosomes and covers 724 cM of the rye genome. For comparative studies, additional inventory sets of EST-based markers were included which originated from the rye-mapping data published by other authors. Altogether, 502 EST-based markers with known chromosomal localizations in rye were used for BlastN search and 334 of them could be in silico mapped in the rice genome. Additionally, 14 markers were included which lacked sequence information but had been genetically mapped in rice. Based on the 348 markers, each of the seven rye chromosomes could be aligned with distinct portions of the rice genome, providing improved insight into the status of the rye-rice genome relationships. Furthermore, the aligned markers provide genomic anchor points between rye and rice, enabling the identification of conserved ortholog set markers for rye. Perspectives of rice as a model for genome analysis in rye are discussed.


Proactive nurse management guidelines for managing intensive chemotherapy regimens in patients with advanced gastric cancer.
Patients with advanced gastric cancer have a poor prognosis. Intensive chemotherapy regimens may be effective for the treatment of this disease but may be associated with a significant number of severe adverse events. Optimal management of these adverse events can improve outcome for the patient. Currently, there is little information in the literature about the nursing management of this particular group of patients. This American study involved the nursing management of all patients with gastric or gastroesophageal cancer enrolled in clinical trials at a single center. Patients had close contact with research nurses and received education about adverse events and how to deal with them. Patients completed a detailed treatment diary for each cycle of treatment. Protocols were established for the management of emergent adverse events. The guidelines developed during this study could help to underpin the role of the specialist oncology nurse and improve the management of patients undergoing intensive chemotherapy for gastric and gastroesophageal cancer, with the potential of improving outcome, or at least quality of life, for the patients. The nurses' role should be pivotal in the management of intensive chemotherapy for gastric and gastroesophageal cancer.


Obstructive sleep apnea in Parkinson's disease: A prevalent, clinically relevant and treatable feature.
Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by motor and non-motor symptoms, including obstructive sleep apnea (OSA), a common comorbid sleep disorder. The prevalence of OSA in PD is high, and its impact on quality of life, accident risk, and limited treatment options underscores the need for vigilant monitoring and effective interventions. OSA is observed in 20-70% of PD patients, whereas the general population exhibits a lower prevalence ranging from 2 to 14%. These discrepancies in prevalence may be attributed to differences in demographic characteristics, sample sizes with selection bias, and variations in scoring systems for apnea and hypopnea events used across different studies. This review highlights the potential pathogenesis of comorbid OSA in PD and provides an overview of ongoing clinical trials investigating interventions for this condition. Several mechanisms have been implicated in the development of OSA in PD, including intermittent hypoxemia, sleep fragmentation, alterations in the glymphatic system homeostasis, upper airway obstruction, and inflammation. Given the adverse effects of PD comorbid OSA, early intervention measures are crucial. It is imperative to conduct longitudinal studies and clinical trials to elucidate the pathogenesis and develop novel and effective interventions for OSA in PD patients. These efforts aim to delay the progression of PD, enhance patients' quality of life, and alleviate the burden on society and families.


Effects of exercise and training on blood rheology.
The effects of exercise on the rheological properties of blood have not received much research attention. Recent, limited evidence indicates that the viscosities of whole blood and plasma increase in response to a variety of exercise protocols. The increase in whole blood viscosity is mainly attributed to an increase in haematocrit and plasma viscosity, whereas the deformability and aggregability of red blood cells remain unaltered. The increases in plasma viscosity and haematocrit have been ascribed to exercise-induced haemoconcentration as a result of fluid transfer from the blood to the interstitial spaces. Although the long term effects of endurance training on blood rheology have been very briefly examined, the exact effect of training has not as yet been determined. However, available cross-sectional and longitudinal studies indicate that the blood of endurance athletes is more dilute and this has been attributed to an expansion of plasma volume as a result of training. It has been suggested that this blood dilutional effect of endurance training may be advantageous in delivering oxygen to the exercising muscles because of a reduced resistance to blood flow. The increase in plasma volume may also contribute to the body water pool and help offset dehydration. The influence of strength and power training on blood rheology is not known.


Distinct local immunogenic stimuli dictate differential requirements for CD4+ and CD8+ T cell subsets in the pathogenesis of spontaneous autoimmune diabetes.
The strong MHC class II association in human as well as murine Type 1 diabetes (T1D) suggests a central role for CD4+T cells in the disease pathogenesis. Nonetheless, CD8+T cells also play a role in the pathogenic process. We describe how CD4+ or CD8+T cells can contribute differentially to the pathogenesis of T1D using the HLA-DQ8 transgenic mouse models. HLA-DQ8 transgenic mice expressing the costimulatory molecule, B7.1 (RIP.B7.1), or the proinflammatory cytokine, TNF-alpha (RIP.TNF) or both (RIP.B7.RIP.TNF) under the control of rat insulin promoter (RIP) were used. Our observations indicate that in the RIP-B7 model, CD4+T cells were absolutely required for diabetes to occur. However, when CD8+ T cells were also present, the incidence of diabetes increased. On the other hand, in the RIP-TNF model, CD8+T cells were absolutely required for diabetes to occur. Interestingly, when CD4+T cells were also present, the incidence of diabetes decreased. In the RIP-B7.RIP-TNF double transgenic mouse model, either CD4+ or CD8+T cells were sufficient to precipitate diabetes in 100% of the animals. Thus, the relative roles of CD4+ or CD8+T cells in the pathogenesis of T1D are possibly determined by the local inflammatory stimuli.


Risks and complications of clinical cardiac electrophysiologic studies: a prospective analysis of 1,000 consecutive patients.
The complications of clinical cardiac electrophysiologic studies were prospectively evaluated in 1,000 consecutive patients studied in one laboratory with an unaltered protocol to better assess the risks of this procedure. There were 728 men and the mean age of the entire group was 58 years (range 16 to 84). Coronary artery disease was the most common type of heart disease (56%) and 200 patients had no identifiable organic heart disease. The indication for study was a ventricular tachyarrhythmia or cardiac arrest in 582 patients. Each patient underwent an initial (baseline) study and 444 patients underwent serial drug studies (2.7/patient). There was one death during these studies. Other major complications included arterial injury (0.4%), thrombophlebitis (0.6%), systemic arterial embolism (0.1%), pulmonary embolism (0.3%) and cardiac perforation (0.2%). Significant arrhythmic complications included catheter-induced permanent complete atrioventricular (AV) block in 1 patient, nonclinical atrial fibrillation that required therapy in 10 patients and severe proarrhythmic events in 12 (3%) of 397 patients undergoing drug studies for ventricular tachyarrhythmias. Cardioversion was required for termination of ventricular tachyarrhythmias in 179 baseline studies (53% of patients with inducible arrhythmia), and in an additional 35 patients, cardioversion was required at least once during follow-up studies. Although clinical cardiac electrophysiologic studies are associated with complications, the risks are small and acceptable.


Microbial circadian clocks: host-microbe interplay in diel cycles.
Circadian rhythms, observed across all domains of life, enable organisms to anticipate and prepare for diel changes in environmental conditions. In bacteria, a circadian clock mechanism has only been characterized in cyanobacteria to date. These clocks regulate cyclical patterns of gene expression and metabolism which contribute to the success of cyanobacteria in their natural environments. The potential impact of self-generated circadian rhythms in other bacterial and microbial populations has motivated extensive research to identify novel circadian clocks. Daily oscillations in microbial community composition and function have been observed in ocean ecosystems and in symbioses. These oscillations are influenced by abiotic factors such as light and the availability of nutrients. In the ocean ecosystems and in some marine symbioses, oscillations are largely controlled by light-dark cycles. In gut systems, the influx of nutrients after host feeding drastically alters the composition and function of the gut microbiota. Conversely, the gut microbiota can influence the host circadian rhythm by a variety of mechanisms including through interacting with the host immune system. The intricate and complex relationship between the microbiota and their host makes it challenging to disentangle host behaviors from bacterial circadian rhythms and clock mechanisms that might govern the daily oscillations observed in these microbial populations. While the ability to anticipate the cyclical behaviors of their host would likely be enhanced by a self-sustained circadian rhythm, more evidence and further studies are needed to confirm whether host-associated heterotrophic bacteria possess such systems. In addition, the mechanisms by which heterotrophic bacteria might respond to diel cycles in environmental conditions has yet to be uncovered.


COVID-19 and the risk of Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis.
The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on the healthcare system, economy, and society. Studies have reported that COVID-19 may cause various neurologic symptoms, including cognitive impairment. We aimed to assess the causal effect of COVID-19 on neurodegenerative diseases using two-sample Mendelian randomization (MR) study. Genetic variants were obtained from genome-wide association studies (GWAS) summary-level data and meta-analyses. We used the inverse variance-weighted (IVW) method as the primary analysis to estimate causal effects. Sensitivity analyses were performed to make the conclusions more robust and reliable. We found that the COVID-19 infection phenotype was associated with a higher risk of AD and inverse associated with the risk of ALS and MS. The hospitalized COVID-19 phenotype was associated with the risk of AD and wasn't associated with ALS and MS. We also found that the severe COVID-19 (main analysis) phenotype was associated with the AD outcome from UK biobank datasets but was not associated with other outcomes. The severe COVID-19 infection phenotype, the severe COVID-19 (subtype analysis) phenotype and the hospitalization risk of COVID-19 were not associated with each outcome. This MR study suggests a potential association between genetically predicted COVID-19 and a higher risk of AD and a reduced risk of ALS and MS. Further elucidations of this association and underlying mechanisms may inform public health messages to prevent COVID-19 and AD.


Deletion of NH2- and COOH-terminal sequences destroys function of the Ca2+ ATPase of rabbit fast-twitch skeletal muscle sarcoplasmic reticulum.
Deletion mutants of the Ca2+ ATPase of rabbit fast-twitch skeletal muscle sarcoplasmic reticulum (SERCA1a) were constructed and expressed in COS-1 cells. The mutants were expressed at levels 7- to 15-fold lower than the wild-type and were inactive. In vitro transcription-translation-insertion experiments showed that deletion of transmembrane sequences M1 and M2, but not of M8, M9, M10 or the NH2-terminal 30 amino acids inhibited the stable insertion of the enzyme into the membrane. Thus there was no correlation between loss of function and membrane insertion. A signal sequence for membrane insertion may exist in M1 and M2.


Compulsory notification of injuries in aesthetic procedures. Impact on patient safety.
The disparity between the number of aesthetic procedures performed worldwide, and the complications described in the literature is remarkable. Doubts regarding the underreporting are reasonable and should be considered. The aim of this study is to demonstrate the scarcity of scientific publications on complications in aesthetic procedures compared to the abundance of these procedures performed worldwide. Based on this knowledge, it will be demonstrated to the health authorities the importance of compulsory notification of complications in aesthetic procedures that require medical attention so that the available data will allow their prevention. The limitation of knowledge regarding complications was demonstrated in the data collection for the preparation of the thesis "Deaths Related to Liposuction in Brazil" presented in 2018 and published in Surgical and Cosmetical Dermatology in 2020. The definition of complication in aesthetic procedures needs to be objective to prevent different and subjective interpretations. With the compulsory notification of complications in aesthetic procedures, it is intended to learn about their causes to develop guidelines for their prevention.


Suitability of environmental indices in assessment of soil remediation with conventional and next generation washing agents.
Remediation of soils contaminated with metal must ensure high efficiency of metals removal, reduce bioavailability of residual metals and decrease ecological risk. Thus, for comprehensive environmental soil quality assessment, different indices must be used. In this study, suitability of 8 indices was used for soil highly contaminated with Cu (7874.5 mg kg-1), moderately with Pb (1414.3 mg kg-1) and low with Zn (566.1 mg kg-1), washed in batch and dynamic conditions with both conventional and next-generation washing agents. The following indices were used: modified contamination factor (mCf), modified contamination factor degree (mCdeg), mobility factor (MF), reduced partition index (IR), potential ecological risk factor (Er,Z), modified potential ecological risk factor (Er,m), potential ecological risk index (RIZ) and modified ecological risk index (RIm). For mCf, mCdeg and IR own classification scale was proposed. It was proven that most useful indices for assessment of soil pollution with metals were mCf and mCdeg. The mCf together with the IR allow to simultaneous assessment of soil pollution and stability for individual metals. These indices were appropriate for soil contaminated with different concentrations of metals, washed under both hydrodynamic conditions using various washing agents and different effectiveness of metals removal. Thus, they may be considered as most useful for evaluation of remediation method, feasibility of washing agent and assessing soil quality after washing.


Retrobulbar hemodynamic parameters in open-angle and angle-closure glaucoma patients.
The purpose of this study is to compare the retrobulbar hemodynamic parameters in the ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary arteries (PCA), in open-angle glaucoma (OAG) and angle-closure glaucoma (ACG) patients. A total of 52 eyes from 52 patients with OAG and 25 eyes from 25 ACG patients who met the inclusion/exclusion criteria were included in this cross-sectional study. Peak-systolic velocity, end-diastolic velocity, and Pourcelot resistivity index (RI) were assessed in the OA, CRA, and PCA. Intraocular pressure (IOP) was measured both with the Goldmann applanation tonometer (GAT) and with the Dynamic Contour tonometer (DCT) three times, respectively. Ocular pulse amplitude was measured using DCT. The RI was significantly higher in both the ophthalmic and short PCA in the OAG patients as compared with that in those ACG patients, P=0.003 and 0.048, respectively. There was no correlation between the IOP measured with GAT and the retrobulbar hemodynamic parameters in either OAG or ACG. There was an increased resistance to blood flow in the OA of OAG as compared with ACG patients. Additionally, the degree of circulatory disturbance was not related to either the IOP or the visual-field damage.


Differences in intraoperative and surgical outcomes between normotensive pheochromocytomas and sympathetic paragangliomas (PPGLs) and hypertensive PPGLs: results from the PHEO-RISK STUDY.
To compare the intraoperative and surgical outcomes of normotensive pheochromocytomas and sympathetic paragangliomas (PPGLs), hypertensive PPGLs and non-PPGL adrenal lesions. This a retrospective multicenter cohort study of patients with PPGLs from 18 tertiary hospitals. A control group of histologically confirmed adrenocortical adenomas (non-PPGL group) was selected to compare intraoperative and surgical outcomes with of the normotensive PPGLs. Two hundred and ninety-six surgeries performed in 289 patients with PPGLs were included. Before surgery, 209 patients were classified as hypertensive PPGLs (70.6%) and 87 as normotensive PPGLs. A higher proportion of normotensive PPGLs than hypertensive PPGLs did not receive alpha presurgical blockade (P = 0.009). When we only considered those patients who received presurgical alpha blockers (200 hypertensive PPGLs and 76 normotensive PPGLs), hypertensive PPGLs had a threefold higher risk of intraoperative hypertensive crisis (OR 3.0 [95% 1.3-7.0]) and of hypotensive episodes (OR 2.9 [95% CI 1.2-6.7]) than normotensive PPGLs. When we compared normotensive PPGLs (n = 76) and non-PPGLs (n = 58), normotensive PPGLs had a fivefold higher risk of intraoperative complications (OR 5.3 [95% CI 1.9-14.9]) and a six times higher risk of postoperative complications (OR 6.1 [95% CI 1.7-21.6]) than non-PPGLs. Although the risk of intraoperative hypertensive and hypotensive episodes in normotensive PPGLs is significantly lower than in hypertensive PPGLs, normotensive PPGLs have a greater risk of intraoperative and postoperative complications than non-PPGL adrenal lesions. Therefore, it is recommended to follow the standard of care for presurgical and anesthetic management of PPGLs also in normotensive PPGLs.


[Antiasthma therapy with laser radiation of the stellate ganglia].
The authors present a 42-case series of bronchial asthma treated with laser therapy. The technique consists in the use of a diode laser with transcutaneous irradiation projected anteriorly into stellar ganglion. The clinical cases are presented together with the therapeutical results, pointing out how children are more receptive to this therapy and outlining the importance of timing and hour of treatment.


Plasmid transfer from Streptomyces to Mycobacterium smegmatis by spontaneous transformation.
Hybrids of the Streptomyces coelicolor conjugative plasmid SCP2* and the Mycobacterium plasmid pAL5000 were transferred from Streptomyces coelicolor or Streptomyces lividans to Mycobacterium smegmatis mc2155 in plate crosses. Inactivation of the SCP2* transfer function did not prevent or reduce plasmid transfer. This transfer was DNase I sensitive and thus involved release of DNA from Streptomyces, followed by transformation of M. smegmatis. M. smegmatis growing on specific solid media was also transformed by pure CCC and linear plasmid DNA. Small plasmids were taken up intact but large plasmids suffered deletions. Competence developed within 24 h of incubation at 30 degrees C or 37 degrees C, and up to 400 transformants were obtained per microg of CCC plasmid DNA. Transformation frequencies were higher when M. smegmatis was co-cultivated with plasmid-free Streptomyces, but unaffected by resident homologous sequences or inactivation of recA in M. smegmatis. Spontaneous transformation was also observed with a circular Streptomyces transposable element which inserted into chromosomal sites. Transformative plasmid transfer was also shown to occur between M. smegmatis strains. This is the first report of non-artificially induced, spontaneous plasmid transformation in Mycobacterium.


Endarterectomy as the procedure of choice for atherosclerotic occlusive lesions of the common femoral artery.
Isolated atherosclerotic lesions of the common femoral artery, though uncommon, are frequently associated with disabling peripheral ischemic symptoms when compared with similar lesions in the superficial femoral artery since claudication involves the thigh and calf and usually limits walking distance to less than one block. From 1969 to 1987, 29 patients underwent common femoral endarterectomy with vein patch angioplasty for symptoms of disabling claudication in 17, rest pain in 6 and ischemic ulceration in 6 patients. Endarterectomy was confined to the common femoral artery in 10 patients whereas endarterectomy was carried into either or both the deep or superficial femoral arteries in 19 patients. There was one immediate failure, secondary to residual disease in the outflow tract. All patients were discharged with patent reconstructions. Amputations were avoided in the 12 patients with advanced ischemic symptoms. Patients were followed long-term. Three patients were lost to follow-up with patent repairs to that time. There was one late occlusion. The cumulative patency rate 5 years postoperatively was 94 percent. The only complication was aneurysmal dilatation of the end-arterectomy site in one patient.


An Update on Temporal Bone Paragangliomas.
Temporal bone paragangliomas (TBPs) are indolent, classically benign and highly vascular neoplasms of the temporal bone. There are two types of TBPs, tympanomastoid paragangliomas (TMPs) and tympanojugular paragangliomas (TJPs). The most common symptoms are hearing loss and pulsatile tinnitus. Diagnostic workup, besides conventional physical and laboratory examinations, includes biochemical testing of catecholamine and genetic testing of SDHx gene mutations as well as radiological examination. Although surgery is traditionally the mainstay of treatment, it is challenging due to the close proximity of tumor to critical neurovascular structures and thus the high risk of complications, especially in patients with advanced lesions. Radiotherapy and active surveillance have been increasingly recommended for selected patients. Decision on treatment should be made comprehensively. Curative effect depends on various factors. Long-term follow-up with clinical, laboratory, and radiological examinations is essential for all patients.


Online registry of genetic and clinical immunodeficiency diagnostic laboratories, IDdiagnostics.
Primary immunodeficiencies (IDs) are caused by inherited genetic defects leading to intrinsic defects in cells of the immune systems. Most IDs are rare diseases and can be difficult to diagnose because similar symptoms characterize several disorders. Mutation detection is the most reliable method in such cases. These tests are not available at most centers and physicians can have difficulties in finding laboratories that could analyze the genetic defects because certain genes are possibly analyzed by just one laboratory. The IDdiagnostics registry has been established to provide information for physicians and other health care professionals. The database at http://bioinf.uta.fi/IDdiagnostics contains currently information for the analysis of defects in 30 ID-related genes. Another part of IDdiagnostics is a database of clinical tests. Laboratories performing these analyses, either gene or clinical tests, are asked to submit their information to the database by using a printed form or electronic submission at http://bioinf.uta.fi/cgi-bin/submit/IDClini.cgi. The clinical test database contains information about tests for clinical data, immune status, and studies of function, antibody response, cell function, enzyme assays, clinical function, and apoptosis assays. Both the services are freely available and regularly updated. The services aim at increasing the awareness of IDs and helping to obtain exact and early diagnosis.


Interaction of granulocytes and endothelial cells upon stimulation with tumor necrosis factor-alpha: an ultrastructural study.
By the production of microbicidal agents, such as reactive oxygen species, activated PMN are capable of inducing tissue damage in the host. TNF-alpha was recently shown to be a potent activator of PMN oxidative metabolism. To further evaluate the interaction between activated PMN with physiological target cells, the effect of human PMN on cultured bovine aortic and human umbilical vein endothelial cells (EC) upon stimulation with human TNF-alpha was investigated by ultrastructural techniques: Scanning and transmission electron microscopy (SEM and TEM resp.) and ultrastructural detection of H2O2 production. When isolated PMN were added to EC in the presence of recombinant human TNF-alpha (10(3) U/ml) the EC-monolayer was disrupted within 4 h and EC changed their shape by exhibiting a spindle-like structure. PMN were seen in the intercellular spaces. Release of H2O2 was observed at the surface of the PMN plasma membrane, the luminal part of the small intracytoplasmic vacuoles in the PMN as well as in the contact zone between PMN and EC, but not within the EC. Scavengers of reactive oxygen species, such as superoxide dismutase and catalase or D-mannitol failed to block the effect of TNF-alpha-stimulated PMN on EC. In contrast, addition of NaN3 (0.1 mM), an inhibitor of myeloperoxidase activity, almost completely inhibited the disruption of EC-monolayers. Subsequent addition of NaN3-insensitive horseradish peroxidase reconstituted the effect. The results obtained suggest that TNF-alpha-stimulated PMN effectively cause the disruption of EC monolayers by an adherence-dependent mechanism which is mediated by the release of myeloperoxidase. The results may be of major importance for the pathogenesis of inflammatory vascular reactions.


Requirement of water-flow for sustainable growth of Pocilloporid corals during high temperature periods.
Reef-building corals are threatened worldwide by mass-scale coral bleaching episodes that are pronounced in high sea surface temperature (SST) conditions. Although water-flow has been suggested to be a mitigating factor for bleaching, long-term effects of flow-mediated bleaching suppression are as yet not fully understood. In order to investigate flow effects, we monitored the corals Pocillopora damicornis and Stylophora pistillata grown for 20 months in experimental outdoor flumes with the flow rates of 20 cms(-1) (flow) and <3 cms(-1) (still). Although bleaching was observed under high SST conditions, both species showed a shorter period or entirely no visible bleaching under the flow conditions. Better colony growth was found in the flow conditions whereas significant growth suppression and higher mortality were observed in still conditions. We conclude that water-flow is an essential environmental factor for the corals P. damicornis and S. pistillata, especially under high SST conditions.


A CpG oligodeoxynucleotide acts as a potent adjuvant for inactivated rabies virus vaccine.
To develop a CpG containing oligodeoxynucleotide (CpG ODN)-enhanced rabies vaccine for stimulating an earlier production of rabies virus neutralizing antibody (RVNAb) with high titers, we designed a CpG ODN (BW006) and evaluated its adjuvant activities in enhancing the immune response to rabies vaccine with or without aluminum in mice. It was found that BW006 could facilitate the rabies vaccine to induce an earlier and more vigorous RVNAb response, resulting in more effective protection of mice from rabies virus challenge. In addition, three shots of rabies vaccine with BW006 induced compatible RVNAb level with that induced by five shots of aluminum-adjuvanted rabies vaccine. These data reveal that BW006 could be used as a promising adjuvant to replace of or combine with aluminum for developing more effective rabies vaccines.


Postpartum contraceptive planning of women with substance abuse disorders.
Women with substance abuse disorders have lower use of contraception. Unplanned pregnancies increase risk of fetal exposure to addictive and teratogenic substances. Postpartum inpatient periods for these women can be challenging times to facilitate contraception planning. To explore postnatal contraceptive planning practices, patient preferences for contraception, and supply challenges, and to identify how clinical pharmacists may best provide care in this context. A tertiary maternity referral hospital in metropolitan Victoria, Australia (January 2015-December 2018). A retrospective cohort study was conducted on postnatal women with substance abuse disorders. Patients were excluded if they had delivered at another health service, had inadequate documented evidence of a substance abuse disorder, or had incomplete or unavailable medical records. Records were reviewed for demographic data, admission details, and documented contraceptive planning. Documented contraceptive planning, patient contraception preferences and identified supply challenges. Ninety-three women were included. Seventy-one (76.3%) had psychiatric disorders or impairments, and 92 (98.9%) had identifiable follow-up challenges (eg. Homelessness). Nine (9.7%) self-discharged/absconded. Eighty-seven (93.5%) had documented postnatal contraception discussions. Sixty-two of 87 (71.3%) considered a medicine/device, three (3.4%) preferred condoms, 10 (11.5%) considered sterilisation, 2 (2.3%) preferred no contraception, and 16 (18.4%) undecided. Etonogestral 68 mg implants were most commonly prescribed (28 of 42; 66.7%). Inpatient postpartum periods for this cohort were characterised by psycho-social complexities, inconsistent contraceptive planning documentation, and patients seemingly unprepared to consider contraception. This study highlights a need for an earlier decision-making process and pragmatic counselling with antenatal pharmacists.


Myopia in Bulgarian school children: prevalence, risk factors, and health care coverage.
The prevalence of myopia has increased in recent years, with changes being dynamic and uneven in different regions. The purpose of this study is to evaluate the prevalence of visual impairment caused by myopia in Bulgarian school children, associated risk factors, and health care coverage. A cross-sectional study among 1401 children (mean age 10.38, standard deviation 2.70) is conducted in three locations in Bulgaria from 2016 to 2020. Refractive error is measured with an auto-refractor in the absence of cycloplegia, the visual acuity is assessed without refractive error correction. A paper-based preliminary questionnaire is used to collect data on previous eye examinations, prescribed optical vision correction, regularity of wearing corrective glasses and risk factors. Children with myopic objective refraction ≤ -0.75 D and decimal visual acuity ≤ 0.8 on at least one of the eyes are 236 out of 1401 or 16.85%. The prevalence of myopia varies depending on age, geographical location, and school profile. The rate of myopic children in age group 6-10 is 14.2% compared to 19.9% in age group 11-15. The prevalence of myopic children in the urban populations is 31.4% (capital) and 19.9% (medium-sized town) respectively, and only 8.4% in the rural population. Our results show 53% increase of the prevalence of myopia in the age group 11-15 compared to a 2009 report. The analysis of data associated with health care coverage factors of all myopic pupils shows that 71.6% had a previous eye examination, 43.2% have prescription for corrective glasses, 27.5% wear their glasses regularly. Risk factors for higher odds of myopia are gender (female), age (adolescence), and parents with impaired vision. Residence in a small town and daily sport activities correspond to lower odds for myopia. The screen time (time in front of the screen calculated in hours per day) is self-reported and is not associated with increased odds of myopia when accounted for the other risk factors. The prevalence of myopia in this study is higher compared to previous studies in Bulgaria. Additional studies would be helpful in planning adequate prevention and vision care.


Binding of D-glucose to insulin.
Binding of D-glucose to insulin has been studied by equilibrium dialysis. The binding is not very specific and probably takes place in two steps. The average amount of glucose molecules bound per insulin molecule is eight, two molecules in the first and six during the second step of binding. The intrinsic binding constants for both steps are almost the same (6-10-2 M-minus 1 and 1-10-3 M-minus 1) which can be explained by assuming: (1) that after binding of the first two molecules a conformational change of insulin occurs which facilitates the binding of the next six molecules of D-glucose; or (2) that in the second step of binding the glucose binds to hydrophobic regions which are unmasked by dissociation of the insulin dimer. Using a three-dimensional model of the insulin molecule areas of the protein molecule where binding of glucose can occur were selected. The glucose-binding site very probably involves the area at the insulin surface where most of the invariant and modification-selective residues are present.


Delayed aortic rupture after aortic endograft placement in patient with spinal hardware.
Aortic injuries presenting in a delayed fashion after attempted repair of an acute injury are uncommon. We report a case of a patient presenting with an initial aortic injury associated with thoracic spinal hardware placement, which was repaired with an open and endovascular approach, and 5 months later presented with hemoptysis. The cause of hemoptysis was erosion of the descending thoracic aorta between the spinal hardware and the thoracic endograft. The patient underwent descending aorta replacement with a Dacron tube graft, removal of the hardware, and coverage with a pedicled omental flap. This is a unique presentation of erosion of the aorta between the spinal hardware and the earlier placed endovascular stent-graft.


Irregularly calcified eggs and eggshells of Caiman latirostris (Alligatoridae: Crocodylia).
We describe irregularly calcified egg and eggshell morphologies for the first time in nests of the broad-snouted caiman, Caiman latirostris. Research is based on detailed descriptions of 270 eggs from a total sample of 46,800 collected between 2005 and 2011 in Santa Fe Province, Argentina, and encompasses animals from both natural habitats and held in captivity. We discuss possible reasons for the occurrence of eggs with different mineralisation patterns in our extensive C. latirostris field sample and its conservation significance; the chemistry of egg laying in amniotes is sensitive to environmental contamination which, in turn, has biological implications. Based on our egg sample, we identify two caiman eggshell abnormalities: (1) regularly calcified eggs with either calcitic nodules or superficial wrinkles at one egg end and (2) irregularly calcified eggs with structural gaps that weaken the shell. Some recently laid clutches we examined included eggs with most of the shell broken and detached from the flexible membrane. Most type 1 regularly calcified eggs lost their initial calcified nodules during incubation, suggesting that these deposits do not affect embryo survival rates. In contrast, irregularly calcified caiman eggs have a mean hatching success rate of 8.9% (range 0-38%) across our sample compared to a mean normal success of 75%. Most irregularly calcified caiman eggs probably die because of infections caused by fungi and bacteria in the organic nest material, although another possible explanation that merits further investigation could be an increase in permeability, leading to embryo dehydration.


Glycopyrrolate versus atropine for preventing bradycardia induced by neostigmine injection after general anesthesia surgery: a randomized open, parallel-controlled multicenter clinical trial.
With atropine as a positive control, randomized controlled clinical trials were conducted to verify the efficacy of glycopyrrolate injection in preventing bradycardia caused by neostigmine. Patients undergoing elective general anesthesia and non-cardiac surgery were randomly divided into an experimental group (129 cases) and control group (127 cases) (ChiCTR2100046022, http://www.chictr.org.cn/showproj.aspx?proj=126075). At the end of the operation, the test group was given glycopyrrolate 6 ug/kg + neostigmine 0.04 mg/kg, and the control group was given atropine 0.016 mg/kg + neostigmine 0.04 mg/kg, bolus time 1 min, to antagonize muscle residual effects of relaxants. We compared the area under the time curve (AUC) of the difference between heart rate and baseline heart rate within 15 minutes of administration, the measured value of heart rate per minute, and the change in heart rate compared with baseline. We verified the safety of glycopyrrolate injection through laboratory tests, clinical symptoms, signs, and adverse events/serious adverse events. The AUC of the experimental group's heart rate within 15 minutes after the administration was lower than the baseline heart rate change value, (P<005). The measured value of the heart rate at each time changed less than the control group; the experimental group's heart rate remained at the baseline level for longer than the control group (P<005). There was no significant difference in the incidence of adverse reactions between the two groups of patients (P>005). Glycopyrrolate and atropine are safe to prevent heart rate slowing induced by the non-depolarizing muscle relaxant antagonist neostigmine, and glycopyrrolate is more conducive to maintaining a stable heart rate in patients.


Visually confirmed post-systolic shortening during the recovery period in four cases of Takotsubo cardiomyopathy.
We report visually confirmed post-systolic shortening (PSS) during the recovery period and the relationship between PSS and electrocardiographic abnormalities in 4 cases of Takotsubo cardiomyopathy (TTC). In these 4 cases, the appearance of visually confirmed PSS during the recovery period coincided with observation of the deepest T wave and the longest QT interval. The transmural repolarization gradient and heterogeneous duration of myocardial contractions may cause PSS in the TTC recovery period.


Expression of the FGF-related proto-oncogene int-2 during gastrulation and neurulation in the mouse.
The proto-oncogene int-2 has been implicated in the formation of mouse mammary-tumour-virus-induced mammary tumours. Analysis of the predicted coding sequence indicates that int-2 is a member of the fibroblast growth factor family. Previous studies using Northern blot analysis suggested that normal expression of int-2 may be confined to extra-embryonic endoderm lineages of embryonic stages of mouse development. We have used in situ hybridization and Northern blot analysis to examine directly int-2 expression in embryo stem cells and in the developing embryo from early gastrulation to midsomite stages. Complex patterns of accumulation of int-2 RNA were observed in embryonic and extra-embryonic tissues. The data suggest multiple roles for int-2 in development which may include migration of early mesoderm cells and induction of the otocyst.


Bovine interleukin 2: cloning, high level expression, and purification.
We utilized a human IL2 probe to isolate bovine IL2 sequences from a lymph node cDNA library. Bovine IL2 was subsequently expressed in both bacteria and yeast. Using a rapid, two-step purification scheme, we have been able to isolate over 20 mg/l of homogenous bovine rIL2 secreted from the yeast. The availability of sizable quantities of bovine rIL2 should make it possible to ascertain potential therapeutic or prophylactic utility of this lymphokine in cattle.


New tetradecyltrimethylammonium-selective electrodes: surface composition and topography as correlated with electrode's life span.
Two conventional plastic membrane electrodes that are selective for the tetradecyltrimethylammonium cation (TTA) have been prepared. The ion exchangers of these sensors were the ion associate, TTA-PT, and the ion aggregate, TTA-PSS, where PT and PSS are phosphotungstate and polystyrene sulfonate, respectively. The following performance characteristics of the TTA-PT- and TTA-PSS-containing electrodes were found: conditioning time of 30 and 20 min; potential response of 58.2 and 61.1 mV/TTA concentration decade; rectilinear concentration ranges of 2.0 × 10(-5)-5.0 × 10(-2) and 1.5 × 10(-5)-7.9 × 10(-2) mol L(-1); average working pH ranges of 4.0-10.5 and 3.8-10.7; life spans of 20 and 28 weeks, and isothermal temperature coefficients of 4.44 × 10(-4) and 6.10 × 10(-4)V/°C, respectively. Both electrodes exhibited high selectivity for TTA with an increasing number of inorganic and quaternary ammonium surfactant cations. These electrodes have been successfully applied to assay an antiseptic formulation containing TTA. Surface analyses using electron microscopy and X-ray photoelectron spectroscopy were used to determine the cause of the limited life span of plastic membrane electrodes.


Partial consumption of prey: the significance of prey water loss on estimates of biomass intake.
A number of studies on the feeding behaviour of sucking predators have estimated the weight of biomass the predator extracts from the prey by measuring the weight change occurring in the prey. This method does not consider that a proportion of the prey weight change is lost to the immediate environment. I examined the spider Diaea sp. feeding on the fruit fly Drosophila immigrans and found that the prey lost approximately 28% more weight than the predator gained. This difference was largely explained by water loss from the prey. My results suggest that water loss, which is not available to the predator, is an important part of prey weight loss. To avoid overestimating predator biomass gain it is necessary to measure the predator weight gain directly or take into account water loss as a component of prey weight change.


Multiomic Medulloblastomas.
Epigenomics and transcriptomics of medulloblastoma-an important childhood brain tumor-segregate the disease into four clinically relevant subtypes. In this issue of Cancer Cell, Archer et al. and Forget et al. add the proteome to our multiomic map of this disease, revealing posttranscriptional and posttranslational variations with potential therapeutic implications.


A dystrophin missense mutation showing persistence of dystrophin and dystrophin-associated proteins yet a severe phenotype.
A muscle biopsy from an X-linked muscular dystrophy pedigree showed normal dystrophin and dystrophin-associated proteins. Linkage to multiple markers within the dystrophin gene (LOD=2.7, theta=0) indicated a primary dystrophinopathy. Sequencing of the entire dystrophin RNA revealed a single missense mutation (D3335H) in the unique carboxyl-terminal domain. This is the first report showing that a relatively severe dystrophinopathy can occur despite the correct localization of dystrophin and dystrophin-associated proteins.


Detection of potentially inappropriate prescribing in the very old: cross-sectional analysis of the data from the BELFRAIL observational cohort study.
Little is known about the prevalence and clinical importance of potentially inappropriate prescribing instances (PIPs) in the very old (>80 years). The main objective was to describe the prevalence of PIPs according to START (Screening Tool to Alert doctors to Right Treatment; omissions) and,STOPP (Screening Tool of Older Person's Prescriptions; over/misuse) and the Beers list (over/misuse). Secondary objectives were to identify determinants if PIPs and to assess the clinical importance to modify the treatment in case of PIPs. Cross-sectional analysis of baseline data of the BELFRAIL cohort, which included 567 Belgian patients aged 80 and older in primary care. Two independent researchers applied the screening tools to the study population to detect PIPs. Next, a multidisciplinary panel of experts rated the clinical importance of the PIPs on a subsample of 50 patients. In this very old population (median age 84 years, 63 % female), the screening detected START-PIPs in 59 % of patients, STOPP-PIPs in 41 % and Beers-PIPs in 32 %. Assessment of the clinical importance revealed that the most frequent PIPs were of moderate or major importance. In 28 % of the subsample, the relevance of the PIP was challenged by the global medical, functional and social background of the patient hence the validity of some criteria was questioned. Potentially inappropriate prescribing is highly prevalent in the very old. A good understanding of the patients' medical, functional and social context is crucial to assess the actual appropriateness of drug treatment.


Magnetic resonance: in vivo tissue characterization of the testes in patients with carcinoma-in-situ of the testis and healthy subjects.
Six patients with carcinoma-in-situ (CIS) of the testis and five healthy volunteers were examined with magnetic resonance imaging (MRI), relaxation time measurements (T1 and T2) and magnetic resonance spectroscopy. The study was carried out on a Siemens Magnetom (1.5 Tesla) whole body MR scanner. All patients with CIS had a biopsy taken before MR examination and histology was compared with the MR results. Significant difference between T1 relaxation processes for normals and patients with CIS was shown. It remains to be seen whether these findings are related to the neoplasia or the reduced spermatogenesis.


Immunohistochemical studies on glucagon, glicentin and pancreatic polypeptide in human stomach: normal and pathological conditions.
Endocrine-like cells containing glucagon, glicentin or pancreatic polypeptide immunoreactivity in human foetal and adult stomach, with or without disease, were studied with the indirect immunoperoxidase method and mirror sectioning technique. In foetal and neonatal oxyntic mucosae, there were endocrine-like cells with glucagon and glicentin immunoreactivities and argyrophilia. Cells containing glicentin immunoreactivity alone were detected earlier than glucagon cells during foetal development, and were also distributed throughout foetal to neonatal life. Bovine pancreatic polypeptide immunoreactivity coexisted in a subpopulation of the glucagon-glicentin cells. These cells were absent from normal oxyntic mucosa in the postneonatal period and from normal antral mucosa throughout life. Hamartomatous polyp in adult oxyntic mucosa, hyperplastic oxyntic mucosa in Menetrier's disease and atrophic oxyntic mucosa in a remnant stomach with cancer showed scattered glucagon-glicentin cells, but few or no cells containing bovine pancreatic polypeptide. Intestinalized mucosa showed plentiful glicentin cells with occasional glucagon and/or bovine pancreatic polypeptide immunoreactivity. Some gastric cancer cells of both diffuse and adenoplastic types contained immunoreactive glicentin and, less frequently, glucagon. Bovine pancreatic polypeptide immunoreactivity was detected in a few adenoplastic cancer cells, but not in diffuse type cells. Three different anti-pancreatic polypeptide sera against bovine, porcine or human pancreatic polypeptide detected basically the same cells mentioned above, but pancreatic polypeptide cells lacking human pancreatic polypeptide immunoreactivity were also present in foetal oxyntic mucosa. Immunoabsorption tests revealed that the bovine pancreatic polypeptide immunoreactivity was remote from peptide YY and neuropeptide Y.


Three-dimensional cardiac cine imaging using the kat ARC acceleration: Initial experience in clinical adult patients at 3T.
Three-dimensional cardiac cine imaging has demonstrated promising clinical 1.5-Tesla results; however, its application to 3T scanners has been limited because of the higher sensitivity to off-resonance artifacts. The aim of this study was to apply 3D cardiac cine imaging during a single breath hold in clinical patients on a 3T scanner using the kat ARC (k- and adaptive-t auto-calibrating reconstruction for Cartesian sampling) technique and to evaluate the interchangeability between 2D and 3D cine imaging for cardiac functional analysis and detection of abnormalities in regional wall motion. Following institutional review board approval, we obtained 2D cine images with an acceleration factor of two during multiple breath holds and 3D cine images with a net scan acceleration factor of 7.7 during a single breath hold in 20 patients using a 3T unit. Two readers independently evaluated the wall motion of the left ventricle (LV) using a 5-point scale, and the consistency in the detection of regional wall motion abnormality between 2D and 3D cine was analyzed by Cohen's kappa test. The LV volume was calculated at end-diastole and end-systole (LVEDV, LVESV); the ejection fraction (LVEF) and myocardial weight (LVmass) were also calculated. The relationship between functional parameters calculated for 2D and 3D cine images was analyzed using Pearson's correlation analysis. The bias and 95% limit of agreement (LA) were calculated using Bland-Altman plots. In addition, a qualitative evaluation of image quality was performed with regard to the myocardium-blood contrast, noise level and boundary definition. Despite slight degradation in image quality for 3D cine, excellent agreement was obtained for the detection of wall motion abnormalities between 2D and 3D cine images (κ=0.84 and 0.94 for each reader). Excellent correlations between the two imaging methods were shown for the evaluation of functional parameters (r>0.97). Slight differences in LVEDV, LVESV, LVEF and LVmass were observed, with average values of 1.6±8.9mL, -0.6±5.9mL, 1.4±3.6%, and 1.3±8.7g, respectively. Images obtained using the kat ARC 3D and conventional 2D cine techniques were equivalent in the detection of regional wall motion abnormalities and the evaluation of cardiac functional parameters.


Tuberculosis in solid organ transplant patients.
Tuberculosis is an opportunistic infection with high morbidity and mortality in solid organ transplant patients. The reasons for this high morbidity and mortality lie mostly in diagnostic difficulties, which cause delays in starting treatment, and associated pharmaceutical toxicity. There are still major issues and difficulties in managing tuberculosis in solid organ transplant patients. These include problems due to interactions between antituberculosis and immunosuppressant drugs, the high risk of toxicity of antituberculosis drugs (particularly in liver transplant patients) and the absence of clear indications for the treatment of latent tuberculous infection. This article updates current understanding of tuberculosis in solid organ transplant patients.


Factors influencing the contamination rate of human organ-cultured corneas.
To assess the influence of donor, environment and storage factors on the contamination rate of organ-cultured corneas, to consider the microbiological species causing corneal contamination and to investigate the corresponding sensitivities. Data from 1340 consecutive donor corneas were analysed retrospectively. Logistic regression analysis was used to assess the influence of different factors on the contamination rate of organ-cultured corneas for transplantation. The mean annual contamination rate was 1.8 ± 0.4% (range: 1.3-2.1%); 50% contaminations were of fungal origin with exclusively Candida species, and 50% contaminations were of bacterial origin with Staphylococcus species being predominant. The cause of donor death including infection and multiple organ dysfunction syndrome increased the risk of bacterial or fungal contamination during organ culture (p = 0.007 and p = 0.014, respectively). Differentiating between septic and aseptic donors showed an increased risk of contamination for septic donors (p = 0.0020). Mean monthly temperature including warmer months increased the risk of contamination significantly (p = 0.0031). Sex, donor age, death to enucleation, death to corneoscleral disc excision and storage time did not increase the risk of contamination significantly. The genesis of microbial contamination in organ-cultured donor corneas seems to be multifactorial. The main source of fungal or bacterial contamination could be resident species from the skin flora. The rate of microbial contamination in organ-cultured donor corneas seems to be dependent on the cause of donor death and mean monthly temperature.


Limonene protects osteoblasts against methylglyoxal-derived adduct formation by regulating glyoxalase, oxidative stress, and mitochondrial function.
Methylglyoxal (MG) is a potent protein glycating agent and an important precursor of advanced glycation end products, which are involved in the pathogenesis of diabetic osteopathy. In this study, we investigated the effects of limonene on MG-induced damage in osteoblastic MC3T3-E1 cells. Pretreating cells with limonene prevented MG-induced protein adduct formation, tumor necrosis factor alpha and interleukin-6 release, mitochondrial superoxide production, and cardiolipin peroxidation. In addition, limonene increased glyoxalase I activity, and glutathione and heme oxygenase-1 levels in the presence of MG. Pretreatment with limonene prior to MG exposure reduced MG-induced mitochondrial dysfunction by preventing mitochondrial membrane potential dissipation and adenosine triphosphate loss, and reduced the levels of adenosine monophosphate-activated protein kinase, peroxisome proliferator activated receptor γ coactivator 1α, and nitric oxide. These results demonstrate that limonene may prevent the development of diabetic osteopathy.


Differential effects of the muscarinic M1 receptor agonist RS-86 and the acetylcholine-esterase inhibitor donepezil on REM sleep regulation in healthy volunteers.
Broad evidence from preclinical and clinical research indicates that cholinergic neurotransmission contributes significantly to the generation of rapid eye movement (REM) sleep. However, a potential role of different acetylcholine receptor (AChR) subtypes for the regulation of three main aspects of REM sleep, (1) REM onset, (2) REM maintenance, and (3) generation of REMs, are not clear. In the present double-blind, randomized and placebo-controlled study, we investigated the differential effects of the M1 muscarinic AChR (mAChR) agonist RS-86 and the ACh-esterase inhibitor donepezil to further specify the AChR subtype function on REM sleep regulation in n = 20 healthy volunteers. We found that RS-86 selectively shortened REM latency (multivariate analysis of variance post hoc contrast p = 0.024 compared to placebo, not significant for donepezil) and that donepezil specifically enhanced the duration of REM sleep (% sleep period time, p = 0.000 compared to placebo; p = 0.003 compared to RS-86) and the number of REMs (p = 0.000 compared to placebo; p = 0.000 compared to RS-86). These results provide evidence that the onset of REM sleep is, in part, mediated by M1 mAChR activity, whereas the maintenance of REM sleep and the number of REMs are mediated by non-M1, but presumably M2 mAChR activity. These findings are of interest for the understanding of sleep regulation and of neuropsychiatric disorders, such as Alzheimer's dementia and depressive disorders, whose etiopathology may involve alterations in cholinergic neurotransmission.