Intronic Variant of MUTYH Gene Exhibits A Strong Association with Early Onset of Breast Cancer Susceptibility in Indonesian Women Population.
Several studies have recently indicated a huge shifting pattern toward early age onset cases in breast cancer (BC) patients. However, the studies exerted relatively limited to the Caucasian population. This preliminary study is aimed to investigate the genetic risk factors for young BC patients specifically in Indonesia population. DNA samples were extracted from 79 BC patients aged younger than 40 years old and 90 healthy samples. These DNA samples were sequenced using Illumina NextSeq 500 platform and preprocessed to extract the single-nucleotide polymorphisms (SNPs) data. Firstly, multiple univariate logistic regressions were performed to test the association between each SNP and BC incidence in young patients. Furthermore, to analyze the polygenic effects derived from multiple SNPs, we employed a multivariate logistics regression. There were only 15 SNPs passed our 95% call rate threshold thus subsequently were used in the association test. One of these variants, rs3219493, emerged to be significantly associated with early-onset BC (p-value = 0.025, OR = 3.750, 95% CI = 1.178-11.938). This result is consistent with the multivariate logistic regression model, where the pertinent variant was found statistically significant (p-value = 0.008, OR = 8.398, 95% CI = 1.720-40.920). This variant was identified as an intronic variant within MUTYH gene which has been reported in several published studies to exhibit an association with the incidence of breast cancer in China, Italy and Sephardi Jews population. However, there is no evident this gene impacting the risk of developing early onset of BC in Indonesia population. Despite our limitation in terms of sample size analyzed in this preliminary study, our finding on significant association of intronic MUTHY with the early onset of BC in Indonesia led to a broadened insight of population-based unique aspect to being taken into an in-depth account for and advancement of chemotherapy.


Toe temperature versus transcutaneous oxygen tension monitoring during acute circulatory failure.
Measurements of toe temperature and transcutaneous PO2 (PtcO2) have been both suggested for non-invasive assessment of peripheral blood flow in acute circulatory failure. The underlying principle of the two methods is that cutaneous vasoconstriction occurs early when tissue perfusion is altered. In 15 patients, we compared the two measurements during cardiogenic shock (27 measurements) or septic shock (29 measurements). Toe-ambiant temperature gradient and PtcO2 correlated well together (r = 0.66, p less than 0.001) especially in hyperkinetic septic shock (r = 0.79, p less than 0.001). In cardiogenic shock, toe-ambiant temperature correlated well with cardiac index (r = 0.63), stroke index (r = 0.64) and oxygen transport (r = 0.65), and these correlations were stronger than for PtcO2. In septic shock, both techniques were poor indicators of blood flow indexes but PtcO2 rather correlated with arterial pressure (r = 0.66) and left ventricular work (r = 0.66). Trend evaluation of data revealed in cardiogenic shock that the increase in toe temperature usually preceded the increase in PtcO2. Since measurement of PtcO2 is technically more complicated, correlates less well with standard hemodynamic parameters and later reflects cardiovascular improvement, it has no advantage over measurement of toe temperature in circulatory shock. In cardiogenic shock, measurements of toe temperature can reliably track cardiac output changes. In septic states, however, non-invasive assessment of skin perfusion is of limited interest.


Mimosa pudica seed mucilage: isolation; characterization and evaluation as tablet disintegrant and binder.
In the present study Mimosa pudica seed mucilage was isolated, characterized and evaluated as tablet binder and disintegrant. Several properties of mucilage like high swelling index and gelling nature prompted us to explore its applications as disintegrating and binding agent. Disintegrant properties were evaluated by formulating directly compressed hydrochlorothiazide tablets containing 1%-10% (w/w) of seed mucilage as disintegrant and compared with the standard disintegrants. The disintegration time of mucilage containing tablets was found to be in the order of 3%>1%>5%>7.5%>10%. On comparative evaluation with standard disintegrants, it was observed that the order of disintegration of tablets was Ac-Di-Sol<mucilage (3%, w/w)<corn starch. The results of liquid uptake studies were consistent with the disintegration time studies. The binding and granulating properties of mucilage were evaluated by formulating the paracetamol tablets using the Mimosa mucilage at 6%, 8%, and 10% (w/w) concentration as the binder and compared with tablets prepared using PVP-K25 (1.7%, w/w) and acacia (6.8%, w/w) as the binder. Mimosa mucilage at 10% (w/w) concentration provided tablets with adequate hardness and friability. In conclusion, M. pudica seed mucilage is a potential tablet disintegrant and binder.


Nipple sparing subcutaneous mastectomy: sixty-six months follow-up.
Validation of oncological and reconstructive efficacy of nipple sparing subcutaneous mastectomy. We enrolled 50 patients on behalf of Humanitas Centro Catanese di Oncologia fulfilling appropriate reconstructive and oncological criteria to undergo nipple sparing subcutaneous mastectomy. We preferably selected women with medium size-small breast affected by early stage breast cancer peripherally located with intra-operative negative frozen section of the major ducts. fourty-six patients were alive after a mean follow-up of 5.5 years. We observed a single case of local recurrence in the nipple successfully treated with local excision. Five patients presented metastatic disease. One is currently alive, 4 died because of progressive disease. Our study supports other findings regarding safety and efficacy of nipple sparing subcutaneous mastectomy for selected patients.


Performance aware shared memory hierarchy model for multicore processors.
Despite the fact that multicore processors have a better instruction execution speed and lower power consumption, they also encounter a set of design challenges. The appearance of multicore and many core architectures has raised the problem of managing shared hierarchical memory systems. The main focus of this paper is to evaluate the behavior of shared hierarchical memory systems by modeling their response time analytically. Since the gap between the memory and processor speed increases rapidly, it gets more crucial to find an analytical model that includes the significant factors that affect the performance of hierarchical memory systems. The proposed model considers the interdependence between different memory layers and differentiates between the memory response time and memory system time. Moreover, the model evaluates the effect of memory hierarchy on the variance of the memory access time. The existence of a large variance can lead to extremely long wait queues which can dramatically affect the performance of multicore processors.


Evaluation and remediation of bulk soap dispensers for biofilm.
Recent studies evaluating bulk soap in public restroom soap dispensers have demonstrated up to 25% of open refillable bulk-soap dispensers were contaminated with ~ 6 log(10)(CFU ml(-1)) heterotrophic bacteria. In this study, plastic counter-mounted, plastic wall-mounted and stainless steel wall-mounted dispensers were analyzed for suspended and biofilm bacteria using total cell and viable plate counts. Independent of dispenser type or construction material, the bulk soap was contaminated with 4-7 log(10)(CFU ml(-1)) bacteria, while 4-6 log(10)(CFU cm(-2)) biofilm bacteria were isolated from the inside surfaces of the dispensers (n = 6). Dispenser remediation studies, including a 10 min soak with 5000 mg l(-1) sodium hypochlorite, were then conducted to determine the efficacy of cleaning and disinfectant procedures against established biofilms. The testing showed that contamination of the bulk soap returned to pre-test levels within 7-14 days. These results demonstrate biofilm is present in contaminated bulk-soap dispensers and remediation studies to clean and sanitize the dispensers are temporary.


[Changes in skeletal bones in residents of the Baltic area studied on the paleoanthropological material].
Examinations of 4481 skeletons revealed 70 cases of chronic osteomyelitis, 9 cases of osteotuberculosis and 10 cases of concha bullosa of the concha media nasalis in bronze age. Metadiaphysary forms of osteomyelitis in the long tubular bones with prevalence of ossific proliferation were observed most frequently. Osteotuberculosis existed in Latvia since the most ancient times mainly in the form of spondylitis tuberculosa.


A retrospective review of ampicillin-sulbactam and amoxicillin + clavulanate vs cefazolin/cephalexin and erythromycin in the setting of preterm premature rupture of membranes: maternal and neonatal outcomes.
The purpose of this study was to compare the efficacy and outcomes of 2 different antibiotic regimens that are used to prolong latency in preterm premature rupture of membranes. The primary objective was to determine whether the use of ampicillin-sulbactam/amoxicillin + clavulanate was associated with an increased risk of necrotizing enterocolitis. A retrospective review of pregnancies that were complicated by preterm premature rupture of membranes from 1999-2006 at 2 institutions was performed. Outcomes were compared between subjects who received parenteral ampicillin-sulbactam followed by oral amoxicillin + clavulanate (protocol A) and subjects who received parenteral cefazolin and erythromycin followed by oral cephalexin and erythromycin (protocol B). There were 147 women who were evaluated; 88 women received protocol A, and 59 women received protocol B. There were no differences in latency period, gestational age at delivery, or route of delivery. The incidence of necrotizing enterocolitis was 8.0% and 10.2% for protocol A and protocol B, respectively (P = .64). Ampicillin-sulbactam/amoxicillin + clavulanate was not associated with an increase in neonatal necrotizing enterocolitis. Erythromycin in combination with cefazolin and cephalexin is an effective latency antibiotic regimen.


Electrochemical aptamer sensor for small molecule assays.
Detection and quantification of small molecules have played essential roles in environmental analysis and clinical diagnosis. Aptamers are oligonucleic acids that bind to a specific target molecule with high specificity and affinity which are promising features for sensing small molecules. Electrochemical detection is an attractive way to exploit aptamer sensors (aptasensors) because of its high sensitivity, simple instrumentation, low cost, fast response and portability. Herein, we describe a label-free small molecular aptasensor based on a signal-amplification mechanism which uses gold nanoparticles. This aptasensor can selectively detect low nanomolar levels of ATP, the example target compound.


High-performance liquid chromatographic analysis of chlorhexidine in saliva after mouthrinsing.
A high-performance liquid chromatographic method was developed to quantify chlorhexidine in human saliva. After addition of an internal standard and acidic-deproteinization, saliva samples were chromatographed by the reversed-phase ion-pair system using pentanesulfonate as a counterion and the eluates were detected by a diode array detector. Under optimal conditions, the baseline separation of analytes was achieved within 4.5 min without interference from components in saliva matrix. The method showed high selectivity to salivary chlorhexidine, quantitative range (50. 0ng/ml-50.0 microg/ml), recovery (96.0-97.8%) and analytical precision (intra- and interassay CVs within 0.41%), permitting the effective application to both saliva and aqueous solutions. Chlorhexidine was found in saliva at microgram per milliliter levels for at least 8 h after mouthrinsing with 10 ml of an aqueous solution of chlorhexidine (0.1 or 1.0 mg/ml) for 1 min. The concentrations of salivary chlorhexidine were reduced by ingesting the acidic beverage and food, but not by ingesting the neutral beverage. The adsorption experiments in artificial saliva revealed that chlorhexidine was significantly adsorbed to saliva-coated hydroxyapatite, buccal epithelial cells and mucin. The proposed method will be a useful tool to study salivary chlorhexidine after oral application and its retention in the oral cavity.


Out-of-pocket expenditure by private households for dental services - empirical evidence from Austria.
Dental services differ from other health services in several dimensions. One important difference is that a substantial share of costs of dental services-especially costs beyond routine dental treatment-is paid directly by the patient out-of-pocket. This study analyses the socio-economic determinants of out-of-pocket expenditure for dental services (OOPE) in Austria at the household level. Cross-sectional information on OOPE and household characteristics provided by the Austrian household budget survey 2009/10 was analysed. A two-part model (Logit/GLM) and one-part GLM was applied. The probability of OOPE is strongly affected by the life cycle (structure) of the household. It is higher for higher age classes, higher income, and partially higher levels of education. The type of public insurance has an influence on expenditure probability while the existence of private health insurance has no significant effect. In contrast to the highly statistically significant coefficients in the first stage, the covariates of the second stage remain predominantly insignificant. According to the results, the level of expenditure is driven mainly by the level of education and income. The results of the one-part GLM confirm the results of the two-part model. The results allow new insights into the determinants of OOPE for dental care. The household level turns out to be an adequate basis to study the determinants of OOPE, although caution should be applied before jumping to conclusions for the individual level.


Management of Adult Elbow Fracture Dislocations.
Elbow fracture dislocations are complicated injuries that are difficult to manage and fraught with complications. A complete series of radiographs is typically complemented with CT scan to evaluate the elbow and assist preoperative planning. Typically, operative intervention is necessary and a systematic approach to the elbow injuries should be chosen. This article addresses the coronoid and proceeds to the radial head, lateral soft tissues, and finally the medial ligaments if elbow instability persists. With a focused, systematic surgical approach, improved outcomes have been demonstrated and patients may recover full function and range of motion in the affected elbow.


Toxicity of silver in water and sediment to the freshwater amphipod Hyalella azteca.
Hyalella azteca was exposed to Ag as AgNO3 over a 10-d period in water and two lake sediments that were selected on the basis of their differences in metal-binding properties. The median lethal concentrations (LC50s) for waterborne exposures were 5.4 and 4.9 microg/L for total and dissolved Ag, respectively. In the sediment containing a lesser quantity of total Ag-binding ligands (i.e., Bond Lake, Douglas County, WI, USA, sediment), an Ag-amended sediment toxicity test resulted in a 10-d LC50 of 0.084 g (i.e., 84,000 microg) Ag/kg dry sediment or 8.6 microg Ag/L of pore water (PW). The no-observed-effect concentration (NOEC) to lowest-observed-effect concentration (LOEC) range was 0.012 to 0.031 g Ag/kg dry sediment, or less than 5.0 to 6.0 microg Ag/L of PW. In the sediment with a greater quantity of total Ag-binding ligands (i.e., West Bearskin Lake, Cook County, MN, USA, sediment), the 10-d LC50 was 2.98 g Ag/kg dry sediment, and the NOEC to LOEC range was 2.15 to 4.31 g Ag/kg dry sediment. Because "dissolved" concentrations of Ag in PW were less than 5.0 microg/L at the critical exposures in the latter test, the bioavailable and toxic form of Ag may have been a weakly associated coprecipitate or colloidal complex with hydrous iron oxides that competitively partitioned to the surface of the gills.


Mitochondrial genome of Megaphragma amalphitanum (Hymenoptera: Trichogrammatidae).
The mitochondrial genome of the parasitic wasp Megaphragma amalphitanum is published in this paper. The mitochondrial DNA (mtDNA) is 15 041 base pairs (bp) in length and contained 13 protein-coding genes, 2 rRNA genes and 22 tRNA genes. The overall base composition of the genome in descending order was 45.67% A, 8.71% C, 39.63% T and 5.99% G, with a significant AT bias of 85.30%.


High-dose Tiger-Gian formula protects the knee joint from surgically induced osteoarthritis in rats.
Although the Tiger-Gian formula (TGF) has proven clinically effective at improving the symptoms of knee osteoarthritis (KOA), the pharmacological effects and underlying mechanisms of TGF have not been examined in any animal model. This study assessed the effects of TGF in male Sprague-Dawley rats with anterior cruciate ligament transection (ACLT) -induced KOA. Thirty rats underwent ACLT surgery and were assigned to either the control group, ACLT alone, ACLT + low-dose TGF (1000 mg/kg), ACLT + high-dose TGF (3000 mg/kg), or ACLT + celecoxib (30 mg/kg). All rats were subjected to micro-computed tomography (micro-CT), weight-bearing behavioral testing, and histological inspections of the knee joint for evidence of structural changes in articular bone, cartilage and synovium. After 6 weeks, force discrepancies in weight-bearing distribution between the normal hind and postoperative limbs revealed superiority with high-dose TGF (18.00 ± 5.93 g) and celecoxib (18.68 ± 5.29 g) versus both ACLT alone (41.29 ± 7.06 g) and low-dose TGF (37.00 ± 7.40 g). Micro-CT images revealed that high-dose TGF and celecoxib similarly improved subchondral bone architecture, protected articular cartilage after ACLT, and downregulated proinflammatory cytokines interleukin-1β and tumor necrosis factor-α in the cartilage and synovial sections. High-dose TGF induced the smallest amount of KOA-associated bone loss. Anti-inflammatory, anti-oxidative, and immunomodulatory effects of TGF were accompanied by reductions in proinflammatory cytokines and improvements in pain and function. TGF-induced anti-osteoporotic activity and inhibition of cartilage degradation were reflected by micro-CT and histological analysis. The findings help to explain how TGF alleviates symptoms of KOA.


Pan-tropical Sentinel-2 cloud-free annual composite datasets.
Sentinel-2 MSI is one of the core missions of the Copernicus Earth Observation programme of the European Union. This mission shows great potential to map the regional high-resolution spatio-temporal dynamics of land use and land cover. In tropical regions, despite the high revisiting time of 5 days including both Sentinel-2A and 2B satellites, the frequent presence of clouds, cloud-shadows, haze and other atmospheric contaminants are precluding the visibility of the Earth surface up to several months. In this paper we present four annual pan-tropical cloud-free composites computed and exported from Google Earth Engine (GEE) by making use of available Sentinel-2 L1C collection for the period spanning from 2015 to 2020. We furthermore propose empirical approaches to reduce the BRDF effect over tropical forest areas by showing pros and cons of image-based versus swath-based methodologies. Additionally, we provide a dedicated web-platform offering a fast and intuitive way to browse and explore the proposed annual composites as well as layers of potential annual changes as a ready-to-use means to visually identify and verify degradation and deforestation activities as well as other land cover changes.


Regulation of lipoprotein lipase gene expression by insulin and troglitazone in rainbow trout (Oncorhynchus mykiss) adipocyte cells in culture.
Adipose tissue plays a central role regulating the balance between deposition and mobilization of lipid reserves. Lipoprotein lipase (LPL) is a key enzyme controlling lipid accumulation in mammals and fish. In the present study, we have examined the expression of LPL in rainbow trout cultured adipocytes and we have investigated the effect of troglitazone, a member of thiazolidinediones (TZDs), and insulin on its expression. LPL gene expression increased from day 1 until day 12 of culture, and the level was maintained up to day 21. The addition of insulin at 10 nM and 1.7 μM increased significantly LPL gene expression in undifferentiated cells (days 7 to 12 maintained in growth medium). Nevertheless, treatment of day 7 cells incubated in growth medium with troglitazone (5 μM) or troglitazone plus insulin (1 μM each), tended to enhance LPL expression. In addition, LPL mRNA levels increased significantly in the presence of 1 μM and 5 μM of troglitazone (days 7 to 12) when the cells were induced to differentiate by addition of differentiation medium. Although troglitazone alone (1 μM) did not stimulate lipid accumulation in the cells neither in growth nor in differentiation medium, the simultaneous presence of troglitazone (1 μM) and insulin (1 μM) increased significantly the content of triglycerides in adipocyte cells maintained in growth medium (days 7 to 12). These results indicate that insulin and troglitazone regulate LPL gene expression during adipocyte differentiation and suggest that both factors may have combined effects in the modulation of adipogenesis.


Bereaved parents' quality of life: resilience and professional support.
The study aimed to compare the quality of life (QoL) among cancer-bereaved parents with a control group and explore how resilience and support from healthcare professionals associated with QoL of parents 2-8 years after the loss of a child to cancer. This nationwide, cross-sectional survey was administered among parents (n=161) who lost their child to cancer between 2009 and 2014, compared with a matched control parent group (n=77). A study-specific questionnaire, Resilience Scale for Adults (six factors: 'Perception of self', 'Planned future', 'Social competence', 'Structured style', 'Family cohesion' and 'Social resources'), and a single-item measure of parents' QoL were included for the study. There was a lower QoL in both bereaved parents (mean=5.1) compared with the control parents (mean=5.8) (p<0.001). Two resilience factors, 'Perception of self' (OR=1.8, p=0.004) and 'Planned future' (OR=2.05, p<0.001), and given sufficient information during the child's last month (OR=2.63, p=0.003) were positively associated with long-term QoL in cancer-bereaved parents. The findings indicate lower QoL among both fathers and mothers 2-8 years after losing a child to cancer. The study also highlights the positive role of resilience and the importance of informational support on long-term QoL in cancer-bereaved parents. Bereavement support should be tailored for supporting individual needs.


Vitamin D status and tic disorder: a systematic review and meta-analysis of observational studies.
Tic disorders (TD) are a common neurodevelopmental disorder, it can be divided into transient tic disorder (TTD), chronic motor or vocal tic disorder (CTD), and Tourette syndrome (TS). Our research is to evaluate the clinical relationship between tic disorders and vitamin D level in children. Online databases, including CNKI, Wanfang, VIP, Cochrane Library, PubMed and Embase digital knowledge service platform, were checked up to June 2022 for relevant observational studies published in Chinese and English. A random-effects model was incorporated to summarize the study results. The RevMan5.3 software was used for meta-analysis. Out of 132 retrieved articles, 13 observational studies were eligible for inclusion in the systematic review and meta-analysis, comparing serum Vitamin D levels between children with TD and HC (healthy controls), including different subtypes of TD (TTD, CTD and TS). The results showed that the serum vitamin D levels in the TD group were lower than those in the HC group (MD = -6.64, 95% CI: -9.36 to -3.93, P < 0.001, Heterogeneity test: P < 0.001, I2 = 94%). There were no statistically significant differences in serum vitamin D levels between the TTD group and the CTD group (MD = 3.84, 95% CI: -0.59 to 8.26, P = 0.09, Heterogeneity test: P < 0.001, I2 = 90%), or between the CTD group and the TS group (MD = 1.06, 95% CI: -0.04 to 2.16, P = 0.0, Heterogeneity test: P = 0.54, I2 = 0%). However, there was a statistically significant difference in serum vitamin D levels between the TTD group and the TS group (MD = 5.24, 95% CI: 0.68-9.80, P = 0.02, Heterogeneity test: P < 0.001, I2 = 92%). The study also found a statistically significant difference in the ratio of male children between the TD group and the HC group (OR = 1.48, 95% CI: 1.07-2.03, P = 0.02, Heterogeneity test: P < 0.001, I2 = 74%), but no statistically significant difference in the age of children between the TD group and the HC group (OR = 0.46, 95% CI: -0.33 to 1.24, P = 0.25, Heterogeneity test: P < 0.001, I2 = 96%). Our meta-analysis showed that the vitamin D level of children with TD was lower than that of healthy children. However, there was no difference between the subgroup. Due to the limitations of included studies in research design and diagnostic criteria, large samples, multi-center and high-quality studies are still needed for further analysis and confirmation.


Permethrin induced arterial retention of native and oxidized LDL in rats by promoting inflammation, oxidative stress and affecting LDL receptors, and collagen genes.
This study is the first to examine the possible mechanism by which long-term exposure to permethrin (PER) can promote arterial retention of proatherogenic lipid and lipoproteins and related vascular dysfunction in rats. Experimental animals were administered two doses of oral PER, PER-1 (2.5 mg/kg/bw) and PER-2 (5 mg/kg/bw), for 90 consecutive days. The results indicated that both PER-1 and PER-2 increased plasmatic and aortic total cholesterol, low-density lipoprotein cholesterol (LDL-C), apo B-100, and oxidized LDL together with arterial scavenger LDL receptors (CD36) but markedly reduced plasmatic and hepatic high-density lipoprotein cholesterol and native LDL receptors in aortic and hepatic tissue. The levels of malondialdehyde, protein carbonyl, and reactive oxygen species were significantly higher, and glutathione content as well as catalase, superoxide dismutase, and glutathione peroxidase activities were suppressed in the aorta of the PER-1 and PER-2 groups. The arterial oxidative damage possibly caused by PER was clearly demonstrated by hematoxylin and eosin histological analysis. Moreover, PER treatment aggravated the inflammatory responses through enhancement of the production of proinflammatory cytokines (tumor necrosis factor-α, interleukin-2, and interleukin-6) in both plasma and aorta. Furthermore, PER-1 and PER-2 potentiated the dysregulation of the aortic extracellular matrix (ECM) content by increasing mRNA activation of collagens I and III. The abundant histological collagen deposition observed in the media and adventitia of intoxicated rats using Masson's trichrome staining corroborates the observed change in ECM. These data showed that oxidative stress related to PER exposure increases the arterial accumulation of lipoprotein biomarkers, likely by actions on both LDL and CD36 receptors, together with the disruption of the aortic ECM.


Metastatic choriocarcinoma with hemorrhagic complications and spontaneous ovarian hyperstimulation syndrome: A case report.
Gestational choriocarcinoma is a malignant trophoblastic tumor arising from any gestational event, even with a long latency period, generally in the reproductive female. It is associated with a high level of beta-human chorionic gonadotropin. Its primary site is usually the uterus but not all patients have a detectable lesion in this site. Regression of the primary tumor after it has metastasized is not uncommon, and one-third of cases manifest as complications of metastatic disease. In this report we present an uncommon case of gestational choriocarcinoma with lung, liver and jejunal metastases at the time of diagnosis without evidence of pelvic disease, in 34-year-old woman. The main points of interest of our case were the development of the ovarian hyperstimulation syndrome with massive multicystic ovarian enlargement induced by high level of beta-human chorionic gonadotropin and the bleeding of jejunal and liver metastases, due to the high vascularity of the tumor tissue, a condition known as "Choriocarcinoma Syndrome". We will focus on the radiological findings of metastases, bleeding complications and ovarian hyperstimulation syndrome.


Trends in hospitalization and factors associated with in-hospital death among pediatric admissions with implantable cardioverter defibrillators.
As pediatric implantable cardioverter-defibrillator (ICD) utilization increases, hospital admission rates will increase. Data regarding hospitalizations among pediatric patients with ICDs are lacking. In addition, hospital mortality rates are unknown. This study aimed to evaluate (1) trends in hospitalization rates from 2000 to 2016, (2) hospital mortality, and (3) factors associated with hospital mortality among pediatric admissions with ICDs. The Kids' Inpatient Database (2000, 2003, 2006, 2009, 2012, 2016) was used to identify all hospitalizations with an existing ICD ≤20 years of age. ICD9/10 codes were used to stratify admissions by underlying diagnostic category as: (1) congenital heart disease (CHD), (2) primary arrhythmia, (3) primary cardiomyopathy, or (4) other. Trends were analyzed using linear regression. Hospital and patient characteristics among hospital deaths were compared to those surviving to discharge using mixed multivariable logistic regression, accounting for hospital clustering. Of 42 570 716 hospitalizations, 4165 were admitted ≤20 years with an ICD. ICD hospitalizations increased four-fold (p = .002) between 2000 and 2016. Hospital death occurred in 54 (1.3%). In multivariable analysis, cardiomyopathy (odds ratio [OR]: 3.5, 95% confidence interval [CI]: 1.1-11.2, p = .04) and CHD (OR: 4.8, 95% CI: 1.5-15.6, p = .01) were significantly associated with mortality. In further exploratory multivariable analysis incorporating a coexisting diagnosis of heart failure, only the presence of heart failure remained associated with mortality (OR: 8.6, 95% CI: 3.7-20.0, p < .0001). Pediatric ICD hospitalizations are increasing over time and hospital mortality is low (1.3%). Hospital mortality is associated with cardiomyopathy or CHD; however, the underlying driver for in-hospital death may be heart failure.


In vitro control analysis of an enzyme system: experimental and analytical developments.
In this paper we describe a flow-through system for reconstituting parts of metabolism from purified enzymes. This involves pumping continuously into a reaction chamber, fresh enzymes and reagents so that metabolic reactions occur in the chamber. The waste products leave the chamber via the outflow so that a steady state can be setup. The system we chose consisted of a single enzyme, lactate dehydrogenase. This enzyme was chosen because it consumes NADH in the chamber which could be monitored spectrophotometrically. The aim of the work was to investigate whether a steady state could be achieved in the flow system and whether a metabolic control analysis could be done. We measured two control coefficients, CLDH and Cpump for the enzyme flux and NADH concentration and confirmed that the summation theorem applied to this system. The advantage of a flow-through system is that the titrations necessary to estimate the control coefficients can be easily and precisely controlled; this means that accurate estimates for the control coefficients can be obtained. In the paper, we discuss some statistical aspects of the data analysis and some possible applications of the technique, including a method to determine the presence of metabolic channelling between two different enzymes.


Changes in progesterone-induced-blocking-factor expression rates following mifepristone administration in termination of pregnancy at 5 to 8 weeks.
To study changes in the expression rate of PIBF by peripheral lymphocytes in healthy pregnant women after administration of mifepristone for non-surgical termination of pregnancy at 5-8 wks of gestation. Patients requesting early social termination of pregnancy, in a 3-month period, were included. A first venous blood sample was taken before oral administration of 600 mg of mifepristone (day 0). A second venous blood sample was taken 2 days later. PIBF on lymphocytes was determined by immunocytochemistry using a PIBF-specific polyclonal antibody. Termination of pregnancy was successful and complete in all cases. In 17 out of 21 patients, the percentage of PIBF positive lymphocytes decreased after anti-progesterone administration. The percentage of PIBF-expressing lymphocytes significantly decreased from 52.8%+/-21.6% (day 0) to 39.8%+/-18.2% by day 2 (p=0.001). These data suggest a strong relationship between early termination of pregnancy induced with mifepristone and disturbances of progesterone-mediated immunosuppression.


[Marriage and Migratory Characteristic of Circassians (Late 20th Century)].
This paper analyzes 2052 marriage records for 1990-2000 in the Khabezsky district of Karachay-Cherkessia. The main marriage and migration characteristics of Circassians are studied: index of endogamy, ethnic mar- riage assortativity, intensity of metisation, and Malecot's parameters of isolation by distance.


Tissue-preserving feminizing clitoroplasty: a preliminary report.
To describe a tissue-preserving feminizing clitoroplasty that potentially allows for future total reversal to male and report on its initial result. A potentially reversible operation for feminizing clitoroplasty that preserves all available tissue was performed in three patients: two girls with congenital adrenal hyperplasia and a '46XY male' with androgen insensitivity. The phallus was disassembled into its individual components of the phallic skin, left and right corpus cavernosum, dorsal neurovascular bundle with the dorsal portion of the glans, and 'urethral plate-corpus spongiosum complex' with the ventral portion of the glans attached. Each corpus cavernosum was folded upon itself and then hidden in the subcutaneous fat to increase the size of the labia majora. The partially divided urethral plate was used to form the inner part of the labia minora and the clitoral hood. The phallic skin was partially divided and used to form the outer part of the labia minora. This operation allowed feminizing clitoroplasty to be completed without significant excision of any tissue, including the corpora cavernosa. The operation was completed successfully in all three patients, two with concomitant inverted 'V' flap vaginoplasty. One patient had postoperative haematoma. All three have a cosmetically acceptable 'female look' to the satisfaction of themselves and their parents. This preliminary result suggests that a cosmetically acceptable feminizing clitoroplasty can be performed with preservation of all phallic tissue, in particular the corpora cavernosa. This potentially reversible operation may be advantageous when feminizing genitoplasty has to be performed in a young child with disorders of sex development.


The exposome for kidney stones.
The exposome is the assembly and measure of all the exposures of an individual in a lifetime. An individual's exposures begin before birth and include insults from environmental and occupational sources. The associated field is called exposomics, which relies on the application of internal and external exposure assessment methods. Exposomics has not yet been thoroughly applied to the study of kidney stones although much is known about how diet and fluid intake affect nephrolithiasis. Some other novel exposures that may contribute to kidney stones are discussed including use of antibiotics, urbanization and migration to urban heat islands, and occupation. People whose school and jobs limit their access to fluids and adequate bathroom facilities may have higher prevalence of stones. Examples include athletes, teachers, heathcare workers, and cab drivers. Occupational kidney stones have received scant attention and may represent a neglected, and preventable, type of stone. An exposomic-oriented history would include a careful delineation of occupation and activities.


Polyphenols from Lycium barbarum (Goji) Fruit European Cultivars at Different Maturation Steps: Extraction, HPLC-DAD Analyses, and Biological Evaluation.
Goji berries are undoubtedly a source of potentially bioactive compounds but their phytochemical profile can vary depending on their geographical origin, cultivar, and/or industrial processing. A rapid and cheap extraction of the polyphenolic fraction from Lycium barbarum cultivars, applied after homogenization treatments, was combined with high-performance liquid chromatography (HPLC) analyses based on two different methods. The obtained hydroalcoholic extracts, containing interesting secondary metabolites (gallic acid, chlorogenic acid, catechin, sinapinic acid, rutin, and carvacrol), were also submitted to a wide biological screening. The total phenolic and flavonoid contents, the antioxidant capacity using three antioxidant assays, tyrosinase inhibition, and anti-Candida activity were evaluated in order to correlate the impact of the homogenization treatment, geographical origin, and cultivar type on the polyphenolic and flavonoid amount, and consequently the bioactivity. The rutin amount, considered as a quality marker for goji berries according to European Pharmacopeia, varied from ≈200 to ≈400 µg/g among the tested samples, showing important differences observed in relation to the influence of the evaluated parameters.


STEPS - a patient centric and low-cost solution to ensure standards of TB care to patients reaching private sector in India.
More than half of the TB patients in India seek care from the private sector. Two decades of attempts by the National TB Program to improve collaboration between the public and private sectors have not worked except in a few innovative pilots. The System for TB Elimination in Private Sector (STEPS) evolved in 2019 as a solution to ensure standards of TB care to every patient reaching the private sector. We formally evaluated the STEPS to judge the success of the model in achieving its outcomes and to inform decisions about scaling up of the model to other parts of the country. An evaluation team was constituted involving all relevant stakeholders. A logic framework for the STEPS model was developed. The evaluation focused on (i) processes - whether the activities are taking place as intended and (ii) proximal outcomes - improvements in quality of care and strengthening of TB surveillance system. We (i) visited 30 randomly selected STEPS centres for assessing infrastructure and process using a checklist, (ii) validated the patient data with management information system of National TB Elimination Program (NTEP) by telephonic interview of 57 TB patients (iii) analysed the quality of patient care indicators over 3 years from the management information system (iv) conducted in-depth interviews (IDI) with 33 beneficiaries and stakeholders to understand their satisfaction and perceived benefits of STEPS and (v) performed cost analysis for the intervention from the perspective of NTEP, private hospital and patients. Evaluation revealed that STEPS is an acceptable model to all stakeholders. IDIs revealed that all patients were satisfied about the services received. Data in management information system of NTEP were consistent with the hospital records and with the information provided by the patient. Quality of TB care indicators for patients diagnosed in private hospitals showed improvements over years as proportion of TB patients notified from private sector with a microbiological confirmation of diagnosis improved from 25% in 2018 to 38% in 2020 and the documented treatment success rate increased from 33% (2018 cohort) to 88% (2019 cohort). Total additional programmatic cost (deducting cost for patient entitlements) per additional patient with successful treatment outcome was estimated to be 67 USD. Total additional expense/business loss for implementing STEPS for the hospital diagnosing 100 TB patients in a year was estimated to be 573 USD while additional minimum returns for the hospital was estimated to be 1145 USD. Evaluation confirmed that STEPS is a low cost and patient-centric strategy. STEPS successfully addressed the gaps in the quality of care for patients seeking care in the private sector and ensured that services are aligned with the standards of TB care. STEPS could be scaled up to similar settings.


Separation of the Azeotropic Mixture Methanol and Toluene Using Extractive Distillation: Entrainer Determination, Vapor-Liquid Equilibrium Measurement, and Modeling.
For separating the azeotropic mixture methanol and toluene, an extractive distillation is applied with butyl propanoate, triethylamine, and butyl butanoate as the extractive solvents, which were screened by relative volatility, selectivity, and the x-y curve. The vapor-liquid equilibrium data of the binary and ternary systems for (toluene + butyl propanoate), (toluene + triethylamine), (toluene + butyl butanoate), and (methanol + toluene + butyl butanoate) were determined. The reliability for the experimental vapor-liquid equilibrium (VLE) data was assessed with the van Ness method. The measured data was fitted by the UNIQUAC, Wilson, and NRTL models, and the correlated results were consistent with the determined VLE data. In addition, the COSMO-UNIFAC model was used to predict the VLE data for comparison.


Review on the delivery of steroids by carrier proteins.
Due to the poor solubility of steroids in aqueous solution, delivery of these biomaterials is of major biomedical importance. We have reviewed the conjugation of testosterone and it aliphatic dimer and aromatic dimer with several carrier proteins, human serum albumin (HSA), bovine serum albumin (BSA) and milk beta-lactoglobulin (b-LG) in aqueous solution at physiological pH. The results of multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling were compared here. Steroid-protein bindings are via hydrophilic and H-bonding contacts. HSA forms more stable conjugate than BSA and b-LG. The stability of steroid-protein conjugates is testosterone>dimer-aromatic>dimer-aliphatic. Encapsulation of steroids by protein is shown by TEM images. Modeling showed the presence of H-bonding, which stabilized testosterone-protein complexes with the free binding energy of -12.95 for HSA and -11.55 for BSA and -8.92kcal/mol for b-LG conjugates. Steroid conjugation induced major perturbations of serum protein conformations. Serum proteins can transport steroids to the target molecules.


Moving Toward Opioid-Free Breast Surgery: Regional Blocks and a Novel Technique.
Perioperative pain control is of increasing importance as awareness regarding the risks of under-controlled pain and opioid abuse rise. Enhanced recovery protocols and multimodal analgesia, including regional blocks, are useful tools for the plastic surgeon. The thoracic paravertebral block, pectoralis nerve I and pectoralis nerve II blocks, and proximal intercostal blocks are 3 described methods that provide regional anesthesia for breast surgery. The widespread use of these methods may be limited by the requirements for ultrasound equipment and anesthesiologists skilled in regional blocks. This article describes a novel technique of the intercostal field block under direct visualization that is safe and efficient.


Gravimetric and electrochemical statistical optimizations for improving copper corrosion resistance in hydrochloric acid using thiosemicarbazone-linked 3-acetylpyridine.
Thiosemicarbazone-linked 3-acetylpyridine (T3AP), was synthesized and tested on copper strips in hydrochloric acid. Gravimetric measurements and electrochemical impedance spectroscopy were used to investigate the optimized inhibitory behavior of T3AP using the response surface methodology (RSM), with the optimized result obtained using a temperature of 42.90 °C, acid concentration of 2.38 M, inhibitor concentration of 3.80 mM, and time of 18.97 h, with inhibition efficiency up to approximately 93%. Validation of the experimental and predicted RSM showed that no significant difference in the inhibition efficiency with the confidence level value up to 97% was obtained. The isotherm study shows that T3AP obeys the Langmuir isotherm adsorption model, with physisorption and chemisorption adsorption mechanisms. The effectiveness of inhibitor performance of T3AP can be visually observed using scanning electron microscopy and X-ray photoelectron spectroscopy. The characterization revealed that the reactive S and N atoms in the T3AP inhibitor form strong chemical adsorption through N-Cu and Cu-S bonds on the copper surface. Computational analysis was also carried out, and we found that the stable energy gap between the occupied and unoccupied molecular orbitals (4.6891 eV) and high binding energy (540.962 kJ mol-1) adsorption from molecular dynamics were in agreement with the experimental findings.


Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles.
In the present study, we created a nanoscale platform that can deliver nutrients to pancreatic islets in a controlled manner. Our platform consists of a mesoporous silica nanoparticle (MSNP), which can be loaded with glutamine (G: an essential amino acid required for islet survival and function). To control the release of G, MSNPs were coated with a polydopamine (PD) layer. With the optimal parameters (0.5 mg/mL and 0.5 h), MSNPs were coated with a layer of PD, which resulted in a delay of G release from MSNPs over 14 d (57.4 ± 4.7% release). Following syngeneic renal subcapsule islet transplantation in diabetic mice, PDG-MSNPs improved the engraftment of islets (i.e., enhanced revascularization and reduced inflammation) as well as their function, resulting in re-establishment of glycemic control. Collectively, our data show that PDG-MSNPs can support transplanted islets by providing them with a controlled and sustained supply of nutrients.


HIV postexposure prophylaxis practices by US ED practitioners.
To determine how often US ED practitioners have prescribed HIV post-exposure prophylaxis (HIV PEP) and to discern how willing they are to offer it to patients, the authors surveyed 600 ED practitioners attending a national conference. According to their self-report, 11% had taken HIV PEP themselves. Sixty-eight percent had prescribed HIV PEP at some time. Of these, 92% had treated needlestick-injured health care workers, 48% sexual assault survivors, and 49% nonhealth care needlestick-injured persons. ED practitioners were more willing to offer HIV PEP after exposures to HIV-infected or high-risk sources than unknown or low- risk sources, as well as after sexual assault than consensual sex. Female practitioners, those who had themselves taken HIV PEP, resident physicians, and ED practitioners with fewer than 6 years of clinical practice were generally more apt to offer HIV PEP. Educational campaigns appear to be necessary to help ED practitioners determine when HIV PEP is appropriate.


Dosage finding and outcome in the treatment of schizophrenic inpatients with amisulpride. Results of a drug utilization observation study.
Amisulpride is an unique neuroleptic drug insofar as it has a dual pharmacodynamic effect. At low doses it blocks selectively presynaptic autoreceptors, and at high doses it blocks postsynaptic D(2)/D(3) receptors. This allows the dosage to be adjusted and the treatment tailored to various clinical situations. It is unknown whether this pharmacological property has any bearing for routine treatment. The questions are: which dosages of amisulpride are chosen by physicians in the treatment of schizophrenic inpatients and does this dosage handling deviate from prescription guidelines?; which factors can explain dosage selection, and what is the treatment outcome with different dosages? The study pertains to drug management and dosage finding as principal factors in explaining positive and negative medication results. In a drug utilization observation study the prescribing of amisulpride for 811 schizophrenic inpatients from 240 psychiatric hospitals was monitored for 8 weeks. Standardized assessment included dosage, the positive and negative symptom scale (PANSS), the clinical global impression rating (CGI), the patients' subjective reaction to amisulpride, psychosocial functioning, EPS and other adverse events. The mean observation period was 49 days. The mean initial daily dose of amisulpride was 361 mg/day. The mean daily dose at day 56 was on average 550 (SD 266) mg/d, ranging from 100 mg to 1600 mg. 17.9% of patients received a maximum dose up to 399 mg/d, 48.1% between 400 and 799 mg/d, and 25.5% 800 mg/d and higher. Higher doses were preferably prescribed for males, patients with involuntary admission, patients with paranoid schizophrenia with acute exacerbation, high CGI and high PANSS-positive scores. Patients with higher doses of amisulpride at the same time received higher rates of additional other neuroleptic drugs. Higher doses yield better results in very severe cases. Prescribed dosages were in the lower range of what is recommended for acute cases. Dosage was significantly influenced by the severity of the illness. Polypharmacy was the rule rather than the exception. Efficacy rates under conditions of routine care were similar to the results from controlled clinical trials, which speaks for their generalizability. Very severe cases profit from higher doses.


Allergic contact dermatitis with a fertilizer containing hydrogen cyanamide (Dormex).
Cyanamide is a chemical substance used in the treatment of chronic alcoholism as well in agriculture as a fertilizer. We report the case of a 28-year-old healthy non-atopic man that developed a severe skin eruption after the accidental penetration of a small amount of Dormex (a plant growth regulator containing cyanamide) through the patient's gloves. Patch tests revealed positive reactions to Dormex 1% pet. and cyanamide at a dilution of 0.1% pet. and 1% pet. We discuss the causes of sensitization in a patients that regularly used protective measures during anti-parasites treatments.


Alpha-1-antitrypsin: evidence for a fifth PI M subtype and a new deficiency allele PI*Z augsburg.
The phenotypes of the protease inhibitor (PI) alpha-1-antitrypsin have been analyzed by isoelectric focusing on polyacrylamide gels. With improved resolution by a modified procedure it was possible to demonstrate a fifth PI*M suballele. The bands of PI M5 are located between PI M1 and PI M3. In addition, a further deficiency allele similar to PI*Z was found in a female patient with obstructive pulmonary disease. This variant was provisionally named PI Z augsburg (PI Z aug). Family data confirm a simple codominant mode of inheritance for PI Z aug.


Kindling-induced changes in the EEG recorded during stimulation from the site of stimulation. II. Comparison between spontaneous and evoked potentials.
We previously described how the EEG activity recorded during kindling-inducing tetanic stimulation, from the site of stimulation, consists of three major components. Here, we investigate the nature and role of component 1, an initial evoked potential, seen at the beginning of tetanus, and we compare it with the potential evoked by single-pulse stimulation and with the spontaneous interictal discharges seen after kindling in both the amygdala and hippocampus. The amplitude of component 1 increased during kindling, and the waveform, latency, and stimulus-response curve of component 1 were all similar to those of potentials evoked by single-pulse stimulation. Furthermore, in acute experiments, in which the amygdala was kindled by tetanic stimulation at 1-h intervals, the evoked potentials in the amygdala and pyriform cortex were markedly potentiated, whereas no obvious potential was recorded at the same latency from the ventral or dorsal hippocampus, subiculum, nor the prepyriform region. Thus, we conclude that, in the case of amygdala kindling, the nature of component 1 is a local direct and monosynaptic response involving the amygdala and pyriform cortex, and that the increased amplitude of component 1 after kindling may be related to long-term potentiation. Although the single-pulse stimulation produced late burst-like components in the amygdala and hippocampus after kindling, it produced neither EEG suppression, well-formed rhythmic synchronous bursts, nor epileptiform discharge, suggesting that component 1 alone is not sufficient for the subsequent events that may be essential to the seizure-triggering mechanism.


Clinical use of oral antihistamines and intranasal corticosteroids in patients with allergic rhinitis.
Second-generation oral antihistamines (AH) and intranasal corticosteroids (ICS) are the most widely used drugs for allergic rhinitis (AR). To obtain information on the preferences for and applications of these drugs under conditions of routine clinical practice. We performed a multicenter multidisciplinary observational study. Participating physicians completed a questionnaire with information on preferences for and application of drugs for AR, patient characteristics, and physician/patient satisfaction with the treatment provided (visual analog scale). A total of 1008 physicians participated in the study (primary care physicians, 53%; ear, nose, and throat specialists, 28%; allergologists, 19%). Treatment preferences in AR were AH combined with ICS (7.68), AH (7.25), and ICS (6.94). AH and ICS were used continuously by 58% and 71% of patients, respectively. Physicians reported having a good knowledge of the Allergic Rhinitis and its Impact on Asthma guidelines (93%), and 90% claimed to follow the guidelines. A total of 4040 patients were recruited (52% females, mean [SD] age 34 [14] years). The findings for AR were as follows: mean (SD) duration, 9 (8) years; persistent AR, 52%; mild AR, 72%; moderate AR, 7%; and severe AR, 1%. Patients considered the disorder to be well controlled/almost controlled (79%). As for treatment, 77% followed the regimen recommended by the physician. Oral treatment (41%) and intranasal treatment (22%) were preferred, while 35% showed no preference for any given administration route. The treatments prescribed were AH combined with ICS (66%), AH (20%), ICS (11%), other antihistamines (4%), and other drugs (6%). Combination treatment was the preferred therapy, regardless of the type of rhinitis. Physicians prefer and more often use combination treatment with oral AH and ICS, regardless of the frequency and intensity of AR.


Association of protein-tyrosine phosphatase PTP-BAS with the transcription-factor-inhibitory protein IkappaBalpha through interaction between the PDZ1 domain and ankyrin repeats.
PTP-BAS is a membrane-associated protein tyrosine phosphatase containing a band-4.1 homology region and five PDZ (PSD-95 Dlg ZO-1) [discs-large homology region ('DHR')/Gly-Leu-Gly-Phe ('GLGF')] domains. The second and fourth PDZ domains were reported to associate with Fas/CD95. By using the first PDZ domain as a bait in yeast two-hybrid screening, we have identified IkappaBalpha as a binding protein. IkappaBalpha associated with PDZ1 through the stretch of the N-terminal three ankyrin repeats. The association was also confirmed in HeLa cells by co-immunoprecipitation experiments. Inhibition of PTP-BAS by expression of dominant-negative PTP-BAS mutant resulted in tyrosine-phosphorylation of IkappaBalpha. Tyrosine-phosphorylation of IkappaBalpha is a key event in activation of nuclear factor (NF)-kappaB during reoxygenation. PTP-BAS may thus play a regulatory role in activation of NF-kappaB under high oxidative stress.


Distribution of autoantibodies to insulinoma-associated antigen-2 and zinc transporter 8 in type 1 diabetes and latent autoimmune diabetes: A nationwide, multicentre, cross-sectional study.
This study investigated insulinoma-associated-2 autoantibody (IA-2A) and zinc transporter 8 autoantibody (ZnT8A) distribution in patients with type 1 diabetes (T1D) and latent autoimmune diabetes (LAD) and the autoantibodies' association with clinical characteristics and HLA-DR-DQ genes. This cross-sectional study recruited 17,536 patients with diabetes from 46 hospitals across China. A total of 189 patients with T1D and 58 patients with LAD with IA-2A positivity, 126 patients with T1D and 86 patients with LAD with ZnT8A positivity, and 231 patients with type 2 diabetes (T2D) were selected to evaluate islet autoantibodies, clinical phenotypes, and HLA-DR-DQ gene frequency. IA-2A was bimodally distributed in patients with T1D and LAD. Patients with low IA-2A titre LAD had lower fasting C-peptide (FCP) (p < 0.01), lower postprandial C-peptide (PCP) (p < 0.001), and higher haemoglobin A1c (HbA1c) levels (p < 0.05) than patients with T2D. Patients with high IA-2A titre LAD were younger than patients with low IA-2A titre LAD (p < 0.05). Patients with low IA-2A titre T1D had lower FCP (p < 0.01), lower PCP (p < 0.01), and higher HbA1c levels (p < 0.05) than patients with high IA-2A titre LAD. HLA-DR-DQ genetic analysis demonstrated that the frequency of susceptible HLA haplotypes was higher in IA-2A-positive patients (p < 0.001) than in patients with T2D. Patients with high ZnT8A titre LAD had lower FCP (p = 0.045), lower PCP (p = 0.023), and higher HbA1c levels (p = 0.009) and a higher frequency of total susceptible haplotypes (p < 0.001) than patients with low ZnT8A titre LAD. IA-2A in patients with T1D and LAD was bimodally distributed, and the presence of IA-2A could demonstrate partial LAD clinical characteristics. ZnT8A titre had a certain predictive value for islet functions in patients with LAD.


Molecular testing of multiple HIV-1 transmissions in a criminal case.
To test the a priori hypothesis of HIV-1 transmission from one suspect to six recipients in a criminal case. Partial pol and/or env sequences were obtained for at least two samples of the suspect and the victims. Appropriate local controls were sampled based on epidemiological and subtype criteria. Phylogenetic testing was performed using different reconstruction methods. Phylogenetic analyses consistently inferred a monophyletic cluster for the suspect and victim samples in both genome regions. This was highly supported by parametric and non-parametric bootstrapping techniques. Moreover, the controls most closely related to the suspect-victim cluster had a similar geographical origin to the suspect. Taking into account the limitations on the conclusions that can be drawn from molecular investigations we could infer that our molecular data is consistent with a scenario of multiple HIV transmission between suspect and victims.


Comparison of receptive field expansion produced by GABA(B) and GABA(A) receptor antagonists in raccoon primary somatosensory cortex.
Recordings were made from 62 neurons in the forepaw representation of primary somatosensory cortex in anesthetized raccoons. Microiontophoretic administration of a specific GABA(B) receptor antagonist, CGP 55845, produced receptive field expansion in 74% of 46 neurons, in which it was tested first. The mean receptive field area was approximately doubled, with increases ranging from 12 to 500%. The GABA(B) receptor agonist baclofen reduced the receptive field in most (11 of 16) neurons, but increased the size in 4 neurons. Comparison of the effects of GABA(B) and GABA(A) antagonists in the same cells showed that GABA(A) receptor blockade produced greater expansion than GABA(B) blockade (144% vs 114%, respectively). Simultaneous administration of the two antagonists produced additional expansion in 16 of 25 neurons. There was no evidence of separate skin regions being masked by the two GABA receptor subtypes, as the larger expansion usually included the skin that was unmasked by the less effective drug. These results indicate that both GABA(B) and GABA(A) receptors play a role in shaping the normal receptive fields in somatosensory cortex.


Variability of endonucleolytic activity indicates high genetic diversity within the natural population ofSelenomonas ruminantium.
The population of bacteria ofSelenomonas ruminantium species in the rumen of fallow-deer was analyzed using endonucleolytic activity assay and plasmid profiles. This analysis indicated a high diversity within the population ofS. ruminantium. At least 12 different restriction profiles, indicating the presence of the different specificity nucleases, have been observed. Site-specific endonucleases were detected in 17 out of 45 strains tested. In other strains a various level of nonspecific activity was detected. Plasmid DNAs ranging in size from 0.9 to more than 25 kbp were detected in 60% of strains analyzed. No or little correlation was observed between the endonuclease activity and the plasmid content. The presence of different specificity endonucleases, as well as differences of plasmid profiles of isolates possessing identical specific activity indicate that the population ofS. ruminantium in the rumen of an individual animal consists of at least 10 different clones.


Teacher-student interactions and attachment states of mind as predictors of early romantic involvement and risky sexual behaviors.
Adolescents' capacities to negotiate sexual behavior in romantic relationships have important implications for their reproductive and health outcomes. This study examined adolescents' interactions with teachers and attachment states of mind as predictors of their romantic involvement and risky sexual behavior in an economically disadvantaged sample. Negative interactions with teachers predicted increased sexual risk-taking behaviors and females' early romantic involvement. Preoccupied states of mind increased risk for early romantic involvement and the likelihood that females would engage in risky sexual behavior. The findings demonstrate how adolescents' school experiences contribute to adaptation in romantic relationships in mid to late adolescence above and beyond representations of parent-child attachment.


Sarcopenia is a useful risk stratification tool to prognosticate splenic abscess patients in the emergency department.
Splenic abscess is a life-threatening surgical emergency which requires early diagnosis and intervention to maximize patient outcomes. This can be achieved through accurate risk stratification in the emergency department (ED). Sarcopenia refers to an age-related loss of skeletal muscle mass and strength that is accompanied by major physiologic and clinical ramifications, and often signifies decreased physiologic reserves. It is associated with poor clinical outcomes in sepsis, acute respiratory failure, oncological surgery, and liver transplantation. This study evaluates the utility of sarcopenia as a radiological stratification tool to predict in-hospital mortality of splenic abscess patients in the ED. This will assist emergency physicians, internists and surgeons in rapid risk stratification, assessing treatment options, and communicating with family members. 99 adult patients at four training and research hospitals who had undergone an abdominal contrast computed tomography scan in the ED with the final diagnosis of splenic abscess from January 2004 to November 2017 were recruited. Evaluation for sarcopenia was performed via calculating the psoas cross-sectional area at the level of the third lumbar vertebra and normalising for height, before checking it against pre-defined values. Univariate analyses were used to evaluate the differences between survivors and non-survivors. Sensitivity, specificity, and predictive values of the presence of sarcopenia in predicting in-hospital mortality were calculated. Kaplan-Meier methods, log-rank test, and Cox proportional hazards model were also performed to examine survival between groups with sarcopenia versus non-sarcopenia. Splenic abscess patients with sarcopenia were 7.56 times more at risk of in-hospital mortality than those without sarcopenia (multivariate-adjusted HR: 7.56; 95% CI: 1.55-36.93). Presence of sarcopenia was found to have 84.62% sensitivity and 96.49% negative predictive value in predicting mortality. Sarcopenia is associated with poor prognoses of in-hospital mortality in patients with splenic abscess presenting to the ED. We recommend its use in the ED to rapidly risk stratify and predict outcome to guide treatment strategies.


Interleukin-6 (IL-6) serum concentrations in dogs with hepatitis and hepatic tumours compared with those with extra-hepatic inflammation and tumours.
Cytokines are part of pathogenesis in many diseases. Their measurement could be interesting for diagnostic purposes. One cytokine which participates in different inflammatory and neoplastic diseases is interleukin-6 (IL-6). The aim of this study was to investigate the IL-6 serum concentration in dogs with different liver diseases to show if there is any association between the cytokine serum level and the disease aetiology or the degree of the disease. IL-6 was measured in dogs with acute hepatitis, chronic hepatitis of different degrees and primary and secondary liver tumours. The data were compared with clinically healthy dogs and dogs with extra-hepatic diseases. For measurement, a commercial ELISA Kit (R&D Systems) was used. Compared with clinically healthy dogs and dogs with diabetes mellitus, all dogs with an intra- or extra-hepatic inflammatory or neoplastic disease have increased serum levels of IL-6. Dogs with acute hepatitis have significantly increased IL-6 serum concentrations compared with dogs with chronic hepatitis (P < 0.05). No significant difference between mild and moderate chronic hepatitis exists (P > 0.05). Dogs with secondary liver tumours have significantly increased IL-6 serum concentrations in comparison to dogs with primary liver tumours (P < 0.01), but both groups have comparable IL-6 serum concentration to dogs with extra-hepatic tumours. Measurement of IL-6 serum concentration may help differentiate between acute and chronic hepatitis and between primary and secondary liver tumours. Further information about the aetiology of the liver disease cannot be obtained by measuring IL-6 in the serum.


Homobimetallic Au(I)-Au(I) and Heterotrimetallic Au(I)-Fe(II)-Au(I) Complexes with Dialkyldithiophosphates and Phosphine Ligands: Structural Characterization, DFT Analysis, and Tyrosinase Inhibitory and Biological Effects.
The role of bridging and terminal ligand electronic and steric properties on the structure and antiproliferative activity of two-coordinated gold(I) complexes was investigated on seven novel binuclear and trinuclear gold(I) complexes synthesized by the reaction of either Au2(dppm)Cl2, Au2(dppe)Cl2, or Au2(dppf)Cl2 with potassium diisopropyldithiophosphate, K[(S-OiPr)2], potassium dicyclohexyldithiophosphate, K[(S-OCy)2], or sodium bis(methimazolyl)borate, Na(S-Mt)2, which afforded air-stable gold(I) complexes. In 1-7, the gold(I) centers adopt a two-coordinated linear geometry and are structurally similar. However, their structural features and antiproliferative properties highly depend upon subtle ligand substituent changes. All complexes were validated by 1H, 13C{1H}, 31P NMR, and IR spectroscopy. The solid-state structures of 1, 2, 3, 6, and 7 were confirmed using single-crystal X-ray diffraction. A density functional theory geometry optimization calculation was used to extract further structural and electronic information. To investigate the possible cytotoxicities of 2, 3, and 7, in vitro cellular tests were carried out on the human cancerous breast cell line MCF-7. 2 and 7 show promising cytotoxicity.


Critical issues on opioids in chronic non-cancer pain: an epidemiological study.
The aim of the study was epidemiologically to evaluate the long-term effects of opioids on pain relief, quality of life and functional capacity in long-term/chronic non-cancer pain. The study was based on data from the 2000 Danish Health and Morbidity Survey. As part of a representative National random sample of 16,684 individuals (>16 years of age), 10,066 took part in an interview and completed a self-administered questionnaire. Cancer patients were excluded. The interview and the self-administered questionnaire included questions on chronic/long-lasting pain (>6 months), health-related quality of life (SF-36), use of the health care system, functional capabilities, satisfaction with medical pain treatment and regular or continuous use of medications. Participants reporting pain were divided into opioid and non-opioid users. The analyses were adjusted for age, gender, concomitant use of anxiolytics and antidepressants and pain intensity. Pain relief, quality of life and functional capacity among opioid users were compared with non-opioid users. Opioid usage was significantly associated with reporting of moderate/severe or very severe pain, poor self-rated health, not being engaged in employment, higher use of the health care system, and a negative influence on quality of life as registered in all items in SF-36. Because of the cross-sectional nature causative relationships cannot be ascertained. However, it is remarkable that opioid treatment of long-term/chronic non-cancer pain does not seem to fulfil any of the key outcome opioid treatment goals: pain relief, improved quality of life and improved functional capacity.


Erratum: [Corrigendum] Differential regulation of mitochondrial complex I and oxidative stress based on metastatic potential of colorectal cancer cells.
[This corrects the article DOI: 10.3892/ol.2020.12176.].


Crystal structure of cobalt hydroxide carbonate Co2CO3(OH)2: density functional theory and X-ray diffraction investigation.
The cobalt carbonate hydroxide Co2CO3(OH)2 is a technologically important solid which is used as a precursor for the synthesis of cobalt oxides in a wide range of applications. It also has relevance as a potential immobilizer of the toxic element cobalt in the natural environment, but its detailed crystal structure is so far unknown. The structure of Co2CO3(OH)2 has now been investigated using density functional theory (DFT) simulations and powder X-ray diffraction (PXRD) measurements on samples synthesized via deposition from aqueous solution. Two possible monoclinic phases are considered, with closely related but symmetrically different crystal structures, based on those of the minerals malachite [Cu2CO3(OH)2] and rosasite [Cu1.5Zn0.5CO3(OH)2], as well as an orthorhombic phase that can be seen as a common parent structure for the two monoclinic phases, and a triclinic phase with the structure of the mineral kolwezite [Cu1.34Co0.66CO3(OH)2]. The DFT simulations predict that the rosasite-like and malachite-like phases are two different local minima of the potential energy landscape for Co2CO3(OH)2 and are practically degenerate in energy, while the orthorhombic and triclinic structures are unstable and experience barrierless transformations to the malachite phase upon relaxation. The best fit to the PXRD data is obtained using a rosasite model [monoclinic with space group P1121/n and cell parameters a = 3.1408 (4) Å, b = 12.2914 (17) Å, c = 9.3311 (16) Å and γ = 82.299 (16)°]. However, some features of the PXRD pattern are still not well accounted for by this refinement and the residual parameters are relatively poor. The relationship between the rosasite and malachite phases of Co2CO3(OH)2 is discussed and it is shown that they can be seen as polytypes. Based on the similar calculated stabilities of these two polytypes, it is speculated that some level of stacking disorder could account for the poor fit of the PXRD data. The possibility that Co2CO3(OH)2 could crystallize, under different growth conditions, as either rosasite or malachite, or even as a stacking-disordered phase intermediate between the two, requires further investigation.


[Nonspecific resistance to heterologous viral infection after immunization with smallpox vaccine].
The level of development of nonspecific resistance to influenza virus infection after immunization with variola vaccine, the dynamics of changes in DNA synthesis in the spleen cells and concentration of nonspecific immunoglobulins in the blood serum of mice after immunization and infection with influenza virus were studied. A close correlation between DNA synthesis, concentration of immunoglobulins, and the level of nonspecific resistance to heterologous virus infection was found.


Cyclooxygenase-1 haplotype modulates platelet response to aspirin.
Aspirin (acetylsalicylic acid) irreversibly inhibits platelet cyclooxygenase (COX)-1, the enzyme that converts arachidonic acid (AA) to the potent platelet agonist thromboxane (TX) A2. Despite clear benefit from aspirin in patients with cardiovascular disease (CAD), evidence of heterogeneity in the way individuals respond has given rise to the concept of 'aspirin resistance.' To evaluate the hypothesis that incomplete suppression of platelet COX as a consequence of variation in the COX-1 gene may affect aspirin response and thus contribute to aspirin resistance. Aspirin response, determined by serum TXB2 levels and AA-induced platelet aggregation, was prospectively studied in patients (n = 144) with stable CAD taking aspirin (75-300 mg). Patients were genotyped for five single nucleotide polymorphisms in COX-1 [A-842G, C22T (R8W), G128A (Q41Q), C644A (G213G) and C714A (L237M)]. Haplotype frequencies and effect of haplotype on two platelet phenotypes were estimated by maximum likelihood. The four most common haplotypes were considered separately and less common haplotypes pooled. COX-1 haplotype was significantly associated with aspirin response determined by AA-induced platelet aggregation (P = 0.004; 4 d.f.). Serum TXB2 generation was also related to genotype (P = 0.02; 4 d.f.). Genetic variability in COX-1 appears to modulate both AA-induced platelet aggregation and thromboxane generation. Heterogeneity in the way patients respond to aspirin may in part reflect variation in COX-1 genotype.


HIV-related risk behaviors among Roma youth in Serbia: results of two community-based surveys.
The Roma constitute a large ethnic minority in Serbia, and are one of the poorest and most marginalized groups in Europe. Roma youth may be at high risk for hepatitis C, HIV, and other sexually transmitted infections, but little is known about the prevalence of these infectious diseases, HIV-related knowledge, and risky sexual behaviors in this vulnerable population. We used a respondent-driven sampling to conduct biobehavioral surveys of Roma youth (aged 15-24 years) in Belgrade and Kragujevac, and to document HIV-related knowledge and risky sexual behaviors, health-seeking behaviors, and seroprevalence of HIV, hepatitis C virus (HCV), and syphilis. Four hundred eleven Roma youth participated in this study. One participant had HIV, four had HCV, and none had syphilis. Risky sexual behaviors were highly prevalent, especially among male subjects: 36.2% (Belgrade) and 45.1% (Kragujevac) had sexual debut before the age of 15 years; 53.9% (Belgrade) and 61.1% (Kragujevac) had more than one sexual partner in the past year; 11.5% (Belgrade) and 4.6% (Kragujevac) reported engaging in commercial sex; and 4.0% (Belgrade) and 3.2% (Kragujevac) reported having anal sex with other men. Among female subjects aged <25 years, 33.5% (Belgrade) and 25.7% (Kragujevac) reported having an abortion. One-quarter of all participants answered all five HIV knowledge questions correctly. Fortunately, the current prevalence of HIV, HCV, and syphilis is low; however, the high prevalence of reported risky behaviors suggests that Roma youth in Serbia are at high risk of contracting sexually transmitted infections.


Consumer perspectives on the usability and value of the iBOT(®) wheelchair: findings from a case series.
The iBOT(®) is an advanced power wheelchair introduced in 2003 for people with mobility impairments to enhance their independence and community access. Although this innovation soon gained popularity, the production of this wheelchair was recently stopped owing to the lower-than-expected sale figures. In this scenario, this study examines the impact of this wheelchair on current consumers by highlighting its usability in multiple contexts and verifying the value associated with its ownership. Seven active consumers of the iBOT(®) were interviewed using a mixed method approach. Participants discussed and rated the iBOT's usability in relation to their standard power wheelchair and shared their perceived value for it. A content analysis was used to elucidate the qualitative data, whereas the quantitative data was analyzed using descriptive and non-parametric comparisons to compute differences in consumer ratings for the two wheelchairs. Results, although statistically non-significant (α < 0.05), indicated the iBOT(®) to be a highly multi-functional wheelchair with relatively superior usability in workplace (p = 0.15), community (p = 0.18) and outdoors (p = 0.1). Participants greatly valued its capability to expand their mobility in otherwise inaccessible environments and to enhance their social participation through eye level communication. The iBOT(®) serves as an exemplar to promote interest and funding for advanced AT devices for people with disabilities. [Box: see text].


Speech recognition in background noise of cochlear implant patients.
The performances of adult patients using Spectral peak (Nucleus 22 or Nucleus 24 patients) or Continuous Interleaved Sampling or Advanced Combination Encoder (Clarion patients) were evaluated in their ability to perform in quiet and in 2 levels of background noise. Ninety-six patients were tested with the City University of New York Sentences presented at 70 dB in quiet and at signal-to-noise ratios (SNR) of +10 and +5 dB. Patients were scored on the number of words perceived correctly. Scores were different at each condition (P < 0.05): 88% words correct in quiet, 73% correct at an SNR of +10 dB, and 47% correct at an SNR of +5 dB. Linear regression analysis found no significant correlation between test score and age at implantation or time using the implant. A weak negative correlation was found between years of hearing loss and score. Competing noise interferes with comprehension of connected speech for most cochlear implant patients.


Role of surgery in the treatment of osteoradionecrosis and its complications after radiotherapy for nasopharyngeal carcinoma.
The purpose of this study was to review the efficacy of surgery for patients with osteoradionecrosis (ORN) after radiotherapy for nasopharyngeal carcinoma (NPC). Between 2000 and 2016, we identified 162 patients with skull base ORN, among which 58 patients required surgery. A retrospective medical chart review was performed and the indications and results of surgical interventions were recorded. All surgeries were performed for the treatment of secondary complications of ORN, including central nervous system (CNS) infection (48.4%), blowout bleeding (24.1%), and severe pain (17.2%). Endoscopic debridement was done in 12 patients, whereas the rest required either maxillary swing or mandibulotomy, depending on the location of the necrosis. The majority of the patients required free vastus lateralis flap (72.5%) for reconstruction. Surgery was effective in the control of infection, bleeding, and pain. Multivariate analysis identified reirradiation and bone exposure on MRI as the significant independent risk factors predicting the future need of surgery. Surgery is effective in the treatment of secondary complications of skull base ORN after previous radiotherapy for NPC.


Effect of octanoate injection on rat blood-brain barrier.
Serum concentrations of short and medium chain fatty acids, including octanoate, are elevated in hepatic encephalopathy and Reye syndrome. Injection of octanoate into animals produces features reminiscent of Reye syndrome, but the mechanisms are unknown. To evaluate the effect of octanoate on blood-brain barrier permeability, three techniques were used. Entry of horseradish peroxidase and trypan blue into brain was not observed after octanoate injection. Brain uptake of tryptamine, tyrosine and methionine was increased significantly by octanoate, while uptake of insulin was unchanged. This study suggests that octanoate may produce central nervous system alterations by facilitating entry of certain low molecular weight compounds into brain. This may represent one mechanism for the development of encephalopathy in liver disease and Reye syndrome.


Bismuth-inhibitory effects on bacteria and stimulation of fungal growth in vitro.
Bismuth salicylate was found to inhibit the growth of a range of bacteria and yeast, "Candida albicans". In general the growth of bacteria did not result in increase in bismuth solubilisation, in contrast, bismuth solubilisation increased following the growth of C. albicans. A significant increase in the biomass (dry weight) of Aspergillus niger and Aspergillus oryzae occurred in vitro when these fungi were grown in the presence of bismuth salicylate. Biomass increase occurred over a range of bismuth compound additions, which in the case of A. oryzae was associated with increase in the solubilisation of the insoluble bismuth compounds.


Improving the decolorization activity of Bacillus pumilus W3 CotA-laccase to Congo Red by rational modification.
Congo Red (CR) is a typical azo dye with highly toxic and carcinogenic properties. This study aimed to improve the decolorization activity of Bacillus pumilus W3 CotA-laccase for azo dye CR. This work analyzed the interaction between CotA-laccase and CR based on homology modeling and molecular docking. The three amino acids (Gly323, Thr377, Thr418) in the substrate-binding pocket were rationally modified through saturation mutation. Finally, the obtained multi-site mutants T377I/T418G and G323S/T377I/T418G decolorized 76.59% and 59.37% of CR within 24 h at pH 8.0 without a mediator, which were 3.15- and 2.44-fold higher than the wild-type CotA. The catalytic efficiency of the multi-site mutants T377I/T418G and G323S/T377I/T418G to CR were increased by 2.21- and 2.01-fold compared with the wild-type CotA, respectively. The mechanism of activity enhancement of mutants was proposed by structural analysis. This evidence suggests that the mutants T377I/T418G and G323S/T377I/T418G could be used as novel bioremediation tools.


A survey on the degree of eye discomfort caused by video terminal use among college students in different altitudes.
To analyze the risk factors associated with different levels of eye discomfort due to video terminal use among college students at different altitudes. This cross-sectional study was conducted to assess the prevalence and extent of eye discomfort by distributing an questionnaire to university students via the Internet. To analyze the causes and risk factors of eye discomfort among college students at different altitudes after using video terminals. A total of 647 participants who met the criteria were included in this survey, of whom 292 (45.1%) were males and 355 (54.9%) were females. The results of the survey showed 194 (30.0%) participants without eye discomfort and 453 (70.0%) participants with eye discomfort. The results of the univariate comparison of the degree of eye discomfort in the study subjects with different characteristics showed that the differences in the degree of eye discomfort were statistically significant (P < 0.05) for the 7 groups of indicators: gender, region, wearing corneal contact lenses for more than 2 h per day, frequent use of eye drops, sleep time, total time of VDT use per day, and total time per VDT use, while the remaining indicators, including age, profession, and whether refractive surgery or other eye surgery was performed, whether frame glasses were worn for a long time, and duration of daily mask wear were not statistically significant. The results of multi-factor logistic analysis of the degree of eye discomfort in the study subjects with different characteristics showed that gender, region, frequent use of eye drops, sleep time, and total time of VDT use per day were the risk factors affecting the degree of eye discomfort. Female, high altitude, frequent use of eye drops, shorter daily sleep duration and longer daily VDT use were associated risk factors for the development of severe eye discomfort, where the severity of eye discomfort was significantly negatively correlated with increased sleep duration and significantly positively correlated with increased total time of VDT use.


Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis.
Despite vaccine availability, influenza remains a substantial global public health concern. Here, we report interim findings on the primary and secondary objectives of the safety, reactogenicity, and humoral immunogenicity of a quadrivalent messenger RNA (mRNA) vaccine against seasonal influenza, mRNA-1010, from the first 2 parts of a 3-part, first-in-human, phase 1/2 clinical trial in healthy adults aged ≥18 years (NCT04956575). In the placebo-controlled Part 1, a single dose of mRNA-1010 (50 µg, 100 µg, or 200 µg) elicited hemagglutination inhibition (HAI) titers against vaccine-matched strains. In the active-comparator-controlled Part 2, mRNA-1010 (25 µg, 50 µg, or 100 µg) elicited higher HAI titers than a standard dose, inactivated seasonal influenza vaccine for influenza A strains and comparable HAI titers for influenza B strains. No safety concerns were identified; solicited adverse reactions were dose-dependent and more frequent after receipt of mRNA-1010 than the active comparator. These interim data support continued development of mRNA-1010.


Dynamics of PO2 and VO2 in resting and contracting rat spinotrapezius muscle.
This study examined changes in interstitial PO2, which allowed calculation of VO2 during periods of rest, muscle contraction and recovery using an in situ rat spinotrapezius muscle preparation. The PO2 was measured using phosphorescence quenching microscopy and the muscle VO2 was calculated as the rate of O2 disappearance during brief periods of muscle compression to stop blood flow with a supra-systolic pressure. The PO2 and VO2 measurements were made during "5 s compression and 15 s recovery" (CR) cycles. With all three stimulation frequencies, 1, 2 and 4 Hz, the fall in interstitial PO2 and rise in VO2 from resting values occurred within the first 20 s of contraction. The PO2 during contraction became lower as stimulation frequency increased from 1 to 4 Hz. VO2 was higher at 2 Hz than at 1 Hz contraction. With cessation of stimulation, PO2 began increasing exponentially towards baseline values. After 1 and 2 Hz contraction, the fall in muscle VO2 was delayed by one CR cycle and then exponentially decreased towards resting values. After 4 Hz stimulation, VO2 increased for 2 cycles and then decreased. The post-contraction transients of PO2 and VO2 were not synchronous and had different time constants. With further analysis two distinct functional responses were identified across all stimulation frequencies having PO2 during contraction above or below 30 mmHg. The corresponding VO2 responses were different - for "high" PO2, muscle VO2 reached high levels, while for the "low" PO2 data set muscle VO2 remained low. Recovery patterns were similar to those described above. In summary, local microscopic PO2 and VO2 were measured in resting and contracting muscle in situ and the post-contraction transients of PO2 and VO2 were all much slower than the onset transients.


Total parenteral nutrition-associated cholestasis in surgical neonates may be reversed by intravenous cholecystokinin: a preliminary report.
Neonatal infants who require total parenteral nutrition (TPN) after major operations are susceptible to total parenteral nutrition-associated cholestasis (TPNAC). A therapeutic dilemma ensues if cholestasis does not resolve after the institution of full enteral nutrition. The authors report the reversal of TPN-associated cholestasis by intravenous cholecystokinin in eight infants who had undergone major surgery during the neonatal period. The indications for surgery were necrotizing enterocolitis in three patients, midgut volvulus in one, gastroschisis in one, diaphragmatic hernia in one, necrosis of the stomach in one, and cardiac anomaly in one. Four of the infants were premature. Median duration of TPN was 25 days (range, 20 to 150 days). Seven patients were weaned from TPN before treatment with cholecystokinin was instituted Mean duration of pretreatment full enteral nutrition in these seven patients was 35 days (range, 20 to 55 days). One girl with short gut syndrome tolerated only 10% of her caloric needs via the enteral route. All patients had alcoholic stools, conjugated hyperbilirubinemia, no excretion of Technetium-labeled HIDA to the biliary tree or duodenum (six patients), and significantly elevated liver enzyme values. In three patients, echography showed biliary sludge or stones in the gall bladder. Porcine cholecystokinin (2 IDU/kg) was administered intravenously for 3 to 5 days. If the stool color did not normalize, cholecystokinin injections were repeated using a larger dose (4 IDU/kg). In seven patients, including the girl with short gut syndrome, the clinical jaundice and conjugated hyperbilirubinemia completely resolved within 1 to six weeks. No biliary sludge or stones were seen in the posttreatment echography in any of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Long-term persistence of antianginal effect of oral verapamil in chronic stable angina.
The long-term antianginal effect of orally administered verapamil over 1 year of continuous treatment was assessed in 11 patients with effort-induced angina. In the short-term phase of the study, patients were given, in random order, placebo and verapamil (360 mg/day). The tolerated work load during a bicycle exercise test was 531.8 +/- 123.0 kg/min on placebo and 763.6 +/- 124.7 kg/min on verapamil (p less than 0.001). Subsequently all patients entered a long-term study of 1-year continuous treatment with 120 mg t.i.d. verapamil. The tolerated work load at 8-week (736.4 +/- 105.1 kg/min) and 1-year (804.6 +/- 101.1 kg/min) tests did not significantly differ from the results in the short-term study. The average verapamil plasma level was 138.5 +/- 90.6 ng/ml before and 357.8 +/- 199.2 ng/ml 90 min after drug administration; the average norverapamil plasma levels were, respectively, 248.0 +/- 84.4 and 368.0 +/- 135.9 ng/ml. There was no correlation between verapamil or norverapamil plasma concentrations and the antianginal effect. No patient developed signs of heart failure during the treatment. Two patients had mild constipation. The average P-R interval was slightly, although significantly (p less than 0.01) prolonged, but no patient developed first-degree atrioventricular block. We conclude that verapamil proves an effective and safe drug in the treatment of effort-induced angina; the beneficial effects of the short-term treatment are sustained during 1 year of continuous treatment.


First day post-operative review following uncomplicated phacoemulsification.
To determine whether the first day review is essential in management of patients following uncomplicated phacoemulsification with intraocular lens implantation. Patients are routinely seen on the day following surgery. This can produce logistical problems in patient attendance that can necessitate an overnight stay. If the first day review were abandoned this would lead to an increased uptake of day case surgery and a reduction in health care costs. A retrospective cohort study was performed on all cases of uncomplicated phacoemulsification with intraocular lens implant surgery over a 6 month period. Slit lamp examination findings on the first post-operative day were reviewed. Visual acuity, corneal clarity, anterior chamber activity, intraocular pressure and configuration of the pupil were recorded. Any cases that failed to meet predetermined criteria underwent full case-note review. The subsequent management of these patients was analysed. Of the 201 cases of uncomplicated surgery, 74 cases (37%) failed to meet the study criteria and underwent review. Of these only 12 (6%) had their management altered as a result of the first day post-operative findings. This was entirely due to raised intraocular pressure. Visual acuity, corneal oedema and activity in the anterior chamber all improved on subsequent follow-up. The first day review of uncomplicated phacoemulsification with lens implant surgery provides the opportunity to treat raised intraocular pressure. A prospective randomised study is needed to identify means to prevent the post-operative intraocular pressure rise before we are able to consider abandoning the first review.


Nitric oxide in wound-healing.
Modulation of the complex process of wound-healing remains a surgical challenge. Little improvement beyond controlling infection, gentle tissue handling, and debridement of necrotic tissue has been had in the modern era. However, increasing appreciation of the process from a biomolecular perspective offers the potential for making significant strides in wound modulation. The bioactive molecule nitric oxide was found to have wide-ranging impact on cellular activities, including the cellular responses engendered by wound healing. Current research suggests that nitric oxide and several nitric oxide donors can exert biologic effects, although the particular net responses of cells contributing to wound repair are context-dependent.


Secretion rates of human nasal submucosal glands from patients with chronic rhinosinusitis or cystic fibrosis.
A majority of patients with cystic fibrosis (CF) have chronic rhinosinusitis (CRS) and/or nasal polyps, both of which may be secondary to reduced fluid secretion from nasal submucosal glands. To determine whether decreased fluid secretion from nasal submucosal glands also occurs in patients without CF and with CRS. Inferior turbinates of the nasal cavity were harvested from controls, subjects with CRS, and subjects with CF (n = 5-7 per group). The secretion rates of the nasal submucosal glands of the three groups in response to carbachol and forskolin were measured by using time lapse digital imaging of mucus bubbles from single glands as they formed on the mucosal surface under oil. Carbachol-stimulated secretion rates were the following: controls, 1670 ± 381 pl·min(-1)·gland(-1); CRS, 965 ± 440 pl·min(-1)·gland(-1); and CF, 933 ± 588 pl·min(-1)·gland(-1) (p = 0.23, Kruskal-Wallis test). Forskolin-stimulated secretion rates were the following: controls, 229 ± 14 pl·min(-1)·gland(-1); CRS, 154 ± 48 pl·min(-1)·gland(-1); and CF, 22 ± 15 pl·min(-1)·gland(-1) (p = 0.008, Kruskal-Wallis test). The ratio of the average secretion rate induced by forskolin to that induced by carbachol was 13.7% in the controls, and 15.9% in CRS and 2.3% in CF groups. The only significant difference in this small study was decreased forskolin-stimulated secretion in subjects with CF relative to the other subjects. However, there was a trend toward reduced carbachol-stimulated secretion rates in subjects with CRS and with and without CF relative to controls. Additional studies are needed to determine if nasal submucosal gland hyposecretion occurs in CRS either as a contributor to or as a consequence of CRS pathogenesis.


[Surgical management of strabismus in dysthyroid orbitopathy: A retrospective single-center study of 32 cases].
Thyroid-related immune orbitopathy often results in a restrictive strabismus. We report our experience of surgical management in these cases. We present a retrospective case series conducted on 32 patients, operated between 2008 and 2017. Strabismus surgery was proposed in the postinflammatory stage with stable clinical findings for at least 6 months. It was performed under general anesthesia by recessions of restrictive muscles using a fixed suture technique. Outcomes were graded as excellent, good or poor, according to the presence or absence of diplopia in primary or reading positions, and according to whether prism prescription was necessary. The study included 32 patients (21 women, 11 men) with a mean age of 53 years. Average follow-up was 9.6 months. Eight patients developed diplopia after orbital decompression. Fifteen patients had vertical surgery, 8 horizontal surgery, 9 mixed surgery. A mean of 1.31 surgeries (range 1-3) were performed. After all surgeries, 28 patients (87.5 %) had an excellent outcome, 4 (12.5 %) had a good outcome, and none had a poor outcome. There was a significant improvement in stereoscopic acuity (P<0.01), but not motility. Among the 8 patients who developed diplopia after orbital decompression, a clinically acceptable final outcome was achieved after only one surgery. Strabismus surgery using conventional non-adjustable sutures provides excellent ocular alignment and relief from diplopia in the majority of patients with dysthyroid strabismus. The reoperation rate is similar to other techniques, such adjustable suture and intraoperative relaxed muscle technique.