An analysis of hospital costs by cost center, 1971 through 1978.
Hospital cost analyses generally have not used costs broken down by hospital department or function due to the unavailability of appropriate data. The Medicare Cost Reports display direct cost by cost center, and the Health Care Financing Administration (HCFA) funded a project to abstract, edit, and categorize these data from a sample of 457 hospitals into meaningful groups. The author used the resulting data base to analyze trends in hospital costs, with cross tabulations by a hospital's teaching status, type of control, and bed size class, from 1971 through 1978. The author also used this data base to preliminarily assess whether introduction of the Medicare Section 223 reimbursement limits altered cost center growth trends. The study found that the largest cost increases occurred among Ancillary Services. It also found slightly higher than average increases in Inpatient Services (concentrated in Special Care Units), and General Services increased at a below average rate. Outpatient Service costs escalated rapidly in absolute terms but rose much more slowly in per unit terms. The fastest growing cost quantity in the study was Other Ancillary Services, a miscellaneous group encompassing many of the new advanced technology services, which increased at a rate of 24 percent per year between 1973 and 1978. The study found costs per unit of output to be positively associated and bed size across all cost center categories, including General Services, where some evidence of economics of scale might have been expected. The study found no evidence that the Section 223 limits affected cost growth longitudinally, but an understanding of the impact of these limits will require considerably more study.


Reduced renal papillary plasma flow in non-ascitic cirrhotic rats.
1. The purpose of the present investigation was to determine whether an abnormality of the renal papillary circulation is present in a well-established model of cirrhosis without ascites (carbon tetrachloride/phenobarbital). 2. Compared with the control animals, cirrhotic rats showed a reduced diuretic (61.0 +/- 5.1 versus 18.0 +/- 2.5%) and natriuretic (67.8 +/- 8.3 versus 29.6 +/- 3.6%) response to a volume expansion (3% body weight infusion of 0.9% NaCl). The volume expansion-induced increase in renal interstitial hydrostatic pressure was also blunted in the cirrhotic rats (control 9.3 +/- 0.9 versus cirrhotic 6.1 +/- 1.0 mmHg) and there were no differences in mean arterial blood pressure, renal blood flow or glomerular filtration rate between control and cirrhotic animals. 3. Papillary plasma flow was determined by the 125I-albumin accumulation technique and expressed as ml min-1 100 g-1. In the basal state, papillary plasma flow was significantly lower in cirrhotic rats (59.1 +/- 4.4, n = 9) than in the control animals (81.8 +/- 6.9, n = 9). An isotonic saline expansion similar to the one described above significantly increased papillary plasma flow in control rats (108.4 +/- 9.1, n = 7) but did not change it in cirrhotic rats (60.2 +/- 4.9, n = 6). 4. Our results indicate the existence of a selective alteration in the renal papillary circulation in cirrhotic rats, both in the basal state and after a well-established vasodilatory stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)


Normative perceptions in relation to substance use and HIV-risky sexual behaviors of college students.
In this study, 410 college students completed a survey assessing their personal substance use patterns and sexual behavior and their perceptions of other students' substance use and sexual behavior. Two parallel sets of questions were presented to reflect the two contextual conditions of being drunk or high versus being not drunk or high. Results indicated that number of recent sexual partners and normative perceptions of HIV-risky sexual behavior were the strongest predictors of personal HIV-risky behavior when not drunk or high. HIV-risky behavior when drunk or high was predicted by personal substance use as well as by number of recent partners and normative perceptions of peer sexual behavior. These findings suggest that HIV-prevention programs for college students should aim to correct overinflated perceptions of other students' high-risk sexual behavior.


Hormonal regulation of S-adenosylmethionine synthase transcripts in pea ovaries.
Two cDNA clones coding for S-adenosyl-L-methionine synthase (SAMs, EC 188.8.131.52) have been isolated from a cDNA library of gibberellic acid-treated unpollinated pea ovaries. Both cDNAs were sequenced showing a high degree of identity but coding for different SAMs polypeptides. The presence of two SAMs genes in pea was further confirmed by Southern analysis. Expression of the SAMs genes in the pea plant was found at different levels in vegetative and reproductive tissues. We characterized the expression levels of SAMs genes during the development or senescence of pea ovaries. Northern analysis showed that transcription of SAMs genes in parthenocarpic fruits was upregulated by auxins in the same manner as in fruits from pollinated ovaries. In both pollinated and 2,4-dichlorophenoxyacetic acid-treated ovaries, and benzyladenine, although able to induce parthenocarpic development, did not affect SAMs mRNA levels. These data are consistent with an active participation of auxins in the upregulation of SAMs during fruit setting in pea and suggest that, at the molecular level, parthenocarpic development of pea ovaries is different for gibberellin- and cytokinin-treated ovaries than for auxin-induced parthenocarpic biosynthesis since treatment of the ovaries with aminoethoxyvinylglycine resulted in a delay of senescence and prevention of SAMs mRNA accumulation. A possible mechanism for hormonal regulation of SAMs during ovary development is discussed.


Autocrine netrin function inhibits glioma cell motility and promotes focal adhesion formation.
Deregulation of mechanisms that control cell motility plays a key role in tumor progression by promoting tumor cell dissemination. Secreted netrins and their receptors, Deleted in Colorectal Cancer (DCC), neogenin, and the UNC5 homologues, regulate cell and axon migration, cell adhesion, and tissue morphogenesis. Netrin and netrin receptor expression have previously been shown to be disrupted in invasive tumors, including glioblastoma. We determined that the human glioblastoma cell lines U87, U343, and U373 all express neogenin, UNC5 homologues, and netrin-1 or netrin-3, but only U87 cells express DCC. Using transfilter migration assays, we demonstrate DCC-dependent chemoattractant migration of U87 cells up a gradient of netrin-1. In contrast, U343 and U373 cells, which do not express DCC, were neither attracted nor repelled. Ectopic expression of DCC by U343 and U373 cells resulted in these cells becoming competent to respond to a gradient of netrin-1 as a chemoattractant, and also slowed their rate of spontaneous migration. Here, in addition to netrins' well-characterized chemotropic activity, we demonstrate an autocrine function for netrin-1 and netrin-3 in U87 and U373 cells that slows migration. We provide evidence that netrins promote the maturation of focal complexes, structures associated with cell movement, into focal adhesions. Consistent with this, netrin, DCC, and UNC5 homologues were associated with focal adhesions, but not focal complexes. Disrupting netrin or DCC function did not alter cell proliferation or survival. Our findings provide evidence that DCC can slow cell migration, and that neogenin and UNC5 homologues are not sufficient to substitute for DCC function in these cells. Furthermore, we identify a role for netrins as autocrine inhibitors of cell motility that promote focal adhesion formation. These findings suggest that disruption of netrin signalling may disable a mechanism that normally restrains inappropriate cell migration.


Chinese deaf adolescents' free recall of taxonomic, slot-filler, and thematic categories.
Four experiments were conducted to show that deaf adolescents tended to process information in different ways from hearing adolescents. Memorizing items sequentially shown on computer screens under the control of their articulators' movements, deaf adolescents tended to treat items that cohered as taxonomic, thematic, or slot-filler categories as isolated pieces of information. Having to perceive information by means of sign language, however, their achievements were not worse than those of hearing adolescents anymore, no matter whether the stimuli were presented as words or pictures. They could not only utilize categories relations to help memorize categories exemplars but were relatively better aware of slot-filler or thematic than taxonomic relations as well, suggesting that they had a relatively delayed development of taxonomic category representations in comparison with hearing adolescents.


Do All Fractures Need Surgery?
Common fractures managed by orthopaedic surgeons include ankle fractures, proximal humerus fractures in patients older than 60 years, humeral shaft fractures, and distal radius fractures. Recent trends indicate that surgical management is the best option for most fractures. However, there is limited evidence regarding whether most of these fractures need surgery, or whether there is a subset that could be managed without surgery, with no change in outcomes, or even possibly having improved results with lower complication rates with nonsurgical care.


Subchronic inhalation toxicity of the chlorinated propane 1,1,1,3,3,3-hexachloropropane (HCC-230fa).
Male and female rats were exposed by inhalation (whole body) to HCC-230fa (1,1,1,3,3,3-hexachloropropane) for 6 h/day, 5 days/week over a 15-week period. Concentrations of 0, 0.50, 2.5, and 25 ppm were studied. A total of eight groups/sex were exposed. Four groups of male and four groups of female rats were used to measure clinical signs and growth, clinical pathology, and tissue pathology. The remaining four groups of male rats were used for immunotoxicological and sperm assessment evaluations, and the remaining four groups of female rats were used for immunotoxicological evaluation. Following the exposure period, surviving male rats were kept for a 1- or 3-month recovery period. Male and female rats exposed to 25 ppm had lower mean body weights, mean body weight gains, and food consumption during the exposure period. Male and female rats exposed to 25 ppm and sacrificed immediately after the exposure period had minimally decreased total leukocyte and lymphocyte counts. These changes were considered to be marginally adverse. Pathologic examination revealed hepatocellular hypertrophy in 0-day recovery males and an increased incidence and/or severity in chronic progressive nephropathy in 0-day, 1-month recovery, and 3-month recovery males at 25 ppm. No other pathological changes, including the testis, epididymis, and other accessory sex organs, were noted in rats during the study. Evaluation of sperm parameters at the end of the exposure period showed statistically significant decreases in epididymal sperm number per cauda epididymis, percent motile sperm, and percent normal sperm morphology at 25 ppm. The biological significance of the slight changes observed in the sperm parameters in the absence of histopathological changes is unclear. After a 1-month recovery period, no biologically significant differences in sperm parameters were noted at 25 ppm compared with controls. Exposure to HCC-230fa did not significantly alter the primary humoral immune response to sheep red blood cell (SRBC). Under the conditions of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 2.5 ppm.


[Effects of pentoxifylline on leukocyte adhering to endothelial cell].
Using flow chamber, we quantitatively studied the effects of pentoxifylline on normal leukocytes adhering to cultured human umbilical vein endothelial cells. The results showed that pentoxifylline reduced the adhesive number of leukocytes to endothelial cells by acting mainly on leukocytes. The mechanism may be that pentoxifylline inhibits the adherence caused by oxygen free radicals from the leukocytes.


A pilot study on efficacy treatment of acne vulgaris using a new method: results of a randomized double-blind trial with Acne Dressing.
For many years the positive effect of hydrocolloid dressings on skin-related conditions attracted the attention of the medical scientific community. The use of Acne Dressing, a tape of hydrocolloid dressing, for the treatment of acne has not been reported previously. The aim of this study was to evaluate the clinical efficacy and beneficial effect of Acne Dressing on the marker for sebum output evaluations. We also determined the cosmetic outcome of this application during the treatment of acne and whether the material could prevent hand touching and UVB light from reaching the skin surface. The objective of this study was to assess improvement in acne vulgaris and tolerability during one week of short contact treatment with Acne Dressing compared to skin tapes. Efficacy data specific to treatment of acne vulgaris with Acne Dressing (3M Health Care) from a double-blind, randomized, skin types-controlled study is reported. A total of 20 patients with mild-to-moderate acne vulgaris applied the skin tapes or Acne Dressing every two days for up to one week. Twenty patients were enrolled in this study: ten patients received Acne Dressing and ten patients received skin tapes. Both groups showed decreases from baseline to the end of treatment in the mean of the overall severity scale (decrease of 1.37 from 1.8 to 0.43 with Acne Dressing and 0.28 from 1.08 to 0.8 with skin tapes). A statistically significant greater reduction was observed over a period of three to seven days in the overall severity of acne and inflammation in the Acne Dressing group compared with the mono-therapy (skin tapes) group. Similarly, Acne Dressing resulted in a significantly greater improvement in the redness, oiliness, dark pigmentation, and sebum casual level at days 3, 5, and 7. The ratio of transmission of UVB light with Acne Dressing was 7.4%, and 38% with skin tapes, which shows less UVB light reaching the skin surface with the Acne Dressing. No significant adverse events were identified in either group. The pilot study shows the benefit of treatment with Acne Dressing in improving mild-to-moderate inflammatory acne vulgaris. A future study will investigate a large set of patients in longer followup periods.


RAPD markers as predictors of infectious hypodermal and hematopoietic necrosis virus (IHHNV) resistance in shrimp (Litopenaeus stylirostris).
Random amplified polymorphic DNA (RAPD) fingerprints of two shrimp populations (Litopenaeus stylirostris) were compared to find genetic marker(s) that may be associated with infectious hypodermal and hematopoietic necrosis virus (IHHNV) resistance or susceptibility. Of the 100 10-mer random primers and 100 intersimple-sequence repeat (ISSR) primers screened, five provided markers specific to the Super Shrimp population and three provided markers specific to the wild caught population. The two populations were further characterized for relative viral load (reported as cycle threshold, CT) using real-time quantitative PCR with primers specific to the IHHNV genome. The beta-actin gene was amplified to serve as a control for normalization of the IHHNV viral load. The mean viral load was significantly lower (C(T) = 34.58; equivalent to 3.3 x 10(1) copies of IHHNV genome/ng DNA) in Super Shrimp than in the wild caught population (CT = 23.49; equivalent to 4.2 x 10(4) copies/ng DNA; P < 0.001; CT values are inversely related to viral load). A preliminary prediction model was created with Classification and Regression Tree (CART) software (Salford Systems, San Diego, Calif.), where the resultant decision tree uses the presence or absence of seven RAPD markers as predictors of the relative viral load.


Preoperative evaluation and risk management.
All colorectal operations carry significant associated risk. To facilitate the best outcomes it is essential to perform a comprehensive evaluation of patient risk preoperatively. Once risk factors are identified the appropriate steps must be taken to minimize their effects. The evaluation of the patient can be broken down by organ systems such as cardiac, pulmonary, hepatic, renal, and gastrointestinal. Additionally, one can assess whether the patient is at risk for infection, hyperglycemia, malnutrition, venous thromboembolism, and anemia. There are many preemptive steps that can be taken to improve patient outcomes in all of these categories.


Pd-Catalyzed C(sp(3))-H Carbonylation of Alkylamines: A Powerful Route to γ-Lactams and γ-Amino Acids.
A novel Pd-catalyzed direct C(sp(3))-H carbonylation of alkylamines for the synthesis of γ-lactams and γ-amino acids has been developed, in which TEMPO was used as the crucial sole oxidant. The synthetic prospect was demonstrated by the concise total synthesis of rac-Pregbalin.


[Fleas (Siphonaptera): a new old infestant in urban environment. Analysis of the cases verified in the South Piedmont in the years 2005-2008].
In the present study, ten cases of human and environmental infestation, observed between 2005 and 2008 in the Southern part of Piedmont, are reported. The infestation were caused by fleas and in particular by Ctenocephalides felis. The importance of human pulicasis transmitted by animals you have with (cats) and related risks to human health is inderlined. In the past pulicasis, mainly due to Pulex irritans, was related to poor hygienic conditions. On the contrary nowadays, pulicasis in urban habitats seems to be caused, on the basis of the observed cases, by particular fleas species of low host specificity and to linked to the available host species.


Hierarchical saw-like ZnO nanobelt/ZnS nanowire heterostructures induced by polar surfaces.
Saw-like nanostructures composed of single-crystalline ZnO nanobelts and single-crystalline ZnS nanowires have been successfully synthesized by a vapor-solid process. Several techniques, including scanning electron microscope, transmission electron microscopy, and photoluminescence spectroscopy, were used to investigate the structures, morphology, and photoluminescence properties of the products. Due to the similar crystal habits of wurtzite ZnO and ZnS with chemically active Zn-terminated (0001) and chemically inactive O-terminated (or S-terminated) (000) polar surfaces, hierarchical saw-like nanostructures were considered to be formed by the initiation of a chemically active Zn-terminated ZnO (0001) polar surface. Photoluminescence properties of the heterostructures, different from pure ZnO nanobelts or ZnS nanowires, were also studied at room temperature.


Evaluation of telephone triage and advice services: a systematic review on methods, metrics and results.
Telephone triage and advice services (TTAS) have been increasingly used to assess patients' symptoms, provide information and refer patients to appropriate levels of care (attempting to pursue efficiency and quality of care gains while ensuring safety). However, previous reviews have pointed out for the need for adequately evaluating TTAS. To review TTAS evaluation studies, compile methodologies and metrics used and compare results. Systematic search in PubMed database; data collection and categorization by TTAS features and context, type of evaluation, methods, metrics and results; critical assessment of studies; discussion on research needs. 395 articles screened, 55 of them included in the analysis. In conclusion, several aspects of TTAS impact on healthcare systems remain unclear either due to a lack of research (e.g. on long term clinical outcomes, clinical pathways, safety, enhanced access) or because of huge disparities in existing studies on the accuracy of advice, patient compliance, system use, satisfaction and economic evaluation. Further research on TTAS impact is required, comprising multiple perspectives and broad range of metrics.


The Impact of Elevated Left Atrial Pressure in Sinus Rhythm After Cardioversion on Outcomes After Catheter Ablation for Atrial Fibrillation.
Some patients with atrial fibrillation (AF) exhibit elevated left atrial pressure (LAP) in sinus rhythm (SR). The aim of the study was to investigate whether LAP changes between SR and AF are associated with outcomes after catheter ablation (CA) for AF. We retrospectively studied 110 patients (70 men, 66 ± 8 years, 37 with non-paroxysmal AF) who underwent CA of AF. In all patients, AF was induced by programmed stimulation and then terminated with cardioversion during CA. LAP was measured in SR and AF. The LAPSR-AF was defined as the difference between mean LAP in SR and mean LAP in AF (mean LAPSR - mean LAPAF ). Recurrence of AF after CA was detected in 37/110 patients (33.6%) during the follow-up period (13 ± 5 months). Univariate analysis revealed higher LAPSR-AF , larger left atrial diameter, and persistent AF (PeAF) as significant variables. On multivariate analysis, higher LAPSR-AF and PeAF were independently associated with recurrence of AF after CA. All patients were divided into the non-elevated LAPSR-AF group (LAPSR-AF <0 mmHg) or the elevated LAPSR-AF group (LAPSR-AF ≥0 mmHg) using the optimal cut-off value of LAPSR-AF . During a mean follow-up period of 13 ± 5 months, the AF recurrence ratio was higher in the elevated LAPSR-AF group than in the non-elevated LAPSR-AF group (20/42 patients, 48% vs. 17/68 patients, 25%, log-rank, P = 0.0306). Elevated LAP after cardioversion is associated with poor outcome after CA of AF. Sustained pressure overload of the LA in SR could be a cause of the recurrent AF.


Relationship between Chloroplast Membrane Fatty Acid Composition and Photosynthetic Response to a Chilling Temperature in Four Alfalfa Cultivars.
The photosynthetic responses of four alfalfa (Medicago sativa L.) cultivars to 10 and 22 C air temperatures were examined and the relationship between the photosynthetic response at 10 C and the fatty acid composition of the chloroplast membranes was determined. Chilling-resistant cultivars exhibited moderate reductions in photosynthesis at 10 C, compared to 22 C, and contained a significantly greater percentage of polyunsaturated fatty acids in the chloroplast membrane and a greater double bond index than the chilling-sensitive cultivars. The chilling-sensitive cultivars exhibited severe reductions in photosynthesis at 10 C, compared to 22 C. The reduction in photosynthesis at 10 C is shown to be negatively correlated (r = -0.94) with the double bond index of the chloroplast membranes of the cultivars observed.The results support the hypothesis that reduced photosynthesis due to chilling temperatures is influenced by the unsaturated fatty acid composition of the chloroplast membrane which affect temperature-induced phase changes in chloroplast membrane lipids.


Higher Peak Fat Oxidation During Rowing vs. Cycling in Active Men and Women.
Astorino, TA, Oriente, C, Peterson, J, Alberto, G, Castillo, EE, Vasquez-Soto, U, Ibarra, E, Guise, V, Castaneda, I, Marroquin, JR, Dargis, R, and Thum, JS. Higher peak fat oxidation during rowing vs. cycling in active men and women. J Strength Cond Res 35(1): 9-15, 2021-This study compared fat and carbohydrate oxidation (CHOOx) between progressive rowing and cycling. Initially, 22 active healthy adults (age = 27 ± 8 years) performed incremental cycling and rowing to volitional fatigue to assess maximal oxygen uptake (V̇o2max) and maximal heart rate (HRmax). The order of 2 subsequent sessions was randomized, performed 2 hours postmeal, and included a warm-up followed by three 8-minute stages of rowing or cycling at 60-65, 70-75, and 80-85 %HRmax. During exercise, power output was modified to maintain work rate in the desired range. Gas exchange data and blood samples were obtained to measure fat and CHOOx and blood lactate concentration. Fat oxidation (FOx) increased during exercise (p < 0.001) and there was a main effect of mode (p = 0.03) but no modeXintensity interaction (p = 0.33). Peak FOx was higher in response to rowing vs. cycling (0.23 ± 0.09 g·min-1 vs. 0.18 ± 0.07 g·min-1, p = 0.01). Carbohydrate oxidation increased during exercise (p < 0.001) but there was no effect of mode (p = 0.25) or modeXintensity interaction (p = 0.08). Blood lactate concentration was lower (p = 0.007) at the end of rowing vs. cycling (3.1 ± 1.0 mM vs. 3.9 ± 1.6 mM, d = 1.1). Prolonged rowing having equivalent calorie expenditure and intensity vs. cycling elicits higher peak FOx, which is likely attributed to greater muscle mass used during rowing.


Development of temporal modelling for forecasting and prediction of malaria infections using time-series and ARIMAX analyses: a case study in endemic districts of Bhutan.
Malaria still remains a public health problem in some districts of Bhutan despite marked reduction of cases in last few years. To strengthen the country's prevention and control measures, this study was carried out to develop forecasting and prediction models of malaria incidence in the endemic districts of Bhutan using time series and ARIMAX. This study was carried out retrospectively using the monthly reported malaria cases from the health centres to Vector-borne Disease Control Programme (VDCP) and the meteorological data from Meteorological Unit, Department of Energy, Ministry of Economic Affairs. Time series analysis was performed on monthly malaria cases, from 1994 to 2008, in seven malaria endemic districts. The time series models derived from a multiplicative seasonal autoregressive integrated moving average (ARIMA) was deployed to identify the best model using data from 1994 to 2006. The best-fit model was selected for each individual district and for the overall endemic area was developed and the monthly cases from January to December 2009 and 2010 were forecasted. In developing the prediction model, the monthly reported malaria cases and the meteorological factors from 1996 to 2008 of the seven districts were analysed. The method of ARIMAX modelling was employed to determine predictors of malaria of the subsequent month. It was found that the ARIMA (p, d, q) (P, D, Q)s model (p and P representing the auto regressive and seasonal autoregressive; d and D representing the non-seasonal differences and seasonal differencing; and q and Q the moving average parameters and seasonal moving average parameters, respectively and s representing the length of the seasonal period) for the overall endemic districts was (2,1,1)(0,1,1)12; the modelling data from each district revealed two most common ARIMA models including (2,1,1)(0,1,1)12 and (1,1,1)(0,1,1)12. The forecasted monthly malaria cases from January to December 2009 and 2010 varied from 15 to 82 cases in 2009 and 67 to 149 cases in 2010, where population in 2009 was 285,375 and the expected population of 2010 to be 289,085. The ARIMAX model of monthly cases and climatic factors showed considerable variations among the different districts. In general, the mean maximum temperature lagged at one month was a strong positive predictor of an increased malaria cases for four districts. The monthly number of cases of the previous month was also a significant predictor in one district, whereas no variable could predict malaria cases for two districts. The ARIMA models of time-series analysis were useful in forecasting the number of cases in the endemic areas of Bhutan. There was no consistency in the predictors of malaria cases when using ARIMAX model with selected lag times and climatic predictors. The ARIMA forecasting models could be employed for planning and managing malaria prevention and control programme in Bhutan.


Peripheral blood inflammation indices are effective predictors of anastomotic leakage in elective esophageal surgery.
This study investigated the predictive value of peripheral inflammatory indices, including neutrophil count, lymphocyte count, platelet count, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in anastomotic leakage during elective esophageal surgery. This retrospective study included all patients who underwent esophagectomy for esophageal squamous cell carcinoma from 2016 to 2020 in our institution. The peripheral blood inflammatory indices were obtained on preoperative days 1-7 (PRD 1-7), and postoperative days 1-3 (POD 1-3) and 4-7 (POD 4-7). Univariate, multivariate logistic, and receiver operating characteristic curve analyses were conducted to evaluate the diagnostic value of these peripheral blood inflammatory indices. A total of 198 patients were included in the study, and 25 (13%) patients experienced anastomotic leakage. Multivariate analyses identified diet, neutrophil count, and PLR on POD 1-3, and NLR on POD 4-7 as independent factors associated with anastomotic leakage. Using the receiver operating characteristic curve, the variable with the best area under curve was a neutrophil cutoff count of 4.1 [0.737; 95% CI: 0.639-0.835], with a sensitivity and specificity of 60.0% and 66.5%, respectively. This was followed by an NLR cutoff value of 9.5 on POD 4-7 (0.628; 95% CI: 0.505-0.752) and a cutoff PLR value of 220.1 on POD 1-3 (0.643; 95% CI: 0.536-0.750). Diet showed a poor result on the receiver operating characteristic curve analysis. Neutrophil count and PLR on POD 1-3 and NLR on POD 4-7 were shown to have predictive value for anastomotic leakage in elective esophageal surgery.


Roles of the C-terminal end of SecY in protein translocation and viability of Escherichia coli.
SecY, a central component of the membrane-embedded sector of protein translocase, contains six cytosolic domains. Here, we examined the importance of the C-terminal cytosolic region of SecY by systematically shortening the C-terminal end and examining the functional consequences of these mutations in vivo and in vitro. It was indicated that the C-terminal five residues are dispensable without any appreciable functional defects in SecY. Mutants missing the C-terminal six to seven residues were partially compromised, especially at low temperature or in the absence of SecG. In vitro analyses indicated that the initial phase of the translocation reaction, in which the signal sequence region of the preprotein is inserted into the membrane, was affected by the lack of the C-terminal residues. SecA binding was normal, but SecA insertion in response to ATP and a preprotein was impaired. It is suggested that the C-terminal SecY residues are required for SecA-dependent translocation initiation.


Low-Dose Cadmium Causes Metabolic and Genetic Dysregulation Associated With Fatty Liver Disease in Mice.
Cadmium (Cd) is present in food at low levels and accumulates in humans throughout life because it is not effectively excreted. Cd from smoking or occupational exposure shows adverse effects on health, but the mechanistic effect of Cd at low dietary intake levels is poorly studied. Epidemiology studies found that nonalcoholic fatty liver disease (NAFLD), common in U.S. adults, is associated with Cd burden. In cell studies, we found that environmental low-dose Cd oxidized proteins and stimulated inflammatory signaling. However, little is known about low-dose Cd effects on liver function and associated metabolic pathways in vivo. We investigated effects of low-level Cd exposure on liver gene transcripts, metabolites, and associated metabolic pathways and function after challenging mice with Cd (10 mg/l) by drinking water. Results showed liver Cd in treated mice was similar to adult humans without occupational or smoking exposures and 10-fold higher than control mouse values. Pathway analysis of significantly altered liver genes and metabolites mapped to functional pathways of lipid metabolism, cell death and mitochondrial oxidative phosphorylation. These are well-recognized pathways associated with NAFLD. Cd-treated mice had higher liver enzymes in plasma and a trend toward fat accumulation in liver. To verify low-dose Cd-induced stimulation of cell death pathways, phosphorylation of c-Jun N-terminal kinase (JNK) was examined in cultured hepatic cells. Consistent with mouse liver data, low-dose Cd stimulated JNK activation. Together, the results show that low-dose Cd exposure causes liver function changes consistent with a role in NAFLD and possibly also nonalcoholic steatohepatitis.


Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine - a review.
The impact on patients' health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE.NET ( www.peddose.net ), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed ( www.ncbi.nlm.nih.gov/pubmed ). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained.


Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population.
Ferritin is considered to be a marker of the body's iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, population-based, case-control study (KNHNES IV and V). All native Koreans aged ≥ 20 years and who had no medical illness were eligible to participate. Among them, 2.9% had AMD, and its prevalence was found to increase in the higher ferritin quintile groups (Ptrend < 0.0001). In multiple linear regression analysis, serum ferritin level was closely related to conventional risk factors for AMD. Comparison of early AMD with a control group showed that serum ferritin levels were closely associated with AMD (OR = 1.004, 95% CI = 1.002-1.006), and further adjustment for age, gender, serum iron, and kidney function did not reduce this association (OR = 1.003, 95% CI = 1.001-1.006). Furthermore, the relationship between ferritin quintile and early AMD was dose-dependent. Thus, an increased level of serum ferritin in a healthy person may be a useful indicator of neurodegenerative change in the macula. A large population-based prospective clinical study is needed to confirm these findings.


WAIS-IV Seven-Subtest Short Form: Validity and Clinical Use in Schizophrenia.
This study assesses the psychometric properties of Ward's seven-subtest short form (SF) for WAIS-IV in a sample of adults with schizophrenia (SZ) and schizoaffective disorder. Seventy patients diagnosed with schizophrenia or schizoaffective disorder were administered the full version of the WAIS-IV. Four different versions of the Ward's SF were then calculated. The subtests used were: Similarities, Digit Span, Arithmetic, Information, Coding, Picture Completion, and Block Design (BD version) or Matrix Reasoning (MR version). Prorated and regression-based formulae were assessed for each version. The actual and estimated factorial indexes reflected the typical pattern observed in schizophrenia. The four SFs correlated significantly with their full-version counterparts, but the Perceptual Reasoning Index (PRI) correlated below the acceptance threshold for all four versions. The regression-derived estimates showed larger differences compared to the full form. The four forms revealed comparable but generally low clinical category agreement rates for factor indexes. All SFs showed an acceptable reliability, but they were not correlated with clinical outcomes. The WAIS-IV SF offers a good estimate of WAIS-IV intelligence quotient, which is consistent with previous results. Although the overall scores are comparable between the four versions, the prorated forms provided a better estimation of almost all indexes. MR can be used as an alternative for BD without substantially changing the psychometric properties of the SF. However, we recommend a cautious use of these abbreviated forms when it is necessary to estimate the factor index scores, especially PRI, and Processing Speed Index.


Peri-operative oxygen consumption revisited: An observational study in elderly patients undergoing major abdominal surgery.
Monitoring oxygen consumption (VO2) is neither recommended nor included in peri-operative haemodynamic algorithms aiming at optimising oxygen delivery (DO2) in major abdominal surgery. Estimates of peri-operative VO2 changes are uncertain in earlier publications and have limited generalisability in the current high-risk surgical population. In a prospective non-interventional observational study in elderly patients undergoing major abdominal procedures, we investigated the change of VO2 after induction of anaesthesia and secondarily, the further changes during and after surgery in relation to DO2 and estimated oxygen extraction ratio (O2ER) by routine monitoring. VO2 was determined by indirect calorimetry (QuarkRMR) in 20 patients more than 65 years (ASA II to IV), scheduled for elective open upper abdominal surgery with combined epidural and general anaesthesia. Data were collected during 20-minute periods pre-operatively and after anaesthesia induction, with subsequent measurements during surgery and postoperatively. Simultaneously, DO2 was monitored using LiDCOplus. The O2ER was estimated from arterial-central venous oxygen content calculation. Mixed models were used to analyse the peri-operative changes. VO2 decreased after induction of anaesthesia by a mean of 34% (95% CI, 28 to 39). After 2 h of surgery, VO2 was reduced by 24% (95% CI, 20 to 27) compared with the awake baseline measurements. Pre-operative mean DO2 was 440 (95% CI, 396 to 483) ml min m and decreased by a mean of 37% (95% CI, 30 to 43) during anaesthesia. The estimated O2ER did not change intra-operatively 0.24 (95% CI, 0.21 to 0.26) but increased postoperatively to 0.31 (95% CI, 0.27 to 0.36). The changes of VO2 were parallel with changes of DO2 and O2ER in the intra-operative period. General anaesthesia reduced VO2 by approximately a third in elderly patients undergoing major abdominal surgery. Parallel changes of intra-operative VO2 and delivery were demonstrated while oxygen extraction was low. The relevance of these changes needs further assessment in relation to outcomes and haemodynamic interventions. Clinicaltrials.gov NCT03355118.


Pathological situations characterized by altered actin isoform expression.
Modulation of actin isoform expression is a well-established feature of developmental phenomena. As one might expect, it is also characteristic of several pathological situations that are the subject of the present review. alpha-Smooth muscle actin has proven to be a reliable marker for identifying (a) vascular smooth muscle cells during vascular development and vascular diseases, and (b) myofibroblasts during wound healing, fibrocontractive diseases, and stromal reaction to epithelial tumours. The hallmark of a differentiated myofibroblast relies on the acquisition of an organized contractile apparatus characterized by alpha-smooth muscle actin-expressing stress fibres. More and more data suggest that alpha-smooth muscle actin plays a direct role in myofibroblast contractile activity through its N-terminal domain AcEEED. Newly developed antibodies against alpha-skeletal and alpha-cardiac actins have allowed the detection of subpopulations of alpha-skeletal positive cardiomyocytes in adult, hypertrophic, and failing heart. These antibodies have also permitted us to identify the differentiation degree of malignant cells in tumours such as rhabdomyosarcoma. Whether the differential expression of actin isoforms in human diseases is functionally relevant is not yet fully established, although studies on human actin mutations, actin null mice, and the N-terminal end of alpha-smooth muscle actin support this possibility.


Trehalase is required for sex pheromone biosynthesis in Helicoverpa armigera.
Trehalase (Treh) hydrolyzes trehalose to generate glucose and it plays important role in many physiological processes. Acetyl-CoA, the precursor of sex pheromone biosynthesis in the pheromone gland (PG) of Helicoverpa armigera, originates from glucose during glycolysis. However, the function of Treh in sex pheromone biosynthesis remains elusive. In the present study, H. armigera was used as a model to investigate the function of two Trehs (Treh1 and Treh2) in sex pheromone biosynthesis. Results demonstrated that knockdown of HaTreh1 or HaTreh2 in female PGs led to significant decreases in Z11-16:Ald production, female ability to attract males, and successful mating proportions. Pheromone biosynthesis activating neuropeptide (PBAN) treatment triggered HaTreh1 and HaTreh2 activities in the isolated PGs and Sf9 cells. However, the activities of HaTreh1 and HaTreh2 triggered by PBAN were offset by H-89, the specific inhibitor of protein kinase A (PKA). Furthermore, the H-89 treatment significantly decreased the phosphorylation level of Trhe2, which was induced by PBAN. In addition, sugar feeding (5% sugar) increased the enzyme activities of Treh1 and Treh2. In summary, our findings confirmed that PBAN activates Treh1/2 activities by recruiting cAMP/PKA signalling, promotes glycolysis to ensure the supply of acetyl-CoA, and ultimately facilitates sex pheromone biosynthesis and mating behaviour.


Outcomes of surgical management of xanthelasma palpebrarum.
Xanthelasma palpebrarum (XP) is a benign disorder manifesting as yellowish cholesterol-laden plaques on the eyelids. This paper presents the outcomes in patients with XP who have undergone surgical excision as the main modality of treatment. A retrospective review of patients who received surgery for xanthelasma palpebrarum from March 2007 to March 2011 was conducted. Patients were classified into four grades according to the location and extent of the lesion, with grade I being the mildest and grade IV being the most diffuse. Simple excision was performed in grade I and II lesions, while local flaps and skin grafts were performed in the more advanced grades. Ninety-five cases from March 2007 to March 2011 were included in this study. 66 cases (70%), were treated by simple excision. Twenty-four cases (25%) and 5 cases (5%) were treated by simple excision in combination with or without local flaps and skin grafts. In approximately 1/4 of the patients, orbicularis oris muscle involvement was observed. 4 patients (4.2%) developed scar contracture postoperatively, which required a secondary procedure. Recurrence was reported in 3 patients (3.1%). Otherwise. There were no other reports of major complications or disfigurement. We found that for lesions involving the deep dermis and/or muscle, surgical excision was the most appropriate therapeutic option.


Ruptured seminoma of undescended testis presenting as acute abdomen: case report with literature review.
We present a case of a 28-year-old male who presented with acute abdomen and was later diagnosed to be having ruptured intra-abdominal seminoma with hemoperitoneum, where the pre-operative diagnosis was not made. Laprotomy and complete excision were carried out. Rupture of intra-abdominal testicular seminoma is a rare cause of acute abdomen and hemoperitoneum. The pre-operative diagnosis is often difficult because history of cryptorchidism is not provided and imaging findings may be non-specific. In a male patient with acute abdomen and without previous history of orchidectomy, a testicular aetiology of acute abdomen should be kept as the differential diagnosis.


Intestinal Microbiota in Early Life and Its Implications on Childhood Health.
Trillions of microbes reside in the human body and participate in multiple physiological and pathophysiological processes that affect host health throughout the life cycle. The microbiome is hallmarked by distinctive compositional and functional features across different life periods. Accumulating evidence has shown that microbes residing in the human body may play fundamental roles in infant development and the maturation of the immune system. Gut microbes are thought to be essential for the facilitation of infantile and childhood development and immunity by assisting in breaking down food substances to liberate nutrients, protecting against pathogens, stimulating or modulating the immune system, and exerting control over the hypothalamic-pituitary-adrenal axis. This review aims to summarize the current understanding of the colonization and development of the gut microbiota in early life, highlighting the recent findings regarding the role of intestinal microbes in pediatric diseases. Furthermore, we also discuss the microbiota-mediated therapeutics that can reconfigure bacterial communities to treat dysbiosis.


Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients.
A blood donor infected with human immunodeficiency virus-type 1 (HIV-1) and a cohort of six blood or blood product recipients infected from this donor remain free of HIV-1-related disease with stable and normal CD4 lymphocyte counts 10 to 14 years after infection. HIV-1 sequences from either virus isolates or patient peripheral blood mononuclear cells had similar deletions in the nef gene and in the region of overlap of nef and the U3 region of the long terminal repeat (LTR). Full-length sequencing of one isolate genome and amplification of selected HIV-1 genome regions from other cohort members revealed no other abnormalities of obvious functional significance. These data show that survival after HIV infection can be determined by the HIV genome and support the importance of nef or the U3 region of the LTR in determining the pathogenicity of HIV-1.


Differences in Emotional Conflict Processing between High and Low Mindfulness Adolescents: An ERP Study.
Mindfulness is a state of concentration that allows individuals to focus on their feelings and thoughts without judgment. However, little is known regarding the underlying neural processes of mindfulness. This study used ERPs to investigate the differences between high and low trait mindfulness adolescents during emotional conflict processing. Nineteen low mindfulness adolescents (LMSs) and sixteen high mindfulness adolescent (HMSs) individuals were asked to complete a face Stroop task. The task superimposed emotional words on emotional faces to generate congruent (CC) and incongruent (IC) conditions. Continuous electroencephalogram data were recorded during the face Stroop task. Results revealed that for N450, the interaction of congruency and group was significant. The incongruent trials evoked a larger N450 than the congruent trials in the HMSs, whereas there were no significant differences between the two conditions in the LMSs. There were significant main effects of congruency for SP (slow potential). The incongruent trials evoked a larger SP than the congruent trials. The results suggest that mindfulness may only affect early conflict monitoring rather than later conflict resolution. The findings expand the neural basis of the effect of mindfulness on inhibitory control.


Perinatal exposure to pesticides alters synaptic plasticity signaling and induces behavioral deficits associated with neurodevelopmental disorders.
Increasing evidence from animal and epidemiological studies indicates that perinatal exposure to pesticides cause developmental neurotoxicity and may increase the risk for psychiatric disorders such as autism and intellectual disability. However, the underlying pathogenic mechanisms remain largely elusive. This work was aimed at testing the hypothesis that developmental exposure to different classes of pesticides hijacks intracellular neuronal signaling contributing to synaptic and behavioral alterations associated with neurodevelopmental disorders (NDD). Low concentrations of organochlorine (dieldrin, endosulfan, and chlordane) and organophosphate (chlorpyrifos and its oxon metabolite) pesticides were chronically dosed ex vivo (organotypic rat hippocampal slices) or in vivo (perinatal exposure in rats), and then biochemical, electrophysiological, behavioral, and proteomic studies were performed. All the pesticides tested caused prolonged activation of MAPK/ERK pathway in a concentration-dependent manner. Additionally, some of them impaired metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD). In the case of the pesticide chlordane, the effect was attributed to chronic modulation of MAPK/ERK signaling. These synaptic alterations were reproduced following developmental in vivo exposure to chlordane and chlorpyrifos-oxon, and were also associated with prototypical behavioral phenotypes of NDD, including impaired motor development, increased anxiety, and social and memory deficits. Lastly, proteomic analysis revealed that these pesticides differentially regulate the expression of proteins in the hippocampus with pivotal roles in brain development and synaptic signaling, some of which are associated with NDD. Based on these results, we propose a novel mechanism of synaptic dysfunction, involving chronic overactivation of MAPK and impaired mGluR-LTD, shared by different pesticides which may have important implications for NDD.


Applying the big five personality factors to the impostor phenomenon.
The purpose of this study was to relate the impostor phenomenon (IP) to the Five-factor model of personality. A sample of 190 college students (79 men, 111 women) completed the Clance Impostor Phenomenon Scale (Clance, 1985), the Perceived Fradulence Scale (Kolligian & Sternberg, 1991), and the NEO-Personality Inventory-Revised (Costa & McCrae, 1992). Results of correlational and regression analyses support the predicted relations of imposter measures with high Neuroticism and low Conscientiousness. Facet-level correlations showed that depression and anxiety were particularly important characteristics of those with imposter feelings as well as low self-discipline and perceived competence. Implications for treatment and future research on the IP are discussed.


Titration of four replication factors is essential for the Xenopus laevis midblastula transition.
The rapid, reductive early divisions of many metazoan embryos are followed by the midblastula transition (MBT), during which the cell cycle elongates and zygotic transcription begins. It has been proposed that the increasing nuclear to cytoplasmic (N/C) ratio is critical for controlling the events of the MBT. We show that four DNA replication factors--Cut5, RecQ4, Treslin, and Drf1--are limiting for replication initiation at increasing N/C ratios in vitro and in vivo in Xenopus laevis. The levels of these factors regulate multiple events of the MBT, including the slowing of the cell cycle, the onset of zygotic transcription, and the developmental activation of the kinase Chk1. This work provides a mechanism for how the N/C ratio controls the MBT and shows that the regulation of replication initiation is fundamental for normal embryogenesis.


Cytokine expression in the presence or absence of late airway responses after antigen challenge of sensitized rats.
To assess whether Th-2 cytokines are involved in the late airway response (LR) after antigen challenge, we evaluated cytokine mRNA expression in the lungs of two strains of rats before and 8 h after saline or antigen challenge: Brown Norway (BN) rats, high IgE producers that develop LR after antigen challenge and Sprague-Dawley (SD) rats, low IgE producers that develop little LR and no increased airway responsiveness after antigen challenge. Rats were sensitized with ovalbumin (OA) and 14 days later, lungs were obtained before or after OA challenge and measurement of lung physiology for 8 h. Lung tissue was either fixed for in situ hybridization or frozen for evaluation of mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). We examined mRNA expression for interleukin-4 (IL-4), and IL-5 (Th-2 cytokines) and IL-2 and interferon gamma (IFN-gamma, Th-1 cytokines). In situ hybridization showed that cells expressing IL-4 and -5 mRNA were increased in the airways of the lungs of BN rats after OA challenge (P < 0.05) and that cells expressing mRNA for IFN-gamma and IL-2 were higher in SD than in BN rats after antigen challenge (P < 0.05). Results from PCR showed that prior to antigen challenge, BN rats expressed in their lungs mRNA for IL-4 and -5 and SD rats expressed very little mRNA for IL-5 only. After antigen challenge most BN and SD rats expressed mRNA for IL-4 and -5 but expression of mRNA for IL-2 and IFN-gamma was only found in SD rats. In conclusion, rats that develop a LR after antigen challenge preferentially increase Th-2 cytokine expression in their lungs whereas those without LRs preferentially express Th-1 cytokines. Our results support the role of Th-2 cytokines in the LR and asthma.


The Canadian laboratory initiative on pediatric reference intervals: A CALIPER white paper.
Laboratory investigations provide physicians with objective data to aid in disease diagnosis, clinical decision making, and patient follow up. Clinical interpretation of laboratory test results relies heavily on the availability of appropriate population-based reference intervals (i.e. normative values) or decision limits developed through clinical outcome studies. Although reference intervals are fundamental to accurate laboratory test interpretation, and thus critically important to healthcare, the need for sound evidence-based reference intervals has been largely overlooked, particularly in the pediatric population. In the field of pediatric laboratory medicine, accurate age- and sex-specific reference intervals established using samples from healthy children and adolescents have not been readily available, forcing many clinical laboratories to report adult reference intervals with pediatric test results. When pediatric reference intervals are available, they have often been established with a small sample size, inpatient or outpatient samples, outdated methodologies, and/or inappropriate statistical procedures. To address these unacceptable limitations, several national and global initiatives have begun to close the critical evidence gaps in pediatric reference intervals. Notably, the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has made significant strides towards improving pediatric healthcare in Canada and globally. The present report is a white paper summarizing CALIPER, and provides a comprehensive compendium of the data generated through this project over the past decade as a single resource for clinical laboratory specialists, clinicians, and other healthcare workers. CALIPER launched an outreach campaign in 2008 to recruit healthy community children and adolescents, and developed a robust statistical algorithm, in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines, to develop accurate age- and sex-specific pediatric reference intervals. The first CALIPER direct reference interval study was published in 2012, with age- and sex-specific reference intervals reported for 40 common biochemical markers. To date, CALIPER has collected health information and blood samples from over 9700 community children and adolescents, and has established a comprehensive database of age- and sex-specific reference intervals for over 100 biomarkers of pediatric disease. CALIPER has also performed a series of transference and verification studies to expand the applicability of the CALIPER database to five major analytical platforms, including Abbott, Beckman, Ortho, Roche, and Siemens. Through novel knowledge translation initiatives, the CALIPER Reference Interval Database has been made freely available online ( www.caliperproject.ca ) as well as on a mobile application (CALIPER Reference App), and it is used by clinical laboratories across Canada, the United States, and globally. In addition to establishing this comprehensive pediatric reference interval database, CALIPER has also performed a series of sub-studies, including examining how reference intervals are affected by pre-analytical factors (i.e. sample stability at specific storage conditions, fasting status and time of sample collection), biological variation (i.e. intraindividual and interindividual biological variation, reference change values), and ethnicity and pubertal development stage. In this white paper, extensive tables of pediatric reference intervals are provided for easy reference for clinical laboratories worldwide. All data reported have been published in over 20 peer reviewed publications and are also available through the CALIPER Reference Interval Database as well as the CALIPER Reference App for mobile devices.


The Scw1 RNA-binding domain protein regulates septation and cell-wall structure in fission yeast.
Loss of the nonessential RNA-binding domain protein, Scw1, increases resistance to cell-wall-degrading enzymes in fission yeast. Surprisingly, scw1 null mutations also suppress the lethality of mutations (cdc11-136, cdc7-24, cdc14-118, sid1-239, sid2-250, sid3-106, sid4-A1, and mob1-1) at all levels of the sid pathway. This pathway forms part of the septation initiation network (SIN), which regulates the onset of septum formation and ensures the proper coupling of mitosis to cytokinesis. In contrast, scw1(-) mutations do not suppress ts alleles of the rng genes, cdc12 or cdc15. These mutations also prevent the formation of a septum and in addition block assembly and/or function of the contractile acto-myosin ring. sid mutants exhibit a hyper-sensitivity to cell-wall-degrading enzymes that is suppressed by loss of Scw1. Furthermore, scw1(-)-mediated rescue of sid mutants is abolished in the presence of calcofluor white, a compound that interferes with cell-wall synthesis. These data suggest that Scw1 acts in opposition to the SIN as a negative regulator of cell-wall/septum deposition. Unlike components of the SIN, Scw1 is predominantly a cytoplasmic protein and is not localized to the spindle pole body.


Electrically tunable photonic true-time-delay line.
We present a new application of the acousto-optic superlattice modulation of a fiber Bragg grating based on the dynamic phase and group delay properties of this fiber-optic component. We demonstrate a tunable photonic true-time-delay line based on the group delay change of the light reflected from the grating sidebands. The delay is electrically tuned by adjusting the voltage applied to a piezoelectric transducer that generates the acoustic wave propagating along the grating. In our experiments, a true-time delay of 400 ps is continuously adjusted (300 ps within the 3 dB amplitude range of the first sideband), using a 12 cm long uniform grating.


Raman chemical imaging for spectroscopic screening and direct quantification of falsified drugs.
Falsified drugs are a threat to the health of patients. The analytical control of such products contributes to the fight against this global issue. Raman chemical imaging is a method that relies on consecutive measurements at the surface of a sample, combining spectroscopy, microscopy and chemometrics. This article explores the capabilities of this analytical technique proposing an innovative methodology with spectroscopic screening for the identification of chemical compounds and the direct quantification of the active substance (without prior calibration). Two chemometric methods were used: Multivariate Curve Analysis - Alternate Least Squares for the qualitative analysis and Direct Classical Least Squares for the quantitative analysis. The methodology was optimized with samples prepared in the laboratory and validation parameters were studied. The methodology was then applied to real (authentic and falsified) samples of Viagra® and Plavix®. Despite the presence of fluorescence emission in some samples, the methodology succeeded in the detection of active pharmaceutical ingredients, and in the discrimination of three salts of clopidogrel (in generic formulations of Plavix®). The quantitative deviation from the reference method ranged from -15% to +24% of the active substance content. This deviation may be considered to be acceptable since it is sufficient for assessing the risk to the health of patients and for quickly alerting the health authorities.


Scalar implicatures: experiments at the semantics-pragmatics interface.
In this article we present two sets of experiments designed to investigate the acquisition of scalar implicatures. Scalar implicatures arise in examples like Some professors are famous where the speaker's use of some typically indicates that s/he had reasons not to use a more informative term, e.g. all. Some professors are famous therefore gives rise to the implicature that not all professors are famous. Recent studies on the development of pragmatics suggest that preschool children are often insensitive to such implicatures when they interpret scalar terms (Cognition 78 (2001) 165; Chierchia, G., Crain, S., Guasti, M.T., Gualmini, A., & Meroni, L. (2001). The acquisition of disjunction: evidence for a grammatical view of scalar implicatures. In A.H.-J. Do, L. Dominguez, & A. Johansen (Eds.), Proceedings of the 25th Boston University Conference on Language Development (pp. 157-168). Somerville, MA: Cascadilla Press; Musolino, J., & Lidz, J. (2002). Preschool logic: truth and felicity in the acquisition of quantification. In B. Skarabela, S. Fish, & A.H.-J. Do, Proceedings of the 26th Boston University Conference on Language Development (pp. 406-416). Somerville, MA: Cascadilla Press). This conclusion raises two important questions: (a) are all scalar terms treated in the same way by young children?, and (b) does the child's difficulty reflect a genuine inability to derive scalar implicatures or is it due to demands imposed by the experimental task on an otherwise pragmatically savvy child? Experiment 1 addresses the first question by testing a group of 30 5-year-olds and 30 adults (all native speakers of Greek) on three different scales, <oli, meriki> (<all, some>), <tris, dio> (<three, two>) and <teliono, arxizo> (<finish, start>). In each case, subjects were presented with contexts which satisfied the semantic content of the stronger (i.e. more informative) terms on each scale (i.e. all, three and finish) but were described using the weaker terms of the scales (i.e. some, two, start). We found that, while adults overwhelmingly rejected these infelicitous descriptions, children almost never did so. Children also differed from adults in that their rejection rate on the numerical scale was reliably higher than on the two other scales. In order to address question (b), we trained a group of 30 5-year-olds to detect infelicitous statements. We then presented them with modified versions of the stories of Experiment 1, which now more readily invited scalar inferences. These manipulations gave rise to significantly higher rejection rates than those observed in Experiment 1. Overall, these findings indicate that children do not treat all scalar terms alike and, more importantly, that children's ability to derive scalar implicatures is affected by their awareness of the goal of the task. Developmental and methodological implications as well as theoretical implications for the semantics of numeral terms are discussed.


Parenting Style and Emotional Distress Among Chinese College Students: A Potential Mediating Role of the Zhongyong Thinking Style.
Previous studies suggested that parenting style was associated with college student's emotional distress. However, little is known about the underlying mechanisms of this relation in Chinese culture. The present study investigated the associations between parenting style and college student's emotional distress (depression and anxiety symptoms), examined the mediating effects of Confucian personality-Zhongyong thinking, and explored whether gender, age, and socioeconomic status (SES) moderated the direct and/or indirect effects of parenting style on emotional distress. Results from a large representative sample of Chinese college students (n = 3943) indicated that (a) parental rejection and overprotection was positively and mildly associated with depressive and anxiety symptoms and negatively and mildly related to Zhongyong thinking. Parental warmth significantly correlated with the three variables in the opposite direction; Zhongyong thinking correlated negatively and moderately with depression, and mildly with anxiety; (b) Zhongyong thinking partially mediated the associations of parental rejection and warmth with emotional distress. Specifically, to the extent that students perceived less rejection and more warmth, they were more likely to develop Zhongyong thinking associated with decreased emotional distress; (c) gender and SES moderated the association between parenting style and Zhongyong thinking. Specifically, for students with low SES, the negative relationship between parental overprotection and Zhongyong thinking was stronger; for males and high SES students, the positive link between parental warmth and Zhongyong thinking were stronger. Results highlight the importance of researching potential effects of college student's Zhongyong thinking within the family system in Chinese culture.


Endoscopic Transsphenoidal Surgery for an Adult Patient With Giant Exophytic Chiasmatic/Hypothalamic Glioma.
Optic pathway hypothalamic gliomas are intrinsic low-grade gliomas involving the optic nerve, chiasm, optic tract, and hypothalamus. The rarity of these tumors and their unpredictable course make assessment and standardization of treatment modalities difficult. Tumor debulking via various transcranial approaches was considered to be effective at controlling tumor growth, but with high rates of severe surgery-related complications. In the present case, endoscopic transsphenoidal surgery was initiated to debulk the exophytic chiasmatic/hypothalamic glioma with good preservation of hypothalamic and endocrine functions. The authors suggest transsphenoidal surgery with tumor debulking could be an effective and safe treatment for patients with chiasmatic/hypothalamic gliomas.


Complete blockade of B7 family-mediated costimulation is necessary to induce human alloantigen-specific anergy: a method to ameliorate graft-versus-host disease and extend the donor pool.
Graft-versus-host disease (GVHD) is initiated by adoptively transferred donor T cells that recognize host alloantigens. Whereas the absence of donor T-cell proliferation to host alloantigens in a mixed-leukocyte reaction does not predict freedom from GVHD, the frequency of alloreactive precursor helper T lymphocytes (pHTL) is predictive. Complete blockade of 87 family-mediated costimulation, but not of major histocompatibility complex recognition or adhesion, induces host alloantigenic-specific energy by reducing cytokine production below threshold levels necessary for common gamma chain signaling. The associated reduction of alloreactive pHTL frequency below that predictive for GVHD, without depletion of either nonallospecific T cells or hematopoietic progenitors, has led us to embark upon human clinical trials of haplomismatched allogeneic bone marrow transplantation.


Relating schizotypy and personality to the phenomenology of creativity.
Although a considerable amount of research has addressed psychopathological and personality correlates of creativity, the relationship between these characteristics and the phenomenology of creativity has been neglected. Relating these characteristics to the phenomenology of creativity may assist in clarifying the precise nature of the relationship between psychopathology and creativity. The current article reports on an empirical study of the relationship between the phenomenology of the creative process and psychopathological and personality characteristics in a sample of artists. A total of 100 artists (43 males, 57 females, mean age = 34.69 years) from a range of disciplines completed the Experience of Creativity Questionnaire and measures of "positive" schizotypy, affective disturbance, mental boundaries, and normal personality. The sample of artists was found to be elevated on "positive" schizotypy, unipolar affective disturbance, thin boundaries, and the personality dimensions of Openness to Experience and Neuroticism, compared with norm data. Schizotypy was found to be the strongest predictor of a range of creative experience scales (Distinct Experience, Anxiety, Absorption, Power/Pleasure), suggesting a strong overlap of schizotypal and creative experience. These findings indicate that "positive" schizotypy is associated with central features of "flow"-type experience, including distinct shift in phenomenological experience, deep absorption, focus on present experience, and sense of pleasure. The neurologically based construct of latent inhibition may be a mechanism that facilitates entry into flow-type states for schizotypal individuals. This may occur by reduced latent inhibition providing a "fresh" awareness and therefore a greater absorption in present experience, thus leading to flow-type states.


Galangin inhibits proliferation of hepatocellular carcinoma cells by inducing endoplasmic reticulum stress.
Prolonged endoplasmic reticulum (ER) stress may activate apoptotic pathways in cancer cells. It is suggested that ER stress has the potential of enhancing tumor death in cancer therapy. Galangin, a flavonol derived from Alpinia officinarum Hance, has been shown to suppress the proliferation of hepatocellular carcinoma cells (HCC). The aim of this study was to determine whether galangin was able to induce ER stress in HepG2, Hep3B and PLC/PRF/5 cells. The proliferation of HCC was tested by MTT method. Intracellular Ca(2+) levels were measured with Fluo3-AM.The proteins levels of GRP94, GRP78 and CHOP were detected by Western blot. To further understand the anti-HCC mechanism of galangin, mitogen-activated protein kinases (MAPKs) were detected. The results showed that galangin treatment induced ER stress was evidenced by increased protein levels of GRP94, GRP78 and CHOP, as well as increased free cytosolic Ca(2+) concentration. ER stress inhibitor 4-PBA and CHOP siRNA blocked significantly galangin-induced ER in all three cell lines. Further experiments showed that MAPKs involved in ER stress induced by galangin. In summary, galangin is identified as a stimulator of ER stress to suppress the proliferation of HCC, and may be used as a potential anti-cancer agent.


Glycosaminoglycans inhibit the adherence and the spreading of osteoclasts and their precursors: role in osteoclastogenesis and bone resorption.
The bone microenvironment (e.g. glycosaminoglycans (GAGs), growth factors) plays a major role in bone resorption, especially in the formation of osteoclasts which differentiate from the hematopoietic lineage in the presence of RANKL. Previous studies revealed that GAGs may influence osteoclastogenesis, but data are very controversial, some studies showing an inhibitory effect of GAGs on osteoclastic differentiation whereas others demonstrated a stimulatory effect. To clarify their activities, we investigated the effect of 5 families of GAGs in three different models of human/mouse osteoclastogenesis. The present data revealed that heparin inhibited osteoclastogenesis in these three models, which was confirmed by a decrease in mRNA expression of osteoclastic markers and by an inhibition of the bone resorption capacity. We also demonstrated in RAW 264.7 cells that other families of GAGs different from heparin inhibited RANKL-induced osteoclastogenesis, and that this inhibition was dependent on the length and the level of sulfation of GAGs. In the present work, heparin did not bind to RANKL and did not modulate RANKL signaling. Heparin acted at 2 distinct steps of osteoclastogenesis from human CD14(+) cells: first, heparin strongly decreased the adherence of osteoclast precursors, and secondly inhibited osteoclasts to spread and to be active. Furthermore, the second action of heparin was reversible as the removal of heparin at the end of the culture time allowed the condensed cells to spread out and showed the formation of morphological active osteoclasts. The present work clearly evidences that GAGs inhibit osteoclastogenesis in vitro and strengthens the therapeutic interest of defined GAGs in osteolytic diseases.


Glycine receptor immunoreactivity in the ventral cochlear nucleus of the guinea pig.
Glycine appears to be a major inhibitory neurotransmitter in the cochlear nucleus. In order to determine more precisely the distribution of glycinergic synapses, we have studied the immunocytochemical distribution of the glycine postsynaptic receptor. Two monoclonal antibodies were used, Gly Rec Ab 2, which recognizes the 48kD polypeptide and Gly Rec Ab 7, which primarily recognizes the 93kD subunit of the glycine receptor complex. At the light microscopic level, glycine receptor immunoreactivity was found throughout the ventral cochlear nucleus with a punctuate distribution often found outlining large cell bodies. Indistinguishable patterns of staining were obtained with the two antibodies. Ultrastructural localization was done with Gly Rec Ab 7 because immunoreactivity remained after fixation with glutaraldehyde containing solutions. At the ultrastructural level, immunoreactivity was concentrated at postsynaptic sites on dendrites and cell bodies. In the anteroventral cochlear nucleus, neurons identified as spherical cells contained numerous inmunoreactive synapses on their cell bodies, whereas most immunoreactive synapses on stellate cells were on their proximal dendrites. In the posteroventral cochlear nucleus, neurons identified as octopus cells were immunoreactive on their cell bodies and proximal dendrites. In the granule cell layer, immunoreactivity was found only in the neuropile. Throughout the ventral cochlear nucleus, glycine receptor immunoreactivity was found postsynaptic to terminals containing flattened synaptic vesicles as well as those containing oval/pleomorphic synaptic vesicles.


Away from the mainstream: medical women in one region of rural New South Wales.
Despite recent research on the difficulties associated with attracting women to the rural medical workforce, and the perception that the image of the rural doctor is male, women have had a history in rural medicine in southwest New South Wales that spans a century. This paper explores the contribution to medicine of women medical practitioners working within one geographical area of rural New South Wales. It traces these women, documenting the diversity of women's medical work and some of the challenges faced. Based largely on data from contemporary reports in two local newspapers, the Daily Express and The Daily Advertiser, this paper shows that some of the silence associated with the role of women in rural medicine could be attributed to them holding positions at the margins of what is depicted as 'real' medicine, in fields that include public health and education.


[Hepatic vein catheter technic: method for the detection of metabolic and hormonal variables in the splanchnic area].
The hepatic venous catheterization method permits calculation of net splanchnic output and uptake of substrates and hormones from their respective differences in hepatic venous and arterial concentrations as well as the rate of hepatic plasma or blood flow. Estimates of the latter are made possible by the continuous infusion technique using indocyanine green dye. With determination of splanchnic balance data at hand transsplanchnic and in part even transphepatic handling of metabolic substrates and hormones can be calculated.


Robotic high-throughput assay for isolating apoptosis-inducing genes.
The need to assign functions to genes will increase in upcoming years because of the accumulation of sequence information from various organisms. Here we present a genetic screen for the systematic functional analysis of genes in mammalian cells. The screen is based on high-throughput, transient transfections of individual cDNAs by a robotic system. This construction uses a moveable pipetting head with a novel 96-channel parallel tube-pump array and an integrated de-lidding device. Because of the robot design, the processing speed can reach 2,000 transfections/h. We demonstrate the suitability of the screen to isolate apoptosis-inducing genes as a first read-out. This is achieved in combination with co-transfected reporter plasmids to produce a novel and convenient assay for apoptosis induction.


Derivation of the refraction equations for higher-order aberrations of local wavefronts at oblique incidence.
From the literature the calculation of power and astigmatism of a local wavefront after refraction at a given surface is known from the vergence and Coddington equations. For higher-order aberrations (HOAs) equivalent analytical equations do not exist. Since HOAs play an increasingly important role in many fields of optics, e.g., ophthalmic optics, it is the purpose of this study to extend the "generalized Coddington equation" to the case of HOA (e.g., coma and spherical aberration). This is done by local power series expansions. In summary, with the results presented here, it is now possible to calculate analytically the local HOA of an outgoing wavefront directly from the aberrations of the incoming wavefront and the refractive surface.


Quantifying Glans Width Changes in Response to Preoperative Androgen Stimulation in Patients Undergoing Hypospadias Repair.
Testosterone (T) administration prior to hypospadias surgery to increase glans size remains controversial. Understanding T's effect on glans width (GW) is essential to understanding its potential impact on surgical outcomes. We hypothesized that preoperative T in prepubertal boys significantly increases GW at the time of hypospadias surgery. Our single institutional database was queried to identify patients who underwent hypospadias surgery from 2016 to 2020, in which data for T administration and GW were available. Descriptive, nonparametric and categorical statistics were performed as indicated. A total of 579 patients were eligible for analysis. Median age at surgery was 0.9 years (IQR 0.6-1.6). A total of 247/579 patients (42.7%) received T. The median GW at surgery was 15 mm (IQR 13-17). When comparing patients who had T administered to those who did not, we found a significant difference in GW at surgery (16 mm vs 14 mm, p <0.001). The median change in GW from the office to surgery was 4 mm for those receiving T vs 0 mm for those not receiving T (p <0.001). We identified a greater change in GW from preoperative to intraoperative measurements in patients who received 2 doses of T vs 1 dose (4 mm vs 2 mm, p <0.001). A histogram plot revealed the distribution of GW change at surgery. In our prospectively collected cohort of patients undergoing hypospadias surgery, we were able to quantitate the change in GW from preoperative T. Two doses of T resulted in a significant increase in GW vs 1 dose.


Therapeutic effect of dexmedetomidine on intracerebral hemorrhage via regulating NLRP3.
To investigate the protective effect of dexmedetomidine on intracerebral hemorrhage (ICH) mice and the underlying mechanism. The in vivo ICH model was induced by the injection of autologous blood in C57BL/6 mice. Mice were randomly assigned into control group (no specific treatment) and treatment group (dexmedetomidine administration). Mouse neuronal deficits were evaluated by modified neurological severity scores (mNSS) and Corner Turn Test. ICH volume and cerebral edema at the hemisphere of lesions were determined. Inflammatory response at post-ICH was examined by flow cytometry and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The integrity and permeability of blood brain barrier (BBB) were detected by Western blot and Evans Blue extravasation. Dexmedetomidine treatment markedly alleviated the clinical symptoms of ICH mice, and decreased ICH volume and cerebral edema. QRT-PCR data revealed down-regulated levels of NLRP3, ASC, Caspase-1, and IL-1β in mice of the treatment group relative to controls. Moreover, dexmedetomidine administration decreased contents of CD11b+CD45int, IL-6, and IL-1β, but elevated TGF-β content in treatment group. The Evans Blue leakage was reduced in mice of the treatment group. Both protein and mRNA levels of Claudin-5 and ZO-1 were upregulated in the treatment group. Dexmedetomidine remarkably inhibits the activation of inflammasome, alleviates secondary cerebral injury and inflammation, and protects the integrity and permeability of BBB at post-ICH.


Comparative Evaluation of Postoperative Pain and Success Rate after Pulpotomy and Root Canal Treatment in Cariously Exposed Mature Permanent Molars: A Randomized Controlled Trial.
The aim of this study was to compare postoperative pain and success rate following pulpotomy and root canal treatment. Fifty-four permanent teeth with carious exposures were randomly divided equally into 2 groups. Mineral trioxide aggregate pulpotomy was performed in the experimental group and root canal treatment was performed in the control group, using standardized protocols. The treated teeth were restored with base of glass-ionomer cement followed by composite restoration. Pain was recorded every 24 hours for 7 days after intervention. Clinical and radiographic evaluations were done every 3 months for 18 months. The data collected were statistically analyzed. At the end of follow-up, overall success rate was 85% in the pulpotomy group and 87.5% in the root canal treatment group (P > .05). Significant difference in pain incidence and pain reduction was found between the 2 groups (P < .05), with lower scores reported in the pulpotomy group. Pulpotomy can be an alternative treatment for management of symptomatic permanent teeth with deep caries lesions.


Geochemical Characteristics and Toxic Elements in Alumina Refining Wastes and Leachates from Management Facilities.
A nationwide investigation was carried out to evaluate the geochemical characteristics and environmental impacts of red mud and leachates from the major alumina plants in China. The chemical and mineralogical compositions of red mud were investigated, and major, minor, and trace elements in the leachates were analyzed. The mineral and chemical compositions of red mud vary over refining processes (i.e., Bayer, sintering, and combined methods) and parental bauxites. The main minerals in the red mud are quartz, calcite, dolomite, hematite, hibschite, sodalite, anhydrite, cancrinite, and gibbsite. The major chemical compositions of red mud are Al, Fe, Si, Ca, Ti, and hydroxides. The associated red mud leachate is hyperalkaline (pH > 12), which can be toxic to aquatic life. The concentrations of Al, Cl-, F-, Na, NO₃2-, and SO₄2- in the leachate exceed the recommended groundwater quality standard of China by up to 6637 times. These ions are likely to increase the salinization of the soil and groundwater. The minor elements in red mud leachate include As, B, Ba, Cr, Cu, Fe, Ni, Mn, Mo, Ti, V, and Zn, and the trace elements in red mud leachate include Ag, Be, Cd, Co, Hg, Li, Pb, Sb, Se, Sr, and Tl. Some of these elements have the concentration up to 272 times higher than those of the groundwater quality standard and are toxic to the environment and human health. Therefore, scientific guidance is needed for red mud management, especially for the design of the containment system of the facilities.


Effects of axotomy on the cholinesterase and carbonic anhydrase activities of axons in the proximal and distal stumps of rabbit sciatic nerves: a temporal study.
The temporal changes in transected sciatic nerves of rabbits were studied using recently developed histochemical techniques for discriminating between sensory and motor axons. A segment of the nerve was removed to inhibit spontaneous regeneration across the gap. Staining characteristics of the proximal and distal nerve stumps were studied at 1, 2, 3, 4, 9, and 35 days following axotomy and compared with control sciatic nerves. In the control and test nerves, subpopulations of myelinated sensory axons were identified histochemically by carbonic anhydrase (CA) staining, and a subset of alpha motor axons were visualized by cholinesterase (CE) staining. Axon staining patterns were reciprocal; i.e., sensory axons were CA-positive and CE-negative, whereas motor axons were CE-positive and CA-negative. Histochemical activities persisted at day 35 after axotomy in the proximal stump and until day 9 after axotomy in the distal stump. This implies that these techniques may aid in both immediate and delayed primary nerve repair. With time, there is buildup of scar tissue adding to the proximal and distal stumps. Therefore, sections for demonstrating sensory and motor axons must be taken progressively further back from the nerve stump ends. Histochemical axon typing indicated that sensory axons regenerated earlier and to a greater degree than motor axons in the developing neuroma. Use of both the carbonic anhydrase and cholinesterase staining methods is more accurate than either technique alone as an adjunct for examining normal and injured peripheral nerves.


Evaluation of Pharmacokinetic Drug-Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches.
Pharmacokinetic drug-drug interactions (DDIs) occur when a drug alters the absorption, transport, distribution, metabolism or excretion of a co-administered agent. The occurrence of pharmacokinetic DDIs may result in the increase or the decrease of drug concentrations, which can significantly affect the drug efficacy and safety in patients. Enzyme-mediated DDIs are of primary concern, while the transporter-mediated DDIs are less understood but also important. In this review, we presented an overview of the different mechanisms leading to DDIs, the in vitro experimental tools for capturing the factors affecting DDIs, and in silico methods for quantitative predictions of DDIs. We also emphasized the power and strategy of physiologically based pharmacokinetic (PBPK) models for the assessment of DDIs, which can integrate relevant in vitro data to simulate potential drug interaction in vivo. Lastly, we pointed out the future directions and challenges for the evaluation of pharmacokinetic DDIs.


NR4A1-dependent Ly6Clow monocytes contribute to reducing joint inflammation in arthritic mice through Treg cells.
Monocytes are central to the physiopathology of arthritis, but their roles in progression and resolution of the disease remain to be clarified. Using NR4A1-/- mice, which lack patrolling lymphocyte antigen 6C (Ly6Clow ) monocytes, we found that inflammatory Ly6Chigh monocytes contribute to rapid development of arthritis in a serum transfer-induced arthritis (STIA) model. Our experiments suggest that patrolling monocytes do not promote the initiation and progression of arthritis in mice, as severity of symptoms was amplified in NR4A1-/- mice. Moreover, we show that treatment of arthritic wild type (WT) mice with cytosporone B (Csn-B), a NR4A1-specific agonist, significantly reduces severity of disease. Effects of Csn-B were absent in monocyte-depleted mice treated with clodronate until Ly6Clow monocytes were restored. Adoptive transfer of Ly6Clow monocytes in arthritic NR4A1-/- mice treated with Csn-B reduces joint inflammation, supporting the regulatory role of Ly6Clow subset on disease development. Our results also reveal that administration of Csn-B to arthritic mice enhances levels of circulating CD4+ CD25+ FoxP3+ Treg cells, a process requiring the presence of Ly6Clow monocytes. Together, these data indicate that Ly6Chigh monocytes are involved in the initiation and progression of arthritis and Ly6Clow monocytes contribute to reduce joint inflammation through the mobilization of Treg cells.


Statistical significance testing and clinical trials.
The efficacy of treatments is better expressed for clinical purposes in terms of these treatments' outcome distributions and their overlapping rather than in terms of the statistical significance of these distributions' mean differences, because clinical practice is primarily concerned with the outcome of each individual client rather than with the mean of the variety of outcomes in any group of clients. Reports of the obtained outcome distributions for the comparison groups of all competently designed and executed randomized clinical trials should be publicly available no matter what the statistical significance of the mean differences among these groups, because all of these studies' outcome distributions provide clinically useful information about the efficacy of the treatments compared.


Association of blood pressure in the first-week of hospitalization and long-term mortality in patients with acute left ventricular myocardial infarction.
Previous studies have shown that optimal blood pressure (BP) control is necessary to outcomes in patients with acute myocardial infarction (AMI). Acute left ventricular MI is a prevalent type of AMI with poor prognosis. We aimed to analyze the associations between BP control in the first 7 days of hospitalization and long-term mortality specific to patients with isolated left ventricular MI. A total of 3108 acute left ventricular MI patients were included in this analysis. The average BP on the first seven days of hospitalization was categorized into 10-mmHg increments. The primary and secondary outcomes were all-cause death and cardiac death, respectively. Cox models were used to assess the association of outcomes with BP during hospitalization. The median length-of-stay was 7 (IQR 6-10) days. The relationship between systolic BP (SBP) or diastolic BP (DBP) followed a U-shaped curve association with outcomes. All-cause mortality was higher in patients with lower SBP (≤90 mmHg) (adjusted hazard ratios (HRs) 7.12, 95% confidence interval (CI) 3.13-16.19; p < 0.001) and DBP (<60 mmHg) (HR 1.76, 95% CI 1.14-2.71; p = 0.011) [reference: 110 < SBP ≤120 mmHg; 70 < DBP ≤ 80 mmHg], respectively. Furthermore, primary outcome was higher in patients with higher SBP (>130 mmHg) (HR 1.51, 95% CI 1.12-2.03; p = 0.007) and DBP (>80 mmHg) (HR 1.61, 95% CI 1.20-2.18; p = 0.002), respectively. Maintaining a SBP from 90 to 130 mmHg and a DBP from 60 to 80 mmHg may be beneficial to patients with acute left ventricular MI in the long run.


Intermittent androgen-deprivation therapy in prostate cancer: a critical review focused on phase 3 trials.
Intermittent androgen deprivation (IAD) in prostate cancer (PCa) patients has been proposed to delay development of castration resistance and to reduce the side effects and costs of androgen deprivation therapy (ADT). This review analyzes (1) the oncologic and quality of life (QoL) results from randomized phase 3 trials comparing IAD and continuous ADT and (2) the prognostic parameters for IAD. We searched the Medline and Cochrane Library databases (primary fields: prostate neoplasm and intermittent androgen deprivation; secondary fields: randomized trials, survival, quality of life, predictors) without language restriction. We found seven extensively described phase 3 trials randomizing 4675 patients to IAD versus continuous ADT. Other randomized trials investigating IAD have been performed, but available data are limited and have been published only in preliminary fashion. In all seven trials, patients spent most of their time on, rather than off, ADT. The induction periods ranged from 3 mo to 8 mo; in all but one trial, the PSA level designated for ADT discontinuation was <4 ng/ml. Mean follow-up ranged from 40-108 mo. Collectively, these trials support the concept that, mainly in metastatic cases, IAD can produce oncologic results similar to continuous ADT. In terms of overall survival, the hazard ratios for IAD and continuous ADT were very similar (range: 0.98-1.08). The QoL benefit of IAD appears to be modest at best. With IAD, QoL is likely influenced by the duration of the off-treatment periods and by the rate of testosterone recovery. The evidence indicates that IAD is not inferior to continuous ADT. Data are insufficient to determine whether IAD is able to prevent the long-term complications of ADT. More comparative analysis focused on QoL is warranted.


Modeling of Melt Flow and Heat Transfer in Stationary Gas Tungsten Arc Welding with Vertical and Tilted Torches.
A 3D numerical simulation was conducted to study the transient development of temperature distribution in stationary gas tungsten arc welding with filler wire. Heat transfer to the filler wire and the workpiece was investigated with vertical (90°) and titled (70°) torches. Heat flux, current flux, and gas drag force were calculated from the steady-state simulation of the arc. The temperature in the filler wire was determined at three different time intervals: 0.12 s, 0.24 s, and 0.36 s. The filler wire was assumed not to deform during this short time, and was therefore simulated as solid. The temperature in the workpiece was calculated at the same intervals using heat flux, current flux, gas drag force, Marangoni convection, and buoyancy. It should be noted that heat transfer to the filler wire was faster with the titled torch compared to the vertical torch. Heat flux to the workpiece was asymmetrical with both the vertical and tilted torches when the filler wire was fully inserted into the arc. It was found that the overall trends of temperature contours for both the arc and the workpiece were in good agreement. It was also observed that more heat was transferred to the filler wire with the 70° torch compared with the 90° torch. The melted volume of the filler wire (volume above 1750 °K) was 12 mm3 with the 70° torch, compared to 9.2 mm3 with the 90° torch.


The Relationship Between Sickle Cell Disease and Sudden Onset Sensorineural Deafness.
Sickle cell anemia (SCA) is a hereditary hemoglobin (Hb) disorder associated with a very specific molecular lesion, which is the exchange of glutamic acid for valine in the sixth residue of the Hb beta chain, originating the S Hb. It is characterized by intermittent episodes of vascular occlusion and end-organ damage. Progressive organ damage may affect any organ with brain, eyes, pulmonary, hepatobiliary, spleen, genitourinary, and the musculoskeletal systems being the most commonly involved and reported. Other complications of the disease that have not been well described or studied include cranio-orbital syndromes, oropharyngeal syndromes, periodontal disease, and otologic syndromes. Considering the vaso-occlusive nature of sickle cell disease (SCD), the potential for auditory damage is not unexpected. However, the incidence of subjective hearing impairment among SCA is very low and and little is known about the relationship between SCA and hearing loss. Here we report a 43-year-old female with SCA who presented with sudden bilateral hearing loss and generalized body ache and admitted as a case of sensorineural deafness with vascular crisis; she received IV fluid and analgesia and improved after five days from the therapy.


How common is catamenial epilepsy?
Forty women of childbearing age with refractory epilepsy were asked to record their seizures, the first and last days of their menstrual periods, and symptoms of premenstrual tension for 3 consecutive months. By defining catamenial epilepsy as the occurrence of at least 75% of seizures each month in the 10-day time frame, which included the 4 days preceding menstruation and the 6 days after its onset, only 5 women (12.5%) were identified who fulfilled the criterion. Nevertheless, after the study was completed, 31 (78%) of these patients claimed that most of their seizures occurred near the time of and were exacerbated by menstruation. The patients with catamenial epilepsy reported no more symptoms of premenstrual tension than did the rest of the group. Clustering outside the menstrual cycle was noted in 4 other patients. Catamenial epilepsy is an uncommon condition. Patient claims about frequency of seizures in relation to menstruation are not always accurate. A standard definition should be adopted because the diagnosis has implications for management.


Lysophosphatidylserine analogues differentially activate three LysoPS receptors.
Lysophosphatidylserine (1-oleoyl-2 R-lysophosphatidylserine, LysoPS) has been shown to have lipid mediator-like actions such as stimulation of mast cell degranulation and suppression of T lymphocyte proliferation, although the mechanisms of LysoPS actions have been elusive. Recently, three G protein-coupled receptors (LPS1/GPR34, LPS2/P2Y10 and LPS3/GPR174) were found to react specifically with LysoPS, raising the possibility that LysoPS serves as a lipid mediator that exerts its role through these receptors. Previously, we chemically synthesized a number of LysoPS analogues and evaluated them as agonists for mast-cell degranulation. Here, we used a transforming growth factor-α (TGFα) shedding assay to see if these LysoPS analogues activated the three LysoPS receptors. Modification of the serine moiety significantly reduced the ability of the analogues to activate the three LysoPS receptors, whereas modification of other parts resulted in loss of activity in receptor-specific manner. We found that introduction of methyl group to serine moiety (1-oleoyl-lysophosphatidylallothreonine) and removal of sn-2 hydroxyl group (1-oleoyl-2-deoxy-LysoPS) resulted in reduction of reactivity with LPS1 and LPS3, respectively. Accordingly, we synthesized a LysoPS analogue with the two modifications (1-oleoyl-2-deoxy-lysophosphatidylallothreonine) and found it to be an LPS2-selective agonist. These pharmacological tools will definitely help to identify the biological roles of these LysoPS receptors.