Risk Factors for Cholecystectomy After Laparoscopic Roux-En-Y Gastric Bypass.
Patients who have undergone bariatric surgery are at risk for subsequent cholecystectomy. We aimed to identify risk factors for cholecystectomy after laparoscopic Roux-en-Y gastric bypass (LRYGB). We conducted a retrospective case-control study of patients who underwent LRYGB between 2013 and 2015. Cases underwent cholecystectomy because of biliary symptoms after LRYGB. For each case, two controls were selected without subsequent cholecystectomy. Logistic regression analyses were used to identify risk factors. Between 2013 and 2015, 1780 primary LRYGBs were performed. We identified 233 (13.1%) cases who had undergone cholecystectomy after a median (IQR) of 12 (8-17) months, and 466 controls. Female gender (OR (95% CI) 1.83 (1.06-3.17)), Caucasian ethnicity (OR (95% CI) 1.82 (1.10-3.02)), higher percent total weight loss (%TWL) at 12 months (OR (95% CI) 1.06 (1.04-1.09)), and preoperative pain syndrome (OR (95% CI) 2.72 (1.43-5.18)) were significantly associated with an increased risk for cholecystectomy. Older age (OR (95% CI) 0.98 (0.96-0.99)) and preoperative statin use were associated with a reduced risk (OR (95% CI) 0.56 (0.31-1.00)). A dose-effect relationship was found between the intensity of preoperative statin and risk for cholecystectomy. In our study, higher %TWL and preoperative pain syndrome were associated with an increased risk for cholecystectomy besides the traditional risk factors female gender and Caucasian ethnicity. These factors can be used to identify high-risk patients, who might benefit from preventive measures. Whether statins can protect bariatric patients from developing gallstones should be investigated prospectively.


Variety Is the Spice of Life: Positive and Negative Effects of Noise in Electrical Stimulation of the Nervous System.
Noisy stimuli may hold the key for optimal electrical stimulation of the nervous system. Possible mechanisms of noise's impact upon neuronal function are discussed, including intracellular, extracellular, and systems-level mechanisms. Specifically, channel resonance, stochastic resonance, high conductance states, and network binding are investigated. These mechanisms are examined and possible directions of growth for the field are discussed, with examples of applications provided from the fields of deep brain stimulation or spinal cord injury. Together, this review highlights the theoretical basis and evidence base for the use of noise to enhance current stimulation paradigms of the nervous system.


Optimizing pharmacologic thromboprophylaxis use in pediatric orthopedic surgical patients through implementation of a perioperative venous thromboembolism risk screening tool.
Although rare, venous thromboembolic events (VTE) are a significant challenge in pediatric orthopedic surgical patients (POSP). A VTE thromboprophylaxis screening tool was developed and implemented in POSPs at the IWK Health Centre since October 2016. This retrospective cohort study was designed to evaluate and assess the impact of the VTE thromboprophylaxis screening tool in terms of use of thromboprophylaxis in POSP. Using the tool, POSPs were screened and were categorized into risk groups. Patient groups were compared and spearman correlation analysis was performed to show the strength of association between risk factors and thromboprophylaxis. Retrospective screening of pre-algorithm patients who received thromboprophylaxis was done to further assess the screening tool. After the implementation of the VTE thromboprophylaxis screening tool in POSPs, there was a 47.9% reduction in the use of thromboprophylaxis (P = 0.046) as compared with before. Neither VTE nor significant bleeding complications occurred before or after screening tool implementation. Compliance with the screening tool was excellent (100% of patients in the high-risk category received thromboprophylaxis). High-risk patients were more likely to have body mass index > 30 (35.7%), limited/altered mobility (57.1%), and to be undergoing a complicated/repeat surgery (64.3%). The present study demonstrates successful implementation of a VTE thromboprophylaxis screening tool that resulted in significant reduction in use of thromboprophylaxis in POSPs with no increase in VTE or change in bleeding complications.


The associations between two facets of narcissism and eating disorder symptoms.
The current study sought to examine the relationships between two facets of narcissism (vulnerable and grandiose) and eating disorder symptoms. Based upon previous research (Davis, Claridge, & Cerullo, 1997), it was predicted that the vulnerable narcissism facet would be more strongly associated with eating disorder symptoms because of the tendency for vulnerable narcissists to base their self-worth on their appearance (Zeigler-Hill, Clark, & Picard, 2008). The hypotheses were tested cross-sectionally in a sample of 355 male and female undergraduate students. Results generally conformed to prediction, in that vulnerable narcissism tended to be positively correlated with eating disorder symptoms, and this relationship was partially mediated by self-worth that is contingent upon physical appearance. Our findings are consistent with the notion that vulnerable narcissism is a risk factor for eating disorder symptoms because it is associated with a drive to improve self-worth through the enhancement of physical appearance.


Effect of exogenous bFGF on the proliferation of human adenoid cystic carcinoma ACC-2 cells.
To observe the effects of basic fibroblast growth factor (bFGF) on human adenoid cystic carcinoma ACC-2 cell line proliferation and ERK, cyclin D1/p21(waf/cip1) signaling pathways, human adenoid cystic carcinoma cells (ACC-2) were cultured and the influence of bFGF of different concentrations on cell proliferation was determined by MTT. Protein was detected by immuno-precipitation and ERK activity by using ERK agent kit. p-ERK(1/2) and down-stream cyclin D1, p21(waf/cip1) expression were detected by Western blotting and the interfering role of mitogen protein-activated kinase (MEK) suppressor U0126 in the afore-mentioned indicators was examined. MTT demonstrated ACC-2 cell proliferation was substantially enhanced by bFGF, immuno-precipitation displayed ERK activity was up-regulated by bFGF, and immuno-imprinting also showed p-ERK(1/2), cyclin D1 expression was greatly enhanced and p21(waf/cip1) expression was inhibited by bFGF. U0126 suppressed the effect of bFGF. It is concluded that bFGF can promote the proliferation of human adenoid cystic carcinoma ACC-2 cells, and its pathways are associated with the up-regulated activity and expression of p-ERK(1/2), inhibited p21waf/cip1 expression and enhanced cyclin D1 expression.


Preparation and Characterization of Folate Targeting Magnetic Nanomedicine Loaded with Gambogenic Acid.
To engineer multifunctional nanomedicines for simultaneous imaging and therapy of cancer cells, we have prepared Gambogenic acid (GNA) loaded folic acid (FA) armed MNPs (FA-GNA-MNPs) to target the folate receptor (FR) positive cancer cells. The FA-GNA-MNPs have been prepared by a facile method, which have been further characterized by SEM, TEM, IR and UV-vis spectra. And the cytotoxicity of FA-GNA-MNPs to HeLa and A549 cells was assessed using the MTT assay. The FA-GNA-MNPs (with loading efficiency of 4.35%) showed sustained liberation of GNA molecules (with 73.46% release in 96 h). The mean particle diameter (MD) of FA-GNA-MNPs and the polydispersity index (PDI) are 254.3 nm and 0.139, respectively. The cytotoxicity of free GNA and FA-GNA-MNPs toward HeLa cells showed that FA-GNA-MNPs was more cytotoxic than GNA. Based on these findings, it suggests that FA-GNA-MNPs would be as a novel multifunctional nanomedicine/theranostic for concurrent targeting, imaging and therapy of the FR-positive cancer cells.


Use of soluble recombinant TNF receptor to improve detection of TNF secretion in cultures of tumor infiltrating lymphocytes.
The accurate quantitation of picogram amounts of TNF is possible by ELISA and is useful in many areas of biomedical research, including studies of TNF release in vitro by stimulated lymphocytes and macrophages, and of serum levels in patients with cancer and sepsis. However, we show in this report that the detection of recombinant TNF standards by ELISA falls over time with incubation at 37 degrees C, and is further decreased when incubated with tumor infiltrating lymphocytes (TIL), making accurate quantitation difficult. We demonstrate that the soluble dimeric form of the TNF receptor can prevent this decrease, both in the presence and absence of TIL. In contrast, the soluble monomeric TNF receptor was much less effective in preventing this decrease. In addition, the dimeric but not the monomeric TNF receptor was found to inhibit bioactivity of TNF as measured by L929 cytotoxicity. The dimeric TNF receptor does not interfere with the detection of recombinant TNF standards by ELISA, and entirely stabilizes TNF levels incubated over 48 h at 37 degrees C in the presence and absence of TIL. This protection is specific, and the TNF receptor does not stabilize interferon-gamma. The dimeric form of the soluble TNF receptor has proven useful in detecting TNF released by TIL transduced with the TNF cDNA that are currently being used in studies of the gene therapy of cancer with TIL. The dimeric TNF receptor may also prove useful in the accurate quantitation of TNF released by stimulated lymphocytes and macrophages in vitro, and in the quantitation of serum TNF levels in patients.


Ginsenoside Rg1 ameliorates palmitic acid-induced insulin resistance in HepG2 cells in association with modulating Akt and JNK activity.
Hepatic insulin resistance can be induced by excess dietary intake of saturated fat. Ginsenoside Rg1 (GRg1), the major active ginsenoside enriched in tonic food ginseng, was reported to help alleviate liver diseases. In the present study, GRg1 was evaluated for its impact on palmitic acid (PA)-induced hepatic insulin resistance model in vitro. Insulin resistance in HepG2 cells was induced by 0.5 mM PA exposure for 24 h and then the effect of GRg1 on cellular glucose consumption was measured. Expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphate (G6Pase) were analyzed by Western blot and quantitative real-time polymerase chain reaction. Activation of protein kinases and transcript factor was analyzed by measuring protein phosphorylation. The influence of GRg1 on reactive oxygen species (ROS) production in HepG2 was also examined. GRg1 reversed PA-induced decrease in glucose consumption of HepG2 cells by downregulating gluconeogenesis genes G6pase and PEPCK. GRg1 increased Akt activation but inhibited JNK activation in PA-challenged HepG2 cells. Cellular ROS level was elevated in insulin-resistant HepG2 cells but was reduced by GRg1. Together these findings indicate that GRg1 protects against hepatic insulin resistance via preserving insulin signaling sensitivity and is a promising alternative medicine.


Recognition of cervical neoplasia by the estimation of a free-radical reaction product (octadeca-9,11-dienoic acid) in biopsy material.
Linoleic acid (18:2(9,12)) and its diene-conjugated isomer (18:2(9,11)) were measured in 65 cervical biopsy samples. Both the 18:2(9,11) concentration and the 18:2(9,11)/18:2(9,12) molar ratio showed highly significant differences between the normal and precancerous groups. Both showed a further significant increase in 4 invasive carcinomas. The findings in histologically normal areas from organs with precancer correlated significantly with the results in the precancerous lesions.


Investigating the relationship between menopausal women's health anxiety and sexual performance and attitude towards menopause.
Menopause is a natural event in the life of women. Women's concerns during menopause and the role of health anxiety in the attitude and sexual performance of women during this period affect the quality of life. Therefore, the present study was conducted with the aim of determining the relationship between health anxiety and sexual performance and attitude towards menopause in postmenopausal women. The present study was a cross-sectional study of communication type that was conducted on 200 postmenopausal women with records in Sabzevar Comprehensive Health Centers in 2021-2022. In order to collect information, standard questionnaires of health anxiety, attitude towards menopause, and sexual performance were used. The collected data were analyzed by SPSS version 16 software and descriptive and analytical statistical tests (Spearman). A significance level of less than 0.05 was considered. The results of data analysis showed that health anxiety has a significant relationship with the dimensions of desire (p = 0.045 and r = -0.142) and sexual pain (p < 0.001 and r = 0.274). Also, there was a significant relationship between the attitude towards menopause with sexual performance (p < 0.001 and r = 0.244) and health anxiety with the attitude towards menopause (p < 0.001 and r = 0.27). The results of this study showed that there is an inverse relationship between health anxiety and sexual desire and a significant direct relationship with sexual pain. Also, the attitude towards menopause has a significant direct relationship with sexual behavior and health anxiety. Therefore, it is suggested to pay attention to the mental health of postmenopausal women along with the physical aspect and to pay attention to educational programs to improve the care and health programs of these women.


PmEEA1, the early endosomal protein is employed by YHV for successful infection in Penaeus monodon.
Yellow head disease (YHD) is an infectious disease of Penaeus monodon which is caused by the yellow head virus (YHV). YHV infection invariably leads to 100% shrimp mortality within 3-5 days. Currently, an effective method to prevent or cure shrimp from YHV infection has not been elucidated. Therefore, the molecular mechanism underlying YHV infection should be examined. In this study, early endosome antigen 1 (EEA1) protein that was involved in the tethering step of the vesicle and early endosome fusion was investigated during YHV infection. The open reading frame of P. monodon EEA1 (PmEEA1) was cloned and sequenced (3000 bp). It encoded a putative protein of 999 amino acids and contained the zinc finger C2H2 domain signature at the N-terminus and the FYVE domain at the C-terminus. Suppression of PmEEA1 by specific dsRNA in shrimp showed inhibition of YHV replication after 48 h post YHV injection (hpi). On the other hand, shrimp received only NaCl without any dsRNA showed high YHV levels at approximately one hundred thousand times at 24 hpi and 48 hpi. Moreover, silencing of PmEEA1 by specific dsRNA followed by YHV challenge demonstrated a delay in shrimp mortality from 60 hpi to 168 hpi when compared to the control. These results indicated that YHV required PmEEA1 for trafficking within the infected cells, strongly suggesting that PmEEA1 may be a potential target to control and prevent YHV infection in P. monodon.


Therapeutic drug monitoring in childhood idiopathic nephrotic syndrome: a state of the art review.
Immunosuppressants are commonly used as steroid-sparing agents in childhood idiopathic nephrotic syndrome (NS) to induce and sustain remissions. These drugs have narrow therapeutic indices with high inter- and intra-patient variability. Therapeutic drug monitoring (TDM) would therefore be essential to guide the prescription. Multiple factors in NS contribute to additional variability in drug concentrations, especially during relapses. In this article, we review the currently available evidence of TDM in NS and suggest a practical approach for clinicians' reference.


Localization of exogenous silver in brain and spinal cord of silver exposed rats.
Exogenous silver in brain and spinal cord sections from rats treated with Protargol, silver lactate or silver nitrate was visualized by physical development. The silver penetrated the blood-brain barrier and accumulated in neurones and glia. The distribution of silver in the CNS was heterogeneous. Even with low doses and short survival periods, silver was found to accumulate in large motoneurones in the brain stem and spinal cord and neurones in the cerebellar nuclei. Silver was only found in di- and telencephalic structures after extensive exposure. Silver distribution following oral silver lactate and silver nitrate treatment differed in that silver nitrate resulted in a relatively high content of silver in glia whereas deposition occurred preferentially in neurones following silver lactate treatment. Electron-microscopical studies showed that silver was located intracellularly in the lysosomes and extracellularly in basement membranes and elastic fibres of the vessels.


Thyroid autoantibodies are not associated with recurrent pregnancy loss.
Approximately 1% of all women have recurrent pregnancy loss, defined as >/=3 spontaneous losses of pregnancy; however, a cause is determined in only 50% of cases. Recent studies have associated the presence of thyroid autoantibodies during the first trimester of pregnancy with spontaneous abortion in the current pregnancy among women without a history of recurrent abortion. The objective of this study was to determine whether circulating thyroid autoantibodies were associated with recurrent pregnancy loss. Sera from 74 nonpregnant women with a history of recurrent pregnancy loss and from 75 healthy, fertile control subjects of similar gravidity were tested for thyroglobulin and thyroid peroxidase antibodies by means of radioimmunoassay kits. All women had a third-generation thyroid-stimulating hormone assay performed. Samples were obtained >/=6 months after a pregnancy. Twenty-two of the women with a history of recurrent pregnancy loss (29.3%) and twenty-eight of the control subjects (37%) had positive results for either one or both of the thyroid autoantibodies (P >. 05). Mean thyroid-stimulating hormone levels and the proportion of women with abnormal thyroid-stimulating hormone values did not differ between the 2 groups. Women with a history of recurrent pregnancy loss are no more likely than are fertile control subjects to have circulating thyroid autoantibodies. Testing for antithyroid antibodies is not clinically useful in the evaluation of patients with a history of recurrent pregnancy loss.


DNA methylation is not responsible for p21WAF1/CIP1 down-regulation in osteoarthritic chondrocytes.
In this study, we were interested in the overall methylation level in aged and degenerated cartilage. Also, we looked at one gene which might be involved in the re-initiation of replicative activity in osteoarthritis (OA) chondrocytes, p21(WAF1/CIP1). p21(WAF1/CIP1) was previously suggested to be down-regulated in OA chondrocytes and is known to be regulated by epigenetic modulation. Total methylation levels were analyzed by high pressure liquid chromatography (HPLC), mRNA expression of p21(WAF1/CIP1) and DNMT enzymes by real-time polymerase chain reaction. The methylation status of the p21(WAF1/CIP1)- promotor using bisulfite genomic sequencing was evaluated. General methylation analysis of genomic DNA showed no difference in between normal and aged/OA chondrocytes. Also no difference in methylation of the promotor of the p21(WAF1/CIP1) gene was detectable, which was significantly down-regulated in OA chondrocytes. DNMT1 and DNMT3a were expressed with no significant changes of expression levels found in OA chondrocytes. Cell cycle progression inhibitor p21(WAF1/CIP1) is expressed in normal and significantly down-regulated in OA articular chondrocytes, which may mediate the re-initiation of cell proliferation in OA cartilage. However, the suppression of p21(WAF1/CIP1) mRNA expression is not due to hypermethylation of its promotor. No overall changes in genome methylation levels were found in aged or OA cartilage. Interestingly, significant expression of DNA methyltransferases was found in articular chondrocytes, which supports that DNA methylation could still be a relevant mechanism of gene regulation in (osteoarthritic) chondrocytes, though not on an overall genomic level nor specifically for the regulation of the p21(WAF1/CIP1) gene.


Do bone marrow fat cells or their precursors have a pathogenic role in idiopathic aplastic anaemia?
Idiopathic aplastic anaemia (AA), aplastic anaemia of unknown aetiology, is usually defined as marrow failure with fatty replacement of hemopoietic tissue and peripheral pancytopenia. The pathophysiology is largely unknown, though many mechanisms have been hypothesized. These include the absence of or defects in hemopoietic stem cells (HSC), abnormalities of the bone marrow (BM) microenvironment, immune system disorders and abnormalities of the regulatory factors that control hemopoiesis. The characteristic feature of AA is the replacement of hematopoietically active marrow by fat cells; however, the fat cells themselves have received little attention to date, and this apparent fatty marrow infiltration has been considered a secondary phenomenon. That the marrow fat cells in AA may be abnormal and may have a pathogenic role has never been considered. This communication, postulates that AA may result from an abnormal and excessive proliferation of marrow fat cells and the displacement of the hematopoietic tissue of the marrow; and that the resultant marrow failure could be a secondary phenomenon.


Ki-67 and other proliferation markers useful for immunohistological diagnostic and prognostic evaluations in human malignancies.
The aim of this study is to briefly review proliferation markers that can be applied in immunohistochemistry, with special emphasis on the monoclonal antibody Ki-67. This antibody reacts with a nuclear antigen present in all proliferating cells which are in the active parts of the cell cycle, i.e. G1, S, G2, and mitosis, but which is absent in G0 cells. Thus, with the help of this antibody a determination of the growth fraction of a given human cell population is possible. The use of this method in human tumor diagnostics is illustrated by three examples: malignant melanoma, breast carcinoma, and malignant Non-Hodgkin lymphoma. The results show that evaluation of the growth fractions by Ki-67 is not only a diagnostic importance, but also has independent prognostic value. In addition, preliminary data on the immunobiochemical characterization of native and recombinant Ki-67 antigen are presented. In immunoblot analysis, Ki-67 detects a doublet with apparent molecular weights of greater than 300 kDa. Furthermore, our data show that cDNA clones isolated from Lambda gT11 cDNA libraries encode for parts of the Ki-67 antigen and must contain the sequence that encodes for the epitope recognized by the Ki-67 antibody.


Synthesis of a novel anticancer prodrug designed to target telomerase sequence.
A curcumin conjugate viz. 1,7-bis (4-O-glycinoyl-3-methoxyphenyl)-1,6- heptadiene-3, 5, dione (I) was synthesised and after attachment of linker (-CH2-CH2-OH) phosphitylated. This unit was attached to the deoxy-11 mer, 5'-GTT AGG GTT AG-3', a complementary sequence of telomerase RNA template. Its hybridisation with the telomerase RNA sequence, 5'-CUA ACC CUA AC-3' has been studied employing Tm.


Nosocomial pneumonia: epidemiology, pathogenesis, diagnosis, treatment and prevention.
Nosocomial pneumonia is the second most common nosocomial infection and the leading cause of death from hospital-acquired infection. Supine body position in mechanically ventilated patients, and cardiopulmonary resuscitation and continuous sedation are significant risk factors for developing nosocomial pneumonia. During the past 2 years some new therapeutic approaches for nosocomial pneumonia and modifications to established therapies have been described, such as optimal pharmacodynamic evaluations, monotherapy versus combination therapy, computer-assisted management programmes and antibiotic rotations.


Synthesis and evaluation of quinazoline amino acid derivatives as mono amine oxidase (MAO) inhibitors.
A series of quinazolinone amino acid ester and quinazolinone amino acid hydrazides were prepared under microwave irradiation as well as conventional condition. The microwave irradiation afforded the product in less reaction time, higher yield and purity. The structures of the synthesized compounds were confirmed by IR, NMR, and elemental analysis. The new synthesized compounds were studied for their monoamine oxidase inhibitory activity. They showed more selective inhibitory activity toward MAO-A than MAO-B. Compounds 7, 10, and 15 showed MAO-A inhibition activity (IC50=3.6×10(-9), 2.8×10(-9), 2.1×10(-9) M, respectively) comparable to that of the standard clorgyline (IC50=2.9×10(-9)M). 2-(2-(Benzo[d][1,3]dioxol-5-yl)-4-oxo-1,2-dihydroquinazolin-3(4H)-yl)acetohydrazide 15 showed selective MAO-A inhibition activity (SI=39524) superior to that of the standard clorgyline (SI=33793). The acute toxicity of the synthesized compounds was determined. In addition, computer-assisted simulated docking experiments were performed to rationalize the biological activity.


Reading mirror-reversed text: sinistrals really are inferior.
R. Tankle and K. M. Heilman (1982, Brain and Language, 17, 124-132) reported a sinistral superiority in obligatory reading of left-right mirror-reversed material. Their subjects included weak left- and right-handers. J. L. Bradshaw, N. C. Nettleton, L. Wilson, and V. Burden (1985, Brain and Language, 26, 322-331) employed a variety of geometrically transformed text, including mirror-reversed, and found that strong familial sinistrals were either not different from or were even slightly inferior to dextrals in reading most transformations, including left-right mirror reversals. We now report a study using subjects selected according to criteria similar to those of Tankle and Heilman, and find under these conditions that sinistrals are indeed significantly inferior to dextrals.


Rapid assessment of salivary MMP-8 and periodontal disease using lateral flow immunoassay.
The objective of this study was to determine the efficacy of a novel point-of-care immunoflow device (POCID) for detecting matrix metalloproteinase (MMP)-8 concentrations in oral fluids in comparison with a gold standard laboratory-based immunoassay. Oral rinse fluid and whole expectorated saliva samples were collected from 41 participants clinically classified as periodontally healthy or diseased. Samples were analyzed for MMP-8 by Luminex immunoassay and POCID. Photographed POCID results were assessed by optical scan and visually by two examiners. Data were analyzed by Pearson's correlation and receiver-operating characteristics. MMP-8 was readily detected by the POCID, and concentrations correlated well with Luminex for both saliva and rinse fluids (r = 0.57-0.93). Thresholds that distinguished periodontitis from health were delineated from both the optical scans and visual reads of the POCID (sensitivity: 0.7-0.9, specificity: 0.5-0.7; P < 0.05). Performance of this POCID for detecting MMP-8 in oral rinse fluid or saliva was excellent. These findings help demonstrate the utility of salivary biomarkers for distinguishing periodontal disease from health using a rapid point-of-care approach.


Nicotinamide riboside kinase-2 alleviates ischemia-induced heart failure through P38 signaling.
Nicotinamide riboside kinase-2 (NRK-2), a muscle-specific β1 integrin binding protein, predominantly expresses in skeletal muscle with a trace amount expressed in healthy cardiac tissue. NRK-2 expression dramatically increases in mouse and human ischemic heart however, the specific role of NRK-2 in the pathophysiology of ischemic cardiac diseases is unknown. We employed NRK2 knockout (KO) mice to identify the role of NRK-2 in ischemia-induced cardiac remodeling and dysfunction. Following myocardial infarction (MI), or sham surgeries, serial echocardiography was performed in the KO and littermate control mice. Cardiac contractile function rapidly declined and left ventricular interior dimension (LVID) was significantly increased in the ischemic KO vs. control mice at 2 weeks post-MI. An increase in mortality was observed in the KO vs. control group. The KO hearts displayed increased cardiac hypertrophy and heart failure reflected by morphometric analysis. Consistently, histological assessment revealed an extensive and thin scar and dilated LV chamber accompanied with elevated fibrosis in the KOs post-MI. Mechanistically, we observed that loss of NRK-2 enhanced p38α activation following ischemic injury. Consistently, ex vivo studies demonstrated that the gain of NRK-2 function suppresses the p38α as well as fibroblast activation (α-SMA expression) upon TGF-β stimulation, and limits cardiomyocytes death upon hypoxia/re‑oxygenation. Collectively our findings show, for the first time, that NRK-2 plays a critical role in heart failure progression following ischemic injury. NRK-2 deficiency promotes post-MI scar expansion, rapid LV chamber dilatation, cardiac dysfunction and fibrosis possibly due to increased p38α activation.


Ovarian follicular development in Holstein cows following synchronisation of oestrus with oestradiol benzoate and an intravaginal progesterone releasing insert for 5-9 days and duration of the oestrous cycle and concentrations of progesterone following ovulation.
The aim of this study was to determine if the duration of treatment with an intravaginal progesterone releasing insert (IVP(4)) after treatment with oestradiol benzoate (ODB) at the time of insertion and 24 h after removal would affect selected variables including: size of ovarian follicles at the time of removal of inserts, diameter of ovulatory follicles, plasma concentrations of progesterone following ovulation, and duration of the following oestrous cycle. Characteristics of oestrus at a synchronised and spontaneous oestrus were also monitored. Non-lactating Holstein cows were synchronised with an IVP(4) for 5 (n = 10), 7 (n = 10), 8 (n = 9) or 9 (n = 9) days together with injections of ODB at device insertion (2 mg) and 24 h after removal (1 mg). Ultrasonography showed no significant effect of treatment on the day of emergence of preovulatory follicles relative to the day of removal of inserts (overall mean = -4.22 +/- 0.58; P = 0.15) for cows that ovulated within 120 h insert removal (n = 36). Treatment with ODB and an IVP(4) for 5 days reduced the diameter of preovulatory follicles at the time of removal of inserts and for the following 2 days compared to cows treated for 7-9 days (mean difference 2.56 +/- 1.15 mm; P = 0.033) but did not reduce the diameter of the ovulatory follicle (P = 0.21). Day of emergence relative to removal of inserts was associated with the diameter of the ovulatory follicle (R2 = 0.69; P < 0.001). Concentrations of progesterone and the diameter of the corpus luteum following ovulation were not affected by treatment (P > 0.20), but were affected by the diameter of the ovulatory follicle (P < 0.01). Diameter of the ovulatory follicle did not affect interoestrous and interovulatory intervals (P > 0.40). We conclude that treatment with an IVP(4) for 5 compared to 7-9 days with ODB administered at device insertion, and 24 h after removal reduced the diameter of preovulatory follicles at the time of removal of the insert but did not reduce the diameter of the ovulatory follicle or concentrations of progesterone in plasma. Emergence of preovulatory follicles closer to the time of removal of inserts reduced the diameter of the ovulatory follicle when oestrus was induced with ODB. Ovulation of smaller follicles reduced concentrations of progesterone in plasma following ovulation but did not affect oestrous cycle duration.


Targeted protein degradation in antibacterial drug discovery?
Drug induced degradation of a target protein is a novel concept in drug discovery. Traditionally drugs modulate activity, as opposed to abundance, of their targets. Degradation inducing ligands act catalytically. Thus, one advantage of target degradation over the classical on-target mechanism is that lower drug concentration may be sufficient to cause the desired cellular effects. The first promoters of target degradation were discovered unintentionally: it turned out that some drugs 'accidently' promote degradation of their target by the cellular proteolytic machinery. Elegant methods were developed to target specific proteins of interest for degradation, thus enabling the rational discovery of degradation inducers. The application of targeted degradation has so far been limited to human cells. Recently, we discovered that an antibacterial drug, the anti-tuberculosis antibiotic pyrazinamide, functions as a promotor of degradation of its bacterial target. Increasing antimicrobial resistance makes the discovery of novel antibiotics more urgent than ever. Can rational target degradation be applied for the discovery of anti-bacterials? Here, we first discuss briefly some historic examples and then recent approaches in rational target degradation for human diseases. Then, we describe how the first anti-bacterial target degradation promoter pyrazinamide triggers removal of its target. Efforts are under way to exploit this specific mechanistic knowledge for the discovery of next generation pyrazinamide. We end with the big - and open - question whether targeted protein degradation as an approach to anti-bacterial drug discovery can be generalized, similar to what has been achieved in the area of drug discovery for human diseases.


Choline Rescues Behavioural Deficits in a Mouse Model of Rett Syndrome by Modulating Neuronal Plasticity.
Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls, with 95% of RTT cases resulting from mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Choline, a dietary micronutrient found in most foods, has been shown to be important for brain development and function. However, the exact effects and mechanisms are still unknown. We found that 13 mg/day (1.7 × required daily intake) of postnatal choline treatment to Mecp2-conditional knockout mice rescued not only deficits in motor coordination, but also their anxiety-like behaviour and reduced social preference. Cortical neurons in the brains of Mecp2-conditional knockout mice supplemented with choline showed enhanced neuronal morphology and increased density of dendritic spines. Modelling RTT in vitro by knocking down the expression of the MeCP2 protein with shRNA, we found that choline supplementation to MeCP2-knockdown neurons increased their soma sizes and the complexity of their dendritic arbors. Rescue of the morphological defects could lead to enhanced neurotransmission, as suggested by an observed trend of increased expression of synaptic proteins and restored miniature excitatory postsynaptic current frequency in choline-supplemented MeCP2-knockdown neurons. Through the use of specific inhibitors targeting each of the known physiological pathways of choline, synthesis of phosphatidylcholine from choline was found to be essential in bringing about the changes seen in the choline-supplemented MeCP2-knockdown neurons. Taken together, these data reveal a role of choline in modulating neuronal plasticity, possibly leading to behavioural changes, and hence, a potential for using choline to treat RTT.


Investigations into sequence and conformational dependence of backbone entropy, inter-basin dynamics and the Flory isolated-pair hypothesis for peptides.
The populations and transitions between Ramachandran basins are studied for combinations of the standard 20 amino acids in monomers, dimers and trimers using an implicit solvent Langevin dynamics algorithm and employing seven commonly used force-fields. Both the basin populations and inter-conversion rates are influenced by the nearest neighbor's conformation and identity, contrary to the Flory isolated-pair hypothesis. This conclusion is robust to the choice of force-field, even though the use of different force-fields produces large variations in the populations and inter-conversion rates between the dominant helical, extended beta, and polyproline II basins. The computed variation of conformational and dynamical properties with different force-fields exceeds the difference between explicit and implicit solvent calculations using the same force-field. For all force-fields, the inter-basin transitions exhibit a directional dependence, with most transitions going through extended beta conformation, even when it is the least populated basin. The implications of these results are discussed in the context of estimates for the backbone entropy of single residues, and for the ability of all-atom simulations to reproduce experimental protein folding data.


Aortic and inferior vena cava resection for renal cell carcinoma invading an aberrant renal vein.
Renal cell carcinoma which invades the renal veins is a frequent complicating factor in radical nephrectomy. In a 53-year-old patient with a left renal cell carcinoma, tumor thrombus was present in an aberrant, retroaortic left renal vein, and "en bloc" resection of the overlying aneurysmal aorta with a cuff of inferior vena cava was required. The aorta was reconstructed with a dacron bifurcation graft to the iliac arteries, and the vena cava closed primarily. The patient made an uneventful postoperative recovery. The requirement for extensive aortic and vena cava resection need not compromise attempts to cure locally advanced renal cell carcinoma.


The aging neck: a diagnostic approach to surgical and nonsurgical options.
The neck is a prominent indicator of aging. Loss of subcutaneous fat, prominence of platysmal banding, jowling along the mandibular border, and excessive skin laxity due to loss of collagen and elastin are common conditions that are treated. Laser technology provides additional benefits when treating the first two anatomical layers of the neck. A 7-category classification system of anatomic skin layers of the lower face was developed. Based on the classifications treatments include the use of laser, ultrasonic technology, and toxins. A classification system offering surgical and nonsurgical treatments including a 1440-nm laser fiber with a specifically designed tip to allow targeted energy delivery managed through a thermal sensing device. Treatment options correlate with the presence and severity of conditions. Categories 1 and 2 have only a fat excess condition. Laser application alone, without skin intervention, is utilized. The amount of fat with subsequent aspiration follows guidelines of categories 2 through 5. The 1440-nm laser helps in all treatments. The surgeon may elect to address skin tightening with surgical tightening in categories 6 and 7. Modalities such as toxins and focused ultrasound can be used to address muscle laxity.


Ecological measurements of light exposure, activity, and circadian disruption.
Circadian rhythms are biological rhythms that repeat at approximately 24 hours. In humans, circadian rhythms have an average period of 24.2 hours. The 24-hour patterns of light and dark on the retina synchronize circadian rhythms to the local time on earth. Lighting characteristics affecting circadian rhythms are very different than those affecting visual responses. Lack of synchronization between the endogenous clock and the local time has been associated with a host of maladies. Therefore, it is important to measure circadian light exposures over the course of the 24-hour day and to be able to assess circadian entrainment and disruption in actual living environments. Presented is an overview of the recently developed Daysimeter, a personal measurement device for recording activity and circadian light-exposure. When the Daysimeter is worn on the head, two light sensors near the eye are used to estimate circadian light (CLA) exposures over extended periods of time. Phasor analysis combines the measured periodic activity-rest patterns with the measured periodic light-dark patterns to assess behavioural circadian entrainment/disruption. As shown, day-shift and rotating-shift nurses exhibit remarkably different levels of behavioural circadian entrainment/disruption. These new ecological measurement and analysis techniques may provide important insights into the relationship between circadian disruption and well-being.


Exploring determinants of recalled in-task affective valence during recreational exercise.
Exercise-related affective responses, particularly in-task, have been implicated as influencing behavioral maintenance. An extensive body of literature, primarily using aerobic modes in laboratory settings, has identified a relatively consistent inverse relationship between intensity and affect. This relationship is purported to be partially accounted for by the saliency of interoceptive sensations (i.e., respiratory and heart rates, muscular effort), such that increased saliency elicits decreased affect. In naturalistic settings, exercise is volitional, individuals have comparatively more autonomy over exercise components (i.e., volume, duration, exercise intensity), and less is known regarding contributing factors of affective responses. Recalled affect may be perceived as a less invasive, more logistically feasible construct to measure in such settings. Thus, the purpose of the current study is to explore the basis of recalled affective valence following an acute bout of volitional exercise. Upon leaving the designated exercise area of a university recreation center, respondents (N = 236, 23y±10, 176cm±9.5, 76.9kg±16.2, 31.8% identified women, 68.2% identified men) were asked to complete a pen-and-paper survey regarding the bout they had just completed. Recalled affective valence was rated via 100 mm Visual Analog Scale, and respondents were asked to provide written explanation for the basis of recalled affective valence scores. Recalled affective valence scores were non-normally distributed (Mdn=81; IQR=30.5). Qualitative results indicate that interpretation of exertion and salient interoceptive sensations were mixed, resulting in both pleasant and unpleasant affective responses. Pre-exercise readiness factors (i.e., energy levels, substrate intake, and physical components) also contribute to recalled affective valence and could potentially explain variance in the interpretation of interoceptive sensations. Further research should expand on these findings through a more in-depth interview process and measuring factors of readiness before exercise.


Design of catabolic cassettes for styrene biodegradation.
A broad-host range metabolic cassette has been designed that, under the control of the Ptac promoter, expresses the sytABCD catabolic genes from Pseudomonas sp. Y2, which are responsible for the transformation of styrene into phenylacetic acid (styrene upper pathway). This novel cassette confers to phenylacetic acid-degrading bacteria the ability to grow efficiently on styrene as the sole carbon and energy source. By combining both the sty cassette and the archetypal pWW0 TOL plasmid into the well-known Pseudomonas putida F1 aromatic biodegrader, we have constructed a novel derivative strain that shows one of the largest degradative potentials so far described for aromatic hydrocarbons, because it is able to use BTEX compounds (benzene, toluene, ethylbenzene and xylenes) and styrene as a source of carbon and energy. Furthermore, the sty cassette was engineered within a mini-transposon and endowed with a gene containment system, based on the toxic effect of the colicin E3 RNase, to reduce its lateral spread to other hosts. This contained cassette lacks defined transcriptional regulatory signals and, thus, it becomes an alternative strategy to select recombinant strains that efficiently express the desired phenotype from housekeeping regulatory elements.


GABA-like immunoreactive innervation and dendro-dendritic contacts in the ventrolateral dendritic bundle in the cat S1 spinal cord segment: an electron microscopic study.
The motoneurons (MNs) in the ventrolateral nucleus (VLN) of the upper sacral spinal cord segments in the cat supply the external sphincters and the ischiocavernosii muscles. The dendrites of the MNs in the VLN are arranged into rostro-caudally oriented bundles (ventrolateral dendritic bundle, VLB). In this study we describe the distribution and synaptic arrangement of gamma-aminobutyric acid-immunoreactive (GABA-IR) axonal bouton profiles innervating the VLB. This was accomplished using the peroxidase-antiperoxidase technique and a polyclonal antibody raised against glutaraldehyde-conjugated GABA. The VLN receives an extensive innervation of GABA-IR axonal bouton profiles that surround both cell bodies and dendrites. Twenty-five per cent of the total number of vesicle-containing axonal profiles in the VLN neuropil were estimated to be GABA-IR. On cell bodies in the alpha-motoneuron size-range, the membrane covering of GABA-IR bouton profiles was about 18% and they constituted about 29% of the total membrane covering of axonal bouton profiles. Quantitative analysis of GABA-IR bouton profiles on dendrites revealed membrane covering figures rather similar to those on the cell bodies. They were not randomly distributed within the dendritic arborisations. Instead, they were very infrequent (2.5% of the covering) on small calibre dendrites (< 1 microns) as compared to larger dendrites (> 1 microns, 14-18.5% of the covering), although the total membrane covering of axonal bouton profiles was rather similar for all dendrites (42-52%). The data on membrane covering by GABA-IR boutons presented here may be low estimates due to technical limitations, indicating that the GABAergic input to this region might be even more extensive. A frequent finding was that one and the same GABA-IR bouton made synaptic contact with two to three adjacent dendrites. This type of synaptic arrangement among the VLN MNs indicates a divergence of the GABAergic input at the terminal level. In addition, the postsynaptic dendrites involved in such arrangements often disclosed dendro-dendritic contacts. In total, 44% of the bundled dendrites in the VLN disclosed direct dendro-dendritic contact regions. These contacts were most often of the puncta adherentia type, while desmosome-type contacts were less frequent. None of the dendro-dendritic contacts studies had the characteristics of a gap junction. Taken together, the present results indicate that GABA may be a transmitter substance in a large fraction of the synaptic input to the VLN MNs.(ABSTRACT TRUNCATED AT 400 WORDS)


Exercising for weight and shape reasons vs. health control reasons: the impact on eating disturbance and psychological functioning.
The aim of this study was to determine the prevalence and correlates of exercise motivated by health and weight/shape reasons. In total, 301 participants (53.5% males) completed questionnaires assessing eating behaviors, affect, self-esteem and attitudes toward exercise. Almost 48% of the participants reported that their exercise is motivated by weight/shape reasons. These individuals were more likely to report eating problems and more positive affect after exercising. For both groups, gender, ideal weight, and the impact of weight gain on self-esteem significantly predict disordered eating. Body mass index, affect, and attitudes toward exercise also emerged as predictors for the health reasons group. Weight and shape control reasons for exercise participation were very common and related to eating disturbance.


Hippocampal pyramidal cells excite inhibitory neurons through a single release site.
Morphologically a synapse consists of a presynaptic release site containing vesicles, a postsynaptic element with membrane specialization, and a synaptic cleft between them. The number of release sites shapes the properties of synaptic transmission between neurons. Although excitatory interactions between cortical neurons have been examined, the number of release sites remains unknown. We have now recorded excitatory postsynaptic potentials evoked by single pyramidal cells in hippocampal interneurons and visualized both cells using biocytin injections. Light and electron microscopy showed that excitatory postsynaptic potentials were mediated by a single synapse. We also reconstructed the entire axon arborization of single pyramidal cells, filled in vivo, in sections counterstained for parvalbumin, which selectively marks basket and axo-axonic cells. Single synaptic contacts between pyramidal cells and parvalbumin-containing neurons were dominant (> 80%), providing evidence for high convergence and divergence in hippocampal networks.


Definition of severity and treatment response in chronic rhinosinusitis with nasal polyps: a Delphi study among French experts.
The introduction of biotherapies has significantly changed the management of patients with chronic rhinosinusitis with nasal polyps (CRSwNP). These drugs are generally reserved for severe or recurrent CRSwNP. Thus, the concepts of severity of the disease and treatment response must be mastered by otorhinolaryngologists. However, a clear definition of these concepts in CRSwNP is missing. This article focuses on definitions of severity and treatment response in CRSwNP by providing an expert consensus among French rhinologists, using a Delphi study. The severity assessment should seek the presence of uncontrolled asthma, olfactory disorders, nasal blockage, impaired quality of life (QOL) and cumulative annual dose of systemic corticosteroids.The treatment response should assess the presence of olfactory disorders, nasal blockage, QOL impairment, response to background therapy, resistance and/or dependence to oral corticosteroids, cumulative annual dose of systemic corticosteroids, response to surgery and to biologics.A failure after polypectomy should not be considered as a failure of surgical management of CRSwNP and must discuss the realization of an extended sinus surgery procedure before the prescription of biologics. Definitions of severity, control of CRSwNP, as well as therapeutic strategies to improve patients' QOL achieved high level of consensus.


Physiological demands of mountain rescue work.
To characterise the physical fitness of mountain rescue (MR) volunteers and the physical demands of a typical MR callout. Eight MR volunteers (age ± SD: 45.5 ± 8.9 years) completed a laboratory-based treadmill exercise test to exhaustion. One week later subjects completed a field-based simulated callout to retrieve a casualty by stretcher. In both studies exercise intensity was evaluated by determination of oxygen uptake and other cardiovascular measures. The maximal oxygen uptake of the participants was 53 ml/kg/min (95% CI 45 to 60). In an unassisted callout, a typical rucksack load was 17% of body mass. Ascent time was 56 min (95% CI 40 to 72), of which 82% (95% CI 66% to 98%) was completed at hard or very hard intensity (above the respiratory compensation point). Descent time with a stretcher was 58 min (95% CI 52 to 64), of which only 6% (95% CI -4% to 16%) was completed at hard or very hard intensity. Correlations between heart rate and oxygen uptake were similar (p=0.254 by analysis of variance) during laboratory (r=0.72) and field testing, especially for the ascent (r=0.75). Mountain rescuers generally have high levels of physical fitness and are required to perform at very hard intensity for the majority of the ascent to a casualty. Heart rate is a simple yet valid measure of exercise intensity in MR personnel. These findings highlight important information on the unique physical demands faced by MR volunteers and provide direction for future research, volunteer selection and training.


Performance of three colposcopic images for the identification of squamous and glandular cervical precursor neoplasias.
To evaluate prevalence and diagnostic performance of three colposcopic images to diagnose squamous and glandular cervical precursor neoplasias. Cross-sectional study, conducted through analysis of stored digital colposcopic images. To evaluate the diagnostic performance of three images, herein named grouped glands, aceto-white villi, and atypical vessels, for detection of adenocarcinoma in situ (AIS) and cervical squamous intraepithelial neoplasias (CIN) grades 2 and 3, calculations of sensitivity, specificity, accuracy, positive likelihood ratio, receiver operating characteristic (ROC) curve, and area under the curve (AUC) were made, with their respective 95% confidence intervals. Grouped glands, aceto-white villi, and atypical vessels images had: prevalence of 21.3, 53.8, and 33.8% in patients with AIS, and 16.2, 19.5, and 9.3% in those with CIN 2 and 3; for the diagnosis of AIS, sensitivity of 21.3, 53.8, and 33.8%, specificity of 89.8, 95.2, and 94.9%, accuracy of 76.6, 87.2, and 83.1%, positive likelihood ratio of 2.1, 11.2, and 6.6, and AUC of 0.55, 0.74, and 0.64; for the diagnosis of CIN 2 and 3, sensitivity of 16.2, 19.5, and 9.3%, specificity of 89.8, 95.2, and 94.9%, accuracy of 39.4, 43.4, and 36.3%, positive likelihood ratio of 1.6, 4.1, and 1, 8, and AUC of 0.53, 0.57, and 0.52, respectively. Prevalence and accuracy of the three images were higher for the diagnosis of glandular than squamous cervical precursor neoplasias. Sensitivity, specificity, positive likelihood, and AUC of aceto-white villi and atypical vessels images were higher for the diagnosis of glandular than squamous cervical precursor neoplasias.


Determination of Multiclass Pharmaceutical Residues in Milk Using Modified QuEChERS and Liquid-Chromatography-Hybrid Linear Ion Trap/Orbitrap Mass Spectrometry: Comparison of Clean-Up Approaches and Validation Studies.
A multi-residue method was developed to identify and quantify pharmaceutical drug residues in full-fat milk, using a modified QuEChERS extraction procedure and sonication combined with Ultra-High-Performance Liquid Chromatography-High-Resolution Orbitrap Mass Spectrometry (UHPLC-HR-Orbitrap-MS). Sample preparation involves three different QuEChERS extraction procedures and sorbents for the purification step. The optimized modified extraction method, combined with the clean-up approaches using C18 and the EMR-Lipid sorbent, has been validated in terms of linearity, recovery, precision, LOD and LOQ, matrix effects (ME) and expanded uncertainty. The optimized method showed a linearity >0.9903, recoveries within the range 65.1-120.1%, precision (expressed as %RSD) <17.5%, medium (<39.9%) to low (<16.7%) matrix effects and acceptable expanded uncertainty (<33.1%). Finally, the proposed method was applied to representative real samples of milk (by local markets), revealing the existence of one pharmaceutical drug (imidocarb) in one sample.


Release of amino acids encapsulated in PGPR-stabilized W/O/W emulsions is affected by temperature and hydrophobicity.
Double or multiple emulsions have been under study for several decades, due to the possibility of encapsulation and controlled release of various bioactive compounds. This contribution focuses on the decisive parameters for encapsulation and release in double emulsions by considering different amino acids at different environmental conditions. Laser diffraction analysis showed that the double emulsion average droplet size increased from 50 up to 90 µm after 32 days of storage. The emulsions at 4 °C showed a higher increase compared to 37 °C. Dilution in SDS solution revealed that this droplet size increase was due to aggregation rather than coalescence. The results showed that there was no significant change in the entrapped water volume fraction of the double emulsions during 2 weeks of storage. Amino acids were encapsulated within the internal aqueous phase with an efficiency of at least 80%. Regarding the release of the entrapped amino acids, it was found that both the temperature and the hydrophobicity of the amino acid had a significant effect. Fastest release was found at the highest temperature studied (i.e. 37 °C), which was thought to be due to the higher solubility and faster diffusion rate of the amino acid in the oil phase. As hydrophobicity increased, the released amino acid concentration also increased. The pH, on the other hand, did not have a significant effect on the release within the pH range considered (i.e. 7-10). The constant internal water volume fraction, together with the significant effect of temperature and hydrophobicity, indicated that the main release mechanism of amino acids in double emulsions is by direct diffusion from the internal to the external aqueous phase.


Indoor light energy harvesting for battery-powered sensors using small photovoltaic modules.
As interest in Internet-of-Things (IoT) devices like wireless sensors increases, research efforts have focused on finding ways for these sensors to self-harvest energy from the environment in which they are installed. Photovoltaic (PV) cells or mini-modules are an intuitive choice for harvesting indoor ambient light, even under low light conditions, and using it for battery charging and powering of these devices. Characterizations of battery charging, for small rechargeable batteries from low charge to full charge, have been investigated using PV mini-modules of equal area. We present battery charging results using three different PV technologies, monocrystalline silicon (c-Si), gallium-indium-phosphide (GaInP) and gallium-arsenide (GaAs) under a warm color temperature (3000 K) LED lighting at an illuminance of 1000 lx. Battery charging times are shortest for the more efficient GAInP and GaAs mini-modules whose spectral response are a better match to the LED test source, which contains mostly visible photons, and longest for the less efficient Si cells. As a demonstration, a wireless temperature sensor mote was attached to the charging circuit and operated to determine its power consumption in relation to the available charging power. The mote's maximum power draw was less than the charging power from the least efficient c-Si mini-module. Our findings affirm the feasibility of utilizing PV under typical indoor lighting conditions to power IoT devices.


Open space anxiety test in rodents: the elevated platform with steep slopes.
This report describes a behavioral test protocol for assessing anxiety in mice and rats in single or multiple sessions. The test is based on exposure of animals to an open-space elevated platform with suspended steep slopes attached on two opposite sides. In this test, all animals cross frequently onto and spend more time in the areas adjacent to slopes than in the areas adjacent to a void space. Balb/c mice (albinos) were shown consistently to be more anxious than CD-1 mice (albinos), c57/Bl6J and c57/Bl6N (pigmented) mice; they do not cross onto the slopes. When Balb/c mice are treated with amphetamine or diazepam, the number of crossings on the platform is significantly increased but only diazepam-treated mice do cross onto the slopes. In the presence of a protected space on the platform, the behavior of c57/Bl6J compares to that of Balb/c mice; they stop crossings onto the slopes and demonstrate avoidance response. Unlike the current existing tests, the present open-space anxiety test demonstrates reliable and consistent results with strong construct and discriminant validity. It provides unequivocal measures of fear-induced anxiety, which are not confounded with measures of fear-induced escape/avoidance responses, hyperactivity or impulsive responses.


Characterization of the KNOTTED1-LIKE HOMEOBOX (KNOX) gene family in Pinus pinaster Ait.
KNOTTED1-LIKE HOMEOBOX (KNOX) genes are a family of plant-specific homeobox transcription factors with important roles in plant development that have been classified into two subfamilies with differential expression domains and functions. Studies in angiosperms have shown that class I members are related to the maintenance of meristem homeostasis and leaf development, whereas class II members promote differentiation of tissues and organs. However, little is known about its diversification and function in gymnosperms. By combining PCR-based detection and transcriptome data analysis, we identified four class I and two class II KNOX genes in Pinus pinaster. Expression analyses showed that class I members were mainly expressed in meristematic regions and differentiating tissues, with practically no expression in lateral organs, whereas expression of class II members was restricted to lateral organs. Furthermore, overexpression of P. pinaster KNOX genes in Arabidopsis thaliana caused similar phenotypic effects to those described for their angiosperms counterparts. This is the first time to our knowledge that functional analyses of class II members are reported in a conifer species. These results suggest a high conservation of the KNOX gene family throughout seed plants, as the functional differentiation of both subfamilies observed in angiosperms might be partially conserved in gymnosperms.


The effects of strength of religious faith on post-traumatic growth in patients with epilepsy.
This study was conducted to examine the effects of strength of religious faith on post-traumatic growth in patients with epilepsy. This cross-sectional and correlational study was conducted with 112 participants who were admitted to the neurology outpatient clinic of a university hospital in eastern Turkey, who met the research criteria and agreed to participate in the study. The data were collected by using "Descriptive Information Form", "Santa Clara Strength of Religious Faith Questionnaire (SCSRFQ)", and "Post-traumatic Growth Inventory (PTGI)". Santa Clara Strength of Religious Faith Questionnaire SCRFSQ has a maximum strength of faith score of 40 points and the PGTI has a maximum growth after a traumatic event score of 105 points. Mean SCSRFQ total score of the participants was found to be 31.04 ± 5.17. Mean PTGI total score was found to be 60.54 ± 16.50. As a result of the regression analysis, it was found that the independent variable affected the dependent variable PTGI total score significantly (F(1,110) = 13.999, p = 0.000). It was also found that the independent variable affected the PTGI total score positively (β = 0.336) and explained 11% of the PTGI total score (p < 0.001). It was found that the participants had high strength of religious faith score and moderate post-traumatic growth score. It was found that post-traumatic growth increased as strength of religious faith increased.


The VaRP Project: qualitative evaluation of the training effectiveness of Post Graduate Specializations for health professionals.
The healthcare professionals' specialized training has a positive impact on professional values, patient's outcome, and promotion of evidence-based practices. To raise the educational standard, the University of Parma has created Post Graduate Specializations which, in addition to learning sector-specific techniques and skills, include the acquisition of soft skills. Aim of the study is investigating the perception of the tutors dedicated to the organization, management, and teaching of the Post Graduate Specializations on the skills gained and the changes achieved in clinical practice, training, and research. Qualitative research was carried out through a semi-structured interview to 11 tutors who have been coordinating the Post Graduate Specializations. The Qualitative analysis developed "thick" descriptions characterized by analytical density and interpretative richness. The emerging thematic nuclei were: General/unpredicted aspects, Professional empowerment, Satisfaction, Professional outcomes, Limits of the Post Graduate Specializations, and Development areas. We identified the most effective areas of the Post Graduate Specializations that emerged consistently from the interviews. We hypothesized that the values and mission the Scientific Board, are effectively lived and championed in the everyday activities of the Post Graduate Specializations. Some domains still need to be furtherly developed, as the professional record, the absence of a "follow up" relationship with former students, and the effective management of workload both for students and tutors. The rise of these limits, can be particularly fruitful, as it gives the chance to identify the development trajectory the post-graduate trainings should pursue to raise the standard of excellence.


Deoxynivalenol in grain and grain products.
• The results are intermediate data. Investigations have not yet been completed.• Grain and grain products contain different quantities of DON.• The main cause for DON infection is contamination of the grain during the growing season.• DON may also be produced during storage and/or handling and processing of food.• There does not seem to be a zero-tolerance.• It is essential to take appropriate measures during primary production and secondary production to minimize mycotoxin formation.• The results explain a possible consumer risk that has to be taken seriously.• Furthermore it is necessary to determine EC-wide limiting DON values for foodstuff.


Assessing the role of long-distance translocation and spatial heterogeneity in the raccoon rabies epidemic in Connecticut.
Spatial heterogeneity and long-distance translocation (LDT) play important roles in the spatio-temporal dynamics and management of emerging infectious diseases and invasive species. We assessed the influence of LDT events on the invasive spread of raccoon rabies through Connecticut. We identified several putative LDT events, and developed a network-model to evaluate whether they became new foci for epidemic spread. LDT was fairly common, but many of the LDTs were isolated events that did not spread. Two putative LDT events did appear to become nascent foci that affected the epidemic in surrounding townships. In evaluating the role of LDT, we simultaneously revisited the problem of spatial heterogeneity. The spread of raccoon rabies is associated with forest cover--rabies moves up to three-times slower through the most heavily forested townships compared with those with less forestation. Forestation also modified the effect of rivers. In the best overall model, rabies did not cross the river separating townships that were heavily forested, and the spread slowed substantially between townships that were lightly forested. Our results suggest that spatial heterogeneity can be used to enhance the effects of rabies control by focusing vaccine bait distribution along rivers in lightly forested areas. LDT events are a concern, but this analysis suggests that at a local scale they can be isolated and managed.


Respiration-correlated image guidance is the most important radiotherapy motion management strategy for most lung cancer patients.
The purpose of this study was to quantify the effects of four-dimensional computed tomography (4DCT), 4D image guidance (4D-IG), and beam gating on calculated treatment field margins in a lung cancer patient population. Images were acquired from 46 lung cancer patients participating in four separate protocols at three institutions in Europe and the United States. Seven patients were imaged using fluoroscopy, and 39 patients were imaged using 4DCT. The magnitude of respiratory tumor motion was measured. The required treatment field margins were calculated using a statistical recipe (van Herk M, et al. Int J Radiat Oncol Biol Phys 2000;474:1121-1135), with magnitudes of all uncertainties, except respiratory peak-to-peak displacement, the same for all patients, taken from literature. Required margins for respiratory motion management were calculated using the residual respiratory tumor motion for each patient for various motion management strategies. Margin reductions for respiration management were calculated using 4DCT, 4D-IG, and gated beam delivery. The median tumor motion magnitude was 4.4 mm for the 46 patients (range 0-29.3 mm). This value corresponded to required treatment field margins of 13.7 to 36.3 mm (median 14.4 mm). The use of 4DCT, 4D-IG, and beam gating required margins that were reduced by 0 to 13.9 mm (median 0.5 mm), 3 to 5.2 mm (median 5.1 mm), and 0 to 7 mm (median 0.2 mm), respectively, to a total of 8.5 to 12.4 mm (median 8.6 mm). A respiratory management strategy for lung cancer radiotherapy including planning on 4DCT scans and daily image guidance provides a potential reduction of 37% to 47% in treatment field margins. The 4D image guidance strategy was the most effective strategy for >85% of the patients.


Gastric heterotopia in rectum: A literature review and its diagnostic pitfall.
The term heterotopia, in pathology, refers to the presence of normal tissues at foreign sites. Gastric heterotopia has been reported anywhere in the gastrointestinal tract. However, the presence of gastric heterotopia in the rectum is very rare. We, here, report a rare case of a localized 2-cm area of cratered mucosa with heaped-up borders in the rectum of a 51-year-old, asymptomatic woman who underwent screening colonoscopy. Histologic examination of the biopsy from the lesional tissue in rectum demonstrated fragments of rectal mucosa co-mingling with oxyntic- and antral-type gastric mucosa. No intestinal metaplasia or Helicobacter pylori is identified. Patients with gastric heterotopia in rectum usually present with bleeding and/or abdominal pain. Definite treatment of choice is surgical or endoscopic resection, although the lesions also respond to histamine-2 receptor blockers. In this article, most recent literature about gastric heterotopia in rectum is reviewed, following a case presentation about it.


Understanding hunter-gatherer cultural evolution needs network thinking.
Hunter-gatherers past and present live in complex societies, and the structure of these can be assessed using social networks. We outline how the integration of new evidence from cultural evolution experiments, computer simulations, ethnography, and archaeology open new research horizons to understand the role of social networks in cultural evolution.


Monosynaptic facilitatory pathway from the hypothalamic ventromedial nucleus to the frontal cortex in the rat.
Stimulation of the ventromedial nucleus (VMH) evoked a short latency negative wave with two peaks (cN1 and cN2) followed by a small positive wave (cP) at the ipsilateral dorsal frontal cortex (area 10) in the rat. The maximum response was observed from the lateral edge of the frontal pole. From the depth profiles of recordings, cN1 changed polarity at a depth of about 4 mm and the cN1-cN2 changed into a large compound action potential at the medioventral part of the frontal pole at a depth of about 6 mm. Since the surface evoked potential and the compound action potential followed high frequency stimulation, these respective potentials are concluded to be due to antidromic and monosynaptic activation of the cortical neurons. This was verified by unit recording experiments. The cP was concluded to be produced by the initial rise of the monosynaptic EPSP.


Evaluation of lymphocytes subpopulations and natural killer cells in peripheral blood of patients treated for dermatophyte onychomycosis.
Thirty-five patients with dermatophyte onychomycosis caused by Trichophyton rubrum, T. mentagrophytes var. granulosum, T. tonsurans and Epidermophyton floccosum were examined before treatment and 27 of these patients were examined again when they came to the control check up 3 months after completion of treatment. The immunological investigations, including evaluation of immunological competence, were performed in vivo through the determination of lymphoid cell immunophenotype by a flow cytometry technique. The quantitative composition of basic lymphocyte subpopulations and natural killer cells in the peripheral blood of 35 patients before the treatment was compared with a control group of 20 individuals. Statistically significant differences in the percentages of CD3+ T lymphocytes (P<0.05), T helper lymphocytes (CD4+) (P<0.05) and activated T lymphocytes (CD3+/HLA-DR+) (P<0.05) were obtained. In the control check-up examinations of 27 patients 3 months after completion of treatment, in comparison with the control group of 20 healthy individuals, highly statistically significant differences in percehtages of T lymphocytes (CD3+) (P<0.001) and T helper lymphocytes (CD4+) (P<0.01) were obtained. In five of these 27 patients the treatment resulted in failure. Comparing the group of 22 recovered patients with these five patients in whom the treatment result was failure, the only statistically significant difference obtained before as well as after the treatment was in B lymphocytes (CD19+) percentage (P<0.05). The results obtained confirm that impairments of the patients' cellular immunity are crucial factors influencing the course and results of treatment in dermatophyte onychomycosis.


[Effects of AST and ASI on metabolism of free radical in senescent rats treated by HC].
To study the effects of Astragaloside (AST) and Astragalus Saponin I (ASI) on metabolism of free radical and immune function in senescent rats treated by HC. Hydrocorisone (HC) was used to estabilsh the aging model in rats. The content of molondialdehyde (MDA), glutathoine (GSH) and oxidized glutathoine (GSSG) in liver and brain was detected according to kit. The activity of Mn superoride dismulase (Mn-SOD) and catalase (CAT) was also surveyed by kit. Concanavalin (ConA) was used to detect the proliferation and interleukin-2 (IL-2) production of splenocytes. Compared with HC control, AST and ASI could decrease the content of MDA, GSH and GSSG in liver and brain, increase the activity of Mn-SOD and CAT, and promote the proliferation and interleukin-2 (IL-2) activity of splenocytes. AST and ASI could delay the aging effect in rats treated by HC, and its mechanism maybe the antioxidant and regulating immunity.


Spontaneous heparin-induced thrombocytopenia presenting as bilateral adrenal hemorrhages and pulmonary embolism after total knee arthroplasty.
Heparin-induced thrombocytopenia syndrome is an acquired potentially life-threatening prothrombotic disorder caused by antibodies that recognize complexes of platelet factor 4 bound to heparin or heparin-like molecules. It typically occurs after exposure to unfractionated heparin, to a lesser extent after exposure to low-molecular-weight heparins, and rarely after exposure to fondaparinux. Herein, we report the case of a 48-year-old woman who developed severe thrombocytopenia, bilateral pulmonary embolism, and bilateral adrenal hemorrhages after total knee arthroplasty without evidence of heparin exposure. Antibodies to the heparin-platelet factor 4 complex and serotonin-release assay were positive. Spontaneous heparin-induced thrombocytopenia syndrome should be considered in patients with unexplained thrombocytopenia after knee replacement surgery even without heparin exposure, and a high index of suspicion for adrenal hemorrhage is needed in patients with fever, abdominal pain, and shock.


East Versus West: Differences in Surgical Management in Asia Compared with Europe and North America.
In recent decades, there has been considerable worldwide progress in the treatment of gastric cancer. Gastrectomy with a modified D2 lymphadenectomy (sparing the distal pancreas and spleen) has increasingly gained acceptance as a preferable standard surgical approach among surgeons in the East and the West. Despite growing consensus significant differences still exist in surgical techniques in clinical trials and clinical practices secondary to variations in epidemiology, clinicopathologic features, and surgical outcomes among geographic regions. In addition, Western physicians tend to prefer adjuvant chemotherapy and radiotherapy after surgery instead of using S-1 chemotherapy, as is the preference in the East.


Comparison of coronary flow reserve and fractional flow reserve in patients with versus without diabetes mellitus and having elective percutaneous coronary intervention and abciximab therapy (from the PREDICT Trial).
Patients with diabetes mellitus (DM) have poor long-term outcome after percutaneous coronary intervention (PCI) partly because of microvascular disease and distal embolization. Microvascular obstruction can be assessed by measuring coronary flow reserve (CFR). The Prediction of CK-MB RElease During Successful Stenting Correlating with Indicators of Microvascular ObstruCTion (PREDICT) trial compared the CFR in patients with versus without DM during PCI. Patients undergoing elective PCI were prospectively enrolled according to diabetic (n = 36) and nondiabetic (n = 36) status. All patients received drug-eluting stent with abciximab and were followed for 30-day major adverse cardiac events. CFR and FFR (fractional flow reserve) before and after stenting were measured before and after intracoronary adenosine bolus. Procedural success, MB enzyme of creatine-kinase (CK-MB), troponin I, and high-sensitive C-reactive protein elevation, vascular complications, and major adverse cardiac events were not different. FFR before stenting was 0.77 +/- 0.03 in patients with DM versus 0.76 +/- 0.02 in patients without DM (p = 0.69). FFR after stenting was 0.97 +/- 0.03 and 0.99 +/- 0.01 (p = 0.26), respectively. CFR before stenting was 1.36 +/- 0.31 in patients with DM versus 1.49 +/- 0.25 in patients without DM (p = 0.064). However, CFR after stenting was significantly lower in patients with versus without DM (1.89 +/- 0.30 versus 2.44 +/- 0.67, p <0.001, respectively). CFR after stenting only moderately correlated with CK-MB and high-sensitive C-reactive protein after PCI but did not correlate with 30-day major adverse cardiac events. In conclusion, patients with DM have significantly lower CFR after stenting despite equivalent FFR and myonecrosis compared with patients without DM, indicating greater microvascular obstruction after PCI despite abciximab.


Gastric carcinoma resembling submucosal tumor.
Acase of stomach carcinoma showing features of submucosal tumor is reported. The patient was a 50-year-old man presenting with hematemesis. Endoscopic examination was performed and revealed a submucosal tumor-like lesion with central ulceration in the fornix of the stomach. The biopsy specimen from this lesion showed poorly differentiated adenocarcinoma, and surgery was performed. The tumor, measuring 3.5 x 2.7 cm in size, invaded to the muscularis propria with proliferation of the interstitial connective tissue and lymphoid follicles consisting mainly of B lymphocytes in the submucosal layer. In situ hybridization of tumor tissue for Epstein-Barr virus (EBV)-encoded small RNA1 as target revealed negative results. In stomach carcinoma simulating submucosal tumor, as in this patient, preoperative diagnosis is important to plan treatment strategies.


Serum bile acids and oral ursodeoxycholic acid tolerance test in the diagnosis of esophageal varices.
The purpose of this study was to compare the endoscopic findings based on the general rules for recording endoscopic findings on esophageal varices by the Japanese Research Society for Portal Hypertension with liver function tests including serum bile acids and bile acid clearance tests in 64 patients with liver cirrhosis. Cases of esophageal varices showed significantly higher serum bile acid levels and greater ICG retention than those without esophageal varices. The oral ursodeoxycholic acid tolerance test was significantly impaired in the group with esophageal varices (p less than 0.05). In cases with esophageal varices, there was no significant difference in serum bile acid levels between white and blue varix patients, while serum bile acid levels in the red-color sign-positive group were significantly higher than those in the negative group (p less than 0.01). Serum bile acid levels increased in parallel with the form of varices as reflected by the shape and size of varices and with the location of varices which reflects the longitudinal-extent of varices. These results indicate that the impaired clearance of serum bile acids in liver cirrhosis is closely related with the red-color sign on the variceal surface and with the form and location of esophageal varices, which may reflect the grade of portal-systemic shunting.


Incisional recurrence of endometrial adenocarcinoma.
A 73-year-old woman manifested recurrent endometrial carcinoma, which presented as multiple nodular lesions in an abdominal scar from previous pelvic surgery.


Anatomy of the palmar fascia on the ulnar border of the hand.
Dupuytren's disease sometimes seems to arise from the tendon of abductor digiti minimi or the fascia overlying it. The normal anatomy of these structures is described and the tendon is shown to be of central importance in the organisation of the digital fascia. In particular, its connections with the superficial transverse palmar ligament, Grayson's ligaments and the digital band are demonstrated.


Determination of iron(III) based on the fluorescence quenching of rhodamine B derivative.
A new method for determination of iron(III) has been developed using a kind of rhodamine B derivative fluorescent probe, rhodamine amide (RHA), in acidic HAc-NaAc buffer solution. In this approach, the heavy atom effect of I₃(-) was applied to quench the fluorescence of RHA. When iron(III) and KI coexisted in HAc-NaAc buffer solution, iron(III) reacted with the excess KI to produce I₃(-) that quenched the fluorescence of RHA through the formation of a non-fluorescence compound. The results showed that the fluorescence intensity decrease of RHA presented a good linear relationship with the iron(III) concentrations in the range from 0.5 to 5.0 μmol L(-1) with the correlation coefficient of 0.9970, and the detection limit was 0.3 μmol L(-1) iron(III). The approach was applied to determination of iron(III) in water samples, and the recovery was found to be from 80.7% to 100. 8%.


Specification and grade of Saposhnikoviae Radix (Saposhnikovia divaricata).
Saposhnikoviae Radix (Fangfeng in Chinese), the roots of Saposhnikovia divaricata, lacks commodity specification and grade standardization in the current market. This study investigated the existing specifications and grades of Saposhnikoviae Radix to provide a standardized scientific reference for its market use. Based on a textual research of Chinese herbal medicine from the Han Dynasty to the present, medicinal materials of different specifications and grades obtained from Saposhnikoviae Radix in the main producing areas of China were collected and the markets for these materials were investigated. Field investigations were performed in the major producing areas such as Northeast China, Hebei Province, and Inner Mongolia. Four major Chinese herbal medicine markets in China were investigated. Sensory indices were used to categorize the two specifications (wild and cultivated) according to the shape, color, texture, and cross-section. High-performance liquid chromatography was performed to determine the active components. Vernier calipers and measuring tape were used to measure the diameter and length, respectively, of 41 samples. Using Excel and the R Language software, cluster analysis and descriptive statistical analysis were performed to assist in the application of new specifications and grades based on physical characteristics, pharmacological activity, and chemical composition. The two specifications (wild and cultivated) of Saposhnikoviae Radix were divided into three grades each based on the length and diameter. Prim-O-glucosylcimifugin, 5-O-methylvisamminoside, and the length of Saposhnikoviae Radix can be used as a basis for classifying the commodity specifications and grades. The specifications and grade standards of Saposhnikoviae Radix were established based on the following eight aspects: shape, surface characteristics, texture, cross section, taste, prim-O-glucosylcimifugin content, 5-O-methylvisamminoside content and length. The formulation of this standard stipulates the commodity specification level of Saposhnikoviae Radix. It is also suitable for the evaluation of commodity specifications in the process of production, circulation and use of Saposhnikoviae Radix.


[The concept and practical management of frailty in neurology].
Frailty is a clinical situation of decreased homeostatic reserve that, after a minor trigger (acute illness, fall, taking a drug...) increases the risk of an adverse event such as hospital admission, institutionalization, functional and/or cognitive decline, death, etc. Frailty can be understood as physical frailty, Fried's phenotype, a true geriatric syndrome that can be reversible by avoiding its progression to more advanced stages of irreversibility and dependence, and Rockwood's frailty due to accumulation of deficits, as a continuum of health or classification typology of the elderly along the frailty spectrum (healthy, robust, vulnerable, mild-moderate-severe and extreme frailty or end of life). The diagnosis of physical frailty is part of the comprehensive geriatric assessment, recommending the use of a performance test such as gait speed (<0,8m/s), Timed Up and Go (>12 s) or Short Physical Performance Battery (<10). Physical frailty is reversible by a multidisciplinary management based on three fundamental pillars: multicomponent physical exercise and resistance training, adequate protein and micronutrient intake (leucine, vitamin D, etc.) and appropriate pharmacological prescription, management of comorbidity and geriatric syndromes. Frailty is a risk factor for neurological disease progression and increased risk of adverse events in neurodegenerative diseases such as mild cognitive impairment, dementia, Parkinson's disease and cerebrovascular disease. Frailty based on the Clinical Frailty Scale or VIG-Frail shows patient typologies in relation to a greater or lesser state of fragility, being a basic prognostic tool of great utility in making diagnostic and therapeutic management decisions. It opens up a new opportunity for improvement in the management of neurological disease in the diagnosis and treatment of frailty.


Hydrophilic interaction 10 microm I.D. porous layer open tubular columns for ultratrace glycan analysis by liquid chromatography-mass spectrometry.
The sensitivity of glycan analysis using nano-liquid chromatography interfaced with electrospray ionization mass spectrometry (ESI-MS) increases with the decrease of the mobile phase flow rate, accompanied by reduced ion suppression. In this study, we describe the preparation and performance of high efficiency 10 microm I.D. amine-bonded poly(vinylbenzyl chloride-divinylbenzene) hydrophilic interaction (HILIC) porous layer open tubular (PLOT) columns operated at 20 nL/min for the separation and analysis of glycan mixtures. HILIC-PLOT columns with a uniform porous polymer layer were reproducibly prepared ( approximately 4% RSD in retention time from column-to-column) via in situ polymerization, followed by one step modification with ethylenediamine. When coupled on-line with negative ESI-MS, low detection limits (0.3fmol) for a 3-sialyl-tetrasaccharide were achieved using a 2.5mx10 microm I.D. HILIC-PLOT column. A dextran ladder standard was used to evaluate the performance of the column, and high efficiency separation was achieved with detection of the dextrans up to G22 from approximately 50 fmol amounts injected. As an example of the high sensitivity of the column, MS(6) characterization of glycan structures was possible from the injection of 10 fmol of a neutral and sialylated glycan. As another example of high sensitivity LC-MS analysis of 3 ng of a PNGase F digest of ovalbumin allowed 28 N-linked glycans to be confidently identified from a single analysis. High quality MS/MS spectra for each ovalbumin glycan were acquired and manually interpreted for structure analysis. The HILIC-PLOT column is a very promising approach for LC-MS analysis of glycans at the ultratrace level.


Positive drain fluid culture on postoperative day 1 predicts clinically relevant pancreatic fistula in early drain removal with higher drain fluid amylase after pancreaticoduodenectomy.
This study aimed to clarify the risk factors of clinically relevant pancreatic fistula after early drain removal with higher drain fluid amylase after pancreaticoduodenectomy. Clinical evaluation of early drain removal with a higher drain fluid amylase after pancreaticoduodenectomy has been controversial. The safety and effectiveness have not been sufficiently examined. Between 2015 and 2020, prophylactic surgical drains were prospectively removed on postoperative day 4 regardless of drain fluid amylase level in 364 study-eligible patients who underwent pancreaticoduodenectomy. Patients were classified according to drain fluid amylase on postoperative day 1: 281 patients with drain fluid amylase <4,000 U/L, and 83 patients with drain fluid amylase ≥4,000 U/L. Clinically relevant pancreatic fistula occurred in 40 of 364 enrolled patients (11.0%). In the entire cohort, male, positive postoperative day 1 drain fluid culture, and postoperative day 1 drain fluid amylase ≥4,000 U/L were independent risk factors for clinically relevant pancreatic fistula after early drain removal. When stratifying by 4,000 U/L of postoperative day 1 drain fluid amylase, the rate of clinically relevant pancreatic fistula in postoperative day 1 drain fluid amylase <4,000 U/L was significantly lower than that in postoperative day 1 drain fluid amylase ≥4,000 U/L (4% vs 35%, P < .001) after early drain removal. Moreover, in postoperative day 1 drain fluid amylase <4,000 U/L, positive postoperative day 1 drain fluid culture did not develop clinically relevant pancreatic fistula after early drain removal. However, in postoperative day 1 drain fluid amylase ≥4,000 U/L, multivariate analysis clarified that positive postoperative day 1 drain fluid culture was the only independent risk factor of clinically relevant pancreatic fistula after early drain removal (odds ratio 26.27, 95% confidence interval 5.59-123.56, P = .001). Positive drain fluid culture on postoperative day 1 might predict clinically relevant pancreatic fistula in early drain removal with a higher drain fluid amylase.


Chromobacterium violaceum- induced sepsis and multiorgan dysfunction, resembling melioidosis in an elderly diabetic patient: A case report with review of literature.
An elderly diabetic farmer presented with chronic nonhealing ulcer over the left foot, multiple liver abscesses, and right-sided pleural effusion. The patient developed septicemia and multiorgan failure. The pus grew pigment producing Chromobacterium violaceum. He was treated successfully with ciprofloxacin for a total duration of 15 days. This case is reported for its rare clinical presentation and resemblance with melioidosis. Of the 200 C. violaceum cases reported across the globe, this is the 14th case from India and the oldest in the literature.


The ultrastructure and function of follicle cells in Foucartia squamulata (Herbst) (Curculionidae).
The follicle cells of Foucartia squamulata are involved in the formation of both vitelline membrane and chorion. Precursors for these egg coverings are synthesized by the rough endoplasmic reticulum and condensed within dictyosomes. The vitelline membrane and the chorion appear on the oocyte surface simultaneously, which is an unusual phenomenon for insects. The follicular epithelium has not been found to contribute to vitellogenesis in the species under study.


In vitro neogenesis of human islets reflects the plasticity of differentiated human pancreatic cells.
The neogenesis of islets from cultured human adult pancreatic tissue has been reported. The islet progenitors have been thought to be ductal cells. Since previous experiments have been 'contaminated' by a number of pre-existing islet cells, we examined their involvement in islet cell neogenesis. Fresh human pancreatic cells with different purities of islet cells were grown in monolayer culture and labelled with bromodeoxyuridine. Transitional cells were analysed by double immunofluorescence staining. For purified ductal cell culture, pre-existing islets were eliminated on a magnetic cell separation system. We confirmed that less than 1% of the endocrine cells proliferated, mainly during the first 48 h of culture. However, a 10-fold larger proportion of the cells acquired a transitional phenotype by starting to coexpress the ductal marker cytokeratin 19 (CK19). These cells represented more than 10% of all endocrine cells after 1 day in culture, and 6% at 5 days of culture. Using magnetic cell sorting, we eliminated cells expressing neural cell adhesion molecule (N-CAM), after which we obtained 99.7% pure non-endocrine CK19-rich cell populations. These cell populations could be expanded in vitro. However, their endocrine differentiation capacity was severely reduced as compared with the original mixed cell cultures. These results suggest that islet neogenesis in this culture system at least partly represents the de-differentiation of islet cells into a duct-cell-like phenotype, with further re-differentiation in appropriate conditions. The plasticity of differentiated human pancreatic cell types may thus be an important mechanism of human pancreas regeneration.


Serial relaxin concentrations in human pregnancy.
Relaxin is a peptide hormone produced by the corpus luteum during pregnancy in human beings. There are no extraluteal sites of production of relaxin in women. By means of a heterologous porcine radioimmunoassay, serial serum relaxin concentrations were determined in three women throughout pregnancy and into labor. All three demonstrated a first-trimester elevation followed by a second-trimester decline; values then remained stable throughout the second and third trimesters and into labor. This further confirms the functional activity of the corpus luteum throughout pregnancy and the value of relaxin as an index of luteal function during gestation.


Cochrane corner: water for wound cleansing.
Although various solutions have been recommended for cleansing wounds, normal saline is favoured as it is an isotonic solution and does not interfere with the normal healing process. Tap water is commonly used in the community for cleansing wounds because it is easily accessible, efficient and cost effective; however, there is an unresolved debate about its use. The objective of this review was to assess the effects of water compared with other solutions for wound cleansing. For this update we searched the Cochrane Wounds Group Specialised Register (Searched 22 February 2010); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010 Issue 1); Ovid MEDLINE - 2007 to February Week 2 2010; Ovid MEDLINE - In-Process & Other Non-Indexed Citations (Searched19 February 2010); Ovid EMBASE - 2007 to 2010 Week 06; EBSCO CINAHL - 2007 to 22 February 2010. Randomized and quasi-randomized controlled trials that compared the use of water with other solutions for wound cleansing were eligible for inclusion. Additional criteria were outcomes that included objective or subjective measures of wound infection or healing. Two review authors independently carried out trial selection, data extraction and quality assessment. We settled differences in opinion by discussion. We pooled some data using a random-effects model.


Differentiating macrophage activation syndrome in systemic juvenile idiopathic arthritis from other forms of hemophagocytic lymphohistiocytosis.
To identify measures distinguishing macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis (sJIA) from familial hemophagocytic lymphohistiocytosis (FHL) and virus-associated hemophagocytic lymphohistiocytosis (VA-HLH) and to define appropriate cutoff values. To evaluate suggested dynamic measures differentiating MAS in patients with sJIA from sJIA flares. In a cohort of patients referred for evaluation of hemophagocytic lymphohistiocytosis, we identified 27 patients with sJIA and MAS (MAS/sJIA) fulfilling the criteria of the proposed preliminary diagnostic guideline for the diagnosis of MAS in sJIA. Ten measures at diagnosis were compared between the MAS/sJIA group and 90 patients with FHL and 42 patients with VA-HLH, and cutoff values were determined. In addition, 5 measures were analyzed for significant change from before MAS until MAS diagnosis. Neutrophil count and C-reactive protein were significantly higher in patients with MAS/sJIA compared with patients with FHL and patients with VA-HLH, with 1.8×10(9)/L neutrophils (sensitivity 85%, specificity 83%) and 90 mg/L C-reactive protein (74%, 89%) as cutoff values. Soluble CD25<7900 U/L (79%, 76%) indicated MAS/sJIA rather than FHL/VA-HLH. Platelet (-59%) and white blood cell count (-46%) displayed a significant decrease, and neutrophil count (-35%) and fibrinogen (-28%) showed a trend during the development of MAS. However, a substantial portion of patients had values at diagnosis of MAS within or above the normal range for white blood cells (84%), neutrophils (77%), platelets (26%), and fibrinogen (71%). Readily available measures can rapidly differentiate between MAS/sJIA and FHL/VA-HLH. The findings substantiate that a decline of measures may facilitate the distinction of MAS from flares of sJIA.


Reduced in vitro toxicity of fine particulate matter collected during the 2008 Summer Olympic Games in Beijing: the roles of chemical and biological components.
Beijing has implemented systematic air pollution control legislation to reduce particulate emissions and improve air quality during the 2008 Summer Olympics, but whether the toxicity of fine fraction of particles (PM(2.5)) would be changed remains unclear. In present study we compared in vitro biological responses of PM(2.5) collected before and during the Olympics and tried to reveal possible correlations between its chemical components and toxicological mechanism(s). We measured cytotoxicity, cytokines/chemokines, and related gene expressions in murine alveolar macrophages, MH-S, after treated with 20 PM(2.5) samples. Significant, dose-dependent effects on cell viability, cytokine/chemokine release and mRNA expressions were observed. The cytotoxicity caused at equal mass concentration of PM(2.5) was notably reduced (p<0.05) by control measures, and significant association was found for viability and elemental zinc in PM(2.5). Endotoxin content in PM(2.5) correlated with all of the eight detected cytokines/chemokines; elemental and organic carbon correlated with four; arsenic and chromium correlated with six and three, respectively; iron and barium showed associations with two; nickel, magnesium, potassium, and calcium showed associations with one. PM(2.5) toxicity in Beijing was substantially dependent on its chemical components, and lowering the levels of specific components in PM(2.5) during the 2008 Olympics resulted in reduced biological responses.