Noncoding RNPs of viral origin.
Like their host cells, many viruses produce noncoding (nc)RNAs. These show diversity with respect to time of expression during viral infection, length and structure, protein-binding partners and relative abundance compared with their host-cell counterparts. Viruses, with their limited genomic capacity, presumably evolve or acquire ncRNAs only if they selectively enhance the viral life cycle or assist the virus in combating the host's response to infection. Despite much effort, identifying the functions of viral ncRNAs has been extremely challenging. Recent technical advances and enhanced understanding of host-cell ncRNAs promise accelerated insights into the RNA warfare mounted by this fascinating class of RNPs.


Economic factors and the rates of suicide in Germany between 1881 and 1989.
The potential consequence of economic stress most frequently cited in the literature of medical sociology is the increase in the rate of suicide, it probably being the most valid and reliable indicator of collective mental health. To assess the probability of such being the consequence of current economic realignment in the Federal Republic of Germany, we deemed it promising to evaluate the extent to and manner in which economic factors have to date affected the frequency of suicide in Germany. The current study analyzed the effects of four economic variables (growth of the economy, average real income, unemployment and frequency of bankruptcy) on the rates of suicide in Germany from 1881 to 1989. We set the commencement date of the period analyzed as early as possible to include long-term developments as well as the effects of different moderator variables. The annual fluctuations of all four variables, in conformity with our hypothesis, correlated both in the period preceding World War II as well as in the postwar period with those in the rates of suicide. The strongest correlations held for the rate of unemployment and for the frequency of bankruptcy in times of obvious social disintegration coupled with diminished state safeguards against unemployment. Our hypothesis that the effects of economic factors would more strongly influence the rates of suicide by men as opposed to women could not be corroborated.


[Studies on fatigue and stress of anesthesiologist during anesthetic works using Holter ECG].
We evaluated fatigue, stress and workload of anesthesiologists during anesthetic works using Holter ECG. Recorded heart rates of anesthesiologists enable us to draw the task graph and to calculate the workload scores according to their task behavior. We conclude that the application of Holter ECG is useful in measuring the fatigue, stress, and especially workload of anesthesiologists.


Comparison of Undernutrition Prevalence of Children under 5 Years in China between 2002 and 2013.
To describe the undernutrition status of children under 5-year in China, and study the trend between 2002 and 2013). The study was based on two national surveys. Undernutrition was determined against WHO's 2006 growth standards. The prevalence in 2013 and 2002 was weighted by China sixth National Population Census (2010). The relationship between undernutrition and gender/age groups/different areas use weighted logistic regression. The results indicated the overall prevalence of stunting, underweight, and wasting of Chinese children under 5-year was 8.1%, 2.4%, and 1.9% in 2013, respectively. The prevalence of stunting was higher for children aged 12-47 month, while underweight was higher for children aged 48-59 month. The prevalence of undernutrition was higher in rural areas than in urban areas, especially in poor rural areas. There was a decline of stunting, underweight, and wasting between 2002 and 2013 among the children, with greater reduction in rural areas than in urban areas. The prevalence of undernutrition of children under 5-year remains high in rural areas especially in poor rural areas in China. It is urgent to take action to control undernutrition in the vulnerable areas and subgroups.


Evaluation of Neurotized Hypothenar Free Perforator Flaps Used for Fingertip Reconstruction.
In reconstruction of digital amputations of the upper extremity, composite tissue alternatives with similar features are limited for finger tip reconstruction. Among these alternatives, free perforator flaps elevated from the hypothenar region (HFPFs) are defined, but reluctancy goes on for utilization of these flaps.In this study, we aimed to highlight the sensory results of HFPFs when a neural repair is incorporated to the flap and also to justify their usage by presenting functional and aesthetic outcomes of the reconstructions performed with HFPFs. This clinical study was conducted from June 2015 to June 2017. Twelve patients with acute finger tip amputations were examined. Distal amputation levels were subgrouped according to Ishikawa classification. Patient demographics and amputation etiology were listed. All fingertip defects were reconstructed with a neurotized HFPF. All perforator anastomoses were performed in an end-to-end fashion. During follow-up, 2-point discrimination and dynamometric test were conducted. In addition, the Michigan Hand Outcomes Questionnaire was carried out. Evaluation of the results from a cosmetic standpoint was also conducted, with 4 blinded, independent surgeons using the visual analog scale. Of 12 digital amputations reconstructed with neurotized HFPFs, 10 were totally viable during follow-up, whereas partial loss was observed in 2 flaps. The mean age was 38.8 ± 11.8 years. Most of the amputations were classified as Ishikawa subgroup 2 (50%). The mean dynamic 2-point discrimination was 3.2 ± 0.11 mm and slightly greater compared with contralateral digit (P = 0.003). Also minor decreases were measured in forced grip and pulp-to-pulp grip strengths (P = 0.003). Overall satisfaction was 92.7% in Michigan Hand Outcomes Questionnaire. Average visual analog scale score was 7.25 out of 10. Hypothenar free perforator flaps, with incorporation of neural repair, give promising results for reconstruction of the fingertip. In addition to superior sensorial outcomes, HFPFs yield satisfying results from aesthetic and functional perspectives.


A Comparison of Substance Use Patterns Among Lifetime Heroin-Injecting Individuals By Racial Groups.
Studies have identified differential substance use patterns by racial groups. One of the most commonly reported differences is a higher rate of injection drug use (IDU) among Non-Hispanic Whites compared to African Americans, but this is complicated by factors related to IDU (e.g., earlier drug-use initiation) that overlap with being White. We explored differential substance use-patterns by racial groups within a sample of injection heroin users. Substance-use data were collected from 373 not-in-treatment heroin users who endorsed any lifetime injection use (69.4% male). We examined differences in substance-use patterns (e.g., age of initiation, gateway adherence) by racial groups. Multiple t-tests with Bonferroni correction were conducted to understand which demographic and substance-use characteristics varied by racial groups. Relative to Non-Hispanic Whites, African Americans (45.8% of sample) were more likely to start using heroin earlier in their life, but also more likely to experience a longer delay between starting and regularly using heroin. We also identified differences in the degree of (injection) heroin-use consequences by racial groups. After correcting for multiple comparisons and controlling for age and gender, we observed differences for six substance-use and demographic characteristics by racial group. White participants were younger, started cocaine use earlier, and experienced more heroin-use consequences across two separate domains. After controlling for injection use, we observed differential substance-use characteristics by racial groups. The findings could be used to develop targeted prevention and harm-reduction strategies.


Prevalence, incidence, and autoimmune comorbidities of celiac disease: a nation-wide, population-based study in Denmark from 1977 to 2016.
The aim of this study was to describe and identify potential trends with respect to prevalence, incidence, age, sex, and autoimmune comorbidity of celiac disease (CD). A Danish nationwide cohort study of CD using data from The National Patient Register. Patients with a primary or secondary diagnosis code of CD during the period 1977 to 2016 were identified. Information on sex, date of birth, death, or immigration was obtained from the Danish Civil Registration System, and autoimmune comorbidities were identified in the Danish National Patient Register. The CD cohort was compared with the general Danish population using a control cohort and aggregated data obtained from Statistics Denmark. The CD cohort consisted of 11 802 (65% women) patients. The median age at diagnosis of CD varied between 30 years in 1980-1984 and 45 years in 1995-1999 and 27 years in 2015-2016. The prevalence of CD in 1986 and 2016 was 14 and 180 per 100 000 persons, respectively, with a female/male ratio changing from 1.3 to 2.0. Incidence rates (per 100 000 person-years) changed from 1.6 in 1980-1984 to 15.2 in 2015-2016, with the largest increase among females aged 0-9 years. In 2016, prevalence of autoimmune comorbidities was 16.4% among the CD patients compared with 5.3% in the general population. The prevalence of diagnosed CD has doubled every decade in Denmark from 1986 to 2016, and in the same period the female/male ratio has increased and the median age at diagnosis has decreased. The prevalence of autoimmune comorbidity in 2016 was three times higher among CD patients compared with the general Danish population.


Site- and Enantiodifferentiating C(sp3)-H Oxidation Enables Asymmetric Access to Structurally and Stereochemically Diverse Saturated Cyclic Ethers.
A manganese-catalyzed site- and enantiodifferentiating oxidation of C(sp3)-H bonds in saturated cyclic ethers has been described. The mild and practical method is applicable to a range of tetrahydrofurans, tetrahydropyrans, and medium-sized cyclic ethers with multiple stereocenters and diverse substituent patterns in high efficiency with extremely efficient site- and enantiodiscrimination. Late-stage application in complex biological active molecules was further demonstrated. Mechanistic studies by combined experiments and computations elucidated the reaction mechanism and origins of stereoselectivity. The ability to employ ether substrates as the limiting reagent, together with a broad substrate scope, and a high level of chiral recognition, represent a valuable demonstration of the utility of asymmetric C(sp3)-H oxidation in complex molecule synthesis.


Tracheal traction exercise reduces the occurrence of postoperative dysphagia after anterior cervical spine surgery.
We designed a novel anterior cervical spine surgery preoperative treatment comprising mechanical trachea/esophagus traction and compared the postoperative outcome regarding dysphagia with nontreated patients. We investigated whether the newly developed preoperative tracheal/esophageal traction exercise (TTE) treatment has an effect on postoperative dysphagia after anterior cervical spine surgery. Dysphagia is a postoperative complication that occurs after anterior cervical spine surgery, and known treatments are perioperative application of methylprednisolone, monitoring of endotracheal tube cuff pressure, and the use of low-profile plates. METHODS.: We compared the neck disability index, visual analogue scale scores for arm and neck pain, and Bazaz dysphagia scores, a dysphagia index, of 2 randomized groups, 1 week, 3 weeks, 6 weeks, 3 months, and 6 months after cervical spine surgery. One group received TTE treatment for 3 consecutive days before surgery, whereas the control group did not. RESULTS.: In the first week after operation, the Bazaz dysphagia scores for patients with second- to fourth-level fusions in the TTE group were significantly better than that in the control group (P = 0.000 for second- and third-level fusions and P = 0.013 for fourth-level fusion). Also at 3 weeks after surgery, the second- to fourth-level fusion patients in the TTE group had better Bazaz scores than those in the control group (P = 0.000 for second- and third-level fusions and P = 0.004 for fourth-level fusion). There was no significant difference of neck disability index and visual analogue scale scores between the 2 groups. Dysphagia could be reduced in patients with multiple-level fusion after anterior cervical spine surgery by preoperative TTE treatment.


Global inequalities in HIV infection.
HIV infection continues to be one of the world's greatest pandemics, affecting nearly every country on the globe. By September 2018, it is estimated that 38 million people were living with HIV, 30 million people are aware of their status, and 23 million people are taking anti-retroviral therapy (8 million in 2010). Thus, currently 8 million people living with HIV are not aware that they are HIV-positive and 15 million persons are not being treated. There are nearly 15 million orphans (aged 0-17). There is widespread inequality both in the prevalence of HIV infection and in the access to therapy. However, although the number of people living with HIV continues to increase, the number of new infections shows a steady decrease over the last 9 years and in 2018 was 1.7 million. Deaths from AIDS in 2018 also decreased to 750,000 from 1.2 million in 2010. The world prevalence of HIV is about 0.23% but is over 0.3% in South-East Asia, Latin America, North America and Eastern Europe and with particularly high prevalence in the Caribbean (1.1%) and sub-Saharan Africa (5.5%). It is approximately 0.5% in Indonesia. There were approximately 5,000 new HIV infections (adults and children) a day during 2018. About 61% were in sub-Saharan Africa, nearly 50% were in females and 500 were in children. HIV therapy seems to have had a global impact, with AIDS-related deaths decreasing by 33% since 2010, and new infections decreasing by 16%. Nevertheless, the majority of the world's HIV is in low and middle resource countries and social determinants are strongly related. Many people living with HIV or at risk for HIV still do not have access to prevention, care and treatment, and there is still no cure.


[The scope of educational strategy in teaching education of visiting professors].
Professors of Medicine usually lack teaching education apart from their speciality. This kind of education and the development of researchers in education are now a priority. To evaluate the scope of the visit of professors in the development of aptitude for critical reading of reports on educational research and educational texts in a teaching-education program. An educational strategy was implemented to promote the development of a stance on education and on aptitudes for criticism of educational texts and research reports, which were assessed by means of previously validated instruments. A group of 10 professors was studied. After the course, all the participants increased their scores. A p = 0.005 value was obtained with the Wilcoxon test in the three instruments applied. All the participants showed a stance on education in the retest. The educational strategy modified and increased the professors' stance on education. The results showed a significant change of stance for critical reading. Even though they are incipient, these results should be encouraged through continuing formation of teaching education.


RER and LOH association with sporadic colorectal cancer in Taiwanese patients.
This association study was undertaken to determine replication error and loss of heterozygosity in colorectal tumors using a set of 10 microsatellite markers linked to APC, hMSH2, hMLH1, DCC, P53, NM23, HPC1 and MET genes as well as tumor suppressor genes on 8p22. Thirty-nine patients diagnosed and confirmed with sporadic colorectal cancer were biopsied. Their stored frozen tissues were subsequently retrieved for simultaneous analyses of replication error and loss of heterozygosity via an automated fluorescent microsatellite assay. Replication error was observed in 8/39 of the cases (20.5%) and had significantly higher frequency in the patients younger than 60 yr (P = 0.049). More than one third of informative tumors showed loss of heterozygosity at P53, DCC and APC genes (57.9%, 35.3% and 33.3%, respectively). Loss of heterozygosity at TP53-Dint marker was significantly associated with survival status (P = 0.038) in which a higher frequency was observed in the patients who died from colorectal cancer. Of 22 informative tumors, 6 (27.3%) showed loss of heterozygosity at the D8S254 marker that is suspected to be near one or more tumor suppressor genes and was significantly associated with gender (P = 0.046). All 6 cases of loss of heterozygosity at D8S254 were found in male patients. The frequencies of loss of heterozygosity at the NM23, hMSH2, hMLH1 and HPC1 genes were 18.5%, 12.1%, 9.1% and 7.4%, respectively. None of the cases examined displayed loss of heterozygosity at the MET oncogene. Additional microsatellite markers other than those associated with colorectal cancer were used to conduct the study of genomic instability and alterations in colorectal cancer tumors. The present results for the sporadic occurrence of colorectal cancer in Taiwanese patients further extend the correlation of clinical pathology and prognosis with the analysis of replication error and loss of heterozygosity.


Abnormal functional connectivity of brain regions associated with fear network model in panic disorder.
Background: Patients with panic disorder (PD) have an abnormal function in brain regions related to fear network is well recognised. However, the traditional fear network model (FNM) which was based on animals' horrible behaviours has been found that it's not enough to explain the pathological mechanism of PD. This study aims to explore brain regions' abnormalities in the new advanced FNM, and estimate whether it can better explain PD.Methods: Magnetic resonance imaging resting-state scans were acquired in 40 patients with PD (35 drug-naïve and 5 drug-free) and 40 healthy controls (HCs). Twelve brain regions in the advanced FNM were chosen as regions of interest (ROIs) to examine the group difference in the ROIs and whole-brain resting-state functional connectivity (rsFC).Results: We found significantly increased thalamic rsFC with the insula, compared with HCs. And it was significantly correlated with HAMA-somatic score. We also found increased thalamic rsFC with occipital gyrus, temporal gyrus, and frontal gyrus when compared with HCs.Conclusions: Taken together, PD patients exhibit abnormal rsFC alterations within the advanced FNM, especially the increased rsFC within thalamus-insula loop, suggesting that excessive sensitivity to external information plays an important role in PD. The advanced FNM may provide a fuller explanation about PD.


Scoping review: bladder cancer in Nigeria - what are the gaps in clinical care and research?
There are currently no national guidelines regarding bladder cancer treatment and clinical care pathways in Nigeria. The aim of this scoping review was to identify any gaps in the knowledge of epidemiology, clinical care and translational research in order to aid the development of a defined clinical care pathway and guide future research. A scoping review was conducted by searching Medline, Ovid Gateway, The Cochrane library and Open Grey literature using predefined search terms from date of inception to June 2020. Studies were included if they discussed the epidemiology or treatment pathway of bladder cancer. All data were charted and were analysed in a descriptive manner. A consultation phase was also conducted consisting of a multidisciplinary team of clinicians and bladder cancer survivors. A total of 19 studies were deemed suitable for inclusion. The themes included the epidemiology of bladder cancer (high prevalence of schistosomiasis), research surrounding the biology of the disease and translational research including potential biomarkers. The consultation phase highlighted some possible sociocultural and infrastructural issues relating to both the diagnosis and treatment of bladder cancer, with poor knowledge of bladder cancer and its symptoms within the general population identified as a key issue. Even though the factors surrounding the relationship between schistosomiasis and the histopathology of bladder cancer remain unclear, there is potential for screening for schistosomiasis in endemic regions of sub-Saharan Africa. Other key areas for future research include the dissemination of information to the general population surrounding bladder cancer and its symptoms to encourage prompt diagnosis.


Changes in respiratory drive account for the magnitude of dyspnoea during bronchoconstriction in asthmatics.
To evaluate whether the interindividual differences in dyspnoea perceived by asthmatic subjects for the same level of airway narrowing could depend on different changes in respiratory drive, we assessed the relationship between changes in airway calibre, changes in neuromuscular output, and dyspnoea rate during progressive bronchoconstriction induced by methacholine. We studied 18 asymptomatic asthmatic subjects (aged 18-36 yrs; 11 males and 7 females) with normal lung function. Dyspnoea (Borg scale), mouth occlusion pressure (P0.1), and forced expiratory volume in one second (FEV1) were measured at baseline and after inhalation of aerosols of doubling concentrations of methacholine (MCh). The progressive bronchoconstriction induced by MCh was associated with a progressive increase both of P0.1 and dyspnoea. Dyspnoea score was linearly related either to the fall in FEV1, or to the increase in P0.1. However, the slope values of the relationship between dyspnoea score and the corresponding percent fall in FEV1 showed a large interindividual variability (0.05-0.32; coefficient of variability (CoV) 43%). By contrast, the slope values of the relationship between dyspnoea score and the corresponding percent increase in P0.1 ranged 0.02-0.05 (CoV = 14%), indicating a more homogeneous response to dyspnoea for the same change in P0.1. At the highest MCh concentration, the dyspnoea score was linearly related to the corresponding change in P0.1 (r = 0.91; p < 0.01), but not to the corresponding percentage fall in FEV1 (r = 0.28). These results show that the interindividual differences in dyspnoea perceived by asthmatic subjects for the same level of airway narrowing are associated with different changes in respiratory drive during bronchoconstriction.


Differences in release of tumor necrosis factor from THP-1 cells stimulated by filtrates of antibiotic-killed Escherichia coli.
Bacterial products, such as endotoxin, activate mononuclear cells to produce tumor necrosis factor (TNF) and other monokines capable of producing host cell injury. THP-1 cell TNF release in response to bacterial products generated during antibiotic killing of Escherichia coli (ATCC 12014) was evaluated. THP-1 is a mature monocytic leukemia cell line that produces TNF in a dose-dependent fashion in response to purified endotoxin. E. coli were incubated in the presence of amikacin, ciprofloxacin, ceftazidime, cefotaxime, aztreonam, or imipenem at concentrations that killed greater than 99.9% of the organisms. Aliquots of these antibiotic-bacterial cultures were added to THP-1 cells, and TNF concentrations were determined by specific immunoassay. Amikacin and imipenem produced rapid bacterial killing and were associated with low TNF levels. Ceftazidime, aztreonam, and cefotaxime killed E. coli at a slower rate and were associated with significant increases in mononuclear cell TNF responses. Ciprofloxacin produced intermediate TNF levels. Differences exist among bactericidal antibodies in their ability to generate products capable of stimulating mononuclear cell TNF release.


Differential effect of the expression of TGF-β pathway inhibitors, Smad-7 and Ski, on invasive breast carcinomas: relation to biologic behavior.
The aim of our study was to investigate the expression of Smad-7 and Ski proteins in invasive breast carcinomas, to determine their clinicopathological value and their influence on carcinomas biologic behavior. Immunohistochemistry was applied on 150 invasive breast carcinomas to detect the expression of Smad-7 and Ski. Their correlation to clinicopathologic parameters and markers of metastasis was statistically processed using chi-squared test. Overall and disease-free survival was assessed using Kaplan-Meier test and log-rank statistics. Smad-7 was immunodetected in the cytoplasm of cancer cells in 60%, whereas Ski was immunodetected in the cytoplasm and nuclei in 44.5% and 17.6% of the cases, respectively. Smad-7 expression was positively correlated with tumor size, stage, matrix metalloproteinase (MMP)-9, and MMP-14. Cytoplasmic Ski expression was negatively associated with tumor size, stage, and lymph node status, and its nuclear expression was negatively related to histologic grade. Cytoplasmic Ski expression was associated with longer overall and disease-free survival. It appears that two negative regulators of the transforming growth factor-β pathway, Smad-7 and Ski, behave differentially in invasive breast carcinomas. Smad-7 appears to be related with an aggressive phenotype, whereas Ski expression is related to a less aggressive behavior and positively influences patients' survival.


Neutral endopeptidase activity is increased in the skin of subjects with diabetic ulcers.
Cutaneous sensory nerves mediate inflammation and wound healing by releasing neuropeptides, such as substance P, which stimulates pro-inflammatory responses by keratinocytes, fibroblasts, and endothelial cells. The cell surface enzyme, neutral endopeptidase, degrades substance P, thereby regulating its biologic actions. We hypothesized that neutral endopeptidase enzymatic activity is increased in chronic wounds and skin from subjects with diabetes. We compared cutaneous neutral endopeptidase expression and enzymatic activity between normal controls and diabetic subjects with neuropathy and chronic wounds. Skin samples from subjects with diabetes were taken at the time of amputation for nonhealing ulcers. Skin taken from the ulcer margin, 1 cm from the ulcer (adjacent), and from the most proximal region of the amputated leg were studied. Skin biopsies from the leg of healthy control subjects were also studied. Neutral endopeptidase was localized by immunohistochemistry in all tissue sections. Neutral endopeptidase activity was measured using a fluorimetric assay. The median neutral endopeptidase activity of the ulcer margin was 1.21 x higher (p>0.2) than adjacent skin, 5.26 (p<0.001) than proximal skin, and 15.22 x higher (p<0.001) than control skin. Adjacent skin had a median neutral endopeptidase activity 4.34 x higher (p<0.001) than proximal skin and 12.58 x higher (p<0.001) than control skin. The median neutral endopeptidase activity of proximal skin was 2.90 x higher (p<0.001) than control skin. This elevated neutral endopeptidase activity in the skin and chronic ulcers of subjects with diabetes combined with peripheral neuropathy may contribute to deficient neuroinflammatory signaling and may impair wound healing in subjects with diabetes.


[Evaluation of water-soluble vitamins in the vitamin preparation Spofavit dragée using reversed-phase HPLC].
A reversed-phase HPLC gradient method with good separation efficiency was developed and validated for the evaluation of water-soluble vitamins in the pharmaceutical preparation Spofavit dragee. Analyses were performed on a C8 column (LiChrospher RP-select B), the mobile phase was a mixture of phosphate buffer with sodium hexanesulphonate and acetonitrile. Detection was at 280 and 210 nm. The method is capable within 7 minutes to evaluate 6 water-soluble vitamins (ascorbic acid, nicotinamide, panthotenate.Ca, pyridoxine.HCl, thiamine.HCl, and riboflavin). All validated parameters of this method are discussed; the developed method appeared robust and suitable for evaluation of water-soluble vitamins in vitamin preparations.


Direct patterning of CdSe quantum dots into sub-100 nm structures.
Ordered, two-dimensional cadmium selenide (CdSe) arrays have been fabricated on indium-doped tin oxide (ITO) electrodes using the pattern replication in nonwetting templates (PRINT) process. CdSe quantum dots (QDs) with an average diameter of 2.7 nm and a pyridine surface ligand were used for patterning. The PRINT technique utilizes a perfluoropolyether (PFPE) elastomeric mold that is tolerant of most organic solvents, thus allowing solutions of CdSe QDs in 4-picoline to be used for patterning without significant deformation of the mold. Nanometer-scale diffraction gratings have been successfully replicated with CdSe QDs.


Expression and predictive value of HIF-1α and VEGF in patients with burns following treatment.
The present study aimed to investigate the expression and predictive value of serum hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in patients with burns following treatment. A total of 84 patients with burns treated in Jinan City People's Hospital (Jinan, China) between June 2015 and August 2017 were selected and their clinical information was collected. The expression levels of HIF-1α and VEGF before and after treatment were detected via ELISA, and HIF-1α and VEGF levels in patients with effective and ineffective treatment were compared. The predictive values of HIF-1α and VEGF in clinical efficacy were determined using receiver operating characteristic (ROC) curves, and independent risk factors affecting treatment inefficacy were analyzed via multivariate logistic regression. It was revealed that HIF-1α decreased significantly (P<0.05) while VEGF significantly increased in patients after treatment. Patients with effective treatment presented significantly lower HIF-1α levels and higher VEGF levels compared with those with ineffective treatment. The ROC curve indicated that the area under the curve (AUC) of HIF-1α for treatment efficacy was 0.795, the 95% CI was 0.666-0.924, the specificity and sensitivity were 68.75 and 80.88%, respectively, and the Youden index was 49.63%. For VEGF, the AUC, 95% CI, specificity, sensitivity and Youden index were 0.826, 0.725-0.928, 68.75, 82.35 and 51.10% respectively. Moreover, under the joint detection of HIF-1α and VEGF, the AUC was 0.847, 95% CI was 0.746-0.947, specificity and sensitivity were 87.50 and 66.18%, respectively, with a Youden index of 53.68%. Multivariate analysis demonstrated that higher HIF-1α level, lower VEGF level and higher burn degree before treatment were independent risk factors for treatment inefficacy. HIF-1α levels decreased and VEGF levels increased in burn patients after treatment. HIF-1α and VEGF before treatment may therefore serve as predictors for treatment efficacy.


Modified J-CAPRA scoring system in predicting treatment outcomes of metastatic prostate cancer patients undergoing androgen deprivation therapy.
The J-CAPRA score is an assessment tool which stratifies risk and predicts outcome of primary androgen deprivation therapy (ADT) using prostate-specific antigen, Gleason score, and clinical TNM staging. Here, we aimed to assess the generalisability of this tool in multi-ethnic Asians. Performance of J-CAPRA was evaluated in 782 Malaysian and 16,946 Japanese patients undergoing ADT from the Malaysian Study Group of Prostate Cancer (M-CaP) and Japan Study Group of Prostate Cancer (J-CaP) databases, respectively. Using the original J-CAPRA, 69.6% metastatic (M1) cases without T and/or N staging were stratified as intermediate-risk disease in the M-CaP database. To address this, we first omitted clinical T and N stage variables, and calculated the score on a 0-8 scale in the modified J-CAPRA scoring system for M1 patients. Notably, treatment decisions of M1 cases were not directly affected by both T and N staging. The J-CAPRA score threshold was adjusted for intermediate (modified J-CAPRA score 3-5) and high-risk (modified J-CAPRA score ≥6) groups in M1 patients. Using J-CaP database, validation analysis showed that overall survival, prostate cancer-specific survival, and progression-free survival of modified intermediate and high-risk groups were comparable to those of original J-CAPRA (p > 0.05) with Cohen's coefficient of 0.65. Around 88% M1 cases from M-CaP database were reclassified into high-risk category. Modified J-CAPRA scoring system is instrumental in risk assessment and treatment outcome prediction for M1 patients without T and/or N staging.


[Abdomen specific bioelectrical impedance analysis (BIA) methods for evaluation of abdominal fat distribution].
Two novel bioelectrical impedance analysis (BIA) methods have been developed recently for evaluation of intra-abdominal fat accumulation. Both methods use electrodes that are placed on abdominal wall and allow evaluation of intra-abdominal fat area (IAFA) easily without radiation exposure. Of these, "abdominal BIA" method measures impedance distribution along abdominal anterior-posterior axis, and IAFA by BIA method(BIA-IAFA) is calculated from waist circumference and the voltage occurring at the flank. Dual BIA method measures impedance of trunk and body surface at the abdominal level and calculates BIA-IAFA from transverse and antero-posterior diameters of the abdomen and the impedance of trunk and abdominal surface. BIA-IAFA by these two BIA methods correlated well with IAFA measured by abdominal CT (CT-IAFA) with correlatipn coefficient of 0.88 (n = 91, p < 0.0001) for the former, and 0.861 (n = 469, p < 0.01) for the latter. These new BIA methods are useful for evaluating abdominal adiposity in clinical study and routine clinical practice of metabolic syndrome and obesity.


Albuterol isomers modulate platelet-activating factor synthesis and receptor signaling in human bronchial smooth muscle cells.
Racemic albuterol is a 50:50 mixture of the (R)- and (S)-enantiomers of albuterol. Its clinical efficacy resides in the (R)-enantiomer (levalbuterol). Studies have shown that (S)-albuterol induces human bronchial smooth muscle cell (HBSMC) proliferation via a pathway linked to platelet-activating factor (PAF), but the underlying mechanism by which (S)-albuterol augments PAF effects is not clear. In this study, we compared effect of levalbuterol and (S)-albuterol on PAF receptor (PAFr)-mediated signaling and PAF metabolism by HBSMCs after incubation with the albuterol isomers. PAF binding and inositol phosphate (IP(3)) release were studied on adherent cultured cells. PAFr protein expression was measured by Western blotting, PAF synthesis and catabolism were measured in membrane and cytosolic proteins of cells incubated with albuterol isomers. Compared to control conditions, (S)-albuterol increased PAF binding by 70% after 30 min of preincubation and by 150% after 24 h of preincubation. Levalbuterol had no effect on PAF binding under both conditions. (S)-albuterol also augmented PAF stimulation of IP(3) release, while levalbuterol and the racemic mixture had no effect. WEB 2170, a PAFr antagonist, inhibited the ability of (S)-albuterol to increase PAF binding or stimulate IP(3) release. (S)-albuterol stimulated PAFr protein expression. With PAF metabolism, (S)-albuterol treatment augmented PAF synthesis, but significantly inhibited PAF catabolism. Our data suggest that one mechanism by which (S)-albuterol stimulates HBSMC proliferation involves upregulation of PAFr-mediated effects including increased PAF synthesis and decreased PAF catabolism.


Microbiological and Modeling Approach to Derive Performance Objectives for Bacillus cereus Group in Ready-to-Eat Salads.
In this article, the performance objectives (POs) for Bacillus cereus group (BC) in celery, cheese, and spelt added as ingredients in a ready-to-eat mixed spelt salad, packaged under modified atmosphere, were calculated using a Bayesian approach. In order to derive the POs, BC detection and enumeration were performed in nine lots of naturally contaminated ingredients and final product. Moreover, the impact of specific production steps on the BC contamination was quantified. Finally, a sampling plan to verify the ingredient lots' compliance with each PO value at a 95% confidence level (CL) was defined. To calculate the POs, detection results as well as results above the limit of detection but below the limit of quantification (i.e., censored data) were analyzed. The most probable distribution of the censored data was determined and two-dimensional (2D) Monte Carlo simulations were performed. The PO values were calculated to meet a food safety objective of 4 log10 cfu of BC for g of spelt salad at the time of consumption. When BC grows during storage between 0.90 and 1.90 log10 cfu/g, the POs for BC in celery, cheese, and spelt ranged between 1.21 log10 cfu/g for celery and 2.45 log10 cfu/g for spelt. This article represents the first attempt to manage the concept of PO and 2D Monte Carlo simulation in the flow chart of a complex food matrix, including raw and cooked ingredients.


How the ARCH Project Could Contribute to Strengthening ASEAN Regional Capacities on Disaster Health Management (DHM).
The Project for Strengthening the ASEAN Regional Capacity on Disaster Health Management (ARCH Project) developed Regional Collaboration Drills (RCDs) and is proposing an ASEAN Academic Network to strengthen capacity in disaster health management (DHM) in ASEAN Member States (AMS), as well as developing a standard training curriculum in DHM. This study aims to clarify the impacts and sustainability of the ARCH Project. The four previous RCDs and the enhancement of academic activities were reviewed. The ARCH Project developed the RCDs with simulation exercises based on possible disaster scenarios in each host country to test and validate the capacity of AMS International Emergency Medical Teams (I-EMTs), the Standard Operating Procedure (SOP) for I-EMT coordination, and regional tools, as well as the relevant domestic SOPs of the host countries for receiving international assistance. Following the RCD in Thailand, three AMS: Viet Nam, Philippines, and Indonesia, all of which are considered disaster-prone, successfully hosted RCDs with significant improvements. The project also established a sub-working group (SWG) to develop a standard curriculum in DHM. Two curricula developments, the Basic Course on DHM and In-Country Course for Coordination on EMTs, are on-going as part of the project activity. The establishment of the ASEAN Academic Network and the ASEAN Institute for DHM (AIDHM) are currently in the endorsement process of the ASEAN health sector. The RCDs are very effective to test and to validate the SOP and regional tools developed, providing opportunities for AMS I-EMT to familiarize the tools, as well as for host countries to assess their coordination capacity for receiving international assistance and identifying the country's specific challenges, and verifying ASEAN regional coordination mechanism. The development of the standard curriculum can enhance regional capacity both in supporting disaster-affected countries and in receiving international assistance. A sustainable capacity development mechanism in DHM is envisaged through the establishment of the ASEAN Academic Network and AIDHM toward the goal of One ASEAN One Response.


Characterization, isolation, and culture of spermatogonial stem cells in Macaca fascicularis.
Spermatogonial stem cells (SSCs) have great applications in both reproductive and regenerative medicine. Primates including monkeys are very similar to humans with regard to physiology and pathology. Nevertheless, little is known about the isolation, the characteristics, and the culture of primate SSCs. This study was designed to identify, isolate, and culture monkey SSCs. Immunocytochemistry was used to identify markers for monkey SSCs. Glial cell line-derived neurotrophic factor family receptor alpha-1 (GFRA1)-enriched spermatogonia were isolated from monkeys, namely Macaca fascicularis (M. fascicularis), by two-step enzymatic digestion and magnetic-activated cell sorting, and they were cultured on precoated plates in the conditioned medium. Reverse transcription-polymerase chain reaction (RT-PCR), immunocytochemistry, and RNA sequencing were used to compare phenotype and transcriptomes in GFRA1-enriched spermatogonia between 0 day and 14 days of culture, and xenotransplantation was performed to evaluate the function of GFRA1-enriched spermatogonia. SSCs shared some phenotypes with rodent and human SSCs. GFRA1-enriched spermatogonia with high purity and viability were isolated from M. fascicularis testes. The freshly isolated cells expressed numerous markers for rodent SSCs, and they were cultured for 14 days. The expression of numerous SSC markers was maintained during the cultivation of GFRA1-enriched spermatogonia. RNA sequencing reflected a 97.3% similarity in global gene profiles between 0 day and 14 days of culture. The xenotransplantation assay indicated that the GFRA1-enriched spermatogonia formed colonies and proliferated in vivo in the recipient c-KitW/W (W) mutant mice. Collectively, GFRA1-enriched spermatogonia are monkey SSCs phenotypically both in vitro and in vivo. This study suggests that monkey might provide an alternative to human SSCs for basic research and application in human diseases.


The Lasting Influence of a Peer-led Adolescent Relationship Abuse Prevention Program on Former Peer Leaders' Relationships, Identities, and Trajectories in Emerging Adulthood.
Adolescent relationship abuse (ARA) has well-documented detrimental health effects. Adolescence is a window of opportunity to promote development of healthy relationship behaviors. Although peer-led interventions have a history of use in the health education field, there are few rigorously evaluated peer-led interventions targeting ARA. Start Strong leverages peer support by training adolescents to deliver ARA prevention curriculum to younger peers. Although the program has shown positive results in recipients, little is known about the impact on the peer leaders themselves. This qualitative study describes the impact of being an ARA prevention peer leader on former peer leaders' relationships and trajectories in emerging adulthood. Specific objectives include: (a) how being a peer leader shaped participants' norms around romantic relationships and ARA, and (b) the impact of participating in a peer leadership program on their emerging adult lives. Researchers conducted semi-structured interviews with former peer leaders and coded transcripts using thematic analysis. Fourteen former peer leaders aged 18-26 participated. Most participants (99%) identified as Black or Afro-Latinx. Participants described a lasting impact on their relationships, identity formation, future orientation, and professional lives. Participants highlighted the skills they use to avoid unhealthy relationships and help friends and family navigate their relationships. They identified unexpected challenges, including a sense of isolation around how their relationship expectations differ from same-aged peers, and trepidation about dating partners without advanced healthy relationship knowledge. Participants highlighted positive impacts beyond those pertaining to relationships, including their identity development and expanded sense of opportunity. Finally, they identified tangible skills gained from program participation and relevance to their professional paths. This study suggests that peer-led ARA prevention programs have a far-reaching impact on participants' lives that lasts into adulthood. Future studies may examine how professional development within peer-led interventions can influence future orientation and thus bolster protective factors against ARA.


A double-blind, randomized and placebo-controlled trial of Saffron (Crocus sativus L.) in the treatment of anxiety and depression.
Depression and anxiety are prevalent serious psychiatric disorders. Several drugs are used to treat these conditions but these are often associated with serious side effects. For this reason alternative therapies, including herbal medication such as saffron, have been proposed. We aimed to assess the effects of saffron extract for the treatment of anxiety and depression using a 12-week double-blind, placebo-controlled trial design. Sixty adult patients with anxiety and depression were randomized to receive a 50 mg saffron capsule (Crocus sativus L. stigma) or a placebo capsule twice daily for 12 weeks. Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) questionnaires were used at baseline, 6 and 12 weeks after initiating medication. 54 subjects completed the trial. Saffron supplements had a significant effect on the BDI and BAI scores of subjects in comparison to placebo at the 12 week time-point (p<0.001). Saffron appears to have a significant impact in the treatment of anxiety and depression disorder. Side effects were rare.


Parameter extraction of ECG signals in real-time.
In order for a mobile ECG recorder to be able to classify a heart rhythm online, the significant parameters must be extracted. The relevant parameters are the beginning, peak and end of the QRS-complex, the P- and T-waves, the ST-segment and other significant intervals, such as the RR-interval. The aim of the development was, firstly, stable, real-time-capable QRS detection, which finally achieved values for sensitivity of 98.9% and a positive predictivity of 99.9% on standard ECG databases. Also, a filter-based detection of P- and T-waves was implemented, which can also be performed in real-time on a microcontroller platform.


Bilateral Hypertrophic Olivary Degeneration after Pontine Hemorrhage: A Case Report.
Hemorrhage lesions may lead to bilateral hypertrophic olivary degeneration (HOD) through interruption of the dentato-rubral-olivary pathway. The pathological features of HOD are unusual neuronal trans-synaptic degenerative changes. A 56-year-old female was admitted to our hospital because her lower extremities and left upper ones were unable to move for 3 mo, and the swelling of her right lower extremities became worse 3 days ago. She had a hypertension history. Her characteristic clinical manifestations are palatal myoclonus and nystagmus. The patient's magnetic resonance imaging (MRI) results showed that she had bilateral HOD after an acute pontine hemorrhage. She was given symptomatic and supportive treatment. The gabapentin, the memantine and the trihexyphenidyl were taken twice a day each. The rehabilitation and psychotherapy were implemented. After 3 months of treatment, her eye symptoms improved. Bilateral HOD is a rare phenomenon after pontine hemorrhage. The key to diagnosis lies in the clinical manifestations and MRI results.


Optimization of Printing Parameters for Digital Light Processing 3D Printing of Hollow Microneedle Arrays.
3D printing is an emerging technology aiming towards personalized drug delivery, among many other applications. Microneedles (MN) are a viable method for transdermal drug delivery that is becoming more popular for delivery through the skin. However, there is a need for a faster fabrication process with potential for easily exploring different geometries of MNs. In the current study, a digital light processing (DLP) method of 3D printing for fabrication of hollow MN arrays using commercial UV curable resin was proposed. Print quality was optimised by assessing the effect of print angle on needle geometries. Mechanical testing of MN arrays was conducted using a texture analyser. Angled prints were found to produce prints with geometries closer to the CAD designs. Curing times were found to affect the mechanical strength of MNs, with arrays not breaking when subjected to 300 N of force but were bent. Overall, DLP process produced hollow MNs with good mechanical strength and depicts a viable, quick, and efficient method for the fabrication of hollow MN arrays.


Distal penile lymphoedema following hypospadias repair: a case report.
A patient who developed isolated distal penile lymphoedema 10 years following hypospadias repair is reported. The classification and causes of genital lymphoedema and possible reasons for its occurrence in this case are discussed.


If not dieting, now what?
Helping patients to achieve and maintain their most healthy weight is a common challenge. Giving a "one size fits all" set of instructions to patients who are over their most healthy weight does not help. This article discusses approaches to assist weight loss in patients while treating each patient as an individual. By using less emotive, more supportive and accepting language, we can still talk about reality (for example "a patient being above their most healthy weight") while minimising the risk of negatively impacting on the patient's self esteem. It is important to spend time learning from the patient, factors that have influenced their relationship with their body and weight, and the reasons why that person's weight has become above their most healthy weight range. We need to help patients focus on changes to their thinking, attitude and behaviour with weight loss to come as a result of that. Motivational interviewing is a useful counselling approach. It is also helpful to have a range of options to offer patients. This may include reading resources; a team of health professionals to refer to such as dieticians, counsellors, physiotherapists, and exercise specialists; or appropriate community group programs.


Eating Disorder Examination-Questionnaire and Clinical Impairment Assessment norms for intersectional identities using an MTurk sample.
There are limited data to guide the interpretation of scores on measures of eating-disorder psychopathology among underrepresented individuals. We aimed to provide norms for the Eating Disorder Examination-Questionnaire (EDE-Q) and Clinical Impairment Assessment (CIA) across racial/ethnic, gender, and sexual identities, and sexual orientations and their intersections by recruiting a diverse sample of Amazon MTurk workers (MTurkers; N = 1782). We created a comprehensive, quantitative assessment of racial/ethnic identification, gender identification, sex assigned at birth, current sexual identification, and sexual orientation called the Demographic Assessment of Racial, Sexual, and Gender Identities (DARSGI). We calculated normative data for each demographic category response option. Our sample was comprised of 68% underrepresented racial/ethnic identities, 42% underrepresented gender identities, 13% underrepresented sexes, and 49% underrepresented sexual orientations. We reported means and standard deviations for each demographic category response option and, where possible, mean estimates by percentile across intersectional groups. EDE-Q Global Score for a subset of identities and intersections in the current study were higher than previously reported norms for those identities/intersections. This is the most thorough reporting of norms for the EDE-Q and CIA among racial/ethnic, sexual, and gender identities, and sexual orientations and the first reporting on multiple intersections, filling some of the gaps for commonly used measures of eating-disorder psychopathology. These norms may be used to contextualize eating-disorder psychopathology reported by underrepresented individuals. The data from the current study may help inform research on the prevention and treatment of eating-disorder psychopathology in underrepresented groups. We provide the most thorough reporting on racial/ethnic, sexual, and gender identities, and sexual orientations for the Eating Disorder Examination - Questionnaire and Clinical Impairment Assessment, and the first reporting on intersections, which fills some of the gaps for commonly used measures of eating-disorder psychopathology. These norms help inform research on the prevention and treatment of eating-disorder psychopathology in underrepresented groups.


The effect of visual deprivation upon the basal dendrites of Meynert cells in the striate cortex of the monkey.
The basal dendrites of Meynert cells in the striate cortex have been studied with the Golgi method in the brains of monkeys that had been reared for varying periods with the eyelids closed over one eye. The lengths and arrangement of the dendrites were compared with those in normal brains. In the visually deprived brain almost half of the cells had basal dendrites that were apparently normal with the dendritic fields in the form of an ellipse and the long axes parallel to the direction of the ocular dominance bands. The other cells had dendritic fields that have rarely been seen in normal material and two distinct types could be recognized. The 'lop-sided' cell had an ellipsoidal dendritic field with the major axis parallel to the ocular dominance bands, but the extents of the dendrites along the minor axis were very asymmetric; the ratio of the means of the long and short arms of the minor axis of the 'lop-sided' cell is 2.3:1 compared with 1.1:1 in normal brains. The 'perpendicular' type of cell also had an ellipsoidal dendritic field but the relation of the major and minor axes to the direction of the ocular dominance bands was the reverse of the normal cell, with the long axis of the ellipse being aligned perpendicular to the bands. 'Lop-sided' cells formed approximately 18% of the total of Meynert cells studied and the 'perpendicular' 32%. The proportion of the cells with abnormal basal dendritic fields, and particularly the 'perpendicular', increased with longer durations of eyelid closure. It is suggested that the alterations in the dendritic fields of the 'lop-sided' and 'perpendicular' cells may be correlated with the changes in width of the ocular dominance bands that are known to occur after monocular eyelid suture.


Real-time quantification of protein expression at the single-cell level via dynamic protein synthesis translocation reporters.
Protein expression is a dynamic process, which can be rapidly induced by extracellular signals. It is widely appreciated that single cells can display large variations in the level of gene induction. However, the variability in the dynamics of this process in individual cells is difficult to quantify using standard fluorescent protein (FP) expression assays, due to the slow maturation of their fluorophore. Here we have developed expression reporters that accurately measure both the levels and dynamics of protein synthesis in live single cells with a temporal resolution under a minute. Our system relies on the quantification of the translocation of a constitutively expressed FP into the nucleus. As a proof of concept, we used these reporters to measure the transient protein synthesis arising from two promoters responding to the yeast hyper osmolarity glycerol mitogen-activated protein kinase pathway (pSTL1 and pGPD1). They display distinct expression dynamics giving rise to strikingly different instantaneous expression noise.


Evidence for various 20q status using allelotyping, CGH arrays, and quantitative PCR in distal CIN colon cancers.
The genomic aberration profile of chromosome 20q in distal CIN colon carcinomas was analysed using allelotyping and CGH arrays. Allelotyping revealed carcinomas with allelic imbalance along the full long arm, and carcinomas with fully non-aberrant 20q. Oligonucleotide-based CGH showed that among the carcinomas without allelic imbalance, 47% had in fact a gain. In this subgroup, quantitative PCR for the TOPI gene (20q12) confirmed this gain, and fluorescence in situ hybridization showed that the chromosome 20q gain resulted from tetra/polysomy instead of aneusomy. The 20q gain correlated with a high frequency of aberrations, with allelic imbalance at TP53 locus but not at APC locus, and carcinomas with a disomic 20q showed low frequency of genomic aberrations and were significantly associated to mucinous phenotype. The prognostic value of 20q amplification was not demonstrated in this study. These results indicate that on the basis of aberration frequency, chromosome 20q and TP53/APC locus status, distal CIN carcinomas harbor a high degree of genetic heterogeneity suggesting several pathways for carcinogenesis. This study also indicates that allelotyping needs to be carried out with a complementary technique, such as quantitative PCR.


Sensor Arrays Based on Polycyclic Aromatic Hydrocarbons: Chemiresistors versus Quartz-Crystal Microbalance.
Arrays of broadly cross-reactive sensors are key elements of smart, self-training sensing systems. Chemically sensitive resistors and quartz-crystal microbalance (QCM) sensors are attractive for sensing applications that involve detection and classification of volatile organic compounds (VOCs) in the gas phase. Polycyclic aromatic hydrocarbon (PAH) derivatives as sensing materials can provide good sensitivity and robust selectivity towards different polar and nonpolar VOCs, while being quite tolerant to large humidity variations. Here, we present a comparative study of chemiresistor and QCM arrays based on a set of custom-designed PAH derivatives having either purely nonpolar coronas or alternating nonpolar and strongly polar side chain termination. The arrays were exposed to various concentrations of representative polar and nonpolar VOCs under extremely varying humidity conditions (5-80% RH). The sensor arrays' classification ability of VOC polarity, chemical class and compound separation was explained in terms of the sensing characteristics of the constituent sensors and their interaction with the VOCs. The results presented here contribute to the development of novel versatile and cost-effective real-world VOC sensing platforms.


Combined shifted-excitation Raman difference spectroscopy and support vector regression for monitoring the algal production of complex polysaccharides.
The applicability of shifted-excitation Raman difference spectroscopy (SERDS) in combination with signal regression analysis as an alternative and non-invasive approach for monitoring the cultivation of phototrophic microorganisms producing complex molecules of pharmaceutical relevance in a bioreactor is demonstrated. As a model system, the cultivation of the red unicellular algae Porphyridium purpureum is used for focusing on the segregation of sulfated exopolysaccharides (EPS) which exhibit antiviral activity. The spectroscopic results obtained by partial linear least squares regression (PLSR) and by nonlinear support vector regression (SVR) are discussed against the corresponding results from the reference analytics based on the phenol-sulfuric acid assay. The SERDS-approach turns out to have strong potential as a non-invasive tool for online-monitoring of biotechnological processes.


Direct Laser 3D Printing of Refractory Materials.
Direct laser 3D printing of refractory materials such as silicon carbide (SiC), tungsten (W), and tantalum hafnium carbide (TaHfC) have been systematically investigated. High relative density has been achieved for SiC, SiC/Al, W, and W/TaHfC. High density SiC structures and W thin wall were also fabricated. By mixing the metal powders (e.g. Al or W) with ceramic powder such as SiC or TaHfC, a metal/ceramic matrix is formed during the direct laser melting process to tailor the mechanical properties.


Improved fluorescent (calcium indicator) dye uptake in brain slices by blocking multidrug resistance transporters.
ATP-binding cassette (ABC) transporters are a family of transmembrane proteins that, also known as multidrug resistance proteins, transport a wide variety of substrates across biological membranes in an energy-dependent manner. Recently it has been shown that members of this protein family interfere with fluorescent (calcium indicator) dye uptake in taste buds of rat and in cells in the olfactory epithelium of larval Xenopus laevis, including olfactory receptor neurons. It has, however, not been resolved whether this effect only serves to extrude xenobiotics in sensory taste and olfactory cells, or alternatively, whether it is a more general feature of many central nervous system neurons. In the latter case blocking these transporters would improve fluorescent dye uptake in general. Here we show, by means of cell imaging, that also neurons of the olfactory bulb express multidrug resistance transporters, whereby a marked inhomogeneity among cells in the main and accessory olfactory bulb was observed. Blocking these transporters improved the net uptake of fluorescent dyes not only in cell somata of the olfactory bulb, but especially in fine neuronal structures such as individual dendrites or olfactory glomeruli, which consist of a tangle of tiny neuronal processes. We therefore suggest that the expression of multidrug resistance proteins may be common in cells of the central nervous system, and that the application of specific transport inhibitors could generally improve fluorescent dye uptake in brain slices, thereby improving calcium imaging conditions.


Laparoscopic calibrated total vs partial fundoplication following Heller myotomy for oesophageal achalasia.
To compare the mid-term outcomes of laparoscopic calibrated Nissen-Rossetti fundoplication with Dor fundoplication performed after Heller myotomy for oesophageal achalasia. Fifty-six patients (26 men, 30 women; mean age 42.8 ± 14.7 years) presenting for minimally invasive surgery for oesophageal achalasia, were enrolled. All patients underwent laparoscopic Heller myotomy followed by a 180° anterior partial fundoplication in 30 cases (group 1) and calibrated Nissen-Rossetti fundoplication in 26 (group 2). Intraoperative endoscopy and manometry were used to calibrate the myotomy and fundoplication. A 6-mo follow-up period with symptomatic evaluation and barium swallow was undertaken. One and two years after surgery, the patients underwent symptom questionnaires, endoscopy, oesophageal manometry and 24 h oesophago-gastric pH monitoring. At the 2-year follow-up, no significant difference in the median symptom score was observed between the 2 groups (P = 0.66; Mann-Whitney U-test). The median percentage time with oesophageal pH < 4 was significantly higher in the Dor group compared to the Nissen-Rossetti group (2; range 0.8-10 vs 0.35; range 0-2) (P < 0.0001; Mann-Whitney U-test). Laparoscopic Dor and calibrated Nissen-Rossetti fundoplication achieved similar results in the resolution of dysphagia. Nissen-Rossetti fundoplication seems to be more effective in suppressing oesophageal acid exposure.


Remaining life expectancy among older people in a rural area of Vietnam: trends and socioeconomic inequalities during a period of multiple transitions.
Better understanding of the trends and disparities in health at old age in terms of life expectancy will help to provide appropriate responses to the growing needs of health and social care for the older population in the context of limited resources. As a result of rapid economic, demographic and epidemiological changes, the number of people aged 60 and over in Vietnam is increasing rapidly, from 6.7% in 1979 to 9.2% in 2006. Life expectancy at birth has increased but not much are known about changes in old ages. This study assesses the trends and socioeconomic inequalities in RLE at age 60 in a rural area in an effort to highlight this vulnerable group and to anticipate their future health and social needs. An abridged life table adjusted for small area data was used to estimate cohort life expectancies at old age and the corresponding 95% confidence intervals from longitudinal data collected by FilaBavi DSS during 1999-2006, which covered 7,668 people at age 60+ with 43,272 person-years, out of a total of 64,053 people with 388,278 person-years. Differences in life expectancy were examined according to socioeconomic factors, including socio-demographic characteristics, wealth, poverty and living arrangements. Life expectancies at age 60 have increased by approximately one year from the period 1999-2002 to 2003-2006. The increases are observed in both sexes, but are significant among females and relate to improvements among those who belong to the middle and upper household wealth quintiles. However, life expectancy tends to decrease in the most vulnerable groups. There is a wide gap in life expectancy according to poverty status and living arrangements, and the gap by poverty status has widened over the study period. The gender gap in life expectancy is consistent across all socioeconomic groups and tends to be wider amongst the more disadvantaged population. There is a trend of increasing life expectancy among older people in rural areas of Vietnam. Inequalities in life expectancy exist between socioeconomic groups, especially between different poverty levels and also patterns of living arrangements. These inequalities should be addressed by appropriate social and health policies with stronger targeting of the poorest and most disadvantaged groups.


Trabecular and cortical microstructure and fragility of the distal radius in women.
Fragility fractures commonly involve metaphyses. The distal radius is assembled with a thin cortex formed by fusion (corticalization) of trabeculae arising from the periphery of the growth plate. Centrally positioned trabeculae reinforce the thin cortex and transfer loads from the joint to the proximal thicker cortical bone. We hypothesized that growth- and age-related deficits in trabecular bone disrupt this frugally assembled microarchitecture, producing bone fragility. The microarchitecture of the distal radius was measured using high-resolution peripheral quantitative computed tomography in 135 females with distal radial fractures, including 32 girls (aged 7 to 18 years), 35 premenopausal women (aged 18 to 44 years), and 68 postmenopausal women (aged 50 to 76 years). We also studied 240 fracture-free controls of comparable age and 47 healthy fracture-free premenopausal mother-daughter pairs (aged 30 to 55 and 7 to 20 years, respectively). In fracture-free girls and pre- and postmenopausal women, fewer or thinner trabeculae were associated with a smaller and more porous cortical area (r = 0.25 to 0.71 after age, height, and weight adjustment, all p < 0.05). Fewer and thinner trabeculae in daughters were associated with higher cortical porosity in their mothers (r = 0.30 to 0.47, all p < 0.05). Girls and premenopausal and postmenopausal women with forearm fractures had 0.3 to 0.7 standard deviations (SD) fewer or thinner trabeculae and higher cortical porosity than controls in one or more compartment; one SD trait difference conferred odds ratio (95% confidence interval) for fracture ranging from 1.56 (1.01-2.44) to 4.76 (2.86-7.69). Impaired trabecular corticalization during growth, and cortical and trabecular fragmentation during aging, may contribute to the fragility of the distal radius.


Visiting preferences of cardiovascular patients.
The purpose of this study is to compare differences in patient preferences for visitors during hospitalization for a cardiovascular event specifically comparing cardiac intensive care unit (CICU) patients to those on cardiac step down units (SDU). A convenience sample 63 subjects from the CICU, mean age of 61.2 +/- 14.4 years, 21 males and 41 females, were compared with 61 subjects, mean age of 67.9 +/- 14.4 years, 15 females and 46 males, on the "Patient's Perception of Visits in the Hospital" questionnaire. The CICU patient perceived higher value for visiting specifically because visitors assisted with interpretation of information (P<.02), were calming (P<.05), providing information about them to staff (P<.01), helped with care (P<.000), and reinforced treatments (P<.004). There were no differences in total stressor score between CICU and SDU patients, though the CICU patient worried more about their visitors traveling (P<.025). The SDU patient perceived that visitors were disruptive to rest (P<.001) and that visitors intensified their pain (P<.008). The majority of patients preferred unlimited visiting hours, with 3 visitors at a time, and some limits on children. Text data identified unlimited visiting for close family members, the benefit of support from visitors, and the stress of lengthy visits. These data provide voice to cardiovascular patient's perception of visitors.


Biotechnological Insights on the Expression and Production of Antimicrobial Peptides in Plants.
The emergence of drug-resistant pathogens poses a serious critical threat to global public health and requires immediate action. Antimicrobial peptides (AMPs) are a class of short peptides ubiquitously found in all living forms, including plants, insects, mammals, microorganisms and play a significant role in host innate immune system. These peptides are considered as promising candidates to treat microbial infections due to its distinct advantages over conventional antibiotics. Given their potent broad spectrum of antimicrobial action, several AMPs are currently being evaluated in preclinical/clinical trials. However, large quantities of highly purified AMPs are vital for basic research and clinical settings which is still a major bottleneck hindering its application. This can be overcome by genetic engineering approaches to produce sufficient amount of diverse peptides in heterologous host systems. Recently plants are considered as potential alternatives to conventional protein production systems such as microbial and mammalian platforms due to their unique advantages such as rapidity, scalability and safety. In addition, AMPs can also be utilized for development of novel approaches for plant protection thereby increasing the crop yield. Hence, in order to provide a spotlight for the expression of AMP in plants for both clinical or agricultural use, the present review presents the importance of AMPs and efforts aimed at producing recombinant AMPs in plants for molecular farming and plant protection so far.


Maternal zinc status: a determination of central nervous system malformation.
Maternal serum zinc concentrations were estimated during 244 normal pregnancies and 15 abnormal pregnancies. The serum zinc concentrations were lower in the anencephalic pregnancies than in the normal control subjects. The serum zinc levels in women whose pregnancies terminated in a spontaneous abortion were normal. There was no variation of serum zinc level with gestational age between 15 to 18 weeks in normal pregnancies.


[Hemorrhage into a liver adenoma associated with long-term use of oral contraceptives].
A 39-year-old woman was evaluated for acute midepigastric pain. The patient was never severely ill; her only medication was an oral contraceptive (OC) which she took regularly over the last 12 years. Abdominal ultrasonography and computed tomography revealed bleeding into a liver tumor. At laparoscopy, 3 adenomas of the liver were detected. Bleeding was restricted to 1 tumor and did not require surgical intervention. OC medication was discontinued, and the patient was followed over more than 3 years. The patient was doing very well; ultrasonographically, the liver tumors became gradually smaller.


Minimal contribution of fasting hyperglycemia to the incidence of type 2 diabetes in subjects with normal 2-h plasma glucose.
OBJECTIVE To assess the relative contribution of increased fasting and postload plasma glucose concentrations to the incidence of type 2 diabetes in subjects with a normal 2-h plasma glucose concentration. RESEARCH DESIGN AND METHODS A total of 3,450 subjects with 2-h plasma glucose concentration <140 mg/dl at baseline were followed up in the San Antonio Heart Study (SAHS) and the Botnia Study for 7-8 years. The incidence of type 2 diabetes at follow-up was related to the fasting, 1-h, and 2-h plasma glucose concentrations. RESULTS In subjects with 2-h plasma glucose <140 mg/dl, the incidence of type 2 diabetes increased with increasing fasting plasma glucose (FPG) and 1-h and 2-h plasma glucose concentrations. In a multivariate logistic analysis, after adjustment for all diabetes risk factors, the FPG concentration was a strong predictor of type 2 diabetes in both the SAHS and the Botnia Study (P < 0.0001). However, when the 1-h plasma glucose, but not 2-h plasma glucose, concentration was added to the model, FPG concentration was no longer a significant predictor of type 2 diabetes in both studies (NS). When subjects were matched for the level of 1-h plasma glucose concentration, the incidence of type 2 diabetes markedly increased with the increase in 1-h plasma glucose, but the increase in FPG was not associated with a significant increase in the incidence of type 2 diabetes. CONCLUSIONS An increase in postload glycemia in the normal range is associated with an increase in the incidence of type 2 diabetes. After controlling for 1-h plasma glucose concentration, the increase in FPG concentration is not associated with an increase in the incidence of type 2 diabetes.


Scaling and Accommodation of Jaw Adductor Muscles in Canidae.
The masticatory apparatus amongst closely related carnivoran species raises intriguing questions about the interplay between allometry, function, and phylogeny in defining interspecific variations of cranial morphology. Here we describe the gross structure of the jaw adductor muscles of several species of canid, and then examine how the muscles are scaled across the range of body sizes, phylogenies, and trophic groups. We also consider how the muscles are accommodated on the skull, and how this is influenced by differences of endocranial size. Data were collected for a suite of morphological metrics, including body mass, endocranial volume, and muscle masses and we used geometric morphometric shape analysis to reveal associated form changes. We find that all jaw adductor muscles scale isometrically against body mass, regardless of phylogeny or trophic group, but that endocranial volume scales with negative allometry against body mass. These findings suggest that head shape is partly influenced by the need to house isometrically scaling muscles on a neurocranium scaling with negative allometry. Principal component analysis suggests that skull shape changes, such as the relatively wide zygomatic arches and large sagittal crests seen in species with higher body masses, allow the skull to accommodate a relative enlargement of the jaw adductors compared with the endocranium. Anat Rec, 299:951-966, 2016. © 2016 The Authors The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology Published by Wiley Periodicals, Inc.


Flavour Compensation Role of Yeast Strains in Reduced-Salt Dry Sausages: Taste and Odour Profiles.
The effects of different yeast strains including Pichia kudriavzevii, Torulaspora delbrueckii, and Debaryomyces hansenii on the taste and odour profiles of reduced-salt dry sausages were explored. Inoculation of P. kudriavzevii and D. hansenii compensated for the lack of saltiness and umami tastes of reduced-salt sausages. Furthermore, inoculation of P. kudriavzevii and T. delbrueckii resulted in an odour profile in the reduced-salt dry sausages that was similar to traditional dry sausages. According to the volatile analysis, the contents of certain alcohols, acids, esters and terpenes were higher in the inoculated sausages. Finally, the sensory evaluation indicated that the inoculation of P. kudriavzevii and D. hansenii contributed positively to the aroma and saltiness of reduced-salt dry sausages. In conclusion, P. kudriavzevii and D. hansenii can be employed as effective starter cultures to compensate for the flavour deficiencies of reduced-salt dry sausages.


Knot of Henry Variation and the Effect on Plantar Flexion Strength.
The flexor hallucis longus (FHL) and flexor digitorum longus (FDL) tendons are commonly used for tendon transfer in reconstructive foot and ankle procedures. Some patients experience great toe weakness and loss of push-off strength. The objective of this biomechanical study was to quantify plantarflexion force after FHL and FDL harvest and correlate it to variations in tendon crossover patterns at the knot of Henry to determine if specific patterns have an increased tendency toward forefoot weakness. Simulated loads through the Achilles, FHL, and FDL were applied to cadaveric specimens while plantarflexion force was measured using a pressure mapping system. Force was recorded with the FDL and FHL unloaded to simulate tendon transfer. Afterward, specimens were dissected to classify the tendinous slips between the FHL and FDL based on a previously determined system. Functional and anatomical relationships between the classification type and loading patterns were analyzed. There were no statistical differences between the tendon crossover patterns in forefoot force reduction after FHL or FDL harvest. Average decrease in great toe and total forefoot pressure after FHL harvest was 31% and 22%, respectively. Average decrease in lesser toe and total forefoot push-off force after FDL harvest was 23% and 9%, respectively. This study quantified loss of plantarflexion force after simulated FHL and FDL harvest and correlated these losses to variations in anatomic crossover patterns at the knot of Henry. Variations at the knot of Henry do not contribute to differences in forefoot weakness. The decrease in forefoot pressure seen here would help explain the clinical scenario where a patient does note a loss of great toe strength after FHL transfer.


[Personal experience in the treatment of tuberculosis in patients in war areas].
In the four-year period (1991-1995), 96 tuberculosis patients from the war areas of former Yugoslavia were treated in the Clinic for Lung Diseases of Military Medical Academy, that makes 31% of total number of sick and treated for tuberculosis-309 (100%). In group I (patients from war areas) there were 45 cases of cavernous pulmonary tuberculosis (47%), 28 bilateral (29%), 16 pleurisy (16.7%) and 6 cases of extensive pulmonary tuberculosis (5.1%). Among 213 patients (100%) from group II (patients from FR Yugoslavia), 81 patients had cavernous pulmonary tuberculosis (38%), 49 patients had bilateral (23%), 33 patients had pleurisy (15.5%) and 6 patients had extensive pulmonary tuberculosis (2.8%). In group I the diagnosis was bacteriologically and/or histopathologically proved in 94.8% cases: by finding of acid-resistant bacilli in sputum and other biological materials in 69 patients (72%), by positive Löwenstein's cultures in 73 patients (76%) and by histopathological result of tuberculosis inflammation in 34 patients (35.4%). In group II tuberculosis was bacteriologically and/or histopathologically proved in 134 patients (63%) by acid-resistant bacilli in sputum and other biological materials, in 141 patient (66%) by positive Löwenstein's culture and in 71 patient by positive histopathological results. Pulmonary tuberculosis in war areas is characterized by greater frequency of severe clinical forms (cavernous, bilateral and extensive) and by high direct bacillarity.


[Proximal migration of pancreatic "pig tail" stent--a case report].
Proximal migration of pancreatic stents it's serious problem which can need the extensive surgery with following egzo- and endocrine insufficiency. Therefore the possibility of endoscopic solution of mentioned problem is very important. The purpose of this publication is presentation the case of proximal migration "pig tail" pancreatic stent and endoscopic technique removal it. Simultaneously was executed the literature review relating to factors influencing on migration, and also the endoscopic methods enabling the solution of presented complication.


Synthesis and characterization of recombinant abductin-based proteins.
Recombinant proteins are promising tools for tissue engineering and drug delivery applications. Protein-based biomaterials have several advantages over natural and synthetic polymers, including precise control over amino acid composition and molecular weight, modular swapping of functional domains, and tunable mechanical and physical properties. In this work, we describe recombinant proteins based on abductin, an elastomeric protein that is found in the inner hinge of bivalves and functions as a coil spring to keep shells open. We illustrate, for the first time, the design, cloning, expression, and purification of a recombinant protein based on consensus abductin sequences derived from Argopecten irradians . The molecular weight of the protein was confirmed by mass spectrometry, and the protein was 94% pure. Circular dichroism studies showed that the dominant structures of abductin-based proteins were polyproline II helix structures in aqueous solution and type II β-turns in trifluoroethanol. Dynamic light scattering studies illustrated that the abductin-based proteins exhibit reversible upper critical solution temperature behavior and irreversible aggregation behavior at high temperatures. A LIVE/DEAD assay revealed that human umbilical vein endothelial cells had a viability of 98 ± 4% after being cultured for two days on the abductin-based protein. Initial cell spreading on the abductin-based protein was similar to that on bovine serum albumin. These studies thus demonstrate the potential of abductin-based proteins in tissue engineering and drug delivery applications due to the cytocompatibility and its response to temperature.


Evaluation of patients with recurrent symptoms after ulnar nerve transposition.
Focal entrapment of the ulnar nerve occurs most frequently in the region of the elbow, at the ulnar groove or beneath the humeroulnar aponeurosis. Surgical treatment commonly involves transposition of the nerve anterior to the medial epicondyle, in the antecubital fossa. Symptoms may recur after surgery, and, to assess their etiology, we studied 10 patients with recurrent ulnar symptoms after transposition. Conventional motor and sensory conduction studies were performed, as was mapping of nerve position using submaximal stimuli. In 9 of 10 patients, the ulnar nerve at the elbow was located adjacent to the medial epicondyle, rather than in the antecubital fossa. Focal slowing in the region of the elbow was noted in 8 patients, and an additional site of focal slowing was found in the forearm in 3 patients. We conclude that in patients with recurrent symptoms after ulnar nerve transposition postoperative position of the ulnar nerve may be medial, often near the medial epicondyle. This location may predispose the nerve to recurrent trauma or cause traction on the nerve at more distal locations within the forearm. The prevalence of this medial location of the ulnar nerve in asymptomatic postsurgical patients is unknown.


The angiogenic related functions of bone marrow mesenchymal stem cells are promoted by CBDL rat serum via the Akt/Nrf2 pathway.
Hepatopulmonary syndrome (HPS) is a complication of severe liver disease. It is characterized by an arterial oxygenation defect. Recent studies have demonstrated that pulmonary angiogenesis contributes to the abnormal gas exchange found in HPS. Additionally, mesenchymal stem cells (MSCs) are considered the stable source of VEGF-producing cells and have the potential to differentiate into multiple cell types. However, it has not been determined whether bone marrow mesenchymal stem cells (BM-MSCs) are mobilized and involved in the pulmonary angiogenesis in HPS. In this study, a CFU-F assay showed that the number of peripheral blood MSCs was increased in common bile duct ligation (CBDL) rats; however, there was no significant difference found in the number of BM-MSCs. In vitro, CBDL rat serum induced the overexpression of CXCR4 and PCNA in BM-MSCs. Consistently, the directional migration as well as the proliferation ability of BM-MSCs were enhanced by CBDL rat serum, as determined by a transwell migration and MTT assays. Moreover, the secretion of VEGF by BM-MSCs increased after treatment with CBDL rat serum. We also found that the expression of phospho-Akt, phospho-ERK, and Nrf2 in BM-MSCs was significantly up-regulated by CBDL rat serum in a time dependent manner, and the blockage of the Akt/Nrf2 signalling pathway with an Akt Inhibitor or Nrf2 siRNA, instead of an ERK inhibitor, attenuated the migration, proliferation and paracrine capacity of BM-MSCs. In conclusion, these findings indicated that the number of MSCs increased in the peripheral blood of CBDL rats, and the Akt/Nrf2 pathway plays a vital role in promoting the angiogenic related functions of BM-MSCs, which could be a potent contributor to pulmonary angiogenesis in HPS.


Incidence of Childhood Leukemia in Iraq, 2000-2019.
Leukemia is a major concern for children worldwide. Around 30% of malignancies in children (ages 0-14) are caused by leukemia. This study aims to explore the time trends in the incidence of childhood leukemia (aged 0-14 years) in Iraq between 2000 and 2019. Poisson regression with a log link function was used to analyze the long-term trends of incidence related to childhood leukemia cancer based on published data from the Iraqi cancer registry between 2000 and 2019. Annual estimates of the population, by 5-year age groups and by gender obtained from the United Nations, population Division. A total of 8,570 cases of leukemia children in Iraq between 2000 and 2019 were recorded, the boys to girl ratio were 1.32 to 1. The most diagnosed type of leukemia was Acute lymphoblastic leukemia, accounting for about 33.56%, followed by Leukemia Not specify (NOS) (17.3%) with a relatively equal proportion of stated instances between boys and girls in these subsets. The age-standardized incidence rates, aged 0-14 years, from 2000-2019 were 3.45/100,000 for both genders. The Joinpoint regression ASRs analysis of childhood leukemia from 2000-2019 among 0 -14 age group for both genders indicate that there was an overall significant increasing trend at 1.23% per year, while no one joinpoint was identified during the entire study period. Among boys, there was an overall insignificant increasing trend at 0.77% per year. Among girls, there was an overall significant increasing trend at 1.93% per year, while one joinpoint was identified during the entire study period. Conclusions: The overall (both genders) incidence rate of childhood leukemia has been increasing significantly in Iraq. The test for trends was insignificant among boys, while it was significant among girls. The increasing trend of leukemia requires further epidemiological studies to describe incidence by geography in Iraq.


A continuous pathway for fresh water along the East Greenland shelf.
Export from the Arctic and meltwater from the Greenland Ice Sheet together form a southward-flowing coastal current along the East Greenland shelf. This current transports enough fresh water to substantially alter the large-scale circulation of the North Atlantic, yet the coastal current's origin and fate are poorly known due to our lack of knowledge concerning its north-south connectivity. Here, we demonstrate how the current negotiates the complex topography of Denmark Strait using in situ data and output from an ocean circulation model. We determine that the coastal current north of the strait supplies half of the transport to the coastal current south of the strait, while the other half is sourced from offshore via the shelfbreak jet, with little input from the Greenland Ice Sheet. These results indicate that there is a continuous pathway for Arctic-sourced fresh water along the entire East Greenland shelf from Fram Strait to Cape Farewell.


Hemorrhagic bullae caused by Bacteroides fragilis in a patient with intra-abdominal infection.
Skin manifestations due to intra-abdominal infection are uncommon but could be a warning sign of severe infection. We report a 58-year-old uremic female who had acute cholecystitis and pneumatosis intestinalis. She developed periumbilical hemorrhagic bullae and finally had a fatal outcome with medical therapy. Severe intra-abdominal infection such as pneumatosis intestinalis should be suspected when periumbilical bullae increase in size.


Interpretation of Compound Activity Predictions from Complex Machine Learning Models Using Local Approximations and Shapley Values.
In qualitative or quantitative studies of structure-activity relationships (SARs), machine learning (ML) models are trained to recognize structural patterns that differentiate between active and inactive compounds. Understanding model decisions is challenging but of critical importance to guide compound design. Moreover, the interpretation of ML results provides an additional level of model validation based on expert knowledge. A number of complex ML approaches, especially deep learning (DL) architectures, have distinctive black-box character. Herein, a locally interpretable explanatory method termed Shapley additive explanations (SHAP) is introduced for rationalizing activity predictions of any ML algorithm, regardless of its complexity. Models resulting from random forest (RF), nonlinear support vector machine (SVM), and deep neural network (DNN) learning are interpreted, and structural patterns determining the predicted probability of activity are identified and mapped onto test compounds. The results indicate that SHAP has high potential for rationalizing predictions of complex ML models.


Feasibility and safety of a pilot randomized trial of infection rate: neutropenic diet versus standard food safety guidelines.
The neutropenic diet is an intervention that excludes certain foods, especially fresh fruits and vegetables, from the diets of pediatric oncology patients to reduce infection rate. The purpose of this study was to demonstrate a safe and feasible methodology to evaluate the infection rate in pediatric cancer patients randomized to the neutropenic diet or to Food and Drug Administration (FDA)-approved food safety guidelines. Pediatric oncology patients receiving myelosuppressive chemotherapy were randomized to the neutropenic diet or to FDA food safety guidelines and followed through one chemotherapy cycle. The primary outcome was febrile neutropenia. Secondary outcomes were adherence and diet tolerability. Nineteen patients were enrolled. Four patients on each diet arm developed febrile neutropenia. The adherence rate was 94% for the neutropenic diet and 100% for the food safety guidelines. Although patients were able to tolerate both diets, there was more reported difficulty adhering to the neutropenic diet. Infection rates for children with cancer on the neutropenic diet were similar to those for patients following food safety guidelines. The results of this study suggest that a larger randomized trial to determine the effectiveness of food safety guidelines in minimizing the risk of food borne infection is safe and feasible in children with cancer.


Identification of IgE-binding peptide and critical amino acids of Jatropha curcas allergen involved in allergenic response.
Increasing energy demand has spurred interest in the use of biofuels. Jatropha curcas (physic nut), an inedible oilseed, is a potential source of bioenergy. The seeds, however, contain allergens such as Jat c 1, a 2S albumin that can induce hypersensitivity reactions in humans and result in allergic diseases. Recent advances in identifying and characterizing plant allergens and, in particular, their immunoglobulin E (IgE)-binding epitopes have produced a wealth of information. We identified IgE-binding regions and the critical amino acids involved in the degranulation of mast cells and the release of histamine, preliminary steps for the prevention and treatment of this allergy. Four IgE-binding regions were identified in the sequence of Jat c 1. We identified and demonstrated the fundamental role of two glutamic acid residues in IgE binding. The sequence LEKQLEEGEVGS produces a random loop on the most exposed part of Jat c 1. This region is important to the stimulation of the allergic response. The possibility of using this information to produce vaccines and other pharmacological agents for allergy treatment is discussed.


Estimation of Trunk Muscle Forces Using a Bio-Inspired Control Strategy Implemented in a Neuro-Osteo-Ligamentous Finite Element Model of the Lumbar Spine.
Low back pain (LBP), the leading cause of disability worldwide, remains one of the most common and challenging problems in occupational musculoskeletal disorders. The effective assessment of LBP injury risk, and the design of appropriate treatment modalities and rehabilitation protocols, require accurate estimation of the mechanical spinal loads during different activities. This study aimed to: (1) develop a novel 2D beam-column finite element control-based model of the lumbar spine and compare its predictions for muscle forces and spinal loads to those resulting from a geometrically matched equilibrium-based model; (2) test, using the foregoing control-based finite element model, the validity of the follower load (FL) concept suggested in the geometrically matched model; and (3) investigate the effect of change in the magnitude of the external load on trunk muscle activation patterns. A simple 2D continuous beam-column model of the human lumbar spine, incorporating five pairs of Hill's muscle models, was developed in the frontal plane. Bio-inspired fuzzy neuro-controllers were used to maintain a laterally bent posture under five different external loading conditions. Muscle forces were assigned based on minimizing the kinematic error between target and actual postures, while imposing a penalty on muscular activation levels. As compared to the geometrically matched model, our control-based model predicted similar patterns for muscle forces, but at considerably lower values. Moreover, irrespective of the external loading conditions, a near (<3°) optimal FL on the spine was generated by the control-based predicted muscle forces. The variation of the muscle forces with the magnitude of the external load within the simulated range at the L1 level was found linear. This work presents a novel methodology, based on a bio-inspired control strategy, that can be used to estimate trunk muscle forces for various clinical and occupational applications toward shedding light on the ever-elusive LBP etiology.


Characteristics other than the diagnostic criteria associated with metabolic syndrome: an overview.
Metabolic syndrome (MetS), a cluster of dyslipidaemia, central obesity, hypertension and/or insulin resistance, is associated with increased cardiovascular disease (CVD) type 2 diabetes risk. Different diagnostic criteria for MetS have been proposed but in 2009 a joint statement by several scientific societies was released. Apart from the diagnostic criteria, MetS has also been associated with other risk factors including waist to hip ratio, high density lipoprotein dysfunction, small dense low density lipoprotein, postprandial hypertriglyceridaemia, lipoprotein (a), uric acid, liver function tests, prothrombotic factors, cytokines, adipokines, vitamin D, arterial stiffness, renal dysfunction, nephrolithiasis, polycystic ovary syndrome, obstructive sleep apnea. We discuss the extensive list of MetS-associated factors that may influence vascular risk. Furthermore, we discuss the impact of frequently prescribed drugs (e.g. hypolipidaemic agents) on these variables. These effects may need to be taken into consideration when treating MetS patients.


Lymphatic vessel density and vascular endothelial growth factor-C expression correlate with malignant behavior in human pancreatic endocrine tumors.
Metastatic dissemination of tumor cells to regional lymph nodes is a common early feature of many human cancers including pancreatic adenocarcinoma. In contrast, lymph node metastasis is more variably observed in pancreatic endocrine tumors. The objective of this study was to assess the lymphatic system of human pancreatic endocrine tumors and correlate this to clinical behavior. Immunohistochemistry was performed using antibodies to two recently identified markers of lymphatic endothelium, namely, LYVE-1 and podoplanin, and to the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C. As has been reported previously, we observed that in the normal pancreas, islets of Langerhans are devoid of intra-islet lymphatics, but that lymphatics are present in connective tissue in association with ducts and blood vessels. We found that both benign and malignant pancreatic endocrine tumors contain intratumoral lymphatic vessels. Lymphatic vessel density was related to the size of the tumor in benign tumors and to the presence of liver metastasis but not to lymph node metastasis in malignant tumors. VEGF-C was expressed in tumor cells: 4 of 19 (21%) benign tumors were positive, whereas 6 of 9 (67%) borderline tumors and 9 of 11 (82%) carcinomas were positive. These findings strongly suggest that lymphangiogenesis occurs in pancreatic endocrine tumors and that lymphatic invasion and the development of metastases are associated with VEGF-C expression.


Models of delivering palliative and end-of-life care in India.
India is home to one-fifth of the global population. This review aims to explore the structures, functions and relevance of palliative care services in India. Although palliative care has been initiated in India almost 3 decades ago, development of services has been patchy and inadequate. Some of the regions are well covered, but most are not. The Indian palliative care scene, with its diversity in approach and delivery of services, can offer valuable lessons to service development in low-income and middle-income countries. The number of people dying each year in India is more than 9.8 million. The number of people in need of palliative care will be around six million if we assume that 60% of all those who die would benefit from palliative care. Less than 2% of the needy have access to palliative care in India. The available services are very unevenly distributed with the state of Kerala with 3% of the country's population having more than 90% of the palliative care services in the country. The state of palliative care in India is discussed with particular attention to the successful Kerala Model in palliative care. Lessons learned from the experiment in Kerala are listed.