Monitoring progress towards the first UNAIDS 90-90-90 target in key populations living with HIV in Norway.
In line with the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, Norway aims for at least 90% of people living with HIV (PLHIV) to know their HIV-status. We produced current estimates of the number of PLHIV and undiagnosed population in Norway, overall and for six key subpopulations: Norwegian-born men who have sex with men (MSM), migrant MSM, Norwegian-born heterosexuals, migrant Sub-Saharan Africa (SSA)-born heterosexuals, migrant non-SSA-born heterosexuals and people who inject drugs. We used the European Centre for Disease Prevention and Control (ECDC) HIV Modelling Tool on Norwegian HIV surveillance data through 2018 to estimate incidence, time from infection to diagnosis, PLHIV, and the number and proportion undiagnosed. As surveillance data on CD4 count at diagnosis were not collected in Norway, we ran two models; using default model CD4 assumptions, or a proxy for CD4 distribution based on Danish national surveillance data. We also generated alternative overall PLHIV estimates using the Spectrum AIDS Impact Model, to compare with those obtained from the ECDC tool. Estimates of the overall number of PLHIV in 2018 using different modelling approaches aligned at approximately 5000. In both ECDC models, the overall number undiagnosed decreased continuously from 2008. The proportion undiagnosed in 2018 was lower using default model CD4 assumptions (7.1% [95%CI: 5.3-8.9%]), than the Danish CD4 proxy (10.2% [8.3-12.1%]). This difference was driven by results for heterosexual migrants. Estimates for Norwegian-born MSM, migrant MSM and Norwegian-born heterosexuals were similar in both models. In these three subpopulations, incidence in 2018 was < 30 new infections, and the number undiagnosed had decreased in recent years. Norwegian-born MSM had the lowest estimated number of undiagnosed infections (45 [30-75], using default CD4 assumptions) and undiagnosed fraction (3.6% [2.4-5.7%], using default CD4 assumptions) in 2018. Results allow cautious confidence in concluding that Norway has achieved the first UNAIDS 90-90-90 target, and clearly highlight the success of prevention strategies among MSM. Estimates for subpopulations strongly influenced by migration remain less clear, and future modelling should appropriately account for all-cause mortality and out-migration, and adjust for time of in-migration.


Alteration of epidermal growth factor-dependent phosphorylation during rat liver regeneration.
Epidermal growth factor (EGF) stimulates membrane protein phosphorylation in a human cell line, A-431. The known hepatic mitogenic action of EGF and the reduction in EGF receptor number that occurs during liver regeneration led us to study whether EGF-dependent protein kinase activity was present in rat liver and whether its activity was altered after partial hepatectomy. Liver membranes, preincubated with or without EGF, were phosphorylated (0 degrees C, 15 sec) and subjected to NaDodSO4/polyacrylamide gel electrophoresis and autoradiography. In microsomal fractions, EGF at 5-2000 ng/ml produced a dose-related stimulation of 32P incorporation into a single 170,000-dalton protein (p170). In plasma membranes, a similar EGF-dependent phosphorylation was present and was substantially enriched relative to the microsomal fraction. Acid hydrolysis of labeled microsomal fraction followed by phosphoamino acid determination revealed that EGF stimulated 32P incorporation into phosphotyrosine residues. The EGF-dependent phosphorylation of p170 was compared in microsomal fractions isolated from rats 36 hr after partial hepatectomy or sham operation. In the absence of EGF, in vitro labeling of p170 was similar. EGF stimulated the labeling of p170 in both groups, but the response was clearly diminished after partial hepatectomy. In the presence of EGF, the labeling of p170 in microsomal fraction from regenerating livers was only 47 +/- 6% of that observed in membranes from sham-operated rats (p less than 0.005). Reduction of EGF-dependent phosphorylation during liver regeneration paralleled the loss of binding of 125I-labeled EGF. An increase in the EGF-independent phosphorylation of a 130,000-dalton protein was also observed after partial hepatectomy. The increase in the amount of this phosphoprotein was roughly equal to the loss of EGF-stimulated p170 phosphorylation. Several additional proteins showed increased phosphorylation in membranes from partially hepatectomized rats. These findings indicate that alterations in membrane tyrosine residue phosphorylation occur during regulated growth in vivo.


IODINE-131 THYROID DOSE FROM MILK IN ITALY DURING THE PERIOD SEPTEMBER 1962 TO FEBRUARY 1963.
During the period September 1962 to February 1963, iodine-131 was measured in milk sampled in 14 Italian cities. At the end of the period the average intake was 9100 pc, corresponding to a thyroid dose of 0.31 rad; the maximum intake (at Bari) was 16,300 pc, corresponding to a thyroid dose of 0.56 rad.


Relative abdominal adiposity is associated with chronic low back pain: a preliminary explorative study.
Although previous research suggests a relationship between chronic low back pain (cLBP) and adiposity, this relationship is poorly understood. No research has explored the relationship between abdominal-specific subcutaneous and visceral adiposity with pain and disability in cLBP individuals. The aim of this study therefore was to examine the relationship of regional and total body adiposity to pain and disability in cLBP individuals. A preliminary explorative study design of seventy (n = 70) adult men and women with cLBP was employed. Anthropometric and adiposity measures were collected, including body mass index, waist-to-hip ratio, total body adiposity and specific ultrasound-based abdominal adiposity measurements. Self-reported pain and disability were measured using a Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI) questionnaires respectively. Relationships between anthropometric and adiposity measures with pain and disability were assessed using correlation and regression analyses. Significant correlations between abdominal to lumbar adiposity ratio (A-L) variables and the waist-to-hip ratio with self-reported pain were observed. A-L variables were found to predict pain, with 9.1-30.5 % of the variance in pain across the three analysis models explained by these variables. No relationships between anthropometric or adiposity variables to self-reported disability were identified. The findings of this study indicated that regional distribution of adiposity via the A-L is associated with cLBP, providing a rationale for future research on adiposity and cLBP.


Simple model of complex dynamics of activity patterns in developing networks of neuronal cultures.
Living neuronal networks in dissociated neuronal cultures are widely known for their ability to generate highly robust spatiotemporal activity patterns in various experimental conditions. Such patterns are often treated as neuronal avalanches that satisfy the power scaling law and thereby exemplify self-organized criticality in living systems. A crucial question is how these patterns can be explained and modeled in a way that is biologically meaningful, mathematically tractable and yet broad enough to account for neuronal heterogeneity and complexity. Here we derive and analyse a simple network model that may constitute a response to this question. Our derivations are based on few basic phenomenological observations concerning the input-output behavior of an isolated neuron. A distinctive feature of the model is that at the simplest level of description it comprises of only two variables, the network activity variable and an exogenous variable corresponding to energy needed to sustain the activity, and few parameters such as network connectivity and efficacy of signal transmission. The efficacy of signal transmission is modulated by the phenomenological energy variable. Strikingly, this simple model is already capable of explaining emergence of network spikes and bursts in developing neuronal cultures. The model behavior and predictions are consistent with published experimental evidence on cultured neurons. At the larger, cellular automata scale, introduction of the energy-dependent regulatory mechanism results in the overall model behavior that can be characterized as balancing on the edge of the network percolation transition. Network activity in this state shows population bursts satisfying the scaling avalanche conditions. This network state is self-sustainable and represents energetic balance between global network-wide processes and spontaneous activity of individual elements.


RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia.
The Rad50 interacting protein 1 (Rint1) is a key player in vesicular trafficking between the ER and Golgi apparatus. Biallelic variants in RINT1 cause infantile-onset episodic acute liver failure (ALF). Here, we describe 3 individuals from 2 unrelated families with novel biallelic RINT1 loss-of-function variants who presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, and dysmorphic features, broadening the previously described phenotype. Our functional and lipidomic analyses provided evidence that pathogenic RINT1 variants induce defective lipid-droplet biogenesis and profound lipid abnormalities in fibroblasts and plasma that impact both neutral lipid and phospholipid metabolism, including decreased triglycerides and diglycerides, phosphatidylcholine/phosphatidylserine ratios, and inhibited Lands cycle. Further, RINT1 mutations induced intracellular ROS production and reduced ATP synthesis, affecting mitochondria with membrane depolarization, aberrant cristae ultrastructure, and increased fission. Altogether, our results highlighted the pivotal role of RINT1 in lipid metabolism and mitochondria function, with a profound effect in central nervous system development.


Superconductivity in Alkaline Earth Metal-Filled Skutterudites BaxIr4X12 (X = As, P).
We report superconductive iridium pnictides BaxIr4X12 (X = As and P) with a filled skutterudite structure, demonstrating that Ba filling dramatically alters their electronic properties and induces a nonmetal-to-metal transition with increasing the Ba content x. The highest superconducting transition temperatures are 4.8 and 5.6 K observed for BaxIr4As12 and BaxIr4P12, respectively. The superconductivity in BaxIr4X12 can be classified into the Bardeen-Cooper-Schrieffer type with intermediate coupling.


[Working memory impairment in early Parkinson's disease patients].
To investigate the characteristics of working memory impairment in early Parkinson's disease (PD) patients and underlying neuropsychological and patho-physiological mechanisms. Thirty PD cases and 30 normal controls (NCs) were tested with modified Smith's working memory software. The correct rate of coordinate working memory in PD cases was 71.2 +/- 11.0%, significantly lower than that in the NCs (81.9% +/- 10.8%, t =3.78, P < 0.001). The correct rate of categorical working memory was 94.8 +/- 5.7% in the PD cases, not significantly different from that in the NCs (96.6% +/- 3.8%, t =1.46, P > 0.05). There is visuo-spatial working memory impairment, mainly coordinate spatial working memory impairment, in early PD patients. The categorical spatial working memory is relatively intact in early PD. It is postulated that the different working memory subsystems apply for different neurocircuits.


Virtual tabletop simulations for primary care pandemic preparedness and response.
The COVID-19 pandemic prompted widescale use of clinical simulations to improve procedures and practices. We outline our deployment of a virtual tabletop simulation (TTS) method in primary care (PC) clinics across Alberta, Canada. We summarise the quality and safety improvements from this method and report end users' perspectives on key elements. Our virtual TTS used teleconferencing software alongside digital whiteboards to walk clinic stakeholders through patient scenarios. Participants reviewed and rehearsed their workflows and care practices. The goal was for staff to take ownership over gaps and codesigned solutions. After simulation sessions, follow-up interviews were conducted to collect feedback. These sessions helped PC staff identify and codesign solutions for clinical hazards and threats. These included the flow of patients through clinics, communications, redesignation of physical spaces, and adaptation of guidance for cleaning and personal protective equipment use. End users reported sessions provided neutral spaces to discuss practice changes and built confidence in delivering safe care during the pandemic. TTS has not been extensively deployed to improve clinical practice in outpatient environments. We show how virtual TTS can bridge gaps between knowledge and practice by offering a guided space to rehearse clinical changes. We show that virtual TTS can be used in multiple contexts to help identify hazards, improve safety and build confidence in professional teams adapting to rapid changes in both policies and practices. While our sessions were conducted in Alberta, our results suggest this method may be deployed in other contexts, including low-resource settings.


The Effect of Nursing Students' Liking of Children and Attitudes Toward Clinical Practice on Their Comfort and Worry Levels in the Pediatric Clinic.
This research was conducted as a descriptive and cross-sectional study to determine the effects of nursing students' liking of children and attitudes toward clinical practice on their comfort and worry levels in the pediatric clinic. The research was carried out with 270 nursing students who had already taken or were taking the child health and diseases nursing course. Data were collected using a Nursing Student Information Form, the Barnett Liking of Children Scale, the Nursing Students' Attitudes toward Clinical Practices Scale, and the Pediatric Nursing Student Clinical Comfort and Worry Assessment Tool. Mean values, percentage calculations, and linear regression analysis were used for the analysis of the research data. Participants' mean scores were 52.30 ± 6.16 on the Barnett Liking of Children Scale, 103.72 ± 19.35 on the Nursing Students' Attitudes toward Clinical Practices Scale, 15.61 ± 3.74 on the comfort sub-dimension, and 11.63 ± 4.32 on the worry sub-dimension of the Pediatric Nursing Student Clinical Comfort and Worry Assessment Tool. It was determined that the liking of children and attitudes toward clinical practice explained 43.6% of the clinical comfort level of pediatric nursing students in Model 1 and 45.2% of their clinical worry level in Model 2. It was determined that the liking of children and attitudes toward clinical practice significantly affected the comfort and worry levels of nursing students in the pediatric clinic.


Clinical Classification, Pregnancy Outcomes and Risk Factors Analysis of Severe Preeclampsia Complicated With HELLP Syndrome.
To investigate the clinical classification, pregnancy outcomes and risk factors of pregnant women with severe preeclampsia (SPE) complicated with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. The clinical data of 50 pregnant women diagnosed with SPE complicated with HELLP syndrome in our hospital from January 2014 to January 2021 were retrospectively analyzed, and they were selected as the observation group. An additional 50 maternities diagnosed with preeclampsia (PE) during the same period were selected as the control group. The clinical classification and pregnancy outcomes of pregnant women in the observation group were recorded. The age and gestational age of onset of pregnancy were recorded and compared between the two groups. Univariate analysis and multivariate logistic regression model were used to analyze the risk factors for its occurrence. Among the 50 maternities in the observation group, there were 10 cases of type I, accounting for 20.00%; 35 cases of type II, accounting for 70.00%; 5 cases of type III, accounting for 10.00%. Partial 33 cases, the composition ratio of 66.00%; complete 17 cases, the composition ratio of 34.00%. Among the fetuses of 50 maternities in the observation group, 35 were premature, accounting for 70.00%; 13 had fetal growth restriction, accounting for 26.00%; and 2 died during perinatal period, accounting for 4.00%. Among the 50 maternities in the observation group, 48 cases were cesarean section, the composition ratio was 96.00%; 2 cases were induced labor, the composition ratio was 4.00%; there was no natural birth, the composition ratio was 0.00%. Univariate analysis showed that age, gestational age at onset, gestational age at termination of pregnancy, HGB, LDH, ALT, AST, TBIL, PLT, PT, and FIB were all associated with the occurrence of SPE complicated with HELLP syndrome (P < 0.05). Multivariate logistic analysis showed that gestational age at onset, gestational age at termination of pregnancy, HGB, LDH, ALT, AST, TBIL, PLT, and FIB were independent risk factors for SPE complicated with HELLP syndrome (P < 0.05). SPE complicated with HELLP syndrome has significantly increased adverse pregnancy outcomes. Understanding its clinical classification is of great significance for the preventive application of platelet transfusion therapy and the selection of transfusion timing. Gestational age at onset and gestational age at termination of pregnancy are independent risk factors for its occurrence. Fully understanding the high-risk factors of HELLP syndrome, taking preventive measures in time, and carrying out targeted nursing can effectively improve the prognosis of pregnant women and reduce the risk of HELLP syndrome.


Follicle-stimulating hormone promotes growth of human prostate cancer cell line-derived tumor xenografts.
Chemical castration in prostate cancer can be achieved with gonadotropin-releasing hormone (GnRH) agonists or antagonists. Their effects differ by the initial flare of gonadotropin and testosterone secretion with agonists and the immediate pituitary-testicular suppression by antagonists. While both suppress luteinizing hormone (LH) and follicle-stimulating hormone (FSH) initially, a rebound in FSH levels occurs during agonist treatment. This rebound is potentially harmful, taken the expression of FSH receptors (R) in prostate cancer tissue. We herein assessed the role of FSH in promoting the growth of androgen-independent (PC-3, DU145) and androgen-dependent (VCaP) human prostate cancer cell line xenografts in nude mice. Gonadotropins were suppressed with the GnRH antagonist degarelix, and effects of add-back human recombinant FSH were assessed on tumor growth. All tumors expressed GnRHR and FSHR, and degarelix treatment suppressed their growth. FSH supplementation reversed the degarelix-evoked suppression of PC-3 tumors, both in preventive (degarelix and FSH treatment started upon cell inoculation) and therapeutic (treatments initiated 3 weeks after cell inoculation) setting. A less marked, though significant FSH effect occurred in DU145, but not in VCaP xenografts. FSHR expression in the xenografts supports direct FSH stimulation of tumor growth. Testosterone supplementation, to maintain the VCaP xenografts, apparently masked the FSH effect on their growth. Treatment with the LH analogue hCG did not affect PC-3 tumor growth despite their expression of luteinizing hormone/choriongonadotropin receptor. In conclusion, FSH, but not LH, may directly stimulate the growth of androgen-independent prostate cancer, suggesting that persistent FSH suppression upon GnRH antagonist treatment offers a therapeutic advantage over agonist.


Aerobic exercise reduces hippocampal ERK and p38 activation and improves memory of middle-aged rats.
Aging is often accompanied by cognitive decline, memory impairment, and an increased susceptibility to neurodegenerative disorders. Although the physiological processes of aging are not fully understood, these age-related changes have been interpreted by means of various cellular and molecular theories. Among these theories, alterations in the intracellular signaling pathways associated with cell growth, proliferation, and survival have been highlighted. Based on these observations and on recent evidence showing the beneficial effects of exercise on cognitive function in the elderly, we investigated the cell signaling pathways in the hippocampal formation of middle-aged rats (18 months old) submitted to treadmill exercise over 10 days. To do this, we evaluated the hippocampal activation of intracellular signaling proteins linked to cell growth, proliferation, and survival, such as Akt, mTOR, p70S6K, ERK, CREB, and p38. We also explored the cognitive performance (inhibitory avoidance) of middle-aged rats. It was found that physical exercise reduces ERK and p38 activation in the hippocampal formation of aged rats, when compared to the control group. The hippocampal activation and expression of Akt, mTOR, p70S6K, and CREB were not statistically different between the groups. It was also observed that aged rats from the exercise group exhibited better cognitive performance in the inhibitory avoidance task (aversive memory) than aged rats from the control group. Our results indicate that physical exercise reduces intracellular signaling pathways linked to inflammation and cell death (i.e., ERK and p38) and improves memory in middle-aged rats.


Impact of cytomegalovirus serology on graft survival in living related kidney transplantation: implications for donor selection.
The impact of cytomegalovirus in living related kidney transplantation remains controversial. This study considers the implications of donor and recipient cytomegalovirus (CMV) serology for the selection of living related donor. Graft survival was estimated by using the bivariate Kaplan-Meier method and multivariate Cox proportional hazards analysis for 7659 living related first transplantations performed in the United States between 1989 and 1994. The effects of donor CMV serology were estimated with respect to recipient CMV serology and compared with human leukocyte antigen (HLA) matching, transplantation, donor, and recipient characteristics. The implications of these estimates for the selection of living related donors were considered. From Kaplan-Meier estimates, donor CMV-seropositive kidneys were associated with significantly reduced graft survival for CMV-seronegative recipients (p = 0.0002) but not CMV-seropositive recipients (p = 0.1623). These findings were verified by use of Cox proportional hazards analysis accounting for covariate factors. The impact of donor CMV-seropositive kidneys on CMV-seronegative recipients was similar to one HLA-DR match, greater than one HLA-B match, and significantly greater than one HLA-A match (p = 0.0331). Results identify donor CMV serology as an important determinant of transplantation outcome for living related first kidney transplant recipients who are themselves CMV seronegative. Consideration should be given to donor and recipient CMV serology when selecting an appropriate donor for living related kidney transplantation.


Screening for abdominal aortic aneurysm.
Most abdominal aortic aneurysms are asymptomatic, but rupture is usually fatal. Elective surgery is now a relatively safe procedure, even in the elderly. Screening to identify those harbouring an aneurysm may allow preventive surgery to be offered. To be cost-effective a population at particular risk must be selected and factors predisposing to aneurysm formation include advancing age, hypertension, arteriosclerosis and family history. The screening technique selected should be acceptable to the population, accurate and rapid. Clinical examination and abdominal radiography are both less accurate than ultrasound examination by experienced personnel. Preliminary studies have confirmed a reasonable diagnostic rate.


Endoscopic dilatation sinus surgery (FEDS) versus functional endoscopic sinus surgery (FESS) for treatment of chronic rhinosinusitis: a pilot study.
The objective of the present study was to compare the efficacy of functional endoscopic dilatation sinus surgery (FEDS) with functional endoscopic sinus surgery (FESS) in treatment of chronic rhinosinusitis in patients who failed medical therapy. We enrolled 24 patients suffering with chronic rhinosinusitis, who failed medical treatment and were proceeding to surgery, in a prospective, randomized controlled pilot study carried out between January and December 2008 following ethical committee approval. All patients completed sino-nasal outcome test (SNOT)-20 questionnaires and underwent saccharine test preoperatively and 24 weeks post operatively. Only trained surgeons performed surgery. The SNOT-20 questionnaire and saccharine clearance time (SCT) were used to measure outcomes. The SNOT-20 scores for both patient groups showed similar, consistent symptomatic improvement compared with baseline measures. SCT was reduced in both groups. No significant post-operative complications were recorded in either group. No patient in the FEDS group had any bleeding, and all were ready for discharge within hours of the procedure. Thus, FEDS is as effective as FESS in treatment of chronic rhinosinusitis. It is can be considered an additional tool in endoscopic surgery and has the potential to be undertaken as a day procedure.


Multi-scale modeling predicts a balance of tumor necrosis factor-α and interleukin-10 controls the granuloma environment during Mycobacterium tuberculosis infection.
Interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) are key anti- and pro-inflammatory mediators elicited during the host immune response to Mycobacterium tuberculosis (Mtb). Understanding the opposing effects of these mediators is difficult due to the complexity of processes acting across different spatial (molecular, cellular, and tissue) and temporal (seconds to years) scales. We take an in silico approach and use multi-scale agent based modeling of the immune response to Mtb, including molecular scale details for both TNF-α and IL-10. Our model predicts that IL-10 is necessary to modulate macrophage activation levels and to prevent host-induced tissue damage in a granuloma, an aggregate of cells that forms in response to Mtb. We show that TNF-α and IL-10 parameters related to synthesis, signaling, and spatial distribution processes control concentrations of TNF-α and IL-10 in a granuloma and determine infection outcome in the long-term. We devise an overall measure of granuloma function based on three metrics - total bacterial load, macrophage activation levels, and apoptosis of resting macrophages - and use this metric to demonstrate a balance of TNF-α and IL-10 concentrations is essential to Mtb infection control, within a single granuloma, with minimal host-induced tissue damage. Our findings suggest that a balance of TNF-α and IL-10 defines a granuloma environment that may be beneficial for both host and pathogen, but perturbing the balance could be used as a novel therapeutic strategy to modulate infection outcomes.


Synthesis and characterization of gold nanoparticles based on low generational triethylene glycol-polyamidoamine dendrimers.
Low generational polyamidoamine (PAMAM) dendrimers with triethylene glycol (TEG) core and ester groups at the surface have been synthesized and investigated as templates for preparation of gold nanoparticles (AuNPs), by reducing chloroauric acid (HAuCl4) with potassium borohydride (KBH4) in N,N-dimethylformamide (DMF). UV-vis absorption spectroscopy, fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) were used to confirm the formation of AuNPs. Stable gold nanoparticles with particle size around 10 nm were obtained and the interaction between the dendrimers and Au moieties is discussed.


The emerging field of chemical genetics: potential applications for pesticide discovery.
The use of small molecules to probe biological systems, generally described as 'chemical genetics', has grown considerably in the past 7 years, especially in areas related to human biology and therapeutics. This review describes some aspects of chemical genetics technologies that can be usefully applied to pesticide target discovery and lead generation. The chemical genetics approach (consisting of a phenotype screen, a chemical library and a robust target identification methodology) is compared with conventional and target-based screening. The outcomes of a chemical genetics approach are novel protein targets coupled with in vivo-active chemical ligands. The 'chemistry-first' paradigm of the chemical genetics approach can circumvent some of the obstacles that have emerged for the exploitation of novel but chemically unvalidated targets identified from genetic or genomic screens. Some of the advantages and challenges in using chemical genetics approaches are reviewed.


Patient and center characteristics associated with kidney transplant outcomes: a binational registry analysis.
This registry-based study evaluated the contribution of center characteristics to kidney transplant outcomes in adult first kidney transplant recipients in Australia and New Zealand between 2004 and 2014. Primary outcomes were mortality and graft failure, and secondary outcomes were transplant complications. Overall, 6970 transplants from 17 centers were included. For deceased donor transplants, 5-year patient and graft survival rates varied considerably (81.0-93.9% and 72.2-88.3%, respectively). Variations in mortality and graft failure were partially reduced after adjustment for patient characteristics (1% and 20% reductions) and more markedly reduced after adjustment for center characteristics (41% and 55% reductions). For living donor transplants, 5-year patient and graft survival rates varied (89.7-100% and 79.2-96.9%, respectively). Centers with high average total ischemic times (>14 h) were associated with higher mortality for both deceased (adjusted hazard ratio [(AHR] 2.24, 95% CI 1.21-4.13) and living donor transplants (AHR 1.76, 95% CI 1.02-3.04). Small center size (<35 new kidney transplants/year) was associated with a lower hazard of mortality for living donor kidney transplants (AHR 0.48, 95% CI 0.28-0.81). No center characteristic was associated with graft failure. The appreciable variations in deceased donor kidney transplant recipient and graft survival outcomes across centers were attributable to center effects.


[Repetitive Transcranial Magnetic Stimulation for Intractable Pain].
Electrical motor cortex stimulation (EMCS) for the treatment of pain is approved and supported by health insurance in Japan. However, EMCS requires a craniotomy, and some patients hesitate to undertake EMCS. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method of pain control, and the efficacy of rTMS has been evaluated in several studies. However, the effect of rTMS is temporary, and the response rate is 20-50 %. Therefore, it may be possible to treat intractable pain by selecting the responders and repeating rTMS. We are developing a convenient system to repeat rTMS. In December 2015, an investigator-initiated trial began with a new rTMS machine.


Effect of bombesin and related peptides on the release and action of intestinal hormones on pancreatic secretion.
1. Pancreatic volume flow as well as bicarbonate and protein secretion from pancreatic fistulas have been measured in response to i.v. infusion of graded doses of bombesin and related peptides containing the COOH-terminal fragment of the bombesin molecule in conscious dogs with intact antrum and in anaesthetized animals with antrectomy, or antrectomy and enterectomy. 2. Bombesin and related peptides given to conscious dogs produced a potent and dose-dependent increase in pancreatic protein output reaching a maximum equal to that induced by the octapeptide of cholecystokinin (OP-CCK) as well as a small rise in bicarbonate output attaining a peak amounting to about 10% of that evoked by secretin. The serum gastrin level rose progressively during the infusion of bombesin to reach a peak with the highest dose of peptide. 3. Bombesin infused i.v. in anaesthetized animals with resected antrum also evoked a marked increase in pancreatic protein secretion without significant changes in the serum gastrin level. Following the removal of the antrum and small intestine, bombesin failed to show any stimulation of the pancreatic secretion or any change in the serum gastrin level. It is concluded that the strong stimulatory action of bombesin and related peptides on pancreatic secretion cannot be entirely ascribed to the release of gastrin but might be attributed at least in part to the release of intestinal hormones, particularly CCK. 4. Atropine and the growth hormone-release inhibiting hormone (GH-RIH), which were shown to inhibit the release of CCK induced by duodenal perfusion of an amino acid mixture, also caused the inhibition of pancreatic protein secretion by bombesin but failed to affect the pancreatic response to OP-CCK. The results indicate that bombesin releases, in addition to gastrin, CCK from the gut by a mechanism largely dependent upon cholingeric innervation.


Computed tomographic findings of syphilitic aortitis.
We describe the computerized tomographic (CT) findings of the aortic wall in a case of acute-phase syphilitic arteritis. The delayed phase of the contrast-enhanced CT shows a double-ring configuration of the thick thoracic aortic wall, which is similar to CT findings previously reported for Takayasu arteritis. We speculate that the resemblance of the CT findings for these two diseases accounts for their similar histopathological features.


[Use of glucocorticoids in prevention of the respiratory distress syndrome].
The authors made a review of the literature on the use of glucocorticoids in the prevention of respiratory distress syndrome of the neo-natal, emphasizing the mechanism of action, dosage, metabolic and adverse effects of the drug on both mother and fetus.


Fungal peritonitis complicating peritoneal dialysis: report of 18 cases and analysis of outcomes.
Fungal peritonitis is a significant cause of morbidity and mortality in patients undergoing peritoneal dialysis (PD). This retrospective study evaluated patients with fungal peritonitis in our dialysis unit from December 1999 through September 2003. We analyzed the demographic and clinical characteristics of patients to identify possible risk factors. Main clinical outcomes of interest were technique survival and mortality. During the study period, 18 patients were diagnosed with fungal peritonitis (15 on continuous ambulatory PD, 3 on automated PD). Fungal peritonitis accounted for 6% of all peritonitis episodes during the study period. Candida species were the infecting organism in 15 patients (83%). All 18 patients received antifungal treatment according to the International Society of Peritoneal Dialysis (ISPD) recommendations that were current during the study period. Two patients (11%) died with the PD catheter in situ, and 1 patient died after dialysis was withdrawn because of deterioration in other comorbid conditions. All the surviving patients were switched to hemodialysis. Of the 18 patients, 15 (83%) had history of antibiotic treatment for bacterial peritonitis within the 4 weeks preceding the fungal peritonitis episode. Our study provides further support for the current ISPD recommendation that the PD catheter should be removed as soon as a diagnosis of fungal peritonitis is made in a patient.


Visual failure and sinus thrombosis following depressed skull fracture: management with single session lumboperitoneal shunt and sinus decompression -case report.
Elevation of a depressed skull fracture (DSF) overlying a venous sinus is generally avoided due to risk of sinus injury. Rarely, the sinus may be compressed by the fractured segment, causing intracranial hypertension (IH) or encephalopathy and can only be diagnosed with cerebral angiography or MR imaging techniques. The posterior third of the superior sagittal sinus (SSS) was found involved in all the reported cases. There is no consensus on its management, but most patients did not have any sinus thrombosis and improved after elevation of the compressing DSF alone. There are isolated reports of improvement with serial lumbar punctures or ventriculoperitoneal shunt.We report for the first time, a single session lumboperitoneal shunt and DSF elevation for a patient with thrombosis of the posterior part of SSS due to an overlying DSF, causing florid papilledema and impending blindness. Elevation of the DSF alone would not have achieved patency of the thrombosed sinus immediately to save his vision. Hence a lumboperitoneal shunt was done for immediate relief of IH. This CSF diversion alone was insufficient to achieve patency of the thrombosed sinus in the presence of significant external compression by the DSF; even if anticoagulants were used. Hence we elevated the DSF after craniotomy using a technical modification; by making a wide gutter circumferentially around the DSF with a high speed drill, to avoid sinus injury; prior to its elevation. The patient's vision improved in 48 hours and anticoagulants were used till 2 months when sinuses were found normal on MRI. Serial CT &MR images showing progression to thrombosis and recovery after decompression are presented. Both CSF diversion and DSF elevation are necessary when vision is threatened by IH due to sinus thrombosis with an overlying DSF.


Bcl-2-associated transcription factor 1 interacts with fragile X-related protein 1.
The absence of fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), which is the leading cause of hereditary mental retardation. Fragile X-related protein 1 (FXR1P), which plays an important role in normal muscle development, is one of the two autosomal paralogs of FMRP. To understand the functions of FXR1P, we screened FXR1P-interacting proteins by using a yeast two-hybrid system. The fragile X-related gene 1 (FXR1) was fused to pGBKT7 and then used as the bait to screen the human fetal brain cDNA library. The screening results revealed 10 FXR1P-interacting proteins including Bcl-2-associated transcription factor 1 (BTF). The interaction between FXR1P and BTF was confirmed by using both β-galactosidase assay and growth test in selective media. Co-immunoprecipitation assay in mammalian cells was also carried out to confirm the FXR1P/BTF interaction. Moreover, we confirmed that BTF co-localized with FXR1P in the cytoplasm around the nucleus in rat vascular smooth muscle cells by using confocal fluorescence microscopy. These results provide clues to elucidate the relationship between FXR1P and FXS.


Overexpression of MMP14 predicts the poor prognosis in gastric cancer: Meta-analysis and database validation.
Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite conclusion has been obtained for the contradictory results. We searched PubMed, Web of science, Embase, and Cochrane library for eligible studies. The association between MMP14 expression and prognostic outcomes of GC was evaluated. Hazard ratio (HR) and 95% confidence interval (CI) were integrated to show the effect of MMP14 expression on the overall survival (OS) or recurrence-free survival (RFS). Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to validate the association of MMP14 expression with OS or RFS in GC. A brief bioinformatics analysis was also performed to determine the prognostic role of MMP14 expression in GC. High MMP14 expression was associated with shorter OS compared to low MMP14 expression in GC (HR = 1.95, P < .01). Patients with high MMP14 expression tended to have worse differentiation (P = .03), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), earlier distant metastasis (P < .01) and more advanced clinical stage (P < .01) compared to those with low MMP14 expression. The data from TCGA and GEO showed MMP14 was overexpressed in tumor tissues compared to normal tissues (P < .05), and high MMP14 expression was significantly related to shorter OS (HR = 1.70, 95% CI = 1.32-2.20, P < .01) and RFS (HR = 1.45, 95% CI = 1.15-1.83, P < .01) compared to low MMP14 expression in GC. Expression of MMP14 was linked to functional networks involving the biological process, metabolic process, response to stimulus, cell communication and so on. Functional network analysis suggested that MMP14 regulated the protein digestion and absorption, extracellular matrix receptor interaction, focal adhesion, ribosome, spliceosome, and so on. High MMP14 expression was associated with worse prognosis of GC compared to low MMP14 expression. MMP14 expression could serve as a prognostic factor and potential therapeutic target of GC.


Gene Expression, Oxidative Stress, and Senescence of Primary Coronary Endothelial Cells Exposed to Postprandial Serum of Healthy Adult and Elderly Volunteers after Oven-Cooked Meat Meals.
Epidemiological studies have linked high consumption of meat with major age-related diseases including cardiovascular diseases. Abnormal postprandial increases in plasma lipids after a meat meal have been hypothesized among the pathogenetic mechanisms. However, it is still unknown if the postprandial serum derived after a normal meat meal is able to affect endothelial function, and if the type of meat and the age of the donors are critical factors. Here, we show the effects of postprandial sera derived from healthy adults and elderly volunteers who consumed meat meals on human coronary artery endothelial cell (HCAEC) oxidative stress, gene expression, DNA damage, and cellular senescence. We observed that a single exposure to postprandial serum induces a slight increase in ROS that is associated with modulation of gene expression pathways related to oxidative stress response and metabolism. The postprandial-induced increase in ROS is not associated with a measurable DNA oxidative damage. However, repeated exposure to postprandial serum induces an acceleration of cellular senescence. Taking into account the deleterious role of cellular senescence in age-related vascular diseases, the results suggest a new mechanism by which excessive meat consumption and time spent in postprandial state may affect health status during aging.


Anticoagulation strategies for treatment of ischemic stroke and antiphospholipid syndrome: case report and review of the literature.
A 49-year-old Caucasian man with antiphospholipid syndrome who experienced an ischemic stroke required multidisciplinary decisions regarding acute and long-term care. The patient first received warfarin and unfractionated heparin, followed by low-molecular-weight heparin. However, he developed complications from these drugs (warfarin-induced necrosis and heparin-induced thrombocytopenia), resulting in thigh necrosis and multiple additional cerebral and peripheral infarcts. His condition improved after warfarin and the heparins were discontinued, and a direct thrombin inhibitor, argatroban, was given intravenously for acute treatment. Argatroban is the only anticoagulant known to be safe in patients who experience an acute ischemic stroke in the setting of heparin-induced thrombocytopenia. For long-term anticoagulation, fondaparinux, an indirect, selective factor Xa inhibitor, was given subcutaneously. The patient received intravenous dexamethasone, later changed to azathioprine, for immunomodulatory treatment. He had significant improvement in his neurologic deficits without recurrent events over the next 18 months. Management of anticoagulation therapy in patients with antiphospholipid syndrome is complex and challenging, and therapeutic strategies need to be evaluated further.


Uncompacted lamellae in three patients with POEMS syndrome.
Three patients with POEMS syndrome were studied: two of them had myeloma, whereas the third had M protein without myeloma. Peripheral nerve biopsies showed no deposits of anti-Ig sera at direct immunopathological examination. Ultrastructural study revealed myelino-axonal degeneration in all three cases. This was associated in the first case with a dramatic loss of myelinated fibers and there were lesions consistent with acute degeneration in the second case. In addition, all three had some fibers showing uncompacted myelin lamellae. This peculiar modification has previously been reported only in cases of dysglobulinemia, lymphoma and inflammatory demyelinating polyneuropathy, but its mode of formation remains unclear.


Using genetically engineered mouse models of cancer to aid drug development: an industry perspective.
Recent developments in the generation and characterization of genetically engineered mouse models of human cancer have resulted in notable improvements in these models as platforms for preclinical target validation and experimental therapeutics. In this review, we enumerate the criteria used to assess the accuracy of various models with respect to human disease and provide some examples of their prognostic and therapeutic utility, focusing on models for cancers that affect the largest populations. Technological advancements that allow greater exploitation of genetically engineered mouse models, such as RNA interference in vivo, are described in the context of target and drug validation. Finally, this review discusses stratagems for, and obstacles to, the application of these models in the drug development process.


Investigations of flow and pressure distributions in physical model of the circle of Willis.
The paper presents the results of experiments concerning flow in the model of cerebral supplying arteries and the circle of Willis (CW). Vascular phantom was prepared on the basis of anatomical specimens. The most typical artery shapes and dimensions were considered. Pressure distribution in six characteristic points is provided, and so are the average flow rates in the anterior, middle and posterior section of the brain. Tests were run in the conditions replicating the physiological state (i.e. when the supplying arteries were fully patent) and in pathological conditions, in which the internal carotid and vertebral arteries were occluded on one or both sides. Thus obtained results were compared with the results of computer simulations based on linear and non-linear flow models. To estimate the non-linear resistance of vascular segment two phenomenological formulae were proposed. High degree of correlation between the values obtained from experiments and those registered in non-linear computer model proves usefulness of proposed formulae. It verifies the hypothesis that non-linearity of flow characteristics of the vessel segments to a great extent is caused by their tortuousity and small length in relation to diameter. Non-linear effects are particularly pronounced in conditions of pathological occlusion of supplying vessels.


First trimester diagnosis of 13q-syndrome associated with increased fetal nuchal translucency thickness. Clinical findings and systematic review.
13q-syndrome is a rare chromosomal disorder caused by partial deletion of the long arm of chromosome 13 with variable phenotypic presentation. Further sonographic features involve fetal growth restriction, bradycardia, encephalocele, facial dysmorphism and upper extremity deformity. We report a case of 13q-syndrome presenting as increased nuchal translucency diagnosed by chromosome studies and confirmed by array comparative genomic hybridization (CGH) analysis in the first trimester of pregnancy. Pregnancy was terminated at 14 weeks' gestation. The parents did not give consent for a postmortem examination. Furthermore we performed a systematic review of the international literature on previous cases of 13q-syndrome diagnosed prenatally. Our case emphasizes the importance of a detailed 11-14 week ultrasound assessment in diagnosing fetal chromosomal aberrations in combination with the modern aspects of array CGH, thus providing more precise and rapid prenatal diagnosis.


Driver Injury from Vehicle Side Impacts When Automatic Emergency Braking and Active Seat Belts Are Used.
As an advanced driver assistance system, automatic emergency braking (AEB) can effectively reduce accidents by using high-precision and high-coverage sensors. In particular, it has a significant advantage in reducing front-end collisions and rear-end accidents. Unfortunately, avoiding side collisions is a challenging problem for AEB. To tackle these challenges, we propose active seat belt pretensioning on driver injury in vehicles equipped with AEB in unavoidable side crashes. Firstly, records of impact cases from China's National Automobile Accident In-Depth Investigation System were used to investigate a scenario in which a vehicle is impacted by an oncoming car after the vehicle's AEB system is triggered. The scenario was created using PreScan software. Then, the simulated vehicles in the side impact were devised using a finite element model of the Toyota Yaris and a moving barrier. These were constructed in HyperMesh software along with models of the driver's side seatbelt, side airbag, and side curtain airbag. Moreover, the models were verified, and driver out-of-position instances and injuries were evaluated in simulations with different AEB intensities up to 0.7 g for three typical side impact angles. Last but not least, the optimal combination of seatbelt pretensioning and the timing thereof for minimizing driver injury at each side impact angle was identified using orthogonal tests; immediate (at 0 ms) pretensioning at 80 N was applied. Our experiments show that our active seatbelt with the above parameters reduced the weighted injury criterion by 5.94%, 22.05%, and 20.37% at impact angles of 90°, 105°, and 120°, respectively, compared to that of a conventional seatbelt. The results of the experiment can be used as a reference to appropriately set the collision parameters of active seat belts for vehicles with AEB.


Cross-sectional study on occupational noise and hypertension in the workplace.
To determine whether noise conditions at the workplace are associated with hypertension in Japanese male blue-collar workers, the authors analyzed data obtained in an annual workplace health examination. Two hundred forty-two workers who used ear protectors at their jobs in a paper manufacturing plant served as a noisy workplace group, and 173 individuals who worked in a chemical plant comprised a nonnoisy workplace group. The prevalence of hypertension was 16.9% in the noisy workplace group and 34.7% in the nonnoisy workplace group (p < .01). A Mantel-Haenzel analysis showed the difference between the 2 groups to be significant. A logistic regression analysis with adjustment for confounding factors also showed a significant inverse association between hypertension and noise conditions at the workplace (odds ratio = 0.48; 95% confidence interval = 0.28-0.81). The implementation of guidelines for occupational noise management might have contributed to the workers' concern over the prevention of adverse health effects caused by workplace noise.


Penicillium marneffei--an indicator disease of AIDS: a case report.
Penicillium marneffei (PM), the only dimorphic species of the genus penicillium is the etiological agent of penicilliosis marneffei. This opportunistic fungal infection occurs among human immunodeficiency virus (HIV) infected and other immunocompromised patient in several regions of South-east Asia, where the infection is considered as an indicator disease of AIDS. A case of penicilliosis marneffei is reported in a patient whose HIV status was unknown and later turned to be in the late stage of AIDS. This demonstrates that it is indeed an indicator disease of AIDS. In India, penicilliosis has been reported among the inhabitants of Manipur state where the prevalence of HIV infection / AIDS is very high. The causative agent was first isolated from a captive bamboo rat. Investigation of the prevalence of the organism among bamboo rats of different countries of South East Asia revealed four species of bamboo rats to be harboring the organism. These four species of bamboo rats are Rhizomys sinensis, R. pruinosus, R. sumatrensis and Cannomys badius. In Manipur, Penicillium marneffei has been isolated from Cannomys badius. Any patient presenting with penicilliosis marneffei should be subjected to HIV counselling and testing if the HIV status is not known and further study regarding the ecology and epidemiology of the fungus is needed.


Intramedullary hemorrhage caused by spinal cord hemangioblastoma: a case report.
Hemorrhage caused by spinal cord hemangioblastoma is rare, usually presenting as a subarachnoid hemorrhage. Intramedullary hemorrhage is an extremely rare manifestation of spinal cord hemangioblastoma. Forty-year-old Japanese male patient presented with acute paraplegia. Magnetic resonance (MR) imaging of the spinal cord revealed intramedullary hemorrhage. An intramedullary mass lesion was detected at the 8th thoracic vertebral level (T8) in a gadolinium enhanced-MR image. Spinal angiography revealed an intramedullary tumor stain at the level of T8. Therefore we diagnosed the problem as intramedullary hemorrhage caused by the hemangioblastoma. One month after the onset, extirpation of the intramedullary hemangioblastoma was performed. The tumor was completely removed. Pathological findings revealed a typical hemangioblastoma. At his final follow-up visit, the patient showed no apparent neurological recovery. Hemangioblastoma can be a cause of intramedullary hemorrhage should be considered in such cases.


Continuous electrocardiography for detecting atrial fibrillation beyond 1 year after stroke in primary care.
The diagnostic benefit of using continuous ECG (cECG) for poststroke atrial fibrillation (AF) screening in a primary care setting is unclear. We aimed to assess the diagnostic yield from screening patients who previously had a stroke with a 7-day Holter monitor. Patients older than 49 years, naive to AF, with an ischaemic stroke over 1 year before enrolment were included. In a primary care setting, all patients were screened for AF using pulse palpation, 12-lead ECG and 7-day Holter monitoring. Further, NT-proBNP was determined at baseline. 7-day Holter monitoring uncovered AF in 17 of 366 patients (4.6% (95% CI 2.7 to 7.3)). The number needed to screen was 22 patients (14-37). 12-lead ECG uncovered AF in 3 patients (0.82% (95% CI 0.17 to 2.4)), and 122 patients had irregular pulse during pulse palpation (33.5% (95% CI 28.7 to 38.2)). When using 7-day Holter monitoring as reference standard, the sensitivity of pulse palpation and 12-lead ECG was 47% (95% CI 23% to 72%) and 18% (95% CI 4% to 43%). High levels (≥400 pg/mL) of NT-proBNP versus low levels (≤200 pg/mL) were not associated with AF in the univariate analysis nor when adjusted for age (OR 2.4 (95% CI 0.5 to 8.4) and 1.6 (95% CI 0.3 to 6.0)). A relevant proportion of patients with stroke more than 1 year before inclusion were diagnosed with AF through 7-day Holter monitoring. Given the low sensitivities of pulse palpation and 12-lead ECG, additional cECG may be considered during poststroke primary care follow-up.


Assessment of pasteurisation of milk and cream produced by on-farm dairies using a fluorimetric method for alkaline phosphatase activity.
The alkaline phosphatase test is used as an indicator of adequate pasteurisation of milk and cream. A proprietary fluorimetric technique (Fluorophos) is a sensitive and quantitative method for the determination of alkaline phosphatase (ALP) activity in milk products. Currently, adequate pasteurisation of milk products is regarded as confirmed in samples that contain a residual bovine ALP activity of < or =500 mU/litre. This is equivalent to the statutory acceptable level of 4ug phenol/ml required by the EC analytical method. The purpose of the present study was to assess the effectiveness of pasteurisation of milk and cream produced by on-farm dairies. In a longitudinal study over a four-year period, 4,999 samples of milk and cream were collected from 130 on-farm dairies and from two large commercial dairies in NW England for comparison. Bovine ALP activity of >500 mU/litre was deemed as a failure and was found in 3.5% of whole milk, 2.4% semiskimmed milk, 5.0% of skimmed milk, and 39% of cream samples from on-farm dairies. Bovine ALP activity of >100 and <500 mU/litre was found in 18.4% of whole milk, 9.3% of semi-skimmed milk, 13.2% skimmed milk and 44.5% of cream samples from on-farm dairies. Results with skimmed milk samples showed significantly lower bovine ALP activity than whole milk. All 409 milk and cream samples from two large commercial dairies passed the fluorimetric test at less than 500 mU/litre of bovine ALP, and 99% of these milk and cream samples had bovine ALP activity of less than 100 mU/litre. The presence of residual bovine phosphatase indicates a failure and may be due to either inadequate pasteurisation or post pasteurisation contamination with raw milk. Residual bovine phosphatase was demonstrated in 108/114 (94.7%) of milk samples with a bovine ALP activity greater than 500 mU/litre, i.e. true failures. Of more concern is that residual bovine phosphatase was found in 395/401 (98.5%) of samples that gave bovine ALP activity greater than 100 mU/litre but equal to or less than 500 mU/litre. Residual bovine phosphatase was demonstrated in 37/108 (30.2%) of cream samples with bovine ALP activity greater than 500 mU/litre. Presence of reactivated bovine phosphatase is not an indication of a failure but can mask the presence of residual bovine phosphatase. Reactivated bovine phosphatase was found in 74/106 (69.8%) of cream samples. Our results confirm that the more sensitive fluorimetric method is suitable for testing pasteurised whole milk and semiskimmed milk, but for statutory purposes the acceptable level of residual bovine phosphatase should be <100 mU/litre. Our findings have highlighted a potential problem when testing skimmed milk and cream samples from on-farm dairies. To ensure public safety we need more stringent standards for the ALP test and new methods that will accurately confirm that pasteurisation of these products has been achieved.


Regulation of glycolysis in Lactococcus lactis: an unfinished systems biological case study.
The unexpectedly long, and still unfinished, path towards a reliable mathematical model of glycolysis and its regulation in Lactococcus lactis is described. The model of this comparatively simple pathway was to be deduced from in vivo nuclear magnetic resonance time-series measurements of the key glycolytic metabolites. As to be expected from any nonlinear inverse problem, computational challenges were encountered in the numerical determination of parameter values of the model. Some of these were successfully solved, whereas others are still awaiting improved techniques of analysis. In addition, rethinking of the model formulation became necessary, because some generally accepted assumptions during model design are not necessarily valid for in vivo models. Examples include precursor-product relationships and the homogeneity of cells and their responses. Finally, it turned out to be useful to model only some of the metabolites, while using time courses of ubiquitous compounds such as adenosine triphosphate, inorganic phosphate, nicotinamide adenine dinucleotide (oxidised) and nicotinamide adenine dinucleotide (reduced) as unmodelled input functions. With respect to our specific application, the modelling process has come a long way, but it is not yet completed. Nonetheless, the model analysis has led to interesting insights into the design of the pathway and into the principles that govern its operation. Specifically, the widely observed feedforward activation of pyruvate kinase by fructose 1,6-bisphosphate is shown to provide a crucial mechanism for positioning the starving organism in a holding pattern that allows immediate uptake of glucose, as soon as it becomes available.


Nursing leadership succession planning in Veterans Health Administration: creating a useful database.
An electronic database was developed for succession planning and placement of nursing leaders interested and ready, willing, and able to accept an assignment in a nursing leadership position. The tool is a 1-page form used to identify candidates for nursing leadership assignments. This tool has been deployed nationally, with access to the database restricted to nurse executives at every Veterans Health Administration facility for the purpose of entering the names of developed nurse leaders ready for a leadership assignment. The tool is easily accessed through the Veterans Health Administration Office of Nursing Service, and by limiting access to the nurse executive group, ensures candidates identified are qualified. Demographic information included on the survey tool includes the candidate's demographic information and other certifications/credentials. This completed information form is entered into a database from which a report can be generated, resulting in a listing of potential candidates to contact to supplement a local or Veterans Integrated Service Network wide position announcement. The data forms can be sorted by positions, areas of clinical or functional experience, training programs completed, and geographic preference. The forms can be edited or updated and/or added or deleted in the system as the need is identified. This tool allows facilities with limited internal candidates to have a resource with Department of Veterans Affairs prepared staff in which to seek additional candidates. It also provides a way for interested candidates to be considered for positions outside of their local geographic area.


Predicting clinically significant prostate cancer from quantitative image features including compressed sensing radial MRI of prostate perfusion using machine learning: comparison with PI-RADS v2 assessment scores.
To investigate if supervised machine learning (ML) classifiers would be able to predict clinically significant cancer (sPC) from a set of quantitative image-features and to compare these results with established PI-RADS v2 assessment scores. We retrospectively included 201, histopathologically-proven, peripheral zone (PZ) prostate cancer lesions. Gleason scores ≤3+3 were considered as clinically insignificant (inPC) and Gleason scores ≥3+4 as sPC and were encoded in a binary fashion, serving as ground-truth. MRI was performed at 3T with high spatiotemporal resolution DCE using Golden-angle RAdial SParse (GRASP) MRI. Perfusion maps (Ktrans, Kep, Ve), apparent diffusion coefficient (ADC), and absolute T2-signal intensities (SI) were determined in all lesions and served as input parameters for four supervised ML models: Gradient Boosting Machines (GBM), Neural Networks (NNet), Random Forest (RF) and Support Vector Machines (SVM). ML results and PI-RADS scores were compared with the ground-truth. Next ROC-curves and AUC values were calculated. All ML models outperformed PI-RADS v2 assessment scores in the prediction of sPC (RF, GBM, NNet and SVM vs. PI-RADS: AUC 0.899, 0.864, 0.884 and 0.874 vs. 0.595, all P<0.001). Using quantitative imaging parameters as input, supervised ML models outperformed PI-RADS v2 assessment scores in the prediction of sPC. These results indicate that quantitative imagining parameters contain relevant information for the prediction of sPC from image features.


[Association of TNF-α gene polymorphisms with Graves disease susceptibility and early course thyroid stimulating hormone receptor antibody level in Chinese Han population in Anhui region].
To assess the association of tumour necrosis factor-α (TNF-α) gene polymorphisms at positions -863C/A, -857C/T, -238G/A and Graves disease (GD) susceptibility in Chinese Han population in Anhui region. The polymorphisms of TNF-α gene were determined by polymerase chain reaction with specific primers in 254 patients affected with GD and 212 healthy controls. Allelic and genotypic frequencies in GD group and normal controls as well as in different genders were compared. The allelic and genotypic frequencies for different thyroid stimulating hormone receptor antibody (TRAb) levels (TRAb > 12 U/L; ≤12 U/L) were also compared among patients with earlier onset GD. (1) The A allele at -863C/A locus in GD group (16.73%) was significantly greater than that of the control group (11.79%) (P< 0.05, OR = 1.503); the frequency of AA+CA genotype of -863C/A locus in GD group (32.68%) was significantly greater than that of control group (23.58%) (P< 0.05, OR = 1.573). There was no significant difference (P> 0.05) in the allelic and genotypic frequencies of -857C/T, -238G/A loci between the two groups. (2) There was no significant difference (P> 0.05) in the allelic and genotypic frequencies of -863C/A, -857C/T, -238G/A loci between patients of different genders. (3) There was no significant difference (P>0.05) in such frequencies between patients with earlier onset GD and different TRAb levels (TRAb > 12 U/L; ≤12 U/L). (1) The -863 A allele of TNF-α gene may contribute to the development of GD in Chinese Han population in Anhui, whilst -857C/T, -238G/A alleles may not. (2) There is no association between TNF-α gene -863C/A, -857C/T, -238G/A polymorphisms and development of GD in different genders. (3) There was no association between above polymorphisms and TRAb levels in patients with earlier onset GD.


[Recent advances in diagnosis of pulmonary nodule].
With the popularization of health screening and the widespread use of low-dose computed tomography, the detection rate of lung nodules has increased year after year. However, the false positive rates testified by surgery of these lung nodules are still high. Therefore, it is vital in clinical practice to avoid overtreatment or undertreatment. But a series of problems on how to make an accurate diagnosis, how to reduce the psychological pressure of patients and follow up with regular imaging, how to clarify the indications for surgery and adopt the most minimally invasive diagnosis and treatment methods, etc. remain unsolved. Over the past decade, the diagnostic techniques for pulmonary nodules have improved significantly, including imaging progress such as the optimization of traditional imaging techniques (CT, MRI) and the emergence of new technologies (radiomics, artificial intelligence). In addition, histological improvements including percutaneous transthoracic needle biopsy, bronchoscopy, and minimally invasive surgical biopsy, etc. have brought more reliable and precise options for characterization of pulmonary nodules.


First core microsatellite panel identification in Apennine brown bears (Ursus arctos marsicanus): a collaborative approach.
The low cost and rapidity of microsatellite analysis have led to the development of several markers for many species. Because in non-invasive genetics it is recommended to genotype individuals using few loci, generally a subset of markers is selected. The choice of different marker panels by different research groups studying the same population can cause problems and bias in data analysis. A priority issue in conservation genetics is the comparability of data produced by different labs with different methods. Here, we compared data from previous and ongoing studies to identify a panel of microsatellite loci efficient for the long-term monitoring of Apennine brown bears (Ursus arctos marsicanus), aiming at reducing genotyping uncertainty and allowing reliable individual identifications overtimes. We examined all microsatellite markers used up to now and identified 19 candidate loci. We evaluated the efficacy of 13 of the most commonly used loci analyzing 194 DNA samples belonging to 113 distinct bears selected from the Italian national biobank. We compared data from 4 different marker subsets on the basis of genotyping errors, allelic patterns, observed and expected heterozygosity, discriminatory powers, number of mismatching pairs, and probability of identity. The optimal marker set was selected evaluating the low molecular weight, the high discriminatory power, and the low occurrence of genotyping errors of each primer. We calibrated allele calls and verified matches among genotypes obtained in previous studies using the complete set of 13 STRs (Short Tandem Repeats), analyzing six invasive DNA samples from distinct individuals. Differences in allele-sizing between labs were consistent, showing a substantial overlap of the individual genotyping. The proposed marker set comprises 11 Ursus specific markers with the addition of cxx20, the canid-locus less prone to genotyping errors, in order to prevent underestimation (maximizing the discriminatory power) and overestimation (minimizing the genotyping errors) of the number of Apennine brown bears. The selected markers allow saving time and costs with the amplification in multiplex of all loci thanks to the same annealing temperature. Our work optimizes the available resources by identifying a shared panel and a uniform methodology capable of improving comparisons between past and future studies.


SecA2-dependent secretion of autolytic enzymes promotes Listeria monocytogenes pathogenesis.
Pathogenic bacteria secrete proteins that promote invasion of host tissues and resistance to immune responses. However, secretion mechanisms that contribute to the enormous morbidity and mortality of Gram-positive bacteria are largely undefined. An auxiliary protein secretion system (SecA2) has recently emerged in Listeria monocytogenes and eight other Gram-positive pathogens. Here, a proteomics approach identified seventeen SecA2-dependent secreted and surface proteins of L. monocytogenes, the two most abundant of which [the p60 and N-acetylmuramidase (NamA) autolysins] hydrolyze bacterial peptidoglycan (PGN) and contribute to host colonization. SecA2-deficient (DeltaSecA2) bacteria were rapidly cleared after systemic infection of murine hosts, and in cultured cells showed reduced cell-cell spread. p60 or NamA deficiencies (Deltap60 and DeltaNamA) caused intermediate reductions in bacterial virulence in vivo, yet showed no defect for infection of cultured cells. Restoration of virulence in Deltap60 bacteria required full-length p60 with an intact catalytic domain, suggesting that PGN hydrolysis by p60 is crucial for L. monocytogenes virulence. Coordinated PGN hydrolysis by p60 and NamA activities is predicted to generate a muramyl glycopeptide, glucosaminylmuramyl dipeptide (GMDP), which is known to modify host inflammatory responses. Thus, SecA2-dependent secretion may promote release of muramyl peptides that subvert host pattern recognition.


FLCN Maintains the Leucine Level in Lysosome to Stimulate mTORC1.
The intracellular amino acid pool within lysosome is a signal that stimulates the nutrient-sensing mTORC1 signalling pathway. The signal transduction cascade has garnered much attention, but little is known about the sequestration of the signalling molecules within the lysosome. Using human HEK293 cells as a model, we found that suppression of the BHD syndrome gene FLCN reduced the leucine level in lysosome, which correlated with decreased mTORC1 activity. Both consequences could be reversed by supplementation with high levels of leucine, but not other tested amino acids. Conversely, overexpressed FLCN could sequester lysosomal leucine and stimulate mTORC1 in an amino acid limitation environment. These results identify a novel function of FLCN: it controls mTORC1 by modulating the leucine signal in lysosome. Furthermore, we provided evidence that FLCN exerted this role by inhibiting the accumulation of the amino acid transporter PAT1 on the lysosome surface, thereby maintaining the signal level within the organelle.


Managing psychosocial issues in a family with diabetes.
Managing diabetes in a child or teen requires constant attention and adjustment of insulin, carbohydrate intake, and activity level. Intensive diabetes management has the potential to improve diabetes outcomes; however, negotiating the many lifestyle accommodations essential to optimal diabetes control can place a significant burden on some children and families. Parenting a child with diabetes also involves a complex process of helping the child to achieve age-appropriate independence while assuring the child's safety in managing his or her diabetes. Each developmental stage brings new challenges to achieving the delicate balance between optimal diabetes control and age-appropriate independence in self-care management. Despite the laborious and intensive nature of diabetes treatment, an overarching goal of parenting a child with diabetes is to ensure that the family's quality of life is maintained and the child is able to participate in all academic and social activities that their peers enjoy. Although many families adapt and thrive, others struggle to make these adjustments. Working with families who are overwhelmed, encouraging them to identify and develop networks involving schools, extended family, community, and church groups can help them to increase available support. Helping families to access treatment when they are struggling can relieve further pain and improve management adherence and diabetes outcomes. Nurses are in a key position to evaluate the family's adaptive and coping skills and assist them to negotiate the psychosocial challenges that living with diabetes entails.


Choosing upper limb muscles for focal intervention after traumatic brain injury.
The upper motoneuron syndrome (UMNS) resulting from lesions of corticospinal pathways is an important source of disability after traumatic brain injury (TBI). Classic expressions of motor behavior in UMNS are of 2 kinds: (1) manifestation of muscle underactivity, termed negative signs, and (2) manifestation of a variety of forms of muscle overactivity, termed positive signs. Combinations of negative and positive signs give rise to clinical patterns of movement dysfunction such as the flexed elbow, the clenched fist, and the thumb-in-palm deformity. These clinical patterns can be viewed as reflecting a net balance of muscle forces acting across the joints of a limb. Individual muscles are amenable to a variety of focal interventions such as neurolysis, chemodenervation, or surgery. Since more than one muscle acts across most joints, choices among muscles for focal intervention are many. This article will focus on focal interventions of upper limb muscles of patients with TBI who have UMNS and will explore the theme of choosing upper limb muscles for focal interventions after TBI.


[Time parameters of dental hypnosis].
Dental treatments of high dental anxiety patients (n = 20) under hypnotic conditions were investigated. Time need of main hypnotic events like rapport; induction: deepening; calming: developing imagination; dehypnosis; discussion was measured. Total time was significantly higher (p < or = 0.05) than pure dental treatment time, but the time the patients percepted was significantly less then total (p < or = 0.05), even somewhat less then pure dental treatment time. Time distortion correlated significantly (negative Pearson's correlation; p < or = 0.05) with the time need of rapport (-0.50), calming (-0.51) and dehipnosis (-0.46), and with the time need of developing delightful imagination (+0.57) (positive Pearson's correlation; p < or = 0.05). There was no significant correlation between time distortion and the time need of hypnotic induction, deepening, total time need of hypnosis, or pure dental treatment time.


Metabolic and Kidney Diseases in the Setting of Climate Change, Water Shortage, and Survival Factors.
Climate change (global warming) is leading to an increase in heat extremes and coupled with increasing water shortage, provides a perfect storm for a new era of environmental crises and potentially, new diseases. We use a comparative physiologic approach to show that one of the primary mechanisms by which animals protect themselves against water shortage is to increase fat mass as a means for providing metabolic water. Strong evidence suggests that certain hormones (vasopressin), foods (fructose), and metabolic products (uric acid) function as survival signals to help reduce water loss and store fat (which also provides a source of metabolic water). These mechanisms are intricately linked with each other and stimulated by dehydration and hyperosmolarity. Although these mechanisms were protective in the setting of low sugar and low salt intake in our past, today, the combination of diets high in fructose and salty foods, increasing temperatures, and decreasing available water places these survival signals in overdrive and may be accelerating the obesity and diabetes epidemics. The recent discovery of multiple epidemics of CKD occurring in agricultural workers in hot and humid environments may represent harbingers of the detrimental consequences of the combination of climate change and overactivation of survival pathways.


Nerve puncture and apparent intraneural injection during ultrasound-guided axillary block does not invariably result in neurologic injury.
Nerve puncture by the block needle and intraneural injection of local anesthetic are thought to be major risk factors leading to neurologic injury after peripheral nerve blocks. In this study, the author sought to determine the needle-nerve relation and location of the injectate during ultrasound-guided axillary plexus block. Using ultrasound-guided axillary plexus block (10-MHz linear transducer, SonoSite, Bothel, WA; 22-gauge B-bevel needle, Becton Dickinson, Franklin Parks, NJ), the incidence of apparent nerve puncture and intraneural injection of local anesthetic was prospectively studied in 26 patients. To determine the onset, success rate, and any residual neurologic deficit, qualitative sensory and quantitative motor testing were performed before and 5 and 20 min after block placement. At a follow-up 6 months after the blocks, the patients were examined for any neurologic deficit. Twenty-two of 26 patients had nerve puncture of at least one nerve, and 21 of 26 patients had intraneural injection of at least one nerve. In the entire cohort, 72 of a total of 104 nerves had intraneural injection. Sensory and motor testing before and 6 months after the nerve injections were unchanged. Under the conditions of this study, puncturing of the peripheral nerves and apparent intraneural injection during axillary plexus block did not lead to a neurologic injury.


Barometric pressure fluctuations: effects on the activity of laboratory mice.
Fluctuations in naturally occurring levels of barometric pressure appear to be an important determinant of activity in laboratory mice. In three experiments, activity was higher after increases in barometric pressure than it was after decreases. When the barometric pressure remained relatively stable, intermediate levels of activity were observed.


A human squamous cell carcinoma cell line.
An epithelial cell line COLO 16 has been established from a human squamous carcinoma, characterized and maintained for over two years. The cells produce a parathyroid-like hormone and carcinoembryonic antigen. The line is definitely not a "HeLa contaminant." The cell line is available to other investigators.


Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1.
Circular RNAs (circRNAs) represent a widespread class of non-coding RNAs generated from back-splicing, with a circular loop structure. Many circRNAs have been reported to play essential roles in cancer development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNA in osteosarcoma (OS) remains largely unknown. In the current study, we examined the expression level of circular RNA PVT1 (circPVT1), previously screened and identified the oncogenic role in gastric cancer, in OS and found that circPVT1 was significantly up-regulated in the OS tissues, serums and chemoresistant cell lines, correlated with poor prognosis of OS patients. Besides, ROC curve demonstrated that circPVT1 may be a better diagnostic biomarker than alkaline phosphatase (ALP) in OS with more sensitivity and specificity. In addition, functional assays revealed that circPVT1 knockdown by siRNA could weaken the resistance to doxorubicin and cisplatin of OS cells through decreasing the expression of classical drug resistance-related gene ABCB1. These findings may provide a new insight into the role of circPVT1 as a biomarker for the diagnosis and treatment target of OS.


Combined Estrogen Receptor and Progesterone Receptor Level Can Predict Survival Outcome in Human Epidermal Growth Factor Receptor 2-positive Early Breast Cancer.
In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, emerging evidence imply that clinical behaviors differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2+ breast cancer. Our study aimed to determine the influence of different ER/PR levels on survival outcome of HER2+ early breast cancer. Nine hundred and nineteen early HER2+ breast cancer patients treated between 2009 and 2016 were retrospectively reviewed and HR+/HER2+ patients were further divided based on ER level (Low/L: 1%-9%; Median/M: 10%-79%; High/H: 80%-100%) and PR level (Low/L: 0%-19%; High/H: 20%-100%) according to restricted cubic spline (RCS) smoothing curve. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and log rank test. Four hundred and forty two HR+/HER2+ and 477 HR-/HER2+ breast cancer patients were included in our study and 73.2% received target therapy (HR+ 69.7%, HR- 76.5%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 93.0% vs. 86.8%, P < .001), no significant difference was observed between DFS in ER+/PR+ and ER+/PR- subgroup (94.4% vs. 90.4%, P = .22). However, a potential correlation was found between ER/PR levels and DFS in HR+/HER2+ (P = .074) tumors. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR. In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.10 (95%CI 0.01-0.74, P = .024) in all patients and 0.14 (95%CI, 0.02-1.02, P = .053) in patients receiving anti-HER2 therapy. ER/PR expression may become a predictor of survival benefit in HER2+ early breast cancer and a higher ER/PR level might be associated with better DFS.


Unique symptoms at midlife of women with osteoporosis and cardiovascular disease in Taiwan.
This study compared symptoms at midlife, menopause attitudes, and depression among three groups of late peri- or postmenopausal women, namely, women with cardiovascular disease (CVD group), women with osteoporosis (Os group), and women in generally good health (Co group). We used a cross-sectional method. Participants were purposively sampled from a medical center and a residential community in southern Taiwan. A total of 500 women between 45 and 60 years of age participated in the study. Four measures were used: a demographics and health habits questionnaire, the Women's Health Initiative Symptom Scale, the Attitudes Towards Menopause Scale, and the Center for Epidemiological Studies-Depression Scale. Significant demographic differences among the groups were found in age, number of children, educational level, family income, employment status, exercise duration per session, smoking status, daily cigarette consumption, and number of years smoking. After significant covariates had been controlled for, the CVD group reported significantly more severe symptoms at midlife than did the Co group; significantly more severe "psychosomatic symptoms" than did the Co group; and significantly more severe "gastrointestinal symptoms and swelling" and "vasomotor symptoms" than did either the Os group or the Co group. The CVD group also reported significantly greater depressive symptoms than did the Os group. This study identified a number of differences in symptoms at midlife and depressive symptoms among the three groups. Results support the importance of providing unique care for peri- and postmenopausal women in different health categories. Findings may help healthcare professionals better appreciate the diversity of menopausal experiences and support the development of appropriate care strategies.


Simple new methods for deducing lifetimes in recoil distance Doppler-shift measurements.
New approaches for lifetime determination using data from recoil distance Doppler-shift experiments are presented based on the fundamental properties of the functions describing the time evolution of the population of excited nuclear states. To some extent, one of them represents a contraction of the well-known Differential decay-curve method (DDCM) by using the most reliable data point [the maximum of the ni(t) function describing the population of level i in time] and a purely numerical procedure avoiding any fitting of decay curves. The combination with the standard DDCM analysis is promising for improving the reliability and the precision of the results for the lifetimes obtained. The novel part of the approach consists of using a chain of equations at the consecutive maxima of the ni(t) functions, which allow us to precisely determine the ratio of the lifetimes of two consecutive levels and, in the case where one of these lifetimes is known, to determine the unknown one. In addition, a simple integral derivation of the lifetime is presented involving the peak areas measured at different distances, and an application of the first moments (expectation values and centroids in time) of the ni(t) functions for determining lifetimes is also demonstrated to be useful.


Thermoresponsive swelling of photoacoustic single-chain nanoparticles.
NIR-fluorescent LCST-type single-chain nanoparticles (SCNPs) change their photophysical behaviour upon heating, caused by depletion of water from the swollen SCNP interiors. This thermoresponsive effect leads to a fluctuating photoacoustic (PA) signal which can be used as a contrast mechanism for PA imaging.


Bilateral simultaneous hypertensive intracerebral hemorrhages.
Bilateral simultaneous hypertensive intracerebral hemorrhages (HICH) are a rare occurrence. Computed tomography (CT) enables us to diagnose such a condition which is difficult to recognize clinically. In the series, six patients (2.6%) from a series of 553 HICH cases had suffered from simultaneous rehemorrhage in the contralateral hemisphere. It comprised four males and two females. Their ages ranged from 54 to 64 years with a mean age of 58 years. The clinical symptoms were excessively sever and were characterized by severe consciousness disturbance (semicoma to coma, 6 cases), aphasia (5 cases) and bilateral paresis (3 cases). CT density profiles were identical, implying that the hematomas were of similar age but located areas; two were bilateral basal ganglia, one was bilateral specular thalamus, pontine-ganglia (right), thalamo (left)-ganglia (right) and occipito (right)-thalamus (left) individually. All of the hematomas had ruptured into the ventricles. The predominant sites of hemorrhage were in the putamen (50%, 6/12) and the thalamus (33%, 4/12). Two patients received emergency craniotomy for evacuation of the hematomas. However, they died soon after the operations. In the remaining four non-surgical cases, two died of central failure, another died of pneumonia and the remain one survived but retained hemiplegia sequelae. The serious surgical results and outcome in bilateral HICH was compared that of unilateral HICH. Hemodynamically, poor cerebral blood flow and diaschisis phenomenon may contribute to the poor prognosis in these patients.


Epidemiology and clinical manifestations of visceral and cutaneous leishmaniasis in Baringo District, Rift Valley, Kenya. A literature review.
Visceral leishmaniasis (VL), caused by Leishmania donovani, is endemic in Baringo District, Kenya. The disease has a focal distribution in the dry, hot areas below 1500 metres. Infections may be characterized as follows: 1) asymptomatic, 2) subclinical and self-limiting (not medically identifiable), and 3) clinically manifest disease (that is medically identifiable). Half of the reported VL patients are between 5 and 14 years of age and 66% of them are males. The reasons for the focal distribution and for the age and sex preference are discussed. Phlebotomus martini is the vector of the parasite, and man is the only known reservoir. Cutaneous leishmaniasis (CL), due to Leishmania major, is rare in humans, but underreporting is likely. The vector, Phlebotomus duboscqui, is mainly found in animal burrows where it feeds on rodents which are frequently infected. A human case of a mixed L. donovani and L. major infected. A human case of a mixed L. donovani and L. major infection has been reported in this dual focus of VL and CL.


Phosphorylation of the same specific protein during amylase release evoked by beta-adrenergic or cholinergic agonists in rat and mouse parotid glands.
Stimulation of amylase secretion from the rat parotid gland by beta-adrenergic agonists is associated with a specific phosphorylation of three membrane-bound proteins designated as proteins I, II, and III [Jahn, R., Unger, C. & Söling, H. D. (1980) Eur. J. Biochem. 112, 345-352]. In contrast, stimuliation by carbachol induced significant phosphorylation of only protein I. This phosphorylation was low compared to isoproterenol-induced phosphorylation but corresponded to the smaller enhancement of amylase secretion. The mouse organ, however, is almost equally sensitive to beta-adrenergic and to cholinergic agonists. Incubation of mouse parotid gland slices with either 20 microM isoproterenol or 10 microM carbachol resulted in strong and comparable releases of amylase, which were accompanied by comparable phosphorylations of protein I. Proteins II and III were phosphorylated only in the presence of isoproterenol. Removal of external calcium by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetate abolished the carbachol-induced release of amylase but not the phosphorylation of protein I. Isoproterenol-induced secretion of amylase and phosphorylation of proteins I, II, and III were not inhibited under these conditions. Amylase release stimulated by the ionophore A-23187 was accompanied by the phosphorylation of protein I. Two-dimensional electrophoresis revealed that the radioactive spot corresponding to protein I was located at the same position after cholinergic and after beta-adrenergic stimulation, indicating that both stimuli led to the phosphorylation of the same membrane-associated protein. These findings strongly support the view that the phosphorylation of protein I is an important step in the sequence of events leading from receptor activation to exocytosis.


Relationship of leptin concentration to gender, menopause, age, diabetes, and fat mass in African Americans.
This investigation was designed to determine the relationship of leptin concentration to gender, sex hormones, menopause, age, diabetes, and fat mass in African Americans. Participants included 101 African Americans, 38 men (mean age, 34.2 +/- 7.4 years), 29 age-matched premenopausal women (mean age, 32.6 +/- 3.7 years), and 36 postmenopausal women (mean age, 57.8 +/- 5.9 years). The women were not taking exogenous sex hormones, and 12 subjects were diabetic. Percent body fat was calculated with the Siri formula, fat mass (FM) was calculated as weight x percent body fat, and Fat-free mass (FFM) was calculated as weight minus FM. Fasting plasma was assayed for leptin, estradiol, free testosterone, glucose, and insulin concentrations. The nondiabetics had an oral glucose tolerance test (OGTT). The diabetics compared with the non-diabetics had a higher central fat index (p=0.04) but otherwise were similar to nondiabetics in all parameters measured. Body mass index, percent body fat, and FM were greater in women than men (p<0.001). Leptin concentrations in men, premenopausal, and postmenopausal women were: 7.51 +/- 8.5, 33.9 +/- 17.3, 31.4 +/- 22.3 ng/mL. Leptin/FM x 100 in the three groups were: 28.9 +/- 16.1, 98.65 +/- 44.9, 77.1 +/- 44.5 ng/mL/kg. The gender difference in leptin concentration and leptin/FM was significant (p<0.001), but the difference between premenopausal and postmenopausal women was not. In each group, weight, percent body fat, and FM were highly correlated with leptin concentration. Multiple regression analyses with leptin concentration as the dependent variable and age, diabetic status, percent body fat, weight, FM, FFM, estradiol, and free testosterone concentrations as independent variables demonstrated that the determinants of leptin concentration in men was weight only (R=0.83, p<0.001), in premenopausal women it was FM only (R=0.57, p<0.001), and in postmenopausal women it was weight only (R=0.67, p<0.001). With diabetics excluded, the multiple regression analysis was repeated with fasting insulin concentration and the area under the insulin curve during the OGTT included as independent variables. The results for this multiple regression analyses were the same as the first. Therefore, leptin concentration in African Americans is determined by gender and fat mass. Menopause, age, and diabetes do not affect leptin concentration.


Patterned carbon nanotubes fabricated by the combination of microcontact printing and diblock copolymer micelles.
A convenient approach to synthesize patterned carbon nanotubes (CNTs) of three morphologies on printed substrates by combination of microcontact printing (microCP) and a plasma-enhanced chemical vapor deposition (PECVD) process is presented. Micelles of polystyrene-block-poly-(2-vinylpyridine) (PS-b-P2VP) in toluene were used as nanoreactors to fabricate FeCl3 in the core domains, and the complex solution was used as an ink to print films with polydimethylsiloxane (PDMS) stamps, different morphologies (porous, dots and stripes patterns) of the FeCl3-loaded micellar films were left onto silicon substrates after printed. After removing the polymer by thermal decomposition, the left iron oxide cluster arrays on the substrate were used as catalysts for the growth of CNTs by the process of PECVD, where the CNTs uniformly distributed on the substrates according to the morphologies of patterned catalysts arrays.


Reliability of maximal voluntary isometric contraction testing in a multicenter study of patients with amyotrophic lateral sclerosis. Syntex/Synergen Neuroscience Joint Venture rhCNTF ALS Study Group.
Maximal voluntary isometric contraction (MVIC) is becoming widely used for monitoring disease progression in amyotrophic lateral sclerosis (ALS). We evaluated the variability of MVIC in a large multicenter (29 sites) drug trial in ALS. Intra- and interrater variability were assessed twice during the 19-month study. Intrarater reliability increased from the first to the second test, approaching the reliability reported for a single experienced clinical evaluator, but interrater reliability did not. Multiple clinical evaluators in a single site increased the variability of MVIC measurements. Rigorous quality assurance standards and monitoring of clinical evaluators should be incorporated into the design of multicenter studies using MVIC, since low variability is necessary to detect a modest treatment effect.


Three in One: Superoleophilic, Chemically and Mechanically Resistant ZIF-7 and ZIF-11 Percolation Networks for Selective Permeation of Oils and Chlorinated Solvents.
Imbuing superwetting functions to organic-inorganic hybrid networks displaying chemical resistance, self-cleaning ability, and selective permeation of liquids has received increasing attention in recent years. Here we report superhydrophobic ZIF-7 and ZIF-11 on multilayer fluorinated graphene (FG) nanosheets with long-lasting water-repellent features. By exploring the solution processing of these chemically resistant dispersions, superoleophilic FG-ZIF-7 stainless steel mesh (FG-ZIF-7-SSM) and FG-ZIF-11 over cotton cloth (FG-ZIF-11-CC) possessing superior adhesion were fabricated. These permselective oil-liking prototypes were explored toward mesitylene and crude oil pickup from chemically harsh marine conditions such as seawater, acidic water, and alkaline water, with a separation efficiency of 96-94% up to 10 cycles. Furthermore, using an FG-ZIF-11-CC-wrapped glass pipet, upward diffusion of chloroform from sea, acidic, and alkaline water in 45 s was demonstrated with a separation efficacy of 94% up to 20 cycles. In addition to the chemical resistance and reusability, the mechanical stability of FG-ZIF-7-SSM and FG-ZIF-11-CC was investigated through folding, tape peeling, and dragging through sandpaper up to 250 cycles, showing no signs of changes in the hydrophobic responses. This research sheds light on the application of physiochemically resistant percolation coatings based on fluorinated graphene multilayers supporting ZIF-7 and ZIF-11 toward oil/water separation.


Combined 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy and Platinum-Based Chemotherapy in Recurrent, Metastatic Sinonasal Neuroendocrine Carcinoma: A Promising Therapeutic Option.
Sinonasal neuroendocrine carcinomas (SNCs), in contrast to neuroendocrine carcinomas at other sites, are notorious for their recurrent and locally aggressive nature. The clinical concern is primarily due to their complex anatomy and close proximity to vital structures, compounded by lack of proper understanding of pathogenesis, no definitive classification or staging system, and no established treatment guidelines. We present the promise of combined treatment with 177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) and platinum-based chemotherapy in a patient with high-grade, recurrent, and metastatic SNC (that demonstrated high uptake on both 68Ga-DOTATATE and 18F-FDG PET/CT), which showed a significant partial response. The case report highlights the feasibility and effectiveness of applying a combined protocol of 177Lu-DOTATATE and platinum-based chemotherapy in the management of high-grade, recurrent, metastatic SNC.