Salinity stress increases the severity of ranavirus epidemics in amphibian populations.
The stress-induced susceptibility hypothesis, which predicts chronic stress weakens immune defences, was proposed to explain increasing infectious disease-related mass mortality and population declines. Previous work characterized wetland salinization as a chronic stressor to larval amphibian populations. Thus, we combined field observations with experimental exposures quantifying epidemiological parameters to test the role of salinity stress in the occurrence of ranavirus-associated mass mortality events. Despite ubiquitous pathogen presence (94%), populations exposed to salt runoff had slightly more frequent ranavirus related mass mortality events, more lethal infections, and 117-times greater pathogen environmental DNA. Experimental exposure to chronic elevated salinity (0.8-1.6 g l-1 Cl-) reduced tolerance to infection, causing greater mortality at lower doses. We found a strong negative relationship between splenocyte proliferation and corticosterone in ranavirus-infected larvae at a moderate elevation of salinity, supporting glucocorticoid-medicated immunosuppression, but not at high salinity. Salinity alone reduced proliferation further at similar corticosterone levels and infection intensities. Finally, larvae raised in elevated salinity had 10 times more intense infections and shed five times as much virus with similar viral decay rates, suggesting increased transmission. Our findings illustrate how a small change in habitat quality leads to more lethal infections and potentially greater transmission efficiency, increasing the severity of ranavirus epidemics.


Patellar tendon-bearing, patten-bottom caliper suspension orthosis in active Charcot arthropathy: crutch-free ambulation with no weight bearing in the foot.
A custom, patellar-tendon bearing (PTB), patten-bottom, caliper suspension orthosis was constructed for six patients with severe, active (Eichenholtz stage I) Charcot arthropathy of the ankle and hindfoot. With the orthosis, the suspended foot and ankle remained completely non-weight-bearing, and the lower extremity supported full weight bearing along the posterior and anterior leg shells and PTB crest. Four of the six patients used the orthosis to ambulate without crutches, leaving the upper extremities free for functional use. Frequent adjustment of the orthosis and skin examination were required. Minor problems with the orthosis included superficial skin breakdown and downward pistoning of the leg associated with improper, loose donning. Patient compliance was poor in four of the six patients because of general debility, difficulty with balance, and discomfort. However, in the other two patients, the absence of mechanical forces on the foot and ankle in the orthosis allowed the swelling and erythema of the active phase of Charcot arthropathy to resolve within several weeks, with maintenance of functional ambulation during the months required for healing of the Charcot process.


Multiple balloon rupture during coronary angioplasty. A case report.
The authors report a case of coronary angioplasty of the left anterior descending artery complicated by multiple balloon rupture. Various balloon types including polyethylene terephthalate and PE 600 (ACS) ruptured at low atmospheric pressure. During balloon rupture, a septal side branch was dissected with severe intimal staining. The authors postulate that a particular lesion morphology was responsible for balloon rupture. Approaches to such lesions using alternative coronary angioplasty techniques and newer technologies are discussed.


Discrimination between spinal extradural meningioma and both intra and extradural meningioma: Case Report.
Meningiomas are common spinal tumor and mostly located at intradura. Recurrence rate after surgery for extradural meningioma was higher than intradural meningioma. A patient with intra and extradural spinal meningioma was treated and discussed its features and clinical management. A 41-year-old woman noted numbness of bilateral legs, gait disturbance, and mild bladder disturbance for over the two-month period. Magnetic resonance imaging revealed an epidural mass at T8-9 involving the dura mater from the left side. Intraoperatively, ultrasonography showed extradural tumor suppress the dura from the left side and no subarachnoid space. Therefore, it was difficult to diagnose the tumor was located at only extradural or both intra and extradural. The extradural tumor was resected as much as possible, then ultrasonography was performed for the second time. The spinal cord was decompressed and subarachnoid space was appeared with intradural tumor. The dura mater was opened in the midline for intradural exploration, and the intradural tumor appeared beside the spinal cord. The dura mater with attachment to the tumor was rescected. To prevent a recurrence, ultrasonography after removing extradural tumor is recommended to detect intra dural tumor and invasion of tumor into dura mater. In such case, removing only extradural meningioma is not enough, and gross total resection including intradural meningioma and dura mater is required.


Conductivity exponents in stick percolation.
On the basis of Monte Carlo simulations, the present work systematically investigates how conductivity exponents depend on the ratio of stick-stick junction resistance to stick resistance for two-dimensional stick percolation. Simulation results suggest that the critical conductivity exponent extracted from size-dependent conductivities of systems exactly at the percolation threshold is independent of the resistance ratio and has a constant value of 1.280+/-0.014 . In contrast, the apparent conductivity exponent extracted from density-dependent conductivities of systems well above the percolation threshold monotonically varies with the resistance ratio, following an error function, and lies in the vicinity of the critical exponent.


Use of topical vancomycin powder in total joint arthroplasty: Why the current literature is inconsistent?
Periprosthetic joint infection (PJI) is a rare but terrible complication in hip and knee arthroplasty, and the use of topical vancomycin powder (VP) has been investigated as a tool to potentially reduce its incidence. However, there remains no consensus on its efficacy. Therefore, the aim of this review is to provide an overview on the application of topical vancomycin in orthopaedic surgery focusing on the recent evidence and results in total joint arthroplasty. Several systematic reviews and meta-analyses on topical VP in hip and knee arthroplasty have been recently published reporting sometimes conflicting results. Apart from all being limited by the quality of the included studies (mostly level III and IV), confounding variables are often included potentially leading to biased conclusions. If taken into consideration the exclusive use of VP in isolation, the available data, although very limited, suggest that it does not reduce the infection rate in routine primary hip and knee arthroplasty. Therefore, we still cannot advise for a routinary application. A properly powered randomized-controlled trial would be necessary to clarify the role of VP in hip and knee arthroplasty. Based on the analysis of the current evidence, the use of topical VP appears to be safe when used locally in terms of systemic adverse reactions, hence, if proven to be effective, it could bring great benefits due to its low cost and accessibility.


Estimating the circadian rhythm in the risk of occupational injuries and accidents.
The authors recently published a prototypic Risk Index (RI) to estimate the risk of critical errors associated with shift systems. This RI was based on published trends in the relative risk of injuries and accidents, and a simple additive model was proposed to estimate the risk for a given shift system. However, extending the RI to irregular work schedules requires an estimation of the phase and amplitude of the circadian rhythm in risk. This paper integrates the published evidence on three independent sources of data that allow such estimations to be made: the trend in risk over a 24 h day, over the course of the night shift, and across the three different (8 h) shifts. Despite potential confounders, maximum risk (i.e., acrophase = peak time) estimates across these three trends showed a remarkable consistency, with all three estimates occurring at about midnight, although the amplitude estimates varied considerably. The best estimate of the amplitude of the circadian rhythm in risk would appear to be that based on trend over the three (8 h) shifts, as this trend is the least confounded. The estimated acrophase (peak time) in risk appeared earlier than would be predicted from consideration of the circadian rhythm in alertness, fatigue, or performance on simple interpolated tasks, such as reaction time or performance on the Psychomotor Vigilance Test.


Intrathoracic neuroblastoma presenting with neonatal cardiorespiratory distress.
We report an unusual presentation of congenital intrathoracic neuroblastoma. Severe respiratory distress was present at birth and several salient clinical signs were suggestive of neonatal myocarditis. Excessive catecholamine secretions may have caused the observed cardiac dysfunction. Peculiar previously unreported cutaneous lesions were also noted in this case.


Electroacupuncture to treat painful diabetic neuropathy: study protocol for a three-armed, randomized, controlled pilot trial.
The purpose of this study is to conduct a basic analysis of the effectiveness and safety of electroacupuncture in the treatment of painful diabetic neuropathy (PDN) as compared to placebo and usual care and to evaluate the feasibility of large-scale clinical research. This study is a protocol for a three-armed, randomized, patient-assessor-blinded (to the type of treatment), controlled pilot trial. Forty-five participants with a ≥ six month history of PDN and a mean weekly pain score of ≥ 4 on the 11-point Pain Intensity Numerical Rating Scale (PI-NRS) will be assigned to the electroacupuncture group (n = 15), sham group (n = 15) or usual care group (n = 15). The participants assigned to the electroacupuncture group will receive electroacupuncture (remaining for 30 minutes with a mixed current of 2 Hz/120 Hz and 80% of the bearable intensity) at 12 standard acupuncture points (bilateral ST36, GB39, SP9, SP6, LR3 and GB41) twice per week for eight weeks (a total of 16 sessions) as well as the usual care. The participants in the sham group will receive sham electroacupuncture (no electrical current will be passed to the needle, but the light will be seen, and the sound of the pulse generator will be heard by the participants) at non-acupuncture points as well as the usual care. The participants in the usual care group will not receive electroacupuncture treatment during the study period and will receive only the usual care. The follow-up will be in the 5th, 9th and 17th weeks after random allocation. The PI-NRS score assessed at the ninth week will be the primary outcome measurement used in this study. The Short-Form McGill Pain Questionnaire (SF-MPQ), a sleep disturbance score (11-point Likert scale), the Short-Form 36v2 Health Survey (SF-36), the Beck Depression Inventory (BDI) and the Patient Global Impression of Change (PGIC) will be used as outcome variables to evaluate the effectiveness of the acupuncture. Safety will be assessed at every visit. The result of this trial will provide a basis for the effectiveness and safety of electroacupuncture for PDN. Clinical Research information Service. Unique identifier: KCT0000466.


Critical factors determining the variation in SOA yields from terpene ozonolysis: a combined experimental and computational study.
A substantial fraction of the total ultrafine particulate mass is comprised of organic compounds. Of this fraction, a significant subfraction is secondary organic aerosol (SOA), meaning that the compounds are a by-product of chemistry in the atmosphere. However, our understanding of the kinetics and mechanisms leading to and following SOA formation is in its infancy. We lack a clear description of critical phenomena; we often don't know the key, rate limiting steps in SOA formation mechanisms. We know almost nothing about aerosol yields past the first generation of oxidation products. Most importantly, we know very little about the derivatives in these mechanisms; we do not understand how changing conditions, be they precursor levels, oxidant concentrations, co-reagent concentrations (i.e., the VOC/NOx ratio) or temperature will influence the yields of SOA. In this paper we explore the connections between fundamental details of physical chemistry and the multitude of steps associated with SOA formation, including the initial gas-phase reaction mechanisms leading to condensible products, the phase partitioning itself, and the continued oxidation of the condensed-phase organic products. We show that SOA yields in the alpha-pinene + ozone are highly sensitive to NOx, and that SOA yields from beta-caryophylene + ozone appear to increase with continued ozone exposure, even as aerosol hygroscopicity increases as well. We suggest that SOA yields are likely to increase substantially through several generations of oxidative processing of the semi-volatile products.


Biodegradation of lignocellulose in Bermuda grass by white rot fungi analyzed by solid-state 13C nuclear magnetic resonance.
Following the solid-state fermentation of Bermuda grass by two lignin-degrading white rot fungi, compositional changes have been observed in situ by utilization of cross-polarization and magic angle spinning 13C nuclear magnetic resonance difference spectra and interrupted decoupling spectra. Intensity differences in the 13C resonances assigned to specific components of the cell wall were used to observe these changes. Bermuda grass treated with Phanerochaete chrysosporium K-3 exhibited losses primarily in the polysaccharide components, with a smaller proportion of phenolic components also being degraded. In contrast, Ceriporiopsis subvermispora FP 90031-sp removed a proportionate amount of phenolic components compared with polysaccharide components. The results also indicated that C. subvermispora preferentially removes guaiacyl phenolic components relative to syringyl phenolic components, while P. chrysosporium was nonspecific in its attack on phenolic components.


The ompU Paralogue vca1008 is required for virulence of Vibrio cholerae.
We made single and combined mutations in ompU, ompT, and the two putative porin genes vca1008 and vc0972. The fitness of the strains was tested in vitro and in the infant mouse model of intestinal infection. We also studied the transcriptional induction of vca1008 in vitro and during mouse infection. We show that vca1008 is induced during infection and is necessary and sufficient (in the absence of ompU, ompT, and vc0972) for infection.


Logic circuit upon angiogenic response controlled by enzyme-linked iron oxide microparticles--towards biocomputing in human cells.
In the present study, we designed a logic circuit upon angiogenic response controlled by a combination of enzyme-functionalized magnetic microparticles operating in human umbilical vein endothelial cells (HUVECs). The reported results represent the first example of a biocomputing system operating in controlling angiogenesis.


Cell-in-Cell-Mediated Entosis Reveals a Progressive Mechanism in Pancreatic Cancer.
Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with high intratumoral heterogeneity. There is a lack of effective therapeutics for PDAC. Entosis, a form of nonapoptotic regulated cell death mediated by cell-in-cell structures (CICs), has been reported in multiple cancers. However, the role of entosis in PDAC progression remains unclear. CICs were evaluated using immunohistochemistry and immunofluorescence staining. The formation of CICs was induced by suspension culture. Through fluorescence-activated cell sorting and single-cell RNA sequencing, entosis-forming cells were collected and their differential gene expression was analyzed. Cell functional assays and mouse models were used to investigate malignant phenotypes. Clinical correlations between entosis and PDAC were established by retrospective analysis. Entosis was associated with an unfavorable prognosis for patients with PDAC and was more prevalent in liver metastases than in primary tumors. The single-cell RNA sequencing results revealed that several oncogenes were up-regulated in entosis-forming cells compared with parental cells. These highly entotic cells demonstrated higher oncogenic characteristics in vitro and in vivo. NET1, neuroepithelial cell transforming gene 1, is an entosis-related gene that plays a pivotal role in PDAC progression and is correlated with poor outcomes. Entosis is correlated with PDAC progression, especially in liver metastasis. NET1 is a newly validated entosis-related gene and a molecular marker of poor outcomes. PDAC cells generate a highly aggressive subpopulation marked by up-regulated NET1 via entosis, which may drive PDAC progression.


Can mutualistic morality predict how individuals deal with benefits they did not deserve?
An individual obtains an unfair benefit and faces the dilemma of either hiding it (to avoid being excluded from future interactions) or disclosing it (to avoid being discovered as a deceiver). In line with the target article, we expect that this dilemma will be solved by a fixed individual strategy rather than a case-by-case rational calculation.


Pharmacotherapy for hyperuricemia in hypertensive patients.
High blood pressure represents a major public health problem. Worldwide, approximately one fourth of the adult population has hypertension. Epidemiological and experimental studies suggest a linkage between hyperuricemia and hypertension. Hyperuricemia affects 25-40 % of patients with untreated hypertension. A much lower prevalence has been reported in normotensives or in the general population. However, whether lowering serum uric acid (SUA) might lower blood pressure (BP) is an unanswered question. To determine whether uric acid lowering agents reduce BP in patients with primary hypertension. Electronic searches of the following sources were performed without language restriction: Cochrane Hypertension Group Specialised Register (1946 to May 2012), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012 Issue 4), MEDLINE (1946 to May 2012), EMBASE (1974 to May 2012), LILACS (1982 to July 2012), Scirus and ClinicalTrials.gov. Authors of relevant papers were also contacted regarding further published and unpublished work. To be included in this review, the studies had to meet the following criteria: 1) Randomised or quasi-randomised with a group assigned to receive a uric acid lowering agent and another group assigned to receive placebo; 2) Double-blind, single-blind or open label; 3) Parallel or crossover trial; 4) For crossover trial, a washout period of at least two weeks; 5) Minimum treatment duration of four weeks; 6) Participants with diagnosis of essential hypertension and hyperuricemia, serum uric acid greater than 6 in women, 7 in men and 5.5 in children/adolescents; 7) Outcome measures includes change in casual or ambulatory, systolic or diastolic blood pressure. Two independent reviewers collected the data using a data extraction form. Disagreements were resolved by discussion. Risk of bias was accessed by the Cochrane Collaboration Risk of Bias Tool. Three hundred and thirty-six abstracts were examined. One study (enrolling hypertensive and hyperuricemic patients) met the inclusion criteria for the review and was independently rated by both authors. No other studies were identified by the supplementary searches. The study identified as eligible for this review was a randomised controlled trial conducted in the USA (FEIG 2008 ) . This well designed double-blind, placebo-controlled, crossover trial randomised 30 adolescents (11-17 years), newly diagnosed stage 1 primary hypertension and with SUA ≥ 6mg/dl, to receive allopurinol 200 mg twice daily for 4 weeks, and placebo for 4 weeks, with a 2 week washout period between treatments. Casual BP during the allopurinol phase decreased - 6.9 mmHg (95 % CI, - 4.5 to - 9.3), systolic, and - 5.1 mmHg (95 % CI, - 2.5 to - 7.8), diastolic, versus during the placebo phase, - 2.0 mmHg (95 % CI, 0.3 to - 4.3) systolic and - 2.4 mmHg (95 % CI, 0.2 to - 4.1) diastolic. For the secondary outcome (change in 24 ambulatory BP), change in systolic BP with allopurinol was - 6.3 mmHg (95 % CI, - 3.8 to - 8.9), systolic, and - 4.6 mmHg (95% CI, - 2.4 to - 6.8), diastolic, and with placebo, 0.8 mmHg (95 % CI, 3.4 to - 2.9) systolic and - 0.3 mmHg (95 % CI, 2.3 to - 2.1) diastolic. P-value results ranged from 0.004 to 0.05. No participant dropout occurred and no adverse effects were seen in patients treated with allopurinol. Meta-analysis was not possible in this systematic review. In the one study that matched the inclusion criteria allopurinol decreased "in office" and ambulatory systolic and diastolic BP. Because there was only one included RCT, the number of patients providing data on pharmacotherapy for hyperuricemia in hypertension is small and restricted to adolescents with recently diagnosed mild essential hypertension. Hence, there is insufficient evidence to recommend the use of allopurinol or other hypouricemic drugs as an initial or adjuvant treatment of hypertension and more RCTs are needed.


Distal radial artery approach is safe and effective for cerebral angiography and neuroendovascular treatment: A single-center experience with ultrasonographic measurement.
The transradial artery approach to cerebral angiography can reduce both patient stress following examination and the risk of major complications due to hematoma. Recently, the distal radial artery approach (DRA) has garnered attention in cardiology as a minimally invasive method. DRA is also considered applicable to neurosurgery, although concerns about procedural difficulty and complications persist. Therefore, this study aimed to evaluate the efficacy of the DRA in cerebral angiography and neuroendovascular treatment. We retrospectively selected 30 consecutive patients for whom the DRA was attempted for cerebral angiography at our hospital. The patients' age, sex, height, weight, and medical history information was collected and correlated with successful puncture and complications. The diameter of the distal radial artery (RA) was measured using ultrasonography. The median patient age was 67 years (range, 32-87 years) and 21 (70%) were men. The median diameter of the distal RA was 2.3 mm (range, 1.7-3.2 mm). Distal RA puncture was successful in 23 patients (77%) and no complications were noted; however there was no significant correlation between successful puncture and any of the patient factors. Carotid artery stenting and preoperative tumor embolization were performed via DRA in six and three cases, respectively. Although puncture site hematoma occurred in only one case, all treatments were successful, and no major complications were observed. DRA can be safely used for cerebral angiography and neuroendovascular treatment.


Sirt1 Protects Subventricular Zone-Derived Neural Stem Cells from DNA Double-Strand Breaks and Contributes to Olfactory Function Maintenance in Aging Mice.
DNA damage is assumed to accumulate in stem cells over time and their ability to withstand this damage and maintain tissue homeostasis is the key determinant of aging. Nonetheless, relatively few studies have investigated whether DNA damage does indeed accumulate in stem cells and whether this contributes to stem cell aging and functional decline. Here, we found that, compared with young mice, DNA double-strand breaks (DSBs) are reduced in the subventricular zone (SVZ)-derived neural stem cells (NSCs) of aged mice, which was achieved partly through the adaptive upregulation of Sirt1 expression and non-homologous end joining (NHEJ)-mediated DNA repair. Sirt1 deficiency abolished this effect, leading to stem cell exhaustion, olfactory memory decline, and accelerated aging. The reduced DSBs and the upregulation of Sirt1 expression in SVZ-derived NSCs with age may represent a compensatory mechanism that evolved to protect stem cells from excessive DNA damage, as well as mitigate memory loss and other stresses during aging.


Endothelial nitric oxide synthase gene polymorphisms and the risk of silent brain infarction.
Silent brain infarction (SBI), a unique cerebrovascular disorder, is frequently detected on magnetic resonance imaging (MRI) of apparently healthy elderly persons, and it is known to increase the risk of stroke and other related diseases. Although detailed mechanisms of SBI pathogenesis have yet to be determined, recent studies suggest that SBI is significantly influenced by genetic factors. In this study, we investigated polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (i.e., -786T>C, 4a4b and 894G>T) as possible risk factors for SBI. We enrolled 269 patients with SBI and 234 control subjects and examined their fasting plasma homocysteine and folate levels, and analyzed for eNOS polymorphisms and haplotypes. The prevalence of SBI was shown to be significantly higher in patients with the eNOS 894GT genotype (OR, 2.00; 95% CI, 1.30-3.08) and 894GT+TT genotype (OR, 2.05; 95% CI, 1.34-3.16), compared with the 894GG genotype. However, in the case of -786T>C and 4a4b polymorphisms, no significant difference was observed between SBI patients and normal subjects. Interestingly, we found that the prevalence of SBI can increase twice as high when either -786T>C or 4a4b polymorphism was combined with 894G>T polymorphism, -786TC+CC/894GT+TT (OR, 3.83; 95% CI, 1.24-11.80) and 4a4b+4a4a/894GT+TT (OR, 4.08; 95% CI, 1.34-12.40), respectively. According to haplotype analysis, we found that three haplotypes (-786T-4b-894G, -786T-4b-894T and -786C-4a-894T) were shown to be significantly different between SBI patients and control subjects. These results indicate that eNOS polymorphisms and haplotypes serve as risk factors for SBI, and three different polymorphic loci in the eNOS gene play interactively, thereby leading to synergistic effects for the generation of SBI.


Determination of urinary norandrosterone excretion in females during one menstrual cycle by gas chromatography/mass spectrometry.
Conjugated norandrosterone is the main urinary metabolite of anabolic steroids like nandrolone, norandrostenedione and norandrostenediol. Nandrolone traces of endogenous origin have been identified in human follicular fluid, and further investigations revealed urinary excretion of norandrosterone in pregnant and non-pregnant females and even males. A threshold level for the norandrosterone concentration in urine has been established when controlling the administration of prohibited nandrolone or its precursors in human doping control. This level has been set to 2 ng/mL for males and females. To investigate the excretion of conjugated norandrosterone in females more systematically, we collected daily urine samples from 12 female volunteers during a whole menstrual cycle. These samples were analysed for norandrosterone down to a limit of quantification and identification of 0.05 ng/mL (180 pmol/L). The results clearly show that all the volunteers excreted norandrosterone glucuronide in a characteristic pattern during one menstrual cycle. Concentrations in urine were considerably lower at the beginning of the follicular and the end of the luteal phases than midcyclic. Peak concentrations up to 0.8 ng/mL (2.9 nmol/L) were recorded and they were three to four times higher than the values at the beginning and end of the cycle. The time of the peak concentration was clearly related to the increased excretion of luteinizing hormone. These results strongly support the possibility of endogenous nandrolone production as a side reaction to enzymatic aromatisation. However, a threshold value of 2 ng/mL for reporting adversed findings in doping control of females was never reached in any of the samples.


Differential spheroid formation by oral cancer cells.
Squamous cell carcinomas (SCC) make up 96% of all oral cancers. Most laboratory SCC studies grow cells as a monolayer, which does not accurately represent the disease in vivo. We used a more relevant multicellular spheroid (MCS) model to study this disease. The SCC9β6KDFyn cell line, which expresses full-length β6 and a kinase dead Fyn formed the largest MCS. Cell adhesive properties are dynamic and N-cadherin was increased in the largest MCS. c-Raf mediates the survival of tumor cells and was consistently expressed both in monolayers and in the MCS by SCC9β6D1 cells which lack the β6 cytoplasmic tail and, do not activate Fyn. SCC9β6KDFyn cells also express high levels of c-Raf when grown as spheroids in which Fyn suppression stimulates MCS formation. Tumor microenvironment and growth patterns modulate cell behavior and suppression of Fyn kinase may promote MCS growth.


The Health Resources and Services Administration diversity data collection.
The Health Resources and Services Administration maintains a strong emphasis on increasing the diversity of the health-care workforce through its grant programs. Increasing the diversity of the workforce is important for reducing health disparities in the population caused by socioeconomic, geographic, and race/ethnicity factors because evidence suggests that minority health professionals are more likely to serve in areas with a high proportion of underrepresented racial and ethnic minority groups. The data show success in increasing the diversity of enrollees in five nursing programs.


Crescentic proximal metatarsal osteotomy for moderate to severe hallux valgus: a mean 12.2 year follow-up study.
The senior author's (R.C.) first 25 patients (37 feet) treated with a combination proximal crescentic osteotomy and distal soft-tissue reconstruction made up the patient cohort. All 25 patients were reviewed at a minimum of one year post-op (short-term follow-up) and 20/25 (31/37 feet) were reviewed again at a mean 12.2 years (range 11.4 to 13.0 yrs) post-op (long-term follow-up). This allowed for a comparison of short- and long-term results and led to a long-term follow-up rate of 84% (31/37 feet, mean 12.2 yrs). Clinical, radiographic and patient outcome measures were obtained and compared pre-op and at short- and long-term follow-up. The mean preoperative hallux valgus (HVA) and intermetatarsal angles (IMA) were 37degrees and 16 degrees respectively. The mean HVA correction was 24 degrees and IMA correction 10 degrees at long-term follow-up with no tendency toward recurrence. Sesamoid position and first MTP subluxation was markedly improved postoperatively and the correction was maintained at long-term follow-up. Patients were asked about their satisfaction in terms of pain, appearance and motion. At long-term follow-up, more than 90% of patients were completely satisfied with pain and motion and greater than 80% with their appearance. Ninety-four percent of patients said they would have the operation again. The AOFAS clinical rating scale for the hallux was calculated retrospectively for pre-op and short-term follow-up and prospectively for long-term follow-up. The mean pre-op score was 37/100 (16 to 60) which significantly improved to 92/100 (67 to 100) at both follow-up periods, suggesting no evidence of decrease in outcome over time. Complications included two patients (5%) that were over-corrected into varus (one symptomatic, one asymptomatic), and four patients (11%) that were undercorrected, developing asymptomatic recurrences (>10 degrees increase HVA) at long-term follow-up. In addition, two patients (5%) developed new transfer lesions postoperatively, likely related to technical error (one varus overcorrection, one dorsiflexion malunion). In conclusion, the long-term results, with a mean follow-up of 12.2 years, of the resection realignment procedure for moderate to severe hallux valgus are generally excellent and the complication rate is low and acceptable. Attention to detail, avoiding both undercorrection, which can lead to recurrence, and overcorrection, which can cause symptomatic varus, is essential.


HDAC inhibitors show differential epigenetic regulation and cell survival strategies on p53 mutant colon cancer cells.
Besides inactivating tumour suppressor activity in cells, mutations in p53 confer significant oncogenic functions and promote metastasis and resistance to anticancer therapy. A variety of therapies involving genetic and epigenetic signalling events regulate tumorogenesis and progression in such cases. Pharmacological interventions with HDAC inhibitors have shown promise in therapy. This work explores the changes in efficacy of the four HDAC inhibitors SAHA, MS-275, valproic acid and sodium butyrate on a panel of colon cancer cell lines - HCT116 (p53 wt), HCT116 p53-/-, HT29 and SW480 (with mutations in p53). Clonogenic assays, gene profiling and epigenetic expression done on these cells point to p53 dependent differential activity of the 4 HDAC inhibitors which also elevate methylation levels in p53 mutant cell lines. In silico modelling establishes the alterations in interactions that lead to such differential activity of valproic acid, one of the inhibitors considered for the work. Molecular Dynamic simulations carried out on the valproic acid complex ensure stability of the complex. This work establishes a p53 dependent epigenetic signalling mechanism triggered by HDAC inhibition expanding the scope of HDAC inhibitors in adjuvant therapy for p53 mutant tumours.


Benzodiazepine requirements during alcohol withdrawal syndrome: clinical implications of using a standardized withdrawal scale.
An accurate characterization of the severity of the alcohol withdrawal syndrome is likely to provide clear guidelines for drug therapy in this disorder. We studied (retrospectively) the usefulness of a standardized withdrawal scale on benzodiazepine drug requirements for patients undergoing alcohol detoxification in a general hospital. One hundred thirty-three patients received the revised Clinical Institute withdrawal Assessment Scale for Alcohol and were medicated only if the score was greater than 10. A comparison group of 117 patients was treated without reference to the scale. The groups were evenly matched with respect to age, sex, concurrent drug use, and laboratory abnormalities. Subjects treated according to the scale required less benzodiazepine (median dose, 50 mg diazepam equivalent compared with 75 mg) (p = 0.04). Rates of complications, discharge against medical advice, and length of stay did not differ between the groups. Rank correlation coefficients revealed a closer relationship between the degree of alcohol exposure (as determined by admitting blood alcohol levels, creatine phosphokinase, and SGOT) and benzodiazepine requirements during withdrawal for the group treated with the scale. Findings suggest that when the scale is used, patients with a greater degree of physical dependence receive (appropriately) a higher dose of benzodiazepine and those with a lesser degree of dependence receive (appropriately) a lower dose of benzodiazepine. Use of the scale appears to minimize both under- and overdosing with benzodiazepine for alcohol withdrawal syndrome.


Growth transformation of human T cells by herpesvirus saimiri requires multiple Tip-Lck interaction motifs.
Lymphoma induction and T-cell transformation by herpesvirus saimiri strain C488 depends on two viral oncoproteins, StpC and Tip. The major interaction partner of Tip is the protein tyrosine kinase Lck, a key regulator of T-cell activation. The Lck binding domain (LBD) of Tip comprises two interaction motifs, a proline-rich SH3 domain-binding sequence (SH3B) and a region with homology to the C terminus of Src family kinase domains (CSKH). In addition, biophysical binding analyses with purified Lck-SH2 domain suggest the phosphorylated tyrosine residue 127 of Tip (pY127) as a potential third Lck interaction site. Here, we addressed the relevance of the individual binding motifs, SH3B, CSKH, and pY127, for Tip-Lck interaction and for human T-cell transformation. Both motifs within the LBD displayed Lck binding activities and cooperated to achieve a highly efficient interaction, while pY127, the major tyrosine phosphorylation site of Tip, did not enhance Lck binding in T cells. Herpesvirus saimiri strain C488 recombinants lacking one or both LBD motifs of Tip lost their transforming potential on human cord blood lymphocytes. Recombinant virus expressing Tip with a mutation at position Y127 was still able to transform human T lymphocytes but, in contrast to wild-type virus, was strictly dependent on exogenous interleukin-2. Thus, the strong Lck binding mediated by cooperation of both LBD motifs was essential for the transformation of human T cells by herpesvirus saimiri C488. The major tyrosine phosphorylation site Y127 of Tip was particularly required for transformation in the absence of exogenous interleukin-2, suggesting its involvement in cytokine signaling pathways.


[Community-acquired pneumonia associated with influenza virus].
Pneumonia is one of the most common complications of influenza infection. However, its characteristics are not well-known. Our aim was to assess the frequency of community-acquired pneumonia (CAP) associated with influenza virus and to determine its clinical and epidemiological characteristics. A total of 240 patients with CAP were evaluated and cases with serological evidence of influenza virus infection were identified. Patients in whom there was no evidence of infection by other microbial agents were selected and defined as influenza virus infection-associated CAP (CAP-i). Clinical and epidemiological features of CAP-i patients were compared with the rest of patients with CAP. A microbial diagnosis was achieved in 143 (59.6%) of 240 patients with CAP. In 12 cases (5%) there was serological evidence of infection by influenza A virus. In 8 patients no other respiratory pathogens were detected (CAP-i). In a multivariate analysis, the presence of arthromyalgias (odds ratio [OR] = 30, 68; 95% confidence interval [CI], 1-946), plasmatic sodium < 133 mEq/l (OR = 16.92; 95% CI, 1.48-193), bilateral infiltrates in chest X-ray (OR = 8.83; 95% CI, 1.35-57.6), diagnosis of CAP in January or February (OR = 5.60; 95% CI, 0.87-35.8) and blood neutrophil cell count >= 14,000/l, (OR = 5.23; 95% CI, 0.85-32) were all independently associated with CAP-i. The simultaneous presence of all these characteristics had a positive and negative predictive value of 95% and 99%, respectively, to differentiate CAP-i from other CAP. Influenza virus infection-associated CAP is uncommon. Some clinical and radiographic variables could differentiate CAP-i from other CAP. These parameters could also help identify patients who are more likely to benefit from specific antiviral therapy.


Computational Intelligence Approaches in Developing Cyberattack Detection System.
The Internet plays a fundamental part in relentless correspondence, so its applicability can decrease the impact of intrusions. Intrusions are defined as movements that unfavorably influence the focus of a computer. Intrusions may sacrifice the reputability, integrity, privacy, and accessibility of the assets attacked. A computer security system will be traded off when an intrusion happens. The novelty of the proposed intelligent cybersecurity system is its ability to protect Internet of Things (IoT) devices and any networks from incoming attacks. In this research, various machine learning and deep learning algorithms, namely, the quantum support vector machine (QSVM), k-nearest neighbor (KNN), linear discriminant and quadratic discriminant long short-term memory (LSTM), and autoencoder algorithms, were applied to detect attacks from signature databases. The correlation method was used to select important network features by finding the features with a high-percentage relationship between the dataset features and classes. As a result, nine features were selected. A one-hot encoding method was applied to convert the categorical features into numerical features. The validation of the system was verified by employing the benchmark KDD Cup database. Statistical analysis methods were applied to evaluate the results of the proposed study. Binary and multiple classifications were conducted to classify the normal and attack packets. Experimental results demonstrated that KNN and LSTM algorithms achieved better classification performance for developing intrusion detection systems; the accuracy of KNN and LSTM algorithms for binary classification was 98.55% and 97.28%, whereas the KNN and LSTM attained a high accuracy for multiple classification (98.28% and 970.7%). Finally, the KNN and LSTM algorithms are fitting-based intrusion detection systems.


Contact angle measurement system with liquid sodium in inert atmosphere.
Liquid sodium is the heat transport medium in fast breeder reactors due to its favorable chemical, physical, and nuclear properties. Wetting of liquid sodium with the material of reactor components is essential for the effective functioning of the reactor. Liquid sodium wetting plays a crucial role, such as in (i) heat transfer and (ii) image reconstruction under sodium ultrasonic scanners. Contact angle is the inverse measure of the wetting of liquids over solid surfaces. A contact angle measurement system was set up in an inert atmosphere glow box to study the wetting behavior of liquid sodium on reactor materials. The contact angle of liquid sodium on nickel surface was measured as a function of temperature, and the results obtained were found to be in good agreement with the literature values. The contact angle of liquid sodium on SS316LN as a function of temperature was measured for the first time using this facility.


Accounting for patient size in the optimization of dose and image quality of pelvis cone beam CT protocols on the Varian OBI system.
The purpose of this study was to develop size-based radiotherapy kilovoltage cone beam CT (CBCT) protocols for the pelvis. Image noise was measured in an elliptical phantom of varying size for a range of exposure factors. Based on a previously defined "small pelvis" reference patient and CBCT protocol, appropriate exposure factors for small, medium, large and extra-large patients were derived which approximate the image noise behaviour observed on a Philips CT scanner (Philips Medical Systems, Best, Netherlands) with automatic exposure control (AEC). Selection criteria, based on maximum tube current-time product per rotation selected during the radiotherapy treatment planning scan, were derived based on an audit of patient size. It has been demonstrated that 110 kVp yields acceptable image noise for reduced patient dose in pelvic CBCT scans of small, medium and large patients, when compared with manufacturer's default settings (125 kVp). Conversely, extra-large patients require increased exposure factors to give acceptable images. 57% of patients in the local population now receive much lower radiation doses, whereas 13% require higher doses (but now yield acceptable images). The implementation of size-based exposure protocols has significantly reduced radiation dose to the majority of patients with no negative impact on image quality. Increased doses are required on the largest patients to give adequate image quality. The development of size-based CBCT protocols that use the planning CT scan (with AEC) to determine which protocol is appropriate ensures adequate image quality whilst minimizing patient radiation dose.


Visualisation of the T cell differentiation programme by Canonical Correspondence Analysis of transcriptomes.
Currently, in the era of post-genomics, immunology is facing a challenging problem to translate mutant phenotypes into gene functions based on high-throughput data, while taking into account the classifications and functions of immune cells, which requires new methods. Here we propose a novel application of a multidimensional analysis, Canonical Correspondence Analysis (CCA), to reveal the molecular characteristics of undefined cells in terms of cellular differentiation programmes by analysing two transcriptomic datasets. Using two independent datasets, whether RNA-seq or microarray data, CCA successfully visualised the cross-level relationships between genes, cells, and differentiation programmes, and thereby identified the immunological features of mutant cells (Gata3-KO T cells and Stat3-KO T cells) in a data-oriented manner. With a new concept, differentiation variable, CCA provides an automatic classification of cell samples, which had a high sensitivity and a comparable performance to other classification methods. In addition, we elaborate how CCA results can be interpreted, and reveal the features of CCA in comparison with other visualisation techniques. CCA is a visualisation tool with a classification ability to reveal the cross-level relationships of genes, cells and differentiation programmes. This can be used for characterising the functional defect of cells of interest (e.g. mutant cells) in the context of cellular differentiation. The proposed approach fits with common hypothesis-oriented studies in immunology, and can be used for a wide range of molecular and genomic studies on cellular differentiation mechanisms.


Compartment syndrome: time from diagnosis to fasciotomy.
A definitive safe time to fasciotomy for compartment syndrome has not been established. Therefore, the records of 28 patients who had a fasciotomy for compartment syndrome at two trauma centers (18 level I, 10 level II) were reviewed to determine time from diagnosis to fasciotomy and clinical outcome. Average times at the two trauma centers (level I: 160 minutes, range, 50-315 minutes; level II: 105 minutes, range, 51-185 minutes) were significantly different. Ten patients (5 level I, 5 level II) with an average time from diagnosis to fasciotomy of 122 minutes (range, 70-185 minutes) sustained residual deficits. There was no correlation between time from diagnosis to fasciotomy and residual deficits. A time from diagnosis to fasciotomy as short as 70 minutes was associated with residual deficit, but a time as long as 315 minutes (patient with deficits) was associated with no functional deficits.


Antimicrobial properties of liposomal azithromycin for Pseudomonas infections in cystic fibrosis patients.
This work was carried out to construct a novel liposomal azithromycin formulation and examine its antimicrobial effects against Pseudomonas aeruginosa. The liposomal azithromycin formulation was prepared by the dehydration-rehydration vesicle method and its characterizations were tested. The MIC and the MBC of the liposomal formulation were determined by the microbroth dilution method. Liposomal azithromycin activity against biofilm-forming P. aeruginosa was assessed using a Calgary biofilm device. The effect of subinhibitory concentrations of liposomal azithromycin on bacterial virulence factors and motility studies was tested on P. aeruginosa strains. The bacteria and liposome interactions were studied using flow cytometry analysis. The toxicities of the liposomal formulation on erythrocytes and A549 lung cells were evaluated in vitro. The average diameter of the liposomal azithromycin was 406.07 ± 45 nm and the encapsulation efficiency was 23.8% ± 0.2%. The MIC and MBC values of liposomal azithromycin were significantly lower than those of free azithromycin. The liposomal azithromycin significantly reduced the bacteria in the biofilm and attenuated the production of different virulence factors; it also reduced the different patterns of bacterial motilities. By flow cytometry analysis data, it was shown that there are interactions of liposomes with the bacterial membranes. No significant haemolysis or cell toxicity was observed with the liposomal formulation. The results of this research indicate that this novel liposomal azithromycin formulation could be a useful therapy to enhance the safety and efficacy of azithromycin against P. aeruginosa-infected persons.


Astrocyte-derived lipocalin-2 mediates hippocampal damage and cognitive deficits in experimental models of vascular dementia.
Lipocalin-2 (LCN2) has diverse functions in multiple pathophysiological conditions; however, its pathogenic role in vascular dementia (VaD) is unknown. Here, we investigated the role of LCN2 in VaD using rodent models of global cerebral ischemia and hypoperfusion with cognitive impairment and neuroinflammation. Mice subjected to transient bilateral common carotid artery occlusion (tBCCAo) for 50 min showed neuronal death and gliosis in the hippocampus at 7 days post-tBCCAo. LCN2 expression was observed predominantly in the hippocampal astrocytes, whereas its receptor was mainly detected in neurons, microglia, and astrocytes. Furthermore, Lcn2-deficient mice, compared with wild-type animals, showed significantly weaker CA1 neuronal loss, cognitive decline, white matter damage, blood-brain barrier permeability, glial activation, and proinflammatory cytokine production in the hippocampus after tBCCAo. Lcn2 deficiency also attenuated hippocampal neuronal death and cognitive decline at 30 days after unilateral common carotid artery occlusion (UCCAo). Furthermore, intracerebroventricular (i.c.v) injection of recombinant LCN2 protein elicited CA1-neuronal death and a cognitive deficit. Our studies using cultured glia and hippocampal neurons supported the decisive role of LCN2 in hippocampal neurotoxicity and microglial activation, and the role of the HIF-1α-LCN2-VEGFA axis of astrocytes in vascular injury. Additionally, plasma levels of LCN2 were significantly higher in patients with VaD than in the healthy control subjects. These results indicate that hippocampal damage and cognitive impairment are mediated by LCN2 secreted from reactive astrocytes in VaD.


Cloning and nucleotide sequence of the brnQ gene, the structural gene for a membrane-associated component of the LIV-II transport system for branched-chain amino acids in Salmonella typhimurium.
The genetically defined gleR-brnQ region responsible for the branched-chain amino acid transport in Salmonella typhimurium was mapped in the 3.3-kilobase SalI-PstI segment of plasmid pOH56 by complementation analysis. By subcloning and genetic recombination analysis, the gleR and brnQ3 mutational sites were localized within the 0.85-kilobase SalI-EcoRV segment, and brnQ4 within the 0.8-kilobase EcoRV-HindIII segment. The nucleotide sequence of the brnQ gene and its flanking regions was determined. The brnQ gene is encoded by the sequence starting 24 base pairs upstream from the EcoRV site. Transcription of the brnQ gene starts at three sites separated by 171, 173 and 174 nucleotides, respectively, from the initiation codon. The promoter sequences can be seen in the immediate upstream region of the transcription initiation sites. There is a long silent region between the transcription initiation sites and a potential Shine-Dalgarno nucleotide sequence. The coding sequence of the brnQ gene, which is 1317 base pairs long, specifies a very hydrophobic protein of 439 amino acid residues.


Silencing DNA methyltransferase 1 (DNMT1) inhibits proliferation, metastasis and invasion in ESCC by suppressing methylation of RASSF1A and DAPK.
Our previous study showed DNMT1 is up-regulated in esophageal squamous cell carcinoma (ESCC), which is associated with methylation of tumor suppressors. In the current study, we investigate the role of DNMT1 in ESCC. We found silencing DNMT1 inhibited proliferation, metastasis and invasion of three different ESCC cells, K150, K410 and K450. We also found silencing DNMT1 induced G1 arrest and cell apoptosis in K150, K410 and K450 cells. In vivo study showed silencing DNMT1 suppressed tumor growth in nude mice. In addition, silencing DNMT1 increased expression of tumor suppressor genes, RASSF1A and DAPK, in ESCC cells and ESCC xenograft in nude mice. Moreover, silencing DNMT1 decreased methylation in promoter of RASSF1A and DAPK. In conclusion, our data demonstrated that silencing DNMT1 inhibits proliferation, metastasis and invasion in ESCC by suppressing methylation of RASSF1A and DAPK.


Critical mutation rate has an exponential dependence on population size in haploid and diploid populations.
Understanding the effect of population size on the key parameters of evolution is particularly important for populations nearing extinction. There are evolutionary pressures to evolve sequences that are both fit and robust. At high mutation rates, individuals with greater mutational robustness can outcompete those with higher fitness. This is survival-of-the-flattest, and has been observed in digital organisms, theoretically, in simulated RNA evolution, and in RNA viruses. We introduce an algorithmic method capable of determining the relationship between population size, the critical mutation rate at which individuals with greater robustness to mutation are favoured over individuals with greater fitness, and the error threshold. Verification for this method is provided against analytical models for the error threshold. We show that the critical mutation rate for increasing haploid population sizes can be approximated by an exponential function, with much lower mutation rates tolerated by small populations. This is in contrast to previous studies which identified that critical mutation rate was independent of population size. The algorithm is extended to diploid populations in a system modelled on the biological process of meiosis. The results confirm that the relationship remains exponential, but show that both the critical mutation rate and error threshold are lower for diploids, rather than higher as might have been expected. Analyzing the transition from critical mutation rate to error threshold provides an improved definition of critical mutation rate. Natural populations with their numbers in decline can be expected to lose genetic material in line with the exponential model, accelerating and potentially irreversibly advancing their decline, and this could potentially affect extinction, recovery and population management strategy. The effect of population size is particularly strong in small populations with 100 individuals or less; the exponential model has significant potential in aiding population management to prevent local (and global) extinction events.


Bowel obsession syndrome in a patient with ulcerative colitis.
Gastroenterologists are often faced with the diagnostic problem of differentiating acute symptoms of ulcerative colitis from functional intestinal disorders. Bowel obsession syndrome (BOS) is an OCD-like, functional syndrome characterized by fear of fecal incontinence and compulsive behaviors of evacuation-checking. Only sparse case studies on treatment of BOS with antidepressants have been published. This is the first study on successful psychotherapy of a male patient with ulcerative colitis overlapping functional bowel symptoms and marked symptoms of BOS. Clinical recognition of BOS may help clinicians in differential diagnosis, prevent unnecessary investigations, and give patients the most appropriate treatment.


Green determination of eight water-soluble B vitamins in cosmetic products by liquid chromatography with ultraviolet detection.
B vitamins are a group of compounds with beneficious properties for dermatologic care, and therefore they are included in the cosmetic formulations as high added-value ingredients. In this paper, an analytical method for the simultaneous determination of eight water-soluble B vitamins in cosmetic products is reported for the first time. This method is based on liquid chromatography with ultraviolet detection (LC-UV) analysis after simple water leaching of the analytes from the cosmetic matrix. No organic solvents are required, beyond the ethanol used in the chromatographic mobile phase. The proposed method has been successfully validated showing good linearity, limits of detection in the low μg mL-1 range (from 0.14 to 0.43 μg mL-1) and good repeatability (relative standard deviation below 11 %). The accuracy of the method has been proven by the analysis of laboratory-made samples (i.e., a cream and a gel) with known concentrations of the analytes, providing low relative errors (below 12 %). Finally, the method has been successfully applied to four commercial cosmetic samples of different formulations without significant matrix effects. The results obtained and the environmentally friendly features of the method showed its usefulness for carrying out both pre- and in-market quality control of final cosmetic products.


B-cell acute lymphoblastic leukemia in patients with germline RUNX1 mutations.
Germline RUNX1 mutations underlie a syndrome, RUNX1-familial platelet disorder (RUNX1-FPD), characterized by bleeding symptoms that result from quantitative and/or qualitative defect in platelets and a significantly increased risk for developing hematologic malignancies. Myeloid neoplasms are the most commonly diagnosed hematologic malignancies, followed by lymphoid malignancies of T-cell origin. Here, we describe the first 2 cases of B-cell acute lymphoblastic leukemia (B-ALL) in patients with confirmed germline RUNX1 mutations. While 1 of the patients had a known diagnosis of RUNX1-FPD with a RUNX1 p.P240Hfs mutation, the other was the index patient of a kindred with a novel RUNX1 variant, RUNX1 c.587C>T (p.T196I), noted on a targeted genetic testing of the B-ALL diagnostic sample. We discuss the clinical course, treatment approaches, and the outcome for the 2 patients. Additionally, we describe transient resolution of the mild thrombocytopenia and bleeding symptoms during therapy, as well as the finding of clonal hematopoiesis with a TET2 mutant clone in 1 of the patients. It is critical to consider testing for germline RUNX1 mutations in patients presenting with B-ALL who have a personal or family history of thrombocytopenia, bleeding symptoms, or RUNX1 variants identified on genetic testing at diagnosis.


Meal replacements in the treatment of adolescent obesity: a randomized controlled trial.
Use of meal replacements (MRs) in lifestyle modification programs (LMPs) for obese adults significantly increases weight loss, compared with prescription of an isocaloric conventional diet (CD). This 12-month randomized trial examined 113 obese adolescents (mean ± s.d. age of 15.0 ± 1.3 years and BMI of 37.1 ± 5.1 kg/m2) who were assigned to a LMP, combined with meal plans of 1300-1500 kcal/day of CD (self-selected foods) or MR (three SlimFast shakes, one prepackaged meal, five vegetable/fruit servings). After month 4 (phase 1), participants originally treated with MR were unmasked to their phase 2 (months 5-12) random assignment: continued use of MR (i.e., MR+MR) or transitioned to CD (i.e., MR+CD). Participants initially treated with CD in phase 1, continued with CD (i.e., CD). All three groups were treated for an additional 8 months (phase 2). Regression models were used to evaluate percentage change in BMI from baseline to month 4 (phase 1), months 5-12 (phase 2), and baseline to month 12. At month 4, participants assigned to MR (N = 65) achieved a mean (±s.e.) 6.3 ± 0.6% reduction in BMI, compared to a significantly (P = 0.01) smaller 3.8 ± 0.8% for CD participants (N = 37). In phase 2, BMI increased significantly (P < 0.001) in all three conditions, resulting in no significant (P = 0.39) differences between groups in percentage change in BMI at month 12. Across groups, mean reduction in BMI from baseline to month 12 was 3.4 ± 0.7% (P < 0.01). Use of MR significantly improved short-term weight loss, compared with CD, but its continued use did not improve maintenance of lost weight.


mRNA vaccines against respiratory viruses.
The successes of the coronavirus disease 2019 (COVID-19) mRNA vaccines have accelerated the development of mRNA vaccines against other respiratory pathogens. The aim of this review is to highlight COVID-19 mRNA vaccine advances and provide an update on the progress of mRNA vaccine development against other respiratory pathogens. The COVID-19 mRNA vaccines demonstrated effectiveness in preventing severe COVID-19 and death. H7N9 and H10N8 avian influenza mRNA vaccines have demonstrated safety and immunogenicity in phase 1 clinical trials. Numerous seasonal influenza mRNA vaccines are in phase 1-3 clinical trials. Respiratory syncytial virus (RSV) mRNA vaccines have progressed to phase 2-3 clinical trials in adults and a phase 1 clinical trial in children. A combined human metapneumovirus and parainfluenza-3 mRNA vaccines was found to be well tolerated and immunogenic in a phase 1 trial among adults and trials are being conducted among children. Clinical trials of mRNA vaccines combining antigens from multiple respiratory viruses are underway. The development of mRNA vaccines against respiratory viruses has progressed rapidly in recent years. Promising vaccine candidates are moving through the clinical development pathway to test their efficacy in preventing disease against respiratory viral pathogens.


Novel RAB3GAP1 compound heterozygous mutations in Japanese siblings with Warburg Micro syndrome.
Warburg Micro syndrome (WARBM) is a rare autosomal recessive disease characterized by postnatal growth retardation, microcephaly, severely delayed motor and intellectual development, microcornea, congenital cataracts, optic atrophy, and hypogonadism. While WARBM is a genetically heterogeneous condition, RAB3GAP1 mutations account for ∼40% of WARBM patients, and 69 different mutations of various types (nonsense, missense, frameshift, and splice site mutations) have been identified to date. Japanese siblings (a 7 years 3 months old male and a 2 years 1month old female) were found to have WARBM-compatible phenotypes. Direct sequencing of RAB3GAP1 revealed novel compound heterozygous mutations in the siblings: a paternally inherited missense mutation (c.560G>C; p.Arg187Pro) in exon 7 and a maternally derived nonsense mutation (c.1009C>T; p.Arg337Ter) in exon 12. The siblings had WARBM caused by novel mutations in RAB3GAP1. Since molecular diagnosis permits adequate genetic counseling and appropriate management for predicted complications such as adequate sex steroid supplementation therapy for hypogonadism, in addition to standard supportive therapies for developmental delay and visual dysfunction, we recommend molecular studies for this rare condition.


A pediatric non-protein losing Menetrier's disease successfully treated with octreotide long acting release.
Pediatric Menetrier's disease (MD) is an uncommon, acute, self-limited hypertrophic gastropathy characterized by enlarged gastric folds associated with epithelial hyperplasia and usually accompanied by protein losing gastropathy. Gastric cytomegalovirus infection is found in one third of MD children and its treatment is often associated with remission. Diagnosis often requires full-thickness biopsy due to inability to detect typical histological findings with conventional endoscopic biopsy. We report an uncommon case of non self-limited pediatric MD needing endoscopic mucosal resection for diagnosis which was then successfully treated with octreotide long-acting release (LAR). To the best of our knowledge, this is the first pediatric MD case successfully treated with octreotide LAR. Our experience suggests octreotide LAR as treatment for refractory MD before gastrectomy.


Cell growth and death rates as factors in the long-term performance, modeling, and design of immobilized cell reactors.
The viable fraction of immobilized cells in a bioreactor may be critical in predicting long-term or steady-state reactor performance. The assumption of near 100% viable cells in a bioreactor may not be valid for portions of immobilized cell reactors (ICRs) characterized by conditions resulting in appreciable death rates. A mathematical model of an adsorbed cell type ICR is presented in which a steady-state viable cell fraction is predicted, based on the assumptions of no cell accumulation in the reactor and a random loss of cells from the reactor. Data on cell death rates, cell growth rates, and productivity rates as functions of temperature, substrate, and ethanol concentration for the lactose utilizing yeast K. fragillis were incorporated into this model. The steady-state reactor viable cell fraction as predicted by this model is a strong function of both temperature and ethanol concentration. For example, a stable 20% viable fraction of the immobilized cells is predicted in ICR locations experiencing continuous conditions of either 30 g/L ethanol at 40 degrees C, or 95 g/L ethanol at 25 degrees C. Steady-state ICR "plug flow" concentration profiles and column productivities are predicted at three operating temperatures, 20, 30, and 40 degrees C using two different models for ethanol inhibition of productivity. These profiles suggest that the reactor operating temperature should be low if higher outlet ethanol concentrations are desired. Three reactor design strategies are presented to maximize the viable cell fraction and improve long-term ethanol productivity in ICR's: (1) reducing outlet ethanol concentrations, (2) rotating segments of an ICR between high and low ethanol environments, and (3) simultaneous removal of the ethanol produced from the reactor as it is formed.


Risk factors for ventilator-associated pneumonia by Pseudomonas aeruginosa in presence of recent antibiotic exposure.
To facilitate the decision-making process for therapy and prevention of ventilator-associated pneumonia (VAP) in patients undergoing recent antibiotic exposure, this study investigated whether the development of VAP episodes caused by Pseudomonas aeruginosa or other pathogens are related to different risk factors, thereby distinguishing two risk population for this serious complication. A 5-year retrospective case-control observational study was conducted. Cases of VAP caused by P. aeruginosa were compared with those caused by other pathogens. Univariate and multivariate analysis was performed using SPSS 11.0 software (SPSS Inc., Chicago, IL). Two groups were identified: P. aeruginosa (group P) was isolated in 58 (63.7%) episodes, and 33 episodes served as controls (group C), after a median of 12 days (interquartile range, 4-28 days) and 9 days (interquartile range, 3-12.5 days) of mechanical ventilation, respectively. P. aeruginosa was identified in 34.7% of episodes with early-onset pneumonia and in 73.5% with late-onset pneumonia. In a logistic regression analysis, P. aeruginosa was independently associated with duration of stay of 5 days or longer (relative risk = 3.59; 95% confidence interval, 1.04-12.35) and absence of coma (relative risk = 8.36; 95% confidence interval, 2.68-26.09). Risk for pathogens different from P. aeruginosa (group C) in early-onset pneumonia associated with coma was estimated to be 87.5%. Risk factors in episodes under recent antibiotic treatment caused by P. aeruginosa or other microorganism are not the same, a fact that could have implications for preventive and therapeutic approaches for this infection.


Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas.
The mammalian pancreas develops by the expansion and morphogenesis of the epithelial cells of the foregut endoderm via the sequential activation of transcription factors that direct differentiation into the various pancreatic lineages. Implicit in this growth and differentiation are the temporal and spatial processes of cell migration and three-dimensional organization, which cooperate to form a properly functioning organ. In many organ systems, such as the kidney, heart, and neural crest derivatives, migration and tissue morphogenesis is accomplished by the transient conversion of stationary epithelial cells to migratory mesenchymal-like cells in a process known as epithelial-mesenchymal transition (EMT). We report the identification of the expression of the transcription factor Snail2/Slug, a known inducer of EMT and cell movement, in both the endocrine and exocrine cells of the developing mouse pancreas. Snail2 is expressed in Neurogenin3-positive endocrine progenitor cells, and expression is maintained during endocrine cell differentiation where it becomes increasingly restricted to the insulin-producing beta cells and somatostatin-producing delta cells. In the adult pancreas, the expression of Snail2 is maintained at low but detectable levels in all beta cells, indicating a latent role for Snail2 in the mature islet. These findings of Snail2 expression during endocrine pancreas development are relevant to the recent evidence demonstrating the involvement of EMT in the expansion of human islet tissue in vitro. EMT-like events appear to be involved in the development of the mammalian pancreas in vivo.


The Correlation Between Schizophrenic Patients' Level of Internalized Stigma and Their Level of Hope.
The aim of this study is to determine the correlation between schizophrenic patients' level of internalized stigma and their level of hope. The population of the study consisted of patients who had been diagnosed with schizophrenia and also met the study inclusion criteria. The study sample selection from the population was not further divided; the study was conducted with 76 patients. The data of the study were collected using a personal information form, the Internalized Stigma of Mental Illness (ISMI) Scale, and Herth Hope Scale. The patients' mean score on the Internalized Stigma Scale was 72.78±16.05. Their score on the Hope Scale is 50.36±11.91. A significant negative correlation was found between the total mean scores of ISMI and the Herth Hope Scale (r=-0.360, p<0.01). A significant positive correlation was found between the stigma resistance subscale mean score of ISMI and the total mean score of the Herth Hope Scale (r=0.510, p<0.01). The internalized stigma levels of schizophrenic patients were found to be high, whereas their hope levels were found to be moderate. A significant negative correlation was found between internalized stigma and hope. This study also found a significant positive correlation between the stigma resistance of patients and their hope levels.


The histopathology of Neoechinorhynchus hutchinsoni Datta, 1936 (Neoacanthocephala): Neoechinorhynchidae) infection in Nemacheilus kashmirensis Hora.
Histopathological studies of Neoechinorhynchus hutchinsoni infection in Nemacheilus kashmirensis show partial or complete damage of the host intestinal wall, depending upon the degree of penetration. Increased number of goblet cells are seen at the site of unperforated wounds but where the intestinal wall is completely perforated the goblet cells were undifferentiated. The parasite destroys the mucosa, lamina propria, muscle layer and serosa leading to perforation. This report of perforation by Neoechinorhynchus hutchinsoni is the first in the genus Neoechinorhynchus.


The results of treatment of bone defects and non-union within the femoral shaft with shortening of femur using Ilizarov method.
The non-union within the femur with shortening of the limb as a consequence of trauma is an indication to choose external stabilisation as a method of treatment for that reason, that healing of the bone and surrounded soft tissues is disordered. Authors discuss the results of treatment of 16 patients with post-traumatic bone defect and pseudarthroses with femur shortening. The injury was located in femur shaft in 8 cases, distal epiphysis in 5 cases and proximal epiphysis in 3 cases. 11 patients were treated in one stage, 4 patients were treated in two stages and 1 was held in three stages. First operation was made for achievement of union in place of bone loss or pseudarthrosis- the second and third- for elongation and correction of the axis of the femur. The follow-up consisted of 10 patients. In most cases subjective and objective improvement was achieved. The bone union was reached in 15 patients and in 1 case pseudarthrosis was observed. Patients who were considered to have next procedures due to remaining femur shortening or other limb deformity didn't see necessity of following treatment. The results of the current study indicated that Ilizarov's method can be successfully used in most patients with post-traumatic bone defect and pseudarthrosis with femur shortening. The method allows to reach the bone union, correct the deformity and lengthen the limb as well, what need mostly multi-stage treatment.


Two-photon absorption of the spatially confined LiH molecule.
In the present contribution we study the influence of spatial restriction on the two-photon dipole transitions between the X1Σ+ and A1Σ+ states of lithium hydride. The bond-length dependence of the two-photon absorption strength is also analyzed for the first time in the literature. The highly accurate multiconfiguration self-consistent field (MCSCF) method and response theory are used to characterize the electronic structure of the studied molecule. In order to render the effect of orbital compression we apply a two-dimensional harmonic oscillator potential, mimicking the topology of cylindrical confining environments (e.g. carbon nanotubes, quantum wires). Among others, the obtained results provide evidence that at large internuclear distances the TPA response of lithium hydride may be significantly enhanced and this effect is much more pronounced upon embedding of the LiH molecule in an external confining potential. To understand the origin of the observed variation in the two-photon absorption response a two-level approximation is employed.


C9ORF72 expansions, parkinsonism, and Parkinson disease: a clinicopathologic study.
To determine the histopathologic bases for the observed incidence of parkinsonism in families with C9ORF72 expansions, which typically cause amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia. DNA was extracted from 377 brains with the histopathologic diagnosis of idiopathic Parkinson disease or related disorders and analyzed for C9ORF72 expansions. α-Synuclein and p62 immunohistochemistry of the substantia nigra (SN) was undertaken in brains of 17 ALS cases with (C9ORF72+) and 51 without (C9ORF72-) the C9ORF72 expansion. Only 1 of 338 cases with pathologically confirmed idiopathic Parkinson disease had a C9ORF72 expansion. Similarly, only 1 of 17 C9ORF72+ brains displayed features suggestive of α-synucleinopathy. In contrast, p62-positive, TDP-43-negative neuronal cytoplasmic inclusions within the SN were considerably more frequent in C9ORF72+ brain tissue than in the C9ORF72- brains (p = 0.005). Furthermore, there was a more marked loss of dopaminergic neurons in the SN of C9ORF72+ ALS brains than C9ORF72- ALS brains (p = 0.029). SN involvement is common in C9ORF72+ ALS but can be clearly distinguished from Parkinson disease-related mechanisms by the presence of p62-positive inclusions and the absence of α-synuclein-positive Lewy bodies or Lewy neurites.


The efficacy and tolerability of quetiapine versus divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorder(s).
The aim of this study was to compare the efficacy and tolerability of quetiapine and divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorders. Patients were included in this post hoc analysis if they scored > or = 14 on the Positive and Negative Syndrome Scale (PANSS) Excited Component (EC) and > or = 4 on at least one of the PANSS EC items, had a current diagnosis of bipolar I disorder, manic or mixed episode, and had a lifetime and/or current diagnosis of a disruptive behavioral disorder (DBD) [conduct disorder (CD) or oppositional defiant disorder (ODD)]. Thirty-three (92%) of the 36 subjects with bipolar disorder and DBD met the PANSS EC inclusion criteria. These thirty-three adolescents were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 microg/mL) for 28 days in this double-blinded study. The primary efficacy measure was change in PANSS Excited Component (EC) score over the study period and at each time point. Repeated measures analysis of variance (ANOVA) demonstrated statistically significant within-treatment-group effects for divalproex (baseline = 20.6, end point = 13.3, p < 0.0001) and quetiapine (baseline = 18.8, end point = 10.8, p < 0.0001) for the PANSS EC. There were no statistically significant treatment group differences in PANSS EC changes from baseline to end point scores (p = 0.7, d = 0.14). Mixed regression analyses (comparison of slopes, DAY*TREATMENT) revealed that there was no significant difference in the rate of improvement in the PANSS EC scores between the two treatment groups [F(1,31) = 0.78, p = 0.39, d = 0.28]. Quetiapine and divalproex showed similar efficacy for the treatment of impulsivity and reactive aggression related to co-occurring bipolar and disruptive behavior disorders in adolescents. Quetiapine and divalproex are both useful as monotherapy for the treatment of impulsivity and reactive aggression in adolescents with bipolar and disruptive behavior disorders. Placebo-controlled studies are necessary.


Enzyme profiles of single muscle fibers never exposed to normal neuromuscular activity.
Do muscle fiber properties commonly associated with fiber types in adult animals and the population distribution of these properties require normal activation patterns to develop? To address this issue, the activity of an oxidative [succinic dehydrogenase (SDH)] and a glycolytic [alpha-glycerophosphate dehydrogenase (GPD)] marker enzyme, the characteristics of myosin adenosinetriphosphatase (myosin ATPase, alkaline preincubation), and the cross-sectional area of single fibers were studied. The soleus and medial gastrocnemius of normal adult cats were compared with cats that 6 mo earlier had been spinally transected at T12-T13 at 2 wk of age. In control cats, SDH activity was higher in dark than light ATPase fibers in the soleus and higher in light than dark ATPase fibers in the medial gastrocnemius. After transection, SDH activity was similar to control in both muscles. GPD activity appeared to be elevated in some fibers in each fiber type in both muscles after transection. The cross-sectional areas most affected by spinal transection were light ATPase fibers of the soleus and dark ATPase fibers of the medial gastrocnemius, the predominant fiber type in each muscle. These data demonstrate that although the muscle fibers of cats spinalized at 2 wk of age presumably were never exposed to normal levels of activation, the activity of an oxidative marker enzyme was maintained or elevated 6 mo after spinal transection. Furthermore, although the absolute enzyme activities in some fibers were elevated by transection, three functional protein systems commonly associated with fiber types, i.e., hydrolysis of ATP by myosin ATPase and glycolytic (GPD) and oxidative (SHD) metabolism, developed in a coordinated manner typical of normal adult muscles.


Interest in Long-Acting Injectable PrEP in a Cohort of Men Who have Sex with Men in China.
Long-acting injectable (LAI) formulations of antiretrovirals (ARVs) as pre-exposure prophylaxis (PrEP) could be an attractive alternative for men who have sex with men (MSM) who are interested in ARV-based biomedical prevention but will not use a daily pill. This study investigated interest in LAI-PrEP in a cohort of MSM in China and characterized how MSM willing to use only injectable PrEP differed from MSM who would use PrEP regardless of modality or not at all. Demographic, behavioral, and risk perception measures were collected and associations investigated. A licensed LAI-PrEP agent would increase the proportion interested in PrEP by 24.5% over oral PrEP alone. Combining interest in oral and injectable PrEP, 78.5% of the sample could be covered if reported interest in PrEP translated into actual uptake. Partnership factors differentiated those who would be willing to use only LAI-PrEP versus any PrEP modality, while higher self-perception of risk was associated with interest in LAI-PrEP versus no PrEP. The addition of a second PrEP modality could yield increased population coverage of PrEP. Social and behavioral research should be undertaken in parallel with clinical development of injectable PrEP agents to identify characteristics of those who are not interested in oral PrEP but would take advantage of ARV-based prevention with the introduction of an injectable product.


Combination of transcatheter arterial embolization and percutaneous ethanol injection for hepatocellular carcinoma: comparison of efficacies of doxorubicin and epirubicin in transcatheter arterial embolization.
We administered a combination of transcatheter arterial embolization (TAE) and percutaneous ethanol injection (PEI) (ie, pretreatment with TAE and subsequent PEI) to treat 56 patients with multiple lesions (number of nodules < or = 3) or a single large (diameter > or = 3 cm) encapsulated lesion of hepatocellular carcinoma. The TAE included doxorubicin (40 mg) in 32 cases and epirubicin (mean, 82 mg) in the remaining 24 cases, and the efficacies of the two were compared. The therapeutic efficacy was evaluated on the basis of the survival rate and recurrence-free survival rate revealed by clinical follow-up. Both rates showed significant differences between the doxorubicin and epirubicin groups, with both being superior in the epirubicin group. It was surmised that epirubicin is a useful chemotherapeutic agent in TAE for patients with hepatocellular carcinoma.


Drug induced hepatitis with anti-tubercular chemotherapy: challenges and difficulties in treatment.
Tuberculosis is a major health burden worldwide. In Nepal, it is a significant cause of morbidity and mortality. Although better drugs are available for managing tuberculosis, treatment failure is one of the common problems encountered. Among the various causes which can cause treatment interruption, drug induced hepatotoxicity is a common cause. Isoniazid and Pyrazinamide are the common drugs causing hepatotoxicity. Upon occurrence of hepatotoxicity, the hepatotoxic drugs should be stopped and reintroduced as per the available guidelines. The healthcare professional should also counsel the patients for recognizing the early symptoms due to hepatotoxicity which could prevent morbidity.


The Clinical Characteristics of ADHD Diagnosed in Adolescents in Comparison With Younger Children.
Objective: The aim of this study is to identify the clinical characteristics in adolescents newly diagnosed with ADHD. Method: Data of patients aged 7 to 17 years diagnosed with ADHD were collected and analyzed. The patients were divided into adolescents aged 13 to 17 years (Group I) and children aged 7 to 12 years (Group II): 592 males and 231 females. Group I consists of 450 participants, and Group II consists of 373 participants. Results: Adolescents were predominantly inattentive (63.8%); most of Group II patients had combined or hyperactive ADHD (70.8%). Learning disorders were more common in adolescents (51.2% vs. 39.7%) and treated mainly with long-acting methylphenidate (MPH), and Group II patients were treated mainly with short- and medium-acting MPH. Newly diagnosed adolescents were less likely to exhibit behavioral comorbidities. Headache and insomnia were reported more in adolescents, and stimulant rebound effect was more in younger children. Conclusion: Although the biological nature of ADHD is similar in both age groups, the primary symptomatology and associated comorbidities are prone to age-dependent changes.


Teenage pregnancy: issues, interventions, and direction.
The positive health trends and overall improvement in health status among the US population cause health professionals, human service providers, educators, and policy makers to be encouraged about the fitness of our nation. When taking a closer look at these trends and related changes, however, a dilemma exists among a portion of our population that cannot be dismissed. While the health status of the US population as a whole has steadily improved over the past decades, such progress has not been sustained for adolescents. In fact, adolescence (15 to 21 years of age) is the only age group in which mortality rates have increased over the past decade.One of the principal threats to adolescent health is unwanted pregnancy. More than one million teenage pregnancies occur each year in the United States, 75 percent of which are unintended. Teenage pregnancy is a multifaceted problem that requires multifaceted intervention. It is not just the pregnant teenager's problem either, but may involve up to three generations of family members and a host of other significant relationships. The impact and cost to society can become staggering.If such a great proportion of these pregnancies are unintended, what steps can be taken to offer acceptable and accessible alternatives to adolescents? An assessment of the magnitude of this problem, its impact on the family and society, and the measures implemented to date reveal a major challenge facing our policy makers, health and human service providers, and concerned citizenry.


Recombinant retroviral vector delivered intramuscularly localizes to the site of injection in mice.
A murine retroviral vector encoding the human immunodeficiency virus type 1 (HIV-1) env and rev genes can be used to induce cytotoxic T lymphocyte responses. Immune responses can be induced by an ex vivo treatment, in which autologous cells are transduced in vitro and re-introduced to the donor, or by direct administration of retroviral vector via intramuscular injection. In this study we have used polymerase chain reaction (PCR) analysis to examine the distribution of recombinant murine retrovirus directly administered to mice. Mice were injected intramuscularly with HIV-IT(V), an amphotropic murine leukemia virus (MLV)-based retroviral vector carrying the HIV-1 env/rev genes and a neomycin resistance marker gene. Detection of the HIV-1 env gene in DNA isolated from injection sites demonstrated in vivo transduction. No evidence of transduction was observed in the testes, spleen, kidney, or thymus. Retroviral DNA was detected in the liver of one animal in the study. These data suggest that retroviral vector administered intramuscularly to mice localizes primarily to the site of injection and that measurable transduction in the testes does not occur.


A decrease in VEGF and inflammatory markers is associated with diabetic proliferative retinopathy.
Diabetic retinopathy is the most severe ocular complication of diabetes mellitus (DM), is associated with micro-vascular damage. The more advanced stage, proliferative diabetic retinopathy, has been linked to an increased risk of cardiovascular morbidity and mortality. Our hypothesis was that inflammatory and angiogenic markers will detect the different stages of type 2 diabetes, and may predict development of micro-vascular damage. Methods. Seventy three type II diabetic patients were randomly assigned to three groups (A - 25 patients {12 males], no diabetic retinopathy; B - 25 patients {19 males], non-proliferative retinopathy; and C - 23 patients {13 males], proliferative retinopathy),when they came for a routine follow-up visit in the ophthalmologic outpatient clinic. Twenty-three healthy subjects (14 males) served as controls. High-sensitivity C reactive protein (hs-CRP), soluble vascular cell adhesion molecule 1(sVCAM-1) and vascular endothelial growth factor (VEGF) were studied. Results. The duration of type II diabetes differed between group A (9 ± 6 years) and B (17 ± 9 years) patients (p = 0.001). No such difference was revealed between groups B and C (19 ± 6 years) (p = 0.30). A difference in hemoglobin A1C (HBgA1C) levels was detected between groups A (7.1 ± 2.7%) and B (8.5 ± 1.5%) (p = 0.02), but none was found between groups B and C (8.5 ± 1.6%) (p = 0.98). Only six patients (out of 23) used insulin treatment in group A, compared with 16 in group B (out of 25) and 17 in group C (out of 25) (p = 0.004). All three groups of diabetic patients were older (62.8 ± 10.8, 61.9 ± 9.4, 59.2 ± 10.3 years, respectively) than the controls(44.3 ± 11.6 years) (p≤0.001). Hs-CRP levels were higher in diabetic patients (4,391 ± 4,175, 4,109 ± 4,533, 3,005 ± 3,842 ng/mL, respectively) than in controls (1,659 ± 1,866 ng/mL); however, only the levels in patients of groups A (p = 0.01) and B (p = 0.03) were significantly different from those of the controls, in contrast to group C, which did not differ (p = 0.180). Similar findings were observed for sVCAM-1 (706 ± 347, 746 ± 328, 638 ± 208 ng/mL, respectively, vs. controls {552 ± 143 ng/mL]); sVCAM-1 levels of groups A and B, but not C, differed from the controls (p = 0.05, p = 0.01 and p = 0.125, respectively). With the exception of group B (p = 0.03), soluble VEGF DM type II levels (493 ± 353, 625 ± 342, 368 ± 223 pg/mL, respectively) did not vary from those of the controls (392 ± 355 pg/mL, p≥0.05). However, as the disease progressed, there was a significant decrease in VEGF levels, accompanied by a significant difference between groups B and C (p = 0.006). Conclusions. Patients with diabetes type 2with no-retinopathy and with non-proliferative retinopathy had high levels of inflammatory and angiogenic markers, which decreased in patients with diabetic proliferative retinopathy. Biomarkers of inflammation and angiogenesis may detect the progression of diabetic vascular disease and may lead towards earlier interventions that would prevent systemic complications.


Care staff responses to people with learning disabilities and challenging behaviour: a cognitive-emotional analysis.
This study explores the application of Weiner's cognitive-emotional model of helping behaviour to care staff responses to challenging behaviour of people with learning disabilities. Participants were 20 residential care staff who worked with people with challenging behaviour and 20 who did not. Six examples of challenging behaviour were presented, and for each behaviour participants were asked to give a probable cause, rate attributions of stability, internality, globality and controllability for their cause, their optimism for change of the behaviour, their evaluation of the behaviour and a person showing the behaviour, their emotional response to the behaviour and their willingness to put extra effort in to helping change the behaviour. Data were analysed using correlation and regression methods. Carers working with people with challenging behaviour were more likely to evaluate the person more positively and report they would be more likely to offer extra effort in helping. A path analysis showed that helping behaviour was best predicted by optimism, which was best predicted by negative emotion which was best predicted by the attribution of controllability. We conclude that attributions and emotions reported by carers in response to challenging behaviour are consistent with Weiner's cognitive-emotional model of helping behaviour. Formulating carer behaviour using such models offers the possibility of using cognitive-behavioural methods in working with staff beliefs, emotions and behaviour in response to challenging behaviour.


The Diagnostic Value of SCUBE1 in Acute Appendicitis.
SCUBE1 has recently been studied as a diagnostic biomarker for acute coronary syndrome, ischemic stroke, and acute mesenteric ischemia. The aim of this study is to evaluate the value of SCUBE1 and routine parameters used in patients diagnosed with acute appendicitis. Of the 150 patients admitted to the emergency department whose initial diagnosis were acute appendicitis (AA), 103 patients were excluded from the study for various reasons. Forty-seven patients with a definitive diagnose of AA and 43 volunteers were enrolled in the study. SCUBE1, Alvarado scoring (ASK), C-reactive protein (CRP), and routine tests were compared between the two groups. SCUBE1 was not statistically significant between the patient and the control groups (p = 0.209). SCUBE1 was significantly higher in the CRP (+) group (p = 0.048). Both the diameter of the appendix on computerized tomography (CT) and SCUBE1 levels increased proportionally (p = 0.043). CRP was significantly higher in the perforated appendicitis (PA) compared to non-perforated appendicitis (NPA) (p = 0.007). White blood cell (WBC) count was not differential for perforation (p = 0.06). Although SCUBE1 was significantly higher in CRP (+) patients, it was not a diagnostic biomarker for AA. There was a positive correlation between SCUBE1 values and the diameter of appendix measured on CT.


Renal Cell Carcinoma: Alternative Nephron-Sparing Treatment Options for Small Renal Masses, a Systematic Review.
The standard treatment of T1 renal cell carcinoma (RCC) is (partial) nephrectomy. For patients where surgery is not the treatment of choice, for example in the elderly, in case of severe comorbidity, inoperability, or refusal of surgery, alternative treatment options are available. These treatment options include active surveillance (AS), radiofrequency ablation (RFA), cryoablation (CA), microwave ablation (MWA), or stereotactic body radiotherapy (SBRT). In the present overview, the efficacy, safety, and outcome of these different options are summarized, particularly focusing on recent developments. Databases of MEDLINE (through PubMed), EMBASE, and the Cochrane Library were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search was performed in December 2016, and included a search period from 2010 to 2016. The terms and synonyms used were renal cell carcinoma, active surveillance, radiofrequency ablation, microwave ablation, cryoablation and stereotactic body radiotherapy. The database search identified 2806 records, in total 73 articles were included to assess the rationale and clinical evidence of alternative treatment modalities for small renal masses. The methodological quality of the included articles varied between level 2b and level 4. Alternative treatment modalities, such as AS, RFA, CA, MWA, and SBRT, are treatment options especially for those patients who are unfit to undergo an invasive treatment. There are no randomized controlled trials available comparing surgery and less invasive modalities, leading to a low quality on the reported articles. A case-controlled registry might be an alternative to compare outcomes of noninvasive treatment modalities in the future.


Research Status of Systemic Adjuvant Therapy for Early Breast Cancer.
Breast cancer has surpassed lung cancer as the most common cause of cancer deaths, worldwide. Early breast cancers are treatment sensitive and patients under standardized treatment have prolonged. Breast cancer treatment has significantly evolved from the conventional surgical approach and radiotherapy to local and systemic adjuvant therapies. Though localized breast cancers are clinically manageable, distant recurrence is a cause of morbid concern. Adjuvant systemic therapy is effective in both distant and local recurrences and hence gained significant attention. Early breast cancer prognosis has greatly improved in the past 3 decades with reduced mortality rates due to the widespread use of adjuvant therapy. It can markedly increase the cure rate of breast cancers, and postoperative adjuvant therapy became a part of comprehensive breast cancer treatment. Further research to understand the early breast cancer characteristics could expand the treatment modalities that can improve the outcomes and survival benefits of breast cancer patients.


Hydration-state change of horse heart cytochrome c corresponding to trifluoroacetic-acid-induced unfolding.
We investigate the hydration state of horse-heart cytochrome c (hh cyt c) in the unfolding process induced by trifluoroacetic acid (TFA). The conformation of hh cyt c changes from the native (N) state (2.9 < pH < 6.0) to the acid-unfolded (U(A)) state (1.7 < pH < 2.0) to the acid-induced molten globule (A) state (pH ∼1.2). Hydration properties of hh cyt c during this process are measured at 20°C by high-resolution dielectric relaxation (DR) spectroscopy, UV-vis absorbance, and circular dichroism spectroscopy. Constrained water of hh cyt c is observed at every pH as an ∼5-GHz Debye component (DC) (DR time, τ(D) ∼30 ps) and its DR amplitude (DRA) is increased by 77% upon N-to-U(A) transition, when pH changes from 6.0 to 2.0. Even in the N state, the DRA of the constrained-water component is found to be increased by 22% with decreasing pH from 6.0 to 2.9, suggesting an increase in the accessible surface area of native hh cyt c. Moreover, hypermobile water around native hh cyt c is detected at pH 6.0 as a 19-GHz DC (τ(D) ∼ 8.4 ps <τ(DW) = 9.4 ps), but is not found at other pH values. The DRA signal of constrained water is found to return to the pH 2.9 (N-state) level upon U(A)-to-A transition. Fast-response water (slightly slower than bulk) around A-state hh cyt c is detected at pH 1.2, and this suggests some accumulation of TFA(-) ions around the peptide chain. Thus, this high-resolution DR spectroscopy study reveals that hh cyt c exhibits significant hydration-state change in the TFA-unfolding process.


INTERCELLULAR DIFFUSION.
Fluorescein-sodium, a fluorescent tracer whose molecular weight is 376, diffuses rather freely from the interior of one cell to another in a gland epithelium (Drosophila) but does not diffuse along the intercellular space to the exterior. The permeability of the junctional surfaces of the cell membranes appears to be high, in contrast to the nonjunctional surfaces and intercellular spaces which represent strong diffusion barriers.