Prevalence of nocturnal hypoglycemia in free-living conditions in adults with type 1 diabetes: What is the impact of daily physical activity?
Studies investigating strategies to limit the risk of nocturnal hypoglycemia associated with physical activity (PA) are scarce and have been conducted in standardized, controlled conditions in people with type 1 diabetes (T1D). This study sought to investigate the effect of daily PA level on nocturnal glucose management in free-living conditions while taking into consideration reported mitigation strategies to limit the risk of nocturnal hyoglycemia in people with T1D. Data from 25 adults (10 males, 15 females, HbA1c: 7.6 ± 0.8%), 20-60 years old, living with T1D, were collected. One week of continuous glucose monitoring and PA (assessed using an accelerometer) were collected in free-living conditions. Nocturnal glucose values (midnight-6:00 am) following an active day "ACT" and a less active day "L-ACT" were analyzed to assess the time spent within the different glycemic target zones (<3.9 mmol/L; 3.9 - 10.0 mmol/L and >10.0 mmol/L) between conditions. Self-reported data about mitigation strategies applied to reduce the risk of nocturnal hypoglycemia was also analyzed. Only 44% of participants reported applying a carbohydrate- or insulin-based strategy to limit the risk of nocturnal hypoglycemia on ACT day. Nocturnal hypoglycemia occurrences were comparable on ACT night versus on L-ACT night. Additional post-meal carbohydrate intake was higher on evenings following ACT (27.7 ± 15.6 g, ACT vs. 19.5 ± 11.0 g, L-ACT; P=0.045), but was frequently associated with an insulin bolus (70% of participants). Nocturnal hypoglycemia the night following ACT occurred mostly in people who administrated an additional insulin bolus before midnight (3 out of 5 participants with nocturnal hypoglycemia). Although people with T1D seem to be aware of the increased risk of nocturnal hypoglycemia associated with PA, the risk associated with additional insulin boluses may not be as clear. Most participants did not report using compensation strategies to reduce the risk of PA related late-onset hypoglycemia which may be because they did not consider habitual PA as something requiring treatment adjustments.


[Anti-Borrelia burgdorferi antibodies in chronic erythema migrans, benign lymphadenosis cutis, scleroderma and scleroatrophic lichen].
Fiftyone patients with a diagnosis of erythema chronicum migrans (ECM), lymphadenosis cutis benigna (LABC), systemic progressive sclerosis, localized scleroderma and lichen sclerosus et atrophicans were investigated in order to obtain serological evaluation of Borrelia burgdorferi circulating antibodies. In addition sera from 9 patients with pellagroid erythema, prurigo and panniculitis were performed: in these dermatoses there was no evidence of a possible borrelia relationship. Indirect immunofluorescence assay was used for serologic testing. Elevated IgG antibody titers were detected in one female patient with localized scleroderma (1:128) and in one male patient with LABC (1:64). Serologic testing was not positive in the other 58 patients. The very small number of patients with positive antibodies in our study would indicate that Borrelia burgdorferi infection is sporadic in Lazio.


Calf- and herd-level factors associated with dairy calf reactivity.
A positive relationship between handlers and animals in farm systems is essential because the human-animal relationship has implications for welfare and productivity. For this reason, on-farm animal welfare assessment protocols often include the behavioral response of animals to humans to measure the quality of the human-animal relationship. The existing literature has described this relationship as being multifactorial in nature. In the current study, we aimed to investigate the potential influence of farm management and infrastructure characteristics, calf manager traits, and intrinsic features of dairy calves on the human-animal relationship. To this end, an escape test was conducted with 698 calves on 30 dairy farms in Chile. This test measured the calf's response to the active approach of an unfamiliar human (and was scored from 0 [fearful] to 4 [friendly]). The explanatory variables used to predict calves' response in the escape test were grouped according to the following categories: (1) farm management and infrastructure (e.g., calf-dam separation age, space allowance); (2) calf manager (e.g., attitudes, behavior, and background); and (3) calf (e.g., breed, sex, age). We concluded that calf managers with additional jobs on the farm, no training, low job satisfaction, a greater proportion of negative contacts, and more negative attitudes were predictive of fearfulness in the escape test. Holstein breed (compared with Holstein and Jersey crossbreeds) was associated with greater odds of fearful calves. Our study confirms the association between animals' fear and handlers' features, which can potentially be used to select employees on a farm. Understanding the factors that influence fear responses in calves may highlight ways to improve the relationship between animals and humans.


Navigating Uncertainty in the Management of Incidental Findings.
The lack of prospective outcomes studies for many types of incidental findings limits our understanding of both their natural history and the potential efficacy of treatment. To support decision making for the management of incidental findings, major sources of uncertainty in management pathways can be mapped and analyzed using mathematical models. This process yields important insights into how uncertainty influences the best treatment decision. Here, we consider a classification scheme, grounded in decision science, which exposes various levels and types of uncertainty in the management of incidental findings and addresses (1) disease-related risks, which are considered in context of a patient's competing causes of mortality; (2) potential degrees of intervention; (3) strength of evidence; and (4) patients' treatment-related preferences. Herein we describe how categorizing uncertainty by the sources, issues, and locus can build a framework from which to improve the management of incidental findings. Accurate and comprehensive handling of uncertainty will improve the quality of related decision making and will help guide future research priorities.


Phylogenetic and biogeographic relationships of eastern Asian and eastern North American disjunct Suillus species (fungi) as inferred from nuclear ribosomal RNA ITS sequences.
Species of Suillus produce fleshy, pored mushrooms. They are important symbiotic (ectomycorrhizal) partners of many coniferous trees. The genus includes several putative eastern Asian and eastern North American disjunct species, i.e., the S. americanus-S. sibiricus and S. decipiens-S. spraguei complexes. Phylogenetic relationships among the groups were determined to further understand the biogeographic pattern. Analyses were based on 40 sequences of the ITS region of the nuclear ribosomal RNA tandem repeats, representing 18 distinct species/populations. Our phylogenetic analyses suggested that: (1) Chinese and United States' (U.S.) S. spraguei plus S. decipiens form a strongly supported monophyletic group, with North American S. decipiens and Chinese S. spraguei being sister taxa; (2) S. americanus, Asian and U.S. S. sibiricus, plus S. umbonatus form a clade supported by a high bootstrap value; and (3) little ITS sequence divergence exists within the latter group compared to the S. decipiens-S. spraguei clade. Phylogenetic patterns revealed by this study imply a close phylogenetic relationship between eastern Asian and eastern North American disjunct population/species of Suillus. These fungi display relatively high host fidelity (at least to the host subgenus level), suggesting potential coevolutionary/comigratory trends.


[Gluten-free cookies prepared with sorghum flour].
Considering that sorghum is a gluten free flour, it could be proposed as an ingredient to produce alternative bakery products for the subjects with Celiac Disease, since they do not have many food options available in the market. For this reason, the main goal of this study is to develop chocolate cookies with sorghum flour (Sorghum vulgare). The experimental design used was the simplex-lattice factor to compare the following variables: sorghum flour (50-100%), rice flour (0-50%) and corn starch (0-50%), totaling up to ten experiments. The formulations IX and X were selected as the ones with the highest sensorial scores The sorghum flour, regular chocolate cookies and gluten free cookies were submitted to physicochemical analysis. Physical and sensorial analysis using Quantitative Descriptive Analysis (QDA) and hedonic analysis were performed for the two cookies preparation. Sorghum flour presented characteristics compared with the described by the food regulation laws. The preparations that presented satisfactory sensorial characteristics were the ones that had 58 and 67% of sorghum flour, 8 and 17% of rice flour, 33 and 17% of corn starch, respectively. The performance for both IX and X formulations was 0,92 and the specific volume was 1,54 and 1.46 cm3/g, respectively. When compared with regular cookies, the differences on most of the sensorial attributes evaluated on sorghum cookies were not statistically significant (P < 0.05), except for the color and the odour. All the sensorial scores reached values equal or higher than 7 for both samples and most of them scored 8. The results showed the feasibility of including sorghum flour on the manufacture of gluten free cookies.


[Effects of harmaline and fluorouracil (5-FU) on human retinoblastoma cell line SO-Rb 50].
Harmaline and 5-FU were incubated with human retinoblastoma (Rb) cell line SO-Rb50 for 72 hours separately before subjected to sampling, viable cell counting and inhibition rate (IR) calculation. With concentration of 12 micrograms/ml, the IR of harmaline to SO-Rb50 cells was 96.6 +/- 1.98%, and that of 5-FU was 93.5 +/- 0.90%; the 50% inhibition concentration (IC50) was 1.437 micrograms/ml for harmaline and 0.321 micrograms/ml for 5-FU. The fact that Rb cells were sensitive to chemical therapy in vitro, but not in vivo, could be due to the blood-retinal barrier. For effective treatment of Rb, besides attempts at early diagnosis and the search for sensitive drugs, studies of the mode of drug delivery are also important.


MHC-I-restricted epitopes conserved among variola and other related orthopoxviruses are recognized by T cells 30 years after vaccination.
It is many years since the general population has been vaccinated against smallpox virus. Here, we report that human leukocyte antigen (HLA) class I restricted T cell epitopes can be recognized more than 30 years after vaccination. Using bioinformatic methods, we predicted 177 potential cytotoxic T lymphocyte epitopes. Eight epitopes were confirmed to stimulate IFN-gamma release by T cells in smallpox-vaccinated subjects. The epitopes were restricted by five supertypes (HLA-A1, -A2, -A24 -A26 and -B44). Significant T cell responses were detected against 8 of 45 peptides with an HLA class I affinity of K(D) less than or equal to 5 nM, whereas no T cell responses were detected against 60 peptides with an HLA affinity of K(D) more than 5 nM. All epitopes were fully conserved in seven variola, vaccinia and cowpox strains. Knowledge of the long-term response to smallpox vaccination may lead to a better understanding of poxvirus immunity and may aid in the development of new improved vaccines and diagnostic tools.


A comparison of leukotriene and prostaglandin binding to human myometrium.
The binding of radiolabelled leukotriene (LT) C4 to 50,000 g membrane preparations of human myometrium was characterized and compared to the binding of prostaglandin (PG) E2 by the same tissue. 3H-LTC4 binding was temperature-sensitive, proportional to the amount of protein, reversible, specific (LTC4 greater than LTD4 greater than LTE4 much much greater than LTB4, PGE2, PGF2 alpha, arachidonic acid) and saturable (10 pmol/mg protein) with a Kd of 15 nM. These data were obtained in the presence of serine-borate to prevent the conversion of LTC4 to LTD4. The binding of PGE2 to the same membrane preparations was more stable, of lower capacity (200 fmol/mg protein) and of higher affinity (Kd 1 nM). The effect of LTs on the contractility of human myometrial strips in vitro and in comparison with the effect of PGs was studied. LTC4, LTD4 and LTE4 had no stimulatory effect in the dose range 0.05-1.25 microM, but a weak inhibitory effect was noted with 1.25 microM LTC4. As expected, PGF2 alpha stimulated and PGE2 inhibited contractility. In contrast to PGE2, the binding of LTC4 in human myometrium is unlikely to represent true receptors because LTs have little direct influence on myometrial contractility in vitro.


Protection after transient focal cerebral ischemia by the N-methyl-D-aspartate antagonist dextrorphan is dependent upon plasma and brain levels.
Dextrorphan is a dextrorotatory morphinan and a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. We studied the dose response characteristics of dextrorphan's neuroprotective efficacy and side effects, correlating these beneficial and adverse responses with plasma and brain levels in a rabbit model of transient focal cerebral ischemia. Thirty-three rabbits, anesthetized with halothane, underwent occlusion of the left internal carotid and anterior cerebral arteries for 1 h, followed by 4.5 h of reperfusion. One hour after the onset of ischemia, they were treated with an i.v. infusion of varying dextrorphan doses or normal saline. After killing, the brains were analyzed for ischemic high signal intensity using magnetic resonance imaging (MRI) and for ischemic neuronal damage with histopathology. A separate group of 12 anesthetized ischemic rabbits received similar doses of dextrorphan, correlating plasma with brain dextrorphan levels. Twenty-six additional dextrorphan unanesthetized, nonischemic rabbits received infusions of dextrorphan to correlate behavioral side effects with dextrorphan dose and levels. Compared with controls, dextrorphan 15 mg/kg group had significantly less cortical ischemic neuronal damage (5.3 versus 33.2%, p = 0.01) and a reduction in cortical MRI high signal area (9.1 versus 41.2%, p = 0.02). The dextrorphan 10 mg/kg rabbits showed less cortical ischemic neuronal damage (27.2%) and less MRI high signal (34.8%) but this was not statistically significant (p = 0.6). Dextrorphan 5 mg/kg had no benefit on either neocortical ischemic neuronal damage (35.8%) or MRI high signal (42.9%). The protective effect of dextrorphan was correlated with plasma free dextrorphan levels (r = -0.50, p less than 0.02 for ischemic neuronal damage; r = -0.66, p less than 0.001 for ischemic MRI high signal). All the rabbits with plasma levels greater than 2,000 ng/ml had less than 12% cortical ischemic neuronal damage and less than 34% MRI high signal. All rabbits with plasma levels greater than 3,000 ng/ml showed less than 7% ischemic neuronal damage and less than 11% MRI high signal. Plasma levels of approximately 2,500 ng/ml correlated with brain dextrorphan levels of approximately 6,000 ng/g. Unanesthetized rabbits with plasma levels of approximately 2,500 ng/ml demonstrated loss of the righting reflex. These results demonstrate that systemic treatment with dextrorphan after 1 h focal ischemia can significantly protect against cerebral damage if adequate plasma and brain levels of dextrorphan are achieved. The brain levels necessary to obtain in vivo protection are similar to concentrations that prevent glutamate or NMDA-induced injury in neuronal culture.


Bilateral reconstruction of the nipple-areola complex.
We present a method for reconstructing the nipple and areola bilaterally in one stage, one which produces a corrugated, elevated nipple and a glabrous pigmented areola. A satisfactory appearance has been maintained in 4 cases during a follow-up period of up to two years.


Patterns of psychotropic drug use in a Spanish rural community.
Psychotropic drug use was investigated using a two-stage survey of a random sample of persons aged 17 and over from a rural Spanish community. It was found that 6.9%, 11.8% and 25.1% of the population were consuming psychotropic, analgesic and somatic medicines respectively. Women presented a higher rate of psychotropic use than men (prevalence for women 10.7%, for men 2.6%). This female predominance was found to be significantly related to sociodemographic and medical factors. Psychotropic use was also associated with the physical health of the respondent. The coexistence of physical and mental illness generated an increase of consumption, whereas the absence of both types of illness was associated with a very low rate. The rates for physical and for mental illness alone were intermediate and were almost equal.


Supporting every school to become a foundation for healthy lives.
As a setting where children and adolescents live and learn, linked to the family and embedded within the wider community, schools have an important influence on every student's health. Many health interventions have used schools as a platform, often for standalone programmatic initiatives to reduce health risks, and sometimes for more comprehensive approaches, but the interventions, uptake, and sustainability are generally disappointing. Evidence shows that, to improve health and to reduce inequality, all students must attend school from a young age and for as long as possible, and their educational success therein must be maximised. Thus, beyond educational benefits, schools are also important for health. Coherence between each school's policies, structures and systems, human resources, and practices is required to advance both academic and health outcomes. Beyond simply implementing ready-made programmes into schools, health professionals can position themselves as catalysts for structural change as they have many opportunities to advocate for, and participate in, the intersectoral implementation of reforms and innovations in school systems to promote the health of all students.


[Coding practice in fatal poisonings].
Each year, nearly 100 deaths and more than 10,000 admissions to Norwegian hospitals can be attributed to acute poisoning from non-medical substances and drugs in supra-therapeutic doses. The aim of this study was to evaluate hospitals' routines for coding of acute poisoning deaths and to provide information on the toxic agents involved. Medical records of deaths (at 6 Norwegian hospitals in the period 1.1.1999 -31.12.2005) due to acute poisoning were re-examined to assess accuracy of diagnosis codes. Acute poisoning was registered as the cause of 225 deaths in the study period. The re-evaluation concluded that 45 of these deaths had other causes. In 125 of the remaining 180 deaths, acute poisoning was only registered as a side diagnosis, although re-examination revealed it was the major contribution to death in 66 % (83 of 125) of cases. The hospitals had classified the drugs according to ATC codes in 16 % (28 of 180) of patients with acute poisoning. The present Norwegian coding practice does not document acute poisoning deaths in hospital correctly, and registry studies based on diagnosis codes should be interpreted with care. Current registration of poisoning agents' ATC-codes is insufficient and the Norwegian version of ICD-10 alone is not suitable for classification of acute drug poisoning. Replacement of the Norwegian ICD-10 version by the original international version should be considered and/or the routines for registration of ATC-codes should be improved.


Association between victimization by bullying and direct self injurious behavior among adolescence in Europe: a ten-country study.
Previous studies have examined the association between victimization by bullying and both suicide ideation and suicide attempts. The current study examined the association between victimization by bullying and direct-self-injurious behavior (D-SIB) among a large representative sample of male and female adolescents in Europe. This study is part of the Saving and Empowering Young Lives in Europe (SEYLE) study and includes 168 schools, with 11,110 students (mean age = 14.9, SD = 0.89). Students were administered a self-report survey within the classroom, in which they were asked about three types of victimization by bullying (physical, verbal and relational) as well as direct self-injurious behavior (D-SIB). Additional risk factors (symptoms of depression and anxiety, suicide ideation, suicide attempts, loneliness, alcohol consumption, drug consumption), and protective factors (parent support, peer support, pro-social behavior) were included. The three types of victimization examined were associated with D-SIB. Examination of gender as moderator of the association between victimization (relational, verbal, and physical) and D-SIB yielded no significant results. As for the risk factors, depression, but not anxiety, partially mediated the effect of relational victimization and verbal victimization on D-SIB. As for the protective factors, students with parent and peer support and those with pro-social behaviors were at significantly lower risk of engaging in D-SIB after being victimized compared to students without support/pro-social behaviors. This large-scale study has clearly demonstrated the cross-sectional association between specific types of victimization with self-injurious behavior among adolescents and what may be part of the risk and protective factors in this complex association.


Expression levels of p18INK4C modify the cellular efficacy of cyclin-dependent kinase inhibitors via regulation of Mcl-1 expression in tumor cell lines.
Because cyclin-dependent kinases (CDK) play a pivotal role in cancer progression, the development of CDK inhibitors has attracted attention in antitumor therapy. However, despite significant preclinical and clinical developments, CDK inhibition biomarkers for predicting efficacy against certain cancers in individual patients have not been identified. Here, we characterized a macrocyclic quinoxalin-2-one CDK inhibitor, compound A, and identified a gene biomarker for predicting its efficacy. Compound A showed 100-fold selectivity for CDK family proteins over other kinases and inhibited both E2F transcriptional activity and RNA polymerase II phosphorylation. Compound A treatment resulted in decreased proliferation in various tumor cell lines; however, the apoptosis induction rate differed significantly among the cell lines examined, which was consistent with roscovitine. By comparing the mRNA expression profiles of sensitive and resistant cell lines, we found that expression levels of an endogenous CDK inhibitor, p18(INK4C), showed a strong negative correlation to the sensitivity. In fact, p18 status was correlated with the response to CDK inhibitor in an independent data set of multiple myeloma cell lines and silencing p18 expression increased the susceptibility of resistant cells to CDK inhibitors. The analysis of molecular mechanisms revealed that cells with lowered p18 had aberrant CDK6 and E2F activities, which resulted in a transcriptional down-regulation of Mcl-1, a key molecule associated with flavopiridol-induced apoptosis, thereby leading to susceptibility to therapeutic intervention with CDK inhibitors. These results identified a molecular basis for CDK inhibitors to exert an antitumor effect in p18-deficient cancers and support the clinical use of CDK inhibitors.


Assessing the effects of using high-quality data and high-resolution models in valuing flood protection services of mangroves.
The rate of change on coastlines is accelerating from climate change and coastal development. Coastal flooding is a particularly pressing and increasing problem, which affects hundreds of millions of people and damages trillions of US$ in property. Scientists, practitioners and managers must be able to quickly assess flood risk and identify appropriate adaptation and risk reduction measures often with limited data and tools, particularly in developing countries. To inform these decision-making processes, we identify how sensitive flood risk and adaptation analyses are to changes in the resolution of data and models. We further do these comparisons in the context of assess the benefits of an ecosystem-based approach for risk reduction. There is growing interest in these ecosystem-based approaches as cost effective measures for adaptation and risk reduction. We assess flood risks from tropical cyclones and the flood risk reduction benefits provided by mangroves in Pagbilao (the Philippines). Then, we also compare risks and risk reduction (benefits) using different quality data and models, to identify where to invest in in new modeling and data acquisition to improve decision-making. We find that coastal flood risk valuation improves by using high resolution topography and long time series of data on tropical cyclones, while flood reduction benefits of mangroves are better valued by using consistent databases and models along the whole process rather than investing in single measures.


Early and long-term postoperative management following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
Peritoneal surface malignancies have been traditionally regarded as end-stage conditions amenable to merely palliative options. The combination of aggressive cytoreductive surgery (CRS), involving peritonectomy procedures and multivisceral resections, with intra-operative hyperthermic intra-peritoneal chemotherapy (HIPEC) and/or early postoperative intra-peritoneal chemotherapy (EPIC) to treat the microscopic residual tumor is a new concept. In recent years, promising results have been reported for peritoneal mesothelioma and carcinomatosis of gastrointestinal and gynaecologic origin treated by this combined protocol. However, CRS with HIPEC and/or EPIC is a complex procedure associated with high rates of potentially life-threatening complications. Furthermore, disease progression following comprehensive treatment is not uncommon and represents a relevant cause of treatment failure. The present paper reviews the available information on early postoperative management and long-term follow-up in patients treated with CRS and intraperitoneal chemotherapy. The peculiar clinical and biological alterations that can be expected during an uncomplicated postoperative course, as compared to standard digestive surgery, are discussed. Early recognition and appropriate management of the most common adverse events are addressed, in order to minimize the impact of treatment-related morbidity on survival and quality of life results. Since re-operative surgery with additional HIPEC, has proven to be useful in selected patients with recurrent disease, long-term surveillance aiming at early detection of postoperative disease progression has become a relevant issue. Current results on follow-up investigations are presented.


Nerve Regeneration and Functional Recovery With Neurorrhaphy Performed at the Early Distraction Osteogenesis: An Experimental Study.
Distraction osteogenesis is widely used in many clinical situations, but distraction in cases accompanying nerve injury has been avoided due to concern of unfavorable effect on nerve regeneration by traction. This study evaluated the feasibility of early distraction lengthening after neurorrhaphy. Thirty-six rats were evenly distributed into 3 groups (12 rats in each group); neurorrhaphy and distraction (group I), neurorrhaphy and osteotomy without distraction (group II), and only distraction without neurorrhaphy (group III), respectively. After osteotomy on the right tibia, distraction started after 1 week and was continued for 40 days with 0.25 mm per day. Histological evaluation was carried out to identify nerve regeneration at 4, 8, and 12 weeks after surgery. Walking tract analysis was performed to assess the functional recovery preoperatively and 1, 4, 8, and 12 weeks postoperatively. Histologically, axon number ratio was significantly impaired in group I (0.48 ± 0.14) and group II (0.53 ± 0.13) compared with group III (0.88 ± 0.04) at 4 weeks (P = 0.020). There was no significant difference at both 8 and 12 weeks. Walking tract analysis showed significant differences between groups I and III (-40.5 ± 4.3), and groups II and III (-35.5 ± 5.0) at 1 week (P = 0.001), but no difference was observed at 8 and 12 weeks. Distraction osteogenesis in early stage after nerve repair is safe and effective, when performed at a rate of 0.25 mm per day in rats.


Hepatitis C virus recurrence after liver transplantation: a 10-year evaluation.
To evaluate the predictors of 10-year survival of patients with hepatitis C recurrence. Data from 358 patients transplanted between 1989 and 2010 in two Italian transplant centers and with evidence of hepatitis C recurrence were analyzed. A χ(2), Fisher's exact test and Kruskal Wallis' test were used for categorical and continuous variables, respectively. Survival analysis was performed at 10 years after transplant using the Kaplan-Meier method, and a log-rank test was used to compare groups. A P level less than 0.05 was considered significant for all tests. Multivariate analysis of the predictive role of different variables on 10-year survival was performed by a stepwise Cox logistic regression. The ten-year survival of the entire population was 61.2%. Five groups of patients were identified according to the virological response or lack of a response to antiviral treatment and, among those who were not treated, according to the clinical status (mild hepatitis C recurrence, "too sick to be treated" and patients with comorbidities contraindicating the treatment). While the 10-year survival of treated and untreated patients was not different (59.1% vs 64.7%, P = 0.192), patients with a sustained virological response had a higher 10-year survival rate than both the "non-responders" (84.7% vs 39.8%, P < 0.0001) and too sick to be treated (84.7% vs 0%, P < 0.0001). Sustained virological responders had a survival rate comparable to patients untreated with mild recurrence (84.7% vs 89.3%). A sustained virological response and young donor age were independent predictors of 10-year survival. Sustained virological response significantly increased long-term survival. Awaiting the interferon-free regimen global availability, antiviral treatment might be questionable in selected subjects with mild hepatitis C recurrence.


Visible light-induced specific protein reaction delineates early stages of cell adhesion.
Light is well established for control of bond breakage, but not for control of specific bond formation in complex environments. We previously engineered diffusion-limited reactivity of SpyTag003 peptide with its protein partner SpyCatcher003 through spontaneous transamidation. This system enables precise and irreversible assembly of biological building blocks, with applications from biomaterials to vaccines. Here, we establish a system for rapid control of this amide bond formation with visible light. We have generated a caged SpyCatcher003, which allows light triggering of covalent bond formation to SpyTag003 in mammalian cells. Photocaging is achieved through site-specific incorporation of an unnatural coumarin-lysine at the reactive site of SpyCatcher003. We showed uniform specific reaction in cell lysate upon light activation. We then used the spatiotemporal precision of a 405 nm confocal laser for uncaging in seconds, probing the earliest events in mechanotransduction by talin, the key force sensor between the cytoskeleton and extracellular matrix. Reconstituting talin induced rapid biphasic extension of lamellipodia, revealing the kinetics of talin-regulated cell spreading and polarization. Thereafter we determined the hierarchy of recruitment of key components for cell adhesion. Precise control over site-specific protein reaction with visible light creates diverse opportunities for cell biology and nanoassembly.


Topiramate in the treatment of myoclonic-astatic epilepsy in children: a retrospective hospital audit.
Myoclonic-Astatic Epilepsy (MAE) usually starts before five years of age and is associated with very frequent seizures and is highly resistant to treatment. To investigate the outcome of adjunctive topiramate (TPM) therapy in children with a diagnosis of MAE syndrome. In an outpatient setting, case notes of 27 children who received TPM were retrieved and analysed. Records of 6 children with MAE, who were experiencing 2-8 atonic seizures daily before starting TPM were studied. Improvement was noted after addition of TPM (mean dose at steady-state 7.4+/-2.5mg/kg/day) to the regimen of 1-3 anti-epileptic drugs they were receiving concurrently. All but one child improved following the titration period: one had 50-80% improvement in the frequency of atonic seizures and three had over 80% improvement. However, one child who showed over 80% improvement and was free of atonic seizures, later developed increased frequency of other seizure types. In one child there was no significant improvement. Improvement has been sustained for over 6 months in three patients and over 4 months in one; three have continued TPM. TPM was stopped in three patients (reduction in seizure control/no improvement). This study supports the efficacy of TPM in controlling atonic seizures in MAE and indicates that it should be considered as an add-on drug in the management of this 'difficult-to-treat' epileptic syndrome.


In situ observations of catalyst dynamics during surface-bound carbon nanotube nucleation.
We present atomic-scale, video-rate environmental transmission electron microscopy and in situ time-resolved X-ray photoelectron spectroscopy of surface-bound catalytic chemical vapor deposition of single-walled carbon nanotubes and nanofibers. We observe that transition metal catalyst nanoparticles on SiOx support show crystalline lattice fringe contrast and high deformability before and during nanotube formation. A single-walled carbon nanotube nucleates by lift-off of a carbon cap. Cap stabilization and nanotube growth involve the dynamic reshaping of the catalyst nanocrystal itself. For a carbon nanofiber, the graphene layer stacking is determined by the successive elongation and contraction of the catalyst nanoparticle at its tip.


Contributions and Challenges of Non-Professional Patient Care: A Key Component of Contemporary Canadian Healthcare.
The Canadian public is aging. Population levels of excellent, or very good, health are decreasing, and the prevalence of chronic diseases is increasing. Timely access to caring and respectful care from health professionals, with supporting information transfer, are key qualities in patients' sense of centricity and hope for best outcomes. Data from the 2013-2014 Health Care in Canada (HCIC) survey reveal, however, that 38% of such patients do not always, or often, access this support. The lack of timely access may be one underlying driver for non-professional caregivers to contribute to the care, as well as the personal and financial management, of family members or friends with chronic disease. Previous HCIC surveys, in 2005, 2006 and 2007, reported non-professional caregivers' prevalence in the adult public at 21, 23 and 26%, respectively, compared with 19% in the 2013-2014 survey. In all the surveys, a notable feature of non-professional care providers has been their universality of contribution, across age, sex, geography and time. Caregivers pay, however, a price. They have a lower level of self-related health, a higher incidence of chronic illness and net-negative impacts on relationships, career and finances, including use of personal savings (53%) and necessity of quitting their job (12%). Conversely, they infrequently claim available tax (12%) or compassionate care (11%) benefits. Interestingly, non-professional caregivers work in team-care settings with health professionals more frequently (29%) than patients in the general population with chronic illnesses (18%). Nonetheless, their current levels of always, or often, receiving assisting support (46%) and information (53%) from health professionals are lower than the respective results reported by the general public (65% and 68%). In conclusion, non-professional patient care in Canada is a common, longstanding and not-for-profit enterprise. It is more likely driven by altruistic caring or sense of duty that balance, or overwhelm, its associated personal, medical and financial burdens. In the short term, practical opportunities for enhancement include broader recognition of caregivers' contributions, their improved access to professional support and communication and wider use of available governmental financial support. All are likely to enhance both patient-centred care and lessen the practical burdens of caregivers. Things can be better.


C Spine Fracture on OPG.
Maxillofacial injuries are common and they occur in a variety of situations. All patients who undergo maxillofacial or head trauma, are presumed to sustain cervical spine injuries. Identification of cervical spine injuries is essential in management of trauma, because a missed injury can result in a catastrophic spinal cord injury. Advanced Trauma Life Support (ATLS) guidelines have suggested that routine use of cervical spine radiographs may not be required in an asymptomatic patient. We are presenting here a case with a cervical spine injury with no clinical deficits, found incidentally on panoramic radiographs which were advised for evaluation of the mandibular fracture. We suggest that importance has to be given to examination of the cervical spine on the panoramic radiographs as well.


Virtual staining for pixel-wise and quantitative analysis of single cell images.
Immunocytochemical staining of microorganisms and cells has long been a popular method for examining their specific subcellular structures in greater detail. Recently, generative networks have emerged as an alternative to traditional immunostaining techniques. These networks infer fluorescence signatures from various imaging modalities and then virtually apply staining to the images in a digital environment. In numerous studies, virtual staining models have been trained on histopathology slides or intricate subcellular structures to enhance their accuracy and applicability. Despite the advancements in virtual staining technology, utilizing this method for quantitative analysis of microscopic images still poses a significant challenge. To address this issue, we propose a straightforward and automated approach for pixel-wise image-to-image translation. Our primary objective in this research is to leverage advanced virtual staining techniques to accurately measure the DNA fragmentation index in unstained sperm images. This not only offers a non-invasive approach to gauging sperm quality, but also paves the way for streamlined and efficient analyses without the constraints and potential biases introduced by traditional staining processes. This novel approach takes into account the limitations of conventional techniques and incorporates improvements to bolster the reliability of the virtual staining process. To further refine the results, we discuss various denoising techniques that can be employed to reduce the impact of background noise on the digital images. Additionally, we present a pixel-wise image matching algorithm designed to minimize the error caused by background noise and to prevent the introduction of bias into the analysis. By combining these approaches, we aim to develop a more effective and reliable method for quantitative analysis of virtually stained microscopic images, ultimately enhancing the study of microorganisms and cells at the subcellular level.


A route toward fabrication of 3D printed bone scaffolds based on poly(vinyl alcohol)-chitosan/bioactive glass by sol-gel chemistry.
Among different methods for the fabrication of bone scaffolds, 3D printing has created great advances in tissue engineering and regenerative medicine owing to its ability to make objects mimicking native tissues. Thanks to its abundant availability, structural features, and favorable biological properties, chitosan (CS) hydrogel was selected to be used for preparation of the bone scaffolds. However, the 3D printing of CS-based hydrogels is still under early exploration. Knowing the fact that natural polymers are not so competent at holding large amounts of water, poly(vinyl alcohol) as the second polymer was employed. The novelty of the present research lies in the concept of employing sol-gel chemistry in order to attain proper viscosity and rheological behavior to give self-standing filaments of the polymer blends. Employing sol-gel reaction in the preparation of the hybrid hydrogels had the advantage of endowing shape fidelity to the polymer blend without any solidifying in the needle. The obtained organic-inorganic hybrids were directly printed and subsequently cross-linked. The best performance in terms of mechanical strength, cell viability, and bio-mineralization was observed for the 50:50 ratio. The in vitro cell culture and the bioactivity results showed that the printed scaffolds with this method have great potential in bone tissue engineering. Further, this method could be expandable to print other hydrogels with diverse applications such as implantable devices, soft robotics, etc.


Effectiveness of Case Management for 'At Risk' Patients in Primary Care: A Systematic Review and Meta-Analysis.
An ageing population with multimorbidity is putting pressure on health systems. A popular method of managing this pressure is identification of patients in primary care 'at-risk' of hospitalisation, and delivering case management to improve outcomes and avoid admissions. However, the effectiveness of this model has not been subjected to rigorous quantitative synthesis. We carried out a systematic review and meta-analysis of the effectiveness of case management for 'at-risk' patients in primary care. Six bibliographic databases were searched using terms for 'case management', 'primary care', and a methodology filter (Cochrane EPOC group). Effectiveness compared to usual care was measured across a number of relevant outcomes: Health--self-assessed health status, mortality; Cost--total cost of care, healthcare utilisation (primary and non-specialist care and secondary care separately), and; Satisfaction--patient satisfaction. We conducted secondary subgroup analyses to assess whether effectiveness was moderated by the particular model of case management, context, and study design. A total of 15,327 titles and abstracts were screened, 36 unique studies were included. Meta-analyses showed no significant differences in total cost, mortality, utilisation of primary or secondary care. A very small significant effect favouring case management was found for self-reported health status in the short-term (0.07, 95% CI 0.00 to 0.14). A small significant effect favouring case management was found for patient satisfaction in the short- (0.26, 0.16 to 0.36) and long-term (0.35, 0.04 to 0.66). Secondary subgroup analyses suggested the effectiveness of case management may be increased when delivered by a multidisciplinary team, when a social worker was involved, and when delivered in a setting rated as low in initial 'strength' of primary care. This was the first meta-analytic review which examined the effects of case management on a wide range of outcomes and considered also the effects of key moderators. Current results do not support case management as an effective model, especially concerning reduction of secondary care use or total costs. We consider reasons for lack of effect and highlight key research questions for the future. The review protocol is available as part of the PROSPERO database (registration number: CRD42014010824).


Plantar motoneuron columns in the rat.
In the rat, the numbers and locations of motoneurons innervating the short plantar muscles of the hindlimb (supplied by the medial and lateral plantar nerves, as well as a branch of the sural nerve) were determined by using both horseradish peroxidase (HRP) and fluorochromes as retrograde labels. Topographical organization within the plantar motor nucleus was examined by exposing individually the cut ends (encapsulated in low melting-point paraffin) of medial plantar, lateral plantar, and sural nerves to HRP. In addition, double-labeling experiments were conducted in which the medial plantar nerve was labeled with one fluorochrome (either true blue or diamidino yellow) and the lateral plantar nerve with another. The plantar motor pool is located in the extreme dorsolateral portion of the ventral horn, usually concentrated in the fifth lumbar (L5) spinal segment. Labeled motoneurons extended caudally into the sixth lumbar (L6) segment and rostrally into portions of the fourth lumber (L4) segment. Motoneurons of the medial plantar, lateral plantar, and sural nerve have overlapping territories. Sural motoneurons (about 70 cells per side) are generally confined to L5, medial plantar motoneurons (about 180 cells per side) tend to be concentrated in caudal L5 and rostral L6, whereas the lateral plantar motoneurons (about 310 cells per side) extend throughout the entire length of the plantar motor pool. The distribution of motoneuronal cell size is unimodal (mean cross-sectional area = 610 +/- 150 microns2). Cell bodies of plantar motoneurons tend to have similar geometries in all three major planes of sectioning. In all, the combined plantar plus sural nerve population amounts to about 560 motoneurons on each side of the spinal cord. On the basis of these data, and those published by others, the innervation of the small muscles of the foot accounts for about 25% of the motor axons carried by the entire sciatic nerve.


Bt crop effects on functional guilds of non-target arthropods: a meta-analysis.
Uncertainty persists over the environmental effects of genetically-engineered crops that produce the insecticidal Cry proteins of Bacillus thuringiensis (Bt). We performed meta-analyses on a modified public database to synthesize current knowledge about the effects of Bt cotton, maize and potato on the abundance and interactions of arthropod non-target functional guilds. We compared the abundance of predators, parasitoids, omnivores, detritivores and herbivores under scenarios in which neither, only the non-Bt crops, or both Bt and non-Bt crops received insecticide treatments. Predators were less abundant in Bt cotton compared to unsprayed non-Bt controls. As expected, fewer specialist parasitoids of the target pest occurred in Bt maize fields compared to unsprayed non-Bt controls, but no significant reduction was detected for other parasitoids. Numbers of predators and herbivores were higher in Bt crops compared to sprayed non-Bt controls, and type of insecticide influenced the magnitude of the difference. Omnivores and detritivores were more abundant in insecticide-treated controls and for the latter guild this was associated with reductions of their predators in sprayed non-Bt maize. No differences in abundance were found when both Bt and non-Bt crops were sprayed. Predator-to-prey ratios were unchanged by either Bt crops or the use of insecticides; ratios were higher in Bt maize relative to the sprayed non-Bt control. Overall, we find no uniform effects of Bt cotton, maize and potato on the functional guilds of non-target arthropods. Use of and type of insecticides influenced the magnitude and direction of effects; insecticde effects were much larger than those of Bt crops. These meta-analyses underscore the importance of using controls not only to isolate the effects of a Bt crop per se but also to reflect the replacement of existing agricultural practices. Results will provide researchers with information to design more robust experiments and will inform the decisions of diverse stakeholders regarding the safety of transgenic insecticidal crops.


Comparison between two methods of subsampling blubber of northern fur seals for total DDT plus PCB's.
Samples of 100 g blubber were collected from each of twelve 8- to 13-year-old fur seals (Callorhinus ursinus) taken off the coast of Washington State in March 1972. Two methods of subsampling the blubber were compared. The mean level of total DDT (DDE, DDD, and DDT) plus polychlorinated biphenyls (PCB's) from a 5-g chunk of blubber taken from a 100-g sample was significantly less than the mean level from a 5-g subsample taken from the remainder of the blubber sample after it had been thoroughly ground. Total DDT plus PCB residues ranged from 5.66 to 72.17 ppm, with a mean of 23.69 ppm in the chunks, and from 5.33 to 95.70 ppm, with a mean of 28.64 ppm in the homogenized blubber.


Surgical peritonitis in patients on peritoneal dialysis.
In this short review we highlight the diagnostic challenge presented by surgical peritonitis in peritoneal dialysis patients, giving attention to etiology, clinical presentation, diagnosis, and management. Despite improvements in medical imaging and a reduction in overall rates of peritonitis in peritoneal dialysis, the mortality of surgical peritonitis has not changed in recent years and remains a challenge for the clinical team.


Expression of single calcium channels in Xenopus oocytes after injection of mRNA from rat heart.
Oocytes of Xenopus laevis, after microinjection with mRNA from rat heart, display typical high-threshold calcium (Ca) whole cell currents. To prepare to study structure-function relationships of the cardiac Ca channel molecule, we examined the fidelity of expression of biophysical and pharmacological properties at the molecular level. Cell-attached gigaseal recordings in five K-depolarized oocytes injected with adult rat heart mRNA showed single channel Ba currents with mean amplitude 1.3-1.5 pA at 0 mV, slope conductance 18-25 pS, and extrapolated reversal potential 57-68 mV. Openings were predominantly brief (mean 1.2 ms) but longer openings (mean 9 ms) were greatly enhanced in 10(-6) M BAY-K 8644, increasing the ensemble average current at 0 mV by more than fivefold. These features are typical of high-threshold cardiac Ca channels. In two patches from one injected oocyte, we saw multiple Ca channel conductances, as recently observed in other preparations. We conclude that X. laevis oocytes injected with adult rat heart mRNA produce high-threshold cardiac Ca channels with molecular properties identical to native cells.


Evaluating the macroscopic yield behaviour of trabecular bone using a nonlinear homogenisation approach.
Computational homogenisation approaches using high resolution images and finite element (FE) modelling have been extensively employed to evaluate the anisotropic elastic properties of trabecular bone. The aim of this study was to extend its application to characterise the macroscopic yield behaviour of trabecular bone. Twenty trabecular bone samples were scanned using a micro-computed tomography device, converted to voxelised FE meshes and subjected to 160 load cases each (to define a homogenised multiaxial yield surface which represents several possible strain combinations). Simulations were carried out using a parallel code developed in-house. The nonlinear algorithms included both geometrical and material nonlinearities. The study found that for tension-tension and compression-compression regimes in normal strain space, the yield strains have an isotropic behaviour. However, in the tension-compression quadrants, pure shear and combined normal-shear planes, the macroscopic strain norms at yield have a relatively large variation. Also, our treatment of clockwise and counter-clockwise shears as separate loading cases showed that the differences in these two directions cannot be ignored. A quadric yield surface, used to evaluate the goodness of fit, showed that an isotropic criterion adequately represents yield in strain space though errors with orthotropic and anisotropic criteria are slightly smaller. Consequently, although the isotropic yield surface presents itself as the most suitable assumption, it may not work well for all load cases. This work provides a comprehensive assessment of material symmetries of trabecular bone at the macroscale and describes in detail its macroscopic yield and its underlying microscopic mechanics.


Plating isolation of various catalase-negative microorganisms from soil.
A procedure using nutritionally minimal media is presented for the plating isolation, but not enumeration, of various catalase-negative microorganisms from soil.


A novel multimeric form of FasL modulates the ability of diabetogenic T cells to mediate type 1 diabetes in an adoptive transfer model.
Activation induced cell death (AICD) via Fas/FasL is the primary homeostatic molecular mechanism employed by the immune system to control activated T-cell responses and promote tolerance to self-antigens. We herein investigated the ability of a novel multimeric form of FasL chimeric with streptavidin (SA-FasL) having potent apoptotic activity to induce apoptosis in diabetogenic T cells and modulate insulin-dependent type 1 diabetes (IDDM) in an adoptive transfer model. Diabetogenic splenocytes from NOD/Lt females were co-cultured in vitro with SA-FasL, SA control protein, or alone without protein, and adoptively transferred into NOD/Lt-Rag1(null) recipients for diabetes development. All animals receiving control (Alone: n=16 or SA: n=17) cells developed diabetes on average by 6 weeks, whereas animals receiving SA-FasL-treated (n=25) cells exhibited significantly delayed progression (p<.001) and decreased incidence (70%). This effect was associated with an increase in CD4(+)CD25(+) T cells and correlated with FoxP3 expression in pancreatic lymph nodes. Extracorporeal treatment of peripheral blood lymphocytes using SA-FasL during disease onset represents a novel approach that may alter the ability of pathogenic T cells to mediate diabetes and have therapeutic utility in clinical management of IDDM.


Thermal inactivation of uricase (urate oxidase): mechanism and effects of additives.
Uricase (Urc) is an oxidoreductase enzyme of both general and commercial interest, the former because of its lack of a cofactor and the latter because of its use in the treatment of hyperuricemic disorders. Results of fluorometry and circular dichroism (CD) spectroscopy indicate that the main phase of thermal Urc inactivation follows an irreversible two-state mechanism, with loss of ~20% of the helical structure, loss of the majority of the tertiary structure, and partial exposure of tryptophan residues to solution being approximately concurrent with activity loss. Results of size exclusion chromatography and 8-anilinonaphthalene-1-sulfonate binding studies confirm that this process results in the formation of aggregated molten globules. In addition to this process, CD studies indicate the presence of a rapid reversible denaturation phase that is not completely coupled to the main phase. Urc inactivation is inhibited by the presence of glycerol and trimethylamine oxide, stabilizers of hydrophobic interactions and backbone structure respectively, confirming that loss of hydrophobic bonding and loss of helical structure are key events in the loss of Urc activity. NaCl, however, destabilizes the enzyme at elevated temperature, emphasizing the importance of ionic interactions to Urc stability. A model is developed in which interfacial disruption, involving local loss of hydrophobic interactions, ionic bonds, and helical structure, leads to Urc inactivation and aggregation. Additional studies of Urc inactivation at a more ambient temperature indicate that the inactivation process followed under such conditions is different from that followed at higher temperatures, highlighting the limitations of high-temperature enzyme stability studies.


Decoupling dual-stimuli responses in patterned lamellar hydrogels as photonic sensors.
This work developed a photonic hydrogel that is responsive to, and can distinguish between two stimuli of stress and pH. Patterning is used to locally change the chemistry of a one-dimensional (1D) photonic gel, such that the native region is responsive to mechanical stress while the chemically modified region is responsive to both mechanical stress and pH. By combining the optical signals in the native region and the modified region, one can distinguish the stimuli between pH and stress. Specifically, the native 1D photonic gel is composed of periodically aligned polymeric bilayers in a soft polyacrylamide (PAAm) network. The chemical modification is done by partially hydrolyzing PAAm into sodium polyacrylic acid in some patterned regions, which imparts pH sensitivity, in addition to the stress sensitivity, to these regions.


The dynamics of platelet thrombus formation rate, thrombus retention time, and rate of embolization on a control and heparin bonded polyurethane angio-catheter.
The dynamics of platelet deposition and embolization from control and heparin bonded polyurethane catheters (CPC and HBPC) was evaluated with In-111 labeled autologous platelets (IN-PLT) and a computerized gamma camera (CGC). Ten non-heparinized dogs (18-25 kg) were catheterized in both femoral arteries with 10 cm of CPC and HBPC (5 Fr., Cordis) 24 hr after injection of 300-420 microCi of In-PLT, and imaged for 3 hr with the computerized gamma camera. The regional platelet deposition curves (RPDC) indicated multiple peaks and valleys; the curves were analyzed for early rate of thrombus formation (upswing), thrombus retention time (full width at half maxima of the RPDC-peak), and rate of embolization (downswing) on both catheters. The four parameters (mean +/- SD) of thrombosis on catheters and integral of the radioactivity time curve for the 3 hr duration of imaging were calculated from normalized counts/sec. The rate of thrombus formation and rate of embolization are higher for the control than HBPC, suggesting that heparin-bonding decreases the early rate of thrombosis and embolization. The thrombus adhesivity and retention time appear shorter for the control catheter, indicating that the control thrombogenic catheter forms multiple thrombi and emboli than HBPC. The integral appears larger for the control catheter than HBPC. In vivo (dynamic) studies, in vitro studies, and critical analyses of the radioactivity time curve were essential for complete evaluation of thrombogenicity of catheters and other cardiovascular prostheses.


Effects of fluoxetine and venlafaxine and pilocarpine on rat parotid glands.
This study assessed the effect of the antidepressants, Fluoxetine and Venlafaxine, on the size (GS), mass (M), cellular volume (CV), of rat parotid salivary glands and salivary flow rate (SFR), as well as the secretagogue action of pilocarpine on this flow. Ninety animals were divided into 9 treatment groups with the antidepressants, antidepressants associated with the application of pilocarpine, antidepressants and physiologic serum, physiologic serum (control) and pilocarpine (positive control). Thirty hours after the end of treatment, saliva collection began, to determine the SFR. Next, the salivary glands were removed, GS and M measured, and the specimens processes for histomorphometric analysis and CV determination. The variable GS presented statistically significant increase among the groups that were treated for 30 days with Fluoxetine (p=0.0002) and Venlafaxine (p=0.0112) when compared with the group treated with physiologic serum (control). The group treated with Fluoxetine for 30 days revealed increase in M (p=0.0190) and diminished SFR (p=0.0031), statistically significant, when compared with the control group. CV revealed increase in acinic cells between the Fluoxetine (30 days) (p=0.0005) and Venlafaxine (30 days) (p=0.0004) groups as well, when compared with the control group. The group treated with Venlafaxine for 60 days in association with pilocarpine presented SFR similar to the control group treated for 60 days. Both Fluoxetine and Venlafaxine reduced the SFR and caused increase in CV, resulting in hypertrophy of the glands, with Fluoxetine having a more pronounced anticholinergic action. The pilocarpine increased the SFR in the group that received Venlafaxine.


Prognostic value of antinuclear antibodies in juvenile idiopathic arthritis and anterior uveitis. Results from a systematic literature review.
To analyze the prognostic role of antinuclear antibodies (ANA) for the onset of uveitis in the context of juvenile idiopathic arthritis (JIA), its correlation with uveitis course and severity and its prognostic role for the development of arthritis in children with uveitis. We conducted a systematic review analysis of the literature on the prognostic value of ANA on JIA associated uveitis and its complications. We included series published between January 1990 and December 2011 reporting the prognostic value of ANA positivity on uveitis in consecutive patients diagnosed with JIA. We identified 246 studies from our search, of which 25 were selected for detailed analysis and only 9 fulfilled the inclusion criteria. Some authors have mentioned that uveitis could preceed arthritis and that ANA positivity might represent a predictive factor for subsequent joint involvement. A chronic course and insidious onset of uveitis are predictors for an association with JIA. Although recognized as a possible predictor of uveitis development, presence of positive ANA does not represent a predictor of severity. The presence of ANAs seems to be a risk factor for ocular involvement in patients with JIA. These autoantibodies, however, did not have any correlation with the recurrence of either idiopathic anterior uveitis or JIA-related uveitis and cannot be used as a marker to predict the clinical course of ocular inflammation. Any analysis of the literature is subjected to the limitations of each of the studies under evaluation. A large, prospective population-based study of JIA patients would be certainly ideal.


Effects of Temperature and pH on Fusarium oxysporum and Soybean Seedling Disease.
Fusarium oxysporum (Fo) is an important pathogen that reduces soybean yield by causing seedling disease and root rot. This study assessed the effects of pH and temperature on Fo fungal growth and seedling disease. In an in vitro assay, 14 Fo isolates collected from symptomatic soybean roots across Iowa in 2007 were grown on artificial culture media at five pH levels (4, 5, 6, 7, and 8) and incubated at four temperatures (15, 20, 25, or 30°C). In a rolled-towel assay, soybean seeds from Fo-susceptible cultivar Jack were inoculated with a suspension of a pathogenic or a nonpathogenic Fo isolate; both isolates were previously designated for their relative aggressiveness in causing root rot at 25°C. The seeds were placed in rolled germination paper, and the rolls were incubated in all combinations of buffer solutions at four pH levels (4, 5, 6, and 7), and four temperatures (15, 20, 25, or 30°C). There was a significant interaction between temperature and pH (P < 0.05) for in vitro radial growth and root rot severity. Isolates showed the most in vitro radial growth after incubation at pH 6 and 25°C. For the rolled-towel assay, the pathogenic isolate caused the most severe root rot at pH 6 and 30°C. Gaussian regression analysis estimates for optimal conditions were pH 6.3 at 27.1°C for maximal fungal growth and pH 5.9 at 30°C for maximal root rot severity. These results indicate that optimal pH and temperature conditions are similar for Fo growth and disease in soybean seedlings and suggest that Fo may be a more important seedling pathogen when soybeans are planted under warm conditions in moderately acidic soils.


Evaluation of the RESIST-4 O.K.N.V immunochromatographic lateral flow assay for the rapid detection of OXA-48, KPC, NDM and VIM carbapenemases from cultured isolates.
This study aimed to evaluate the performance of the RESIST-4 O.K.N.V immunochromatographic lateral flow assay for the detection of OXA-48, KPC, NDM and VIM carbapenemases in 100 clinical Enterobacteriaceae isolates using solid culture media. In total, 100 clinical Enterobacteriaceae isolates with characterized β-lactamase enzymes (OXA-48 n=46, KPC n =4, NDM n =43 and VIM n =10) were evaluated using the RESIST-4 O.K.N.V assay. The assay was also evaluated using carbapenem-sensitive control strains and confirmed non-carbapenemase-producing Enterobacteriaceae clinical isolates resistant to carbapenems. Inter-rater agreement of the test was evaluated by four different users who tested 11 randomly selected isolates daily over 3 days. Overall accuracy of the assay was 99.5 %. For the detection of KPC, OXA-48 and its variants and VIM the assay correctly identified 100 % of the isolates when compared to PCR. Initial performance for NDM detection was sensitivity=95.3 %, specificity=100 %. Two PCR positive Providencia rettgeri isolates rendered false negative results on the assay. Retesting from a carbapenem zone of inhibition rendered a positive result for both isolates increasing the sensitivity to 100 %. No false positive results or cross reactions were detected. The RESIST-4 O.K.N.V is reliable, sensitive and specific for the detection of OXA-48, KPC, NDM and VIM carbapenemases. Further evaluation on improving NDM detection in organisms from the Proteeae tribe is warranted to determine optimal test conditions.


Helmet noninvasive ventilation for weaning from mechanical ventilation.
We saw a patient who presented with carbon dioxide narcosis and acute respiratory failure due to an exacerbation of chronic obstructive pulmonary disease. We intubated and 12 hours later he had recovered consciousness and could cooperate with noninvasive ventilation, at which point we extubated and used a helmet to provide noninvasive positive-pressure ventilation in assist/control mode, and then during the ventilator-weaning process, pressure support, and finally continuous positive airway pressure. The patient had no complications from the helmet, and he was discharged from intensive care 48 hours after helmet ventilation was initiated. Helmet noninvasive ventilation is a potentially valuable ventilator-weaning method for certain patients.


[The legal awareness of medical workers in the system of medical care quality management].
The article presents the results of comprehensive study of the level of legal awareness of medical workers. The knowledge of physicians, paramedical personnel and health administrators concerning the rights of patients was assessed. The role of factor of legal awareness in the system of medical care quality management was analyzed. The effective system of measures of development of legal competence of medical personnel was marked out.


Surveillance for Lyme disease--United States, 1992-1998.
Lyme disease is caused by infection with the spirochete Borrelia burgdorferi and is the most commonly reported vector-borne disease in the United States. Borrelia burgdorferi is transmitted to humans by infected Ixodes scapularis and I. pacificus ticks. Lyme disease is typically evidenced in its early stage by a characteristic rash (erythema migrans), accompanied by nonspecific symptoms (e.g., fever, malaise, fatigue, headache, myalgia, and arthralgia). Lyme disease can usually be treated successfully with standard antibiotic regimens. 1992-1998. Lyme disease surveillance data are reported to CDC through the National Electronic Telecommunication System for Surveillance, a computerized public health database for nationally notifiable diseases. During 1992-1998, data regarding reported cases of Lyme disease included county and state of residence, age, sex, and date of onset. Descriptive analyses were performed, and cumulative incidence by state, county, age group, and sex were calculated. During 1992-1998, a total of 88,967 cases of Lyme disease was reported to CDC by 49 states and the District of Columbia, with the number of cases increasing from 9,896 in 1992 to 16,802 in 1998. A total of 92% of cases was reported from eight northeastern and mid-Atlantic states and two north-central states. Children aged 5-9 years and adults aged 45-54 years had the highest mean annual incidence. Lyme disease is a highly focal disease, with the majority of reported cases occurring in the northeastern and north-central United States. The number of reported cases of Lyme disease increased during 1992-1998. Geographic and seasonal patterns of disease correlate with the distribution and feeding habits of the vector ticks, I. scapularis and I. pacificus. The results presented in this report will help clinicians evaluate the prior probability of Lyme disease and provide the framework for targeting human Lyme disease vaccine use and other prevention and treatment interventions.


Chronic administration of nonsteroidal-antiinflammatory drugs (NSAIDS): effects upon mouse reproductive functions.
Although nonsteroidal-antiinflamatory drugs (NSAIDs) are widely employed, reproductive side effects of prostaglandins long-term inhibition remain unknown. The objective of the present study was to evaluate the effects of chronic low/moderate NSAIDs doses upon mice reproductive functions. Male or female mice were injected (i.p. for 60 or 35 days respectively) with: ibuprofen doses A, B or C (0.56, 1.12 or 1.68 mg/100 g/day respectively) or piroxicam doses A, B or C (0.028, 0.056 or 0.084 mg/100 g/day respectively). Parameters evaluated were: a) in females, spontaneous and induced ovulation, oocyte maturity and spermatozoa migration through genital tract, b) in males, epididymal spermatozoa concentration, motility, viability, resistance to hypoosmotic shock, acrosomal status and membrane maturity and c) in both genders, in vitro and in vivo fertilization, reproductive hormones plasma levels and cyclooxigenase inhibition in reproductive tissues. In females ibuprofen (dose A) elicited a significant reduction in spontaneous and induced ovulation rates and piroxicam (dose A) diminished the concentration of spermatozoa found in the uterus after mating. Males treated with ibuprofen (dose B) showed a reduction in the in vitro fertilization ability. Our data reveal that chronic administration of ibuprofen or piroxicam can exert detrimental effects upon reproductive physiology, which depends on the doses and/or the drug employed.


Metabolic engineering of monoterpene synthesis in yeast.
Terpenoids are one of the largest and most diverse families of natural compounds. They are heavily used in industry, and the trend is toward engineering modified microorganisms that produce high levels of specific terpenoids. Most studies have focused on creating specific heterologous pathways for sesquiterpenes in Escherichia coli or yeast. We subjected the Saccharomyces cerevisiae ERG20 gene (encoding farnesyl diphosphate synthase) to a set of amino acid mutations in the catalytic site at position K197. Mutated strains have been shown to exhibit various growth rate, sterol amount, and monoterpenol-producing capacities. These results are discussed in the context of the potential use of these mutated strains for heterologous expression of monoterpenoid synthases, which was investigated using Ocimum basilicum geraniol synthase. The results obtained with up to 5 mg/L geraniol suggest a major improvement compared with previous available expression systems like Escherichia coli or yeast strains with an unmodified ERG20 gene that respectively delivered amounts in the 10 and 500 µg/L range or even a previously characterized K197E mutation that delivered amounts in the 1 mg/L range.


Correction of motion artifact in cardiac optical mapping using image registration.
Cardiac motion is one of the main sources of artifacts in epifluorescence imaging experiments. It can cause significant error in electrophysiological measurements such as action potential duration. We present a novel approach that uses image registration based on maximization of mutual information to correct for in-plane cardiac motion in such experiments. The approach is relatively fast (a few seconds per frame) and is performed entirely post acquisition. The image registration approach is an alternative to traditional approaches such as mechanical restraint of the heart or addition of chemical uncouplers. Our results show that the image registration method significantly reduces motion-related artifacts in experimental data.


Effects of prenatal exposure to cannabinoids.
Prenatal exposure to cannabinoids does not produce gross malformations in humans and only does so with any consistency in mice following exposure to relatively high doses and following the intraperitoneal route of administration. Resorption rates are reliably increased in mice but not rats following in utero cannabinoid exposure. There is also a reliable decrease in maternal food and water consumption and weight gain during pregnancy associated with maternal cannabinoid administration. This effect may account for many of the effects associated with prenatal exposure to cannabinoids, e.g., increased resorption rate. Prenatal exposure to cannabinoids produces a reliable decrease in birth weight in animals, but this is the only postnatal effect on offspring that has been reliably documented. Studies examining long-term postnatal effects are generally inconsistent. This inconsistency may be due to methodological flaws in experimental design, such as absence of controls for drug-related undernutrition and residual effects of maternal cannabinoid exposure during postnatal nursing. When such controls have been implemented, postnatal effects of prenatal cannabinoid exposure have not been reliably observed.


Treatment patterns of pediatric nontuberculous mycobacterial (NTM) cervical lymphadenitis as reported by nationwide surveys of pediatric otolaryngology and infectious disease societies.
To describe physician diagnostic and therapeutic strategies for pediatric nontuberculous mycobacterial (NTM) lymphadenitis, a disease for which surgical excision is recommended. We surveyed members of the Infectious Diseases Society of America Emerging Infections Network (EIN) and the American Society of Pediatric Otolaryngology (ASPO). We asked them to report clinical and microbiologic details of recent cases of NTM lymphadenitis seen in their practices. 200 physicians reported a total of 277 NTM lymphadenitis cases. Cervical lymph nodes (84%) were most frequently involved, and a majority of patients were non-Hispanic white (62%) males (54%) with median age 3.0 years. Tissue culture (61%) or polymerase chain reaction (12%) was utilized most frequently to confirm NTM etiology. In most (59%) cases, an etiologic organism was not identified. In cases, where an NTM organism isolate was identified, Mycobacterium avium complex (n=82, 72%) was the most common. Surgical excision followed by adjunctive antibiotic therapy was favored in the majority (59%) of cases where a treatment method was reported. The use of surgical excision alone or antibiotic therapy alone was reported respectively in 24% and 17% of cases. Antibiotics were prescribed without diagnostic confirmation of infectious organisms in 28% of cases. Pediatric otolaryngologists and infectious disease specialists frequently treat cervical lymphadenitis empirically as NTM disease without bacteriologic confirmation. Antibiotic therapy is frequently employed with or without surgical excision.


Serum lipopolysaccharide-binding protein levels and the incidence of metabolic syndrome in a general Japanese population: the Hisayama Study.
The association between chronic lipopolysaccharide exposure and the development of metabolic syndrome (MetS) is unclear. In this study we examined the association between serum lipopolysaccharide-binding protein (LBP) levels, an indicator of lipopolysaccharide exposure, and the development of MetS in a general Japanese population. 1,869 community-dwelling Japanese individuals aged ≥40 years without MetS at baseline examination in 2002-2003 were followed up by repeated examination in 2007-2008. MetS was defined according to the Japanese criteria. Serum LBP levels were classified into quartiles (quartiles 1-4: 2.20-9.56, 9.57-10.78, 10.79-12.18, and 12.19-24.34 μg/mL, respectively). Odds ratios (ORs) for developing MetS were calculated using a logistic regression model. At the follow-up survey, 159 participants had developed MetS. Higher serum LBP levels were associated with greater risk of developing MetS after multivariable adjustment for age, sex, smoking, drinking, and exercise habits (OR [95% confidence interval] for quartiles 1-4: 1.00 [reference], 2.92 [1.59-5.37], 3.48 [1.91-6.35], and 3.86 [2.12-7.03], respectively; P for trend <0.001). After additional adjustment for homeostasis model assessment of insulin resistance, this association was attenuated but remained significant (P for trend=0.007). On the other hand, no significant association was observed after additional adjustment for serum high-sensitivity C-reactive protein (P for trend=0.07). In the general Japanese population, our findings suggest that higher serum LBP levels are associated with elevated risk of developing MetS. Low-grade endotoxemia could play a role in the development of MetS through systemic chronic inflammation and insulin resistance.


The Genoa experience of prenatal diagnosis in NF1.
Type 1 neurofibromatosis (NF1) is an autosomal dominant disorder with an incidence of about 1 in 3500 live births. Symptoms are highly variable from a few cafè-au-lait spots and axillary freckling to plexiform neurofibromas, optic gliomas, pseudarthrosis, and malignancy. Since disease causing mutations are dispersed throughout the gene, prenatal diagnosis is usually performed in familial cases by linkage analysis and rarely by direct characterization of the mutation. We have characterized 48 families and have performed four prenatal diagnoses. In three cases, the linkage analysis was carried out using informative markers. A direct approach using the protein truncation test (PTT) and sequencing was performed in one case in which a R1947X mutation was identified. The extreme variability of the phenotypic expression of the NF1 gene makes reproductive decisions in NF1 families very difficult, as molecular diagnosis cannot predict clinical expression of the disease. The psychological management of the couple is therefore difficult. In two of the three examined families the reproductive choices were not influenced by the specific manifestations of the disease in that family.


High-dose estrogen treatment at reperfusion reduces lesion volume and accelerates recovery of sensorimotor function after experimental ischemic stroke.
Estrogens have previously been shown to protect the brain against acute ischemic insults, by potentially augmenting cerebrovascular function after ischemic stroke. The current study hypothesized that treatment with sustained release of high-dose 17β-estradiol (E2) at the time of reperfusion from middle cerebral artery occlusion (MCAO) in rats would attenuate reperfusion injury, augment post-stroke angiogenesis and cerebral blood flow, and attenuate lesion volume. Female Wistar rats underwent ovariectomy, followed two weeks later by transient, two-hour right MCAO (tMCAO) and treatment with E2 (n=13) or placebo (P; n=12) pellets starting at reperfusion. E2 treatment resulted in significantly smaller total lesion volume, smaller lesions within striatal and cortical brain regions, and less atrophy of the ipsilateral hemisphere after six weeks of recovery. E2-treated animals exhibited accelerated recovery of contralateral forelimb sensorimotor function in the cylinder test. Magnetic resonance imaging (MRI) showed that E2 treatment reduced the formation of lesion cysts, decreased lesion volume, and increased lesional cerebral blood flow (CBF). K(trans), a measure of vascular permeability, was increased in the lesions. This finding, which represents lesion neovascularization, was not altered by E2 treatment. Ischemic stroke-related angiogenesis and vessel formation was confirmed with immunolabeling of brain tissue and was not altered with E2 treatment. In summary, E2 treatment administered immediately following reperfusion significantly reduced lesion size, cyst formation, and brain atrophy while improving lesional CBF and accelerating recovery of functional deficits in a rat model of ischemic stroke.


Protein Biomarkers for the Identification of Forensically Relevant Human Hair from Different Body Parts in Intimate Contact Cases.
Correctly identifying the human hair anatomic location found at crime scenes can link biological sample donors with the actual crime event, thus providing significant insight into the crime scene reconstruction. Forensic proteomic studies on human hairs can facilitate the development of new biomarkers for hair identification while compensating for the limitations of the conventional morphologic hair comparison and DNA analysis. Herein, the LC-MS/MS platform was used to find differentially expressed protein biomarkers in hairs from different body sites. The findings indicated that a total of 296 protein biomarkers with statistically significant differences in body sites were initially identified, and hair samples from the scalp, pubic, and armpit parts were distinguished from each other, which were validated by multiple bioinformatic methods. Fewer differences in protein patterns between armpit and pubic hairs while larger differences between hair and armpit as well as pubic hairs provided reasonable evidence of sexual or close intimate contact in crimes. This study lays the foundation for the development of a more reliable strategy to distinguish human hairs of various body areas from Chinese and will also support microscopic hair comparison analysis and assist in the proper handling of legal proceedings in relative cases by judicial officers, deserving special attention and further in-depth investigation. The MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository with the dataset identifier PXD038173.


Robot-Assisted Fracture Surgery: Surgical Requirements and System Design.
The design of medical devices is a complex and crucial process to ensure patient safety. It has been shown that improperly designed devices lead to errors and associated accidents and costs. A key element for a successful design is incorporating the views of the primary and secondary stakeholders early in the development process. They provide insights into current practice and point out specific issues with the current processes and equipment in use. This work presents how information from a user-study conducted in the early stages of the RAFS (Robot Assisted Fracture Surgery) project informed the subsequent development and testing of the system. The user needs were captured using qualitative methods and converted to operational, functional, and non-functional requirements based on the methods derived from product design and development. This work presents how the requirements inform a new workflow for intra-articular joint fracture reduction using a robotic system. It is also shown how the various elements of the system are developed to explicitly address one or more of the requirements identified, and how intermediate verification tests are conducted to ensure conformity. Finally, a validation test in the form of a cadaveric trial confirms the ability of the designed system to satisfy the aims set by the original research question and the needs of the users.


Trophic factors and cell therapy to stimulate brain repair after ischaemic stroke.
Brain repair involves a compendium of natural mechanisms that are activated following stroke. From a therapeutic viewpoint, reparative therapies that encourage cerebral plasticity are needed. In the last years, it has been demonstrated that modulatory treatments for brain repair such as trophic factor- and stem cell-based therapies can promote neurogenesis, gliogenesis, oligodendrogenesis, synaptogenesis and angiogenesis, all of which having a beneficial impact on infarct volume, cell death and, finally, and most importantly, on the functional recovery. However, even when promising results have been obtained in a wide range of experimental animal models and conditions these preliminary results have not yet demonstrated their clinical efficacy. Here, we focus on brain repair modulatory treatments for ischaemic stroke, that use trophic factors, drugs with trophic effects and stem cell therapy. Important and still unanswered questions for translational research ranging from experimental animal models to recent and ongoing clinical trials are reviewed here.


Minimally invasive aortic valve surgery.
Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease.


Toward an empirically based classification of personality disorder.
A framework for an empirically based classification of personality disorder is proposed that has two components: (a) a definition of personality disorder, and (b) a scheme for describing individual differences in personality disorder traits. It is suggested that the diagnosis process should begin by establishing the presence of personality disorder and then proceed to a description of the personality on a set of trait dimensions. It is argued that a definition of personality disorder should reflect an understanding of the nature of the "harmful dysfunction" implied by a diagnosis of personality disorder. With this approach, personality disorder is defined as the failure to solve life tasks involving the development of integrated representations of self and others, and the capacity for adaptive kinship and societal relationships. The second component of a classification is a system to describe individual differences. It is suggested that these should be based on taxonomies of normal and disordered traits, and that the classification incorporates both higher-order patterns and more specific basic traits. Given that personality appears to be inherited as a large number of genetic dimensions, it is suggested that the primary level for describing individual differences is that of the basic or lower-level traits rather than broader or higher-level traits used in descriptions of normal personality.


Accessory spleen located in the right parietal peritoneum: The first case report.
Accessory spleen is a congenital abnormality caused by failure of the splenic anlage to fuse during embryology. The presence of an accessory spleen located in the parietal peritoneum has not been reported so far, and an accessory spleen situated on the right side is extremely rare. In the present study, we describe the first case of an accessory spleen located in the right parietal peritoneum. A 65-year-old man, presented with pain in his left abdomen for 1 month. With ultrasonography and computed tomography, it was difficult to determine the accurate location and diagnosis, and an abdominal fibroma was preoperatively considered. By laparotomy, we found a mass connected to the right parietal peritoneum by a vascular pedicle. We resected it completely, and the gross specimen measured 5.0 × 3.0 × 2.5 cm and was a localized tumor with a capsule. Microscopically, sinusoids were visible, as well as scattered lymphoid follicles, eosinophils, histiocytes, plasma cells, neutrophils, and red blood cells, indicative of splenic tissue. Finally, the lesion was diagnosed as an accessory spleen located in the right parietal peritoneum. Postoperatively, he recovered well and was followed up for a 31 months, during which he was well with no complication. We present the first accessory spleen located in the right parietal peritoneum. Awareness of the accessory spleen and familiarity with typical imaging findings are necessary for surgeons to make a precise preoperative diagnosis.


[Israel Naval Medical Institute: 20 years of applied research, and future goals].
The Israel Naval Medical Institute (INMI) is unique as a research center located in a naval base and having close inter-relations with naval underwater units. It is ideal for applied research, and for mutual exchange of needs and of ideas and instructions. Factors making this institute so suitable for applied research include: direct personal communication with combat divers, professional naval divers, submariners, civilian recreational divers and professional civilian divers, as well as naval vessel crews prone to seasickness; hyperbaric oxygen therapy is administered in cooperation with a large neighboring hospital. Close spatial and personal relations with an academic institution (the Technion, with its Faculties of Medicine, Biology and Biophysics) provide a basis for cooperative research which expands research capabilities, and allows access to extensive expertise, instrumentation and equipment. Close ties with physicians who served at the INMI in the past also bring them into this research community. During their specialization, physicians may spend up to 6 months working with us on a research project. Undergraduate, graduate and post-graduate students may complete their research at our institute with the agreement of their parent academic institutions. Much of the research can be released to the international community. However, some is classified, serves only internal needs or is not of public interest. The number of published papers has stabilized since 1991 at about 16 a year. Studies of gas exchange and oxygen toxicity originate mainly in the Hyperbaric Research Unit, research on motion sickness in the Motion Sickness and Human Performance Laboratory, and work on hyperbaric and diving medicine in the Clinical Section of the INMI.


Early-onset diabetes in Africa: A mini-review of the current genetic profile.
Early-onset diabetes is poorly diagnosed partly due to its heterogeneity and variable presentations. Although several genes have been associated with the disease, these genes are not well studied in Africa. We sought to identify the major neonatal, early childhood, juvenile, or early-onset diabetes genes in Africa; and evaluate the available molecular methods used for investigating these gene variants. A literature search was conducted on PubMed, Scopus, Africa-Wide Information, and Web of Science databases. The retrieved records were screened and analyzed to identify genetic variants associated with early-onset diabetes. Although 319 records were retrieved, 32 were considered for the current review. Most of these records (22/32) were from North Africa. The disease condition was genetically heterogenous with most cases possessing unique gene variants. We identified 22 genes associated with early-onset diabetes, 9 of which had variants (n = 19) classified as pathogenic or likely pathogenic (PLP). Among the PLP variants, IER3IP1: p.(Leu78Pro) was the variant with the highest number of cases. There was limited data from West Africa, hence the contribution of genetic variability to early-onset diabetes in Africa could not be comprehensively evaluated. It is worth mentioning that most studies were focused on natural products as antidiabetics and only a few studies reported on the genetics of the disease. ABCC8 and KCNJ11 were implicated as major contributors to early-onset diabetes gene networks. Gene ontology analysis of the network associated ion channels, impaired glucose tolerance, and decreased insulin secretions to the disease. Our review highlights 9 genes from which PLP variants have been identified and can be considered for the development of an African diagnostic panel. There is a gap in early-onset diabetes genetic research from sub-Saharan Africa which is much needed to develop a comprehensive, efficient, and cost-effective genetic panel that will be useful in clinical practice on the continent and among the African diasporas.


Safety and efficacy of pharmacological approaches available for multisystem inflammatory syndrome in children (MIS-C): a systematic review.
To describe the existing pharmacological managements for Multisystem Inflammatory Syndrome in Children (MIS-C) in a systematic way, to identify the available pharmacological managements in MIS-C, evaluate its safety and efficacy and identify the best treatment procedures for practice recommendation. A systematic search using six databases was conducted on August 18, 2021, updated in January 26th 2023. Terminologies that were used in this search are children, MIS-C/PIMS and SARS-CoV-2. A PRISMA flow diagram was used to report the study selection process. Quality analysis was done based on NOS and GRADE tools. Data synthesis was conducted by extracting the information on drugs used, efficacy and side effects. From the 32 articles included, a total of 2331 children with MIS-C were studied. The main pharmacological approaches were immunomodulatory therapy, i.e., intravenous immunoglobulin (IVIG) (77.3%), steroids (60.5%), and a combination of IVIG and steroids (41.3%). IVIG and steroids were found to be potentially effective and safe treatments for MIS-C. Combination of IVIG and steroids was found favorable in severe cases with higher recovery rate. Refractory treatments include second dose of initial treatment and biological response modifier drugs like anakinra, tocilizumab, infliximab. A small number of studies investigating supportive treatment consisted of vasoactive, inotropic and anticoagulation. The mortality rate was 1.28% and only three studies reported side effects from the treatment. Evidence of outcome from GRADE were mostly at moderate, low and very low levels. This review provides preliminary evidence to support the current standard treatment practices in managing MIS-C pharmacologically. However, comprehensive investigation is required using clinical trials to provide stronger outcome evidence.


Do women expose themselves to more health-related risks in certain phases of the menstrual cycle? A meta-analytic review.
Researchers have increasingly examined the menstrual cycle as a potential source of day-to-day variation in women's cognitions, motivations, and behavior. Within this literature, several lines of research have examined the impact of the menstrual cycle on women's engagement in activities that could negatively affect their health (alcohol and tobacco consumption, sexual behavior, risk recognition). However, findings have been mixed, leaving it unclear whether women may expose themselves to more health-related risks during certain phases of the cycle. We conducted a meta-analysis of 22 published and four unpublished studies (N = 7529, https://osf.io/xr37j/). The meta-analysis revealed shifts across the menstrual cycle in women's sexual behavior with others and risk recognition (higher in ovulatory phase), whereas there was no consistent pattern of difference for alcohol and cigarette consumption. These findings help to clarify the proximate physiological and evolutionary mechanisms underlying women's health-related risk-taking and may inform new interventions.


Control of nonspecific staining in the fluorescent antibody technique for the detection of salmonellae in foods.
A fluorescent antibody conjugate, prepared from the IgG (immunoglobulin G) fraction of Salmonella polyvalent flagellar antiserum, gave better specific staining intensities and significantly lower nonspecific staining than did conjugates prepared from globulin fractions of ammonium sulfate-fractionated Salmonella polyvalent antisera. IgG was purified by affinity chromatography against protein A, a normal cell wall component of Staphylococcus aureus. Affinity chromatography yielded high-purity IgG in a one-step purification procedure. The conjugate prepared from affinity-purified IgG was compared with commercially available fluorescent antibody conjugates for the detection of salmoneallae in retail samplings of meats and poultry and gave better correlations with the cultural method than did the commercial conjugates.


Source identification of heavy metal contamination using metal association and Pb isotopes in Ulsan Bay sediments, East Sea, Korea.
To determine the characteristics of metal pollution sources in Ulsan Bay, East Sea, 39 surface and nine core sediments were collected within the bay and offshore area, and analyzed for metals and stable lead (Pb) isotopes. Most surface sediments (>95% from 48 sites) had high copper (Cu), zinc (Zn), cadmium (Cd), and Pb concentrations that were as much as 1.3 times higher than background values. The primary source of metal contamination came from activities related to nonferrous metal refineries near Onsan Harbor, and the next largest source was from shipbuilding companies located at the mouth of the Taehwa River. Three different anthropogenic sources and background sediments could be identified as end-members using Pb isotopes. Isotopic ratios for the anthropogenic Pb revealed that the sources were imported ores from Australia, Peru, and the United States. In addition, Pb isotopes of anthropogenic Pb discharged from Ulsan Bay toward offshore could be determined.