Evidence for eosinophil activation in cancer patients receiving recombinant interleukin-4: effects of interleukin-4 alone and following interleukin-2 administration.
Interleukin-4 (IL-4) is a T-cell-derived cytokine that may mediate murine tumor rejection through the activation of host eosinophils. In association with a Phase I clinical trial of IL-4 in cancer patients, we have examined changes in eosinophil counts and characterized systemic eosinophil degranulation. As previously reported, IL-4 administration induced a modest eosinophilia in all 17 evaluated patients. Here, we report that IL-4 therapy induced systemic eosinophil degranulation based on increases in serum major basic protein (MBP) (P = 0.018) and urine MBP (P = 0.031). The increase in serum MBP was IL-4 dose dependent (P = 0.001). Following the highest dose (600 microgram/m2/day) of IL-4 administered, mean serum MBP levels were >2000 ng/ml. Skin biopsies of rashes from patients receiving IL-4 revealed MBP deposition. Sera from eight patients receiving IL-4 at 360 and 600 microgram/m2/day exhibited eosinophil survival-enhancing activity (on days 3, 5, 7, and 9) significantly above pretreatment (on day 1) activity (P values 0. 0469, 0.0039, 0.0395, and 0.0313, respectively). This enhanced eosinophil survival could be neutralized by antibodies to IL-5, granulocyte-macrophage-colony-stimulating factor, and IL-3. The eosinophil activation demonstrated in this trial may be relevant to the clinical effects of IL-4 in cancer patients. Furthermore, an association between IL-4 and eosinophil activation should be explored in other disease states.


Postoperative rhabdomyolysis following pars-plana vitrectomy under general anesthesia.
Rhabdomyolysis is a known, but rare, complication of general anesthesia. To the authors' knowledge, it has never before been reported following an ocular surgery, and we could find no similar cases in the surgical literature following any brief surgical procedure. We believe this case to be unique in those regards and aim to raise awareness among ophthalmologists of this postoperative complication, as timely intervention can prevent renal failure and death. We report the case of a 58-year-old male who developed rhabdomyolysis following vitrectomy for retinal detachment repair under general anesthesia. The patient had several risk factors for this complication including morbid obesity, type II diabetes mellitus, and American Society of Anesthesia class III risk profile. His postoperative course was notable for significant myalgias in the postoperative recovery area, followed several hours later by oliguria, "root beer" colored urine, and a markedly elevated creatinine kinase level. He was hospitalized for two days for intravenous hydration and monitoring of his renal function and has fully recovered. As the prevalence of obesity and type II diabetes mellitus increase worldwide, ophthalmologists need to be aware of the signs and symptoms of postoperative rhabdomyolysis. Treatment often requires inpatient hospitalization to prevent the associated morbidity and mortality.


Inverted regioselectivity of C-H amination: Unexpected oxidation at beta- rather than gamma-C-H.
A rare example of beta- over gamma-C-H selectivity during Rh-catalysed sulfamate ester cyclisation is presented; from derivatives of 1,6-anhydro-beta-d-mannopyranose, five-membered sulfamidates were formed in preference to the typical six-membered oxathiazinane intramolecular insertion products. A 3D structure of sulfamate 1 helps to rationalise this unusual selectivity and analyses suggest that n-->sigma*(CH) interactions may be a key controlling factor.


The Computerized Table Setting Test for Detecting Unilateral Neglect.
Patients with unilateral neglect fail to respond normally to stimuli on the left side. To facilitate the evaluation of unilateral spatial neglect, we developed a new application that runs on a tablet device and investigated its feasibility in stroke patients. We made the computerized table setting test (CTST) to run on the tablet computer. Forty acute ischemic stroke patients (20 patients with right hemispheric infarction with neglect, 10 patients with right hemispheric infarction without neglect, and 10 patients with left hemispheric infarction) and 10 healthy controls were prospectively enrolled to validate the CTST. The test requires subjects to set a table by dragging 12 dishes located below the table on the tablet screen. The horizontal deviation of the 12 dishes from the midline of the table, the selection tendency measured by the sequence of the dish selection, and the elapsed time for table setting were calculated automatically. Parameters measured by the CTST were correlated with the results of conventional neglect tests. The horizontal deviation was significantly higher in patients with right hemispheric infarction with neglect compared with the other groups. The selection tendency and elapsed time also were significantly different in patients with right hemispheric infarction with neglect compared with the left hemispheric infarction and control groups, but were similar to those with right hemispheric infarction without neglect. The CTST is feasible to administer and comparable with conventional neglect tests. This new application may be useful for the initial diagnosis and follow-up of neglect patients.


The origin and evolution of activity analysis.
Practitioners of occupational therapy in the early 1900s selected therapeutic activities with an intuitive understanding of their characteristics and operations. The term activity analysis and the methodology for breaking down and examining tasks scientifically, however, were borrowed from industry during World War I. Methods originally used in time and motion study of jobs were applied to vocational retraining and therapeutic crafts; later, they were applied to a broader range of activities. The most systematic early use of activity analysis was in occupational therapy for physical dysfunction, particularly in military hospitals. Development of the concept was gradual until the 1970s, when the delineation of theoretical frames of reference for practice led to important changes. Today, activity analysis is viewed as a multifaceted process that involves both generic and specific components.


Muscle dissatisfaction in young adult men.
Appearance concerns are of increasing importance in young men's lives. We investigated whether muscle dissatisfaction is associated with psychological symptoms, dietary supplement or anabolic steroid use, or physical activity in young men. As a part of a questionnaire assessment of health-related behaviors in the population-based FinnTwin16 study, we assessed factors associated with muscle dissatisfaction in 1245 men aged 22-27 using logistic regression models. Of men, 30% experienced high muscle dissatisfaction, while 12% used supplements/steroids. Of highly muscle-dissatisfied men, 21.5% used supplements/steroids. Mean body mass index, waist circumference, or leisure aerobic activity index did not differ between individuals with high/low muscle dissatisfaction. Muscle dissatisfaction was significantly associated with a psychological and psychosomatic problems, alcohol and drug use, lower height satisfaction, sedentary lifestyle, poor subjective physical fitness, and lower life satisfaction. Muscle dissatisfaction and supplement/steroid use are relatively common, and are associated with psychological distress and markers of sedentary lifestyle.


Anterior cruciate ligament injuries in young females playing soccer at senior levels.
The aim of this investigation was to study the consequences of anterior cruciate ligament injuries in female soccer players. Special interest was focused on young female soccer players (< 16 years) sustaining anterior cruciate ligament injuries when playing at a senior level, which means playing together with players 19 years or older. In Sweden, all players belonging to an organized soccer club are insured by the same insurance company, the Folksam Insurance Company. Data of all soccer-related knee injuries in females reported to the Folksam Insurance Company between 1994 and 1998 were collected. A questionnaire was sent to 978 females who were registered to have sustained a knee injury before the age of 20 years. The response rate was 79%. Three hundred and ninety-eight female soccer players who had sustained an anterior cruciate ligament injury before the age of 19 years were analysed. Most of their anterior cruciate ligament injuries had been diagnosed using arthroscopy or magnetic resonance imaging (84%). Thirty-eight percent of the players had been injured before the age of 16 years. Of these, 39% were injured when playing in senior teams. When playing in senior teams 59% of the players below the age of 16 years and 44% of the players 16 years or older sustained their ACL injuries during contact situations. At the time of this investigation (2-7 years after the anterior cruciate ligament injury), altogether 78% (n = 311) reported that they had stopped playing soccer. The most common reason (80%) was symptoms from their anterior cruciate ligament-injured knee. It appears that many young female soccer players injure their anterior cruciate ligament when playing at a senior level. Therefore, we suggest that female soccer players under the age of 16 years should be allowed to participate only in practice sessions but not games at a senior level.


Are GIS-modelled routes a useful proxy for the actual routes followed by commuters?
Active commuting offers the potential to increase physical activity among adults by being built into daily routines. Characteristics of the route to work may influence propensity to walk or cycle. Geographic information system (GIS) software is often used to explore this by modelling routes between home and work. However, if the validity of modelled routes depends on the mode of travel used, studies of environmental determinants of travel may be biased. We aimed to understand how well modelled routes reflect those actually taken, and what characteristics explain these differences. We compared modelled GIS shortest path routes with actual routes measured using QStarz BT-Q1000X Global Positioning System (GPS) devices in a free-living sample of adults working in Cambridge and using varying travel modes. Predictors of differences, according to length and percentage overlap, between the two route sets were assessed using multilevel regression models and concordance coefficients. The 276 trips, made by 51 participants, were on average 27% further than modelled routes, with an average geographical overlap of 39%. However, predictability of the route depended on travel mode. For route length, there was moderate-to-substantial agreement for journeys made on foot and by bicycle. Route overlap was lowest for trips made by car plus walk (22%). The magnitude of difference depended on other journey characteristics, including travelling via intermediate destinations, distance, and use of busy roads. In conclusion, GIS routes may be acceptable for distance estimation and to explore potential routes, particularly active commuting. However, GPS should be used to obtain accurate estimates of environmental contexts in which commuting behaviour actually occurs. Public health researchers should bear these considerations in mind when studying the geographical determinants and health implications of commuting behaviour, and when recommending policy changes to encourage active travel.


Activation of the ACE2/angiotensin-(1-7)/Mas receptor axis enhances the reparative function of dysfunctional diabetic endothelial progenitors.
We tested the hypothesis that activation of the protective arm of the renin angiotensin system, the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis, corrects the vasoreparative dysfunction typically seen in the CD34(+) cells isolated from diabetic individuals. Peripheral blood CD34(+) cells from patients with diabetes were compared with those of nondiabetic controls. Ang-(1-7) restored impaired migration and nitric oxide bioavailability/cGMP in response to stromal cell-derived factor and resulted in a decrease in NADPH oxidase activity. The survival and proliferation of CD34(+) cells from diabetic individuals were enhanced by Ang-(1-7) in a Mas/phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner. ACE2 expression was lower, and ACE2 activators xanthenone and diminazine aceturate were less effective in inducing the migration in cells from patients with diabetes compared with controls. Ang-(1-7) overexpression by lentiviral gene modification restored both the in vitro vasoreparative functions of diabetic cells and the in vivo homing efficiency to areas of ischemia. A cohort of patients who remained free of microvascular complications despite having a history of longstanding inadequate glycemic control had higher expression of ACE2/Mas mRNA than patients with diabetes with microvascular complications matched for age, sex, and glycemic control. Thus, ACE2/Ang-(1-7)\Mas pathway activation corrects existing diabetes-induced CD34(+) cell dysfunction and also confers protection from development of this dysfunction.


Syndecan-1 (CD138) and Ki-67 expression in odontogenic cystic lesions.
The aim of this study was to assess the immunohistochemical expression of syndecan-1 (CD138) and Ki-67 in radicular cysts (RC), dentigerous cysts (DC) and keratocystic odontogenic tumors (KOT). Thirty-five RC, 22 DC and 17 KOT were used in the study and immunohistochemical reactions using anti-syndecan-1 and anti-Ki-67 antibodies were performed by the streptavidin-biotin-peroxidase method. Fisher's exact test and Spearman's correlation coefficient were used for statistical analysis of data. Among the studied lesions, no differences in the syndecan-1 expression were observed, but the suprabasal expression of Ki-67 was significantly higher in KOT (p<0.0001), when compared with RC and DC. In RC, there was positive correlation between the expression (p=0.02) and intensity (p=0.0001) of syndecan-1 and between the intensity of syndecan-1 and Ki-67 expression (p=0.01). In the KOT, Ki-67 expression in the suprabasal layer correlated positively with the expression (p=0.01) and intensity (p=0.01) of syndecan-1. The expression of syndecan-1 does not seem to be a determinant factor of the distinct histopathological features and biological behavior of the studied lesions. Nevertheless, positive correlation between syndecan-1 and a cell proliferation marker was observed in RC and KOT.


CNS Demyelinating Attacks Requiring Ventilatory Support With Myelin Oligodendrocyte Glycoprotein or Aquaporin-4 Antibodies.
Severe attacks of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) and aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) may require ventilatory support, but data on episodes are limited, particularly for MOGAD. We sought to compare the frequency, characteristics, and outcomes of MOGAD and AQP4-NMOSD attacks requiring ventilatory support. This retrospective descriptive study identified Mayo Clinic patients (January 1, 1996-December 1, 2020) with MOGAD or AQP4-NMOSD and an attack requiring noninvasive or invasive ventilation at Mayo Clinic or an outside facility by searching for relevant terms in their electronic medical record. Inclusion criteria were (1) attack-related requirement for noninvasive (bilevel positive airway pressure or continuous positive airway pressure) or invasive respiratory support (mechanical ventilation); (2) MOG or AQP4 antibody positivity with fulfillment of MOGAD and AQP4-NMOSD clinical diagnostic criteria, respectively; and (3) sufficient clinical details. We collected data on demographics, comorbid conditions, indication for and duration of respiratory support, MRI findings, treatments, and outcomes. The races of those with attacks requiring respiratory support were compared to those without such attacks in MOGAD and AQP4-NMOSD. Attacks requiring ventilatory support were similarly rare in patients with MOGAD (8 of 279, 2.9%) and AQP4-NMOSD (11 of 503 [2.2%]) (p = 0.63). The age at attack (median years [range]) (MOGAD 31.5 [5-47] vs AQP4-NMOSD 43 [14-65]; p = 0.01) and percentage of female sex (MOGAD 3 of 8 [38%] vs AQP4-NMOSD 10 of 11 [91%]; p = 0.04) differed. The reasons for ventilation differed between MOGAD (inability to protect airway from seizure, encephalitis or encephalomyelitis with attacks of acute disseminated encephalomyelitis 5 [62.5%] or unilateral cortical encephalitis 3 [37.5%]) and AQP4-NMOSD (inability to protect airway from cervical myelitis 9 [82%], rhombencephalitis 1 [9%], or combinations of both 1 [9%]). Median ventilation duration for MOGAD was 2 days (range 1-7 days) vs 19 days (range 6-330 days) for AQP4-NMOSD (p = 0.01). All patients with MOGAD recovered, but 2 of 11 (18%) patients with AQP4-NMOSD died of the attack. For AQP4-NMOSD, Black race was overrepresented for attacks requiring ventilatory support vs those without these episodes (5 of 11 [45%] vs 88 of 457 [19%]; p = 0.045). Ventilatory support is rarely required for MOGAD and AQP4-NMOSD attacks, and the indications differ. Compared to MOGAD, these attacks in AQP4-NMOSD may have higher morbidity and mortality, and those of Black race were more predisposed, which we suspect may relate to socially mediated health inequality.


The Hepatoprotective and MicroRNAs Downregulatory Effects of Crocin Following Hepatic Ischemia-Reperfusion Injury in Rats.
Background. Liver ischemia-reperfusion (IR) injury is one of the chief etiologies of tissue damage during liver transplantation, hypovolemic shock, and so forth. This study aimed to evaluate hepatoprotective effect of crocin on IR injury and on microRNAs (miR-122 and miR-34a) expression. Materials and Methods. 32 rats were randomly divided into four groups: sham, IR, crocin pretreatment (Cr), and crocin pretreatment + IR (Cr + IR) groups. In sham and Cr groups, animals were given normal saline (N/S) and Cr (200 mg/Kg) for 7 consecutive days, respectively, and laparotomy without inducing IR was done. In IR and Cr + IR groups, N/S and Cr were given for 7 consecutive days and rats underwent a partial (70%) ischemia for 45 min/reperfusion for 60 min. Blood and tissue samples were taken for biochemical, molecular, and histopathological examinations. Results. The results showed decreased levels of antioxidants activity and increased levels of liver enzymes improved by crocin. The expression of miR-122, miR-34a, and p53 decreased, while Nrf2 increased by crocin. Crocin ameliorated histopathological changes. Conclusion. The results demonstrated that crocin protected the liver against IR injury through increasing the activity of antioxidant enzymes, improving serum levels of liver enzymes, downregulating miR-122, miR-34a, and p53, and upregulating Nrf2 expression.


Identification of a new catenin: the tyrosine kinase substrate p120cas associates with E-cadherin complexes.
p120cas is a tyrosine kinase substrate implicated in ligand-induced receptor signaling through the epidermal growth factor, platelet-derived growth factor, and colony-stimulating factor receptors and in cell transformation by Src. Here we report that p120 associates with a complex containing E-cadherin, alpha-catenin, beta-catenin, and plakoglobin. Furthermore, p120 precisely colocalizes with E-cadherin and catenins in vivo in both normal and Src-transformed MDCK cells. Unlike beta-catenin and plakoglobin, p120 has at least four isoforms which are differentially expressed in a variety of cell types, suggesting novel means of modulating cadherin activities in cells. In Src-transformed MDCK cells, p120, beta-catenin, and plakoglobin were heavily phosphorylated on tyrosine, but the physical associations between these proteins were not disrupted. Association of p120 with the cadherin machinery indicates that both Src and receptor tyrosine kinases cross talk with proteins important for cadherin-mediated cell adhesion. These results also strongly suggest a role for p120 in cell adhesion.


Aflatoxin levels in locally grown maize from Makueni District, Kenya.
Investigations were carried out to determine aflatoxin levels in household maize in Makueni District and to correlate aflatoxin levels to maize drying and storage practices. Also, aflatoxin exposure in villages that reported aflatoxicosis cases in 2005 was compared with that in villages that did not report cases to assess whether aflatoxin exposure levels could be used to identify high-risk villages for targeted prevention interventions. A cross-sectional study. Three divisions of Makueni district, Kibwezi, Makindu and Mtito Andei in Eastern Province, Kenya. Ninety six households were surveyed, and 104 maize samples were analysed for total aflatoxin levels from June to July 2005. The households were selected from high and low aflatoxicosis risk areas. Out of the 104 maize samples collected from 96 households, 37 (35.5%) had aflatoxin levels above the World Health Organisation (WHO) recommended maximum limit of 20 ppb. All of these samples were homegrown or purchased. Twenty one samples (20.1%) had levels above 100 ppb. Eleven (10.6%) had extremely high levels above 1000 ppb. No relief supply maize had aflatoxin levels above the WHO maximum limit. High levels of aflatoxin in homegrown and purchased maize suggested that aflatoxin exposure was widespread.


Microbiota formed on attached stainless steel coupons correlates with the natural biofilm of the sink surface in domestic kitchens.
Stainless steel coupons are frequently used in biofilm studies in the laboratory, as this material is commonly used in the food industry. The coupons are attached to different surfaces to create a "natural" biofilm to be studied further in laboratory trials. However, little has been done to investigate how well the microbiota on such coupons represents the surrounding environment. The microbiota on sink wall surfaces and on new stainless steel coupons attached to the sink wall for 3 months in 8 domestic kitchen sinks was investigated by next-generation sequencing (MiSeq) of the 16S rRNA gene derived from DNA and RNA (cDNA), and by plating and identification of colonies. The mean number of colony-forming units was about 10-fold higher for coupons than sink surfaces, and more variation in bacterial counts between kitchens was seen on sink surfaces than coupons. The microbiota in the majority of biofilms was dominated by Moraxellaceae (genus Moraxella/Enhydrobacter) and Micrococcaceae (genus Kocuria). The results demonstrated that the variation in the microbiota was mainly due to differences between kitchens (38.2%), followed by the different nucleic acid template (DNA vs RNA) (10.8%), and that only 5.1% of the variation was a result of differences between coupons and sink surfaces. The microbiota variation between sink surfaces and coupons was smaller for samples based on their RNA than on their DNA. Overall, our results suggest that new stainless steel coupons are suited to model the dominating part of the natural microbiota of the surrounding environment and, furthermore, are suitable for different downstream studies.


Behavioral impulsivity paradigms: a comparison in hospitalized adolescents with disruptive behavior disorders.
Behavioral impulsivity paradigms vary widely and studies using these measures have typically relied on a single measure used in isolation. As a result, comparisons between measures are difficult, with little consensus regarding which method may be most sensitive to individual impulsivity differences of different populations. A single testing session of each of four different impulsivity tasks was completed by two groups of adolescents aged 13-17: hospitalized inpatients with disruptive behavior disorders (DBD; n = 22) and controls (n = 22). Tasks included two rapid-decision (IMT/DMT and GoStop) and two reward-directed (TC and SKIP) impulsivity paradigms. Behavioral testing took place within 3 days of hospitalization for the adolescents with DBD. Compared to controls, the DBD group exhibited higher commission error rates, lower inhibited response rates after a stop-signal, and twice as many reward-directed responses even after IQ differences between the groups were taken into account. When the four paradigms were compared, effect-size calculations indicated that the two rapid-decision paradigms were more sensitive to group differences than the reward-directed tasks. Despite the initiation of pharmacotherapy within the first 3 days of hospitalization, in contrast to the control group, the adolescents with DBD performed consistently with what has been operationally defined as impulsivity. Based on these results, these tasks appear to measure similar, but unique components of the impulsivity construct. With further study, laboratory behavioral paradigms may prove to be useful additions to current clinical diagnostic and treatment procedures in a variety of psychiatric populations.


Long-term tumor control of spinal dissemination of cerebellar glioblastoma multiforme by combined adjuvant bevacizumab antibody therapy: a case report.
Glioblastoma multiforme located in the posterior fossa is extremely rare with a frequency up to 3.4%. Compared with glioblastoma of the hemispheres the prognosis of infratentorial glioblastoma seems to be slightly better. Absence of brainstem invasion and low expression rates of epidermal growth factor receptor are described as factors for long-time survival due to the higher radiosensitivity of these tumors. In this case study, we report a German female patient with an exophytic glioblastoma multiforme arising from the cerebellar tonsil and a secondary spinal manifestation. Furthermore, the tumor showed no O (6)-Methylguanine-DNA methyltransferase promotor-hypermethylation and no isocitrate dehydrogenase 1 mutations. All these signs are accompanied by significantly shorter median overall survival. A long-term tumor control of the spinal metastases was achieved by a combined temozolomide/bevacizumab and irradiation therapy, as part of a standard care administered by the treating physician team. To our knowledge this is the first published case of a combined cerebellar exophytic glioblastoma with a subsequent solid spinal manifestation. Furthermore this case demonstrates a benefit undergoing this special adjuvant therapy regime in terms of overall survival. Due to the limited overall prognosis of the disease, spinal manifestations of glioma are rarely clinically relevant. The results of our instructive case, however, with a positive effect on both life quality and survival warrant treating future patients in the frame of a prospective clinical study.


Pathological studies of CT findings in supratentorial astrocytoma. Correlation between low-density lesions and changes in fine structure.
CT findings and pathological features of 102 supratentorial astrocytomas were evaluated, and the surgically removed specimens of 10 cases studied by electron microscopy. Five pathological indices-anaplasia, vascularity, interstitial water content, necrosis and tumor fibers were graded from 1 to 4, and studies by the double-blind method. CT scans were divided into 4 groups according to attenuation coefficients and contrast enhancement. The data were statistically analysed. The results showed that the interstitial water content and tumor fibers were statistically different in low-density lesions and isodensity or hyperdensity lesions. The peritumoral low-density specimens correlated well with infiltrated tumor cells, which had swollen mitochondria. No definite correlation was found between the histological subtypes of astrocytomas and CT images. These findings suggest that high water content and lower physical density are responsible for the low-density of astrocytomas. Abnormalities of capillary ultrastructure result in the accumulation of contrast medium. The peritumoral area of low-density seen on CT scans is the real extent of the edematous tumor. But it is impossible to distinguish the histological subtypes of astrocytomas by CT findings.


[Life lessons of eight families donating organs of deceased family members].
Most organ donors are already death. Therefore family members become an essential link in the final decision for organ donation. To get acquainted about the life lessons of people who accepted donating an organ of a deceased family member. Qualitative research, in depth interviews to eight families that accepted donating an organ of a deceased family member. The interviews were analyzed using the method proposed by Streubert et al and modified by Rivera. The life lessons are described in six comprehensive categories. The painful experience changed towards the feeling that the loved one remains alive. This sensation generated a sense of pride in family members and sensitized them towards the painful experience of other people. Therefore, a desire to help and improve as humans beings was awakened. A compassionate approach towards families donating organs with improve organ donation and humanize the process.


Electrical injury causing ventricular arrhythmias.
Dangerous or long lasting ventricular arrhythmias developed in three patients who had sustained an electrical injury in which current passed through the thorax. In all three cases there was a delay of 8-12 hours between the injury and the onset of symptoms. The ventricular arrhythmias were severe and long lasting. In two of the three patients, ventricular tachycardia or ventricular fibrillation or both occurred and in one patient ventricular parasystole developed. No enzymatic evidence of myocardial necrosis was found but the results of an endomyocardial biopsy carried out in two of the three patients showed focal myocardial fibrosis and increased numbers of Na, K-pumps. The two patients with ventricular tachycardia became symptom free after appropriate antiarrhythmic treatment and in the third patient ventricular parasystole disappeared spontaneously within two years. Patients sustaining electrical injury in which current passes through the thorax should be monitored electrocardiographically for at least 24 hours, and patients with unexpected arrhythmias should be questioned about previous electrical injury.


Human Monoclonal Antibodies: The Benefits of Humanization.
The major reasons for developing human monoclonal antibodies were to be able to efficiently manipulate their effector functions while avoiding immunogenicity seen with rodent antibodies. Those effector functions involve interactions with the complement system and naturally occurring Fc receptors on diverse blood white cells. Antibody immunogenicity results from the degree to which the host immune system can recognize and react to these therapeutic agents. Thus far, there is still no generally applicable technology guaranteed to render therapeutic antibodies antigenically silent. This is not to say that the task is impossible, but rather that we need to train the immune system to help us. This can be achieved if we take advantage of natural mechanisms by which an individual can be rendered tolerant of "foreign" antigens, and as a corollary minimize the potential immunogenicity of any contaminating protein aggregates, or "aggregates" arising from antibodies complexing with their antigen. I here summarize our efforts to engineer antibodies to harness optimal effector functions, while also minimizing their immunogenicity. Potential avenues to achieve the latte are predicted from classical work showing that monomeric "foreign" immunoglobulins are good tolerogens, while aggregates of immunoglobulins ate intrinsically immunogenic. Consequently, I argue that one solution to the immunogenicity problem lies in ensuring a temporal quantitative advantage of tolerogenic non-cell-bound monomer over the cell-binding immunogenic form.


Rituximab: a new monoclonal antibody therapy for non-Hodgkin's lymphoma.
To review the use of monoclonal antibodies (MAbs), specifically rituximab, in the treatment of non-Hodgkin's lymphoma (NHL) and to describe the nursing management of patients receiving rituximab. Published articles, abstracts, book chapters, drug manufacturer, lectures, and personal experience with rituximab. NHL ranks sixth among malignancies in incidence and mortality in the United States. The most common subtype, low-grade follicular lymphoma, is considered incurable. Lack of specificity may limit the usefulness of chemotherapy for low-grade follicular NHL. However, MAb therapy may deliver a cytotoxic effect specifically to the targeted cancer cell. Rituximab is the first MAb approved for cancer therapy. Clinical trials indicate that rituximab is efficacious and safe for recurrent or chemotherapy-resistant, B-cell, low-grade NHL. Infusion-related side effects are the most common and can be managed effectively by following the infusion rate recommendations. Monoclonal antibody therapy is an effective and safe treatment modality for cancer. Infusion-related side effects are managed effectively by following infusion rate recommendations. Nurses need to be knowledgeable about MAb therapy to educate patients and families regarding the mechanism of action and side-effect profiles of these agents, which often differ from those of chemotherapy or radiation therapy. Nurses should be familiar with the unique side effects of rituximab and also specific infusion-rate instructions, measures to reduce the incidence of side effects, and criteria for stopping the infusion when necessary.


Involvement of human amygdala and orbitofrontal cortex in hunger-enhanced memory for food stimuli.
We used positron emission tomography to measure regional cerebral blood flow (rCBF) in 10 healthy volunteers performing a recognition memory task with food and non-food items. The biological salience of the food stimuli was manipulated by requiring subjects to fast before the experiment and eat to satiation at fixed time points during scanning. All subjects showed enhanced recognition of food stimuli (relative to non-food) in the fasting state. Satiation significantly reduced the memory advantage for food. Left amygdala rCBF covaried positively with recognition memory for food items, whereas rCBF in right anterior orbitofrontal cortex covaried with overall memory performance. Right posterior orbitofrontal rCBF covaried positively with hunger ratings during presentation of food items. Regression analysis of the neuroimaging data revealed that left amygdala and right lateral orbitofrontal rCBF covaried as a function of stimulus category (i.e., food vs non-food). These results indicate the involvement of amygdala and discrete regions of orbitofrontal cortex in the integration of perceptual (food), motivational (hunger), and cognitive (memory) processes in the human brain.


The disciplining of self-help: Doing self-help the Norwegian way.
We explore how Norwegian self-help groups are defined and managed to create a particular form of health system governmentality. Self-help groups are typically framed as therapeutic communities where participants define the agenda creating a space where open and equal interaction can produce individual learning and personal growth. In Norway, however, self-help groups are managed in a way that integrates them in to the health system but insulates them from clinical medicine; an approach that disciplines participants to act in a particular way in relation to the health system. We draw on the analysis of 1456 pages of public documents and websites from the National Nodal Point for Self-Help (NPSH), the organisation that manages self-help groups, and central government including individual testimonies from participants published between 2006 and 2014. We argue, drawing on Foucault, that self-help premised on lay-leadership and self-determination is at odds with the centrally defined regulation apparent in the model adopted in Norway and an example of disciplining that reinforces health system governmentality and serves the interests of the medical profession and the state. Further we propose that this illustrates the contestation between the pastoral power of medics, the National Nodal Point for Self-Help and the Ministry of Health. Our analysis of Norwegian self-help as a mechanism to create a particular form of health system governmentality helps explain the expansion of self-help and self-management within developed health systems and provides an explanation for why self-help within health systems, is typically situated adjacent to, rather than integrated into, clinical medicine.


Adherence to Clinical Practice Guidelines and Colorectal Cancer Survival: A Retrospective High-Resolution Population-Based Study in Spain.
Colorectal cancer (CRC) is the third most common cancer worldwide. Population-based, high-resolution studies are essential for the continuous evaluation and updating of diagnosis and treatment standards. This study aimed to assess adherence to clinical practice guidelines and investigate its relationship with survival. We conducted a retrospective high-resolution population-based study of 1050 incident CRC cases from the cancer registries of Granada and Girona, with a 5-year follow-up. We recorded clinical, diagnostic, and treatment-related information and assessed adherence to nine quality indicators of the relevant CRC guidelines. Overall adherence (on at least 75% of the indicators) significantly reduced the excess risk of death (RER) = 0.35 [95% confidence interval (CI) 0.28-0.45]. Analysis of the separate indicators showed that patients for whom complementary imaging tests were requested had better survival, RER = 0.58 [95% CI 0.46-0.73], as did patients with stage III colon cancer who underwent adjuvant chemotherapy, RER = 0.33, [95% CI 0.16-0.70]. Adherence to clinical practice guidelines can reduce the excess risk of dying from CRC by 65% [95% CI 55-72%]. Ordering complementary imagining tests that improve staging and treatment choice for all CRC patients and adjuvant chemotherapy for stage III colon cancer patients could be especially important. In contrast, controlled delays in starting some treatments appear not to decrease survival.


Urinary creatinine excretion, bioelectrical impedance analysis, and clinical outcomes in patients with CKD: the CRIC study.
Previous studies in chronic disease states have demonstrated an association between lower urinary creatinine excretion (UCr) and increased mortality, a finding presumed to reflect the effect of low muscle mass on clinical outcomes. Little is known about the relationship between UCr and other measures of body composition in terms of the ability to predict outcomes of interest. Using data from the Chronic Renal Insufficiency Cohort (CRIC), the relationship between UCr, fat free mass (FFM) as estimated by bioelectrical impedance analysis, and (in a subpopulation) whole-body dual-energy x-ray absorptiometry assessment of appendicular lean mass were characterized. The associations of UCr and FFM with mortality and ESRD were compared using Cox proportional hazards models. A total of 3604 CRIC participants (91% of the full CRIC cohort) with both a baseline UCr and FFM measurement were included; of these, 232 had contemporaneous dual-energy x-ray absorptiometry measurements. Participants were recruited between July 2003 and March 2007. UCr and FFM were modestly correlated (rho=0.50; P<0.001), while FFM and appendicular lean mass were highly correlated (rho=0.91; P<0.001). Higher urinary urea nitrogen, black race, younger age, and lower serum cystatin C level were all significantly associated with higher UCr. Over a median (interquartile range) of 4.2 (3.1-5.0) years of follow-up, 336 (9.3%) participants died and 510 (14.2%) reached ESRD. Lower UCr was associated with death and ESRD even after adjustment for FFM (adjusted hazard ratio for death per 1 SD higher level of UCr, 0.63 [95% confidence interval, 0.56 to 0.72]; adjusted hazard ratio for ESRD per 1 SD higher level of UCr, 0.70 [95% confidence interval, 0.63 to 0.75]). Among a cohort of individuals with CKD, lower UCr is associated with death and ESRD independent of FFM as assessed by bioelectrical impedance analysis.


Fortification methods of coenzyme Q10 in yogurt and its health functionality-a review.
Coenzyme Q10 (CoQ10) is an antioxidant, fat-soluble component present in the mitochondrial cells. It provides beneficial results in the treatment of male infertility. In the current scenario, the sedative lifestyle, diet and stress in human lead to excessive free radicals (ROS), leading to health aliments. The review is conducted to compare the effect of different fortification methods of CoQ10 in the Yogurt. The study showed that nanoparticles form of CoQ10 in yogurt showed higher bioaccesiblity rates in humans, and the microencapsulation of CoQ10 showed a low amount of Ubiquinone released during its shelf life. The functional Yogurt produced by the Monascus-fermented soybean powder (MFSP) co-fermentation has been shown to have high free radicals scavenging activity. Thus, the review observes that each fortified sample is useful in its way as CoQ10 supplements. Further studies must be done for accurate conclusions on its effect on male infertility, and other fortification media can be explored.


Scent marking in Sunda clouded leopards (Neofelis diardi): novel observations close a key gap in understanding felid communication behaviours.
Intraspecific communication is integral to the behavioural ecology of solitary carnivores, but observing and quantifying their communication behaviours in natural environments is difficult. Our systematic literature review found that basic information on scent marking is completely lacking for 23% of all felid species, and information on 21% of other felid species comes solely from one study of captive animals. Here we present results of the first systematic investigation of the scent marking behaviours of Sunda clouded leopards in the wild. Our observations using motion-triggered video cameras in Indonesian Borneo are novel for clouded leopards, and contrary to previous descriptions of their behaviour. We found that clouded leopards displayed 10 distinct communication behaviours, with olfaction, scraping, and cheek rubbing the most frequently recorded. We also showed that males make repeated visits to areas they previously used for marking and that multiple males advertise and receive information at the same sites, potentially enhancing our ability to document and monitor clouded leopard populations. The behaviours we recorded are remarkably similar to those described in other solitary felids, despite tremendous variation in the environments they inhabit, and close a key gap in understanding and interpreting communication behaviours of clouded leopards and other solitary felids.


The Anterior Interosseus Artery Perforator Flap: Anatomical Dissections and Clinical Study.
Reconstruction of upper extremity deformities continues to be a challenge to the reconstructive surgeon. Various loco regional, distant and free flaps are available for reconstruction. However, each has its own set of advantages and disadvantages. Of the commonly performed local flaps, radial artery forearm flap, and the posterior interosseus artery flap stand out prominently. Recently, perforator propeller flaps have been used for resurfacing the upper extremity. The anterior interosseus artery perforator flap is an uncommonly used and described flap. This study was divided into anatomical study and clinical application in a IV level of evidence. In the anatomical study, five upper extremities were studied. Clinically, 12 patients underwent reconstruction using the anterior interosseus artery perforator flap. Flaps were performed by a single surgeon. A retrospective review of these cases from November 2008 to May 2014 is presented. The anterior interosseus artery perforator was identified in four out of five cadaver limbs. The septocutaneous perforator was in the fifth extensor compartment around 4 cm proximal to the wrist joint. Of the twelve flaps, there was complete necrosis in one flap, and partial necrosis in one flap. The patient with complete necrosis underwent skin grafting at a later date. The wound healed secondarily in case of partial flap necrosis. Anterior interosseus artery perforator flap must be considered as an important reconstructive option in the armamentarium of the plastic surgeon, while managing hand and wrist defects.


Murine viral hepatitis involves NK cell depletion associated with virus-induced apoptosis.
Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent animal model for the study of immunological disorders related to acute and chronic hepatitis. In this study, we have verified if the fulminant hepatitis induced by MHV3 could be related to an impairment of innate immunity. Groups of three C57BL/6 mice were infected with the pathogenic L2-MHV3 or attenuated YAC-MHV3 viruses, and the natural killer (NK) cell populations from liver, spleen and bone marrow were analysed. The percentage of intrahepatic NK1.1(+)T cell receptor (TCR)- cells did not increase while NK1.1(+)TCR(inter) cells decreased in both L2-MHV3- and YAC-MHV3-infected mice. Concurrently, splenic and myeloid NK1.1+ cells decreased in L2-MHV3-infected mice. However, the cytotoxic activity of NK cells increased in liver and decreased in bone marrow from pathogenic L2-MHV3-infected mice while no modification was detected in YAC-MHV3-infected mice. Flow cytometric analysis revealed that both normal and larger splenic or myeloid NK cells decreased more in pathogenic L2-MHV3-infected mice than in attenuated YAC-MHV3-infected mice. In vitro viral infections of interleukin (IL)-15-stimulated lymphoid cells from liver and bone marrow revealed that L2-MHV3 induced higher decreases in cell viability of NK1.1+ cells than the YAC-MHV3 variant. The NK cell decreases were due to the viral permissivity leading to cytopathic effects characterized by cell rounding, syncytia formation and apoptosis. Larger NK+ syncytia were observed in L2-MHV3-infected cells than in YAC-MHV3-infected cells. These results suggest that NK cell production is impaired by viral infection favouring fulminant hepatitis.


Palmitic acid increases medial calcification by inducing oxidative stress.
Aortic medial calcification is a cellular-regulated process leading to arterial stiffness. Although epidemiological studies have suggested an association between the saturation of fatty acids (FA) and arterial stiffness, there is no evidence that saturated FA can induce arterial calcification. This study investigated the capacity of palmitic acid (PA) to induce medial calcification and the signaling pathway(s) implicated in this process. Rat aortic segments and vascular smooth muscle cells (VSMC) were exposed to calcification medium supplemented with PA. In vivo, rats were treated with warfarin to induce calcification and fed a PA-enriched diet. In vitro and ex vivo, palmitate increases calcification and ROS production. Palmitate increases extracellular-signal-regulated kinase (ERK1/2) phosphorylation and osteogenic gene expression. Inhibition of NADPH oxidase with apocynin or an siRNA prevents these effects. ERK1/2 inhibition attenuates the amplification of osteogenic gene expression and calcification induced by palmitate. In vivo, a PA-enriched diet amplified medial calcification and pulse wave velocity (PWV). These effects are mediated by ROS production as indicated by the inhibition of calcification and PWV normalization in rats concomitantly treated with apocynin. ROS induction by palmitate leads to ERK1/2 phosphorylation and subsequently induces the osteogenic differentiation of VSMC. © 2013 S. Karger AG, Basel.


Training cognitive skills in virtual reality: measuring performance.
Across a variety of operational environments, virtual reality (VR) is being increasingly used as a means of simulating hazardous work conditions in order to allow trainees to practice advanced cognitive skills such as problem-solving and decision-making. Replicating dangerous conditions particularly involving heavy machinery in the real world can be dangerous and costly. The use of VR is therefore appealing across many industries such as aviation, mining, and rail. However, while the number of training prototypes increase less focus is being given to appropriate evaluation of the training provided via this technology. Increasing skills acquisition and performance does not depend solely on the appropriate design of simulation training. Of equal importance are strong performance measures which can ultimately feedback on the success or otherwise of training and highlight any deficits to guide ongoing improvements. To ensure cognitive skills acquired in a virtual training environment (VTE) are transferable to the real world, training objectives need to be tied directly to realistic scenario events which in turn are directly linked to measures of specific required behaviors.


Evaluating a composite cartridge for small system drinking water treatment.
A pilot-scale evaluation was conducted at the U.S. Environmental Protection Agency (EPA) Test & Evaluation (T&E) Facility in Cincinnati, Ohio, on a multi-layer, cartridge-based system that combines physical filtration with carbon adsorption and ultraviolet (UV) light disinfection to serve as a home-base water treatment security device against accidental or intentional contaminant events. The system was challenged with different levels of turbidity, a number of biological contaminants including Bacillus subtilis, Escherichia coli, MS2 bacteriophage and Polystyrene Latex (PSL) beads as a surrogate for Cryptosporidium and a number of chemical contaminants including super-chlorination, methyl tertiary butyl ether (MTBE), water chlorination disinfection byproducts (DBPs) and diazinon. The results demonstrated that the performance of the system varies as a function of the specific contaminant or surrogate. The overall performance indicated the potential of the system to improve the quality and safety of household water and to serve as an additional treatment barrier in circumstances where there is little or no treatment or where the quality of treated water may have deteriorated during distribution. The results also demonstrated that B. subtilis spore can serve as a more conservative surrogate for Cryptosporidium than PSL beads.


Hierarchical organization of cognition reflected in distributed frontoparietal activity.
Organization of behavior into a nested hierarchy of tasks and subtasks is characteristic of purposive cognition in humans. While frontoparietal regions have been shown to represent many kinds of task events, their representation of task/subtask structure has not been directly investigated. On each trial of the current study, participants carried out a sequence of four visual target detections organized by task context into subtasks of different structure (three and one or two and two). Through extended regions of frontoparietal cortex, activity elicited by target detections depended upon the hierarchical level of the episode completed. Target detections completing the entire trial elicited greatest activity, followed by targets completing a subtask, and finally targets within one subtask. Results depended on task and subtask completion, rather than the complexity of the next task stage to be established. We suggest that, through large regions of frontoparietal cortex, control representations direct each step of a behavioral program. Completion of a subtask revises control representations related just to this subtask, leaving those related to the overarching task episode intact, while completion of the entire task revises the entire assembly of representations.


A Targeted RNAi Screen Identifies Endocytic Trafficking Factors That Control GLP-1 Receptor Signaling in Pancreatic β-Cells.
The glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) is a key target for type 2 diabetes (T2D) treatment. Because endocytic trafficking of agonist-bound receptors is one of the most important routes for regulation of receptor signaling, a better understanding of this process may facilitate the development of new T2D therapeutic strategies. Here, we screened 29 proteins with known functions in G protein-coupled receptor trafficking for their role in GLP-1R potentiation of insulin secretion in pancreatic β-cells. We identify five (clathrin, dynamin1, AP2, sorting nexins [SNX] SNX27, and SNX1) that increase and four (huntingtin-interacting protein 1 [HIP1], HIP14, GASP-1, and Nedd4) that decrease insulin secretion from murine insulinoma MIN6B1 cells in response to the GLP-1 analog exendin-4. The roles of HIP1 and the endosomal SNX1 and SNX27 were further characterized in mouse and human β-cell lines and human islets. While HIP1 was required for the coupling of cell surface GLP-1R activation with clathrin-dependent endocytosis, the SNXs were found to control the balance between GLP-1R plasma membrane recycling and lysosomal degradation and, in doing so, determine the overall β-cell incretin responses. We thus identify key modulators of GLP-1R trafficking and signaling that might provide novel targets to enhance insulin secretion in T2D.


Deletion of the dominant autoantigen in NZB mice with autoimmune hemolytic anemia: effects on autoantibody and T-helper responses.
The mechanisms underlying apparently spontaneous autoimmune diseases, such as autoimmune hemolytic anemia (AIHA) in New Zealand Black (NZB) mice, are unknown. Here, we determine the contribution of the dominant red blood cell (RBC) autoantigen, the anion exchanger protein Band 3, to the development of NZB autoimmune responses. The approach was to prevent Band 3 expression in NZB mice by disrupting the AE1 gene. AE1(-/-) NZB mice produced RBC autoantibodies at the same levels as the wild-type strain, but they differed in recognizing antigens that correspond to glycophorins, rather than Band 3. Splenic T-helper (Th) cells from wild-type NZB mice proliferated strongly against multiple Band 3 peptides, particularly the dominant epitope within aa861-874. This helper response was severely attenuated in AE1(-/-) animals, leaving only weak proliferation to peptide aa861-874. The results demonstrate that the defect in self-tolerance in NZB AIHA is directed to the RBC type, and is not specific for, or dependent on, Band 3. However, the predisposition to RBC autoimmunity may be focused onto Band 3 by weak Th cell cross-reactivity between the helper dominant epitope and an exogenous antigen. The redundancy of the major autoantigen illustrates the requirement for specific therapy to induce dominant forms of tolerance, such as T-cell regulation.


ADAM33 is not essential for growth and development and does not modulate allergic asthma in mice.
A disintegrin and metalloprotease 33 (ADAM33) is a transmembrane protease and integrin ligand that has been identified as an asthma susceptibility gene product. To determine whether ADAM33 plays important roles in mammalian development and the modulation of allergic airway dysfunction, we generated ADAM33-null mice by gene targeting. ADAM33-null mice were born at expected Mendelian ratios, and both male and females developed normally and were fertile. No anatomical or histological abnormalities were detected in any tissues. In an animal model of allergic asthma, ADAM33-null mice showed normal allergen-induced airway hyperreactivity, immunoglobulin E production, mucus metaplasia, and airway inflammation. Our results demonstrate that ADAM33 is not essential for growth or reproduction in the mouse and does not modulate baseline or allergen-induced airway responsiveness.


Proline inhibition of a sea anemone alarm pheromone response.
1. L-proline, by itself or in animal tissue extracts, inhibits the response of the sea anemone Anthopleura elegantissima to the alarm phermone, anthopeurine. 2. The effect of proline is mediated by a receptor that is specific for the structure and configuration of the part of the L-proline molecule containing the carboxyl and imino groups. 3. Proline inhibition is competitive, in the sense that the effects of a given proline concentration can be overridden by an increase in anthopeurine concentration. 4. The magnitude of proline inhibition increases with proline concentration and decreases as the duration of exposure to proline increases. 5. Neither the final conducting system mediating the alarm response nor the responding muscles are inhbited by proline. Inhibition presumably occurs at or soon after the level of anthopleurine receptors. 6. Proline inhibition may resolve the potential conflict between Anthopleura's mutually exclusive feeding and alarm pheromone responses.


Genomic and Gene-Expression Comparisons among Phage-Resistant Type-IV Pilus Mutants of Pseudomonas syringae pathovar phaseolicola.
Pseudomonas syringae pv. phaseolicola (Pph) is a significant bacterial pathogen of agricultural crops, and phage Φ6 and other members of the dsRNA virus family Cystoviridae undergo lytic (virulent) infection of Pph, using the type IV pilus as the initial site of cellular attachment. Despite the popularity of Pph/phage Φ6 as a model system in evolutionary biology, Pph resistance to phage Φ6 remains poorly characterized. To investigate differences between phage Φ6 resistant Pph strains, we examined genomic and gene expression variation among three bacterial genotypes that differ in the number of type IV pili expressed per cell: ordinary (wild-type), non-piliated, and super-piliated. Genome sequencing of non-piliated and super-piliated Pph identified few mutations that separate these genotypes from wild type Pph--and none present in genes known to be directly involved in type IV pilus expression. Expression analysis revealed that 81.1% of gene ontology (GO) terms up-regulated in the non-piliated strain were down-regulated in the super-piliated strain. This differential expression is particularly prevalent in genes associated with respiration--specifically genes in the tricarboxylic acid cycle (TCA) cycle, aerobic respiration, and acetyl-CoA metabolism. The expression patterns of the TCA pathway appear to be generally up and down-regulated, in non-piliated and super-piliated Pph respectively. As pilus retraction is mediated by an ATP motor, loss of retraction ability might lead to a lower energy draw on the bacterial cell, leading to a different energy balance than wild type. The lower metabolic rate of the super-piliated strain is potentially a result of its loss of ability to retract.


Effects of maternal and provider characteristics on up-to-date immunization status of children aged 19 to 35 months.
We examined the effects of maternal and provider characteristics on the up-to-date immunization status of children. We used data from the 2003 National Immunization Survey to determine variations in children's up-to-date status in the 4:3:1:3 immunization series. Low maternal educational levels and low socioeconomic status were associated with high 4:3:1:3 series completion rates. Also, completion rates were high in Hispanic and non-Hispanic Black families with low income-to-poverty ratios. We found that children of less educated mothers and children in Hispanic and non-Hispanic Black families with low income-to-poverty ratios were more likely to have completed the 4:3:1:3 series. Although the reasons for these results need further exploration in other data sets, possible factors are Hispanics' positive cultural attitudes regarding the needs and importance of young children and provision of information on immunizations to low-income minority mothers who access government-subsidized health care programs.


Antibody-dependent enhancement infection facilitates dengue virus-regulated signaling of IL-10 production in monocytes.
Interleukin (IL)-10 levels are increased in dengue virus (DENV)-infected patients with severe disorders. A hypothetical intrinsic pathway has been proposed for the IL-10 response during antibody-dependent enhancement (ADE) of DENV infection; however, the mechanisms of IL-10 regulation remain unclear. We found that DENV infection and/or attachment was sufficient to induce increased expression of IL-10 and its downstream regulator suppressor of cytokine signaling 3 in human monocytic THP-1 cells and human peripheral blood monocytes. IL-10 production was controlled by activation of cyclic adenosine monophosphate response element-binding (CREB), primarily through protein kinase A (PKA)- and phosphoinositide 3-kinase (PI3K)/PKB-regulated pathways, with PKA activation acting upstream of PI3K/PKB. DENV infection also caused glycogen synthase kinase (GSK)-3β inactivation in a PKA/PI3K/PKB-regulated manner, and inhibition of GSK-3β significantly increased DENV-induced IL-10 production following CREB activation. Pharmacological inhibition of spleen tyrosine kinase (Syk) activity significantly decreased DENV-induced IL-10 production, whereas silencing Syk-associated C-type lectin domain family 5 member A caused a partial inhibition. ADE of DENV infection greatly increased IL-10 expression by enhancing Syk-regulated PI3K/PKB/GSK-3β/CREB signaling. We also found that viral load, but not serotype, affected the IL-10 response. Finally, modulation of IL-10 expression could affect DENV replication. These results demonstrate that, in monocytes, IL-10 production is regulated by ADE through both an extrinsic and an intrinsic pathway, all involving a Syk-regulated PI3K/PKB/GSK-3β/CREB pathway, and both of which impact viral replication.


Comparison of self-report versus accelerometer - measured physical activity and sedentary behaviors and their association with body composition in Latin American countries.
Most population-based studies from Latin America have used questionnaires to measure physical activity (PA) and sedentary behaviors (SB). Low reliability and validity of the questionnaires has limited the capacity to examine associations between PA and health. The purpose of this study was to compare self-reported and accelerometer-measured PA and SB and their associations with body composition in Latin American countries. Data were obtained from the Latin American Study of Nutrition and Health (aged 15-65 years), collected from September 2014 to February 2015. PA and SB were assessed using the International Physical Activity Questionnaire (long version) and the Actigraph GT3X+ accelerometer. Outcomes of interest included: body mass index (BMI), waist (WC) and neck circumference (NC). We used the Pearson and intraclass correlation coefficient, Bland-Altman plots, and multilevel linear regression models. Mean moderate-to-vigorous physical activity (MVPA) by accelerometer and IPAQ were 34.4 min/day (95% CI: 33.4 to 35.4) and 45.6 min/day (95% CI: 43.2 to 48.1), respectively. For SB (accelerometer and IPAQ) the means were 573.1 (95% CI: 568.2 to 577.9) and 231.9 min/day (95% CI: 225.5 to 238.3). MVPA, measured by the accelerometer was negatively associated with BMI (β = -1.95; 95% CI: -2.83 to -1.08), WC (β = -5.04; 95% CI: -7.18 to -2.89) and NC (β = -1.21; 95% CI: -1.79 to -0.63). The MVPA estimated through IPAQ was not significantly associated with any of the three outcome variables. SB, measured by the accelerometer, was positively associated with BMI (β = 0.26; 95% CI: 0.08 to 0.44) and WC (β = 0.48; 95% CI: 0.13 to 0.91). SB estimated through IPAQ was positively associated with NC only. Low correlation coefficients were observed for accelerometer-derived and IPAQ-reported estimates of PA and SB. Caution is advised when making comparisons between accelerometer-measured and self-reported PA and SB. Further, studies examining associations between movement and health should discuss the impact of PA and SB measurement methodology on the results obtained.


Prevention of bone loss by oil extract of garlic (Allium sativum Linn.) in an ovariectomized rat model of osteoporosis.
The effects of oil extract of garlic (Allium sativum Linn.) on different primary and secondary osteoporotic marker changes were tested in an ovariectomized rat model of osteoporosis. Experiments were performed on three different rat models: sham-operated control, ovariectomized and ovariectomized supplemented with garlic oil. In ovariectomized group, there has been a significant increase in different relative organ weights compared to sham-operated control, while the uterine weight was found to be decreased. Supplementation with oil extract of garlic could effectively reverse these changes. Also low bone densities that developed in the ovariectomized group were significantly recovered in the garlic oil supplemented group. In our study, the development of high rate of bone turnover and osteoporosis in the ovariectomized animals were confirmed by significant alteration of serum alkaline phosphatase activity, serum tartrate resistant acid phosphatase activity, urinary excretion of calcium, phosphate, hydroxyproline and urinary calcium to creatinine ratio, when compared with the sham-operated control group. Garlic oil extract supplementation, apart from its unique influence in lowering blood cholesterol, could also prevent ovariectomy-induced rise in all the above-mentioned marker changes. The results of this study emphasize that oil extract of garlic possibly has a positive role in suppressing ovariectomy-induced bone resorption.


Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice.
Disrupted homeostasis of the microtubule binding protein tau is a shared feature of a set of neurodegenerative disorders known as tauopathies. Acetylation of soluble tau is an early pathological event in neurodegeneration. In this work, we find that a large fraction of neuronal tau is degraded by chaperone-mediated autophagy (CMA) whereas, upon acetylation, tau is preferentially degraded by macroautophagy and endosomal microautophagy. Rerouting of acetylated tau to these other autophagic pathways originates, in part, from the inhibitory effect that acetylated tau exerts on CMA and results in its extracellular release. In fact, experimental blockage of CMA enhances cell-to-cell propagation of pathogenic tau in a mouse model of tauopathy. Furthermore, analysis of lysosomes isolated from brains of patients with tauopathies demonstrates similar molecular mechanisms leading to CMA dysfunction. This study reveals that CMA failure in tauopathy brains alters tau homeostasis and could contribute to aggravate disease progression.


Aberrant expression and localization of decorin in human oral dysplasia and squamous cell carcinoma.
The small leucine-rich proteoglycan decorin has been associated with negative regulation of cell growth. It has a prominent role in transforming growth factor (TGF)-beta and epidermal growth factor receptor activation pathways that contributes to its role in cellular proliferation, angiogenesis, and immunomodulation. Our studies are directed toward analysis of decorin gene expression, identified through DNA microarray studies, in oral premalignant and malignant tissues as well as representative cell lines of an oral cancer progression model. We have used long oligonucleotide microarray analysis, immunohistochemistry, confocal microscopy, reverse transcription-PCR, sequencing, and Western immunoblot techniques to characterize decorin expression in oral premalignant archival tissues and an oral cancer progression cellular model. We have further analyzed the deduced amino acid sequence derived from full-length cDNA that do not show any deletion or mutations of the decorin expressed in oral premalignant and malignant cell lines. In our studies, we show aberrant expression of decorin in dysplastic oral epithelial cells. Both promoters P1 and P2 drive the aberrant expression resulting in exon 1a as well as exon 1b carrying transcripts. Intracellular accumulation and nuclear localization of aberrantly expressed decorin were observed in dysplastic oral tissues and in the respective cell lines. Decorin expressed in oral cancer may have lost its ability to inhibit TGF-beta signaling and activate epidermal growth factor receptor signaling pathways because of such aberrant nuclear localization, resulting in a major dysfunction of otherwise a natural extracellular antagonist of TGF-beta and a putative tumor suppressor protein. The aberrant nuclear localization of a leucine-rich repeat protein might result in additional protein-protein interactions and resulting changes in gene expression. Further studies to characterize such interacting proteins and localization-dependent effects of aberrant decorin expressed in oral cancer progression are warranted.


The sirtuin-2 inhibitor AK7 is neuroprotective in models of Parkinson's disease but not amyotrophic lateral sclerosis and cerebral ischemia.
Sirtuin deacetylases regulate diverse cellular pathways and influence disease processes. Our previous studies identified the brain-enriched sirtuin-2 (SIRT2) deacetylase as a potential drug target to counteract neurodegeneration. In the present study, we characterize SIRT2 inhibition activity of the brain-permeable compound AK7 and examine the efficacy of this small molecule in models of Parkinson's disease, amyotrophic lateral sclerosis and cerebral ischemia. Our results demonstrate that AK7 is neuroprotective in models of Parkinson's disease; it ameliorates alpha-synuclein toxicity in vitro and prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine depletion and dopaminergic neuron loss in vivo. The compound does not show beneficial effects in mouse models of amyotrophic lateral sclerosis and cerebral ischemia. These findings underscore the specificity of protective effects observed here in models of Parkinson's disease, and previously in Huntington's disease, and support the development of SIRT2 inhibitors as potential therapeutics for the two neurodegenerative diseases.


A rice ABC transporter, OsABCC1, reduces arsenic accumulation in the grain.
Arsenic (As) is a chronic poison that causes severe skin lesions and cancer. Rice (Oryza sativa L.) is a major dietary source of As; therefore, reducing As accumulation in the rice grain and thereby diminishing the amount of As that enters the food chain is of critical importance. Here, we report that a member of the Oryza sativa C-type ATP-binding cassette (ABC) transporter (OsABCC) family, OsABCC1, is involved in the detoxification and reduction of As in rice grains. We found that OsABCC1 was expressed in many organs, including the roots, leaves, nodes, peduncle, and rachis. Expression was not affected when plants were exposed to low levels of As but was up-regulated in response to high levels of As. In both the basal nodes and upper nodes, which are connected to the panicle, OsABCC1 was localized to the phloem region of vascular bundles. Furthermore, OsABCC1 was localized to the tonoplast and conferred phytochelatin-dependent As resistance in yeast. Knockout of OsABCC1 in rice resulted in decreased tolerance to As, but did not affect cadmium toxicity. At the reproductive growth stage, the As content was higher in the nodes and in other tissues of wild-type rice than in those of OsABCC1 knockout mutants, but was significantly lower in the grain. Taken together, our results indicate that OsABCC1 limits As transport to the grains by sequestering As in the vacuoles of the phloem companion cells of the nodes in rice.


The effect of rainfall on the incidence of cholera in Bangladesh.
The incidence of cholera in Bangladesh shows clear seasonality, suggesting that weather factors could play a role in its epidemiology. We estimated the effects of rainfall on the incidence of cholera in Dhaka, Bangladesh. We examined time-series patterns of the weekly number of hospital visits due to cholera in relation to weekly rainfall from 1996 to 2002. We used Poisson regression models, adjusted for seasonal variation, between-year variation, public holidays, and temperature. The role of river level on the rainfall-cholera relationship was also examined by incorporating river-level terms into the models. The weekly number of cholera cases increased by 14% (95% confidence interval = 10.1%-18.9%) for each 10-mm increase above the threshold of 45 mm for the average rainfall, over lags 0 to 8 weeks. Conversely, the number of cholera cases increased by 24% (10.7%-38.6%) for a 10-mm decrease below the same threshold of average rainfall, over lags 0 to 16 weeks. River level partly explained the association between high rainfall and the number of cholera cases. The number of cholera cases increased with both high and low rainfall in the weeks preceding hospital visits. These results suggest that factors associated with river level are on the causal pathway between high rainfall and incidence of cholera.


Layered metal-dielectric waveguide: subwavelength guidance, leveraged modulation sensitivity in mode index, and reversed mode ordering.
We describe a layered metal-dielectric waveguide, whose fundamental mode has an effective index as high as 7.35 at 1.55 μm, enabling subwavelength spatial confinement. The loss is found to be reasonable in relation to the confinement. The indefinite dielectric tensor of the stratified metamaterial core generally leads to multimode operation of the waveguide, exhibiting a "reversed" mode ordering contrary to conventional waveguides. The waveguide features a strong leveraging in modal index change subject to a change of index in the dielectric layers, opening the design possibilities of very compact active electro-optic devices.


Push-out strength of modified Portland cements and resins.
Modified calcium-silicate cements derived from white Portland cement (PC) were formulated to test their push-out strength from radicular dentin after immersion for 1 month. Slabs obtained from 42 single-rooted extracted teeth were prepared with 0.6 mm diameter holes, then enlarged with rotary instruments. After immersion in EDTA and NaOC1, the holes were filled with modified PCs or ProRoot MTA, Vitrebond and Clearfil SE. Different concentrations of phyllosilicate (montmorillonite-MMT) were added to experimental cements. ProRoot MTA was also included as reference material. Vitrebond and Clearfil SE were included as controls. Each group was tested after 1 month of immersion in water or PBS. A thin-slice push-out test on a universal testing machine served to test the push-out strength of materials. Results were statistically analyzed using the least squares means (LSM) method. The modified PCs had push-out strengths of 3-9.5 MPa after 1 month of immersion in water, while ProRoot MTA had 4.8 MPa. The push-out strength of PC fell after incubation in PBS for 1 month, while the push-out strength of ProRoot MTA increased. There were no significant changes in Clearfil SE Bond or Vitrebond after water or PBS storage.


Clinical experience with microindentation in vivo in humans.
Densitometry and imaging techniques are currently used in clinical settings to measure bone quantity and spatial structure. Recently, Reference Point Indentation has opened the possibility of directly assessing the mechanical characteristics of cortical bone in living individuals, adding a new dimension to the assessment of bone strength. Impact microindentation was specifically developed for clinical studies and has been tested in several populations where there are discrepancies between bone density and fracture propensity, such as type 2 diabetes, atypical femoral fracture, stress fractures, glucocorticoid treatment, patients with osteopenia and fragility fractures, and individuals infected with HIV, among others. Microindentation will complement, not replace, existing bone analysis methods, particularly where bone mineral density does not fully explain fracture propensity. The available evidence provides solid proof of concept; future studies will fully define the role of microindentation for the assessment of bone health both in clinics and in research.


A density functional theory investigation of the electronic structure and spin moments of magnetite.
We present the results of density functional theory (DFT) calculations on magnetite, Fe3O4, which has been recently considered as electrode in the emerging field of organic spintronics. Given the nature of the potential applications, we evaluated the magnetite room-temperature cubic [Formula: see text] phase in terms of structural, electronic, and magnetic properties. We considered GGA (PBE), GGA + U (PBE + U), and range-separated hybrid (HSE06 and HSE(15%)) functionals. Calculations using HSE06 and HSE(15%) functionals underline the impact that inclusion of exact exchange has on the electronic structure. While the modulation of the band gap with exact exchange has been seen in numerous situations, the dramatic change in the valence band nature and states near the Fermi level has major implications for even a qualitative interpretation of the DFT results. We find that HSE06 leads to highly localized states below the Fermi level while HSE(15%) and PBE + U result in delocalized states around the Fermi level. The significant differences in local magnetic moments and atomic charges indicate that describing room-temperature bulk materials, surfaces and interfaces may require different functionals than their low-temperature counterparts.


Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo.
Peptide epitopes derived from differentiation antigens of the melanocyte lineage were recently identified in human melanomas as targets for MHC-restricted cytotoxic T lymphocytes (CTL). The characterization of multiple CTL-defined antigenic determinants has opened possibilities of development of antigen-targeted vaccines. In the present study, we determined CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase, and gp100/Pmel17 in 3 HLA-A2+ melanoma patients. Then, we assessed the immune responses to synthetic melanoma-associated peptides injected intradermally. After 3 cycles of immunization with peptide alone, we used systemic GM-CSF as an adjuvant during the fourth cycle of immunization. Enhanced DTH reactions and CD8+ CTL responses were observed after treatment with systemic GM-CSF. Immunohistochemical characterization of DTH-constituting elements revealed infiltrates of CD4+ and CD8+ T lymphocytes and strong expression of IL-2 and gammaIFN, suggesting the activation of CD4+ ThI and CD8+ CTL by peptides presented by MHC-class-I molecules of dermal APC. Objective tumor regression was documented in all patients. We conclude that systemic GM-CSF enhances immune responses to melanoma-associated peptides and supports CTL-mediated tumor rejection in vivo.


An ethical evaluation of the 2006 Centers for Disease Control and Prevention Recommendations for HIV testing in health care settings.
When in 2006 the Centers for Disease Control and Prevention issued revised recommendations for HIV testing in health care settings, vocal opponents charged that use of an "opt-out" approach to presenting HIV testing to patients; the implementation of nontargeted, widespread HIV screening; the elimination of a separate signed consent; and the decoupling of required HIV prevention counseling from HIV testing are unethical. Here we undertake the first systematic ethical examination of the arguments both for and against the recommendations. Our examination reveals that the ethical concerns raised by the critics predominantly pertain not to ethically suspect elements of the recommendations themselves, but to suspicions that they will be implemented improperly. It has not been shown that the recommendations cannot be implemented properly. Here we show that in the United States the recommendations are morally justifiable and that safeguards or regulatory oversight may serve to ensure that the recommendations are properly implemented.


The diversification of the antimicrobial peptides from marine worms is driven by environmental conditions.
Antimicrobial peptides (AMPs) play a key role in the external immunity of animals, offering an interesting model for studying the influence of the environment on the diversification and evolution of immune effectors. Alvinellacin (ALV), arenicin (ARE) and polaricin (POL, a novel AMP identified here), characterized from three marine worms inhabiting contrasted habitats ('hot' vents, temperate and polar respectively), possess a well conserved BRICHOS domain in their precursor molecule despite a profound amino acid and structural diversification of the C-terminal part containing the core peptide. Data not only showed that ARE, ALV and POL display an optimal bactericidal activity against the bacteria typical of the habitat where each worm species lives but also that this killing efficacy is optimal under the thermochemical conditions encountered by their producers in their environment. Moreover, the correlation between species habitat and the cysteine contents of POL, ARE and ALV led us to investigate the importance of disulfide bridges in their biological efficacy as a function of abiotic pressures (pH and temperature). The construction of variants using non-proteinogenic residues instead of cysteines (α-aminobutyric acid variants) leading to AMPs devoid of disulfide bridges, provided evidence that the disulfide pattern of the three AMPs allows for a better bactericidal activity and suggests an adaptive way to sustain the fluctuations of the worm's environment. This work shows that the external immune effectors exemplified here by BRICHOS AMPs are evolving under strong diversifying environmental pressures to be structurally shaped and more efficient/specific under the ecological niche of their producer.


Protonation Dependent Topological Dichotomy of Core Modified Hexaphyrins: Synthesis, Characterization, and Excited State Dynamics.
Two hitherto unknown core modified hexaphyrin analogues have been synthesized and characterized where the conformational dynamics of these macrocycles in the free base form is achieved by the rotation of thienothiophene units. Further unique property of these macrocycles is the Hückel-Möbius topological switching. The thermodynamic equilibrium and kinetics of the interconversion leading to Hückel-Möbius switches have been triggered by external stimuli, such as protonation and/or temperature. We have provided a thorough solution-state spectroscopic characterization, solid-state structural evidence combined with in-depth theoretical calculations to investigate the crucial factors involved in such interconversion between Hückel and Möbius topologies for these hexaphyrins which will be useful in designing future new members to expanded porphyrin chemistry.


Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program.
Ectopic expression of defined transcription factors can force direct cell-fate conversion from one lineage to another in the absence of cell division. Several transcription factor cocktails have enabled successful reprogramming of various somatic cell types into induced neurons (iNs) of distinct neurotransmitter phenotype. However, the nature of the intermediate states that drive the reprogramming trajectory toward distinct iN types is largely unknown. Here we show that successful direct reprogramming of adult human brain pericytes into functional iNs by Ascl1 and Sox2 encompasses transient activation of a neural stem cell-like gene expression program that precedes bifurcation into distinct neuronal lineages. During this transient state, key signaling components relevant for neural induction and neural stem cell maintenance are regulated by and functionally contribute to iN reprogramming and maturation. Thus, Ascl1- and Sox2-mediated reprogramming into a broad spectrum of iN types involves the unfolding of a developmental program via neural stem cell-like intermediates.


The Correlation of Pars Plana Incision and Transient Hypotony After Silicone Oil Removal.
To evaluate the correlation between pars plana incision and transient hypotony after silicone oil removal in aphakic eyes PATIENTS AND METHODS:Twenty-two patients with aphakia and a high degree of myopia with silicone oil tamponade were recruited for this prospective study and randomly scheduled to two groups for silicone oil removal: 3.5-mm corneal incision with suture corneal or 20-gauge pars plana incision with suture. Intraocular pressure (IOP) was measured and fundus and anterior structure were examined preoperatively on the first, third, and seventh postoperative day and at 1 month after surgery. IOPs in the pars plana group were significantly lower than the corneal group on the first and third day after surgery (P < .001). Nine of the 11 patients in the pars plana group suffered ciliary detachment accompanied by hypotony (IOP < 8 mm Hg), among whom three patients exhibited excessive hypotony (IOP < 5 mm Hg), whereas the ciliary bodies remained tightly attached and IOP was normal in the corneal group. Among these nine patients, six eyes were observed to have multiple silicone oil granules in the supraciliary cavity, three exhibited gaps of pars plana below the scleral incision site, and two had vitreous hemorrhage. Hypotony spontaneously relieved at the seventh postoperative day for all patients. Pars plana incision is the crucial cause of ciliary detachment and consequent transient hypotony after silicone oil removal. Using corneal limbus incision in patients with aphakic eyes to avoid the par plana incision is expected to reduce the incidence of hypotony with minimal complications. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e44-e51.].


Patients' perceptions of teleconsultation during COVID-19: A cross-national study.
In recent months, humanity has had to deal with a worldwide pandemic called COVID-19, which has caused the death of hundreds of thousands of people and paralyzed the global economy. Struggling to cure infected patients while continuing to care for patients with other pathologies, health authorities have faced the lack of medical staff and infrastructure. This study aimed to investigate the acceptance of teleconsultation solutions by patients, which help to avoid the spread of the disease during this pandemic period. The model was built using some constructs of the technology acceptance model UTAUT2, Personal traits, Availability, and Perceived Risks. A new scale on Contamination Avoidance was developed by the authors. The questionnaire was disseminated in several countries in Europe and Asia and a total sample of 386 respondents was collected. The results emphasize the huge impact of Performance Expectancy, the negative influence of Perceived Risk, and the positive influence of Contamination Avoidance on the adoption of teleconsultation solutions. The findings highlight the moderating effects of Age, Gender, and Country.


Validation studies for population-based intervention coverage indicators: design, analysis, and interpretation.
Population-based intervention coverage indicators are widely used to track country and program progress in improving health and to evaluate health programs. Indicator validation studies that compare survey responses to a "gold standard" measure are useful to understand whether the indicator provides accurate information. The Improving Coverage Measurement (ICM) Core Group has developed and implemented a standard approach to validating coverage indicators measured in household surveys, described in this paper. The general design of these studies includes measurement of true health status and intervention receipt (gold standard), followed by interviews with the individuals observed, and a comparison of the observations (gold standard) to the responses to survey questions. The gold standard should use a data source external to the respondent to document need for and receipt of an intervention. Most frequently, this is accomplished through direct observation of clinical care, and/or use of a study-trained clinician to obtain a gold standard diagnosis. Follow-up interviews with respondents should employ standard survey questions, where they exist, as well as alternative or additional questions that can be compared against the standard household survey questions. Indicator validation studies should report on participation at every stage, and provide data on reasons for non-participation. Metrics of individual validity (sensitivity, specificity, area under the receiver operating characteristic curve) and population-level validity (inflation factor) should be reported, as well as the percent of survey responses that are "don't know" or missing. Associations between interviewer and participant characteristics and measures of validity should be assessed and reported. These methods allow respondent-reported coverage measures to be validated against more objective measures of need for and receipt of an intervention, and should be considered together with cognitive interviewing, discriminative validity, or reliability testing to inform decisions about which indicators to include in household surveys. Public health researchers should assess the evidence for validity of existing and proposed household survey coverage indicators and consider validation studies to fill evidence gaps.


Participants' perceptions of research benefits in an African genetic epidemiology study.
Both the Council for International Organization of Medical Sciences and the Helsinki Declaration emphasize that the potential benefits of research should outweigh potential harms; consequently, some work has been conducted on participants' perception of benefits in therapeutic research. However, there appears to be very little work conducted with participants who have joined non-therapeutic research. This work was done to evaluate participants' perception of benefits in a genetic epidemiological study by examining their perception of the potential benefits of enrollment. In-depth interviews lasting between 45 and 60 minutes were conducted with a convenient sample of 25 ill patients and 25 healthy accompanying relatives enrolled in a genetic epidemiological study of tuberculosis. Recorded interviews were transcribed and analyzed using content analysis. Participants perceived that research was beneficial and some of the benefits included the generation of new knowledge, finding the cause of diseases, as well as the control, eradication and prevention of disease. Some thought that research was risky whilst others thought that the benefits outweighed the risks. Participants perceived research to be beneficial and most of them thought that, though it was risky, the benefits outweighed the risks. It is our view that researchers need to give serious consideration to participant's perception of benefits in designing their consent forms, to see to the fulfillment of achievable goals.


First Report of Wet Rot of Withania somnifera Caused by Choanephora cucurbitarum in India.
Withania somnifera (Ashwagandha) is native to India and commercially cultivated for the production of root withanolides that have anticarcinogenic properties. A disease appeared on plantings of W. somnifera during the 2010 monsoon at the CIMAP and in adjoining areas of northern India. Symptoms first appeared as water-soaked lesions on leaves and stems that progressed to a wet rot. Mature lesions harbored black fructifications of the suspect pathogen. Pathogen isolations were done by placing pieces of infected tissues on potato dextrose agar. A fungus tentatively identified as a Choanephora sp. that produced white aerial mycelia that later turned pale yellow was consistently isolated from infected plant parts. Mycelia were hyaline and nonseptate. Sporangiophores bearing sporangiola were erect, hyaline, unbranched, apically dilated to form a clavate vesicle from which arose dichotomously branched distally clavate secondary vesicles. Sporangiola were indehiscent, ellipsoid, brown to dark brown with distinct longitudinal striations, and measured 12 to 20 × 6 to 12 μm. Sporangia were multispored, spherical, initially white to yellow and pale brown to dark brown at maturity, and measured 40 to 160 μm. Sporangiospores from sporangia were ellipsoid to broadly ellipsoid, brown to dark brown, indistinctly striate with fine hyaline polar appendages, and measured 16 to 20 × 8 to 12 μm. On the basis of the cultural as well as morphological characteristics and description in the monograph by Kirk (2), the fungus was identified as a Choanephora sp. The identification was also confirmed by IMTECH, Chandigarh, India with Accession No. MTCC-10731. The species was later characterized as Choanephora cucurbitarum (Berk. & Ravenel) Thaxt (GenBank Accession No. AB470642) by using universal primers ITS-1 and ITS-4. Its sequence comprising of 18S rRNA partial, complete ITS 1, 5.8S rRNA, ITS 2, and 28S rRNA partial was submitted to NCBI GenBank with Accession No. JN639861. Pathogenicity of the fungus was established on five healthy plants by artificial inoculation with spray of an aqueous spore suspension containing 106 spores/ml. Plants sprayed with sterile distilled water were used as controls. Both inoculated and control plants were kept in a humidity chamber (96%) for 3 days and thereafter placed in the glasshouse at 28 ± 2°C. Initial symptoms developed in 2 to 3 days while typical disease symptoms appeared on all the inoculated plants after 7 to 10 days. Control plants were free from infection. The reisolation from artificially infected plants again yielded a Choanephora sp., thus fulfilling Koch's postulates. W. somnifera cultivation has been affected by root rot and wilt caused by Fusarium solani and leaf spot caused by Alternaria dianthicola (3). The occurrence of a Choanephora sp. was reported on periwinkle, petunia (1), and Boerhavia diffusa (4). However, to our knowledge, incidence of this pathogen on W. somnifera has not been reported so far. Thus, wet rot of W. somnifera caused by C. cucurbitarum is a new report from India and worldwide. References: (1) G. E. Holcomb. Plant Dis. 87:751, 2003. (2) P. M. Kirk. Mycol. Pap. 152:1, 1984. (3) C. K. Maiti et al. Plant Dis. 91:467, 2007. (4) N. Singh et al. New Dis. Rep. 23:29, 2011.


False hope: effects of social class and health policy on oral health inequalities for migrant farmworker families.
Few studies have engaged issues of social class and access related to dental health care policy from an ethnographic perspective. The state of Florida in the US has one of the poorest records in the nation for providing dental care for low-income children, falling especially short for Medicaid-enrolled children. In this paper, we discuss unmet dental health needs of children in migrant farmworker families. Although one of the most marginalized populations, most are eligible for Medicaid and are thus covered for dental services. However, serious disparities have been linked to the lack of access through the public insurance system. This study was informed by participant observation at dental clinics and a Migrant Head Start Center and interviews with dental health providers (n = 19) and migrant farmworker parents (n = 48) during 2009. Our results indicate that some typical factors associated with poor oral health outcomes, such as low dental health literacy, may not apply disproportionately to this population. Instead, we argue that structural features and ineffective policies contribute to oral health care disparities. Dental Medicaid programs are chronically underfunded, resulting in low reimbursement rates, low provider participation, and a severe distribution shortage of dentists within poor communities. We characterize the situation for families in Florida as one of "false hope" because of the promise of services with neither adequate resources nor the urgency to provide them. The resulting system of charity care, which leads dentists to provide pro bono care instead of accepting Medicaid, serves to only further persistent inequalities. We provide several recommendations, including migrant-specific efforts such as programs for sealants and new mothers; improvements to the current system by removing obstacles for dentists to treat low-income children; and innovative models to provide comprehensive care and increase the number of providers.


Structures of chaperone-substrate complexes docked onto the export gate in a type III secretion system.
The flagellum and the injectisome enable bacterial locomotion and pathogenesis, respectively. These nanomachines assemble and function using a type III secretion system (T3SS). Exported proteins are delivered to the export apparatus by dedicated cytoplasmic chaperones for their transport through the membrane. The structural and mechanistic basis of this process is poorly understood. Here we report the structures of two ternary complexes among flagellar chaperones (FliT and FliS), protein substrates (the filament-capping FliD and flagellin FliC), and the export gate platform protein FlhA. The substrates do not interact directly with FlhA; however, they are required to induce a binding-competent conformation to the chaperone that exposes the recognition motif featuring a highly conserved sequence recognized by FlhA. The structural data reveal the recognition signal in a class of T3SS proteins and provide new insight into the assembly of key protein complexes at the export gate.


Change of residence and functional status within three months and one year following hip fracture surgery.
To study the recovery of patients in terms of 18 activities of daily living and change of residence within the year following a hip fracture. This prospective cohort study was carried out in a trauma service of an acute hospital in southern Spain including 159 patients with a hip fracture, 65 years or older and allowed weight-bearing after surgery. Patients or their relatives were interviewed about their residential status and functional level at pre-fracture, three months and one year after surgery, using the Functional Independence Measure. Losses of function for the main activities affected were, at the first month, third month and one year relative to the pre-fracture status, 50%, 25% and 12%, respectively, for locomotion, 40%, 25% and 20%, respectively, for mobility and 27%, 17% and 15%, respectively, for self care (p < 0.001). Residential status changed mostly for patients who lived in their own home (73% before fracture to 58% at one year). The loss of independence in the first year after a hip fracture is substantial for specific activities. Recovery mainly takes place during the first three months after surgery. Change of residence mostly involved those patients who lived alone in their own home at pre-fracture. Implications for Rehabilitation One year after fracture, patients did not recover their previous function, and the activities most affected at the one-year follow-up were: dressing lower body, bathing/showering, transfer bathtub/shower and walking up/down stairs. After a hip fracture, most recovery of the function happens within the first three months, though some functional activities continue recovering over the first year. Rehabilitation programs cannot be based only on mobility activities, the recovery of other daily living activities should also be included.