Serum galectin-3, but not galectin-1, levels are elevated in schizophrenia: implications for the role of inflammation.
Previous studies have reported that galectin-3 is involved in inflammatory processes in the central nervous system and that neuroinflammation may play a role in the pathogenesis of schizophrenia. However, the link between schizophrenia and various galectins is unclear. The objective of the present study is to determine whether galectin, a well-known lectin protein that binds to μ-galactoside, is associated with chronic schizophrenia. Thirty-six patients with schizophrenia and 36 healthy controls participated in this study. Schizophrenia symptoms were assessed using the Brief Psychiatry Rating Scale (BPRS). Serum galectin-1 and galectin-3 levels were evaluated using ELISA and compared between the participant groups. Correlation analyses were also performed to examine the relationship between BPRS scores and each galectin level. Serum galectin-3 levels were significantly higher in patients with schizophrenia than they were in controls (p = 0.009, d = 0.640); however, serum galectin-1 levels were not significantly different between the groups (p = 0.513). No significant correlation was identified between serum galectin-3 level and the total BPRS score; however, a significant positive correlation was found between the serum galectin-3 level and the positive symptom score of the BPRS (ρ = 0.355; p = 0.033). Additionally, a significant negative correlation was identified between serum galectin-3 levels and the negative symptom score of the BPRS (ρ = -0.387; p = 0.020). Given the high serum levels of galectin-3 found in patients with schizophrenia compared with that in controls, these findings may support the inflammation hypothesis of schizophrenia.


Family planning among a group of coloured women.
Two-hundred-and-fifty Coloured women were interviewed at family planning and antenatal clinics in an effort to assess the type of person who practices family planning and to determine possible ways of reaching those who do not. The study shows a definite tendency towards the small family ideal and children are seen as an expense rather than as a source of income. Forty-two per cent of the sample had either never used family planning methods or had done so only after their third child was born. Sixty-seven per cent indicated lack of knowledge or fears resulting therefrom as the reason for delaying family planning. Of the antenatal patients interviewed, 69% said their pregnancies were unplanned. This seems to indicate the need for an intensified drive to educate and motivate people, especially teenagers, to plan their families.


Ovarian morphology and follicular systems in yaks of different ages.
Forty-five female yaks of different ages with known reproductive histories were used to determine the morphology and follicular systems of their ovaries. The histological structure of the ovaries in each age group was found to be similar and resembled that of cattle and buffalo. The atresia of primordial follicles took one form (oocyte atresia); that of growing follicles could be divided into two stages (early and late); and that of Graafian follicular were classified as early, definite and late stage. The details of the several types of atresia are described herein. The average total numbers of primordial follicles per ovary pair in 1-month-old calves, 1-year-old heifers, 2-year-old heifers and 7-10-year-old cows were 53,500 +/- 6300, 32,870 +/- 4500, 22,850 +/- 2800 and 9500 +/- 1200, respectively; those of growing follicles were 210 +/- 76, 815 +/- 95, 895 +/- 142 and 445 +/- 88, respectively; and those of Graafian follicles were 36.5 +/- 14.2, 41.7 +/- 12.3, 37.8 +/- 9.8 and 42.5 +/- 14.5, respectively. The percentage of atretic primordial follicles per ovary pair in 1-month-old calves, 1-year-old heifers, 2-year-old heifers and 7 to 10 year-old cows were 51.6, 55.5, 56.7 and 47.4%, respectively. The average total numbers of atretic growing follicles per ovary pair were 119.5 +/- 21.5, 605.5 +/- 74.3, 721.6 +/- 78.5 and 275.8 +/- 66.3, respectively; those of atretic Graafian follicles were 22.1 +/- 5.6, 21.2 +/- 7.6, 21.5 +/- 4.7 and 25.3 +/- 6.7, respectively.


Establishment of ku70-deficient lung epithelial cell lines and their hypersensitivity to low-dose x-irradiation.
In clinical situations, cellular resistance to chemotherapy and radiotherapy is a significant component of tumor treatment failure. The DNA repair protein Ku70 is a key contributor to chemoresistance to anticancer agents, e.g., etoposide and bleomycin, or radioresistance. Ku70 plays a key role as a sensor of DNA double-strand breaks (DSBs) induced following exposure to ionizing radiation as well as treatment with some chemotherapeutic drugs. The responses of different organs to radiation vary widely and likely depend on the cell population in the organs. However, it is not clear whether Ku70 plays a role in the low-dose radioresistance of lung epithelial cells. In this study, we established Ku70-deficient epithelial cell lines from murine lungs lacking Ku70. Ku70-/- lung epithelial cells exhibited reduced Ku80 expression. Moreover, Ku70-/- lung epithelial cells were more sensitive than controls (Ku70+/- lung epithelial cells) to low-dose X-irradiation (< 0.5 Gy). We also found that consistent with the Ku70 function as a sensor of DSBs, Ku70 mainly localized in the nuclei of murine lung epithelial cells. These findings clearly indicate that Ku70 plays a key role in regulation of the Ku80 expression level in and the radioresistance of lung epithelial cells. Our data also suggest that these cell lines might be useful not only for study of Ku70 functions and the DSB repair pathway, but also for study of the molecular mechanism underlying the sensitivity to chemotherapeutic drugs and radiation in lung epithelial cells.


[Inhibitory effects of melatonin on breast cancer].
Melatonin has a significant inhibitory effect on various cancers, especially on breast cancer. In estrogen receptor (ER)-positive human breast cancer, anti-cancer effects of melatonin on breast cancer cells and transplanted tumors mainly achieve by suppressing ER mRNA expression and ER transcriptional activity via the MT1 receptor. In addition, melatonin regulates the transactivation of other members of the nuclear receptor super-family, estrogen metabolizing enzymes, and the expression of related genes. Furthermore, melatonin also suppresses tumor aerobic metabolism, critical cell-signaling pathways relevant to cell proliferation, survival, metastasis, and drug resistance. Melatonin demonstrates both cytostatic and cytotoxic activity in breast cancer cells that appears to be cell-type specific. Studies on animal and human models indicate that disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer, resulting in invalid hormone therapy and chemotherapeutic resistance in breast tumors.


[Changes in various biochemical and physico-chemical properties of hemoglobin during its aging].
It is shown that hemoglobin senescence leads to both a decrease of amide groups in it and redistribution of the radioactive label (55Fe) in electrophoretic fractions. It is supposed that an increase of the radio-active label in highly mobile hemoglobin fractions of the "old" erythrocytes by 78 and 43% as compared to that of the "young" erythrocytes is related to the deamidation-mediate growth of the negative charge of this protein molecule or partial denaturation of its quaternary structure. The resistance of hemoglobin of the "old" erythrocytes is shown to decrease to acid tissue proteinases of the lysosomal fraction as against hemoglobin of the "young" erythrocytes.


Genesis of multipeaked waves of the esophagus: repetitive contractions or motion artifact?
Multipeaked waves (MPW) in the distal esophagus occur frequently in patients with esophageal spastic motor disorders and diabetes mellitus and are thought to represent repetitive esophageal contractions. We aimed to investigate whether the relative motion between a stationary pressure sensor and contracted peristaltic esophageal segment that moves with respiration leads to the formation of MPW. We mathematically modeled the effect of relative movement between a moving pressure segment and a fixed pressure sensor on the pressure waveform morphology. We conducted retrospective analysis of 100 swallow-induced esophageal contractions in 10 patients, who demonstrated >30% MPW on high-resolution manometry (HRM) during standardized swallows. Finally, using HRM, we determined the effects of suspended breathing and hyperventilation on the waveform morphology in 10 patients prospectively. Modeling revealed that relative movement between a stationary pressure sensor and a moving contracted segment, contraction duration, contraction amplitude, respiratory frequency, and depth of respiration affects the waveform morphology. Retrospective analysis demonstrated a close temporal association with the onset of second and subsequent contractions in MPW with respiratory phase reversals. Numbers of peaks in MPW and respiratory phase reversals were closely related to the duration of contraction. In the prospective study, suspended breathing and hyperventilation resulted in a significant decrease and increase in the MPW frequency as well as the number of peaks within MPW respectively. We conclude that MPW observed during clinical motility studies are not indicative of repetitive esophageal contraction; rather they represent respiration-related movement of the contracted esophageal segment in relation to the stationary pressure sensor.


Cortisol response and psychological distress predict susceptibility to false memories for a trauma film.
For eyewitness testimony to be considered reliable, it is important to ensure memory remains accurate following the event. As many testimonies involve traumatic, as opposed to neutral, events, it is important to consider the role of distress in susceptibility to false memories. The aim of this study was to investigate whether cortisol response following a stressor would be associated with susceptibility to false memories. Psychological distress responses were also investigated, specifically, dissociation, intrusions, and avoidance. Participants were allocated to one of three conditions: those who viewed a neutral film (N = 35), those who viewed a real trauma film (N = 35), and a trauma "reappraisal" group where participants were told the film was not real (N = 35). All received misinformation about the film in the form of a narrative. Participants provided saliva samples (to assess cortisol) and completed distress and memory questionnaires. Cortisol response was a significant predictor of the misinformation effect. Dissociation and avoidance were related to confabulations. In conclusion, following a stressor an individual may differ with regard to their psychological response to the event, and also whether they experience a cortisol increase. This may affect whether they are more distressed later on, and also whether they remember the event accurately.


A core undergraduate curriculum in plastic surgery - a Delphi consensus study in Scandinavia.
In recent years, undergraduate medical education has undergone a transition from a speciality-based to a more competence-based training system. Consequently, whilst medical knowledge is rapidly expanding, time for teaching of the surgical specialties is decreasing. Thus, there appears to be a need to define the core competences that are to be taught. The aim of this study was to establish a Scandinavian core undergraduate curriculum of competences in plastic surgery, using scientific methods. The Delphi technique for group consensus was employed. An expert panel was recruited from various plastic surgery subspecialties, institutions, and levels of clinical experience, in four Nordic countries (Denmark, Finland, Norway and Sweden). Questionnaires were sent out and answers collected electronically via Google Forms™. Following completion of three predefined rounds of anonymous questionnaires; a final core curriculum competency list was agreed upon based on a consensus agreement level of 80%. Two hundred and ninety-five competences were suggested in the first round. In the second round, 76 competences (33 skills and 43 knowledge items) received a score ≥3.00 on a 1-4 Likert scale. Final agreement in the third round resulted in a list of 68 competences with agreement above 80% (31 skills and 37 knowledge items). This study proposes the first scientifically developed undergraduate core curriculum in plastic surgery. It comprises of a consensus of competences a recently graduated medical doctor should be expected to possess.


Work Characteristics as Predictors of Correctional Supervisors' Health Outcomes.
This study examined associations among health behaviors, psychosocial work factors, and health status. Correctional supervisors (n = 157) completed a survey that assessed interpersonal and organizational views on health. Chi-square and logistic regressions were used to examine relationships among variables. Respondents had a higher prevalence of obesity and comorbidities compared with the general US adult population. Burnout was significantly associated with nutrition, physical activity, sleep duration, sleep quality, diabetes, and anxiety/depression. Job meaning, job satisfaction, and workplace social support may predict health behaviors and outcomes. Correctional supervisors are understudied and have poor overall health status. Improving health behaviors of middle-management employees may have a beneficial effect on the health of the entire workforce. This paper demonstrates the importance of psychosocial work factors that may contribute to health behaviors and outcomes.


Effectiveness of a balance-focused exercise program for enhancing functional fitness of older adults at risk of falling: A randomised controlled trial.
This study examined the effectivenss of a balance-focused training program (i.e., Exercise for Balance Improvement Program, ExBP) in improving functional fitness of older nonfallers at risk of falling. Sixty-one participants were randomly assigned to receive 16 weeks of ExBP or Tai Chi (TC) training, or no treatment (CON) with an 8-week follow-up. The Senior Fitness Test battery was applied to assess functional fitness. After the intervention, results revealed significant improvements in all fitness components in the ExBP group. Compared with the CON group, the ExBP group demonstrated more improvements in lower extremity muscle strength, agility and balance, and aerobic endurance. The ExBP group also displayed more improvements in aerobic endurance than the TC group in posttest and follow-up test. Therefore, the balance-focused exercise can be applied as an effective way in improving overall functional fitness among older nonfallers who are at risk of falling.


Comparative pharmacokinetic study of chlorogenic acid after oral administration of Lonicerae Japonicae Flos and Shuang-Huang-Lian in normal and febrile rats.
Shuang-Huang-Lian (SHL), a famous traditional Chinese medicine recipe containing Lonicerae Japonicae Flos (LJF), Forsythiae Fructus, and Scutellariae Radix, is clinically used for the treatment of fever and acute upper respiratory tract infection. In this research, a comparative study was conducted to compare the pharmacokinetic difference of chlorogenic acid (ChA) after oral administration of LJF and SHL to normal and febrile rats with approximately the same dose of 60 mg/kg, and the antipyrexia effect of LJF and SHL on rectal temperature changes induced by Baker's yeast was investigated. The results indicated that AUC(0-t) and plasma concentrations of ChA in the febrile rats were significantly higher than normal rats whether in the extract of LJF or SHL. In addition, SHL increased the values of AUC of ChA in both febrile and normal rats compared with LJF alone (p < 0.05), and SHL showed better antipyrexia effect than LJF. These results indicate that fever could play an important role in pharmacokinetic process of ChA. Meanwhile, the combined formula SHL exhibits higher bioavailability of ChA and superior antipyrexia effect than the single herb.


Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation.
Several modalities of ventilatory support have been proposed to gradually withdraw patients from mechanical ventilation, but their respective effects on the outcome of weaning from mechanical ventilation are not known. We conducted a randomized trial in three intensive care units in mechanically ventilated patients who met standard weaning criteria. Those who could not sustain 2 h of spontaneous breathing were randomly assigned to be weaned with T-piece trials, with synchronized intermittent mandatory ventilation (SIMV), or with pressure support ventilation (PSV). Specific criteria for performing tracheal extubation were defined for each modality. The number of patients who could not be separated from the ventilator at 21 d (i.e., who failed to wean) was compared between the groups. Patients in whom tracheal intubation was required in a 48-h period following extubation were also classified as failures. Among 456 mechanically ventilated patients who met weaning criteria, 109 entered into the study (35 with T piece, 43 with SIMV, and 31 with PSV). The three groups were comparable in terms of etiology of disease or characteristics at entry in the study. When all causes for weaning failure were considered, a lower number of failures was found with PSV than with the other two modes, with the difference just reaching the level of significance (23% for PSV, 43% for T piece, 42% for SIMV; p = 0.05). After excluding patients whose weaning was terminated for complications unrelated to the weaning process, the difference became highly significant (8% for PSV versus 33% and 39%, p < 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)


VEGFR1 primes a unique cohort of dental pulp stem cells for vasculogenic differentiation.
Dental pulp stem cells (DPSCs) constitute a unique group of cells endowed with multipotency, self-renewal, and capacity to regenerate the dental pulp tissue. While much has been learned about these cells in recent years, it is still unclear if each DPSC is multipotent or if unique sub-populations of DPSCs are "primed" to undergo specific differentiation paths. The purpose of the present study was to define whether a sub-population of DPSCs was uniquely primed to undergo vasculogenic differentiation. Permanent-tooth DPSCs or stem cells from human exfoliated deciduous teeth (SHED) were flow-sorted for vascular endothelial growth factor receptor 1 (VEGFR1) and exposed to vasculogenic differentiation medium, i.e., Microvascular-Endothelial-Cell-Growth-Medium-2-BulletKit™ supplemented with 50 ng/mL rhVEGF165 in the presence of 0 or 25 μg/mL anti-human VEGF antibody (bevacizumab; Genentech). In addition, sorted SHED (i.e., VEGFR1high or VEGFR1low) were seeded in biodegradable scaffolds and transplanted into the subcutaneous space of immunodeficient mice. Despite proliferating at a similar rate, VEGFR1high generated more in vitro sprouts than VEGFR1low cells (p < 0.05). Blockade of VEGF signaling with bevacizumab inhibited VEGFR1high-derived sprouts, demonstrating specificity of responses. Similarly, VEGFR1high SHED generated more blood vessels when transplanted into murine hosts than VEGFR1low cells (p < 0.05). Collectively, these data demonstrated that DPSCs contain a unique sub-population of cells defined by high VEGFR1 expression that are primed to differentiate into vascular endothelial cells. These data raise the possibility of purifying stem cells with high vasculogenic potential for regeneration of vascularized tissues or for vascular engineering in the treatment of ischemic conditions.


Diagnosis of adult hereditary pulmonary disease and the role of genetic testing.
Genetic testing is becoming a common component of medical practice and is used to determine definitive diagnoses for several adult pulmonary diseases. It is important for pulmonologists to know when to use genetic tests for diagnosis and medical management. This article describes diagnosis of rare hereditary pulmonary disease in adults and the role of genetic testing. A summary on coding and reimbursement is included.


Sexualizing men's touch: male nurses and the use of intimate touch in clinical practice.
Drawn from a larger study, this article reports the experiences of a group of male nurses regarding the use of intimate physical touch. Using discourse analysis, interview data from 18 male nurses were analyzed and related to existing text on men as nurses. The analysis reveals that although touch is important in nursing care, it is problematic for men because discourses have normalized women's use of touch as a caring behavior and have sexualized men's touch. Participants described their vulnerability, how they protected themselves from risk, and the resulting stress. The complicity of nurses in sexualizing men's touch and the neglect of educators in preparing men for providing intimate care are revealed. A paradox emerged whereby the very measures employed to protect both patients and men as nurses exacerbate the perceived risk posed by men carrying out intimate care. Deconstructing and reframing prevailing discourses around nursing, gender, and caring involving touch can help to legitimize men's involvement in physical caring.


An unusual cause for recurrent syncope in a female adult with LEOPARD syndrome.
The LEOPARD syndrome is a rare autosomal dominant, multisystem disease involving the skin, skeletal and cardiovascular systems. Echocardiography including stress testing was used in a patient with LEOPARD syndrome and recurrent syncope to reveal the hemodynamic relevance of a giant aneurysm of the interventricular membraneous septum ballooning into the right ventricular outflow tract. This case impressively underlines the vital necessity of dynamic testing particularly in patients with symptoms during exercise even if these symptoms might be addressed to other findings.


Noble gases in pure lipid membranes.
The mechanism of how a noble gas modifies the excitability of nerve cells and how such excitability can be recovered under hyperbaric pressure remains unclear. Here we present a calorimetric study where the melting point depression of pure lipid membranes induced by noble gases and its recovery with a hydrostatic pressure is addressed. A correlation is found between the electric polarizability (α) of these gases and their effect on the melting transition of the membranes. These results concur with other findings to support the idea that general anesthesia only depends on the ability of a certain atom or molecule to increase the general disorder of the membrane.


The "pumpgate" incident: Stigma against lactating mothers in the U.S. workplace.
Studies conclude that breastfeeding for six months is associated with better lifelong health for the mother and the child. Mothers in the U.S. returning to work after maternity leave report difficulty with the need to take frequent breaks to pump breastmilk so many stop breastfeeding. Factors discouraging pumping breastmilk in the workplace motivated a content analysis of public comments posted in response to a legal deposition that occurred in January of 2011 in which an attorney who was a new mother was challenged about taking a break to pump breastmilk. A total of 899 public comments posted on Yahoo in 2015-2016 in response to this earlier incident were analyzed for content. Of these, only 336 mentioned breastfeeding. Overall, 148 comments showed support for breastfeeding or pumping breastmilk at work, while 182 comments showed moderate to strong disapproval (six unclassified). The majority of disapproving comments were critical of pumping breastmilk in the workplace. Implications of these findings for the duration of breastfeeding after returning to work are discussed.


Vitamin D status and blood group among severe COVID-19 patients.
Prognosis of COVID-19 infection has been indicated to be associated with vitamin D status and ABO blood group. However, owing to discrepancies and an increased number of cases globally, the findings remain unclear. This study aimed to evaluate the association between vitamin D and ABO blood group systems in patients with severe COVID-19. In this cross-sectional study, COVID-19 patients referred to two hospitals in the capital of Iran, Tehran, admitted to the ICU ward due to the severity of COVID-19 were evaluated. Serum vitamin D and ABO levels were evaluated in these patients. The data obtained were statistically analyzed using SPSSv24. Of 305 patients, 33.1% patients had O+ blood type, 27.8% had A+ blood type and 22.4% had B+ blood type. Vitamin D deficiency was significantly associated with a mortality rate among these patients, P<0.05. The blood group of the patients was not correlated with mortality. Thirty-seven percent of the patients in the study died because of COVID-19. In our study population, mortality due to COVID-19 was significantly associated with vitamin D deficiency but not the ABO blood group. We recommend further studies in this regard that include more variable and detailed biochemical analysis.


DDT and BHC residues in some body tissues of goats, buffalo, and chickens, Lucknow, India.
Muscle, liver, brain, and abdominal body fat samples of goats, buffalo, and chickens, all common meat sources in India, were analyzed by gas-liquid chromatography (GLC) for residues of DDT and benzene hexachloride (BHC). A few samples of goat and buffalo bone marrow were also included. Relatively high residue levels were found in body fat and bone marrow compared with other tissues. DDT and BHC residue levels were highest in chicken body fat, averaging 4.157 ppm sigma DDT and 3.879 ppm BHC. DDT content was much higher in goat and buffalo bone marrow than in the corresponding body fat. DDT levels in brain samples were highest (0.138 ppm) in buffalo. p,p'-TDE levels were higher than p,p'-DDE levels in buffalo; overall DDT levels were lowest in goats. BHC residues were generally low in buffalo; alpha-BHC accounted for most BHC residues in brain tissues. Greater accumulations of DDT and BHC were found in leg muscles than in breast muscles of chickens.


Effect of storage time on the urine protein: creatinine ratio in alkaline ovine urine.
The urine protein:creatinine (UPC) ratio is considered the reference method to assess proteinuria. Its diagnostic value in ovine medicine needs further elucidation. In population monitoring and/or for research purposes, it is convenient to collect many samples simultaneously and store them for later analysis. However, analyte stability data are required to ensure reliable results. We used 15 of 90 urine samples collected from sheep to assess the effect of storage time on the UPC ratio. After centrifugation, the supernatant of each sample was divided into 6 aliquots. Urine protein and creatinine concentrations were determined immediately in one aliquot using the pyrogallol red and a modified Jaffè method, respectively. The other aliquots were stored at -18°C. Based on the absence of active sediment, alkaline urine pH, and UPC ratio ≥0.2, we included 15 samples in our study. The UPC ratio was determined in the stored aliquots 2, 7, 14, 21, and 60 d after collection. The data were analyzed with univariate ANOVA. No significant difference was observed in the urinary concentrations of protein, creatinine, and the UPC ratio (0.8 ± 0.84 in conventional units and 0.09 ± 0.095 in SI units) among different times (p > 0.05). The UPC ratio remained stable for 2 mo in ovine urine samples stored at -18°C.


A new approach to understanding adaptive visual-vestibular interactions in the central nervous system.
Recent neurophysiological findings, cited in previous publications imply that some vestibular commissural pathways may form positive feedback loops across the midline. It has already been shown theoretically that such feedback coupling of the vestibular nuclei could play an important role in the realization of the central integrator in the vestibuloocular reflex (VOR). In addition, it was found that known commissural plasticity during vestibular compensation, if placed at the level of such cross-midline loops, could reconcile findings after labyrinthine lesions. This paper examines theoretically the role such commissural feedback loops could play in the adaptation of the dynamics of the VOR in normal behaving animals. A simple static example is used to illustrate that changes in synaptic efficacy along cross-midline feedback loops could serve to adjust both balance and gain in vestibular reflexes. A bilateral model of the VOR and its interactions with vision is used to explore analytically the consequences of parametric changes along cerebellar and/or commissural pathways in three protocols: VOR in the dark, visual pursuit, and visual VOR suppression. Model predictions are systematically related to published findings after short- and long-term adaptation of the VOR. Conclusions arising from the theoretical results point to specific strategies that can be used in experiments on intact alert animals, in the further study of vestibular adaptation, and in the diagnosis of possible sites of plasticity. This should be relevant to arguments on cerebellar versus brain stem sites for vestibular adaptation, currently a highly controversial issue. For example, it is found that observations of responses in the adapted VOR in the dark are not sufficient to distinguish between a brain stem or cerebellar site for VOR plasticity. Also, the analysis shows that, in the model, changes in the VOR gain would often be associated with parallel changes in VOR dynamics; this has often been reported, but previously left unexplained. Model predictions of response changes in the adapted VOR, during VOR suppression, do provide a means of distinguishing between brain stem or cerebellar sites of plasticity; only the brain stem site, postulated here in the commissural loops, would produce cerebellar response changes compatible with the observations of Miles and Lisberger, during long-term adaptation of the VOR. A cerebellar site for VOR adaptation in the model would produce changes in cerebellar responses that would only be compatible with observations to date during rapid, or short-term (hours), modification of the VOR, as reported by Ito and his group.(ABSTRACT TRUNCATED AT 400 WORDS)


Effect of working consecutive night shifts on sleep time, prior wakefulness, perceived levels of fatigue and performance on a psychometric test in emergency registrars.
To evaluate the effect of working consecutive night shifts on sleep time, prior wakefulness, perceived levels of fatigue and psychomotor performance in a group of Australian emergency registrars. A prospective observational study with a repeated within-subjects component was conducted. Sleep time was determined using sleep diaries and activity monitors. Subjective fatigue levels and reciprocal reaction times were evaluated before and after day and night shifts. A total of 11 registrars participated in the study with 120 shifts analysed. Sleep time was found to be similar during consecutive night and day shifts. The mean number of hours spent awake before the end of a night shift was 14.33. Subjective fatigue scores were worst at the end of a night shift. There was no difference in reciprocal reaction time between the end of night shift and the start of day shift. Registrars sleep a similar amount of time surrounding night and day shifts. Despite reporting the highest levels of fatigue at the end of a night shift, there is no significant difference in reaction times at the end of night shift compared with the beginning of day shift. This correlates with the finding that at the end of night shift the registrars have been awake for less than 16 h, which is the point at which psychomotor performance is expected to decline.


Evaluating antidepressant therapies: remission as the optimal outcome.
Depression is the fourth-largest contributor to the global burden of disease, and it causes profound suffering and extreme costs to health care systems and society. Although there have been many new antidepressants introduced, few depressed individuals receive the optimal treatment. One problem is that the traditional definition of response to antidepressant therapy, i.e., a 50% improvement in symptoms, ensures little beyond a reduction of syndromal intensity. Responders who have persistent depressive symptoms experience ongoing psychosocial dysfunction, poorer health, and an increased risk of relapse. The goal of the first or acute-phase treatment should be complete remission of symptoms and a full return to premorbid levels of functioning. Remission is also a necessary, transitional state toward sustained recovery. Within this context, evidence pertaining to various treatment approaches is reexamined, taking into account critical methodological issues such as design sensitivity and statistical power. Whereas results of individual studies are inconsistent, the findings of meta-analyses (i.e., quantitative and pooled) suggest that both psychotherapy-pharmacotherapy combinations and use of antidepressants that enhance serotonergic and noradrenergic neurotransmission increase the likelihood of remission.


The occupational health nurse's role in the corporate alcoholism program.
The problem of alcohol abuse among the nation's employees takes its toll in countless ways -- in absenteeism, lost productivity, increased utilization of health benefits and eventual loss of the employee's services. In all cases both the employee and the employer lose. Like most other health professionals, nurses have received little education in the care and treatment of persons suffering with alcoholism or alcohol-related problems. But with the appropriate training and the total commitment of her company, she can be in a unique position to offer assistance to the alcoholic employee. The seriousness of this problem today demands that all effective means be utilized. We can no longer afford to mitigate or ignore the occupational health nurse's valuable role in contributing to the success of the corporate alcoholism program.


An Intermolecular π-Stacking Interaction Drives Conformational Changes Necessary to β-Barrel Formation in a Pore-Forming Toxin.
The crystal structures of the soluble monomers of the pore-forming cholesterol-dependent cytolysins (CDCs) contain two α-helical bundles that flank a twisted core β-sheet. This protein fold is the hallmark of the CDCs, as well as of the membrane attack complex/perforin immune defense proteins and the stonefish toxins. To form the β-barrel pore, a core β-sheet is flattened to align the membrane-spanning β-hairpins. Concomitantly with this conformational change, the two α-helical bundles that flank the core β-sheet break their restraining contacts and refold into two membrane-spanning β-hairpins of the β-barrel pore. The studies herein show that in the monomer structure of the archetype CDC perfringolysin O (PFO), a conserved Met-Met-Phe triad simultaneously contributes to maintaining the twist in this core β-sheet, as well as restricting the α-helical-to-β-strand transition necessary to form one of two membrane-spanning β-hairpins. A previously identified intermolecular π-stacking interaction is now shown to disrupt the interactions mediated by this conserved triad. This is required to establish the subsequent intermolecular electrostatic interaction, which has previously been shown to drive the final conformational changes necessary to form the β-barrel pore. Hence, these studies show that the intermolecular π-stacking and electrostatic interactions work in tandem to flatten the core β-sheet and initiate the α-helical-to-β-strand transitions to form the β-barrel pore.IMPORTANCE A unique feature of the CDC/MACPF/SNTX (cholesterol-dependent cytolysin/membrane attack complex perforin/stonefish toxin) superfamily of pore-forming toxins is that the β-strands that comprise the β-barrel pore are derived from a pair of α-helical bundles. These studies reveal the molecular basis by which the formation of intermolecular interactions within the prepore complex drive the disruption of intramolecular interactions within each monomer of the prepore to trigger the α-helical-to-β-strand transition and formation of the β-barrel pore.


Microstructure in a settling suspension of hard spheres.
We report direct observations of the structure factor in a settling suspension, using numerical simulations based on a lattice-Boltzmann model of the fluid. We find that the horizontal density fluctuations in bounded suspensions are strongly suppressed by the settling process, vanishing as k(2) at long wavelengths. Our measurements of the structure factor confirm the qualitative predictions of one of several competing theories, although this theory does not yet explain why container walls are so important. Our results contradict the idea that a settling suspension is inevitably stratified by hydrodynamic dispersion at the suspension-supernatent interface.


Nutritional status of adults participating in ambulatory rehabilitation.
To assess the overall nutritional status of older adults participating in ambulatory rehabilitation and determine its association with relevant outcomes including physical function and quality of life. Cross-sectional. Ambulatory rehabilitation service in the Southern region of Adelaide, Australia. A total of 229 participants recruited as part of a RCT between June 2005 and June 2006, stroke (n=83), elective orthopedic procedure (n=44) and other medical condition (n=102). Nutritional status was measured using Mini Nutritional Assessment (MNA), Simplified Nutrition Appetite Questionnaire (SNAQ) and Body Mass Index. Functional performance was assessed using the Modified Barthel Index (MBI) and quality of life was measured using the Short Form-36 (SF-36). Sixty-three percent of participants were malnourished or at risk of malnutrition according to the MNA and a third had a risk of >or= 5% weight loss in the subsequent six months, according to the SNAQ. Participants with a diagnosis other than stroke or elective orthopedic procedure were the most vulnerable, with 53% (n=74/140) classified as at risk of malnutrition or malnourished and a longer length of stay in hospital. Functional performance was no different for participants assessed as at risk of malnutrition or malnourished compared to the well nourished, but the SF-36 mental component score was significantly higher for those who were well nourished (p=0.003). Findings emphasise the magnitude of the malnutrition problem in ambulatory rehabilitation settings. Further research is required to evaluate the resource implications against expected benefits of providing nutrition interventions at this point.


Tunable Mechanics in Electrospun Composites via Hierarchical Organization.
Design strategies from nature provide vital clues for the development of synthetic materials with tunable mechanical properties. Employing the concept of hierarchy and controlled percolation, a new class of polymer nanocomposites containing a montmorillonite (MMT)-reinforced electrospun poly(vinyl alcohol) (PVA) filler embedded within a polymeric matrix of either poly(vinyl acetate) (PVAc) or ethylene oxide-epichlorohydrin copolymer (EO-EPI) were developed to achieve a tunable mechanical response upon exposure to specific stimuli. Mechanical response and switching times upon hydration were shown to be dependent on the weight-fraction of MMT in the PVA electrospun fibers and type of composite matrix. PVA/MMT.PVAc composite films retained excellent two-way switchability for all MMT fractions; however, the switching time upon hydration was decreased dramatically as the MMT content was increased due to the highly hydrophilic nature of MMT. Additionally, for the first time, significant two-way switchability of PVA/MMT.EO-EPI composites was achieved for higher weight fractions (12 wt %) of MMT. An extensive investigation into the effects of fiber diameter, crystallinity, and MMT content revealed that inherent rigidity of MMT platelets plays an important role in controlling the mechanical response of these hierarchical electrospun composites.


Antibiotic prescribing in DR Congo: a knowledge, attitude and practice survey among medical doctors and students.
Antibiotic resistance (ABR) particularly hits resource poor countries, and is fuelled by irrational antibiotic (AB) prescribing. We surveyed knowledge, attitudes and practices of AB prescribing among medical students and doctors in Kisangani, DR Congo. Self-administered questionnaires. A total of 184 questionnaires were completed (response rate 94.4%). Knowledge about AB was low (mean score 4.9/8 points), as was the estimation of local resistance rates of S. Typhi and Klebsiella spp.(correct by 42.5% and 6.9% of respondents respectively). ABR was recognized as a problem though less in their own practice (67.4%) than nation- or worldwide (92.9% and 85.5%, p<.0001). Confidence in AB prescribing was high (88.6%) and students consulted more frequently colleagues than medical doctors when prescribing (25.4% versus 11.6%, p= 0.19). Sources of AB prescribing included pharmaceutical companies (73.9%), antibiotic guidelines (66.3%), university courses (63.6%), internet-sites (45.7%) and WHO guidelines (26.6%). Only 30.4% and 16.3% respondents perceived AB procured through the central procurement and local pharmacies as of good quality. Local AB guidelines and courses about AB prescribing are welcomed (73.4% and 98.8% respectively). This data shows the need for interventions that support rational AB prescribing.


Complete penoscrotal transposition: A three-stage procedure.
Complete penoscrotal transposition (CPST) with an intact scrotum is a rare anomaly in which the scrotum is located cephalic to the penis. It is the most severe degree of malformation of a spectrum of abnormalities in scrotal development. There are few cases reported in the literature, and there are few descriptions of the technique for correction and results. We describe a new case of CPST and its sequential correction.


An overview of sequencing technology platforms applied to HTLV-1 studies: a systematic review.
Human T-lymphotropic virus type 1 (HTLV-1) was the first human retrovirus described. The viral factors involved in the different clinical manifestations of infected individuals are still unknown, and in this sense, sequencing technologies can support viral genome studies, contributing to a better understanding of infection outcome. Currently, several sequencing technologies are available with different approaches. To understand the methodological advances in the HTLV-1 field, it is necessary to organize a synthesis by a rigorous review. This systematic literature review describes different technologies used to generate HTLV-1 sequences. The review follows the PRISMA guidelines, and the search for articles was performed in PubMed, Lilacs, Embase, and SciELO databases. From the 574 articles found in search, 62 were selected. The articles showed that, even with the emergence of new sequencing technologies, the traditional Sanger method continues to be the most commonly used methodology for generating HTLV-1 genome sequences. There are many questions that remain unanswered in the field of HTLV-1 research, and this reflects on the small number of studies using next-generation sequencing technologies, which could help address these gaps. The data compiled and analyzed here can help research on HTLV-1, assisting in the choice of sequencing technologies.


Daycare attendance, stress, and mental health.
Daycare stress can be indexed by cortisol, and elevated levels of cortisol have been implicated in the onset and development of mental health disorders. Our objective was to quantify the associations between daycare and cortisol and to identify individual and environmental conditions under which daycare attendance is associated with cortisol concentrations. We used Cohen effect size statistics to quantify these associations and to compare them across 11 published studies that were identified with MEDLINE and PsycINFO. Cortisol levels increased during the daycare day, whereas they decreased when children stayed at home. The mean effect size was d = 0.72. The magnitude of the daycare-stress relation seemed to vary under 3 specific conditions. First, the effect size was larger for children in low-quality daycare (d = 1.15), whereas there was essentially little or no effect for children in high-quality daycare (d = 0.10). Second, the effect size was larger for preschoolers (aged 39 to 59 months) (d = 1.17) than for infants (aged 3 to 16 months) (d = 0.11) or school-aged children (aged 84 to 106 months) (d = 0.09). Third, children with difficult temperaments in daycare were more likely to exhibit a rising pattern of cortisol, compared with children who were not difficult. Our review suggests that daycare attendance in relatively low-quality daycare conditions and for children with difficult temperaments may result in atypical cortisol elevation. Although the link between atypical cortisol elevation and mental health requires further study, programs aimed at improving the quality of daycare services during the preschool years are expected to lead to better physiological adaptation to daycare and to reduce the risks of mental health problems.


[Cloning and characterization of a beta-glucosidase from marine metagenome].
In the present study, through a functional strategy, a metagenome library of the marine microbes from the surface water of the South China Sea was screened for beta-glucosidase and six positive clones were obtained. One of these clones, pSB47B2, was subcloned and further analysed in sequence. The result showed that there was an open reading frame for a novel beta-glucosidase, which was nominated as bgl1B. Using pET22b(+) as vector and Escherichia coli BL21(DE3) as host, Bgl1B was overexpressed recombinantly with high yield obtained and substantial enzymatic activity detected. The recombinant protein (rBgllB) was purified by Ni-NTA affinity chromatography and further biochemically characterized. The results indicated that, with pNPG as substrate, the optimum pH and temperature for the hydrolytic activity of rBgl1B were about 6.5 and 40 degrees C respectively. Under the optimum conditions, rBgl1B hydrolyzed pNPG with an activity up to 39.7 U/mg, Km and Vmax being 0.288 mmol/L and 36.9 micromol/min respectively. In addition, rBgl1B could also hydrolyze cellobiose, with a Km of 0.173 mmol/L and a Vmax of 35 micromol/min. However, we did not detect evident hydrolytic activity of rBgl1B to lactose, maltose, sucrose, and CMC. The enzymatic activity of rBgl1B to pNPG was stimulated to certain degrees by low concentration of Ca2+ or Mn2+, whereas it exhibited significant tolerance against high Na+. Distinguished from most of the beta-glucosidases derived from fungi, which display the highest activities under acidic conditions, rBgl1B exhibited relatively higher activity and stability at pH between 7.0 and 9.0.


Tuberculosis and excess alcohol use in the United States, 1997-2012.
Excess alcohol use among tuberculosis (TB) patients complicates TB control strategies. To characterize the role of excess alcohol use in TB control, we describe the epidemiology of excess alcohol use and TB in the United States among those aged ⩾15 years. Using data reported to the National Tuberculosis Surveillance System, 1997-2012, we examined associations between excess alcohol use and TB treatment outcomes and markers for increased transmission (involvement in a local genotype cluster of cases) using multivariate logistic regression. We used Cox proportional hazards regression analysis to examine the relationship between excess alcohol use and the rate of conversion from positive to negative in sputum culture results. Excess alcohol use was documented for 31 207 (15.1%) of 207 307 patients. Prevalence of excess alcohol use was greater among male patients (20.6%) and US-born patients (24.6%). Excess alcohol use was associated with a positive sputum smear result (aOR 1.23, 95%CI 1.18-1.28) and death during treatment (vs. completion of treatment) (aOR 1.16, 95%CI 1.10-1.22). The rate of culture conversion was higher among patients without excess alcohol use (adjusted hazard ratio 1.20, 95%CI 1.18-1.23). Excess alcohol use was common among patients with TB, and was associated with TB transmission, lower rates of sputum culture conversion, and greater mortality.


Influence of excitation wavelength (UV or visible light) on the photocatalytic activity of titania containing gold nanoparticles for the generation of hydrogen or oxygen from water.
Gold nanoparticles supported on P25 titania (Au/TiO(2)) exhibit photocatalytic activity for UV and visible light (532 nm laser or polychromatic light λ > 400 nm) water splitting. The efficiency and operating mechanism are different depending on whether excitation occurs on the titania semiconductor (gold acting as electron buffer and site for gas generation) or on the surface plasmon band of gold (photoinjection of electrons from gold onto the titania conduction band and less oxidizing electron hole potential of about -1.14 V). For the novel visible light photoactivity of Au/TiO(2), it has been determined that gold loading, particle size and calcination temperature play a role in the photocatalytic activity, the most active material (Φ(H2) = 7.5% and Φ(O2) = 5.0% at 560 nm) being the catalyst containing 0.2 wt % gold with 1.87 nm average particle size and calcined at 200 °C.


Simple bone cyst of the jaw: review of the literature and report of case.
Analysis of the data from 255 cases of simple bone cyst is presented. A rare case of multiple simple bone cysts in the mandible is also reported. Criteria for diagnosis, nomenclature, treatment, and prognosis of this entity are discussed.


Cell wall lignin is polymerised by class III secretable plant peroxidases in Norway spruce.
Class III secretable plant peroxidases occur as a large family of genes in plants with many functions and probable redundancy. In this review we are concentrating on the evidence we have on the catalysis of lignin polymerization by class III plant peroxidases present in the apoplastic space in the xylem of trees. Some evidence exists on the specificity of peroxidase isozymes in lignin polymerization through substrate specificity studies, from antisense mutants in tobacco and poplar and from tissue and cell culture lines of Norway spruce (Picea abies) and Zinnia elegans. In addition, real time (RT-)PCR results have pointed out that many peroxidases have tissue specific expression patterns in Norway spruce. Through combining information on catalytic properties of the enzymes, on the expression patterns of the corresponding genes, and on the presence of monolignols and hydrogen peroxide in the apoplastic space, we can show that specific peroxidases catalyze lignin polymerization in the apoplastic space of Norway spruce xylem.


Comparison of Febuxostat and Allopurinol in the Treatment of Patients with Chronic Kidney Disease Stage 3∼5 with Hyperuricemia.
To compare the efficacy of febuxostat and allopurinol in the treatment of chronic kidney disease (CKD) at stages 3∼5 with hyperuricemia. A total of 100 patients with stage 3 to 5 CKD with hyperuricemia in our hospital from July 2018 to December 2019 were selected and divided into the control group (n = 50) and the experimental group (n = 50) according to the random number expression method, the control group on the basis of conventional treatment with allopurinol treatment, the experimental group based on conventional treatment using the febuxostat be treatment. The clinical efficacy, incidence of adverse reactions, and renal function indexes, blood urea nitrogen (BUN), serum creatinine (Scr), serum sodium (Na), serum potassium (K), and serum uric acid (UA) before and after treatment were compared between the two groups. The total effective rate of the experimental group and the control group was 82.00% and 78.00%, respectively, with little difference (P > 0.05); compared with before treatment, BUN, Scr, and UA of the two groups were decreased (P < 0.05); and the degree of decline in the experimental group was significantly greater than that in the control group (P < 0.05); the incidence of adverse reactions in the control group was 22.00%, which was significantly higher than that in the experimental group (10.00%) (P < 0.05). Compared with allopurinol, febuxostat can improve renal function, reduce UA levels, and reduce the occurrence of complications, with high safety, which is worthy of further clinical promotion.


Rare mould infections caused by Mucorales, Lomentospora prolificans and Fusarium, in San Diego, CA: the role of antifungal combination therapy.
Non-Aspergillus invasive mould infections (IMIs) are associated with devastating morbidity and mortality rates and are increasingly diagnosed in immunocompromised hosts. The aim of this study was to describe the epidemiology and outcomes of non-Aspergillus IMIs at a university hospital in San Diego, California, USA. A retrospective chart review of the medical records of all patients with cultures growing non-Aspergillus moulds at the microbiology laboratory in the Center for Academic Laboratory Medicine, Department of Pathology, University of California, San Diego (UCSD) Health between mid-2014 and mid-2017 (3-year period) was performed. A total of 23 cases of non-Aspergillus IMI were identified, including 10 cases of mucormycosis, 8 cases of lomentosporiosis and 5 cases of fusariosis. Antifungal susceptibility testing was performed for 14 isolates, and 10/11 Fusarium and Lomentospora isolates had minimum inhibitory concentrations (MICs) of >16 µg/mL for voriconazole and/or posaconazole. Overall 180-day mortality was significantly lower among those who received combination antifungal therapy than among those who received single-agent therapy [3/13 (23%) vs. 9/10 (90%); P = 0.003]. In conclusion, Lomentospora prolificans (35% of non-Aspergillus IMIs) and Fusarium spp. (22%) accounted for high proportions of non-Aspergillus IMIs during the study period. Non-Aspergillus IMIs were detected in patients with various underlying diseases and were associated with high mortality rates, which was significantly lower in those who received antifungal combination therapy.


Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic.
Antibody and T-cell immunity to conserved influenza virus antigens can protect animals against infection with diverse influenza strains. Although immunity against conserved antigens occurs in humans, whether such responses provide cross-protection in humans and could be harnessed as the basis for universal influenza vaccines is controversial. The 2009 pandemic provided an opportunity to investigate whether pre-existing cross-reactive immunity affected susceptibility to infection. In 2009, we banked sera and peripheral blood mononuclear cells (PBMC) from blood donors, then monitored them for pandemic influenza infection (pH1N1) by polymerase chain reaction or seroconversion. Antibodies to hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), matrix 2 (M2), and HA-pseudotypes were measured in sera. T-cell inteferon-γ enzyme-linked immunospot responses were measured in PBMC. There were 13 infections in 117 evaluable donors. Pre-existing T-cell reactivity to pH1N1 was substantial (of 153 donors tested, 146 had >100 spot-forming cells/106 cells). Antibodies reactive with pH1N1 were common: anti-NP (all donors) and anti-M2 (44% of donors). Pseudotype-neutralizing antibodies to H1 were detected, but not to highly conserved HA epitopes. Unexpectedly, donors with symptomatic pH1N1 infection had sharp rises in HA pseudotype-neutralizing antibodies, not only pH1N1 but also against multiple seasonal H1s. In addition, an exploratory study of a T-cell marker (response to NP418-426) identified probable infection missed by standard criteria. Although the number of infections was inadequate for conclusions about mechanisms of protection, this study documents the wide variety of pre-existing, cross-reactive, humoral and cellular immune responses to pandemic influenza virus antigens in humans. These responses can be compared with results of other studies and explored in universal influenza vaccine studies.


Discovery and preclinical characterization of novel small molecule TRK and ROS1 tyrosine kinase inhibitors for the treatment of cancer and inflammation.
Receptor tyrosine kinases (RTKs), in response to their growth factor ligands, phosphorylate and activate downstream signals important for physiological development and pathological transformation. Increased expression, activating mutations and rearrangement fusions of RTKs lead to cancer, inflammation, pain, neurodegenerative diseases, and other disorders. Activation or over-expression of ALK, ROS1, TRK (A, B, and C), and RET are associated with oncogenic phenotypes of their respective tissues, making them attractive therapeutic targets. Cancer cDNA array studies demonstrated over-expression of TRK-A and ROS1 in a variety of cancers, compared to their respective normal tissue controls. We synthesized a library of small molecules that inhibit the above indicated RTKs with picomolar to nanomolar potency. The lead molecule GTx-186 inhibited RTK-dependent cancer cell and tumor growth. In vitro and in vivo growth of TRK-A-dependent IMR-32 neuroblastoma cells and ROS1-overexpressing NIH3T3 cells were inhibited by GTx-186. GTx-186 also inhibited inflammatory signals mediated by NFκB, AP-1, and TRK-A and potently reduced atopic dermatitis and air-pouch inflammation in mice and rats. Moreover, GTx-186 effectively inhibited ALK phosphorylation and ALK-dependent cancer cell growth. Collectively, the RTK inhibitor GTx-186 has a unique kinase profile with potential to treat cancer, inflammation, and neuropathic pain.


[Gemcitabine and ionizing radiations: radiosensitization or radio-chemotherapy combination].
Gemcitabine is a pyrimidine analog which has demonstrated antitumoral activity in a variety of solid tumors including bladder, non-small cell lung and pancreatic cancers. Gemcitabine is a potent radiosensitizer of human tumor cells. This review summarizes preclinical studies designed to elucidate the mechanism of action of gemcitabine with ionizing radiation. Phase I-II ongoing trials of combination of radiation therapy and gemcitabine are trying to determine the optimal dose and schedule which could be used in daily clinical activity. The mechanism of radiosensitization is thought to be simultaneously gemcitabine-induced dATP (deoxyadenosine triphosphate) depletion and cell cycle redistribution into the S phase. Although there are no real study which has proven supra-additive combination, the recent acute side effects in several clinical studies oblige physicists to determine with precision the maximum tolerated dose of gemcitabine in association with ionizing radiation. Radiosensitization conditions can be obtained either with a long exposition to a low concentration or a short exposition to a high concentration. Radiation sensitivity begin to be detected four hours after treatment for 48 hours. A dose about 100 mg/m2/week of gemcitabine could be used with radiation therapy according to recent phase I results. This limiting dose is approaching to a radiosensitization context where the effect of one agent is increased by another agent which is inactive or poorly active for the effect under consideration. In this type of regimen, the two modalities do interact with a frequent inhibition of recovery from potentially lethal damage and a probably increase of late side effects of radiation therapy. In contrast, radio-chemotherapy combination is used for a therapeutic advantage when the drug by itself is active against the tumor but does not enhance late side effects of radiation on the critical normal tissues within the irradiated volume. Gemcitabine surely is a strong radiosensitizer even at low doses with future extended combined modality therapeutic indications. The ultimate goal of combined treatments should be an increased therapeutic ratio.


Anteromedial subtalar dislocation.
Subtalar dislocation is the simultaneous dislocation of the distal articulations of the talus at both the talocalcaneal and talonavicular joints. It can occur in any direction and can always produce significant deformity. The medial dislocation is most common. Less common presentations are lateral, anterior, and posterior dislocations. These dislocations are associated with osteochondral fractures. Closed reduction and immobilization remain the mainstays of treatment. Proper radiographs and computed tomography scan confirm the postreduction alignment stability of subtalar joints and intraarticular fracture fragments. We report a case of anteromedial subtalar dislocation with no osteochondral fracture fragments in a 25-year-old man.


Molecular Understanding of the Activation of CB1 and Blockade of TRPV1 Receptors: Implications for Novel Treatment Strategies in Osteoarthritis.
Osteoarthritis (OA) is a joint disease in which cartilage degenerates as a result of mechanical and biochemical changes. The main OA symptom is chronic pain involving both peripheral and central mechanisms of nociceptive processing. Our previous studies have implicated the benefits of dual- over single-acting compounds interacting with the endocannabinoid system (ECS) in OA treatment. In the present study, we focused on the specific molecular alterations associated with pharmacological treatment. OA was induced in Wistar rats by intra-articular injection of 3 mg of monoiodoacetate (MIA). Single target compounds (URB597, an FAAH inhibitor, and SB366791, a TRPV1 antagonist) and a dual-acting compound OMDM198 (FAAH inhibitor/TRPV1 antagonist) were used in the present study. At day 21 post-MIA injection, rats were sacrificed 1 h after i.p. treatment, and changes in mRNA expression were evaluated in the lumbar spinal cord by RT-qPCR. Following MIA administration, we observed 2-4-fold increase in mRNA expression of targeted receptors (Cnr1, Cnr2, and Trpv1), endocannabinoid degradation enzymes (Faah, Ptgs2, and Alox12), and TRPV1 sensitizing kinases (Mapk3, Mapk14, Prkcg, and Prkaca). OMDM198 treatment reversed some of the MIA effects on the spinal cord towards intact levels (Alox12, Mapk14, and Prkcg). Apparent regulation of ECS and TRPV1 in response to pharmacological intervention is a strong justification for novel ECS-based multi-target drug treatment in OA.


The relationship between needle sugar carbon isotope ratios and tree rings of larch in Siberia.
Significant gaps still exist in our knowledge about post-photosynthetic leaf level and downstream metabolic processes and isotopic fractionations. This includes their impact on the isotopic climate signal stored in the carbon isotope composition (δ(13)C) of leaf assimilates and tree rings. For the first time, we compared the seasonal δ(13)C variability of leaf sucrose with intra-annual, high-resolution δ(13)C signature of tree rings from larch (Larix gmelinii Rupr.). The trees were growing at two sites in the continuous permafrost zone of Siberia with different growth conditions. Our results indicate very similar low-frequency intra-seasonal trends of the sucrose and tree ring δ(13)C records with little or no indication for the use of 'old' photosynthates formed during the previous year(s). The comparison of leaf sucrose δ(13)C values with that in other leaf sugars and in tree rings elucidates the cause for the reported (13)C-enrichment of sink organs compared with leaves. We observed that while the average δ(13)C of all needle sugars was 1.2‰ more negative than δ(13)C value of wood, the δ(13)C value of the transport sugar sucrose was on an average 1.0‰ more positive than that of wood. Our study shows a high potential of the combined use of compound-specific isotope analysis of sugars (leaf and phloem) with intra-annual tree ring δ(13)C measurements for deepening our understanding about the mechanisms controlling the isotope variability in tree rings under different environmental conditions.


Lupeol attenuated the NAFLD and PCOS-induced metabolic, oxidative, hormonal, histopathological, and molecular injuries in mice.
The current study aimed to study the therapeutic effects of lupeol as a nutritional triterpene on non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS) disorders in separate and concurrent models. This study was performed in three sets and each set contained 4 groups of female mice (n = 6), including control, NAFLD or PCOS and/or NAFLD/PCOS, lupeol, and metformin (MET). The treatment groups following the induction of disorders were treated with lupeol (40 mg/kg, orally) or MET (500 mg/kg, orally) for 28 days. The insulin resistance index and hormonal assessments were conducted on the collected serum samples. Moreover, oxidative stress biomarkers were measured in the liver and ovaries. Histopathological studies and ultimately any changes in the expression of androgen receptors, toll-like receptor (TLR)-2 and TLR-4 were analyzed. Results revealed that lupeol reduced significantly the insulin resistance index in NAFLD and NAFLD/PCOS-positive animals. Lupeol attenuated remarkably the PCOS and PCOS/NAFLD-elevated concentration of testosterone. lupeol recovered the metabolic disorders-induced oxidative stress and restored the disorders-depleted glutathione. The NAFLD/PCOS-induced hepatic damages such as microvesicular or macrovesicular steatosis and atretic follicles number in the ovary were attenuated in the lupeol-treated mice. Serum level of TNF-α was reduced and the expression of androgen receptors, TLR-4 and TLR-2 were downregulated in the lupeol-treated NAFLD/PCOS-positive animals. The results suggest that lupeol could be a novel nutraceutical for the treatment of metabolic disorders. Lupeol's anti-metabolic disorders effects attribute to its anti-dyslipidemia, antioxidant, and anti-inflammatory properties.


[ABCG1 transporter gene expression in peripheral blood mononuclear cells of patients with atherosclerosis].
Accumulation of cholesterol in arterial wall macrophages is a main hallmark of atherosclerosis. The ABCG1 transporter mediates cholesterol efflux to high density lipoproteins (HDL) and plays an important role in macrophage foam cell formation. The goal of our study was to investigate the potential role of ABCG1 in atherosclerosis development in humans. ABCG1 gene expression has been examined in leukocytes, monocytes and monocyte-derived macrophages of patients with atherosclerosis and in the control group. Real time PCR and Western blotting were used to determine ABCG1 mRNA and ABCG1 protein levels. Monocyte ABCG1 mRNA level was inversely correlated with the rate of artery occlusion (r = -0.45, P = 0.016). Patients with 100% artery occlusions had decreased monocyte ABCG1 mRNA levels compared to patients who had smaller plaques and controls (P < 0.05). ABCG1 mRNA (P < 0.001) and ABCG1 protein (P < 0.05) levels in macrophages of patients with coronary artery stenosis were significantly reduced compared to the control group. No significant correlation between the ABCG1 gene expression in mononuclear cells and HDL cholesterol concentration has been found. Our study suggests that decrease in the ABCG1 gene expression in macrophages is associated with atherosclerosis.


Pathogenomics of the staphylococci: insights into niche adaptation and the emergence of new virulent strains.
Because of its importance as a major human and animal pathogen, Staphylococcus aureus has been the focus of intensive research efforts. At the time of writing, the genomes of 14 isolates of S. aureus have been published and released into the public domain with many more genome sequencing projects underway, representing an excellent resource for studies of bacterial evolution and pathogenesis. Recently, whole genome sequences of several other species of the Staphylococcus genus have been completed allowing a comparative genomic analysis of the adaptation of different species to their natural habitats. Here, we summarize selected comparative genomic studies that have contributed to our understanding of how staphylococci adapt to different environments, combat antibiotics and acquire increased virulence.


Junctional sequences influence the specificity of gamma/delta T cell receptors.
T lymphocytes bearing the gamma/delta T cell receptor (TCR-gamma/delta) express a limited number of germline variable gene segments, generating receptor sequence diversity primarily through junctional mechanisms. To examine the role of V(D)J junctional sequences in antigen recognition by TCR-gamma/delta, we derived an alloreactive murine TCR-gamma/delta+ T cell line, LKD1, specific for the I-Ad class II major histocompatibility complex (MHC) molecule, and compared its receptor with that expressed by a previously characterized class II MHC alloreactive T cell line, LBK5, specific for I-Ek,b,s Ia molecules. Both LKD1 and LBK5 express receptors encoded by rearranged V gamma 1.2J gamma 2 and V delta 5D delta 2J delta 1 gene elements, differing in sequence only in the V(D)J junctional regions of the gamma and delta genes. These results demonstrate that junctionally encoded sequences corresponding to the putative third complementarity determining region can influence the antigen specificity of TCR-gamma/delta.


Free Energy of Binding and Mechanism of Interaction for the MEEVD-TPR2A Peptide-Protein Complex.
The association between the MEEVD C-terminal peptide from the heat shock protein 90 (Hsp90) and tetratricopeptide repeat A (TPR2A) domain of the heat shock organizing protein (Hop) is a useful prototype to study the fundamental molecular details about the Hop-Hsp90 interaction. We study here the mechanism of binding/unbinding and compute the standard binding free energy and potential of mean force for the association of the MEEVD peptide to the TPR2A domain using the Adaptive Biasing Force (ABF) methodology. We observe conformational changes of the peptide and the protein receptor induced by binding. We measure the binding free energy of -8.4 kcal/mol, which is consistent with experimental estimates. The simulations achieve multiple unbinding and rebinding events along a consistent pathway connecting the binding site to solvent. The MEEVD peptide slowly dissociates disrupting the hydrogen bonds first, then tilting on the side while preserving the interaction with the side chain of residue Asp 5 of the peptide. After this initial displacement, the peptide completely dissociates and moves into the solvent. Rebinding of the MEEVD peptide from the solvent to the receptor binding site occurs slowly through the portal of entry. Unbinding and rebinding go through intermediate states characterized by the peptide interacting with a lateral helix, helix A1, of the receptor with mainly Asp 5, Val 4, and Glu 3 of the peptide. This newly discovered intermediate structure is characterized by numerous contacts with the receptor which lead to complete formation of the bound complex. The structure of the bound complex obtained after rebinding is structurally very similar to the crystal structure of the complex (0.48 Å root-mean square deviation). The residues Asp 5, Val 4, and Glu 3 adopt conformations and intermolecular contacts with excellent structural similarity with the native ones. Finally, the dissociation and reassociation of MEEVD induce hydration/dehydration transitions, which provide insights on the role of desolvation and solvation processes in protein-peptide binding.


Comparative Phytochemical Analyses of Flowers from Primula veris subsp. veris Growing Wild and from Ex Situ Cultivation in Greece.
In the last decades, Primula veris subsp. veris (roots and flowers) has been over harvested through legal and illegal ways in Greece, due to its extremely high commercial demand, as it is used in industry because of its well-known therapeutic properties. As ex situ cultures of the plant have been already developed, in the current comparative study, the herbal teas (infusions) from both flowers of cowslip growing wild in the Prespa Lake Park (NW Greece), and from ex situ propagated and cultivated plant material, have been investigated, with the ultimate goal of assessing them qualitatively. Furthermore, through classic phytochemical studies, the ten most abundant metabolites, belonging to the chemical categories of flavonol-glycosides and methoxy flavones, have been identified and structurally determined. The chemical profile of both infusions has been further analyzed through UHPLC-HRMS, showing that they show only light differences. The total phenolic content (TPC) of both studied samples (wild and ex situ cultivation), was determined by the Folin-Ciocalteau method, followed by an antioxidant activity assay though DPPH where, in both cases, wild plants exerted higher phenolic load and stronger antioxidative properties. According to the reported results, it could be proposed that the ex situ cultivated plant material could facilitate the mass production of plants and the sustainable cultivation of cowslip in the Greek mountains.


Notes from the Front: The Casebook of a Renaissance Hospital Surgeon.
This essay uses the unpublished casebook kept by the Tuscan surgeon Giovanbattista Nardi to examine the provision of urgent medical care in sixteenth-century Italian hospitals. Most major hospitals on the peninsula maintained separate therapeutic spaces known as medicherie for this purpose. Written in the 1580s while Nardi worked as a staff surgeon at a Florentine civic hospital, this rare surgical casebook provides insight into the types of institutional resources devoted to acute medical problems; the clientele seeking immediate assistance and the situations that brought them there; the treatments used to achieve short-term "cures"; and the clinical experiences of hospital surgeons who served as frontline healers. A close analysis of the seventy-nine cases recorded sheds new light on everyday surgical treatments for conditions ranging from serious head injuries requiring trephination to syphilitic lesions and genital trauma. Casebook entries also reveal Nardi's deep engagement with the composition and use of topical remedies as both practitioner and experimenter. Intended as a memory aid for future reference, the casebook shows material traces of the author's shifting occupational identity as he matured from hospital surgeon to university-trained physician. Viewed through multiple lenses, this richly layered source expands our understanding of both the practice and profession of early modern surgery.


Niacin, an old drug with new perspectives for the management of dyslipidaemia.
Niacin has been used for decades to treat dyslipidaemic disorders. Niacin is the most effective agent currently available for increasing levels of high-density lipoprotein. Moreover, significant improvements in cardiovascular outcomes in niacin treated patients have been demonstrated. However, tolerability concerns, particularly flushing, have limited its use in the past. Therefore, ER niacin, a prolonged-release formulation of niacin, has been developed with similar efficacy but a superior tolerability profile compared to the immediate-release formulations. Recent insights on niacin mechanisms of action have led to the development of a new agent called laropiprant. Laropiprant selectively blocks the binding of prostaglandin D2 to its receptor (DP1) in dermal capillaries, which mediates niacin-induced vasodilation. When co-administered with ER niacin, a marked reduction in ER niacin induced flushing is seen.The clinical use of niacin and the novel flush-reducing co-medication, will be discussed.


Regularity extraction from non-adjacent sounds.
The regular behavior of sound sources helps us to make sense of the auditory environment. Regular patterns may, for instance, convey information on the identity of a sound source (such as the acoustic signature of a train moving on the rails). Yet typically, this signature overlaps in time with signals emitted from other sound sources. It is generally assumed that auditory regularity extraction cannot operate upon this mixture of signals because it only finds regularities between adjacent sounds. In this view, the auditory environment would be grouped into separate entities by means of readily available acoustic cues such as separation in frequency and location. Regularity extraction processes would then operate upon the resulting groups. Our new experimental evidence challenges this view. We presented two interleaved sound sequences which overlapped in frequency range and shared all acoustic parameters. The sequences only differed in their underlying regular patterns. We inserted deviants into one of the sequences to probe whether the regularity was extracted. In the first experiment, we found that these deviants elicited the mismatch negativity (MMN) component. Thus the auditory system was able to find the regularity between the non-adjacent sounds. Regularity extraction was not influenced by sequence cohesiveness as manipulated by the relative duration of tones and silent inter-tone-intervals. In the second experiment, we showed that a regularity connecting non-adjacent sounds was discovered only when the intervening sequence also contained a regular pattern, but not when the intervening sounds were randomly varying. This suggests that separate regular patterns are available to the auditory system as a cue for identifying signals coming from distinct sound sources. Thus auditory regularity extraction is not necessarily confined to a processing stage after initial sound grouping, but may precede grouping when other acoustic cues are unavailable.


Erythrocyte encapsulated l-asparaginase (GRASPA) in acute leukemia.
l-asparaginase, an enzyme originally derived from Escherichia coli, represents a major drug in the treatment of acute lymphoblastic leukemia. However, the occurrence of major adverse effects often leads to early withdrawal of the enzyme. Main side effects include immune-allergic reactions, coagulopathy, pancreatitis and hepatic disorders. Novel asparaginase formulations and alternative sources have been developed to address this issue, but the results were not totally satisfactory. l-asparaginase loaded red blood cells (RBCs; GRASPA) represent a new asparaginase presentation with reduced immunological adverse reactions. RBCs protect l-asparaginase, enhance its half-life and reduce the occurrence of adverse events. We reviewed the history, biology and clinical experiences with l-asparaginase, and the characteristics and first clinical experiences with GRASPA in the treatment of acute leukemia.


Use of Advance Directives in US Veterans and Non-Veterans: Findings from the Decedents of the Health and Retirement Study 1992-2014.
Evidence shows that older patients with advance directives such as a living will, or durable power of attorney for healthcare, are more likely to receive care consistent with their preferences at the end of life. Less is known about the use of advance directives between veteran and non-veteran older Americans. Using data from the decedents of a longitudinal survey, we explore whether there is a difference in having an established advance directive between the veteran and non-veteran decedents. Data were taken from the Harmonized End of Life data sets, a linked collection of variables derived from the Health and Retirement Study (HRS) Exit Interview. Only male decedents were included in the current analysis (N = 4828). The dependent variable, having an established advance directive, was measured by asking the proxy, "whether the deceased respondent ever provided written instructions about the treatment or care he/she wanted to receive during the final days of his/her life" and "whether the deceased respondent had a Durable Power of Attorney for healthcare?" A "yes" to either of the two items was counted as having an advance directive. The independent variable, veteran status, was determined by asking participants, "Have you ever served in the active military of the United States?" at their first HRS core interview. Logistic regression was used to predict the likelihood of having an established advance directive. While there was no difference in having an advance directive between male veteran and non-veteran decedents during the earlier follow-up period (from 1992 to 2003), male veterans who died during the second half of the study period (from 2004 to 2014) were more likely to have an established advance directive than their non-veteran counterparts (OR = 1.24, p < 0.05). Other factors positively associated with having an established advance directive include dying at older ages, higher educational attainment, needing assistance in activities of daily living and being bedridden three months before death, while Black decedents and those who were married were less likely to have an advance directive in place. Our findings suggest male veterans were more likely to have an established advance directive, an indicator for better end-of-life care, than their non-veteran counterparts. This observed difference coincides with a time when the Veterans Health Administration (VHA) increased its investment in end-of-life care. More studies are needed to confirm if this higher utilization of advance directives and care planning among veterans can be attributed to the improved access and quality of end-of-life care in the VHA system.


Distribution and morphology of putative catecholaminergic and serotonergic neurons in the brain of the greater canerat, Thryonomys swinderianus.
The distribution, morphology and nuclear subdivisions of the putative catecholaminergic and serotonergic systems within the brain of the greater canerat (sometimes spelt cane rat) were identified following immunohistochemistry for tyrosine hydroxylase and serotonin. The aim of the present study was to investigate possible differences in the complement of nuclear subdivisions of these systems when comparing those of the greater canerat with reports of these systems in other rodents. The greater canerat was chosen for investigation as it is a large rodent (around 2.7kg body mass) and has an average brain mass of 13.75g, more than five times larger than that of the laboratory rat. The greater canerats used in the present study were caught from the wild, which is again another contrast to the laboratory rat. While these differences, especially that of size, may lead to the prediction of significant differences in the nuclear complement of these systems, we found that all nuclei identified in both systems in the laboratory rat and other rodents in several earlier studies had direct homologs in the brain of the greater canerat. Moreover, there were no additional nuclei in the brain of the greater canerat that are not found in the laboratory rat or other rodents. It is noted that the locus coeruleus of the laboratory rat differs in appearance to that reported for several other rodent species. The greater canerat is phylogenetically distant from the laboratory rat, but still a member of the order Rodentia. Thus, changes in the nuclear organization of these systems appears to demonstrate a form of constraint related to the phylogenetic level of the order.


[A comparative evaluation of the effects of local anesthetics combined with morphine and administered epidurally].
The authors compare the efficacies of trimecaine (8 mg/kg), lidocaine (8 mg/kg), azacaine (2 and 3 mg/kg) alone and in combination with morphine (1.2 mg/kg), administered epidurally. Analgesia efficacy and duration were assessed by the electrostimulation method in experimental rabbits. First the pain threshold was defined, then the tested drugs were injected epidurally; the degree of the pain threshold rise permitted a judgment on the analgetic effect of the drugs. Combined injection of morphine and any of the tested anesthetics to the epidural space considerably prolonged the analgesia. The duration of the analgetic effect was the longest (over 24 h) with azacaine-based mixtures. Preliminary injection of morphine (1 h before azacaine) was conducive to a more rapid development of the epidural block and a more smooth course of analgesia. Experiments with mice have shown that addition of morphine to azacaine in the before volumes did not change azacaine toxicity.


The Rep78 gene product of adeno-associated virus (AAV) self-associates to form a hexameric complex in the presence of AAV ori sequences.
The Rep78 and Rep68 proteins of adeno-associated virus (AAV) are replication initiator proteins that bind the viral replicative-form origin of replication, nick the origin in a site- and strand-specific fashion, and mediate vectorial unwinding of the DNA duplex via an ATP-dependent helicase activity, thus initiating a strand displacement mechanism of viral DNA replication. Genetic and biochemical studies have identified Rep mutants that demonstrate a trans-dominant negative phenotype in vitro and in vivo, suggesting the possibility that multimerization of Rep is essential for certain replicative functions. In this study, we have investigated the ability of the largest of the Rep proteins, Rep78, to self-associate in vitro and in vivo. Self-association of Rep78 in vivo was demonstrated through the use of a mammalian two-hybrid system. Rep-Rep protein interaction was confirmed in vitro through coimmunoprecipitation experiments with a bacterially expressed maltose-binding protein-Rep78 fusion protein in combination with [35S]methionine-labeled Rep78 synthesized in a coupled in vitro transcription-translation system. Mapping studies with N- and C-terminal truncation mutant forms of Rep indicate that amino acid sequences required for maximal self-association occur between residues 164 and 484. Site-directed mutagenesis identified two essential motifs within this 321-amino-acid region: (i) a putative alpha-helix bearing a 3,4-hydrophobic heptad repeat reminiscent of those found in coiled-coil domains and (ii) a previously recognized nucleoside triphosphate-binding motif. Deletion of either of these regions from the full-length polypeptide resulted in severe impairment of Rep-Rep interaction. In addition, gel filtration chromatography and protein cross-linking experiments indicated that Rep78 forms a hexameric complex in the presence of AAV ori sequences.


In vivo investigation of antihyperalgesic and antinociceptive effects of peat formulations.
The aim of this study is to evaluate the antihyperalgesic and antinociceptive effects of two formulations containing peat water extracts using a model of carrageenan-induced hyperalgesia, combined with a test with a mechanical stimulus, and a hot plate test. Rats were divided into seven groups (n = 6) and received local treatment with two peat formulations and two diclofenac formulations dissolved in carbopol gel and Wolff® basis creme, respectively. Carbopol gel, Wolff® basis creme and 0.9 % NaCl without tested substances were used as controls. Both peat formulations exerted an unambiguous antihyperalgesic effect 60 minutes after the treatment. In the hot plate test, the rats treated with the Wolff® basis creme peat formulation showed a tendency to prolonged latency on the first hour. The results could be explained by partial activation of peripheral α2-adrenoceptors and the possible COX-2 suppressive activity.


Deubiquitinating function of adenovirus proteinase.
The invasion strategy of many viruses involves the synthesis of viral gene products that mimic the functions of the cellular proteins and thus interfere with the key cellular processes. Here we show that adenovirus infection is accompanied by an increased ubiquitin-cleaving (deubiquitinating) activity in the host cells. Affinity chromatography on ubiquitin aldehyde (Ubal), which was designed to identify the deubiquitinating proteases, revealed the presence of adenovirus L3 23K proteinase (Avp) in the eluate from adenovirus-infected cells. This proteinase is known to be necessary for the processing of viral precursor proteins during virion maturation. We show here that in vivo Avp deubiquitinates a number of cellular proteins. Analysis of the substrate specificity of Avp in vitro demonstrated that the protein deubiquitination by this enzyme could be as efficient as proteolytic processing of viral proteins. The structural model of the Ubal-Avp interaction revealed some similarity between S1-S4 substrate binding sites of Avp and ubiquitin hydrolases. These results may reflect the acquisition of an advantageous property by adenovirus and may indicate the importance of ubiquitin pathways in viral infection.


[Penicillin induced epileptiform activity in hippocampal slice--comparison between CA 3 pyramidal cell and granule cell].
To investigate whether a different type of neurons has a different susceptibility to a drug in producing epileptiform activity, we compared penicillin induced epileptiform activities of the two types of neurons in the hippocampal formation of guinea pigs, i.e. the CA 3 pyramidal cells in the hippocampus proper and the granule cells in the dentate gyrus, using slice preparations. The thin slice of 0.4 mm thickness was cut nearly perpendicularly to the longitudinal axis of the hippocampus and was transferred to a nylon mesh in an observation chamber which was perfused with the oxygenated and warmed medium at a rate of 2 ml/min. Under tenfold magnification stimuli were delivered to the nerve fiber layer through bipolar electrodes and evoked field potentials were recorded from the cell body layer with glass micropipettes of 10 mu tip diameter filled with normal medium. In both cell body layers no epileptiform field potentials could be induced during perfusion of normal medium even if stimulus strength was increased. The CA 3 pyramidal cell body layer showed a delayed multipeaked field potential in response to threshold stimulus applied to the mossy fiber in penicillin-containing medium (Pc concentration = 500, 1000, 2000 I. U./ml). When the strength of stimulation increased, the latency shortened, but the amplitude and the duration of epileptiform activity did not change. The granule cell body layer generated no epileptiform activity in response to weak electrical stimulus applied to the perforant path in penicillin-containing medium (Pc concentration = 500, 1000, 2000 I. U./ml). However, at high penicillin concentrations (1000, 2000 I. U./ml) multiple population spikes having a short latency appeared on intense stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)


Platelet P2Y12 Inhibitor in the Treatment and Prevention of Migraine: A Systematic Review and Meta-Analysis.
There have been speculation and research linking migraine with abnormalities of platelet aggregation and activation. The role of the P2Y12 platelet inhibitor in the treatment of migraine has not been established. We aim to evaluate the efficacy of the platelet P2Y12 inhibitor in the treatment of migraine and prevention of new-onset migraine headache (MHA) following transcatheter atrial septal defect closure (ASDC). We searched the PubMed, Web of Science, and Cochrane Library databases for relevant studies. The primary outcomes were the headache responder rate and the rate of new-onset migraine attacks following ASDC. Four studies for a total of 262 migraine patients with or without patent foramen ovale (PFO) and three studies involving 539 patients with antiplatelet treatment in the prevention of new-onset migraine following ASDC were included. The pooled responder rate of the P2Y12 inhibitor for migraine was 0.64 (95% CI: 0.43 to 0.81). For patients who underwent ASDC, the use of antiplatelet regimens including the P2Y12 inhibitor, compared with regimens excluding P2Y12 inhibitor, resulted in a lower rate of new-onset migraine (OR: 0.41, 95% CI: 0.22 to 0.77, P = 0.005). We concluded that the P2Y12 platelet inhibitor may have a primary prophylactic role in migraine patients with or without PFO and prevent new-onset MHA after ASDC. The responsiveness of the P2Y12 inhibitor could help select candidates who would benefit from PFO closure. It warrants further large-scale research to explore the role of the P2Y12 inhibitor, particularly in a proportion of migraine patients.


The Role of Aquaporins in Spinal Cord Injury.
Edema formation following traumatic spinal cord injury (SCI) exacerbates secondary injury, and the severity of edema correlates with worse neurological outcome in human patients. To date, there are no effective treatments to directly resolve edema within the spinal cord. The aquaporin-4 (AQP4) water channel is found on plasma membranes of astrocytic endfeet in direct contact with blood vessels, the glia limitans in contact with the cerebrospinal fluid, and ependyma around the central canal. Local expression at these tissue-fluid interfaces allows AQP4 channels to play an important role in the bidirectional regulation of water homeostasis under normal conditions and following trauma. In this review, we consider the available evidence regarding the potential role of AQP4 in edema after SCI. Although more work remains to be carried out, the overall evidence indicates a critical role for AQP4 channels in edema formation and resolution following SCI and the therapeutic potential of AQP4 modulation in edema resolution and functional recovery. Further work to elucidate the expression and subcellular localization of AQP4 during specific phases after SCI will inform the therapeutic modulation of AQP4 for the optimization of histological and neurological outcomes.


Variant type and position predict two distinct limb phenotypes in patients with GLI3-mediated polydactyly syndromes.
Pathogenic DNA variants in the GLI-Kruppel family member 3 (GLI3) gene are known to cause multiple syndromes: for example, Greig syndrome, preaxial polydactyly-type 4 (PPD4) and Pallister-Hall syndrome. Out of these, Pallister-Hall is a different entity, but the distinction between Greig syndrome and PPD4 is less evident. Using latent class analysis (LCA), our study aimed to investigate the correlation between reported limb anomalies and the reported GLI3 variants in these GLI3-mediated polydactyly syndromes. We identified two subclasses of limb anomalies that relate to the underlying variant. Both local and published cases were included for analysis. The presence of individual limb phenotypes was dichotomised and an exploratory LCA was performed. Distribution of phenotypes and genotypes over the classes were explored and subsequently the key predictors of latent class membership were correlated to the different clustered genotypes. 297 cases were identified with 127 different variants in the GLI3 gene. A two-class model was fitted revealing two subgroups of patients with anterior versus posterior anomalies. Posterior anomalies were observed in cases with truncating variants in the activator domain (postaxial polydactyly; hand, OR: 12.7; foot, OR: 33.9). Multivariate analysis supports these results (Beta: 1.467, p=0.013 and Beta: 2.548, p<0.001, respectively). Corpus callosum agenesis was significantly correlated to these variants (OR: 8.8, p<0.001). There are two distinct phenotypes within the GLI3-mediated polydactyly population: anteriorly and posteriorly orientated. Variants that likely produce haploinsufficiency are associated with anterior phenotypes. Posterior phenotypes are associated with truncating variants in the activator domain. Patients with these truncating variants have a greater risk for corpus callosum anomalies.


SPECT imaging, immunohistochemical and behavioural correlations in the primate models of Parkinson's disease.
Dopamine active transporter (DAT) single photon emission computerised tomography (SPECT) is considered a useful and practical technique for early diagnosis of Parkinson's disease (PD) and assessment of its progression. The application of this technique, particularly as a surrogate marker for therapeutic and neuroprotective trials in Parkinsonism, however, is dependent on pathological validation. In the absence of human studies, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate models of Parkinsonism to verify correlation between the SPECT, immunohistochemical and behavioural data. The DAT SPECT data correlated strongly and significantly with the substantia nigra pars compacta tyrosine hydroxylase and Nissl cell counts as well as the behavioural scores. Within the limitations of small numbers inherent to such studies, this data provides the first attempt at pathological validation of SPECT in primates.


Strategy of Stem Cell Transplantation for Bone Regeneration with Functionalized Biomaterials and Vascularized Tissues in Immunocompetent Mice.
The use of human bone marrow mesenchymal stem cells (hBMSCs) to regenerate and repair bone tissue defects is a complex research field of bone tissue engineering; nevertheless, it is a hot topic. One of the biggest problems is the limited survival and osteogenic capacity of the transplanted cells within the host tissue. Even for hBMSCs with their low immunogenicity, the body will still cause a local immune-inflammatory response directed against the allogeneic cells and thereby reduce the activity of the transplanted cells. Even in the case of successful transplantation, the lack of vascularization at the transplantation site makes it difficult for the transplanted cells to exchange nutrients and metabolic wastes that ultimately affects bone regeneration. In this study, we covalently modified alginate with RGD and QK peptides that were injected subcutaneously into immunocompetent mice. Histological analysis, as well as ELISA techniques, proved that this method is able to provide bioactive stem cell transplant beds containing functionalized biomaterials and vascularized surrounding tissues. Inflammation-related factors, such as IL-2, IL-6, TNF-α, and IFN-γ, around the cell graft beds decreased with time and were lowest at the second week. Then, the hBMSCs were injected into the cell transplantation beds intended to form vascularized bonelike tissues that were evaluated by micro-computed tomography (Micro CT), histological, and immunohistochemical analyses. The results showed that the expression of osteogenesis-related proteins RUNX2, COL1A1, and OPN, as well as the expression of angiogenic factor vWF and cartilage-related protein COL2A1 were significantly upregulated in the hBMSC-derived osteogenic tissue. These results suggest that the stem cell transplantation strategy by constructing bioactive cell transplant beds is effective to enhance the bone regeneration capacity of hBMSCs and holds great potential in bone tissue engineering.