Postnatal development of acinar cells in rat submandibular gland as revealed by electron microscopic staining for carbohydrates.
The postnatal differentiation of acinar cells in rat submandibular gland was studied by staining with periodic acid-thiosemicarbazide-silver proteinate to identify carbohydrate-containing macromolecules in the electron microscope. This method revealed glycogen particles and internal substructure in the secretory granules of developing acinar cells. On the basis of morphologic and histochemical criteria three phases of acinar cell development were defined. In the pro-acinar phase, during the first week after birth, pro-acinar cells and terminal tubular cells were the main components of the terminal tubules in the rudimentary gland. The secretory granules of the pro-acinar cells contained speckled or rod-like substructures which stained intensively for carbohydrates and were digested by proteolytic enzymes. During the second to third week after birth, which is the immature-acinar-cell phase, thread-like substructures were seen in the secretory granules. These structures, which were not digested by proteolytic enzymes, disappeared gradually. The acinar cells of 4-week-old or older rats displayed no particular substructure in the secretion granules and represented the final, mature phase of development.


Peptide inhibition of neutrophil-mediated injury after in vivo challenge with supernatant of Pseudomonas aeruginosa and immune-complexes.
Neutrophils are recognized for their role in host defense against pathogens as well as inflammatory conditions mediated through many mechanisms including neutrophil extracellular trap (NET) formation and generation of reactive oxygen species (ROS). NETs are increasingly appreciated as a major contributor in autoimmune and inflammatory diseases such as cystic fibrosis. Myeloperoxidase (MPO), a key neutrophil granule enzyme mediates generation of hypochlorous acid which, when extracellular, can cause host tissue damage. To better understand the role played by neutrophils in inflammatory diseases, we measured and modulated myeloperoxidase activity and NETs in vivo, utilizing a rat peritonitis model. RLS-0071 is a 15 amino acid peptide that has been shown to inhibit myeloperoxidase activity and NET formation in vitro. The rat model of inflammatory peritonitis was induced with intraperitoneal injection of either P. aeruginosa supernatant or immune-complexes. After euthanasia, a peritoneal wash was performed and measured for myeloperoxidase activity and free DNA as a surrogate for measurement of NETs. P. aeruginosa supernatant caused a 2-fold increase in MPO activity and free DNA when injected IP. Immune-complexes injected IP increased myeloperoxidase activity and free DNA 2- fold. RLS-0071 injection decreased myeloperoxidase activity and NETs in the peritoneal fluid generally to baseline levels in the presence of P. aeruginosa supernatant or immune-complexes. Taken together, RLS-0071 demonstrated the ability to inhibit myeloperoxidase activity and NET formation in vivo when initiated by different inflammatory stimuli including shed or secreted bacterial constituents as well as immune-complexes.


Escitalopram maintenance treatment for prevention of recurrent depression: a randomized, placebo-controlled trial.
Major depressive disorder is a recurrent illness that often requires maintenance antidepressant treatment. Escitalopram is a selective serotonin reuptake inhibitor (SSRI) that has shown efficacy in both acute and continuation treatment of major depressive disorder. The current trial examined the efficacy of maintenance escitalopram treatment in preventing depression recurrence in patients who responded to acute SSRI therapy. Patients with recurrent DSM-IV-defined major depressive disorder (>or= 2 previous episodes; baseline Montgomery-Asberg Depression Rating Scale [MADRS] score >or= 22) who had responded (MADRS score <or= 12) to acute open-label treatment (8 weeks) with 1 of 4 SSRIs (fluoxetine, sertraline, paroxetine, or citalopram) received open-label, flexible-dose continuation treatment (16 weeks) with escitalopram (10-20 mg/day). At the end of continuation treatment, patients maintaining response criteria were randomly assigned to 52 weeks of double-blind, fixed-dose maintenance treatment with escitalopram (10 or 20 mg/day) or placebo. Recurrence was defined as a MADRS score >or= 22 or insufficient therapeutic response during the double-blind phase. The study was conducted between October 16, 2000, and February 4, 2003. A total of 234 patients who responded to acute open-label treatment with 1 of 4 SSRIs received at least 1 dose of open-label escitalopram continuation treatment. Of 164 patients who completed escitalopram continuation treatment, 139 were randomly assigned to double-blind maintenance treatment with escitalopram (N = 73) or placebo (N = 66). Mean baseline MADRS scores at the start of the maintenance phase were < 5 for both the placebo- and escitalopram-treatment groups. Time to recurrence was significantly longer in patients who received maintenance treatment with escitalopram compared with patients switched to placebo (hazard ratio = 0.26, 95% CI = 0.13 to 0.52, p < .001). Long-term escitalopram treatment was well tolerated. Maintenance treatment with escitalopram was well tolerated and significantly reduced the risk for recurrence of depression. Patients with few residual symptoms following continuation treatment with escitalopram experienced a high rate of depression recurrence when switched to placebo, demonstrating the need for maintenance therapy of recurrent major depressive disorder beyond 4 to 6 months of initial symptom resolution even if few residual symptoms are present.


5-(5,6-Dichloro-2-indolyl)-2-methoxy-2,4-pentadienamides: novel and selective inhibitors of the vacuolar H+-ATPase of osteoclasts with bone antiresorptive activity.
The vacuolar H+-ATPase (V-ATPase), located on the ruffled border of the osteoclast, is a proton pump which is responsible for secreting the massive amounts of protons that are required for the bone resorption process. With the aim to identify new agents which are able to prevent the excessive bone resorption associated with osteoporosis, we have designed a novel class of potent and selective inhibitors of the osteoclast proton pump, starting from the structure of the specific V-ATPase inhibitor bafilomycin A1. Compounds 3a-d potently inhibited the V-ATPase in chicken osteoclast membranes (IC50 = 60-180 nM) and were able to prevent bone resorption by human osteoclasts in vitro at low-nanomolar concentrations. Notably, the EC50 of compound 3c in this assay was 45-fold lower than the concentration required for half-maximal inhibition of the V-ATPase from human kidney cortex. These results support the validity of the osteoclast proton pump as a useful molecular target to produce novel inhibitors of bone resorption, potentially useful as antiosteporotic agents.


Female patients display poorer burn-specific quality of life 12 months after a burn injury.
Although gender differences in morbidity and mortality have been measured in patients with moderate to severe burn injury, little attention has been directed at gender effects on health-related quality of life (HRQoL) following burn injury. The current study was therefore conducted to prospectively measure changes in HRQoL for males and females in a sample of burn patients. A total of 114 adults who received treatment at a statewide burns service for a sustained burns injury participated in this study. Instruments measuring generic health status (Short Form 36 Medical Outcomes Survey version 2), burn-specific HRQoL (Burns Specific Health Scale-Brief), psychological distress (Kessler Psychological Distress Scale) and alcohol use (Alcohol Use Disorders Identification Tool) were prospectively measured at 3, 6 and 12 months post-burn. In the 12 months post-injury, female patients showed overall poorer physical (p=0.01) and mental health status (p<0.001), greater psychological distress (p<0.001), and greater difficulty with aspects of burn-specific HRQoL: body image (p<0.001), affect (p<0.001), interpersonal functioning (p=0.005), heat sensitivity (p=0.01) and treatment regime (p=0.01). While significant interaction effects suggested that female patients had more improvement in difficulties with treatment regime (p=0.007), female patients continued to report greater difficulty with multiple aspects of physical and psychosocial health status 12 months post-injury. Even though demographic variables, injury characteristics and burn care interventions were similar across genders, following burn injury female patients reported greater impairments in generic and burn-specific HRQoL along with psychological morbidity, when compared to male patients. Urgent clinical and research attention utilising an evidence-based research framework, which incorporates the use of larger sample sizes, the use of validated instruments to measure appropriate outcomes, and a commitment to monitoring long-term care, can only improve burn-care.


Stratigraphic and geochemical study of clastic sediments of the Grotte di Stiffe karstic system.
The present work reports the results of a geochemical and stratigraphic study carried out on clastic sediments from the karstic system of the Grotte di Stiffe in Abruzzo. In order to describe in more significant manner the system from which the sediments have been taken, the rocks from which they derive and ground samples from the plateau immediately above the caves have also been examined. Stratigraphic and chemical studies, with particular regard to the presence of heavy metals, have been performed on some 50 cm of drawn sediment, utilising atomic absorption spectrophotometry. The data obtained in this way have been subjected to Principal Components Analysis in order to investigate possible correlations.


Morphology and properties of sulfonated poly(styrene-b-(ethylene-co-butylene)-b-styrene)/ poly(4-styrene sulfonic acid) blends filled with multiwalled carbon nanotubes.
Nanocomposites based on poly(styrene-b-(ethylene-co-butylene)-b-styrene) (SEBS) and multiwalled carbon nanotubes (MWNTs) were prepared. In order to facilitate the dispersion of MWNTs in the nanocomposites, the pristine MWNTs were reduced by Li to anions and SEBS was sulfonated. Poly(4-styrenesulfonic acid) (PSSA) was also added to either SEBS or S-SEBS and the morphology and properties of the nanocomposites were examined. Nanocomposites prepared from S-SEBS, PSSA, and the modified MWNTs showed a threshold decrease in electrical resistivity due to the percolation of MWNTs at a critical MWNT content (P(c)) lower than those for the nanocomposites based on SEBS, PSSA, and the MWNTs. It was found that the P(c) decreased with increasing the concentration of PSSA in the nanocomposites containing S-SEBS. The efficient percolation of MWNTs in the S-SEBS/PSSA nanocomposites was attributed to interactions between the ionic moieties of MWNTs and S-SEBS and the fine dispersion of the MWNTs. Nanocomposites based on S-SEBS showed large increase of rubbery plateau modulus compared with those based on SEBS. PSSA played the role of plasticizer of sulfonated PS blocks above T(g) of PS blocks in S-SEBS.


Roles of p38-MAPK in insulin resistant heart: evidence from bench to future bedside application.
Insulin resistance is associated with the impairment of the response of insulin receptor to insulin, resulting in the reduction of glucose uptake, leading to the alteration of myocardial glucose metabolism, impairment of cardiac electrophysiology, and increased susceptibility to ischemia-induced myocardial injury. Insulin resistance is associated with the impairment of the intracellular insulin signal transduction pathway. Among the MAPK family, p38-MAPK is a serine/threonine protein kinase, which has been shown to play an important role in cellular responses to various kinds of stress, including insulin resistance. Since growing evidence indicates the involvement of p38-MAPK in cardiovascular dysfunction, it is possible that the activation of p38-MAPK is responsible in part as a causative mechanism for cardiovascular complications in the insulin resistant heart. In addition, several anti-diabetic drugs have been shown to affect the myocardial p38-MAPK pathway. The effect of these drugs on p38-MAPK could be associated with their cardiovascular results in patients with insulin resistance. In this article, the signal transduction pathways of myocardial p38-MAPK activation in the insulin resistant heart, as well as the effects of anti-diabetic drugs on the myocardial p38-MAPK pathway, are comprehensively reviewed. Furthermore, the possible therapeutic approach regarding the utilization of a p38-MAPK inhibitor in diabetes patients to prevent cardiovascular complications is also addressed.


Isozyme-Specific Role of SAD-A in Neuronal Migration During Development of Cerebral Cortex.
SAD kinases regulate presynaptic vesicle clustering and neuronal polarization. A previous report demonstrated that Sada-/- and Sadb-/- double-mutant mice showed perinatal lethality with a severe defect in axon/dendrite differentiation, but their single mutants did not. These results indicated that they were functionally redundant. Surprisingly, we show that on a C57BL/6N background, SAD-A is essential for cortical development whereas SAD-B is dispensable. Sada-/- mice died within a few days after birth. Their cortical lamination pattern was disorganized and radial migration of cortical neurons was perturbed. Birth date analyses with BrdU and in utero electroporation using pCAG-EGFP vector showed a delayed migration of cortical neurons to the pial surface in Sada-/- mice. Time-lapse imaging of these mice confirmed slow migration velocity in the cortical plate. While the neurites of hippocampal neurons in Sada-/- mice could ultimately differentiate in culture to form axons and dendrites, the average length of their axons was shorter than that of the wild type. Thus, analysis on a different genetic background than that used initially revealed a nonredundant role for SAD-A in neuronal migration and differentiation.


Small Proportion of Low-Birth-Weight Infants With Ostomy and Intestinal Failure Due to Short-Bowel Syndrome Achieve Enteral Autonomy Prior to Reanastomosis.
It is challenging to provide optimum nutrition in low-birth-weight (LBW) infants with short-bowel syndrome (SBS) and ostomy. This study aims to evaluate the clinical course of LBW infants with SBS and ostomy in response to enteral feeds, recognize characteristics associated with achievement of enteral autonomy prior to reanastomosis, and evaluate associated short-term outcomes. A retrospective analysis of 52 LBW neonates with intestinal failure (IF) caused by SBS and ostomy treated in a neonatal intensive care unit from 2012 to 2018 was performed. Clinical characteristics and short-term outcomes were studied in relation to the location of the ostomy and the success with enteral feeding achieved prior to reanastomosis. Of the 52 infants with SBS, jejunostomy, ileostomy, and colostomy were present in 9, 40, and 3 infants, respectively. Fourteen (26.92%) infants achieved enteral autonomy transiently, and 7 (13.46%) sustained until reanastomosis. All 9 infants with jejunostomy were parenteral nutrition dependent, compared with 22 with ileostomy and none with colostomy (P = 0.002). Infants who achieved enteral autonomy showed lower incidence of cholestasis (P = 0.038) and better growth velocity (P = 0.02) prior to reanastomosis. A minority of LBW infants with SBS and ostomy achieved enteral autonomy prior to reanastomosis. Distal ostomy (ileostomy and colostomy), reduced cholestasis, and better growth were associated with achievement of enteral autonomy. Our report highlights the challenges in establishing enteral autonomy in LBW infants with IF and ostomy, and the feasibility of that approach in a minority of patients, with tangible benefits.


A conditional process model of perfectionism, goal-realization, and post-competition mood.
Research has recently begun to examine the relationship between multidimensional perfectionism and athletes' post-competition mood. However, to date, there have been few attempts to examine the interaction between dimensions of perfectionism or model possible explanatory processes. To address these limitations, in the current study we tested a novel conditional process model whereby the relationship between perfectionistic strivings and post-competition affect was mediated by the degree to which goals were considered to have been met (goal-realization) and that this indirect effect was, in turn, moderated by levels of perfectionistic concerns. We tested this model in a sample of 251 athletes who took part in a "Runmageddon" event - a cross-country obstacle race. Athletes completed measures of perfectionism (perfectionistic strivings and perfectionistic concerns) before the race and measures of goal-realization and mood (tense arousal, energetic arousal, and hedonic tone) between 24 and 48 h after the race. Analyses revealed that perfectionistic strivings were indirectly linked to a more unpleasant post-competition mood (higher tense arousal and lower hedonic tone) via perceptions of lower goal-realization. In addition, these two indirect effects were statistically significant only when perfectionistic concerns were medium and high. The results support the proposed conditional model and suggest the interplay between dimensions of perfectionism is important for athletes' post-competition mood, and the level of perfectionistic concerns, especially.


Efficacy of short-term dynamic psychotherapy : past, present, and future.
The author outlines the history of brief dynamic psychotherapy, describes some of its characteristics, and addresses methodological requirements for assessing the efficacy of psychotherapy. Review of two major meta-analyses suggests that manual-based brief dynamic psychotherapy by trained therapists is likely to be as effective as other forms of psychotherapy and more effective than no treatment. More studies are needed that 1) compare brief dynamic psychotherapy with other forms of treatment for specific psychiatric disorders; 2) use theory-specific measures of outcome in addition to measures of symptoms; and 3) compare brief dynamic psychotherapy with long-term psychotherapy.


The use of glucarpidase as a rescue therapy for high dose methotrexate toxicity - a review of pharmacological and clinical data.
This review aims to summarize recent data on the pharmacodynamic, pharmacokinetic, and safety of glucarpidase. This is an enzymatic agent that catalyzes the conversion of methotrexate (MTX) into inactive metabolites. Glucarpidase is used to manage high-dose MTX (HDMTX) toxic plasma concentration, especially in patients with impaired renal function. In this review, studies on glucarpidase clinical efficacy as a therapeutic option for patients suffering from MTX kidney toxicity were presented. Pharmacodynamic and pharmacokinetic properties of glucarpidase were included. Moreover, potential interactions and safety issues were discussed. The use of glucarpidase is an effective therapeutic strategy in both adults and children treated with high doses of MTX for various types of cancer who have developed acute renal failure. Glucarpidase causes MTX to be converted to nontoxic metabolites and accelerates the time for its complete elimination. After administration of glucarpidase, it is possible to resume HDMTX.


Hydrochloric Acid Infusion for the Treatment of Metabolic Alkalosis in Surgical Intensive Care Unit Patients.
Older reports of use of hydrochloric acid (HCl) infusions for treatment of metabolic alkalosis document variable dosing strategies and risk. This study sought to characterize use of HCl infusions in surgical intensive care unit patients for the treatment of metabolic alkalosis. This retrospective review included patients who received a HCl infusion for >8 hours. The primary end point was to evaluate the utility of common acid-base equations for predicting HCl dose requirements. Secondary end points evaluated adverse effects, efficacy, duration of therapy, and total HCl dose needed to correct metabolic alkalosis. Data on demographics, potential causes of metabolic alkalosis, fluid volume, and duration of diuretics as well as laboratory data were collected. A total of 30 patients were included, and the average HCl infusion rate was 10.5 ± 3.7 mEq/h for an average of 29 ± 14.6 hours. Metabolic alkalosis was primarily diuretic-induced (n = 26). Efficacy was characterized by reduction in the median total serum CO2 from 34 to 27 mM/L ( P < 0.001). The change in chloride ion deficit and change in apparent strong ion difference (SIDa) were not correlated with total HCl administered. There were no documented serious adverse effects related to HCl infusions. HCl was effective for treating metabolic alkalosis, and no serious adverse events were seen. In this clinical setting, the baseline chloride ion deficit and SIDa were not useful for prediction of total HCl dose requirement, and serial monitoring of response is recommended.


[Esophageal manometry for the study of gastroesophageal reflux].
In a medical literature revision, actual concepts about esophageal inferior sphincter's importance are presented. It is the principal object on studies about clinical and surgical therapeutic procedures for gastroesophageal reflux. Thus, esophageal manometric study, fundamental for physiological knowledge of the organ, conducts the reflux esophagitis therapy.


[Sperm DNA fragmentation: association with semen parameters in young men].
Abnormal sperm DNA integrity is an important risk factor for male infertility. The aim of this work was to examine sperm DNA fragmentation in a cohort of young male volunteers (n=111; age 21.0+/-0.2 years) from the general population and establish the association between the level of sperm DNA fragmentation and sperm functional parameters. Sperm DNA fragmentation index (DFI) was determined by SCSA (sperm chromatin structure assay) using flow cytometry. Standard semen parameters (concentration, motility, and morphology) were evaluated according to the WHO guidelines (2010). and conclusions. In the study cohort, 79.0%, 12.4% and 8.6% of men had normal (DFI<15%), borderline (15 less or equal DFI<27%) and high (DFI more or equal 27%) levels of fragmentation, respectively. Men with impaired spermatogenesis had greater IDF values (14.53+/-1.43%) than men with normal semen parameters (8.88+/-0.77%, p<0.05). There was a statistically significant negative correlation between IFD and ejaculate concentration (r=-0.21, p<0.05), fractions of mobile (r=-0.41, p<0.05) and morphologically normal sperm (r=- 0.34, p<0.05). Testing sperm DNA fragmentation using SCSA technique can be employed in epidemiological studies of male fertility.


Whole-genome sequencing distinguishes the two most common giant kelp ecomorphs.
Giant kelp, Macrocystis pyrifera, exists as distinct morphological variants-or "ecomorphs"-in different populations, yet the mechanism for this variation is uncertain, and environmental drivers for either adaptive or plastic phenotypes have not been identified. The ecomorphs Macrocystis "pyrifera" and M. "integrifolia" are distributed throughout temperate waters of North and South America with almost no geographic overlap and exhibit an incongruous, non-mirrored, distribution across the equator. This study evaluates the degree of genetic divergence between M. "pyrifera" and M. "integrifolia" across 18 populations in Chile and California using whole-genome sequencing and single-nucleotide polymorphism markers. Our results based on a principal component analysis, admixture clustering by genetic similarity, and phylogenetic inference demonstrate that M. "pyrifera" and M. "integrifolia" are genetically distinguishable. Analyses reveal separation by Northern and Southern Hemispheres and between morphs within hemispheres, suggesting that the convergent "integrifolia" morphology arose separately in each hemisphere. This is the first study to use whole-genome sequencing to understand genetic divergence in giant kelp ecomorphs, identifying 83 potential genes under selection and providing novel insights about Macrocystis evolution that were not evident with previous genetic techniques. Future studies are needed to uncover the environmental forces driving local adaptation and presumed convergent evolution of these morphs.


Unscheduled care pathways in patients with myocardial infarction in Scotland.
Treatment of acute myocardial infarction (MI) requires rapid transfer of people with chest pain to hospital, however, unscheduled care pathways vary in their directness (the minimal number of contacts to hospital admission). The aim was to examine unscheduled care pathways and the associations with mortality in people admitted with MI. Retrospective population study of all people admitted to Scottish hospitals with a diagnosis of MI between 1 January 2015 and 31 December 2017. Linked data for all National Health Service Scotland unscheduled care services (NHS24 telephone triage service, primary care out of hours, ambulance, emergency department (ED)) was used to define continuous unscheduled care pathways (pathways), which were categorised by initial contact, and whether they were 'direct' (had minimum number of contacts between first contact and admission). Analysis estimated ORs and 95% CIs in adjusted models in which all covariates were included. 26 325 people admitted with MI (63.1% men, 61.6% aged 65+ years), of whom 5.6% died from coronary heart disease within 28 days. For 47.0%, the first unscheduled care contact was ambulance, 23.3% attended ED directly and 18.7% called telephone triage. 92.1% of pathways were direct. Pathways starting with telephone triage were more likely to be indirect compared with other initial contacts (adjusted OR (aOR) 1.97, 95% CI 1.61 to 2.40). Compared to direct pathways, indirect pathways starting with telephone triage were associated with higher mortality (aOR 1.97, 95% CI 1.61 to 2.40) as were indirect pathways starting with another service (aOR 1.55, 95% CI 1.19 to 2.01), but not direct pathways starting with telephone triage (aOR 0.87, 95% CI 0.74 to 1.02). Unscheduled care pathways leading to admission with MI in Scotland are usually direct, but those starting with telephone triage were more commonly indirect. Those indirect pathways were associated with higher mortality.


Discussing Out-of-Pocket Expenses During Clinical Appointments: An Observational Study of Patient-Psychiatrist Interactions.
High out-of-pocket expenses for medical treatment have been associated with worse quality of life, decreased treatment adherence, and increased risk of adverse health outcomes. Treatment of depression potentially has high out-of-pocket expenses. Limited data characterize psychiatrist-patient conversations about health care costs. The authors conducted content analysis from 422 outpatient psychiatrist-patient visits for medication management of major depressive disorder in community-based private practices nationwide from 2010 to 2014. Patients' health care expenses were discussed in 38% of clinic visits (95% confidence interval [CI]= 33%-43%). Uninsured patients were significantly more likely to discuss expenses than were patients enrolled in private or public plans (64%, 44%, and 30%, respectively; p<.001). Sixty-nine percent of cost conversations lasted less than one minute (median=36 seconds; interquartile range [IQR]=16-81 seconds). Cost conversations most frequently addressed psychotropic medications (51%). Physicians initiated 50% of cost conversations and brought up costs for psychotropic medications more often than did patients (62% versus 38%, p=.009). Conversely, a greater percentage of patient-initiated cost conversations addressed provider visit costs (27% versus 10%, p=.008). Overall, 45% of cost conversations mentioned cost-reducing strategies (CI=37%-53%). The most frequently discussed cost-reducing strategies were lowering cost by changing the source or timing of an intervention (for example, changing pharmacies), providing free samples, and switching to a lower-cost therapy or diagnostic test. Psychiatrists and patients regularly discuss patients' health care costs in visits for depression. These discussions cover a variety of clinical topics and frequently include strategies to lower patients' costs.


Regulating sadness and fear from outside and within: mothers' emotion socialization and adolescents' parasympathetic regulation predict the development of internalizing difficulties.
Multilevel models of developmental psychopathology implicate both characteristics of the individual and their rearing environment in the etiology of internalizing problems and disorders. Maladaptive regulation of fear and sadness, the core of anxiety and depression, arises from the conjoint influences of ineffective parasympathetic regulation of emotion and ineffective emotion socialization experiences. In 171 youths (84 female, M = 13.69 years, SD = 1.84), we measured changes of respiratory sinus arrhythmia (RSA) in response to sadness- and fear-inducing film clips and maternal supportive and punitive responses to youths' internalizing emotions. Youths and mothers reported on youths' internalizing problems and anxiety and depression symptoms concurrently and 2 years later at Time 2. Maternal supportive emotion socialization predicted fewer, and punitive socialization predicted more, mother-reported internalizing problems at Time 2 only for youths who showed RSA suppression to fear-inducing films. More RSA suppression to sadness-inducing films predicted more youth-reported internalizing problems at Time 2 in girls only. In addition, less supportive emotion socialization predicted more youth-reported depression symptoms at Time 2 only for girls who showed more RSA suppression to sadness. RSA suppression to sadness versus fear might reflect different patterns of atypical parasympathetic regulation of emotional arousal, both of which increase the risk for internalizing difficulties in youths, and especially girls, who lack maternal support for regulating emotions.


Isolation induced changes in Guinea Pig Cavia porcellus pup distress whistles.
Guinea Pig Cavia porcellus pups emit high-pitched distress whistles when separated from their mother. In order to assess the influence of the duration of a brief isolation period on whistle acoustic structure, we recorded the distress whistles of six 8-day old pups separated for 15 min from their group in a novel environment and compared the mean values of the first and last 30 whistle notes. Acoustic analysis revealed, throughout the session, a significant decrease in whistle duration, an increase in mean frequency and a tendency for a decrease in number of harmonics in the first part of the note. Results demonstrate that, throughout a brief isolation period, the vocal response of Guinea Pig pups to isolation undergoes structural changes possibly related to time-dependent changes in motivational state.


Spiritual/cultural competency: methods in diversity education.
Diversity education in clinical training such as CPE is best developed in an interactive group context, guided by methods and approaches promoting mutual disclosure that includes the leader. Each member is invited to portray a web of meaning with cultural, spiritual and religious threads that comprise a personally knitted reality, a narrative foundational to identity and interaction. Differences between people in the training context challenge previously held notions, distribute authority in the group and foster open ended learning that enriches the activities of clinical supervision. This article describes group educational methods with case examples that foster spiritual/cultural competency, each member a person in context with the opportunity to be distinct and connected, a threshold for all other dimensions of diversity learning in pastoral practice.


Do MZ twins have discordant experiences of friendship? A qualitative hypothesis-generating MZ twin differences study.
Using a qualitative monozygotic (MZ) twin differences design we explored whether adolescent MZ twins report discordant peer relationships and, if so, whether they perceive them as causes, consequences or correlates of discordant behaviour. We gathered free-response questionnaire data from 497 families and conducted in-depth telephone interviews with 97 of them. Within this dataset n = 112 families (23% of the sample) described discordant peer relationships. Six categories of discordance were identified (peer victimisation, peer rejection, fewer friends, different friends, different attitudes to friendship and dependence on co-twin). Participants described peer relationship discordance arising as a result of chance occurrences, enhanced vulnerability in one twin or discordant behaviour. Consequences of discordant peer relationships were seen as discordance in self-confidence, future plans, social isolation, mental health and interests. In all cases the twin with worse peer experiences was seen as having a worse outcome. Specific hypotheses are presented.


Multiple Bony Injuries on Bone Scan in a Case of Unsuspected Child Abuse.
This case is described of an eleven-month-old infant with lower limbs swelling and the left elbow skeletal malformation following a fall. The radionuclide bone scan was performed to exclude bone infection or congenital skeletal anomaly. The images unexpectedly showed multiple increased radioactive foci throughout the whole body. It was a strong probability of child abuse. All lesions are readily apparent on the following plain film radiographs and MRI.


The developmental stages of Bipolar Disorder: a case report.
Bipolar disorder is a developing disorder; its early stages are sometimes misdiagnosed as anxiety or depressive disorders. At the same time, these disorders are often in comorbidity with bipolar disorder. This complex symptomatology can lead to misinterpretation and underdiagnosis of bipolar disorders, mainly at the earliest stages. Consequently, one of the most important challenges for clinicians is to recognize the non specific early symptoms with the aid of clinical information, for example a family history of bipolar disorder. Furthermore, it is well-known that comorbid anxiety disorders can lead to a worse prognosis in bipolar patients but it is not exactly clear to what extent. A deeper understanding of the relationship between these comorbidities and their stage of development will hopefully lead to better care of patients with bipolar disorder from a younger age.


The analgesia efficiency of ultrasmall magnetic iron oxide nanoparticles in mice chronic inflammatory pain model.
Few studies have investigated the effects of iron oxide nanoparticles (NPs) on analgesia. We developed inflammatory pain models via complete Freund's adjuvant injection over the hind paw in CD1 mice. Various doses of magnetite (Fe3O4) NPs were injected into the paw. Analgesia behavior was checked with von Frey microfilament and thermal irradiation measurements. Paw skin tissues were harvested at the maximal analgesia time point. The presence of activated white cells (CD68, myeloperoxidase) and free radical (reactive oxygen species, ROS) production was also checked. Western blotting was used to identify the changes of ROS production enzymes. Fe3O4 NPs demonstrated a dose-related analgesia effect with significant reduction in inflammatory cells, pro-inflammatory markers, and ROS production in the lesion paw. ROS production enzyme expression also declined. The results indicate that local Fe3O4 NP administration induced significant analgesia via attenuation of inflammatory cell infiltration and pro-inflammatory signaling as well as scavenging of microenvironment free radicals in a mouse inflammatory pain model.


Growth of oral Streptococcus species and Actinomyces viscosus in human saliva.
Microorganisms in dental plaque live in constant association with saliva. The role of saliva in the adherence of bacteria to the teeth and the antibacterial properties of saliva have been well investigated; less interest has been shown in the possible role of saliva as a substrate for oral microorganisms. In this study it was shown that saliva can serve as a growth medium for oral Streptococcus spp. and Actinomyces viscosus. The cell production of these organisms on saliva was carbohydrate limited. The doubling times for growth on glucose-supplemented saliva (4 to 5 mmol/liter) ranged from 1.6 to 4.0 h. The availability of carbohydrate sources for the oral microflora is discussed in relation to microbial growth in the oral cavity.


Structural Evolution of MOF-Derived RuCo, A General Catalyst for the Guerbet Reaction.
Guerbet alcohols, a class of β-branched terminal alcohols, find widespread application because of their low melting points and excellent fluidity. Because of the limitations in the activity and selectivity of existing Guerbet catalysts, Guerbet alcohols are not currently produced via the Guerbet reaction but via hydroformylation of oil-derived alkenes followed by aldol condensation. In pursuit of a one-step synthesis of Guerbet alcohols from simple linear alcohol precursors, we show that MOF-derived RuCo alloys achieve over a million turnovers in the Guerbet reaction of 1-propanol, 1-butanol, and 1-pentanol. The active catalyst is formed in situ from ruthenium-impregnated metal-organic framework MFU-1. XPS and XAS studies indicate that the precatalyst is composed of Ru precursor trapped inside the MOF pores with no change in the oxidation state or coordination environment of Ru upon MOF incorporation. The significantly higher reactivity of Ru-impregnated MOF versus a physical mixture of Ru precursor and MOF suggests that the MOF plays an important role in templating the formation of the active catalyst and/or its stabilization. XPS reveals partial reduction of both ruthenium and MOF-derived cobalt under the Guerbet reaction conditions, and TEM/EDX imaging shows that Ru is decorated on the edges of dense nanoparticles, as well as thin nanoplates of CoOx. The use of ethanol rather than higher alcohols as a substrate results in lower turnover frequencies, and RuCo recovered from ethanol upgrading lacks nanostructures with plate-like morphology and does not exhibit Ru-enrichment on the surface and edge sites. Notably, 1H and 31P NMR studies show that through use of K3PO4 as a base promoter in the RuCo-catalyzed alcohol upgrading, the formation of carboxylate salts, a common side product in the Guerbet reaction, was effectively eliminated.


[Chronic small intestine obstructions].
Chronic small bowel obstruction may be related either to disordered motility or to progressive chronic stenoses. Disordered motility (or intestinal pseudo-obstruction) is the consequence for muscular and/or intrinsic nerve impairment with 2 main types, one of which is primary (including so-called visceral myopathies and visceral neuropathies), the other one being secondary (generally due to systemic, or sometimes immunologic disease). Chronic stenoses have a different pathophysiology and occur in the setting of chronic inflammatory bowel disease or of systemic diseases such as vasculities. Chronic stenoses lead to intestinal stasis and in fine to mechanical obstruction. In any case, chronic obstruction poses difficult diagnostic and therapeutic problems. Management calls for tight medico-surgical cooperation. Atypical surgical operations may be warranted, and specific, sometimes aggressive medical care is mandatory. Moreover the nutritional consequences of chronic small bowel obstruction may become highly disabling due to alimentary restriction, disordered transit, bacterial overgrowth and malabsorption. In this setting nutritional support should be a matter of prime concern.


Cell interactions, signals and transcriptional hierarchy governing placode progenitor induction.
In vertebrates, cranial placodes contribute to all sense organs and sensory ganglia and arise from a common pool of Six1/Eya2+ progenitors. Here we dissect the events that specify ectodermal cells as placode progenitors using newly identified genes upstream of the Six/Eya complex. We show in chick that two different tissues, namely the lateral head mesoderm and the prechordal mesendoderm, gradually induce placode progenitors: cells pass through successive transcriptional states, each identified by distinct factors and controlled by different signals. Both tissues initiate a common transcriptional state but over time impart regional character, with the acquisition of anterior identity dependent on Shh signalling. Using a network inference approach we predict the regulatory relationships among newly identified transcription factors and verify predicted links in knockdown experiments. Based on this analysis we propose a new model for placode progenitor induction, in which the initial induction of a generic transcriptional state precedes regional divergence.


Violence and aggression: a literature review.
This paper reports the results of a literature review that was undertaken to provide background for a small pilot study that introduced violence measurement instruments that was to assist the development of nursing practice on an acute psychiatric unit. Multiple databases were searched, focusing on publications since 1994: CINAHL, Ovid Healthstar, Ovid MEDLINE (R), EMBASE, and PsycINFO. The search used the following four groups of key word alternatives (used in truncated form to allow for ending permutations) in combination with each other: violence, aggression, dangerous; prediction, assessment, factor, risk, issue, cause, reason; mental, psychiatric; inpatient, short-term, acute, admission. Searching was supplemented with footnote chasing of those papers retrieved and existing resources of the first author. Consequently, the synthesis of the results discussed cannot be considered a systematic review of the literature and is a reflection of some of the key issues found in the literature.


A New Strategy to Reduce Influenza Escape: Detecting Therapeutic Targets Constituted of Invariance Groups.
The pathogenicity of the different flu species is a real public health problem worldwide. To combat this scourge, we established a method to detect drug targets, reducing the possibility of escape. Besides being able to attach a drug candidate, these targets should have the main characteristic of being part of an essential viral function. The invariance groups that are sets of residues bearing an essential function can be detected genetically. They consist of invariant and synthetic lethal residues (interdependent residues not varying or slightly varying when together). We analyzed an alignment of more than 10,000 hemagglutinin sequences of influenza to detect six invariance groups, close in space, and on the protein surface. In parallel we identified five potential pockets on the surface of hemagglutinin. By combining these results, three potential binding sites were determined that are composed of invariance groups located respectively in the vestigial esterase domain, in the bottom of the stem and in the fusion area. The latter target is constituted of residues involved in the spring-loaded mechanism, an essential step in the fusion process. We propose a model describing how this potential target could block the reorganization of the hemagglutinin HA2 secondary structure and prevent viral entry into the host cell.


Losers can win: Thermoregulatory advantages of regenerated claws of fiddler crab males for establishment in warmer microhabitats.
Fiddler crab males present a hypertrophied claw, which is used for sexual and aggressive displays, fights with competitors, and has been proposed as an important thermoregulatory organ for heat control. Two claw morphologies can be observed within fiddler crab populations: brachychelous claws (unregenerated) and leptochelous claws (regenerated). The leptochelous morphotype presents less muscle mass and longer fingers, resulting in a less advantageous weapon in fights. Considering their slender shape, we hypothesized that the leptochelous morphotype would present lower thermal inertia and be more efficient at body heat dissipation. We evaluated the role of the fiddler crabs' claw shape as a heat sink and how this influences their distribution between unshaded and shaded microhabitats. We tested in the field whether the proportion of adult male Leptuca uruguayensis with leptochelous claws was higher in unshaded microhabitats than shaded ones. In the laboratory, we tested if heat transfer between the body and claw is higher in leptochelous males than in brachychelous males. Spontaneous waving behaviour and active time above the surface were compared between both morphotypes in the field during the hottest period of the day. Leptuca uruguayensis with regenerated claws comprised more than 60% of the sampled male population of unshaded microhabitats compared to 18% in shaded microhabitats. Leptochelous males showed a mean heat transfer between body to claw 35% higher than that observed for brachychelous males. During the hottest period of the day, brachychelous males waved approximately 28% more than leptochelous males. Moreover, brachychelous males spent less time under the sediment surface since the surface temperature increased, while activity of leptochelous males was not associated with a temperature increase. Therefore, regenerated claws may be advantageous for the establishment of L. uruguayensis males in warmer and unshaded microhabitats because they are more efficient for heat loss and allow crabs to cool down, spending less time waving. Our study shows the relevant context of winners and losers in the face of climate change and highlights the importance of morphological variations in thermoregulatory structures for the occupation of thermal niches.


A synopsis of the New World species of Drypetes section Drypetes (Putranjivaceae) with asymmetrical fruits, including description of a new species.
A synopsis of the New World species of Drypetes (Putranjivaceae) with asymmetrical drupes is presented. The group consists of three species: Drypetes alba, with two varieties,from the West Indies, Drypetes gentryi from Mexico, and the newly described Drypetes asymmetricarpafrom Costa Rica. The new species can be distinguished from both its relatives by its longer fruiting pedicels. In addition, the new species differs from Drypetes alba by its larger fruits, and from Drypetes gentryi by having shorter staminate pedicels and stigmas borne on styles (rather than sessile). Lectotypes are designated for Drypetes albavar. latifoliaand Drypetes incurva.


Lung or liver: An imaging dilemma on Tc-99m macroaggregated albumin lung perfusion scintigraphy.
We present a 10-year-old boy having the bronchiectasis who was subjected to lung perfusion scintigraphy before lung resection surgery to assess the lung parenchymal function. It revealed unusual tracer distribution in right upper body that was mimicking to be liver. It was unusual unless there were some shunts bypassing the lung uptake or faulty radiopharmaceutical preparation. However by bringing down the image window, it became clear that radiopharmaceutical distribution was in thorax only correlating with lung uptake, and not in the liver. Corresponding X-ray chest and computed tomography thorax demonstrated multiple cystic lesions in left lung parenchyma.


A practical implementation of physics quality assurance for photon adaptive radiotherapy.
The fast evolution of technology in radiotherapy (RT) enabled the realization of adaptive radiotherapy (ART). However, the new characteristics of ART pose unique challenges for efficiencies and effectiveness of quality assurance (QA) strategies. In this paper, we discuss the necessary QAs for ART and introduce a practical implementation. A previously published work on failure modes and effects analysis (FMEA) of ART is introduced first to explain the risks associated with ART sub-processes. After a brief discussion of QA challenges, we review the existing QA strategies and tools that might be suitable for each ART step. By introducing the MR-guided online ART QA processes developed at our institute, we demonstrate a practical implementation. The limitations and future works to develop more robust and efficient QA strategies are discussed at the end.


Bariatric surgery and calcifediol treatment, Gordian knot of severe-obesity-related comorbidities treatment.
Obesity (OB) is a chronic metabolic disease with important associated comorbidities and mortality. Vitamin D supplementation is frequently administered after bariatric surgery (BS), so as to reduce OB-related complications, maybe including chronic inflammation. This study aimed to explore relations between vitamin D metabolites and components of the inflammasome machinery in OB before and after BS and their relations with the improvement of metabolic comorbidities. Epidemiological/clinical/anthropometric/biochemical evaluation was performed in patients with OB at baseline and 6 months after BS. Evaluation of i) vitamin-D metabolites in plasma and ii) components of the inflammasome machinery and inflammatory-associated factors [NOD-like-receptors (NLRs), inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators] in peripheral blood mononuclear cells (PBMCs) was performed at baseline and 6 months after BS. Clinical and molecular correlations/associations were analyzed. Significant correlations between vitamin D metabolites and inflammasome-machinery components were observed at baseline, and these correlations were significantly reduced 6 months after BS in parallel to a decrease in inflammation markers, fat mass, and body weight. Treatment with calcifediol remarkably increased 25OHD levels, despite 24,25(OH)2D3 remained stable after BS. Several inflammasome-machinery components were associated with improvement in metabolic comorbidities, especially hypertension and dyslipidemia. The beneficial effects of vitamin D on OB-related comorbidities after BS patients are associated with significant changes in the molecular expression of key inflammasome-machinery components. The expression profile of these inflammasome components can be dynamically modulated in PBMCs after BS and vitamin D supplementation, suggesting that this profile could likely serve as a sensor and early predictor of the reversal of OB-related complications after BS.


Validity of foot-to-foot bioelectrical impedance analysis in overweight and obese children and parents.
The aim of this study was to evaluate the validity of foot-to-foot bioelectrical impedance analysis (FF-BIA) in the measurement of body composition in overweight and obese children and their parents by comparison to dual-energy X-ray absorptiometry (DXA). Seventeen, 7-12 year old overweight and obese children (6 boys, 11 girls) and 17 parents (5 fathers, 12 mothers) were evaluated for body composition with FF-BIA and DXA. Measures of percent body fat (PBF), fat mass (FM) and fat free mass (FFM) derived from FF-BIA and DXA were compared. Measures of validity were determined by Pearson correlations between FF-BIA and DXA, paired t-tests to assess mean differences, as well as biases and limits of agreement using the Bland Altman tests. FF-BIA produced estimates of body composition that were highly correlated with DXA in overweight and obese children and parents. For children, the correlations for PBF, FM, and FFM were 0.85, 0.97, and 0.94, respectively. For parents, the correlations for PBF, FM, and FFM were 0.92, 0.97, and 0.91, respectively. However, mean differences between FF-BIA and DXA were significant in children but not in parents. Bland-Altman tests of agreement showed moderate to large within-subject differences in body composition variables between FF-BIA and DXA. FF-BIA is strongly related to DXA in the measurement of body composition in both overweight and obese preadolescent children and parents, but the two measures may not be used interchangeably. Although FF-BIA may lack the precision to assess small changes in body composition in overweight and obese individuals, it is appropriate for epidemiological use.


A randomized, double-blind, active placebo-controlled study of efficacy, safety, and durability of repeated vs single subanesthetic ketamine for treatment-resistant depression.
The strategy of repeated ketamine in open-label and saline-control studies of treatment-resistant depression suggested greater antidepressant response beyond a single ketamine. However, consensus guideline stated the lack of evidence to support frequent ketamine administration. We compared the efficacy and safety of single vs. six repeated ketamine using midazolam as active placebo. Subjects received either six ketamine or five midazolam followed by a single ketamine during 12 days followed by up to 6-month post-treatment period. The primary end point was the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) score at 24 h after the last infusion. Fifty-four subjects completed all six infusions. For the primary outcome measure, there was no significant difference in change of MADRS scores between six ketamine group and single ketamine group at 24 h post-last infusion. Repeated ketamine showed greater antidepressant efficacy compared to midazolam after five infusions before receiving single ketamine infusion. Remission and response favored the six ketamine after infusion 4 and 5, respectively, compared to midazolam before receiving single ketamine infusion. For those who responded, the median time-to-relapse was nominally but not statistically different (2 and 6 weeks for the single and six ketamine group, respectively). Repeated infusions were relatively well-tolerated. Repeated ketamine showed greater antidepressant efficacy to midazolam after five infusions but fell short of significance when compared to add-on single ketamine to midazolam at the end of 2 weeks. Increasing knowledge on the mechanism of ketamine should drive future studies on the optimal balance of dosing ketamine for maximum antidepressant efficacy with minimum exposure.


Experimental Characterization of Droplet Adhesion: The Ejection Test Method (ETM) Applied to Surfaces with Various Hydrophobicity.
We study the wetting and the adhesive behavior of substrates made by electropolymerization of copolymers of pyrene substituted with fluoroalkyl and adamantyl groups. The hydrophobicity and water adhesion properties can be tuned by the molar percentage (mol %) of each pyrene monomer so that the substrate properties can vary from superhydrophobic to parahydrophobic, with respectively low and high water adhesion. The ejection test method (ETM) is proposed as an original tool to discriminate and characterize such substrates. Using a catapult-like apparatus, a droplet initially at rest on the surface is subject to a large acceleration and is subsequently ejected. Depending on the surface properties and initial catapult acceleration, the ejection is more or less efficient and occurs with or without fragmentation of the droplet. The ETM is shown to be a complementary test to the lateral adhesion and hysteresis classical measurements. This work is of importance for the understanding of adhesion phenomena on various surfaces and for a better quantitative characterization of their adhesive properties.


MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene.
MicroRNA-155 (miR-155) is overexpressed in many human cancers; however, the mechanisms by which miR-155 functions as a putative oncomiR are largely unknown. Here, we report that the tumor suppressor gene suppressor of cytokine signaling 1 (socs1) is an evolutionarily conserved target of miR-155 in breast cancer cells. We found that mir-155 expression is inversely correlated with socs1 expression in breast cancer cell lines as well as in a subset of primary breast tumors. We also identified a 24A-->G mutation in the miR-155 binding site of the SOCS1 3' untranslated region in a breast tumor that reduced miR-155 repression, implicating a mechanism for miRNA targets to avoid repression. Ectopic expression of miR-155 significantly promoted the proliferation of breast cancer cells, the formation of soft agar foci in vitro, and the development of tumors in nude mice. In breast cancer cells, RNA interference silencing of socs1 recapitulates the oncogenic effects of miR-155, whereas restoration of socs1 expression attenuates the protumorigenesis function of miR-155, suggesting that miR-155 exerts its oncogenic role by negatively regulating socs1. Overexpression of miR-155 in breast cancer cells leads to constitutive activation of signal transducer and activator of transcription 3 (STAT3) through the Janus-activated kinase (JAK) pathway, and stimulation of breast cancer cells by the inflammatory cytokines IFN-gamma and interleukin-6 (IL-6), lipopolysaccharide (LPS), and polyriboinosinic:polyribocytidylic acid [poly(I:C)] significantly upregulates mir-155 expression, suggesting that miR-155 may serve as a bridge between inflammation and cancer. Taken together, our study reveals that miR-155 is an oncomiR in breast cancer and that miR-155 may be a potential target in breast cancer therapy.


Incomplete recovery of the fecal flora of hematological patients with neutropenia and repeated fluoroquinolone prophylaxis.
Routine fluoroquinolone prophylaxis in neutropenic patients with hematological malignancies is still controversial, because of antibiotic resistance concerns. The recovery of the fecal microbiota to the initial composition in patients receiving multiple courses of quinolone prophylaxis and repeated chemotherapy has not been evaluated. We prospectively examined the changes in the fecal bacterial composition before and after levofloxacin prophylaxis. A sequential observation of bacterial resistance in patients receiving multiple prophylactic courses was also conducted. In this trial, 68 cases, including (35 with the first course and 33 with the second and subsequent courses) were registered. The disappearance of quinolone-susceptible (QS) Entero-bacteriaceae and dominant emergence of quinolone-resistant (QR) coagulase negative staphylococci (CNS) and QR Enterococci were observed after the first prophylaxis. The detection of QS Enterobacteriaceae was recovered before the second and subsequent courses to a level of the initial composition (28/35 samples, 80.0% before the first course vs 23/33 samples, 69.7% before the second and subsequent courses, P=0.41). In contrast, the detection rate of QR CNS and Enterococci significantly increased at the second and subsequent courses, even before prophylaxis (8/35 samples, 22.9% before the first course vs 20/33 samples, 60.6% before the second and subsequent courses, P=0.003). The incomplete recovery of the initial bacterial composition was associated with a prophylactic interval of within 30 days. Of the patients receiving multiple prophylactic courses, six had QR Escherichia coli, including extended-spectrum β-lactamase (ESBL) producers, at the first course, and four (66.3%) of the six patients had persistent detection of QR E. coli at the second course. In patients receiving multiple courses of prophylactic quinolone, along with a common chemotherapy schedule, newly emergent resistant bacteria could be frequently persistent in their fecal flora.


Depression or anxiety: which is best able to predict patterns of lateralisation for the processing of emotional faces?
Previous research has shown that both anxiety and depression are associated with strength of lateralisation for the processing of emotive faces, although these clinical measures have always been considered in separate studies. In the present study, we measure depression and anxiety, within the same non-clinical sample, and consider whether these variables can predict strength of lateralisation, measured using the chimeric faces test. There are two key findings from this study. First, for females only, anxiety is negatively associated with right hemispheric superiority for processing of negative emotional expressions. Second, there was only one finding for depression, showing a relationship with strength of lateralisation for the processing of fearful faces that differed according to sex.


Handedness but not dominance influences variability in endurance time for sustained, submaximal contractions.
The purpose of this study was to compare endurance time and accompanying neuromuscular adjustments when left- and right-handed subjects used the dominant and nondominant arms to sustain submaximal contractions that required either force or position control. Ten left-handed and 10 right-handed healthy adults (21 ± 5 yr) participated in the study. Each subject exerted a similar net torque about the elbow joint during the force and position tasks to achieve a target force of 20% maximal voluntary contraction (MVC) force (56 ± 18 N). MVC force declined to a similar level immediately after task failure for left- and right-handed subjects (27 ± 13 vs. 25 ± 15%, P = 0.9). Endurance time for the position task was similar for the dominant and nondominant arms (task × dominance interaction, P = 0.17). Although the difference in endurance time between the two tasks was similar for left-handed (136 ± 165 s) and right-handed individuals (92 ± 73 s, task × handedness interaction, P = 0.38), there was greater variance in the ratio of the endurance times for the force and position tasks for left-handed (0.77) than right-handed subjects (0.13, P < 0.001; see Fig. 2). Furthermore, endurance time for the force and position tasks was significantly correlated for right-handed subjects (r(2) = 0.62, P < 0.001), but not for left-handed subjects (r(2) = 0.004, P = 0.79). Multiple regression analyses identified sets of predictor variables for each endurance time, and these differed with handedness and task. Hand dominance, however, did not influence endurance time for either group of subjects. These findings indicate that endurance times for the elbow flexors when performing submaximal isometric contractions that required either force or position control were not influenced by hand dominance but did depend on handedness.


Quantum-classical Liouville dynamics in the mapping basis.
The quantum-classical Liouville equation describes the dynamics of a quantum subsystem coupled to a classical environment. It has been simulated using various methods, notably, surface-hopping schemes. A representation of this equation in the mapping Hamiltonian basis for the quantum subsystem is derived. The resulting equation of motion, in conjunction with expressions for quantum expectation values in the mapping basis, provides another route to the computation of the nonadiabatic dynamics of observables that does not involve surface-hopping dynamics. The quantum-classical Liouville equation is exact for the spin-boson system. This well-known model is simulated using an approximation to the evolution equation in the mapping basis, and close agreement with exact quantum results is found.


Continuing with life as normal:: positive psychological outcomes following spinal cord injury.
Research into the psychological sequelae of spinal cord injury (SCI) has focused on reports of psychological distress, despite the low prevalence rates of mental health difficulties. Positive psychological frameworks have begun to explore how some individuals do not report psychological distress, while appraisals have been posited as possible mediators of psychological outcome. Research into positive psychological outcomes in people with SCI is still in its infancy. To provide a description of the positive psychological outcomes experienced by people reporting low levels of psychological distress, to generate an understanding of how these individuals explain their positive outcomes, and to consider the implications for research, theory, and practice. Six participants (2 female, 4 male) reporting low levels of psychological distress were interviewed using a semi-structured interview schedule exploring their experiences. Interpretative phenomenological analysis was used to analyze data. THREE SUPERORDINATE THEMES WERE IDENTIFIED: "living a normal life, just doing things differently," "overcoming challenges: determination to succeed," and "using the resources available to me." The description and explanation of a positive psychological outcome was complex. For participants, positive psychological outcomes did not exclude experiencing psychological difficulty; moreover, they described an ability to overcome difficulty. Challenge-focused appraisals, social support, and meaningful activity were identified by participants as being important to psychological outcome. Positive psychological outcomes following SCI are complex, and research and theory need to better understand the experience of individuals following SCI in order to inform clinical practice.


The effects of levofloxacin on ECG parameters and late potentials.
In this study, our aim was to investigate the proarrhythmic effects of levofloxacin. Twenty-six patients who were diagnosed as having community-acquired pneumonia were enrolled in the study. Intravenous levofloxacin, 500 mg daily, was given, and 12-lead ECG measurements were obtained before the infusion, at 30 and 60 minutes during infusion, and 10 minutes after its cessation. Resting late potentials were recorded before and after infusion. Twelve female and 14 male patients were participated the study. Mean age was 51.3 +/- 22.3 years. Levofloxacin infusion increased the heart rate (HR) and prolonged the corrected QT (QTc) intervals significantly (baseline HR: 84.6 +/- 18.8 vs. HR at 60 minutes: 88.6 +/- 18, P = 0.02; baseline QTc: 413.5 +/- 36.9 milliseconds vs. QTc at 60 minutes: 426.1 +/- 34.7, P = 0,006). There was no significant difference between the late potential values obtained before and after infusion. None of our patients experienced severe arrhythmia that required stopping the treatment. A single dose of IV levofloxacin prolongs the QTc interval without significant change in late potentials. Monitoring ECG during levofloxacin infusion might be necessary in patients who have a condition that could affect the QTc interval.


Frequency of C9orf72 repeat expansions in amyotrophic lateral sclerosis: a Belgian cohort study.
We determined the frequency of C9orf72 repeat expansions in a large cohort of Belgian patients with familial (fALS) and sporadic (sALS) amyotrophic lateral sclerosis (ALS). In total, 119 patients with fALS from 62 kindreds, 471 patients with sALS, and 384 control subjects were included. A C9orf72 repeat expansion was found in 32 of 62 fALS pedigrees (51.6%), in 45 of 471 patients with sALS (9.6%), but in none of the control subjects. Compared with fALS of unknown etiology or fALS caused by mutations in other ALS-causing genes, C9orf72 repeat expansion carriers had a later age at onset (57.3 vs. 51.4 years; p = 0.0061), a higher proportion of bulbar onset (31.9% vs. 12.5%, p < 0.0001), and a reduced survival (29.4 vs. 67.7 months, p = 0.0003). In the sALS cohort, there were no significant differences in these disease characteristics between the C9orf72 repeat expansion carriers and the noncarriers. C9orf72 repeat expansions are a frequent cause of ALS in Belgium, and also in sALS patients. These results might justify genetic testing of C9orf72 in all ALS patients.


The Z-plasty transposition flap for reconstruction of the middle cheek.
Large defects of the middle cheek may prove difficult to repair. Too wide for primary closure, such defects pose challenging reconstructive options because there are no cosmetic unit boundaries in which to camouflage incision lines without resorting to widely undermined flaps. This article summarizes our experience with the Z-plasty and double Z-plasty transposition flaps for reconstruction of the cheek. The Z-plasty transposition flap was used immediately after Mohs micrographic surgery to repair 14 defects of the middle cheek caused by basal cell carcinoma (n = 12) or squamous cell carcinoma (n = 2). In all cases, primary closure of the defect would have resulted in excessively long scars, scars oriented perpendicular to relaxed skin tension lines, and/or free-margin distortion. In 4 of these cases, a double Z-plasty was used. The cosmetic and functional outcomes were judged from good to excellent by patient and surgeon. No cases of infection occurred. In one patient, minor superficial tip necrosis healed without incident. A "spit" subcutaneous suture at one flap tip of another patient left a small nodular scar, which was primarily excised and healed well. The Z-plasty and double Z-plasty transposition flaps offer excellent primary reconstructive modalities for the repair of geographically isolated defects of the cheek that are large or misoriented for primary side-to-side closure. The theoretical and practical geometric characteristics of the Z-plasty transposition require preparation and practice to achieve consistently satisfying results.


Stimulus-dependent functional network topology in mouse visual cortex.
Information is processed by networks of neurons in the brain. On the timescale of sensory processing, those neuronal networks have relatively fixed anatomical connectivity, while functional connectivity, which defines the interactions between neurons, can vary depending on the ongoing activity of the neurons within the network. We thus hypothesized that different types of stimuli, which drive different neuronal activities in the network, could lead those networks to display stimulus-dependent functional connectivity patterns. To test this hypothesis, we analyzed electrophysiological data from the Allen Brain Observatory, which utilized Neuropixels probes to simultaneously record stimulus-evoked activity from hundreds of neurons across 6 different regions of mouse visual cortex. The recordings had single-cell resolution and high temporal fidelity, enabling us to determine fine-scale functional connectivity. Comparing the functional connectivity patterns observed when different stimuli were presented to the mice, we made several nontrivial observations. First, while the frequencies of different connectivity motifs (i.e., the patterns of connectivity between triplets of neurons) were preserved across stimuli, the identities of the neurons within those motifs changed. This means that functional connectivity dynamically changes along with the input stimulus, but does so in a way that preserves the motif frequencies. Secondly, we found that the degree to which functional modules are contained within a single brain region (as opposed to being distributed between regions) increases with increasing stimulus complexity. This suggests a mechanism for how the brain could dynamically alter its computations based on its inputs. Altogether, our work reveals unexpected stimulus-dependence to the way groups of neurons interact to process incoming sensory information.


Molecular dynamics simulation of the docking of substrates to proteins.
A simple method is described to perform docking of substrates to proteins or probes to receptor molecules by a modification of molecular dynamics simulations. The method consists of a separation of the center-of-mass motion of the substrate from its internal and rotational motions, and a separate coupling to different thermal baths for both types of motion of the substrate and for the motion of the receptor. Thus the temperatures and the time constants of coupling to the baths can be arbitrarily varied for these three types of motion, allowing either a frozen or a flexible receptor and allowing control of search rate without disturbance of internal structure. In addition, an extra repulsive term between substrate and protein was applied to smooth the interaction. The method was applied to a model substrate docking onto a model surface, and to the docking of phosphocholine onto immunoglobulin McPC603, in both cases with a frozen receptor. Using translational temperatures of the substrate in the range of 1300-1700 K and room temperature for the internal degrees of freedom of the substrate, an efficient nontrapping exploratory search ("helicopter view") is obtained which visits the correct binding sites. Low energy conformations can then be further investigated by separate search or by dynamic simulated annealing. In both cases the correct minima were identified. The possibility to work with flexible receptors is discussed.


Percutaneous pinning of pediatric supracondylar humerus fractures with the semisterile technique: the Miami experience.
Pediatric supracondylar humerus fractures are common injuries. The standard of care for management of displaced supracondylar fractures has become closed reduction and percutaneous pinning of the fracture in the operating room. We have been using a "semisterile" surgical technique, similar to what is used when placing a traction pin at the bedside. The purpose of this study was to evaluate our cases from 2000-2004 requiring closed reduction and percutaneous pinning to determine if this method had an infection rate comparable to what is reported in the literature. A total of 304 cases were identified. There were no superficial pin track infections or deep infections requiring treatment in any patient. A review of the literature regarding percutaneous pinning of supracondylar humerus fractures reveals an overall infection rate of 2.34% (45/1922) with a deep infection rate of 0.47% (9/1922). Consequently, the use of the semisterile technique is safe and an efficient way to handle these cases in saving time, cost, and materials. We also found that the administration of perioperative antibiotics may not be necessary as 68% of our patients did not receive any antibiotics during the perioperative or postoperative period. Finally, we found that 37% of our patients were discharged home the same day the surgery was performed, and there were no cases of compartment syndrome or Volkmann ischemic contracture. This indicates that observation overnight in the hospital may not be necessary for every patient.


Postnatal psychiatric morbidity: a validation study of the GHQ-12 and the EPDS as screening tools.
To assess the validity of the 12-Item General Health Questionnaire (GHQ-12) and the Edinburgh Postnatal Depression Scale (EPDS) in screening for the most common postnatal psychiatric morbidities (mood, anxiety and adjustment disorders). A two-phase cross-sectional study was designed. First, a sample of 1453 women visiting at 6 weeks postpartum completed the GHQ-12 and the EPDS questionnaires. Second, based upon EPDS outcomes, participants were stratified and randomly selected within each stratum for clinical evaluation [Structured Clinical Interview for DSM-IV (SCID)]. Receiver operating characteristic (ROC) analysis was used. The concurrent validity was satisfactory (0.80). At optimum cut-off scores, both GHQ-12 and EPDS yielded very good sensitivity (80; 85.5) and specificity (80.4; 85.3), respectively. ROC curves showed that the performance of the EPDS (AUC=0.933) is slightly superior to that of GHQ-12 (AUC=0.904). Both GHQ-12 and EPDS are valid instruments to detect postnatal depression as well as postnatal anxiety and adjustment disorders.


Improvement of the surface hydrophilic properties of naproxen particles with addition of hydroxypropylmethyl cellulose and sodium dodecyl sulphate: In vitro and in vivo studies.
In this study, a new surface-modified naproxen was developed to enhance brain concentration in acute migraine treatment. Fast-dissolving naproxen granules were made by mixing hydroxypropylmethylcellulose (HPMC) sodium dodecyl sulphate (SDS) and sodium croscarmellose with micronized naproxen particles. The aim of this study was to evaluate the effect of adding proportions of SDS to the HPMC film caused changes in the polymer chains of the HPMC, producing a new hydrophilic HPMC-SDS structure. These formulations with different HPMC/SDS ratios were characterised using electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). SDS 10% (w/w) produced a highly hydrophilic HPMC-SDS structure on the surface of the naproxen microparticles. The fast dissolution granules (SF-10%) showed a significant improvement in the dissolution rate of naproxen. Pharmacokinetic studies were conducted with mice, showing an improvement of Cmax (1.38 and 1.41-fold) and AUC0-2h (30% and 10% higher) for plasma and brain samples compared to the reference naproxen suspension. The faster Tmax ratio for SF-10% may be related to increased hydration in the gastrointestinal environment, enabling the drug to permeate the gastrointestinal hydration layer more easily due to the presence of the hydrophilic HPMC-SDS structure in the formulation.


Cytokine induction of sol-gel-derived TiO2 and SiO2 coatings on metallic substrates after implantation to rat femur.
Material surface is a key determinant of host response on implanted biomaterial. Therefore, modification of the implant surface may optimize implant-tissue reactions. Inflammatory reaction is inevitable after biomaterial implantation, but prolonged inflammation may lead to adverse reactions and subsequent implant failure. Proinflammatory activities of cytokines like interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) are attractive indicators of these processes and ultimately characterize biocompatibility. The objective of the study was to evaluate local cytokine production after implantation of stainless steel 316L (SS) and titanium alloy (Ti6Al4V) biomaterials coated with titanium dioxide (TiO2) and silica (SiO2) coatings prepared by sol-gel method. Biomaterials were implanted into rat femur and after 12 weeks, bones were harvested. Bone-implant tissue interface was evaluated; immunohistochemical staining was performed to identify IL-6, TNF-α, and Caspase-1. Histomorphometry (AxioVision Rel. 4.6.3 software) of tissue samples was performed in order to quantify the cytokine levels. Both the oxide coatings on SS and Ti6Al4V significantly reduced cytokine production. However, the lowest cytokine levels were observed in TiO2 groups. Cytokine content in uncoated groups was lower in Ti6Al4V than in SS, although coating of either metal reduced cytokine production to similar levels. Sol-gel TiO2 or SiO2 coatings reduced significantly the production of proinflammatory cytokines by local tissues, irrespective of the material used as a substrate, that is, either Ti6Al4V or SS. This suggests lower inflammatory response, which directly points out improvement of materials' biocompatibility.


Clinical profile of dengue during 2005 outbreak in Kolkata and predictive markers of dengue haemorrhagic fever.
Epidemics of dengue outbreak are frequent in south-east Asian countries. Dengue is a major cause of morbidity and mortality in this region. This prospective observational study was done at Dr BC Roy Memorial for Children during the outbreak in 2005 in Kolkata to know the clinical pattern of dengue cases and to find the possible markers of development of dengue hemorrhagic fever. Two hundred and eighty seropositive cases of dengue were included in the study. Among paediatric population, 5 to 10 years age group was most commonly affected. One-sixth of the cases were from villages indicating the extension of the epidemic in rural areas. Abrupt onset of high fever, non-purulent conjunctival injection, erythematous lips, flushed appearance, myalgia, arthralgia, headache and thrombocytopenia were the predominant features. Rhinitis and pharyngitis were rarely found. Prolonged fever more than 7 days, flushed appearance, pharyngeal congestion, shock evidence, serous effusion, bleeding manifestations, thrombocytopenia, elevated liver enzymes and elevated PCV were associated with development of dengue haemorrhagic fever and dengue shock syndrome.


Lifetime cumulative effect of reproductive factors on ischaemic heart disease in a prospective cohort.
This study aimed to examine the association between lifetime oestrogen exposure and ischaemic heart disease (IHD), based on the hypothesis that higher lifetime oestrogen exposure is linked to lower cardiovascular risk. In 2004-2008, lifetime cumulative exposure to reproductive factors was assessed among postmenopausal females from the China Kadoorie Biobank using reproductive lifespan (RLS), endogenous oestrogen exposure (EEE) and total oestrogen exposure (TEE). EEE was calculated by subtracting pregnancy-related and contraceptive use duration from RLS, while TEE by adding up the same components except for lactation. Incident IHD during follow-up (2004-2015) was identified. Stratified Cox proportional hazards models estimated the HRs and 95% CIs of IHD for RLS, EEE and TEE. Among 118 855 postmenopausal females, 13 162 (11.1%) developed IHD during a median follow-up of 8.9 years. The IHD incidence rates were 13.0, 12.1, 12.5, 13.8 per 1000 person-years for RLS Q1-Q4, 15.8, 12.6, 11.3, 12.1 per 1000 person-years for EEE Q1-Q4 and 13.7, 12.3, 12.2, 13.4 per 1000 person-years for TEE Q1-Q4. The highest quartile (Q4) of RLS and TEE were associated with lower risks of IHD (adjusted HR (aHR) 0.95, 95% CI 0.91 to 1.00 and 0.92, 95% CI 0.88 to 0.97, respectively) compared with the lowest quartile (Q1). Longer EEE showed progressively lower risks of incident IHD (aHR 0.93, 95% CI 0.88 to 0.97; 0.88, 95% CI 0.84 to 0.93; 0.87, 95% CI 0.83 to 0.92 for Q2-Q4 vs Q1). Longer RLS, TEE and EEE were associated with lower risks of IHD among Chinese postmenopausal females.


Maxillary sinus augmentation: evidence-based decision making with a biological surgical approach.
Sinus elevation surgery has been used by the dental profession to increase bone quantity in the posterior maxilla for the placement of root-form implants. The original treatment protocol was developed using existing bone-healing theories that relied on expert opinion. In 2003 and 2004, 2 evidence-based literature reviews were published, expanding significantly on the previous review of 1996. The new reviews were based on the best studies available and were designed to present information that would help clinicians achieve more favorable outcomes. This article discusses this information and answers further questions relating to the sinus elevation procedure.


Impaired therapeutic vasculogenesis by transplantation of OxLDL-treated endothelial progenitor cells.
Previous in vitro studies have revealed that oxidized low density lipoprotein (OxLDL) has negative effects on the proliferation and activity of endothelial progenitor cells (EPCs). Here, we evaluated the effect of OxLDL on the therapeutic potential of EPCs in ischemia-induced neovascularization. EPCs derived from mobilized human peripheral blood mononuclear cells were cultured without or with OxLDL before transplantation. Hindlimb ischemia models were surgically induced in athymic nude mice, which then received an intracardiac injection of 3 x 10(5) EPCs. By laser Doppler perfusion image and ischemia damage score, we found that blood perfusion and ischemia damage were less well recovered in the OxLDL-treated EPC transplantation group than in controls. Histological examination showed fewer transplanted EPCs and lower capillary density in ischemic tissue. Local delivery of Stromal cell-derived factor (SDF-1) restored this defect and improved blood perfusion by recruiting OxLDL-treated EPCs to the ischemic area and increasing host capillary density. These results provide for the first time direct evidence that OxLDL impaired the therapeutic potential of EPCs in ischemia-induced neovascularization through an inhibitory effect on the migration, adhesion, and incorporation of EPCs into vasculature and/or entrapment in the perivascular region in vivo. A therapeutic strategy based on SDF-1 administration ameliorated such defects and improved postischemic neovascularization.


Photocatalytic oxidation of organic compounds in a hybrid system composed of a molecular catalyst and visible light-absorbing semiconductor.
Photocatalytic oxidation of organic compounds proceeded efficiently in a hybrid system with ruthenium aqua complexes as catalysts, BiVO4 as a light absorber, [Co(NH3)5Cl](2+) as a sacrificial electron acceptor and water as an oxygen source. The photogenerated holes in the semiconductor are used to oxidize molecular catalysts into the high-valent Ru(IV)=O intermediates for 2e(-) oxidation.


Acquired hyponatremia in pediatric living donor liver transplantation.
The aim of this study was to evaluate the incidence of acquired hyponatremia (AH) in our pediatric living donor liver transplantation (LDLT) patients, and to identify the potential predictive risk factors of the causes of AH. The 189 pediatric LDLT patients were divided into 2 groups: serum sodium level at the end of the surgery lower than 130 mEq/L in GI (n=16) and higher than 130 mEq/L in GII (n=173). Patients' data were analyzed by Mann-Whitney U test, univariate analysis, and multiple binary logistic regression model. The Hosmer-Lemeshow goodness-of-fit test was used to evaluate the logistic model formulated. P value <0.05 was regarded as statistically significant. In the multiple binary logistic regression model, the hypotonic solution administration rate (ml/kg/h) was the only independent predictor of AH with a p<0.017. Receiver operating curve (ROC) analysis indicated that giving more than 3.5 ml/kg/h hypotonic solution infusion may cause AH. Preoperative hyponatremia did not increase the incidence of acquired hyponatremia. Increasing the administration of hypotonic solution by 1 ml/kg/h in pediatric LDLT would increase the risk of developing AH by 1.272 times. The critical administration rate of hypotonic solution was 3.5 ml/kg/h.


[Evaluating the feature of hypoglycemia detected by continuous glucose monitoring system during temporary continuous subcutaneous insulin infusion in type 2 diabetes patients].
To use continuous glucose monitoring system (CGMS) to investigate the features of hypoglycemia in control of hyperglycemia in T2DM patients by continuous subcutaneous insulin infusion (CSII) and to study the influencing factors of hypoglycemia. Sixty-one T2DM patients, 35 males and 26 females, age 23-88, with the disease duration of 0.5-12 years, HbA1c level of (11.1 +/- 1.6)%, and glycosylated serum protein of (32 +/- 6)%, underwent. CSII and finger blood sugar test. On the second day CGMS was used for 72 hours. Logistic regression was used to analyze the correlation among different factors. CGMS discovered 31 hypoglycemic events in 18 patients in the early stage of CSII treatment, 20 events occurring at night, a number significantly higher than that by self-monitoring of blood sugar. The C-peptide and mean blood glucose (BMG) of the patients with hypoglycemia.were significantly lower than those of the patients without hypoglycemia, and the total cholesterol, standard deviation of blood glucose (SDBG), and insulin pump basal rate of the patients with hypoglycemia were significantly higher than those of the patients without hypoglycemia (all P < 0.05). Multiple regression indicated that MBG was negatively correlated with hypoglycemia but SDBG and basal rate were positively correlated with hypoglycemia. (1) Hypoglycemia detected by CGMS occurs in about 1/3 of the type 2 diabetes patients at the early stage of CSII therapy. (2) In addition of MBG and insulin pump basal rate, glycemic excursion is related closely to hypoglycemia.


A Simple Technique to Prevent Early or Late EndoButton Deployment in Anterior Cruciate Ligament Reconstructions: A Technical Note.
The use of suspensory graft fixation methods in arthroscopic reconstruction of the anterior cruciate ligament has become increasingly popular with the more frequent use of tendon grafts and anatomical techniques involving the creation of bone tunnels. An important technical step to ensure adequate fixation of the graft when using EndoButton-type implants, particularly in the femur, involves flipping the EndoButton plate at the correct length to avoid performing this maneuver before the appropriate time or leaving soft tissue between the plate and lateral cortex of the femur. In the present study, we describe a simple arthroscopic technique for indicating the correct time to flip/deploy the EndoButton plate.


The involvement of microRNAs in neurodegenerative diseases.
Neurodegenerative diseases (NDDs) originate from a loss of neurons in the central nervous system and are severely debilitating. The incidence of NDDs increases with age, and they are expected to become more common due to extended life expectancy. Because no cure is available, these diseases have become a major challenge in neurobiology. The increasing relevance of microRNAs (miRNAs) in biology has prompted investigation into their possible involvement in neurodegeneration in order to identify new therapeutic targets. The idea of using miRNAs as therapeutic targets is not far from realization, but important issues need to be addressed before moving into the clinics. Here, we review what is known about the involvement of miRNAs in the pathogenesis of NDDs. We also report the miRNA expression levels in peripheral tissues of patients affected by NDDs in order to evaluate their application as biomarkers of disease. Finally, discrepancies, innovations, and the effectiveness of collected data will be elucidated and discussed.


Baclofen infused in rat hippocampal formation impairs spatial learning.
Recent studies show that baclofen, a selective GABA(B) agonist, impairs different kinds of learning. In the present study we investigated the effect of microinfused baclofen into the hippocampus of male Wistar rats, on the performance in the Morris water maze. Rats of 8-10 weeks of age were implanted with cannulae aimed bilaterally at the hippocampal formation. Baclofen (1 microl of 0.2 mM, 2.0 mM, and 20.0 mM) or sterilized saline was microinfused 1 h before each daily session (3 trials/session, 1 session/day) for 4 days. On the fifth day, the animals did not receive drug or saline injections and the retention of the location of the escape platform was tested in a 30 s free swim trial. Results from the free swim trial indicate that the doses of baclofen used during training affected the ability of the rats to swim to the target quadrant. Although no significant difference compared with the saline group was observed, the experimental rats showed a more generalized swim trajectory in the area of the target and both adjacent quadrants. Moreover, 1 microl of 20.0 mM baclofen also impaired the acquisition. We suggest that baclofen has an impairing action on spatial learning, although more studies should be conducted to reach a more precise conclusion.


Semen parameters can be predicted from environmental factors and lifestyle using artificial intelligence methods.
Fertility rates have dramatically decreased in the last two decades, especially in men. It has been described that environmental factors as well as life habits may affect semen quality. In this paper we use artificial intelligence techniques in order to predict semen characteristics resulting from environmental factors, life habits, and health status, with these techniques constituting a possible decision support system that can help in the study of male fertility potential. A total of 123 young, healthy volunteers provided a semen sample that was analyzed according to the World Health Organization 2010 criteria. They also were asked to complete a validated questionnaire about life habits and health status. Sperm concentration and percentage of motile sperm were related to sociodemographic data, environmental factors, health status, and life habits in order to determine the predictive accuracy of a multilayer perceptron network, a type of artificial neural network. In conclusion, we have developed an artificial neural network that can predict the results of the semen analysis based on the data collected by the questionnaire. The semen parameter that is best predicted using this methodology is the sperm concentration. Although the accuracy for motility is slightly lower than that for concentration, it is possible to predict it with a significant degree of accuracy. This methodology can be a useful tool in early diagnosis of patients with seminal disorders or in the selection of candidates to become semen donors.


In vitro characterisation of the interaction between newly synthesised proteins and a pancreatic isoform of protein disulphide isomerase.
The lumen of the endoplasmic reticulum (ER) contains an array of molecular chaperones and folding factors that modulate the folding and assembly of newly synthesised proteins entering the secretory pathway. One of these components, protein disulphide isomerase (PDI), facilitates the formation of the correct disulphide bonds within newly synthesised polypeptides, and is the archetype for a family of sequence related PDI-like proteins. We have investigated the interaction between a recently identified, pancreas-specific PDI-like protein (PDIp), and in vitro synthesised secretory and membrane proteins produced in the presence of ER-derived canine pancreatic microsomes. We have previously established that a second PDI-like protein, ERp57, interacts specifically with N-glycosylated proteins. In contrast, we find that the interaction of PDIp with newly synthesised proteins occurs independently of any requirement for N-linked glycosylation. In this respect, the properties of PDIp mirror those of archetypal PDI. When the carbohydrate-dependent interactions between glycoproteins and ERp57 are blocked by drug treatment, the association of these precursors with both PDIp and PDI is enhanced. We propose that PDI-like proteins have overlapping specificity and may exhibit some degree of functional redundancy.


A rare case of congenital epidermoid cyst of the hard palate.
Epidermoid cysts are benign conditions that are thought to derive from abnormally situated ectodermal inclusions in the oral cavity. They are generally found in hands, fingers, feet, ovaries and testicles but in oral cavity they represent a very rare event. This is the first case of an intraosseous epidermoid cyst situated in the hard palate. Healing was uneventful and there was no sign of recurrence in 2-years follow-up.


Health care services use by adolescents with intakes into an outpatient alcohol and drug treatment program.
We examined utilization and cost in the 1 year pre- and post-intake among a sample of adolescents (N=419) entering chemical dependency (CD) treatment. Multivariate analyses showed that these youth used significantly more medical services than a demographically matched sample of members without substance use (SU) problems. Their utilization and costs were higher than matched members, and they did not show the same reductions in post-treatment costs that adults do. This is of concern since it would appear that the medical and mental health problems of adolescents entering CD treatment may be so severe that there are no short-term reductions in post-treatment cost, including ER and hospitalizations.


Allogeneic marrow transplantation.
After 15 years of clinical investigation, allogeneic marrow transplantation can be considered the treatment of choice for a variety of hematologic and immunologic diseases. This review has focused upon some of the principles, current results, problems, and future directions in allogeneic marrow grafting.


Activation of 5-HT1A Receptors in the Hypothalamic Paraventricular Nuclei Negatively Regulates Cytochrome P450 Expression and Activity in Rat Liver.
Our recent work suggested a negative effect for the serotonergic innervation of the paraventricular nuclei (PVN) of the hypothalamus on growth hormone secretion and growth hormone-dependent expression of CYP2C11. The aim of our present research was to determine the effect of the activation of the 5-hydroxytryptamine [(5-HT) serotonin] 5-HT1 or 5-HT2 receptors in the PVN on the expression and activity of cytochrome P450 in male rat liver. The serotonergic agonists 5-carboxyamidotryptamine [(5-CT), a 5-HT1 receptor-type agonist], 8-hydroxy-2-(di-n-propyloamino)-tetralin [(8-OH-DPAT), a 5-HT1A receptor agonist], sumatriptan (a 5-HT1B/D receptor agonist), and 2,5-dimethoxy-4-iodoamphetamine [(DOI), a 5-HT2A/C receptor agonist] were individually injected into the PVN. The liver cytochrome P450 activity and expression and the levels of serum and pituitary and hypothalamic hormones were measured. 5-CT and 8-OH-DPAT significantly decreased the activity and expression of CYP2C11 at both the mRNA and protein levels, which was accompanied by an increase in pituitary and hypothalamic somatostatin levels and a decrease in the serum growth hormone concentration. The expression of CYP3A1/23 also decreased. The serum corticosterone concentration declined after the injection of 8-OH-DPAT. The obtained results indicated that 5-HT1A but not the 5-HT1B/D or 5-HT2 receptors in the PVN are engaged in the negative neuroendocrine regulation of cytochrome P450 via the stimulation of hypothalamic somatostatin secretion and in the decreases in the serum growth hormone and corticosterone concentrations. Since the affected enzymes metabolize steroids and drugs and 5-HT1A receptors are engaged in the action of psychotropic drugs, the results obtained may be of both physiologic and pharmacological meaning.