Effectiveness of manual therapy applied to craniomandibular structures in temporomandibular disorders: A systematic review.
Within physical therapy, manual therapy is known to be effective for managing temporomandibular disorders (TMDs). However, manual therapy is a broad term including different approaches applied to different body regions. This is the first systematic review that aims to evaluate the effectiveness of manual therapy applied specifically to the craniomandibular structures (Cranio-Mandibular Manual Therapy [CMMT]) on pain and maximum mouth opening in people with TMD. This systematic review was developed based on a pre-determined published protocol which was prospectively registered with PROSPERO (CRD42019160213). A search of MEDLINE, Embase, CINAHL, ZETOC, Web of Science, SCOPUS, PEDro, PubMed, Cochrane Library and Best Evidence, EBM reviews-Cochrane Central Register of Controlled Trials, Index to Chiropractic Literature ChiroAccess and Google Scholar databases was conducted from inception until October 2020. Randomised controlled trials comparing the effect of CMMT on pain and maximum mouth opening versus other types of treatment in TMDs were included. Two reviewers independently screened articles for inclusion, extracted data, assessed risk of bias with the revised Cochrane risk of bias tool for randomised trials and evaluated the overall quality of evidence with the Grading of Recommendations, Assessment, Development and Evaluations. A total of 2720 records were screened, of which only 6 (293 participants) satisfied the inclusion criteria. All studies showed some concerns in risk of bias, except for one, which was high risk of bias. The overall quality of evidence was very low for all outcomes because of high heterogeneity and small sample sizes. All studies showed a significant improvement in pain and maximum mouth opening for CMMT from baseline in the mid-term, but only two showed superiority compared to other interventions. Given the high heterogeneity and small sample sizes of the included studies, a quantitative synthesis was not performed. There is the need for future high methodology research investigating different manual therapy techniques applied to different regions and different populations (e.g., chronic versus acute TMD) to determine what is most effective for pain and maximum mouth opening in patients with TMDs.


Archaeology, science and forensic anthropology: a tribute to Dr T. Dale Stewart.
The name, T. Dale Stewart is synonymous with physical anthropology. To many members of the physical anthropology section, particularly those born in the latter half of this century, he is perhaps best known for his 1979 Essentials of Forensic Anthropology. Without a doubt, much of the foundation of this discipline rests upon his teachings and influence. Few knew him in the capacity that William M. Bass did, as T. Dale Stewart was a member of Bass doctoral committee. Bass was greatly influenced during the time he spent working with Dr. Stewart in the 1950's and the instruction and guidance Stewart instilled in Bass has and will continue to be passed on to subsequent generations. Research was Dale Stewart's main emphasis and he succeeded in demonstrating the value of investigation and how results were crucial in explaining many of the processes manifest on skeletal material. Clearly his hypothesis-based approach became essential to skeletal biology and numerous procedures and methods employed in the field are synonymous with the teachings of Dr. T. Dale Stewart. By reflecting on several recently completed interdisciplinary research projects, the far-reaching impact of his knowledge and instruction can be demonstrated.


Transcriptional up-regulation of intracellular adhesion molecule-1 in human endothelial cells by the antioxidant pyrrolidine dithiocarbamate involves the activation of activating protein-1.
The redox status of the cell plays an essential role in regulating signal transduction, transcription factor activity, and expression of cell surface molecules. In this study, we show that pyrrolidine dithiocarbamate (PDTC), a potent antioxidant agent, upregulated the cell surface expression of intercellular adhesion molecule-1 (ICAM-1) in human endothelial cells (EC). Further analysis of PDTC-mediated ICAM-1 up-regulation revealed that PDTC increased ICAM-1 mRNA levels and augmented its gene promoter activity. Transfection experiments in EC with reporter constructs harboring nested deletion fragments of the ICAM-1 promoter indicated the presence of a functional PDTC-responsive region located between positions -136 to -353 of the promoter. Gel retardation assays together with supershift analysis revealed that PDTC induced the binding of c-fos and c-jun to a consensus activating protein-1 (AP-1) binding site located at position -284. PDTC alone or in combination with TNF-alpha enhanced AP-1-dependent transactivation in HUVEC, as determined by DNA binding assays. The functional implication of AP-1 in the transcription of the ICAM-1 gene was further demonstrated by cotransfection experiments in which a c-jun expression vector induced the promoter activity of the PDTC-responsive element of the ICAM-1 promoter. Taken together, these results indicate that the antioxidant PDTC induces transcriptional activation of ICAM-1 and that this induction is mediated at least in part by the transcription factor AP-1. This mechanism might be operative in pathologic conditions in which a redox imbalance plays a key role, such as ischemia/reperfusion injury or arteriosclerosis.


Comparing the self concept of children with cerebral palsy to the perceptions of their parents.
Understanding self concept is important for therapists treating children with cerebral palsy because knowing what children and parents think about perceived competencies and adequacies can be taken into account in determining treatment goals. This study investigated: (i) If differences existed between the self concept ratings of children with cerebral palsy compared to their parent's perception of their child's abilities and attributes, and (ii) the strength of association between the child and parent ratings. Thirty children (14 females, 16 males; mean age 11 years 5 months, SD 2 years 6 months, range 8-16 years) with spastic hemiplegia or diplegia and gross motor skills classified as level I or II on the Gross Motor Function Classification System rated their self-concept using the Self-Perception Profile for Children questionnaire. Their parents completed the accompanying Parent Rating Scale. Group differences between the parents and children were found for the domains of Athletic Competence and Physical Appearance. There was either no relationship or a low level of association between the child and parent ratings in all five domains of self concept assessed. Parents were unable to evaluate their child's self concept accurately suggesting health professionals should gather such information from the child themselves.


Cell fusion by Semliki Forest, influenza, and vesicular stomatitis viruses.
Representatives of three families of enveloped viruses were shown to fuse tissue culture cells together. These were: Semliki Forest virus (SFV, a togavirus), vesicular stomatitis virus (a rhabdovirus), and two myxoviruses, fowl plaque virus and Japan influenza virus (Japan)/A/305/57). Unlike paramyxoviruses, whose fusion activity is known to occur over a broad pH range, fusion by these viruses was restricted to mildly acidic pH. The pH thresholds for the four viruses were 6.0, 6.1, 5.5, and 5.1, respectively. The precursor form of Japan influenza, which is not infectious and which contains the uncleaved hemagglutinin, had no fusion activity. This result suggested a role for the influenza hemagglutinin in the low-pH-dependent membrane fusion activity. Taken together, our results show that low-pH-induced fusion is a widespread property of enveloped animal viruses and that it may play a role in the infective process. The fusion reactions with all four viruses were fast, efficient, and easy to induce. With UV-inactivated SFV, the fusion was shown to be nonlytic and the polykaryons were viable for at least 12 h. 30 ng of SFV/1 x 10(6) BHK-21 cells were required for 50% fusion, and 250 ng sufficed to fuse the entire culture into a single polykaryon.


[Influence of vagotomy on gastric histamine secretion and the secretion-inhibiting effect of cimetidine].
The influence of vagotomy on histamine gastric secretion and the ability of the H2-blocker cimetidine to suppress histamine gastric secretion was examined in humans and dogs. It was established that vagotomy in humans decreased histamine acid secretion. The relative ability of cimetidine to suppress gastric secretion remained unchanged. In dogs, vagotomy increased acid rather than pepsin secretion stimulated by histamine. The inhibitory effect of cimetidine on acid secretion was more profound in dogs with an intact vagus nerve. It is suggested that vagotomy in dogs but not in humans increased endogenous histamine secretion which intensified the stimulatory effect of endogenous histamine and led to the potentiation of the inhibitory action of cimetidine on histamine acid secretion.


Expression and regulation of type 2A protein phosphatases and alpha4 signalling in cardiac health and hypertrophy.
Cardiac physiology and hypertrophy are regulated by the phosphorylation status of many proteins, which is partly controlled by a poorly defined type 2A protein phosphatase-alpha4 intracellular signalling axis. Quantitative PCR analysis revealed that mRNA levels of the type 2A catalytic subunits were differentially expressed in H9c2 cardiomyocytes (PP2ACβ > PP2ACα > PP4C > PP6C), NRVM (PP2ACβ > PP2ACα = PP4C = PP6C), and adult rat ventricular myocytes (PP2ACα > PP2ACβ > PP6C > PP4C). Western analysis confirmed that all type 2A catalytic subunits were expressed in H9c2 cardiomyocytes; however, PP4C protein was absent in adult myocytes and only detectable following 26S proteasome inhibition. Short-term knockdown of alpha4 protein expression attenuated expression of all type 2A catalytic subunits. Pressure overload-induced left ventricular (LV) hypertrophy was associated with an increase in both PP2AC and alpha4 protein expression. Although PP6C expression was unchanged, expression of PP6C regulatory subunits (1) Sit4-associated protein 1 (SAP1) and (2) ankyrin repeat domain (ANKRD) 28 and 44 proteins was elevated, whereas SAP2 expression was reduced in hypertrophied LV tissue. Co-immunoprecipitation studies demonstrated that the interaction between alpha4 and PP2AC or PP6C subunits was either unchanged or reduced in hypertrophied LV tissue, respectively. Phosphorylation status of phospholemman (Ser63 and Ser68) was significantly increased by knockdown of PP2ACα, PP2ACβ, or PP4C protein expression. DNA damage assessed by histone H2A.X phosphorylation (γH2A.X) in hypertrophied tissue remained unchanged. However, exposure of cardiomyocytes to H2O2 increased levels of γH2A.X which was unaffected by knockdown of PP6C expression, but was abolished by the short-term knockdown of alpha4 expression. This study illustrates the significance and altered activity of the type 2A protein phosphatase-alpha4 complex in healthy and hypertrophied myocardium.


[Urinary bladder organ culture with a continuous nutrient system].
A system of flowing nutrition for organic cultures has been developed with possible observation of explants at small magnifications of microscope. The nutrient fluid circulates by the gravity. The proposed method permits sustaining the vital capacity of explants of the urinary bladder mucosa of young rats with reservation of characteristic organotypical structures and phenomena of the epithelium proliferation as long as 7 weeks. The described method may be used when modelling different pathological processes in tissues.


A systematic scoping review of rodent models of catatonia: Clinical correlations, translation and future approaches.
Catatonia is a psychiatric disorder, which subsumes a plethora of affective, motor and behavioral symptoms. In the last two decades, the number of behavioral and neuroimaging studies on catatonia has steadily increased. The majority of behavioral and neuroimaging studies in psychiatric patients suggested aberrant higher-order frontoparietal networks which, on the biochemical level, are insufficiently modulated by gamma-aminobutyric acid (GABA)-ergic and glutamatergic transmission. However, the pathomechanisms of catatonic symptoms have rarely been studied using rodent models. Here, we performed a scoping review of literature available on PubMed for studies on rodent models of catatonia. We sought to identify what we could learn from pre-clinical animal models of catatonia-like symptoms, their underlying neuronal correlates, and the complex molecular (i.e. genes and neurotransmitter) mechanisms by which its modulation exerts its effects. What becomes evident is that although many transgenic models present catatonia-like symptoms, they have not been used to better understand the pathophysiological mechanisms underlying catatonia so far. However, the identified neuronal correlates of catatonia-like symptoms correlate to a great extent with findings from neuroscience research in psychiatric patients. This points us towards fundamental cortical-striatal-thalamocortical and associated networks modulated by white matter inflammation as well as aberrant dopaminergic, GABAergic, and glutamatergic neurotransmission that is involved in catatonia. Therefore, this scoping review opens up the possibility of finally using transgenic models to help with identifying novel target mechanisms for the development of new drugs for the treatment of catatonia.


Regenerative Endodontic Procedures for Traumatized Teeth after Horizontal Root Fracture, Avulsion, and Perforating Root Resorption.
Traumatic injury to the teeth can cause horizontal root fractures and inflammatory root resorptions (external and internal). Traditionally, traumatized teeth with horizontal root fractures resulting in pulp necrosis and inflammatory root resorptions are treated with conventional root canal therapy. A 15-year-old boy had a history of traumatic injury to mature tooth #8 resulting in horizontal root fracture and pulp necrosis of the coronal fragment. A 7-year-old girl suffered an avulsion injury to immature tooth #9, which developed inflammatory replacement resorption and subsequently root fractured 15 months later. Another 16-year-old boy also suffered a history of traumatic injury to mature tooth #8, resulting in perforating root resorption. All teeth were treated with regenerative endodontic procedures using chemomechanical debridement, calcium hydroxide/triple antibiotic paste dressing, EDTA rinse, induction of periapical bleeding into the canal space, and a coronal mineral trioxide aggregate plug. In the tooth presenting with horizontal root fracture, only the coronal fragment was treated to preserve pulp vitality in the apical fragment for possible pulp tissue regeneration. After regenerative endodontic procedures, clinical signs/symptoms subsided, and inflammatory osteolytic lesions resolved in all traumatized teeth. Two teeth were followed for 19 months and 1 tooth for 5 years. At the last review of the teeth with horizontal root fractures, the first case showed healing by calcified tissue and the second case showed healing by fibrous connective and hard tissue. Tooth with perforating root resorption demonstrated a decrease in size of the resorptive defect. Based on these case reports, regenerative endodontic procedures have the potential to be used to treat traumatized teeth with horizontal root fracture and inflammatory root resorption.


Direct assay for O6-methylguanine-DNA methyltransferase and comparison of detection methods for the methylated enzyme in polyacrylamide gels and electroblots.
We describe in detail a direct assay for the substrate-inactivated DNA-repair enzyme, O6-methylguanine-DNA methyltransferase (O6-MT), which measures the transfer of radiolabelled methyl groups from a prepared O6-methylguanine-DNA substrate to the protein fraction of an enzyme-containing cell/tissue extract. This assay, a modification of a previously suggested method for monitoring O6-ethylguanine-DNA repair [Renard, Verly, Mehta & Ludlum (1983) Eur. J. Biochem. 136, 461-467], is sensitive, highly reproducible, accurate and is, as described here and relative to previously published methods, well suited for use with a large number of test samples. We identified two problems with the O6-[Me-3H]methylguanine-DNA substrate used in the present work and in other reported assay: firstly, that of progressively higher assay backgrounds with increasing age of substrate, which was nullified by once-only purification of the double-stranded substrate by hydroxyapatite chromatography; secondly, a substrate of high specific radioactivity (30 Ci/mmol), made with freshly prepared tritiated methylnitrosourea, behaved as a substrate of 5 Ci/mmol when referenced against radiolabelled O6-methylguanine-DNA made with either [3H]- or [14C]-methylnitrosourea at the lower specific radioactivities of 1 Ci/mmol and 61 mCi/mmol respectively. This apparently stemmed from the known instability of high-specific-radioactivity [3H]methylnitrosourea and indicated that an expected increase in sensitivity of the assay does not necessarily result from increasing the specific radioactivity of substrates above approx. 1 Ci/mmol. Although O6-MT was stable to preincubation at 25 degrees C, marked losses of activity were observed at 37 degrees C, and more so at 45 degrees C. Enzyme lability at the higher temperatures was not, however, seen during preincubation in the presence of its substrate. O6-[Me-3H]methylguanine-DNA, which apparently protected O6-MT against thermal inactivation. As previously seen with other human cells and tissues, extracts of human spleen in the present study showed wide interindividual differences in O6-MT specific activity (18-fold), which spanned the range 50-900 fmol/mg of protein. Cultured human lymphoblastoid Jurkat cells contained approx. 57,000 enzyme molecules/cell. Substrate-inactivated [Me-3H]methylated O6-MT was analysed by SDS/PAGE and electroblotting. The different but similarly sized forms of this enzyme that we previously detected in human spleen [Major, Gardner, Carne & Lawley (1990) Nucleic Acids Res. 18, 1351-1359] were clearly resolved by fluorography of electroblots, but only at considerable expense of time. As expected, scintillation counting of the protein extracted from gel slices and linear-wire scanning of enzyme-associated radioactivity on electroblots were quicker methods for detecting the [Me-3H]methylated inactivated O6-MT.


Hepatitis C.
Hepatitis C has been identified as the most common cause of post-transfusion hepatitis worldwide, accounting for approximately 90% of this disease in Japan, the United States and Western Europe. Hepatitis C is a major global public health problem. New infections continue to occur, and the source of infection includes transfusion of blood or blood products from unscreened donors; transfusion of blood products that have not undergone viral inactivation; parenteral exposure to blood through use of contaminated and inadequately sterilized instruments and needles used in medical, dental and 'traditional' medicine; procedures such as hemodialysis; high risk sexual practices; household or sexual contacts of hepatitis C virus (HCV)-infected persons; and infants of HCV-infected mothers. In many countries, the relative contribution of the various sources of infection has not been defined with population-based epidemiological studies. Such studies are necessary to enable countries to prioritize their preventive measures and to make the most appropriate use of available resources. Given the substantial morbidity and mortality attributable to HCV-related chronic liver disease, each country, irrespective of economic status, should develop a plan of HCV-related public health activities for the prevention of new HCV infections and the treatment of established chronic infections.


Rapid phase change of lipid microdomains in giant vesicles induced by conversion of sphingomyelin to ceramide.
To understand the role of sphingomyelinase (SMase) in the function of biological membranes, we have investigated the effect of conversion of sphingomyelin (SM) to ceramide (Cer) on the assembly of domains in giant unilamellar vesicles (GUVs). The GUVs were prepared from mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), N-palmitoly-D-erythro-sphingosine (C16Cer), N-palmitoyl-D-erythro-sphingosylphosphorylcholine (C16SM) and cholesterol. The amounts of DOPC, sum of C16Cer and C16SM, and cholesterol were kept constant (the ratio of these four lipids is shown as 1:X:1-X:1 (molar ratio), i.e., X is C16Cer/(C16Cer+C16SM)). Shape and distribution of domains formed in the GUVs were monitored by a fluorescent lipid, Texas Red 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (0.1 mol%). In GUVs containing low C16Cer (X=0 and 0.25), round-shaped domains labeled by the fluorescent lipid were present, suggesting coexistence of liquid-ordered and disordered domains. In GUVs containing intermediate Cer concentration (X=0.5), the fluorescent domain covered most of GUV surface, which was surrounded by gel-like domains. Differential scanning calorimetry of multilamellar vesicles prepared in the presence of higher Cer concentration (X>or=0.5) suggested existence of a Cer-enriched gel phase. Video microscopy showed that the enzymatic conversion of SM to Cer caused rapid change in the domain structure: several minutes after the SMase addition, the fluorescent region spread over the GUV surface, within which regions with darker contrast existed. Image-based measurement of generalized polarization (GP) of 6-dodecanoyl-2-dimethylaminonaphthalene (Laurdan), which is related to the acyl chain ordering of the lipids, was performed. Before the SMase treatment domains with high (0.65) and low (below 0.4) GP values coexisted, presumably reflecting the liquid-ordered and disordered domains; after the SMase treatment regions with intermediate GP values (0.5) and smaller regions with higher GP values (0.65) were present. Generation of Cer thus caused a phase transition from liquid-ordered and disordered phases to a gel and liquid phase.


Sympathetic skin response in multiple sclerosis: a meta-analysis of case-control studies.
The usefulness of sympathetic skin responses (SSR) in multiple sclerosis (MS) has been advocated by several studies in the last 20 years; however, due to a great heterogeneity of findings, a comprehensive meta-analysis of case-control studies is in order to pinpoint consistencies and investigate the causes of discrepancies. We searched MEDLINE, EMBASE and Cochrane databases for case-control studies comparing SSR absence frequency and latency between patients with MS and healthy controls. Thirteen eligible studies including 415 MS patients and 331 healthy controls were identified. The pooled analysis showed that SSR can be always obtained in healthy controls while 34% of patients had absent SSRs in at least one limb (95% CI 22-47%; p < 0.0001) but with considerable heterogeneity across studies (I 2 = 90.3%). Patients' age explained 22% of the overall variability and positive correlations were found with Expanded Disability Status Scale and disease duration. The pooled mean difference of SSR latency showed a significant increase in patients on both upper (193 ms; 95% CI 120-270 ms) and lower (350 ms; 95% CI 190-510 ms) extremities. We tested the discriminatory value of SSR latency thresholds defined as the 95% confidence interval (CI) upper bound of the healthy controls, and validated the results on a new dataset. The lower limb threshold of 1.964 s produces the best results in terms of sensitivity 0.86, specificity 0.67, positive predicted value 0.75 and negative predicted value 0.80. Despite a considerable heterogeneity of findings, there is evidence that SSR is a useful tool in MS.


Bioengineering Approaches for the Pancreatic Tumor Organoids Research and Application.
Pancreatic cancer is a highly lethal form of digestive malignancy that poses significant health risks to individuals worldwide. Chemotherapy-based comprehensive treatment is the primary therapeutic approach for midlife and late-life patients. Nevertheless, the heterogeneity of the tumor and individual genetic backgrounds result in substantial variations in drug sensitivity among patients, rendering a single treatment regimen unsuitable for all patients. Conventional pancreatic cancer tumor organoid models are capable of emulating the biological traits of pancreatic cancer and are utilized in drug development and screening. However, these tumor organoids can still not mimic the tumor microenvironment (TME) in vivo, and the poor controllability in the preparation process hinders translation from essential drug screening to clinical pharmacological therapy. In recent years, many engineering methods with remarkable results have been used to develop pancreatic cancer organoid models, including bio-hydrogel, co-culture, microfluidic, and gene editing. Here, this work summarizes and analyzes the recent developments in engineering pancreatic tumor organoid models. In addition, the future direction of improving engineered pancreatic cancer organoids is discussed for their application prospects in clinical treatment.


Prognostic and Diagnostic Utility of Serum Biomarkers in Pediatric Traumatic Brain Injury.
Traumatic brain injury (TBI) remains a major cause of morbidity and death among the pediatric population. Timely diagnosis, however, remains a complex task because of the lack of standardized methods that permit its accurate identification. The aim of this study was to determine whether serum levels of brain injury biomarkers can be used as a diagnostic and prognostic tool in this pathology. This prospective, observational study collected and analyzed the serum concentration of neuronal injury biomarkers at enrollment, 24h and 48h post-injury, in 34 children ages 0-18 with pTBI and 19 healthy controls (HC). Biomarkers included glial fibrillary acidic protein (GFAP), neurofilament protein L (NfL), ubiquitin-C-terminal hydrolase (UCH-L1), S-100B, tau and tau phosphorylated at threonine 181 (p-tau181). Subjects were stratified by admission Glasgow Coma Scale score into two categories: a combined mild/moderate (GCS 9-15) and severe (GCS 3-8). Glasgow Outcome Scale-Extended (GOS-E) Peds was dichotomized into favorable (≤4) and unfavorable (≥5) and outcomes. Data were analyzed utilizing Prism 9 and R statistical software. The findings were as follows: 15 patients were stratified as severe TBI and 19 as mild/moderate per GCS. All biomarkers measured at enrollment were elevated compared with HC. Serum levels for all biomarkers were significantly higher in the severe TBI group compared with HC at 0, 24, and 48h. The GFAP, tau S100B, and p-tau181 had the ability to differentiate TBI severity in the mild/moderate group when measured at 0h post-injury. Tau serum levels were increased in the mild/moderate group at 24h. In addition, NfL and p-tau181 showed increased serum levels at 48h in the aforementioned GCS category. Individual biomarker performance on predicting unfavorable outcomes was measured at 0, 24, and 48h across different GOS-E Peds time points, which was significant for p-tau181 at 0h at all time points, UCH-L1 at 0h at 6-9 months and 12 months, GFAP at 48h at 12 months, NfL at 0h at 12 months, tau at 0h at 12 months and S100B at 0h at 12 months. We concluded that TBI leads to increased serum neuronal injury biomarkers during the first 0-48h post-injury. A biomarker panel measuring these proteins could aid in the early diagnosis of mild to moderate pTBI and may predict neurological outcomes across the injury spectrum.


[State of suicide and effective efforts in suicide prevention in psychiatric hospitals and clinics].
Although factors related to suicide are complicated, mental health disorders are an important risk factor. It is anticipated that suicide prevention measures will be implemented from the perspective of improved psychiatric medicine. No national-scale study has been carried out in Japan on the state of psychiatric medicine and its influence on suicide since 2000. Moreover, many efforts not intended for suicide prevention have been shown to be effective for this purpose. Here, we conducted surveys to obtain basic data on suicide prevention and improvements in mental health care among 1,728 psychiatric hospitals and clinics in Japan in 2010. The incidence of suicide in psychiatric hospitals and clinics from January to December 2009 was estimated to be 100.5 for outpatients and 154.5 for inpatients per 100,000 patients. Regarding the duration from consultation to suicide, 87% of outpatients committed suicide less than one month following their last consultation. Moreover, approximately two-thirds of patients had undergone consultations for more than one year. A number of suicides in psychiatric hospitals and clinics occurred while patients were continuously undergoing treatment. Efforts shown to be effective in suicide prevention included risk assessment with multiple medical staff (i.e., doctors and nurses), a 24-hour crisis line, and a follow-up system for discontinued outpatients. We expect that the results of this survey will aid in the implementation of effective suicide prevention in psychiatric medicine.


Esential oils extraction: a 24-hour steam distillation systematic methodology.
Steam distillation is known to be the most prevalent method of essential oil extraction. Despite many studies on extraction methods, there is no report about the impact of distillation process duration on the yield and oil quality. A new 24-h steam distillation process for extraction of plant essential oils is presented. For improving the total yield, prolonged and continued isolation was used. A selection of plant species from Lamiaceae and Apiaceae families was subjected to direct steam distillation and essential oils were collected at different times (1, 2, 3, 6, 12 and 24 h). The analysis included either annual or perennial species monitored in terms of different harvesting time. From these studies, it is conclusively that there is no rule about appropriate extraction time, and different plants need different periods for the essential oils to achieve the desired quality or quantity of extract. Thus, extraction duration is directly dependent on what the study is conducted for.


Gluten-free diet may alleviate depressive and behavioural symptoms in adolescents with coeliac disease: a prospective follow-up case-series study.
Coeliac disease in adolescents has been associated with an increased prevalence of depressive and disruptive behavioural disorders, particularly in the phase before diet treatment. We studied the possible effects of a gluten-free diet on psychiatric symptoms, on hormonal status (prolactin, thyroidal function) and on large neutral amino acid serum concentrations in adolescents with coeliac disease commencing a gluten-free diet. Nine adolescents with celiac disease, aged 12 to 16 years, were assessed using the semi-structured K-SADS-Present and Lifetime Diagnostic interview and several symptom scales. Seven of them were followed at 1 to 2, 3, and 6 months on a gluten-free diet. Adolescent coeliac disease patients with depression had significantly lower pre-diet tryptophan/ competing amino-acid (CAA) ratios and free tryptophan concentrations, and significantly higher biopsy morning prolactin levels compared to those without depression. A significant decrease in psychiatric symptoms was found at 3 months on a gluten-free diet compared to patients' baseline condition, coinciding with significantly decreased coeliac disease activity and prolactin levels and with a significant increase in serum concentrations of CAAs. Although our results of the amino acid analysis and prolactin levels in adolescents are only preliminary, they give support to previous findings on patients with coeliac disease, suggesting that serotonergic dysfunction due to impaired availability of tryptophan may play a role in vulnerability to depressive and behavioural disorders also among adolescents with untreated coeliac disease.


Problem-based learning: future challenges for educational practice and research.
Problem-based learning (PBL) is widely used in higher education. There is evidence available that students and faculty are highly satisfied with PBL. Nevertheless, in educational practice problems are often encountered, such as tutors who are too directive, problems that are too well-structured, and dysfunctional tutorial groups. The aim of this paper is to demonstrate that PBL has the potential to prepare students more effectively for future learning because it is based on four modern insights into learning: constructive, self-directed, collaborative and contextual. These four learning principles are described and it is explained how they apply to PBL. In addition, available research is reviewed and the current debate in research on PBL is described. It is argued that problems encountered in educational practice usually stem from poor implementation of PBL. In many cases the way in which PBL is implemented is not consistent with the current insights on learning. Furthermore, it is argued that research on PBL should contribute towards a better understanding of why and how the concepts of constructive, self-directed, collaborative and contextual learning work or do not work and under what circumstances. Examples of studies are given to illustrate this issue.


Seroma development following body contouring surgery for massive weight loss: patient risk factors and treatment strategies.
The most common complications following body contouring surgery for massive weight loss include delayed wound healing and seroma. The authors investigated risk factors for seroma in this patient population and describe treatment strategies. A retrospective review of 222 patients who underwent body contouring surgery for massive weight loss from March of 1997 to December of 2005 was performed. Risk factors assessed included age, sex, medical conditions, tobacco use, body mass index, weight of skin excised, and surgery performed. Within this group, there were 187 women and 35 men, with a mean age of 42 years. Weight loss was achieved by open (n = 167) or laparoscopic (n = 35) gastric bypass surgery, or diet (n = 20). Average body mass index at contouring was 33, ranging from 20 to 69. Surgical areas addressed alone or in combination included the abdomen (n = 205), thigh (n = 71), arm (n = 69), back (n = 59), and chest (n = 57). Average weight of skin excised at surgery was 9.6 lb, ranging up to 49 lb. Seroma occurred in 31 patients, placing the risk at 14 percent in this series. Seroma risk in abdominal panniculectomy was 12 percent; in circumferential belt lipectomy, the risk was 18 percent; and in thigh lift, the risk was 4 percent. On multivariate statistical analysis, the major risk factor for seroma formation was weight of skin excised, with seroma risk increasing 9 percent for each additional pound of skin excised. The most important risk factor for seroma is weight of skin excised at the time of surgery. Treatment strategies include aspiration, drain placement, sclerosis, and surgery.


APUD system neoplasms in renal transplant patients.
Apudomas are uncommon neoplasms composed of neuroendocrine cells. They include carcinoid tumors, islet cell tumors, and small cell lung carcinoma. We found six cases of apudomas in a series of 1028 renal transplants from three medical centers (0.58%). One of these had been reported in 1976. The cases included a carcinoid tumor of a Meckel's diverticulum discovered and removed prior to transplantation, with no evidence of recurrence 9 years later. A small cell lung carcinoma was discovered 40 months after renal transplantation, with a fatal outcome 6 months later. Four clinically occult apudomas were found at autopsy, including one gastric and one bronchial carcinoid tumor, one multicentric pancreatic islet cell neoplasm, and one case of multiple ileal carcinoids. With the exception of the small cell lung cancer, none of the apudomas was clinically significant, and none was associated with carcinoid or other paraneoplastic syndrome. These cases illustrate the difficulty of diagnosis of apudomas in patients with renal failure and the usually benign nature of these tumors despite the administration of potent immunosuppressive agents.


Some routine and novel approaches to chemical dosimetry of far-ultraviolet light emitted by bactericidal tubes.
Detailed protocols are presented of two improved chemical procedures, based upon a photochemical decomposition of uranyl oxalate or potassium ferrioxalate, enabling a reliable measurement of the far-ultraviolet light emitted by a low-pressure mercury-vapour lamp. Besides, an original semi-quantitative method of UV dosimetry is presented and discussed, employing optical detection of a chromophore formed in the photo-oxidized glutathione. In addition to exemplary computations of UV light dose rate, a simple formula is proposed for recalculating its value while varying the distance from the lamp.


Quantitative pathologic changes in the human testis after vasectomy. A controlled study.
To determine whether there are any deleterious changes in the human testis after vasectomy, we obtained testicular biopsy specimens from 31 healthy men undergoing vasectomy reversal and from 21 healthy, fertile volunteers. Morphometric analyses of these specimens revealed a 100 per cent increase in the thickness of the seminiferous tubular walls (P less than 0.001), a 50 per cent increase in the mean cross-sectional tubular area (P less than 0.001), and a significant reduction in the mean number of Sertoli cells (P less than 0.01) and spermatids (P less than 0.01) per tubular cross section in the post-vasectomy group, as compared with the control group. Focal interstitial fibrosis was observed in 23 per cent of the specimens from the post-vasectomy group and in none from the control group. There was a significant correlation (P less than 0.01) between interstitial fibrosis and infertility in patients who underwent a surgically successful vasectomy reversal (sperm in the ejaculate). None of the other measured characteristics correlated with infertility after vasectomy reversal. We conclude that significant morphologic changes occur in the human testis after vasectomy. The presence of focal interstitial fibrosis was associated with a high incidence of infertility in this series.


Islet-specific Th1, but not Th2, cells secrete multiple chemokines and promote rapid induction of autoimmune diabetes.
Migration of CD4 cells into the pancreas represents a hallmark event in the development of insulin-dependent diabetes mellitus. Th1, but not Th2, cells are associated with pathogenesis leading to destruction of islet beta-cells and disease onset. Lymphocyte extravasation from blood into tissue is regulated by multiple adhesion receptor/counter-receptor pairs and chemokines. To identify events that regulate entry of CD4 cells into the pancreas, we transferred Th1 or Th2 cells induced in vitro from islet-specific TCR transgenic CD4 cells into immunodeficient (NOD.scid) recipients. Although both subsets infiltrated the pancreas and elicited multiple adhesion receptors (peripheral lymph node addressin, mucosal addressin cell adhesion molecule-1, LFA-1, ICAM-1, and VCAM-1) on vascular endothelium, entry/accumulation of Th1 cells was more rapid than that of Th2 cells, and only Th1 cells induced diabetes. In vitro, Th1 cells were also distinguished from Th2 cells by the capacity to synthesize several chemokines that included lymphotactin, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1alpha, whereas both subsets produced macrophage inflammatory protein-1beta. Some of these chemokines as well as RANTES, MCP-3, MCP-5, and cytokine-response gene-2 (CRG-2)/IFN-inducible protein-10 (IP-10) were associated with Th1, but not Th2, pancreatic infiltrates. The data demonstrate polarization of chemokine expression by Th1 vs Th2 cells, which, within the microenvironment of the pancreas, accounts for distinctive inflammatory infiltrates that determine whether insulin-producing beta-cells are protected or destroyed.


Age-related different relationships between ectopic adipose tissues and measures of central obesity in sedentary subjects.
Accumulation of fat at ectopic sites has been gaining attention as pivotal contributor of insulin resistance, metabolic syndrome and related cardiovascular complications. Intermuscular adipose tissue (IMAT), located between skeletal muscle bundles and beneath muscle fascia, has been linked to physical inactivity, ageing and body mass index, but little is known about its relationship with the other AT compartments, in particular with increasing age. To address this issue, erector spinae IMAT, epicardial (EAT), intraabdominal (IAAT) and abdominal subcutaneous adipose tissue (SAT) were simultaneously measured by Magnetic Resonance Imaging (MRI) and related to waist circumference measurements and age in 32 sedentary subjects without cardiovascular disease (18 men; 14 women; mean age 48.5 ± 14 years). Fasting glucose, triglycerides and HDL-cholesterol were also assessed. We observed that, after dividing individuals according to age (≤ or > 50 years), IMAT and EAT depots were significantly more expanded in older subjects (63.2 ± 8.3 years) than in the younger ones (38.4 ± 5.2 years) (p < 0.001). Overall, both IMAT and EAT showed stronger positive associations with increasing age (β = 0.63 and 0.67, respectively, p < 0.001 for both) than with waist circumference (β = 0.55 and 0.49, respectively, p < 0.01 for both) after adjusting for gender. In addition, the gender-adjusted associations of IMAT and EAT with waist circumference and IAAT were significant in individuals ≤ 50 years only (p<0.05 for all) and not in the older ones. In contrast, no age-related differences were seen in the relationships of IAAT and SAT with waist circumference. Finally, serum triglycerides levels turned out not to be independently related with ectopic IMAT and EAT. In conclusion, the expansion of IMAT and EAT in sedentary subjects is more strongly related to age than waist circumference, and a positive association of these ectopic depots with waist circumference and IAAT amount can be postulated in younger individuals only.


Effect of Radiofrequency on Dorsal Root Ganglion Versus Transforaminal Steroids Injection on Tumor Necrosis Factor-Alpha Level in Lumbar Radicular Pain.
The mechanism of pain control with pulsed radiofrequency (PRF) is unclear. We aimed to compare the efficacy of combined PRF on dorsal root ganglion (DRG) with transforaminal epidural steroid injection (TFESI) vs TFESI-alone on pain improvement and serum tumor necrosis factor-alpha (TNF-a) level in lumbar disc-related radicular pain. Prospective, randomized, controlled trial. Neurology and Pain Management clinics. A total of 80 patients with lumbar disc prolapse were divided into 2 groups: combined PRF on DRG with TFESI group and TFESI-alone group. The Numeric Rating Scale (NRS-11), Oswestry Disability Index (ODI), and Functional Rating Index (FRI) before intervention and at 2 weeks, 1 month, and 3 months after the intervention were observed. Serum TNF-a level was assessed pre- and post-intervention at 3 months. The scores of NRS-11, ODI, and FRI showed a significant improvement at 2 weeks, 1 month, and 3 months following intervention in both combined PRF & TFESI group and TFESI-alone group (P < 0.001 in all comparisons), with no significant difference between the 2 groups. Serum TNF-a levels showed a statistically significant reduction, 3 months following intervention in the combined PRF & TFESI group (P < 0.001), but not in the TFESI-alone group (P = 0.297) (P between groups < 0.001). The main limitation of this study is that TNF-a level was not assessed earlier to see how long the steroids might reduce TNF-a. On the other hand, further study with extended follow-up periods is needed to confirm the long-term lowering effect of TNF-a provided by PRF. Combined PRF on DRG with TFESI showed similar outcomes to TFESI-alone in relieving pain in patients with lumbar disc prolapse. However, PRF on DRG caused a significant decrease in TNF-a serum levels at 3 months.


Enhanced Enzyme Reuse through the Bioconjugation of L-Asparaginase and Silica-Based Supported Ionic Liquid-like Phase Materials.
L-asparaginase (ASNase) is an amidohydrolase that can be used as a biopharmaceutical, as an agent for acrylamide reduction, and as an active molecule for L-asparagine detection. However, its free form displays some limitations, such as the enzyme's single use and low stability. Hence, immobilization is one of the most effective tools for enzyme recovery and reuse. Silica is a promising material due to its low-cost, biological compatibility, and tunable physicochemical characteristics if properly functionalized. Ionic liquids (ILs) are designer compounds that allow the tailoring of their physicochemical properties for a given task. If properly designed, bioconjugates combine the features of the selected ILs with those of the support used, enabling the simple recovery and reuse of the enzyme. In this work, silica-based supported ionic liquid-like phase (SSILLP) materials with quaternary ammoniums and chloride as the counterion were studied as novel supports for ASNase immobilization since it has been reported that ammonium ILs have beneficial effects on enzyme stability. SSILLP materials were characterized by elemental analysis and zeta potential. The immobilization process was studied and the pH effect, enzyme/support ratio, and contact time were optimized regarding the ASNase enzymatic activity. ASNase-SSILLP bioconjugates were characterized by ATR-FTIR. The bioconjugates displayed promising potential since [Si][N3444]Cl, [Si][N3666]Cl, and [Si][N3888]Cl recovered more than 92% of the initial ASNase activity under the optimized immobilization conditions (pH 8, 6 × 10-3 mg of ASNase per mg of SSILLP material, and 60 min). The ASNase-SSILLP bioconjugates showed more enhanced enzyme reuse than reported for other materials and immobilization methods, allowing five cycles of reaction while keeping more than 75% of the initial immobilized ASNase activity. According to molecular docking studies, the main interactions established between ASNase and SSILLP materials correspond to hydrophobic interactions. Overall, it is here demonstrated that SSILLP materials are efficient supports for ASNase, paving the way for their use in the pharmaceutical and food industries.


Expression and prognostic analyses of the insulin-like growth factor 2 mRNA binding protein family in human pancreatic cancer.
Despite advances in early diagnosis and treatment, cancer remains the leading cause of mortality worldwide. The insulin-like growth factor 2 mRNA binding protein (IGF2BP) family has been reported to be involved in a variety of human malignant tumours. However, little is known about their expression and prognostic value in human pancreatic cancer. Therefore, we performed a detailed cancer versus normal differential analysis. The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to analyse the mRNA expression levels of the IGF2BP family in various cancers, including pancreatic cancer. Then, the LinkedOmics and GEPIA databases were used to assess the relation between the expression levels of IGF2BPs and overall survival (OS). Then, univariate and multivariate Cox regression analyses were performed, and subgroups based on grade and stage were analysed. The signalling pathways associated with IGF2BP2 and IGF2BP3 were then investigated via gene set enrichment analysis (GSEA). IGF2BP2 and IGF2BP3 were associated with each subset of OS based on grade and stage. Further clinical correlation analysis of IGF2BP2 and IGF2BP3 confirmed that IGF2BP2 and IGF2BP3 are fundamental factors in promoting pancreatic cancer progression. IGF2BP2 and IGF2BP3 are key factors in promoting the progression of pancreatic cancer and are closely related to overall survival.


Cell Culture Evolution of a Herpes Simplex Virus 1 (HSV-1)/Varicella-Zoster Virus (VZV) UL34/ORF24 Chimeric Virus Reveals Novel Functions for HSV Genes in Capsid Nuclear Egress.
Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are both members of the alphaherpesvirus subfamily but belong to different genera. Substitution of the HSV-1 UL34 coding sequence with that of its VZV homolog, open reading frame 24 (ORF24), results in a virus that has defects in viral growth, spread, capsid egress, and nuclear lamina disruption very similar to those seen in a UL34-null virus despite normal interaction between ORF24 protein and HSV pUL31 and proper localization of the nuclear egress complex at the nuclear envelope. Minimal selection for growth in cell culture resulted in viruses that grew and spread much more efficiently that the parental chimeric virus. These viruses varied in their ability to support nuclear lamina disruption, normal nuclear egress complex localization, and capsid de-envelopment. Single mutations that suppress the growth defect were mapped to the coding sequences of ORF24, ICP22, and ICP4, and one virus carried single mutations in each of the ICP22 and US3 coding sequences. The phenotypes of these viruses support a role for ICP22 in nuclear lamina disruption and a completely unexpected role for the major transcriptional regulator, ICP4, in capsid nuclear egress. IMPORTANCE Interactions among virus proteins are critical for assembly and egress of virus particles, and such interactions are attractive targets for antiviral therapy. Identification of critical functional interactions can be slow and tedious. Capsid nuclear egress of herpesviruses is a critical event in the assembly and egress pathway and is mediated by two proteins, pUL31 and pUL34, that are conserved among herpesviruses. Here, we describe a cell culture evolution approach to identify other viral gene products that functionally interact with pUL34.


Response of Reticulitermes hesperus (Isoptera: Rhinotermitidae) colonies to baiting with lufenuron in northern California.
The objective of this study was to evaluate lufenuron termite bait (1,500 ppm) for the elimination of colonies of Reticulitermes hesperus Banks (Isoptera: Rhinotermitidae). Dispersion of colonies in six baited and six unbaited sites near Placerville, CA, was determined by genetic (microsatellite) analyses. Twenty-one colonies of R. hesperus inhabited the six baited sites and eight colonies of R. hesperus occurred in the six unbaited sites. Five criteria provided a cause-and-effect link between the deployment of lufenuron termite bait and elimination of baited colonies: 1) association of foragers, as members of the same colony, in the independent monitoring stations and bait stations; 2) quantity of bait consumed; 3) abnormal physical appearance of foragers in bait stations; 4) disappearance of foragers from, and cessation of feeding in, independent monitoring stations visited by baited colonies; and 5) presence of foragers from, and continuation of feeding in, independent monitors visited by unbaited colonies. Baited colonies were devoid of foraging termites within a mean of 70.6 d (range, 37-93 d) of bait deployment. Colonies consumed a mean of 8.0 g of bait (range, 2.2-16.0 g). Wood consumption by baited and unbaited colonies was not significantly different during the 2 mo before baiting, 281.4 versus 590.5 mg/d per colony, respectively, nor during the 3 mo immediately after baiting, 112.5 versus 436.8 mg/d per colony, respectively. However, from 10 to 16 mo after baiting, wood consumption by baited colonies essentially ceased and was significantly less than the unbaited colonies, 7.9 versus 470.1 mg/d per colony, respectively.


Stretched-exponential behavior and random walks on diluted hypercubic lattices.
Diffusion on a diluted hypercube has been proposed as a model for glassy relaxation and is an example of the more general class of stochastic processes on graphs. In this article we determine numerically through large-scale simulations the eigenvalue spectra for this stochastic process and calculate explicitly the time evolution for the autocorrelation function and for the return probability, all at criticality, with hypercube dimensions N up to N=28. We show that at long times both relaxation functions can be described by stretched exponentials with exponent 1/3 and a characteristic relaxation time which grows exponentially with dimension N. The numerical eigenvalue spectra are consistent with analytic predictions for a generic sparse network model.


Dose-dependent and combined effects of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine on the survival of retinal ganglion cells in adult hamsters.
This study investigated the effects of daily intraperitoneal injections of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine (L-NA) on the survival of retinal ganglion cells (RGCs) at 1 and 2 weeks after unilateral optic nerve transection in adult hamsters. The left optic nerves of all animals were transected intraorbitally 1 mm from the optic disc and RGCs were retrogradely labeled with Fluorogold before they received different daily dosages of single MK-801 or L-NA as well as daily combinational treatments of these two chemicals. All experimental and control animals survived for 1 or 2 weeks after optic nerve transection. Our results revealed that the mean numbers of surviving RGCs increased and then decreased when the dosage of MK-801 (1.0, 3.0 and 4.5 mg/kg) and L-NA (1.5, 3.0, 4.5 and 6.0 mg/kg) increased at both 1 and 2 weeks survival time points. Daily combinational use of 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA lead to a highest RGC number that was even higher than the sum of the RGC numbers in 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA subgroups at 2 weeks. These findings indicated that both MK-801 and L-NA can protect axotomized RGCs in a dose-dependent manner and combinational treatment of these chemicals possesses a potentiative and protective effect.


Tyrosine kinase inhibition differentially regulates heterologously expressed HCN channels.
The HCN ion channel subunit gene family encodes hyperpolarization-activated cation channels that are permeable to Na(+) and K(+). There are four members of this channel family, three of which, HCN1, HCN2, and HCN4, are expressed in the heart. Current evidence suggests that the HCN ion channel subunit family is the molecular correlate of the alpha subunit of the cardiac pacemaker current i(f). Our previous work has shown that HCN4 is the dominant isoform expressed in the rabbit sinoatrial (SA) node and that changes in tyrosine phosphorylation, either by kinase inhibition or growth factor activation, lead to changes in rabbit SA node i(f) conductance with no change in voltage dependence. In the present study we investigate the actions of genistein, a tyrosine kinase inhibitor, on heterologously expressed HCN currents in Xenopus oocytes. Genistein had no effect on HCN1-induced currents, but reduced whole-cell currents induced by HCN2 or HCN4 and slowed activation kinetics at voltages near the midpoint of activation. In the case of HCN2 there was also a negative shift in the voltage dependence of activation that accompanies the current reduction. We have shown previously that HCN2 is the dominant isoform expressed in rat ventricular myocytes. The above results predict that genistein should reduce i(f) in the rat ventricle and cause a negative shift of voltage dependence and kinetics of activation. We tested this hypothesis by studying the effects of genistein on isolated rat ventricular myocytes. Genistein significantly reduced i(f) current density (pA/pF) (control: 12.2+/-1.8; genistein: 3.5+/-0.5; washout: 7.7+/-0.8; n=10), and caused a negative shift of the midpoint of activation by 14 mV (-133+/-1 mV for genistein and -119+/-1 mV for washout, n=7) with no change in slope factor. Our results thus suggest that i(f) in the heart and i(f)-like currents in other tissues can be regulated differentially by tyrosine phosphorylation based on isoform expression patterns.


3-Methylpiperidinium ionic liquids.
A wide range of room temperature ionic liquids based on the 3-methylpiperdinium cation core were produced from 3-methylpiperidine, which is a derivative of DYTEK® A amine. First, reaction with 1-bromoalkanes or 1-bromoalkoxyalkanes generated the corresponding tertiary amines (Rmβpip, R = alkyl or alkoxyalkyl); further quaternisation reactions with the appropriate methylating agents yielded the quaternary [Rmmβpip]X salts (X(-) = I(-), [CF3CO2](-) or [OTf](-); Tf = -SO2CF3), and [Rmmβpip][NTf2] were prepared by anion metathesis from the corresponding iodides. All [NTf2](-) salts are liquids at room temperature. [Rmmβpip]X (X(-) = I(-), [CF3CO2](-) or [OTf](-)) are low-melting solids when R = alkyl, but room temperature liquids upon introduction of ether functionalities on R. Neither of the 3-methylpiperdinium ionic liquids showed any signs of crystallisation, even well below 0 °C. Some related non-C-substituted piperidinium and pyrrolidinium analogues were prepared and studied for comparison. Crystal structures of 1-hexyl-1,3-dimethylpiperidinium tetraphenylborate, 1-butyl-3-methylpiperidinium bromide, 1-(2-methoxyethyl)-1-methylpiperidinium chloride and 1-(2-methoxyethyl)-1-methylpyrrolidinium bromide are reported. Extensive structural and physical data are collected and compared to literature data, with special emphasis on the systematic study of the cation ring size and/or asymmetry effects on density, viscosity and ionic conductivity, allowing general trends to be outlined. Cyclic voltammetry shows that 3-methylpiperidinium ionic liquids, similarly to azepanium, piperidinium or pyrrolidinium counterparts, are extremely electrochemically stable; the portfolio of useful alternatives for safe and high-performing electrolytes is thus greatly extended.


Assessment of Preschool Early Literacy Skills: Linking Children's Educational Needs with Empirically Supported Instructional Activities.
The importance of the preschool period for becoming a skilled reader is highlighted by a significant body of evidence that preschool children's development in the areas of oral language, phonological awareness, and print knowledge is predictive of how well they will learn to read once they are exposed to formal reading instruction in elementary school. Although there are now a number of empirically supported instructional activities for helping children who are at -risk of later reading difficulties acquire these early literacy skills, limitations in instructional time and opportunities in most preschool settings requires the use of valid assessment procedures to ensure that instructional resources are utilized efficiently. In this paper, we discuss the degree to which informal, diagnostic, screening, and progress-monitoring assessments of preschool early literacy skills can inform instructional decisions by considering the strengths and weaknesses of each approach to assessment.


TGF-beta 1 induces germ-line transcripts of both IgA subclasses in human B lymphocytes.
Immunoglobulin (Ig) class switching appears to be preceded by induction of germ-line transcripts. In this report, we demonstrate that transforming growth factor beta (TGF-beta) induces germ-line transcripts of both the IgA subclasses (IgA1 and IgA2) in Branhamella catarrhalis (BC)-activated human spleen B cells. Two germ-line bands, one of approximately 1.85 kb and the other of approximately 1.6 kb, could be seen in cultures treated with TGF-beta. The approximately 1.85 kb band contains mRNA for a germ-line transcript of the membrane form. This band co-migrates with the productive secreted form of alpha mRNA. The other, shorter form of approximately 1.6 kb did not correlate in size with any known form of productive alpha mRNA and contained the secreted form of germ-line alpha mRNA. The induction of alpha germ-line transcripts was accompanied by a concomitant suppression of mu and gamma mRNA. We have also identified the location of a putative I alpha sequence (designated according to the generally accepted nomenclature) within approximately 0.5 kb upstream to the switch alpha (S alpha) region. The relative proportions of IgA-subclass-specific mRNA in TGF-beta-stimulated spleen B cells are concordant with the distribution pattern seen in pokeweed mitogen (PWM)-stimulated spleen mononuclear cells (MNC), which was 89 and 11% for the IgA1 and the IgA2 mRNA respectively. These results suggest a role of TGF-beta in regulating IgA class switching in human B lymphocytes.


Neutrophils are mediators of metastatic prostate cancer progression in bone.
Bone metastatic prostate cancer (BM-PCa) significantly reduces overall patient survival and is currently incurable. Current standard immunotherapy showed promising results for PCa patients with metastatic, but less advanced, disease (i.e., fewer than 20 bone lesions) suggesting that PCa growth in bone contributes to response to immunotherapy. We found that: (1) PCa stimulates recruitment of neutrophils, the most abundant immune cell in bone, and (2) that neutrophils heavily infiltrate regions of prostate tumor in bone of BM-PCa patients. Based on these findings, we examined the impact of direct neutrophil-prostate cancer interactions on prostate cancer growth. Bone marrow neutrophils directly induced apoptosis of PCa in vitro and in vivo, such that neutrophil depletion in bone metastasis models enhanced BM-PCa growth. Neutrophil-mediated PCa killing was found to be mediated by suppression of STAT5, a transcription factor shown to promote PCa progression. However, as the tumor progressed in bone over time, neutrophils from late-stage bone tumors failed to elicit cytotoxic effector responses to PCa. These findings are the first to demonstrate that bone-resident neutrophils inhibit PCa and that BM-PCa are able to progress via evasion of neutrophil-mediated killing. Enhancing neutrophil cytotoxicity in bone may present a novel therapeutic option for bone metastatic prostate cancer.


Perceptions on efficacy and side effects of conventional depot antipsychotics (CDA) and atypical depot antipsychotics (ADA): Psychiatrists versus patients in Hong Kong.
Abstract Objectives. We compared the satisfaction level of psychiatrists and psychiatric patients towards conventional (CDA) and atypical (ADA) depot antipsychotics on symptom management, role functioning, and side effects. Method. Patients from an out-patient clinic of a public hospital and psychiatrists from public hospitals participated in the survey in 2007-2008. A total of 153 patients were interviewed by a tailor-made questionnaire and 72 psychiatrists self-administered a similar questionnaire. Results. Both groups shared similar attitudes towards clinical effectiveness and treatment efficacy of ADA and CDA. More patients were ambivalent towards relapse prevention of CDA than psychiatrists (30.7 vs. 16.7%, P<0.044) and three quarters of psychiatrists believed that ADA are associated with less side effects. More than half of the patients showed negative attitudes towards the effectiveness of CDA on improving quality of life (52.40%), work (57.50%), and recreation (55.50%). Psychiatrists were more aware of the limitation of CDA and severity of side effects of CDA. They did not, however, seem to incorporate patients' opinions and research findings into their clinical practice. Conclusion. Evidence-based practice and shared decision-making model between clinicians and mental patients should be advocated. More investigations should be devoted to examine the efficacy of ADA as the alternative to CDA.


Susceptibility of Influenza Viruses to the Novel Cap-Dependent Endonuclease Inhibitor Baloxavir Marboxil.
The novel cap-dependent endonuclease inhibitor baloxavir marboxil was approved for the treatment of influenza A and B virus infections in February 2018 in Japan. Because of the need to monitor influenza viruses for reduced susceptibility to this drug, we used two cell-based screening systems - a conventional plaque reduction assay and a focus reduction assay - to evaluate the susceptibility of influenza viruses to baloxavir. First, we generated a reference virus possessing an I38T substitution in the polymerase acidic subunit (PA), which is known to be associated with reduced susceptibility to baloxavir, and demonstrated the validity of our systems using this reference virus. We then determined the susceptibility of a panel of neuraminidase (NA) inhibitor-resistant viruses and their sensitive counterparts to baloxavir. No significant differences in baloxavir susceptibilities were found between the NA inhibitor-resistant and -sensitive viruses. We also examined seasonal influenza viruses isolated during the 2017-2018 influenza season in Japan and found that no currently circulating A(H1N1)pdm09, A(H3N2), or B viruses had significantly reduced susceptibility to baloxavir and none of the viruses possessed an amino acid substitution at PA residue 38. Use of a combination of methods to analyze antiviral susceptibility and detect amino acid substitutions is valuable for monitoring the emergence of baloxavir-resistant viruses.


Genome Editing, Gene Drives, and Synthetic Biology: Will They Contribute to Disease-Resistant Crops, and Who Will Benefit?
Genetically engineered crops have been grown for more than 20 years, resulting in widespread albeit variable benefits for farmers and consumers. We review current, likely, and potential genetic engineering (GE) applications for the development of disease-resistant crop cultivars. Gene editing, gene drives, and synthetic biology offer novel opportunities to control viral, bacterial, and fungal pathogens, parasitic weeds, and insect vectors of plant pathogens. We conclude that there will be no shortage of GE applications totackle disease resistance and other farmer and consumer priorities for agricultural crops. Beyond reviewing scientific prospects for genetically engineered crops, we address the social institutional forces that are commonly overlooked by biological scientists. Intellectual property regimes, technology regulatory frameworks, the balance of funding between public- and private-sector research, and advocacy by concerned civil society groups interact to define who uses which GE technologies, on which crops, and for the benefit of whom. Ensuring equitable access to the benefits of genetically engineered crops requires affirmative policies, targeted investments, and excellent science.


Glioma-Associated Oncogene-1 Expression in Basal Cell Carcinoma and Its Histologic Mimics.
Basal cell carcinoma (BCC) is the most common skin cancer, and it has numerous histologic mimics with variable prognoses and treatments. Although some immunohistochemical stains can be used for the differential diagnosis of BCC, variability and overlap in results can complicate their interpretation. Immunohistochemical staining for glioma-associated oncogene-1 (Gli-1) was performed on 26 nodular BCCs, 22 infiltrative BCCs, 9 basaloid squamous cell carcinomas, 12 desmoplastic trichoepitheliomas, 19 Merkel cell carcinomas, 11 sebaceous carcinomas, 10 cylindromas, 14 spiradenomas, 12 adenoid cystic carcinomas (AdCC), and 1 solitary trichoepithelioma. Strength of staining was scored as 0, 1+, 2+, or 3+, and distribution of staining was categorized as diffuse, multifocal, or focal. Strong, diffuse Gli-1 expression was seen in all tumors with basal epidermal-type differentiation, including BCC, trichoepithelioma, and basaloid squamous cell carcinoma. All examples of Merkel cell carcinoma were negative for cytoplasmic expression. Seven out of 11 sebaceous carcinomas were negative for Gli-1, and the remaining 4 showed 1+ expression. Cylindroma, spiradenoma, and AdCC, each an adnexal skin tumor, showed the most variable staining, but with cylindroma and spiradenoma demonstrating comparable labeling patterns. Overall, although Gli-1 may not distinguish between basal epidermal-type tumors, it may have a role in separating that group from lesions with adnexal differentiation, particularly sebaceous carcinoma, but also cylindroma, spiradenoma, and AdCC. Any cytoplasmic staining seems to exclude the diagnosis of Merkel cell carcinoma.


Mass and Moment of Inertia Govern the Transition in the Dynamics and Wakes of Freely Rising and Falling Cylinders.
In this Letter, we study the motion and wake patterns of freely rising and falling cylinders in quiescent fluid. We show that the amplitude of oscillation and the overall system dynamics are intricately linked to two parameters: the particle's mass density relative to the fluid m^{*}≡ρ_{p}/ρ_{f} and its relative moment of inertia I^{*}≡I_{p}/I_{f}. This supersedes the current understanding that a critical mass density (m^{*}≈0.54) alone triggers the sudden onset of vigorous vibrations. Using over 144 combinations of m^{*} and I^{*}, we comprehensively map out the parameter space covering very heavy (m^{*}>10) to very buoyant (m^{*}<0.1) particles. The entire data collapse into two scaling regimes demarcated by a transitional Strouhal number St_{t}≈0.17. St_{t} separates a mass-dominated regime from a regime dominated by the particle's moment of inertia. A shift from one regime to the other also marks a gradual transition in the wake-shedding pattern: from the classical two-single (2S) vortex mode to a two-pair (2P) vortex mode. Thus, autorotation can have a significant influence on the trajectories and wakes of freely rising isotropic bodies.


Prevalence of epidermolytic toxin in clinical isolates of Staphylococcus aureus.
One hundred and sixteen strains of Staphylococcus aureus isolated from exfoliative skin lesions were screened for their ability to produce different serotypes of epidermolytic toxin (ET). Toxin production was assessed by immunodiffusion, analytical isoelectric focussing and examination for the Nikolsky sign in mice. Of 84 strains of phage group II, 72 (85.7%) were toxinogenic as were 10 of 32 (31.3%) non-group-II strains. The ability to produce ET serotypes A and B was not confined to a particular phage group.


Description of a New Haemogregarine, Haemogregarina sundarbanensis n. sp. (Apicomplexa: Haemogregarinidae) from Mud Turtle of Sundarban Regions, West Bengal, India.
The aim of this study was to provide a description of a new haemogregarine, Haemogregarina sundarbanensis n. sp., from mud turtles collected from Sundarban regions, West Bengal, India. The turtles were collected from fish markets near Canning, South 24-Parganas District, West Bengal. Thin blood films were prepared using the blood drawn from the head and feet. The blood films were then air-dried, fixed in absolute methanol, and stained with Giemsa. The erythrocytic stages could be differentiated into small and large forms. The young gamonts measured 7.896×3.469 μm, microgamonts measured 8.876×4.425 μm, and macrogamonts measured 8.919×4.272 μm. The cytoplasm of the macrogamonts was stained deep blue with Giemsa, and many metachromatic granules are found uniformly distributed. The oval or rounded nucleus was central in position and stained deep red with Giemsa stain, whereas in microgamonts, the nucleus was not at all compact but with a few dispersed chromatin granules. The prevalence of infection was found to be 33.3% (5/15). The infected erythrocytes reveal shape alteration, marginal and atrophic nucleus, and were larger than non-parasitized erythrocytes. The cytoplasm of the infected erythrocytes stained darker than that of the uninfected erythrocytes.


The Inhibitory Effect of Ginger Extract on Ovarian Cancer Cell Line; Application of Systems Biology.
Purpose: Ginger is a natural compound with anti-cancer properties. The effects of ginger and its mechanism on ovarian cancer and its cell line model, SKOV-3, are unclear. In this study, we have evaluated the effect of ginger extract on SKOV-3. Methods: SKOV-3 cells were incubated with ginger extract for 24, 48 and 72 hours. Cell toxicity assay was performed. Different data mining algorithms were applied to highlight the most important features contributing to ginger inhibition on the SKOV-3 cell proliferation. Moreover, Real-Time PCR was performed to assay p53, p21 and bcl-2 genes expression. For co-expression meta-analysis of p53, mutual ranking (MR) index and transformation to Z-values (Z distribution) were applied on available transcriptome data in NCBI GEO data repository. Results: The ginger extract significantly inhibited cancer growth in ovarian cancer cell line. The most important attribute was 60 µg/ml concentration which received weights higher than 0.50, 0.75 and 0.95 by 90%, 80% and 50% of feature selection models, respectively. The expression level of p53 was increased sharply in response to ginger treatment. Systems biology analysis and meta-analysis of deposited expression value in NCBI based on rank of correlation and Z-transformation approach unraveled the key co-expressed genes and co-expressed network of P53, as the key transcription factor induced by ginger extract. High co-expression between P53 and the other apoptosis-inducing proteins such as CASP2 and DEDD was noticeable, suggesting the molecular mechanism underpinning of ginger action. Conclusion: We found that the ginger extract has anticancer properties through p53 pathway to induce apoptosis.


Markers for proliferation and keratinization in the margin of the active psoriatic lesion.
To study the development of the psoriatic lesion, biopsies were taken from the margin of spreading plaques and acute pinpoint papules. Consecutive sections across the margin were stained using different monoclonal antibodies to characterize epidermal growth (Ki-67) and abnormal keratinization (Ks8.12, RKSE60). All three immunohistochemical markers showed pronounced changes in the lesional skin with a clear transition to the uninvolved skin. The suprabasal Ks8.12 binding was the earliest change found in the epidermis, and its localization high in the suprabasal compartment indicates that metabolic dysregulation in this cell population was not a consequence of the recruitment process in the basal layer.


Deficit of spinal cord glycine/strychnine receptors in inherited myoclonus of Poll Hereford calves.
Inherited myoclonus of Poll Hereford calves is characterized by hyperesthesia and myoclonic jerks of the skeletal musculature, which occur spontaneously and in response to sensory stimuli. The disease shows autosomal recessive inheritance, and significant proportions of the Poll Hereford herds in many countries are thought to be carriers of the mutant gene. Studies revealed a specific and marked (90 to 95 percent) deficit in [3H]strychnine binding sites in spinal cord membranes from myoclonic animals compared to controls, reflecting a loss of, or defect in, glycine/strychnine receptors. Spinal cord synaptosomes prepared from affected animals showed a significantly increased ability to accumulate [3H]glycine, indicating an increased capacity of the high-affinity neuronal uptake system for glycine. In contrast, stimulus-induced glycine release and spinal cord glycine concentrations were unaltered.


Strategies for noise reduction and standardization of milk mid-infrared spectra from dairy cattle.
The use of Fourier-transform mid-infrared (FTIR) spectroscopy is of interest to the dairy industry worldwide for predicting milk composition and other novel traits that are difficult or expensive to measure directly. Although there are many valuable applications for FTIR spectra, noise from differences in spectral responses between instruments is problematic because it reduces prediction accuracy if ignored. The purpose of this study was to develop strategies to reduce the impact of noise and to compare methods for standardizing FTIR spectra in order to reduce between-instrument variability in multiple-instrument networks. Noise levels in bands of the infrared spectrum caused by the water content of milk were characterized, and a method for identifying and removing outliers was developed. Two standardization methods were assessed and compared: piecewise direct standardization (PDS), which related spectra on a primary instrument to spectra on 5 other (secondary) instruments using identical milk-based reference samples (n = 918) analyzed across the 6 instruments; and retroactive percentile standardization (RPS), whereby percentiles of observed spectra from routine milk test samples (n = 2,044,094) were used to map and exploit primary- and secondary-instrument relationships. Different applications of each method were studied to determine the optimal way to implement each method across time. Industry-standard predictions of milk components from 2,044,094 spectra records were regressed against predictions from spectra before and after standardization using PDS or RPS. The PDS approach resulted in an overall decrease in root mean square error between industry-standard predictions and predictions from spectra from 0.190 to 0.071 g/100 mL for fat, from 0.129 to 0.055 g/100 mL for protein, and from 0.143 to 0.088 g/100 mL for lactose. Reductions in prediction error for RPS were similar but less consistent than those for PDS across time, but similar reductions were achieved when PDS coefficients were updated monthly and separate primary instruments were assigned for the North and South Islands of New Zealand. We demonstrated that the PDS approach is the most consistent method to reduce prediction errors across time. We also showed that the RPS approach is sensitive to shifts in milk composition but can be used to reduce prediction errors, provided that secondary-instrument spectra are standardized to a primary instrument with samples of broadly equivalent milk composition. Appropriate implementation of either of these approaches will improve the quality of predictions based on FTIR spectra for various downstream applications.


[The sick sinus syndrome and lipid peroxidation: its possible role in the pathogenesis of the disease].
As many as 196 persons were examined. Of these, 106 were with a normal sinus rhythm and 90 had sick-sinus syndrome (SSS). Measurements were made of the level of malonic dialdehyde and the total antioxidant blood activity, the lipoprotein spectrum. Electrophysiological studies of the heart, ECG monitoring and bicycle ergometry were carried out. Maximal impairment of lipid peroxidation (LP) in type IIA hyperlipoproteinemia (HLP) was identified according to Fredrickson both in patients with SSS and without it. In patients with SSS, the rise of the closeness of the relationship between LP and HLP was observed. In patients with CHD and (or) EH, LP was mostly disturbed in EH and in associated CHD and EH (both in patients with and without SSS). As compared with the respective control groups, SSS patients showed considerable disorders of LP. It is suggested that LP disorders related to HLP may play a role in the pathogenesis of SSS.


Contraceptive Intentions and Use throughout the Extended Postpartum Period: A Panel Study in Ethiopia.
The postpartum period is an ideal time for women to access contraception, but the prevalence of postpartum contraceptive use remains low in sub-Saharan Africa. To better understand the gap between women's desires to space or limit births and their contraceptive behaviors, intention to use contraception has been proposed as a person-centered measure of contraceptive demand. Using data from a panel study of Ethiopian women aged 15-49 who were interviewed at six weeks, six months, and one year postpartum, we examined the dynamics of contraceptive intention in the first year postpartum and its relationship with contraceptive use. Contraceptive intention fluctuated considerably in the year after childbirth. At six weeks, 60.9 percent of women intended to use a contraceptive method in the next year; 23.2% did not. By one year, less than half (43.5 percent) were using a method, and those who had no intention to use doubled (44.5 percent). Women who developed or sustained their intention to use a method in the postpartum period were more likely to adopt a method by one year than those who did not, showing that contraceptive intention is a strong predictor of use and has the potential to inform person-centered reproductive health programming in the extended postpartum period.


[Clinical and laboratory basis for the diagnosis and understanding of neonatal metabolic diseases].
The authors divide neonatal metabolic diseases into two major groups: intoxication and energy deficiency. The main signs which allow for the suspicion of the diagnosis are indicated for each group. The complementary examinations to be carried out by the Clinical Pathology Service of the Central Hospital and those which must be carried out by the metabolic diseases Reference Centre are reviewed. Based on the clinical framework and on the examination results, the authors establish five syndromatic groups to orientate diagnosis. The authors conclude by presenting differential diagnosis tables based on the original systematic classification by Jean-Marie Saudubray, with up-dated modifications from their own experience.


Effects of UV-B radiation on seed yield of Glycine max and an assessment of F1 generation progeny for carryover effects.
Glycine max (L.) Merr plants were grown outdoors in potted sand exposed to elevated ultraviolet-B (UV-B) radiation provided by filtered fluorescent lamps to determine the effects of UV-B on seed yield and UV-B-induced carryover effects in the F1 generation. Increased UV-B radiation had no detectable effects on reproductive parameters except for a reduction on seed number per plant and an increase in the number of unseeded pods per plant and dry weight of unseeded pods per plant in the field supplemental UV-B experiment. Studies on carryover effects in the greenhouse progeny growth trial also showed no effect of parental treatment with UV-B on biomass production, and most symbiotic-N traits and plant metabolite measured. However, the concentrations of N in nodules and starch in roots were significantly increased in the F1 generation progeny from elevated UV-B radiation relative to their F1 counterparts from ambient radiation. Assessing the effects of seed size on plant growth and symbiotic function in the F1 progeny showed that total biomass, dry matter yield of individual organs (leaves, stems, roots and nodules), total plant N and fixed-N rose with increasing seed size. Seed concentration of flavonoids was also enhanced with increasing seed size. These findings suggest that subtle changes did occur in the F1 generation progeny of parental plants exposed to elevated UV-B with potential to accumulate with further exposure to elevated UV-B radiation.


Effects of peptide leukotrienes on cardiac dynamics in rat, cat, and guinea pig hearts.
The purpose of the present investigation was to examine potential inotropic effects of leukotrienes C4 (LTC4) and D4 (LTD4) in relation to their potent coronary constricting effects. The experiments were carried out in isolated Langendorff perfused hearts and isolated electrically driven isometrically contracting papillary muscle preparations. Tissues from cat, rat, and guinea pig were used in the study. Both LTC4 and LTD4 at 50 ng/ml had no effect on papillary muscles isolated from the rat, guinea pig, or cat. These papillary muscles responded to known negative inotropic agents including pentobarbital sodium and methanol. In isolated hearts perfused under constant flow, both LTC4 and LTD4 at 50 ng/ml increased coronary perfusion pressure and decreased contractile force of the heart in all three species. In hearts perfused under constant pressure perfusion, both LTC4 and LTD4 decreased coronary flow with concomitant decreases in contractile force. The leukotriene antagonist, FPL 55712, blocked both the coronary constrictor and the cardiodepressant effects of both leukotrienes. Pentobarbital (100 micrograms/ml) significantly decreased cardiac contractile force without inducing coronary vasoconstriction. These findings demonstrate that LTC4 and LTD4 do not possess direct negative inotropic activity in cardiac muscles of these three species. However, LTC4 and LTD4 are potent coronary constrictors that can secondarily decrease myocardial contractile force via their coronary constrictor action.


Adenocarcinoma of the minor duodenal papilla: report of a case.
An 81-year-old male was found to have a duodenal tumor by screening upper gastrointestinal endoscopy. The tumor was located in the minor duodenal papilla. Pathological examination of the biopsy specimen revealed adenocarcinoma, and endoscopic ultrasound showed an elevated hypoechoic mass in the minor duodenal papilla. The preoperative diagnosis was therefore considered to be either adenocarcinoma of the minor duodenal papilla or duodenal cancer. We performed a subtotal stomach-preserving pancreaticoduodenectomy. Histopathological examination of the resected specimen showed the tumor cells to be primarily located in the submucosa of the minor duodenal papilla, with slight invasion into the pancreatic parenchyma through the accessory pancreatic duct. We therefore diagnosed a primary adenocarcima of the minor duodenal papilla. Adenocarcinoma of the minor duodenal papilla is considered to be a rare disease, but it may be underestimated because of the difficulty in distinguishing advanced adenocarcinoma of the minor duodenal papilla from primary duodenal cancer and cancer of the pancreatic head.


Effect of exposure to hyperoxic, hypobaric, and hyperbaric environments on concentrations of selected and aerobic and anaerobic fecal flora of mice.
Alterations in selected aerobic and anaerobic fecal microflora of the mouse were determined during exposure to hyperoxic and normoxic hypo- and hyperbaric environments. Examination of fecal cultures obtained during exposure for 6 weeks to either 60 or 77% oxygen concentration 1 atmosphere absolute revealed little alteration in the aerobic or anaerobic flora. There appeared to be only a retardation in the reduction of the Klebsiella-Enterobacter flora which normally occurs after weaning. During exposure to hypobaric environments (100% O-2, 0.2 atmosphere absolute), significant alterations in concentrations of Escherichia coli, slow lactose fermenters, Klebsiella-Enterobacter, and enterococci were found in some instances. All alterations were toward increased concentrations. Variations in concentrations of different colony types of obligately anaerobic gram-positive (anGPR) and gram-negative (anGNR) rods cultured during the same experiments also occurred. One colony type of anGPR appeared to decrease while a second type increased in numbers. Concentrations of three colony types of anGNR were generally, but not always, increased. During hyperbaric exposure (2.8% O-2, 7.5 atmospheres absolute), increased concentrations of Klebsiella-Enterobacter, E. coli, slow lactose fermenters and enterococci were also noted. Changes in numbers of both colony types of anGPR, when occurring, were in the direction of lower numbers. Alteration in numbers of anGNR were in both directions but were more frequent in the direction of higher numbers. After return to normal air for 4 weeks of either hypo- or hyperbaric exposure, fecal concentrations of all organisms tended to revert toward control values with the exception of the anGPR which remained in lower concentrations after termination of the hyperbaric exposure. These observations indicate that, despite the great variation in the fecal flora among individual mice, it is possible to discover the effects induced by altered gaseous environments.


[Burns and the family experience as to the hospitalization process].
Hospital admission due to burning is usually fast and unpredictable. There may be different reactions to trauma according to the phase experienced by the patient and his/her family. This study aimed at describing the impact of the hospitalization of burnt patients on family dynamics. The Calgary Family Assessment Model was applied using semi-structured interviews and direct observation of family members. The following phases were considered for data analysis: reading the material and data reduction, data presentation, conclusion presentation, and verification. The findings showed that family members experience a crisis period that affects their physical and emotional status, relationships, daily routine, management of financial resources, and work. All of these aspects change the family dynamics, contributing for the maintenance of a crisis-adjustment-stability cycle during the entire treatment


[Dysfunction of central gray nuclei].
We first recall the anatomical organization of the basal ganglia system (or central grey nuclei), putting forward their macroscopical, hodological and cytological properties and the convergent properties that arise from them. Then we examine the different functional models that have been developed since the eighties, the convergent model in 1984, the parallel model in 1986, the dual circuit in 1989, the "current" model in 1990, and the critics of the latter since 1993. We finally sum up the recent models developed since the nineties.


Blue justice: A survey for eliciting perceptions of environmental justice among coastal planners' and small-scale fishers in Northern-Norway.
Ocean-based economic development arising from an increasing interest in the 'blue economy' is placing ecosystems and small-scale fisheries under pressure. The dominant policy response for dealing with multiple uses is the allocation of coastal space through coastal zone planning (CZP). Recent studies have shown that the rush to develop the blue economy and regulate coastal activity can result in social injustices and the exclusion of less powerful and unrecognized groups (e.g., small-scale fishers, women, Indigenous peoples and youth). To achieve a primary goal of the 2030 sustainable development agenda to "leave no one behind", it is important to understand the implications of coastal planning and development for these groups. Here, we present a social survey protocol for examining perceptions of justice related to small-scale fisheries (SSF) in the context of the blue economy in coastal areas. Specifically, we designed the survey instrument and sampling protocol to assess whether decisions about the use of the coastal zone over the last five years have i) followed principles of good governance, ii) recognized fishers' knowledge, culture and rights and iii) been attentive to impacts of changed coastal zone use on fisheries. The survey will engage coastal planners (N = app. 120) and fishers (N = app. 4300) in all the coastal municipalities (N = 81) in Northern-Norway. The sampling protocol is designed to ensure representation of different sectors of society, including those defined by gender, age, ethnicity and occupation (e.g., small-scale fishers, large-scale fishers, coastal planners).


Degradation of parathion by bacteria isolated from flooded soil.
Two bacteria, Bacillus sp. and Pseudomonas sp., were isolated from parathionamended flooded alluvial soil which exhibited parathion-hydrolyzing ability. Bacillus sp. readily liberated nitrite from the hydrolysis product, p-nitrophenol, but not from intact parathion. Pseudomonas sp. hydrolyzed parathion and then released nitrite from p-nitrophenol. These studies establish bacterial degradation of parathion past the p-nitrophenol stage to the end product, nitrite.


[Educational program in universal precaution measures: a methodological approach].
An updating program on measures of universal precautions (M.U.P.) was developed at the Center of Whole Care of Woman's Health (Centro de Atenção Integral à Saúde da Mulher-CAISM). These measures and the procedures in the case of work accident were published in a booklet. First, servants should be aware of the matter of stress and its influence on the quality of life. Then, updating was carried through encouraging the reflection on the consequences of the non-adoption of M.U.P. The answers to 286 pre-tests and 242 post-tests were analyzed and the results showed a significantly higher index of correct answers (p < 0.01), mainly regarding the appropriate use of glove.


Antifungal Activity of Alkaloids Against Candida albicans.
Candida albicans is a pathogen in the mouth responsible for opportunistic infections that are usually harmless. Natural products have been used to develop several drugs, mostly anticancer and anti-infective agents. Among these, alkaloids have been studied for their medicinal properties. In this study, we examined their antifungal activity against C. albicans in vitro. Among the alkaloids studied in this work, berberine hydrochloride showed the best activity against C. albicans.


Effects of basic FGF and TGF beta 1 on F-actin and ZO-1 organization during cat endothelial wound healing.
Previous studies suggest the existence of two separate and distinct mechanisms of endothelial wound healing (i.e., cell migration and cell spreading), which may be controlled by unique, injury-dependent, wound-related factors. The purpose of our study was to evaluate potential biologic mediators regulating healing of the growth arrested cat endothelium by using an ex vivo, organ-culture model. Three buttons were punched from each cornea of 11 cats with a 6-mm trephine. A 1- to 2-mm diameter endothelial scrape injury (SI) was made, and buttons were cultured in (a) serum-free media (SFM), (b) serum plus media (20% fetal calf serum), (c) SFM plus basic fibroblast growth factor (bFGF), (d) SFM plus bFGF and heparin, (e) SFM plus transforming growth factor-beta 1 (TGF beta 1), or (f) SFM plus TGF beta 1 and anti-TGF beta 1. At various times from 8-48 h after injury, buttons were stained with phalloidin and anti-ZO-1, and imaged by using laser scanning confocal microscopy. Evaluation of SI in cat corneal buttons under serum-free conditions showed maintenance of normal endothelial differentiation, indicating that the organ-culture SI model mimics in vivo SI. Addition of TGF beta 1 produced a dramatic reorganization of apical F-actin and development of stress fibers, as well as the loss of normal cell border-associated ZO-1 distribution. The effects of TGF beta 1 were blocked by the neutralizing antibodies to TGF beta 1. Addition of serum or bFGF produced much less pronounced changes in F-actin and ZO-1 distribution. These results suggest that TGF beta 1 may play a critical role in modulating the wound-healing response of the corneal endothelium.


THE ECONOMIC IMPACT OF A HIGH NATIONAL MINIMUM WAGE: EVIDENCE FROM THE 1966 FAIR LABOR STANDARDS ACT.
This paper examines the short and longer-term economic effects of the 1966 Fair Labor Standards Act (FLSA) which increased the national minimum wage to its highest level of the 20th Century and extended coverage to an additional 9.1 million workers. Exploiting differences in the "bite" of the minimum wage due to regional variation in the standard of living and industry composition, this paper finds that the 1966 FLSA increased wages dramatically but reduced aggregate employment only modestly. However, the disemployment effects were significantly larger among African-American men, forty percent of whom earned below the new minimum wage in 1966.


Digital Mammograms with Image Enhancement Techniques for Breast Cancer Detection: A Systematic Review.
Digital mammograms with appropriate image enhancement techniques will improve breast cancer detection, and thus increase the survival rates. The objectives of this study were to systematically review and compare various image enhancement techniques in digital mammograms for breast cancer detection. A literature search was conducted with the use of three online databases namely, Web of Science, Scopus, and ScienceDirect. Developed keywords strategy was used to include only the relevant articles. A Population Intervention Comparison Outcomes (PICO) strategy was used to develop the inclusion and exclusion criteria. Image quality was analyzed quantitatively based on peak signal-noise-ratio (PSNR), Mean Squared Error (MSE), Absolute Mean Brightness Error (AMBE), Entropy, and Contrast Improvement Index (CII) values. Nine studies with four types of image enhancement techniques were included in this study. Two studies used histogram-based, three studies used frequency-based, one study used fuzzy-based and three studies used filter-based techniques. All studies reported PSNR values whilst only four studies reported MSE, AMBE, Entropy, and CII values. Filter-based was the highest PSNR values of 78.93, among other types. For MSE, AMBE, Entropy, and CII values, the highest were frequency-based (7.79), fuzzy-based (93.76), filter-based (7.92), and frequency-based (6.54) respectively. In summary, image quality for each image enhancement technique is varied, especially for breast cancer detection. In this study, the frequency-based of Fast Discrete Curvelet Transform (FDCT) via the UnequiSpaced Fast Fourier Transform (USFFT) shows the most superior among other image enhancement techniques.


Microtubule dynamics in living root hairs: transient slowing by lipochitin oligosaccharide nodulation signals.
The incorporation of a fusion of green fluorescent protein and tubulin-alpha 6 from Arabidopsis thaliana in root hairs of Lotus japonicus has allowed us to visualize and quantify the dynamic parameters of the cortical microtubules in living root hairs. Analysis of individual microtubule turnover in real time showed that only plus polymer ends contributed to overall microtubule dynamicity, exhibiting dynamic instability as the main type of microtubule behavior in Lotus root hairs. Comparison of the four standard parameters of in vivo dynamic instability--the growth rate, the disassembly rate, and the frequency of transitions from disassembly to growth (rescue) and from growth to disassembly (catastrophe)--revealed that microtubules in young root hairs were more dynamic than those in mature root hairs. Either inoculation with Mesorhizobium loti or purified M. loti lipochitin oligosaccharide signal molecules (Nod factors) significantly affected the growth rate and transition frequencies in emerging and growing root hairs, making microtubules less dynamic at a specific window after symbiotic inoculation. This response of root hair cells to rhizobial Nod factors is discussed in terms of the possible biological significance of microtubule dynamics in the early signaling events leading to the establishment and progression of the globally important Rhizobium/legume symbiosis.