Relationship between blood and urine alcohol concentrations in apprehended drivers who claimed consumption of alcohol after driving with and without supporting evidence.
For various reasons, many people suspected of driving under the influence of alcohol (DUIA) are not apprehended sitting behind the wheel, but some time after the driving. This gives them the opportunity to claim they drank alcohol after the time of driving or after they were involved in a road-traffic crash. Alleged post-offence drinking is not easy for the prosecution to disprove, which often means that the DUIA charge is dropped or the person is acquitted if the case goes to trial. The routine practice of sampling and measuring the concentration of alcohol in blood (BAC) and urine (UAC) and calculating urine/blood ratios (UAC/BAC) and the changes in UAC between two successive voids furnishes useful information to support or challenge alleged drinking after driving. We present here a retrospective case series of DUIA offenders (N=40) in half of which there was supporting evidence of an after-drink (eye witness or police reports) and in the other half no such evidence existed apart from the suspect's admission. When there was supporting evidence of an after-drink, the UAC/BAC ratio for the first void was close to or less than unity (mean 1.04, median 1.08, range 0.54-1.21) and the UAC increased by 0.21 g/L (range 0.02-0.57) between the two voids. Without any supporting evidence of post-offence drinking the mean UAC/BAC ratio was 1.46 (range 1.35-1.93) for the first void, verifying that absorption and distribution of alcohol in all body fluids and tissues was complete. In these cases, the UAC between successive voids decreased by 0.25 g/L on average (range 0.10-0.49), indicating the post-absorptive phase of the BAC curve. Long experience from investigating claims of post-offence drinking leads us to conclude that in the vast majority of cases this lacks any substance and is simply a last resort by DUIA offenders to evade justice. Unless supporting evidence exists (eye witness, police reports, etc.) of post-offence drinking the courts are encouraged to ignore this defence argument.


Perspective: Challenges in Use of Adolescent Anthropometry for Understanding the Burden of Malnutrition.
Improving nutritional status during adolescence is an opportunity to improve the lives of this generation and the next. Estimating the burden of malnutrition at a population level is fundamental to targeting interventions and measuring progress over time, and for adolescents, we usually depend on survey data and the 2007 WHO Growth Reference to do so. There is substantial risk of misguided conclusions regarding adolescent prevalence estimates, however, when underlying methodological limitations of the indicators and reference are not adequately considered. We use national prevalence estimates among girls and young women 10-22 y of age from the 2014 State of Food Security and Nutrition in Bangladesh report as an example to demonstrate that determining the true prevalence of undernutrition, overweight, and obesity is complicated by racial/ethnic variation across populations in timing of the adolescent growth spurt, growth potential, and body build. Further challenging the task are inherent limitations of the body mass index as an indicator of thinness and adiposity, and cutoffs that poorly distinguish a well-nourished population from a malnourished one. We provide recommendations for adolescent nutrition policy and program decision-making, emphasizing the importance of 1) critically interpreting indicators and distributions by age when using the 2007 WHO Growth Reference; 2) examining what is happening before and after adolescence, when interpretation of anthropometry is more straightforward, as well as trends over time; and 3) complementing anthropometry with other information, particularly dietary intake. Finally, we advocate that nutrition researchers prioritize exploration of better methods to predict peak height velocity, for development of standardized indicators to measure dietary quality among adolescents, and for studies that will illuminate causal paths so that we can effectively improve adolescent dietary intake and nutritional status.


Decreasing glioma recurrence through adjuvant cancer stem cell inhibition.
Gliomas remain one of the most challenging solid organ tumors to treat and are marked clinically by invariable recurrence despite multimodal intervention (surgery, chemotherapy, radiation). This recurrence perhaps, is as a consequence of the failure to eradicate a tumor cell subpopulation, termed cancer stem cells. Isolating, characterizing, and understanding these tumor-initiating cells through cellular and molecular markers, along with genetic and epigenetic understanding will allow for selective targeting through therapeutic agents and holds promise for decreasing glioma recurrence.


Malleus to stapes assembly.
The malleus to stapes assembly is the ideal ossicular reconstruction because of its high degree of success. Unfortunately, both the malleus and the stapes have to be in good position to use this type of reconstruction making it much less common than other forms of ossiculoplasty. Over a six year period, 1976-1982, there were 20 such procedures performed, as compared to 85 cases of hemi-incus interposition ossiculoplasty in the same period. The malleus to stapes assembly technique and indications are described in this report. Reconstruction results show an 80% air-bone gap closure within 10 dB with an average improved speech reception threshold of 18 dB.


"Sandwich" bone augmentation technique: rationale and report of pilot cases.
The aim of this article is to present a new technique for augmentation of deficient alveolar ridges and/or correction of osseous defects around dental implants. Current knowledge regarding bone augmentation for treatment of osseous defects prior to and in combination with dental implant placement is critically appraised. The "sandwich" bone augmentation technique is demonstrated step by step. Five pilot cases with implant dehiscence defects averaging 10.5 mm were treated with the technique. At 6 months, the sites were uncovered, and complete defect fill was noted in all cases. Results from this pilot case study indicated that the sandwich bone augmentation technique appears to enhance the outcomes of bone augmentation by using the positive properties of each applied material (autograft, DFDBA, hydroxyapatite, and collagen membrane). Future clinical trials for comparison of this approach with other bone augmentation techniques and histologic evaluation of the outcomes are needed to validate these findings.


Splenic follicular lymphoma: clinicopathologic characteristics of a series of 32 cases.
The spleen is frequently involved in B-cell lymphomas other than splenic marginal zone lymphoma. Here we describe a series of follicular lymphoma (FL) cases diagnosed in the spleen, consisting of 32 patients who presented clinically with splenomegaly, and slight or no peripheral lymphadenopathy. The splenic specimen had a micronodular pattern, germinal center cytologic composition, and frequent presence of marginal zone-like cells at the periphery of the nodules. Twenty cases showed absence or only partial/weak bcl2 protein expression, and 12 cases had homogeneous and strong positive bcl2 expression. The incidences of t(14;18)(q32;q21), CD10 expression, low histologic grade, and low proliferative index were significantly more frequent in FL bcl2-positive cases than in FL bcl2-negative cases. Splenic FL cases showed frequent relapses, with an overall survival of 55% at 5 years. No significant differences in survival were found between bcl2-negative and bcl2-positive cases. Splenic FL cases could be divided into 2 main variants: one was similar to classic FL with t(14;18) and CD10 expression, whereas the other was characterized by a higher proliferation index and histologic grade, and was more frequently diagnosed as a disease restricted to the spleen. Recognition of the distinct nature of these tumors should facilitate appropriate studies for determining the best therapy for such cases.


Unraveling the Complex Hybrid Ancestry and Domestication History of Cultivated Strawberry.
Cultivated strawberry (Fragaria × ananassa) is one of our youngest domesticates, originating in early eighteenth-century Europe from spontaneous hybrids between wild allo-octoploid species (Fragaria chiloensis and Fragaria virginiana). The improvement of horticultural traits by 300 years of breeding has enabled the global expansion of strawberry production. Here, we describe the genomic history of strawberry domestication from the earliest hybrids to modern cultivars. We observed a significant increase in heterozygosity among interspecific hybrids and a decrease in heterozygosity among domesticated descendants of those hybrids. Selective sweeps were found across the genome in early and modern phases of domestication-59-76% of the selectively swept genes originated in the three less dominant ancestral subgenomes. Contrary to the tenet that genetic diversity is limited in cultivated strawberry, we found that the octoploid species harbor massive allelic diversity and that F. × ananassa harbors as much allelic diversity as either wild founder. We identified 41.8 M subgenome-specific DNA variants among resequenced wild and domesticated individuals. Strikingly, 98% of common alleles and 73% of total alleles were shared between wild and domesticated populations. Moreover, genome-wide estimates of nucleotide diversity were virtually identical in F. chiloensis,F. virginiana, and F. × ananassa (π = 0.0059-0.0060). We found, however, that nucleotide diversity and heterozygosity were significantly lower in modern F. × ananassa populations that have experienced significant genetic gains and have produced numerous agriculturally important cultivars.


A novel, smaller scaffold for Affitins: Showcase with binders specific for EpCAM.
Affitins are highly stable engineered affinity proteins, originally derived from Sac7d and Sso7d, two 7 kDa DNA-binding polypeptides from Sulfolobus genera. Their efficiency as reagents for intracellular targeting, enzyme inhibition, affinity purification, immunolocalization, and various other applications has been demonstrated. Recently, we have characterized the 7 kDa DNA-binding family, and Aho7c originating from Acidianus hospitalis was shown to be its smallest member with thermostability comparable to those of Sac7d and Sso7d. Here, after four rounds of selection by ribosome display against the human recombinant Epithelial Cell Adhesion Molecule (hrEpCAM), we obtained novel Aho7c-based Affitins. The binders were expressed in soluble form in Escherichia coli, displayed high stability (up to 74°C; pH 0-12) and were shown to be specific for the hrEpCAM extracellular domain with picomolar affinities (KD = 110 pM). Thus, we propose Aho7c as a good candidate for the creation of Affitins with a 10% smaller size than the Sac7d-based ones (60 vs. 66 amino acids).


Supporting breastfeeding In Local Communities (SILC): protocol for a cluster randomised controlled trial.
Breastfeeding is associated with significant positive health outcomes for mothers and infants. However, despite recommendations from the World Health Organization, exclusive breastfeeding for six months is uncommon. Increased breastfeeding support early in the postpartum period may be effective in improving breastfeeding maintenance. This trial will evaluate two community-based interventions to increase breastfeeding duration in Local Government Areas (LGAs) in Victoria, Australia. A three-arm cluster randomised controlled trial design will be used. Victorian LGAs with a lower than average rate of any breastfeeding at discharge from hospital and more than 450 births per year that agree to participate will be randomly allocated to one of three trial arms: 1) standard care; 2) home-based breastfeeding support; or 3) home-based breastfeeding support plus access to a community-based breastfeeding drop-in centre. The services provided in LGAs allocated to 'standard care' are those routinely available to postpartum women. LGAs allocated to the home-based visiting intervention will provide home-visits to women who are identified as at risk of breastfeeding cessation in the early postnatal period. These visits will be provided by Maternal and Child Health Nurses who have received training to provide the intervention (SILC-MCHNs). In areas allocated to receive the second intervention, in addition to home-based breastfeeding support, community breastfeeding drop-in centres will be made available, staffed by a SILC-MCHN. The interventions will run in LGAs for a nine to twelve month period depending on birth numbers. The primary outcome is the proportion of infants receiving any breast milk at four months of age. Breastfeeding outcomes will be obtained from routinely collected Maternal and Child Health centre data and from a new data item collecting infant feeding 'in the last 24 hours'. Information will also be obtained directly from women via a postal survey. A comprehensive process evaluation will be conducted. This study will determine if early home-based breastfeeding support by a health professional for women at risk of stopping breastfeeding, with or without access to a community-based breastfeeding drop-in centre, increases breastfeeding duration in Victorian LGAs with low breastfeeding rates. Australian New Zealand Clinical Trials Registry: ACTRN12611000898954.


Clinical investigation in Duchenne dystrophy: V. Use of creatine kinase and pyruvate kinase in carrier detection.
We have determined the value of creatine and pyruvate kinase (CK and PK) in carrier detection by evaluating 811 females in 73 families participating in the Collaborative Investigation of Duchenne Dystrophy. Thirty-nine obligate carriers, 244 normal controls (paternal females), as well as 76 possible carriers and 351 carrier suspects had three CK and PK specimens analyzed at a central laboratory. The CK and PK values varied with age in normals: both fell with age early in life, and CK rose after the fifth decade. Discriminant analysis indicated that the combination of mean CK and PK corrected for age yielded the best data for calculation of carrier probability. Using the best model, only 45% of obligate carriers could be identified at a false-positive rate of 2.5%. Daughters of obligate carriers have a disproportionate decline in CK and PK with age as compared to noncarrier females, suggesting that the rate of carrier detection will be higher in the first two decades. Our low rate of carrier detection, as compared to other studies, may reflect both the age of our obligate carrier population and the use of a control group that is more representative of the carrier population.


Detection of implant crevicular fluid prostaglandin E2 levels for the assessment of peri-implant health: a pilot study.
Inflammatory changes in the peri-implant tissues may lead to peri-implantitis and bone loss. Prostaglandin E2 has been shown to have proinflammatory effects on peri-implant tissues, including mediation of bone resorption. The aim of this study was to assess prostaglandin E2 levels in implant crevicular fluid and the possibility of using this method in diagnosing peri-implant mucositis. Twenty-four dental implants with 3 mm or greater probing depths comprised the test group and another 24 implants with probing depths less than 3 mm served as the control group. Plaque index (PI), gingival index (GI), and probing pocket depths (PPD) were recorded. Implant crevicular fluid was obtained by collection onto periopapers. Then, prostaglandin E2 levels were evaluated using a commercially available enzyme immuno-assay kit. PI, GI, PPD, and implant crevicular fluid (ICF) levels of prostaglandin E2 were found to be statistically significantly higher in the test group (P < 0.05). In the test group, gingival index and probing depths were found to be statistically significantly related with ICF prostaglandin E2 levels (P < 0.05). In the control group, there was no statistically significant positive correlation between clinical parameters and ICF prostaglandin E2 levels (P > 0.05). It may be speculated that biochemical tests, such as the detection of prostaglandin E2 levels in the crevicular fluid are useful diagnostic methods for the maintenance of functional dental implants.


[Evidence of snakes in urban areas. Analysis of cases in the province of Cuneo and public health issues].
In this paper the authors analyse the cases of intrusion of snakes into urban environments in southern Piedmont (province of Cuneo) in the years 2010-2012 (up to may). In the study period there were 83 cases of intrusions in urban and domestic areas, mostly due to native harmless species (97.6%), while in 2.4% (n=2) of the cases alien species were responsible, and in 4.8% (n=4) poisonous native species were involved (Vipera aspis). The incidence of bites after a domestic intrusion is found to be 6% (n=5). All bites have resulted in loco-regional minor symptoms and occurred as a result of an accidental contact. In order to limit the risk of poisoning, the authors recommend the intrusions to be handled by properly trained personnel, since it can never be ruled out the presence of dangerous alien species on the national territory.


[Clinical and morphological characteristics of portal gastropathy in patients with liver cirrhosis].
to study the clinical and morphological manifestations of portal gastropathy in patients with liver cirrhosis (LC). One hundred and sixty-nine patients with Child-Pugh Classes B and C CL and 150 patients with gastritis and peptic ulcer disease without LC were examined. All the patients underwent fibrogastroscopy and morphological study of the gastric mucosa (GM). Morphological and serological studies detected Helicobacter pylori in all the patients. The endoscopic signs of portal gastropathy were found in 46.7-50.9% of the patients with LC; dilated capillaries and microbleedings in the GM were recorded in 73.9-83.7%. Ulcerative and erosive defects of the gastroduodenal area were identified in 31.9% of the patients with CL and these were accompanied by nemorrhages in 50% of cases. In patients with ulcers and erosions, the diameter of capillaries in different gastric portions was 23-56% larger than that in patients without these abnormalities. There was a significant direct correlation between the presence of H. pylori IgG and the morphological signs of portal gastropathy in the antrum. An association was found between the signs of portal gastropathy and the presence of ulcerative and erosive defects in the gastroduodenal area in patients with LC.


An innovative lab-based training program to help patient groups understand their disease and the research process.
Genuine partnership between patient groups and medical experts is important but challenging. Our training program meets this challenge by organizing hands-on, lab-based training sessions for members of patient groups. These sessions allow "trainees" to better understand their disease and the biomedical research process, and strengthen links between patients and local researchers. Over the past decade, we and our partner institutes have received more than 900 French patients, with the participation of over 60 researchers and clinicians.


Early changes in proteome levels upon acute deltamethrin exposure in mammalian skin system associated with its neoplastic transformation potential.
Deltamethrin, a pyrethroid insecticide, used extensively for pest control has been reported to cause adverse health effects including carcinogenic/toxic effects in animals but the underlying mechanism remains elusive. In the present study, we investigated the effect of deltamethrin after short exposure on early protein expression changes involved in neoplastic transformation in mouse skin, validated the results in human keratinocyte HaCaT cells and thereby explore the possible underlying mechanism. Deltamethrin (4 mg/kg b.wt) and benzo[a]pyrene (B[a]P, 0.05 mg/kg b.wt) were topically applied on Swiss albino mice, respectively. The comparative protein expression profiles with vehicle control were generated by 2-dimensional gel electrophoresis (2-DE) and mass spectrometry. 2-DE maps of deltamethrin and B[a]P treated mouse skin showed 20 and 24 significant (2 fold change, p < 0.05) differentially expressed protein spots, against vehicle controls. However, comparison between them showed relatively similar expression level of 20 spots. Among them, 5 proteins (carbonic anhydrase III, peroxiredoxin-2, calcyclin, superoxide dismutase [Cu-Zn], ubiquitin) are of particular significance as these are involved in cancer-related key processes. Deregulation of these was confirmed at protein and mRNA levels by immunoblotting and RT-PCR in mouse skin and HaCaT cells. Therefore, we conclude that these preliminarily identified proteins might be responsible for the neoplastic transformation of mouse skin epidermal cells and HaCaT cells by deltamethrin. This study proposes complementary mechanism where inhibition of proteasome activator protein (PA200) is responsible for accumulation of ubiquitinated-calcyclin, regulates deltamethrin-induced neoplastic changes in mouse skin and HaCaT cells.


Preisach models of hysteresis driven by Markovian input processes.
We study the response of Preisach models of hysteresis to stochastically fluctuating external fields. We perform numerical simulations, which indicate that analytical expressions derived previously for the autocorrelation functions and power spectral densities of the Preisach model with uncorrelated input, hold asymptotically also if the external field shows exponentially decaying correlations. As a consequence, the mechanisms causing long-term memory and 1/f noise in Preisach models with uncorrelated inputs still apply in the presence of fast decaying input correlations. We collect additional evidence for the importance of the effective Preisach density previously introduced even for Preisach models with correlated inputs. Additionally, we present some results for the output of the Preisach model with uncorrelated input using analytical methods. It is found, for instance, that in order to produce the same long-time tails in the output, the elementary hysteresis loops of large width need to have a higher weight for the generic Preisach model than for the symmetric Preisach model. Further, we find autocorrelation functions and power spectral densities to be monotonically decreasing independently of the choice of input and Preisach density.


Oral lesions as markers of severe immunosuppression in HIV-infected homosexual men and injection drug users.
We examined the diagnostic utility of the presence of oral lesions, individually and in combination, in identifying severe immunosuppression, defined as CD4 cell count under 200. Data were collected on 82 HIV-seropositive homosexual men and 82 HIV-seropositive injection drug users who volunteered to participate in a longitudinal study of HIV infection. CD4 cell counts were measured within 24 hours of oral examination. Sensitivity, specificity, positive predictive value, negative predictive value, and the odds ratio were computed to assess the association between oral lesions and CD4 less than 200. In addition to the individual lesions, we studied the diagnostic properties of sets of three to six lesions. For each set of lesions, a patient was classified as positive for the set if he or she had one or more lesions in that set. In homosexual men and injection drug users, individual lesions had low sensitivity, high specificity, and moderate positive and negative predictive values. Odds ratios reflected weak correlation to immunosuppression. When lesion sets were considered in homosexual men, sensitivity rose dramatically with only modest decreases in specificity. The positive and negative predictive values remained almost the same. Similar results for lesion sets were obtained in injection drug users, with greater reduction in specificity but stable positive and negative predictive values. Odds ratios indicated that for homosexual men, the more lesions included in the set, the stronger the correlation with immunosuppression. For injection drug users, strong correlations were observed for all lesion sets. Analysis of sensitivities and odds ratios in homosexual men suggest that it may be valid to note the occurrence of a greater number of oral lesions than is currently done in staging patients with HIV infection. Among injection drug users, monitoring a larger number of lesions neither improves nor reduces the correlation to severe immunosuppression.


Positioning intestinal ultrasound in a UK tertiary centre: significant estimated clinical role and cost savings.
Intestinal ultrasound (IUS) is an inexpensive, non-invasive method of diagnosing and monitoring inflammatory bowel disease (IBD). We aimed to establish the proportion of lower gastrointestinal endoscopies (LGIEs) and magnetic resonance enterographies (MREs) that could have been performed as IUS, the potential pathology miss-rates if IUS was used and the associated cost savings. All MREs and LGIEs performed for either assessment of IBD activity or investigation of possible IBD, performed at a single UK tertiary centre in January 2018, were retrospectively reviewed against predetermined criteria for IUS suitability. Case outcomes were recorded and cost of investigation if IUS was performed instead was calculated. 73 of 260 LGIEs (28.1%) and 58 of 105 MREs (55.2%) met the criteria for IUS suitability. Among potential IUS-suitable endoscopy patients, one case each of a <5 mm adenoma and sessile serrated lesion were found; no other significant pathology that would be expected to be missed with IUS was encountered. Among IUS-suitable MRE patients, no cases of isolated upper gastrointestinal inflammation likely to be missed by IUS were found, and extraintestinal findings not expected to be seen on IUS were of limited clinical significance. The predicted cost saving over 1 month if IUS was used instead was £8642, £25 866 and £5437 for MRE, colonoscopy and flexible sigmoidoscopy patients, respectively. There is a significant role for IUS, with annual projected cost savings of up to almost £500 000 at our centre. Non-inflammatory or non-gastrointestinal pathology predicted to be missed in this cohort was of limited clinical significance.


Biomarkers of heart transplant rejection: the good, the bad, and the ugly!
Acute cellular rejection (ACR), antibody-mediated rejection (AMR), and cardiac allograft vasculopathy (CAV) are important limitations for the long-term survival of heart transplant recipients. Although much progress has been made in reducing ACR with modern immunosuppressive treatments and continuous biopsy surveillance, there is still a long way to go to better understand and treat AMR, to enable early detection of patients at risk of CAV, and to reduce the development and sustained progression of this irreversible disease that permanently compromises graft function. This review considers the advances made in ACR detection and treatment allowing a more prolonged survival and the risk factors leading to endothelial injury, dysfunction, inflammation, and subsequent CAV, as well as new treatment modalities for CAV. The review also evaluates the controversies around the definition, pathogenesis, and treatment of AMR. To date, much progress is still needed to significantly reduce post-transplant complications and increase graft and patient survival.


Receptor subtype specific effects of GABA agonists on neurons receiving aortic depressor nerve inputs within the nucleus of the solitary tract.
The inhibitory amino acid gamma amino butyrate (GABA) has been shown to profoundly alter the integration of arterial baroreceptor inputs within the nucleus of the solitary tract (NTS). However, the relative roles of the major GABA receptor subtypes, the GABA(A) and the GABA(B) receptors, in the modulation of monosynaptic compared to polysynaptic afferent transmission within the NTS remain uncharacterized. In anesthetized rats, three types of NTS neuron were identified by their responses to aortic depressor nerve (ADN) stimulation; monosynaptic neurons (MSNs), polysynaptic neurons (PSNs) and ADN non-evoked neurons (NENs). Selective GABA(A) and GABA(B) agonists were applied to these neurons using iontophoretic techniques. The endogenous ligand GABA (2 mM), the selective GABA(A) agonist muscimol (0.04 and 0.02 mM) and the GABA(B) agonist baclofen (10 mM) all inhibited the spontaneous discharge of MSNs, PSNs and NENs (P < 0.01 for each group). In addition, GABA, muscimol and baclofen also inhibited ADN evoked discharge in both MSNs and PSNs (P < 0.05 for each group). Both GABA and baclofen significantly inhibited ADN evoked discharge in PSNs to a greater extent than in MSNs (P < 0.05 for each comparison). Muscimol at both doses, however, similarly inhibited ADN evoked discharge in both MSNs and PSNs. Examination of action potential amplitude and co-iontophoretic application of glutamate and GABA agonists suggested that GABA and muscimol induced inhibition were likely to be post-synaptic in origin, while baclofen produced both pre-synaptic and post-synaptic inhibition, depending upon the cell. In conclusion, GABA can influence baroreceptor afferent integration through both pre-synaptic and post-synaptic mechanisms. Furthermore, the effects of GABA(B) agonists are variable depending upon the level of afferent integration, with MSNs being generally less sensitive than PSNs.


Mobile Volume Rendering: Past, Present and Future.
Volume rendering has been a relevant topic in scientific visualization for the last decades. However, the exploration of reasonably big volume datasets requires considerable computing power, which has limited this field to the desktop scenario. But the recent advances in mobile graphics hardware have motivated the research community to overcome these restrictions and to bring volume graphics to these ubiquitous handheld platforms. This survey presents the past and present work on mobile volume rendering, and is meant to serve as an overview and introduction to the field. It proposes a classification of the current efforts and covers aspects such as advantages and issues of the mobile platforms, rendering strategies, performance and user interfaces. The paper ends by highlighting promising research directions to motivate the development of new and interesting mobile volume solutions.


Comparative analysis of two emerging rice seed bacterial pathogens.
Seed sterility and grain discoloration limit rice production in Colombia and several Central American countries. In samples of discolored rice seed grown in Colombian fields, the species Burkholderia glumae and B. gladioli were isolated, and field isolates were compared phenotypically. An artificial inoculation assay was used to determine that, although both bacterial species cause symptoms on rice grains, B. glumae is a more aggressive pathogen, causing yield reduction and higher levels of grain sterility. To identify putative virulence genes differing between B. glumae and B. gladioli, four previously sequenced genomes of Asian and U.S. strains of the two pathogens were compared with each other and with two draft genomes of Colombian B. glumae and B. gladioli isolates generated for this study. Whereas previously characterized Burkholderia virulence factors are highly conserved between the two species, B. glumae and B. gladioli strains are predicted to encode distinct groups of genes encoding type VI secretion systems, transcriptional regulators, and membrane-sensing proteins. This study shows that both B. glumae and B. gladioli can threaten grain quality, although only one species affects yield. Furthermore, genotypic differences between the two strains are identified that could contribute to disease phenotypic differences.


A mHealth Support Program for Australian Young Adults with Type 1 Diabetes: A Mixed Methods Study.
Young adulthood is a life stage comprised of many turning points. For young adults with type 1 diabetes (T1DM), diabetes self-management support is crucial during this period. There is a lack of diabetes education programs and services tailored to this population. This paper presents the findings, according to the STROBE guidelines, on the usability and acceptability of a patient-informed mHealth support program (Diabetes YES) that was developed for young adults with T1DM. A total of 34 young adults aged 18-35 years with T1DM participated in the Diabetes YES program over 12 weeks. Google analytics was used to tracked website use, while a website usability survey measured ease of use. Facebook analytics was used to measure peer support engagement. Evaluation of the program was completed using Likert scales and open-ended questions. Participants rated the website favourably for its ease of navigation and easy to understand information. Web page visits declined sharply while peer support group engagement through Facebook remained consistent throughout the intervention period. Participants utilised weekly discussion topics to generate conversation within the peer support group. Emotional support from peers was the highest regarded benefit reported by participants. Diabetes YES is an example of an mHealth support program that was readily accepted by young adults living with T1DM. Feasibility studies are an important formative step in the implementation of mHealth programs within mainstream healthcare. Future work should focus on the adaptability of such programs to fit within larger consumer or healthcare organisations.


Elbasvir-grazoprevir: A new direct-acting antiviral combination for hepatitis C.
The chemistry, pharmacology, pharmacodynamics, pharmacokinetics, efficacy, safety, dosage, administration, and role of elbasvir-grazoprevir in the treatment of hepatitis C virus (HCV) infection are reviewed. Elbasvir-grazoprevir was recently approved by the Food and Drug Administration for the treatment of chronic HCV genotype 1 or 4 infections with or without ribavirin in patients with or without compensated cirrhosis. Elbasvir exhibits antiviral activity against HCV genotypes 1a, 1b, 2a, 3a, and 4a. Elbasvir-grazoprevir undergoes fecal excretion, does not require dosage adjustment in patients with renal impairment, and is contraindicated in moderate and severe hepatic impairment. In Phase II and III clinical trials, elbasvir-grazoprevir administered orally for 12 weeks was shown to achieve a high sustained virological response 12 weeks after the end of treatment. Elbasvir-grazoprevir is a once-daily, fixed-dose combination tablet that can be taken without regard to food. The adverse drug reactions most commonly reported include fatigue, headache, and nausea. Elbasvir-grazoprevir is indicated with ribavirin for treatment-naive and treatment-experienced patients with genotype 1a with baseline NS5A polymorphisms, for treatment-experienced patients with genotype 1b, and for treatment-experienced patients with genotype 4. Elbasvir-grazoprevir achieves a high cure rate in the treatment of patients with chronic HCV with a once-daily oral regimen and without serious adverse effects; however, it requires close monitoring of liver function values. It is an effective option for patients with HCV genotype 1a, 1b, or 4 with or without compensated cirrhosis and is a particularly attractive option in patients with chronic kidney disease receiving hemodialysis and in patients with HIV coinfection.


CFIm25 regulates glutaminase alternative terminal exon definition to modulate miR-23 function.
Alternative polyadenylation (APA) and alternative splicing (AS) provide mRNAs with the means to avoid microRNA repression through selective shortening or differential usage of 3'UTRs. The two glutaminase (GLS) mRNA isoforms, termed KGA and GAC, contain distinct 3'UTRs with the KGA isoform subject to repression by miR-23. We show that depletion of the APA regulator CFIm25 causes a strong shift to the usage of a proximal poly(A) site within the KGA 3'UTR and also alters splicing to favor exclusion of the GAC 3'UTR. Surprisingly, we observe that while miR-23 is capable of down-regulating the shortened KGA 3'UTR, it has only minor impact on the full-length KGA 3'UTR, demonstrating that additional potent negative regulation of GLS expression exists beyond this single microRNA targeting site. Finally, we show that the apoptosis induced upon down-regulation of the GAC isoform can be alleviated through concurrent reduction in CFIm25 expression, revealing the sensitivity of glutaminase expression to the levels of RNA processing factors. These results exemplify the complex interplay between RNA processing and microRNA repression in controlling glutamine metabolism in cancer cells.


Experience with suprapubic vesicourethral suspension and endoscopic suspension of the vesical neck for stress urinary incontinence in females.
The morbidity and efficacy of suprapubic vesicourethral suspension and endoscopic suspension of the vesical neck for correction of stress urinary incontinence in females were analyzed. Between 1974 and 1981, 41 women were treated with the former procedure and between 1981 and 1984, 50 were treated with the latter. The two treatment groups were well matched with respect to age, duration of incontinence, grade of incontinence, previous unsuccessful anti-incontinence surgical procedures and experience of the operating surgeon. The incidences of excessive intraoperative blood loss, postoperative abdominal complications and late complications in the suprapubic suspension group were 7, 14 and 2 per cent, respectively, and in the endoscopic suspension group, zero, zero and 2 per cent, respectively. The mean duration of postoperative hospitalization in the suprapubic suspension and the endosocpic suspension groups were 9.4 and 6.9 days, respectively. Seventy-three per cent of the patients treated by suprapubic suspension (mean duration of follow-up 71 months) and 86 per cent of the patients treated by endoscopic suspension (mean duration of follow-up 19 months) were cured. We conclude that the morbidity of endoscopic suspension is less than that of suprapubic suspension and that the early results of endoscopic suspension are equivalent.


Analysis of the Near-Wall Flow in a Turbine Cascade by Splat Visualization.
Turbines are essential components of jet planes and power plants. Therefore, their efficiency and service life are of central engineering interest. In the case of jet planes or thermal power plants, the heating of the turbines due to the hot gas flow is critical. Besides effective cooling, it is a major goal of engineers to minimize heat transfer between gas flow and turbine by design. Since it is known that splat events have a substantial impact on the heat transfer between flow and immersed surfaces, we adapt a splat detection and visualization method to a turbine cascade simulation in this case study. Because splat events are small phenomena, we use a direct numerical simulation resolving the turbulence in the flow as the base of our analysis. The outcome shows promising insights into splat formation and its relation to vortex structures. This may lead to better turbine design in the future.


The isolation and characterization of a novel cDNA demonstrating an altered mRNA level in nontumorigenic Wilms' microcell hybrid cells.
Wilms' tumor, a pediatric nephroblastoma, has been associated with genetic alterations of the 11p13 and 11p15 regions. The introduction of a der(11) chromosome into the G401 Wilms' tumor cell line has been shown previously to revert the tumorigenic phenotype. A subtractive cDNA/RNA hybridization performed between the tumorigenic parent (G401) and a nontumorigenic microcell hybrid of G401 (110.1/G401.1) containing the der(11) chromosome resulted in the identification of a single novel cDNA clone, designated QM. The cDNA is 745 nucleotides in length and encodes a predicted hydrophilic 25 kd basic protein, primarily consisting of alpha helices. The QM transcript is expressed in a wide variety of embryonic and adult tissues and demonstrates a down regulation of expression in adult kidney and heart. QM is also a member of a multigene family members of which map to chromosomes 6 and 14. The QM mRNA level is modulated between the tumorigenic and nontumorigenic cell lines and therefore may be involved in the maintenance of the nontumorigenic phenotype.


Bactericidal efficacy of molybdenum oxide nanoparticles against antimicrobial-resistant pathogens.
Multidrug-resistant bacteria pose a major threat to effective antibiotics and alternatives to fight multidrug-resistant pathogens are needed. We synthetized molybdenum oxide (MoO3) nanoparticles (NP) and determined their antibacterial activity against 39 isolates: (i) eight Staphylococcus aureus, including representatives of methicillin-resistant S. aureus epidemic clones; (ii) six enterococci, including vancomycin-resistant isolates; and (iii) 25 Gram-negative isolates (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae), including extended spectrum beta-lactamases and carbapenemases producers. All isolates showed a MoO3 NP MIC of 700-800 mg l-1. MoO3 NP produced a clear inhibition zone for S. aureus and all Gram-negative isolates at concentrations ≥25 mg ml-1 and ≥50 mg ml-1 for enterococci. When the NP solutions were adjusted to pH ~7, the biocidal activity was completely abolished. MoO3 NP create an acidic pH and show a universal antimicrobial activity against susceptible and resistant isolates belonging to the most relevant bacterial species responsible for hospital-acquired infections.


Assessing smoking prevalence amongst school children in a health board region.
The objective of the study was to provide baseline data for Tayside in 1995 on the prevalence of smoking cigarettes in school children, aged 11 to 15 years. The design was a cross-sectional survey of 4675 children, obtained using a random cluster sample of 79 schools, stratified by school year and deprivation category. The main outcomes measures using a structured questionnaire, were the prevalence and level of smoking, by age and gender. The prevalence rate of regular smoking was 9% (95% CI 8.2%-9.8%). The rate rises appreciably for boys between 13 and 14 years and for girls between 12 and 13 years. Source of cigarettes was also an outcome measure, most cigarettes were obtained from small shops. Health Boards require a standard method for collecting regional baseline data on the prevalence of smoking among children both for evaluation of targeted health promotion initiatives by age and gender and also for comparison of regional smoking prevalence with national targets.


Electrophilic substitution of C60F18 into phenols: HF elimination between OH and a 1,3-shifted fluorine giving benzofurano[2',3':10,26]hexadecafluro[60]fullerene and derivatives.
The reaction of C60F18 with phenol, 2-naphthol and quinol in the presence of ferric chloride leads to initial electrophilic substitution (aryldefluorination). This occurs at both ortho and para positions for phenol, at the ortho position for quinol, and at the relatively hindered but most reactive 1-position for 2-naphthol. It is followed, where sterically favourable, by HF loss either between the OH group and F (rendered adjacent as a result of a 1,3-shift) or to attack of the OH group at an adjacent double bond with loss of a beta-fluorine, giving benzofurano[2',3':10,26]hexadecafluoro[60]fullerene derivatives. The reaction is accompanied by some complete defluorination leading, in reaction with phenol and with 2-naphthol, to the formation of benzofurano[2',3':1,2][60]fullerene and naphtho[2,1:b]furano[d:1,2][60]-fullerene, respectively. The mechanism of base-catalysed reaction of phenols with C60Cl6 is re-evaluated.


Problematic internet use and mental health among British children and adolescents.
Despite concerns about the effects of internet use, little is known about how problematic internet use impacts on British children and adolescents. By adapting the Problematic Internet Use Questionnaire (PIUQ, Demetrovics, Szeredi, & Rózsa, 2008), this study seeks its validation while studying its association with psychopathological and health problems. A sample of 1,814 children and adolescents (aged 10-16 years old) from UK schools completed questionnaires about PIU, behavioural problems, depression, anxiety and health problems. Confirmatory Factor Analysis identified three independent factors: Neglect, Obsession and Control Disorder. Using path analysis, PIU was significantly predicted by conduct problems, hyperactivity, impact on daily life activities, depression and poorer physical health. Males were more likely than females to score higher on PIU. The study shows for the first time that the adapted PIU questionnaire constitutes a valid tool for the assessment of problematic internet use among children/adolescents. The results also suggest an urgent need for the development of intervention strategies.


Maternal health outcomes in the context of fragility: a retrospective study from Lebanon.
The Lebanese healthcare system faces multiple challenges including limited capacities, shortage of skilled professionals, and inadequate supplies, in addition to hosting a significant number of refugees. While subsidized services are available for pregnant women, representing the majority of the refugee population in Lebanon, suboptimal access to antenatal care (ANC) and increased maternal mortality rates are still observed, especially among socioeconomically disadvantaged populations. This study aimed to review the maternal health outcomes of disadvantaged Lebanese and refugee pregnant women seeking ANC services at primary healthcare centers (PHCs) in Lebanon. A retrospective chart review was conducted at twenty PHCs in Lebanon, including Ministry of Public Health (MOPH) and United Nations Relief and Works Agency for Palestine refugees (UNRWA) facilities. Data was collected from medical charts of pregnant women who visited the centers between August 2018 and August 2020. Statistical analysis was performed to explore outcomes such as the number of ANC visits, delivery type, and onset of delivery, using bivariate and multivariable logistic regression models. In the study, 3977 medical charts were analyzed. A multivariate logistic regression analysis, revealed that suboptimal ANC visits were more common in the Beqaa region and among women with current abortion or C-section. Syrians had reduced odds of C-sections, and Beqaa, Mount Lebanon, and South Lebanon regions had reduced odds of abortion. Suboptimal ANC visits and history of C-section increased the odds of C-section and abortion in the current pregnancy. As for preterm onset, the study showed an increased likelihood for it to occur when being Palestinian, having current C-section delivery, experiencing previous preterm onset, and enduring complications at the time of delivery. This study suggests the need for low-cost interventions aiming at enhancing access to ANC services, especially among pregnant women in fragile settings.


An introduction to quality assurance with an application for perfusionists.
Cardiovascular perfusionists have always been interested in quality assurance (QA), most often in the form of equipment maintenance and record keeping. However, these activities have tended to be fragmented. In an attempt to define a more global approach to QA, basic concepts are identified and the steps used to start a formal QA program are illustrated. In the usual approach to QA, three areas are commonly assessed: Structure, Process, and Outcome. Structure evaluates the adequacy of facilities and personnel. Process involves review of the activities concerned with the management of patients. Outcome represents evaluation of the end points of care. In starting our formal QA program, five steps were delineated. These were planning the program, setting up an administration, assessing preexisting activities, initiating the program, and finally evaluating results. A QA specialist helped to define a number of concerns about perfusion from perfusionists, surgeons, anesthesiologists, and nurses. Using a standard approach to QA, these areas were defined according to Structure, Process, and Outcome.


A Cross-sectional Multicentre Qualitative Study Exploring Attitudes and Burnout Knowledge in Intensive Care Nurses with Burnout.
Although nurses in intensive care units (ICUs) are exposed to prolonged stress, no burnout prevention policy has yet been established. This study aims to determine the attitudes and "sense" of knowledge of burnout in nurses with burnout. The study, which has a qualitative exploratory phenomenological design, was carried out in several Croatian ICUs in 2017. ICU nurses suffering from burnout according to their score on the Maslach Burnout Inventory were chosen randomly from five hospitals. Their participation was voluntary. Of the 28 participants, 86% were women (n=24) and 14% men (n=4). They were aged mainly between 36 and 45 (n=11 (40%)) and between 26 and 35 (n=10 (36%)). Semi-structured interviews were conducted up to the saturation point. The conversations were audio-recorded and transcribed verbatim. The text was analysed using inductive thematic analysis, with codes derived and grouped into clusters by similarities in meaning, and interpretation as the final stage. Emergent themes, compromised private life, stressful work demands, stress reduction options, protective workplace measures and sense of knowledge reflected a variety of experiences, attitudes and knowledge of burnout. Nurses with burnout provided an insight into their experience and attitudes, and the problems created by burnout. Given the poor sense of knowledge about this syndrome, there is a need to implement education on burnout in nursing school curricula, and clear strategies in the ICU environment, i.e. information, awareness-raising, and specific guidelines on coping, burnout detection and prevention. Approaching burnout prevention through attitudes/social learning may be a novel and feasible model of addressing this issue.


[Effect of exogenous insulin on in vivo and in vitro antibody formation].
The effect of insulin in different doses on the process of the accumulation of plaque-forming cells in the spleen of immune mice was studied. Antibody response was suppressed in mice receiving various doses of insulin at different stages of immune response. When added in vitro, insulin also suppressed the formation of plaque-forming cells. The effect depended on the doses of insulin. The possible role of cyclic nucleotides in this process is discussed.


Transcriptional activation of glutathione pathways and role of glucose homeostasis during copper imbalance.
Copper is an essential micronutrient for organism health. Dietary changes or pathologies linked to this metal induce changes in intracellular glutathione concentrations. Here, we studied the transcriptional activation of glutathione pathways in Jurkat cell lines, analyzing the effect of change in glucose homeostasis during a physiological and supra-physiological copper exposure. An immortalized line of human T lymphocyte cell line (Jurkat) was exposed to different copper and glucose conditions to mimic concentrations present in human blood. We applied treatments for 6 (acute) and 24 h (sustained) to 2 µM (physiological) or 20 µM (supra-physiological, Wilson disease scenario) of CuSO4 in combination with 25 mg/dL (hypoglycemia), 100 mg/dL (normal) and 200 mg/dL (hyperglycemia, diabetes scenario) of glucose. The results indicate that a physiological concentration of copper exposure does not induce transcriptional changes in the glutathione synthesis pathway after 6 or 24 h. The G6PDH gene (regeneration pathway), however, is induced during a supra-physiological copper condition. This data was correlated with the viability assays, where fluctuation in both glucose conditions (hypo and hyperglycemia scenario) affected Jurkat proliferation when 20 µM of CuSO4 was added to the culture media. Under a copper overload condition, the transcription of a component of glutathione regeneration pathway (G6PDH gene) is activated in cells chronically exposed to a hyperglycemia scenario, indicating that fluctuations in glucose concentration impact the resistance against the metal. Our findings illustrate the importance of glucose homeostasis during copper excess.


An exploration of lifestyle beliefs and lifestyle behaviour following stroke: findings from a focus group study of patients and family members.
Stroke is a major cause of disability and family disruption and carries a high risk of recurrence. Lifestyle factors that increase the risk of recurrence include smoking, unhealthy diet, excessive alcohol consumption and physical inactivity. Guidelines recommend that secondary prevention interventions, which include the active provision of lifestyle information, should be initiated in hospital, and continued by community-based healthcare professionals (HCPs) following discharge. However, stroke patients report receiving little/no lifestyle information.There is a limited evidence-base to guide the development and delivery of effective secondary prevention lifestyle interventions in the stroke field. This study, which was underpinned by the Theory of Planned Behaviour, sought to explore the beliefs and perceptions of patients and family members regarding the provision of lifestyle information following stroke. We also explored the influence of beliefs and attitudes on behaviour. We believe that an understanding of these issues is required to inform the content and delivery of effective secondary prevention lifestyle interventions. We used purposive sampling to recruit participants through voluntary sector organizations (29 patients, including 7 with aphasia; 20 family members). Using focus group methods, data were collected in four regions of Scotland (8 group discussions) and were analysed thematically. Although many participants initially reported receiving no lifestyle information, further exploration revealed that most had received written information. However, it was often provided when people were not receptive, there was no verbal reinforcement, and family members were rarely involved, even when the patient had aphasia. Participants believed that information and advice regarding healthy lifestyle behaviour was often confusing and contradictory and that this influenced their behavioural intentions. Family members and peers exerted both positive and negative influences on behavioural patterns. The influence of HCPs was rarely mentioned. Participants' sense of control over lifestyle issues was influenced by the effects of stroke (e.g. depression, reduced mobility) and access to appropriate resources. For secondary prevention interventions to be effective, HCPs must understand psychological processes and influences, and use appropriate behaviour change theories to inform their content and delivery. Primary care professionals have a key role to play in the delivery of lifestyle interventions.


Endoscopic bulking materials for the treatment of vesicoureteral reflux: a review of our 20 years of experience and review of the literature.
Purpose. We reviewed our 20 years of experience and the current literature regarding the long-term outcome of endoscopic treatment of vesicoureteric reflux (VUR) using the different tissue bulking substances with a special emphasis on the long-term efficacy. Material and Methods. Our own experience and the current literature on the long-term results after endoscopic treatment using various bulking agents were reviewed. Results. Short-term data following endoscopic treatment of VUR is similar to the various substances and comparable in the majority of the series to the success rate following open surgery. Recently, a relatively high recurrence rate was noticed especially with the use of dextranomer hyaluronic acid (Dx/HA) as a tissue augmenting material which raises the need for further search for alternative substances. Conclusions. Unfortunately, there is a significant shortage of evidence-based literature on the long-term followup after endoscopic correction of reflux with various substances. No doubt, there is a high recurrence rate during long-term followup after Dx/HA injection, and there is probably lack of proper evaluation regarding the long-term efficacy of other bulking materials. These facts demand long-term close observation and long-term studies beyond the routine protocols following endoscopic treatment of VUR and the correct parental counseling upon the endoscopic correction.


Evaluation of Transverse Maxillary Expansion After a Segmental Posterior Subapical Maxillary Osteotomy in Cleft Lip and Palate Patients With Severe Collapse of the Lateral Maxillary Segments.
Objective : The purpose of this longitudinal retrospective study was to evaluate transverse maxillary expansion after a Schuchardt or segmental posterior subapical maxillary osteotomy (SPSMO) in patients with cleft lip and palate (CLP). A second aim was to compare these data with data for adult patients without CLP who were receiving a surgical assisted rapid palatal expansion (SARPE). Method : The study group comprised 19 patients with CLP and a severe transversally collapsed maxilla who were treated with SPSMO followed by hyrax expansion at the University Hospitals Leuven. Dental casts of the 19 patients were analyzed before treatment, at maximum expansion, during orthodontic treatment, at the completion of orthodontic treatment. and 2 years after orthodontic treatment and were measured at the canine, premolar, and molar levels. Adult patients without CLP who were enrolled in a prospective study served as the control group. Results : Maxillary expansion within the study group was significantly greater (P < .05) at all measured levels compared with the maxillary arch before treatment. No significant relapse was measured in the study group 2 years after orthodontic treatment. When comparing the study and control groups, the only statistical difference was that canine expansion was significantly greater in the study group. Conclusion : SPSMO followed by maxillary expansion and orthodontic treatment is an appropriate treatment option to correct a severe transversally collapsed maxilla in patients with CLP. The overall treatment effect of SPSMO expansion is comparable with the effects of SARPE, although canine expansion was greater in the SPSMO group.


Constraining the optimization of a fuzzy logic controller using an enhanced genetic algorithm.
Fuzzy logic controllers (FLCs) are gaining in popularity across a broad array of disciplines because they allow a more human approach to control. Recently, the design of the fuzzy sets and the rule base has been automated by the use of genetic algorithms (GAs) which are powerful search techniques. Though the use of GAs can produce near optimal FLCs, it raises problems such as messy overlapping of fuzzy sets and rules not in agreement with common sense. This paper describes an enhanced genetic algorithm which constrains the optimization of FLCs to produce well-formed fuzzy sets and rules which can be better understood by human beings. To achieve the above, we devised several new genetic operators and used a parallel GA with three populations for optimizing FLCs with 3x3, 5x5, and 7x7 rule bases, and we also used a novel method for creating migrants between the three populations of the parallel GA to increase the chances of optimization. In this paper, we also present the results of applying our GA to designing FLCs for controlling three different plants and compare the performance of these FLC's with their unconstrained counterparts.


Web-assisted assessment of professional behaviour in problem-based learning: more feedback, yet no qualitative improvement?
Although other web-based approaches to assessment of professional behaviour have been studied, no publications studying the potential advantages of a web-based instrument versus a classic, paper-based method have been published to date. This study has two research goals: it focuses on the quantity and quality of comments provided by students and their peers (two researchers independently scoring comments as correct and incorrect in relation to five commonly used feedback rules (and resulting in an aggregated score of the five scores) on the one, and on the feasibility, acceptability and perceived usefulness of the two approaches on the other hand (using a survey). The amount of feedback was significantly higher in the web-based group than in the paper based group for all three categories (dealing with work, others and oneself). Regarding the quality of feedback, the aggregated score for each of the three categories was not significantly different between the two groups, neither for the interim, nor for the final assessment. Some, not statistically significant, but nevertheless noteworthy trends were nevertheless noted. Feedback in the web-based group was more often unrelated to observed behaviour for several categories for both the interim and final assessment. Furthermore, most comments relating to the category 'Dealing with oneself' consisted of descriptions of a student's attendance, thereby neglecting other aspects of personal functioning. The survey identified significant differences between the groups for all questionnaire items regarding feasibility, acceptability and perceived usefulness in favour of the paper-based form. The use of a web-based instrument for professional behaviour assessment yielded a significantly higher number of comments compared to the traditional paper-based assessment. Unfortunately, the quality of the feedback obtained by the web-based instrument as measured by several generally accepted feedback criteria did not parallel this increase.


Association between Chewing Difficulty and Dietary Ca, Vitamin D, and Mg Intake in Korean Older Adults: 8th Korea National Health and Nutrition Examination Survey (KNHANES) (2020-2021).
Nutrition intake plays a pivotal role in chewing difficulty (CD). This cross-sectional descriptive study aims to explore the associations between CD and the dietary intake of calcium (Ca), vitamin D, and magnesium (Mg) in adults aged 65 and older, utilizing data from the 8th Korea National Health and Nutrition Examination Survey (2020-2021). The chewing function was assessed using a 5-point scale questionnaire that inquired about discomfort experienced during mastication. "Very uncomfortable" and "uncomfortable," two of the five response options, were categorized as being indicative of CD. Dietary intake was assessed through 24 h dietary recall interviews, and nutrient calculations were based on the 10th revised edition of the Korean Food Composition Table. Data (N = 2942) were analyzed using descriptive statistics and multi-logistic regression analyses in a composite sample plan file. Among the 2942 subjects, groups with insufficient daily nutrient intake had significantly higher odds ratios (ORs) for CD compared to their counterparts. In men, the ORs for Ca (1.56), Mg (1.75), and the combined intake of Mg (1.64) with Ca were elevated. In women, the ORs for Ca (1.74), Mg (1.53), and the combined intake of Mg (1.43) with Ca showed similar trends. After adjusting for age, family income, and family size variables, men's ORs for Mg (1.55) and the combined intake of Mg (1.55) with Ca remained elevated, while women's OR for Ca (1.58), Mg (1.42), and the combined intake of Mg (1.34) with Ca remained significant. Dietary vitamin D intake did not significantly impact the OR for CD. After adjusting for natural tooth numbers, self-perceived oral health, and obesity, no significant association was found between CD and these nutrients. In conclusion, this study underscores the importance of promoting the recommended daily intake of magnesium alongside dietary calcium to address CD.


Sarcocystis caninum and Sarcocystis svanai n. spp. (Apicomplexa: Sarcocystidae) Associated with Severe Myositis and Hepatitis in the Domestic Dog (Canis familiaris).
There are several reports of Sarcocystis sarcocysts in muscles of dogs, but these species have not been named. Additionally, there are two reports of Sarcocystis neurona in dogs. Here, we propose two new names, Sarcocystis caninum, and Sarcocystis svanai for sarcocysts associated with clinical muscular sarcocystosis in four domestic dogs (Canis familiaris), one each from Montana and Colorado in the USA, and two from British Columbia, Canada. Only the sarcocyst stage was identified. Most of the sarcocysts identified were S. caninum. Sarcocysts were studied using light microscopy, transmission electron microscopy (TEM), and polymerase chain reaction. Based on collective results two new species, S. caninum and S. svanai were designated. Sarcocystis caninum and S. svanai were structurally distinct. Sarcocystis caninum sarcocysts were up to 1.2 mm long and up to 75 μm wide. By light microscopy, the sarcocyst wall was relatively thin and smooth. By TEM, the sarcocyst wall was "type 9", 1-2 μm thick, and contained villar protrusions that lacked microtubules. Bradyzoites in sections were 7-9 μm long. Sarcocysts of S. svanai were few and were identified by TEM. Sarcocystis svanai sarcocysts were "type 1", thin walled (< 0.5 μm), and the wall lacked villar protrusions but had tiny blebs that did not invaginate. DNA was extracted either from infected frozen muscle biopsies or formalin-fixed paraffin-embedded sections. Dogs were either singly infected with S. caninum or multiply co-infected with S. caninum and S. svanai (the result of a mixed infection) based on multilocus DNA sequencing and morphology. BLASTn analysis established that the sarcocysts identified in these dogs were similar to, but not identical to Sarcocystis canis or Sarcocystis arctosi, parasites found to infect polar bears (Ursus maritimus) or brown bears (Ursus arctosi), respectively. However, the S. caninum sequence showed 100% identify over the 18S rRNA region sequenced to that of S. arctica, a parasite known to infect Arctic foxes (Vulpes lagopus).


Dioctyl sodium sulphosuccinate increases net ultrafiltration in peritoneal dialysis.
The surface-active substance dioctyl sodium sulphosuccinate (DSS) has been reported to increase the peritoneal clearances of urea and creatinine. This study investigated the effects of DSS on the fluid and solute transport characteristics of the peritoneum. A 4-h single-dwell experiment session of peritoneal dialysis using 25 ml of 3.86% glucose dialysis solution with an intraperitoneal volume maker was performed in 16 male Sprague-Dawley rats. In eight rats, 0.005% (50 p.p.m.) DSS was added to the dialysis fluid. No DSS was given to the other eight rats (control group). The transport of fluid, glucose, potassium, sodium, urea, phosphate and urate were analysed. There was a significant increase in the intraperitoneal volume in the DSS group. At 240 min, the drain volume in DSS group (33.0 +/- 2.9 ml) was significantly higher compared to the control group (28.8 +/- 2.1 ml, P < 0.01). This increase in the drain volume was mainly due to a decrease in peritoneal fluid absorption rate in the DSS group (0.040 +/- 0.013 ml/min) as compared to the control group (0.054 +/- 0.010 ml/min, P < 0.05). There was no significant difference in the diffusive permeability and sieving coefficient for the small solutes between these two groups. However, the clearances for urea and sodium were higher in the DSS group, mainly due to the increase in the dialysate volume. Our results suggest that DSS significantly increases the net ultrafiltration of peritoneal dialysis. This effect, which was mainly due to a decrease in the fluid absorption rate, contributed to the increased clearances for urea and sodium. DSS did not alter the diffusive permeability and sieving coefficient for the small solutes.


Temozolomide pharmacodynamics in patients with metastatic melanoma: dna damage and activity of repair enzymes O6-alkylguanine alkyltransferase and poly(ADP-ribose) polymerase-1.
Temozolomide, a DNA methylating agent used to treat melanoma, induces DNA damage, which is repaired by O6-alkylguanine alkyltransferase (ATase) and poly(ADP-ribose) polymerase-1 (PARP-1)-dependent base excision repair. The current study was done to define the effect of temozolomide on DNA integrity and relevant repair enzymes as a prelude to a phase I trial of the combination of temozolomide with a PARP inhibitor. Temozolomide (200 mg/m2 oral administration) was given to 12 patients with metastatic malignant melanoma. Peripheral blood lymphocytes (PBL) were analyzed for PARP activity, DNA single-strand breakage, ATase levels, and DNA methylation. PARP activity was also measured in tumor biopsies from 9 of 12 patients and in PBLs from healthy volunteers. Temozolomide pharmacokinetics were consistent with previous reports. Temozolomide therapy caused a substantial and sustained elevation of N7-methylguanine levels, a modest and sustained reduction in ATase activity, and a modest and transient increase in DNA strand breaks and PARP activity in PBLs. PARP-1 activity in tumor homogenates was variable (828 +/- 599 pmol PAR monomer/mg protein) and was not consistently affected by temozolomide treatment. The effect of temozolomide reported here are consistent with those documented in previous studies with temozolomide and similar drug, dacarbazine, demonstrating that a representative patient population was investigated. Furthermore, PARP activity was not inhibited by temozolomide treatment and this newly validated pharmacodynamic assay is therefore suitable for use in a proof-of-principle phase I trial a PARP-1 inhibitor in combination with temozolomide.


Tauroursodeoxycholic acid improves the survival and function of nigral transplants in a rat model of Parkinson's disease.
There is accumulating evidence showing that the majority of cell death in neural grafts results from apoptosis when cells are implanted into the brain. Tauroursodeoxycholic acid (TUDCA), a taurine-conjugated hydrophilic bile acid, has been found to possess antiapoptotic properties. In the present study we have examined whether the supplementation of TUDCA to cell suspensions prior to transplantation can lead to enhanced survival of nigral grafts. We first conducted an in vitro study to examine the effects of TUDCA on the survival of dopamine neurons in serum-free conditions. The number of tyrosine hydroxylase (TH)-positive neurons in the TUDCA-treated cultures was significantly greater than that of control cultures 7 days in vitro. In addition, a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assay showed that the number of apoptotic cells in the TUDCA-treated cultures was dramatically smaller than that in the control cultures. In the transplantation study, a 50 microM concentration of TUDCA was added to the media when nigral tissue from Sprague-Dawley (SD) rats was trypsinized and dissociated. Two microliters of cell suspension containing TUDCA was then stereotaxically injected into the striatum of adult SD rats subjected to an extensive unilateral 6-hydroxydopamine lesion of the nigrastriatal dopamine pathway. At 2 weeks after transplantation, the rats that received a cell suspension with TUDCA exhibited a significant reduction in amphetamine-induced rotation scores when compared with pretransplantation value. There was a significant increase (approximately threefold) in the number of TH-positive cells in the neural grafts for the TUDCA-treated group when compared with the controls 6 weeks postgrafting. The number of apoptotic cells was much smaller in the graft areas in the TUDCA-treated groups than in the control group 4 days after transplantation. These data demonstrate that pretreatment of the cell suspension with TUDCA can reduce apoptosis and increase the survival of grafted cells, resulting in an improvement of behavioral recovery.


Impact of Antithrombin Activity Levels Following Recombinant Antithrombin Gamma Therapy in Patients with Sepsis-Induced Disseminated Intravascular Coagulation.
Recombinant antithrombin gamma (rAT) is reported as an effective drug for patients with disseminated intravascular coagulation (DIC) in Japan. As the appropriate dose and targeted AT activity remain unknown, this study aimed to determine these aspects for sepsis-induced DIC. Thirty-one patients with septic shock and DIC with AT levels <70% were treated with rAT between May 2018 and December 2020. The recovery rates from DIC were 32.2% and 63.3% on day 3 and 5 post administration, respectively. Recovery and survival rates were significantly higher in patients who achieved AT activity ≥70% or 80% on day 3 post administration. Receiver operating characteristic curve analysis revealed that the cutoff values of post-treatment AT activity on day 3 for 28-day survival and 5-day recovery from DIC were 79.5% and 81.5%, respectively. Patients who did not achieve AT activity ≥80% on day 3 presented a lower base level of AT activity and lower dose supplementation. Our results suggest that targeted AT activity should be at least 70%, and ideally 80%, and sufficient doses to maintain this activity are required to achieve better outcomes.


Student nurse preferences for their first clinical experience: a thematic analysis.
Shifts in demographic profiles and in the understanding of how to best deliver health care have seen nurses increasingly caring for non-acute client groups outside traditional clinical settings. Evidence suggests that this does not always sit well with nurses, or with nurses in training. This study sought to investigate the influences on student nurse perceptions of the worth of working with various client groups. Thematic analysis of a focus group discussion led to the identification of several themes suggesting that unhelpful opinions are present in some students on entry to the programme; however, programme-related influences also contribute towards unhelpful attitudes. To create a more positive framing of working within such specialisms will require significant focus across nursing, nurse education and society in general.


Trichostasis spinulosa.
Trichostasis spinulosa is a common disorder of follicular hyperkeratosis that is often confused clinically with similar disorders, such as keratosis pilaris and eruptive vellus hair cysts. Six patients from the UTMB dermatology clinic who had trichostasis spinulosa are presented. Two of the six also had keratosis pilaris and one had eruptive vellus hair cysts. The present study was undertaken to compare and contrast the clinical presentation and histopathologic appearance of these three disorders. The results of the study and review of the literature revealed differences in distribution of lesions and microscopic appearance of follicular and histopathologic material.


Dominance of the residential sector in Chinese black carbon emissions as identified from downwind atmospheric observations during the COVID-19 pandemic.
Emissions of black carbon (BC) particles from anthropogenic and natural sources contribute to climate change and human health impacts. Therefore, they need to be accurately quantified to develop an effective mitigation strategy. Although the spread of the emission flux estimates for China have recently narrowed under the constraints of atmospheric observations, consensus has not been reached regarding the dominant emission sector. Here, we quantified the contribution of the residential sector, as 64% (44-82%) in 2019, using the response of the observed atmospheric concentration in the outflowing air during Feb-Mar 2020, with the prevalence of the COVID-19 pandemic and restricted human activities over China. In detail, the BC emission fluxes, estimated after removing effects from meteorological variability, dropped only slightly (- 18%) during Feb-Mar 2020 from the levels in the previous year for selected air masses of Chinese origin, suggesting the contributions from the transport and industry sectors (36%) were smaller than the rest from the residential sector (64%). Carbon monoxide (CO) behaved differently, with larger emission reductions (- 35%) in the period Feb-Mar 2020, suggesting dominance of non-residential (i.e., transport and industry) sectors, which contributed 70% (48-100%) emission during 2019. The estimated BC/CO emission ratio for these sectors will help to further constrain bottom-up emission inventories. We comprehensively provide a clear scientific evidence supporting mitigation policies targeting reduction in residential BC emissions from China by demonstrating the economic feasibility using marginal abatement cost curves.


Variability of BCG strains (Bacillus Calmette-Guérin).
Three different cultures of BCG propagated for over 2 years in a liquid medium containing Tween 80 and albumin were found to differ in several of their intrinsic properties. Cultures of the three strains were found to consist of morphologically heterogeneous populations-each culture being made up of three main colonial types-spreading, intermediate, and non-spreading. The percentage distribution of colonial types was characteristic for each culture and remained constant during cultivation in liquid media. Injection of the various cultures into mice and guinea pigs resulted in a self-limited disease. The distribution, extent, and duration of the lesions were also characteristic for each culture. Both the spreading and non-spreading substrains derived from the various cultures exhibited the degree of attenuation of virulence characteristic of the parent strain.


Neuromuscular patterns and the origin of trophic specialization in fishes.
The pattern of muscle electrical activity in the pharyngeal muscles of the mollusc-eating sunfish Lepomis microlophus is highly specialized in comparison with the pattern displayed by most other members of the sunfish family and does not change when different prey are eaten. The closest genealogical relative of this species has the specialized muscle activity pattern for crushing prey when it feeds on snails but uses the primitive sequence of muscle activity during swallowing of other prey. The ability of species that crush snails to use molluscan prey effectively is due primarily to the evolutionary transformation of the neuromuscular program controlling the trophic apparatus.


Suppression of murine neuroblastoma growth in vivo by mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyzes the formation of mevalonate, an essential precursor for isoprenoid compounds in mammalian cells. Recent studies have shown that mevinolin, a competitive inhibitor of the reductase, inhibits cell proliferation and induces differentiation in cultured C1300 (Neuro-2A) murine neuroblastoma cells. We now report that mevinolin can inhibit neuroblastoma growth in vivo. The specific activity of HMG-CoA reductase in subcutaneous neuroblastomas increased more than 20-fold between the fifth and eighth days after tumor inoculation, and remained elevated for the remainder of the tumor lifetime in mice. The increase in reductase activity was correlated with a marked increase in tumor DNA content and exponential increase in tumor weight. Using an in vitro assay to monitor the ability of mouse serum to suppress sterol synthesis, we determined that mevinolin was inactivated or cleared from the circulation within 3-6 h after a single subcutaneous injection. However, by using subcutaneous osmotic pumps to deliver a constant infusion of mevinolin, we were able to maintain adequate blood levels of the drug for 7 d. Mevinolin (5 mg/kg per h) suppressed tumor growth (wet weight) significantly when treatment was carried out between day 1 and day 8 or between day 5 and day 12 after tumor inoculation. Histopathological examination of tumors from mevinolin-treated mice revealed few or no mitotic figures and marked cellular degeneration. Measurements of incorporation of (3H)acetate into neuroblastoma sterols and ubiquinones 24 h after implantation of osmotic pumps showed that mevinolin produced a marked inhibition of isoprenoid synthesis in the tumors in vivo. The data suggest that, in addition to their demonstrated utility as cholesterol-lowering drugs, competitive inhibitors of HMG-CoA reductase may have considerable potential as novel antineoplastic agents.


Highly cohesive dual nanoassemblies for complementary multiscale bioimaging.
Innovative nanostructures made of a high payload of fluorophores and superparamagnetic nanoparticles (NPs) have simply been fabricated upon self-assembling in a two-step process. The resulting hybrid supraparticles displayed a dense shell of iron oxide nanoparticles tightly attached through an appropriate polyelectrolyte to a highly emissive non-doped nanocore made of more than 105 small organic molecules. Cooperative magnetic dipole interactions arose due to the closely packed magnetic NPs at the nanoarchitecture surface, causing enhanced NMR transverse relaxivity. Large in vivo MRI T2 contrast was thus obtained with unusually diluted solutions after intravenous injection in small rodents. Two-photon excited fluorescence imaging could be performed, achieving unprecedented location resolution for agents combining both magnetic nanoparticles and fluorescence properties. Finally, TEM imaging of the sectioned mouse tissue succeeded in isolating the core-shell structures, which represents the first image of intact complex magnetic and fluorescent nanoassemblies upon in vivo injection. Such highly cohesive dual nanoarchitectures should open great horizons toward the assessment with high spatial resolution of the drug or labeled stem cell biodistribution.


Reconstructing the contour of metallic planar objects from only intensity scattered field data over a single plane.
The inverse scattering problem of recovering the contour of planar metallic scattering objects from only the amplitude of the scattered field is considered. A two step reconstruction procedure is proposed: first the phase of the scattered field is retrieved by solving a phase retrieval problem; then the objects' supports are reconstructed from the retrieved scattered field. Differently form previous approaches, here the amplitude of the scattered field is assumed known over a single plane in near zone but at two different frequencies. In this way, while the frequency diversity increases the number of independent data, relevant for ensuring the reliability of the phase retrieval stage, to perform measurements on a single plane allows some practical advantages. Numerical results show the performances achievable by the proposed reconstruction scheme with respect to the local minima problem and the stability against the noise on data.


A Homozygous Mutation in GPT2 Associated with Nonsyndromic Intellectual Disability in a Consanguineous Family from Costa Rica.
Intellectual disability is a highly heterogeneous disease that affects the central nervous system and impairs patients' ability to function independently. Despite multiples genes involved in the etiology of disease, most of the genetic background is yet to be discovered. We used runs of homozygosity and exome sequencing to study a large Costa Rican family with four individuals affected with severe intellectual disability and found a novel homozygous missense mutation, p. 96G>R, c. 286G>A, in all affected individuals. This gene encodes for a pyridoxal enzyme involved in the production of the neurotransmitter glutamate and is highly expressed in the white matter of brain and cerebellum. Protein modeling of GPT2 predicted that the mutation is located in a loop where the substrate binds to the active site of the enzyme, therefore, suggesting that the catalytic activity is impaired. With our report of a second mutation we fortify the importance of GPT2 as a novel cause of autosomal recessive nonsyndromic intellectual disability and support the premise that GPT2 is highly important for the neurodevelopment of the central nervous system. The mutation p. 96G>R c. 286G>A in GPT2, located in a loop where the substrate binds to the active site of the enzyme, fortifies the importance of GPT2 in the pathogenesis of nonsyndromic intellectual disability.


A specific synbiotic-containing amino acid-based formula in dietary management of cow's milk allergy: a randomized controlled trial.
Here we report follow-up data from a double-blind, randomized, controlled multicenter trial, which investigated fecal microbiota changes with a new amino acid-based formula (AAF) including synbiotics in infants with non-immunoglobulin E (IgE)-mediated cow's milk allergy (CMA). Subjects were randomized to receive test product (AAF including fructo-oligosaccharides and Bifidobacterium breve M-16V) or control product (AAF) for 8 weeks, after which infants could continue study product until 26 weeks. Fecal percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) were assessed at 0, 8, 12, and 26 weeks. Additional endpoints included stool markers of gut immune status, clinical symptoms, and safety assessments including adverse events and medication use. The trial included 35 test subjects, 36 controls, and 51 in the healthy reference group. Study product was continued by 86% and 92% of test and control subjects between week 8-12, and by 71% and 80%, respectively until week 26. At week 26 median percentages of bifidobacteria were significantly higher in test than control [47.0% vs. 11.8% (p < 0.001)], whereas percentages of ER/CC were significantly lower [(13.7% vs. 23.6% (p = 0.003)]. Safety parameters were similar between groups. Interestingly use of dermatological medication and reported ear infections were lower in test versus control, p = 0.019 and 0.011, respectively. Baseline clinical symptoms and stool markers were mild (but persistent) and low, respectively. Symptoms reduced towards lowest score in both groups. Beneficial effects of this AAF including specific synbiotics on microbiota composition were observed over 26 weeks, and shown suitable for dietary management of infants with non-IgE-mediated CMA.Trial Registration NTR3979.


The Mais Médicos (More Doctors) Program in Northeast: evaluation of hospitalizations for Primary Healthcare-sensitive conditions.
This paper analyzes the increase in professionals in Brazil's Northeastern Region resulting from the Mais Médicos (More Doctors) Program. The scale of the increase was analyzed through the indicator Hospitalizations for Primary-Care Sensitive Conditions (HPSCs). The method used was a quantitative approach, based on data on distribution of doctors and service they provided in these states, and on hospitalizations for diarrhea and gastroenteritis in the period September 2012 to August 2015. The choice of this condition took into account the aspects of: its high frequency in the period; the simplicity of intervention; and its historic occurrence in the Northeast. The results show that the Mais Médicos Program had an influence on the reduction of hospitalizations for this type of condition - they fell by 35% in the period investigated, with important differences between the states. In spite of the significant scale of the entry of medical professionals into the health system, it is known that in isolation simply increasing the number of professionals of a particular type has a limited effect in improving primary healthcare.


Evaluation of glucose tolerance during treatment with celiprolol in patients with mild arterial hypertension without diabetes mellitus. The Genker General Practitioners.
A prospective evaluation of the metabolic effects of Celiprolol, a third generation Beta-Blocking agent was done by 10 general practitioners in 45 mildly hypertensive patients. (diastolic blood pressure > or = 95 mm/Hg and < or = 115 mm/Hg. In 43 patients with complete data, blood pressure and resting heart rate decreased significantly after treatment, but weight and metabolic parameters were unchanged. After 6 months therapy the 22 patients with an impaired glucose tolerance test (IGTT) had a significant decrease in plasma glucose and insulin values, and a tendency for increased HDL. These favorable metabolic effects of Celiprolol in mildly hypertensive patients with an abnormal GTT are different from the findings with other beta-blockers and justify further study.


Near-infrared dye loaded polymeric nanoparticles for cancer imaging and therapy and cellular response after laser-induced heating.
In the past decade, researchers have focused on developing new biomaterials for cancer therapy that combine imaging and therapeutic agents. In our study, we use a new biocompatible and biodegradable polymer, termed poly(glycerol malate co-dodecanedioate) (PGMD), for the synthesis of nanoparticles (NPs) and loading of near-infrared (NIR) dyes. IR820 was chosen for the purpose of imaging and hyperthermia (HT). HT is currently used in clinical trials for cancer therapy in combination with radiotherapy and chemotherapy. One of the potential problems of HT is that it can up-regulate hypoxia-inducible factor-1 (HIF-1) expression and enhance vascular endothelial growth factor (VEGF) secretion. We explored cellular response after rapid, short-term and low thermal dose laser-IR820-PGMD NPs (laser/NPs) induced-heating, and compared it to slow, long-term and high thermal dose heating by a cell incubator. The expression levels of the reactive oxygen species (ROS), HIF-1 and VEGF following the two different modes of heating. The cytotoxicity of NPs after laser/NP HT resulted in higher cell killing compared to incubator HT. The ROS level was highly elevated under incubator HT, but remained at the baseline level under the laser/NP HT. Our results show that elevated ROS expression inside the cells could result in the promotion of HIF-1 expression after incubator induced-HT. The VEGF secretion was also significantly enhanced compared to laser/NP HT, possibly due to the promotion of HIF-1. In vitro cell imaging and in vivo healthy mice imaging showed that IR820-PGMD NPs can be used for optical imaging. IR820-PGMD NPs were developed and used for both imaging and therapy purposes. Rapid and short-term laser/NP HT, with a low thermal dose, does not up-regulate HIF-1 and VEGF expression, whereas slow and long term incubator HT, with a high thermal dose, enhances the expression of both transcription factors.


[Hemichorea-hemiballism associated to cryptococcal granuloma in a patient with AIDS: case report].
Movement disorders are not common in acquired immunodeficiency syndrome. Hemichorea-hemiballism (HC-HB) is the most common of them all, and it is usually related to oportunistic toxoplasmosis of the basal ganglia. We present a 28-year-old man, HIV positive with HC-HB caused by a right subthalamic granuloma, which did not respond to treatment for toxoplasmosis. Cryptoccococic antigen was positive in the cerebrospinal fluid and antifungic therapy led to clinical and radiologic improvement, thus the diagnosis of a granulomatous lesion by Cryptococcus neoformans was established. Current literature on HC-HB and its relationship with AIDS is subsequently reviewed.


Therapeutic Potential of Resveratrol for Glioma: A Systematic Review and Meta-Analysis of Animal Model Studies.
Gliomas are aggressive malignant brain tumors, with poor prognosis despite available therapies, raising the necessity for finding new compounds with therapeutic action. Numerous preclinical investigations evaluating resveratrol's anti-tumor impact in animal models of glioma have been reported; however, the variety of experimental circumstances and results have prevented conclusive findings about resveratrol's effectiveness. Several databases were searched during May 2023, ten publications were identified, satisfying the inclusion criteria, that assess the effects of resveratrol in murine glioma-bearing xenografts. To determine the efficacy of resveratrol, tumor volume and animal counts were retrieved, and the data were then subjected to a random effects meta-analysis. The influence of different experimental conditions and publication bias on resveratrol efficacy were evaluated. Comparing treated to untreated groups, resveratrol administration decreased the tumor volume. Overall, the effect's weighted standardized difference in means was -2.046 (95%CI: -3.156 to -0.936; p-value < 0.001). The efficacy of the treatment was observed for animals inoculated with both human glioblastoma or rat glioma cells and for different modes of resveratrol administration. The combined administration of resveratrol and temozolomide was more effective than temozolomide alone. Reducing publication bias did not change the effectiveness of resveratrol treatment. The findings suggest that resveratrol slows the development of tumors in animal glioma models.


New therapeutic modalities to modulate orthodontic tooth movement.
Modulation of orthodontic tooth movement (OTM) is desirable not only to patients because it shortens treatment time, but also to orthodontists, since treatment duration is associated with increased risk of gingival inflammation, decalcification, dental caries, and root resorption. The increased focus on the biological basis of tooth movement has rendered Orthodontics a more comprehensive specialty that incorporates facets of all fields of medicine. Current knowledge raises the possibility of using new therapeutic modalities for modulation of OTM, such as corticotomy, laser therapy, vibration (low-intensity pulsed ultrasound), local injections of biomodulators and gene therapy; with the latter being applicable in the near future. They are intended to enhance or inhibit recruitment, differentiation and/or activation of bone cells, accelerate or reduce OTM, increase stability of orthodontic results, as well as assist with the prevention of root resorption. This article summarizes recent studies on each one of these therapeutic modalities, provides readers with information about how they affect OTM and points out future clinical perspectives.


Informed consent and the capacity for voluntarism.
Informed consent is built upon the elements of information, decisional capacity, and volunteerism. Of these elements, voluntarism in clinical and research consent is the least well understood. This has interfered with the ability to resolve key ethical problems faced by the field of psychiatry. The author suggests that voluntarism encompasses an individual's ability to act in accordance with one's authentic sense of what is good, right, and best in light of one's situation, values, and prior history. Voluntarism further entails the capacity to make this choice freely and in the absence of coercion. Deliberateness, purposefulness of intent, clarity, genuineness, and coherence with prior life decisions are implicitly emphasized in this construction. The author offers and illustrates a framework for voluntarism in clinical and research consent decisions, focusing on four domains of potential influence: 1) developmental factors, 2) illness-related considerations, 3) psychological issues and cultural and religious values, and 4) external features and pressures. It is hoped that improved understanding of voluntarism will help in our efforts to fulfill the principle of respect for persons in clinical care and research.


Receptor-mediated endocytosis of soluble and membrane-tethered Sonic hedgehog by Patched-1.
Patched (Ptc) is the ligand-binding component of the Hedgehog (Hh) receptor complex. In the Drosophila embryo, Ptc and Hh colocalize in vesicular punctate structures. However, receptor-mediated endocytosis of Hh proteins has not been demonstrated. By using chick neural plate explants, we show that Sonic hedgehog (Shh)-responsive neural precursor cells internalize recombinant and endogenous Shh and provide direct evidence for a gradient of endogenous Shh in the ventral neural tube. Shh internalization is blocked by a monoclonal antibody whose epitope overlaps the Ptc-binding site of Shh. These findings suggest that Shh internalization is mediated by Ptc-1 and may be linked to signaling. Concordantly, transfection of mammalian cell lines with a Ptc-1 cDNA confers the ability to internalize multiple forms of Shh, including transmembrane-anchored Shh, by a dynamin-dependent process.


Changes in Na+, K+ concentrations in perspiration and perspiration volume with alternating current iontophoresis in palmoplantar hyperhidrosis patients.
Various treatments are currently available for palmoplantar hyperhidrosis. We have treated palmoplantar hyperhidrosis patients effectively with the use of alternating current (AC) iontophoresis. However, much remains unknown about the physiological changes that occur with AC iontophoresis, and its mechanism of action. We measured the changes in Na(+), K(+) concentration in perspiration and perspiration volume with AC iontophoresis in palmoplantar hyperhidrosis patients. We found that hyperhidrosis patients have significantly higher perspiration volume and Na(+) concentration in perspiration than healthy controls. Looking at the temporal changes with AC iontophoresis, we found a significant decrease in perspiration volume and Na(+) concentration in perspiration after six iontophoresis treatments. This result is further evidence that Na(+) concentration in perspiration is closely involved with perspiration volume. However, looking at the changes in perspiration volume and Na(+) concentration in perspiration before and after a single AC iontophoresis treatment, we found that while perspiration volume did not decrease in hyperhidrosis patients after a single treatment, there was a significant decrease in Na(+) concentration. In healthy controls as well, Na(+) concentration in perspiration decreased significantly after a single treatment. These findings suggest that the effect of AC iontophoresis may be due to a complex mechanism involving changes in reabsorption of ductal Na(+).