Dystrophin genotype-cardiac phenotype correlations in Duchenne and Becker muscular dystrophies using cardiac magnetic resonance imaging.
Duchenne and Becker muscular dystrophies are caused by mutations in dystrophin. Cardiac manifestations vary broadly, making prognosis difficult. Current dystrophin genotype-cardiac phenotype correlations are limited. For skeletal muscle, the reading-frame rule suggests in-frame mutations tend to yield milder phenotypes. We performed dystrophin genotype-cardiac phenotype correlations using a protein-effect model and cardiac magnetic resonance imaging. A translational model was applied to patient-specific deletion, indel, and nonsense mutations to predict exons and protein domains present within truncated dystrophin protein. Patients were dichotomized into predicted present and predicted absent groups for exons and protein domains of interest. Development of myocardial fibrosis (represented by late gadolinium enhancement [LGE]) and depressed left ventricular ejection fraction (LVEF) were compared. Patients (n = 274) with predicted present cysteine-rich domain (CRD), C-terminal domain (CTD), and both the N-terminal actin-binding and cysteine-rich domains (ABD1 + CRD) had a decreased risk of LGE and trended toward greater freedom from LGE. Patients with predicted present CTD (exactly the same as those with in-frame mutations) and ABD1 + CRD trended toward decreased risk of and greater freedom from depressed LVEF. In conclusion, genotypes previously implicated in altering the dystrophinopathic cardiac phenotype were not significantly related to LGE and depressed LVEF. Patients with predicted present CRD, CTD/in-frame mutations, and ABD1 + CRD trended toward milder cardiac phenotypes, suggesting that the reading-frame rule may be applicable to the cardiac phenotype. Genotype-phenotype correlations may help predict the cardiac phenotype for dystrophinopathic patients and guide future therapies.


Protection afforded by heat shock protein 60 from Francisella tularensis is due to copurified lipopolysaccharide.
Heat shock proteins (Hsps) have attracted significant attention as protective antigens against a range of diseases caused by bacterial pathogens. However, more recently there have been suggestions that the protective response is due to the presence of peptide components other than Hsps. We have shown that mice that had been immunized with purified heat shock protein 60 (Hsp60) isolated from Francisella tularensis were protected against a subsequent challenge with some strains of the bacterium. However, this protection appeared to be due to trace amounts of lipopolysaccharide, which were too low to be detected by using the Limulus amoebocyte lysate assay. This finding raises the possibility that the protection afforded by other bacterial Hsp60 proteins may be due to trace quantities of polysaccharide antigens carried by and acting in conjunction with the Hsps.


Insights into the function of the CRM1 cofactor RanBP3 from the structure of its Ran-binding domain.
Proteins bearing a leucine-rich nuclear export signal (NES) are exported from the nucleus by the transport factor CRM1, which forms a cooperative ternary complex with the NES-bearing cargo and with the small GTPase Ran. CRM1-mediated export is regulated by RanBP3, a Ran-interacting nuclear protein. Unlike the related proteins RanBP1 and RanBP2, which promote disassembly of the export complex in the cytosol, RanBP3 acts as a CRM1 cofactor, enhancing NES export by stabilizing the export complex in the nucleus. RanBP3 also alters the cargo selectivity of CRM1, promoting recognition of the NES of HIV-1 Rev and of other cargos while deterring recognition of the import adaptor protein Snurportin1. Here we report the crystal structure of the Ran-binding domain (RBD) from RanBP3 and compare it to RBD structures from RanBP1 and RanBP2 in complex with Ran and CRM1. Differences among these structures suggest why RanBP3 binds Ran with unusually low affinity, how RanBP3 modulates the cargo selectivity of CRM1, and why RanBP3 promotes assembly rather than disassembly of the export complex. The comparison of RBD structures thus provides an insight into the functional diversity of Ran-binding proteins.


Model-based redesign of global transcription regulation.
Synthetic biology aims to the design or redesign of biological systems. In particular, one possible goal could be the rewiring of the transcription regulation network by exchanging the endogenous promoters. To achieve this objective, we have adapted current methods to the inference of a model based on ordinary differential equations that is able to predict the network response after a major change in its topology. Our procedure utilizes microarray data for training. We have experimentally validated our inferred global regulatory model in Escherichia coli by predicting transcriptomic profiles under new perturbations. We have also tested our methodology in silico by providing accurate predictions of the underlying networks from expression data generated with artificial genomes. In addition, we have shown the predictive power of our methodology by obtaining the gene profile in experimental redesigns of the E. coli genome, where rewiring the transcriptional network by means of knockouts of master regulators or by upregulating transcription factors controlled by different promoters. Our approach is compatible with most network inference methods, allowing to explore computationally future genome-wide redesign experiments in synthetic biology.


Increased blood pressure following pupillary dilation with 2.5% phenylephrine hydrochloride in preterm infants.
Heart rate and blood pressure changes following 0.5% tropicamide and 2.5% phenylephrine hydrochloride were evaluated in seven ill preterm infants (birth weight, 910 to 2,060 gm; gestational age, 26 to 36 weeks) during the first day of life. Each infant was monitored continuously for 30 minutes before and for 75 minutes after, instillation of the pupillary dilators. There were no significant changes in the heart rate, whereas a significant increase in systolic, diastolic, and mean arterial blood pressure was found. The increase in arterial blood pressure was detected at two minutes, peaked at eight minutes, and remained at significantly higher levels for 30 minutes after instillation. Because of the potential relationship between increased blood pressure and intraventricular hemorrhage, arterial blood pressure must be monitored during instillation of mydriatic drugs in the preterm infant.


MBW complexes impinge on anthocyanidin reductase gene regulation for proanthocyanidin biosynthesis in persimmon fruit.
MBW protein complexes containing MYB, bHLH and WD40 repeat factors are known transcriptional regulators of secondary metabolites production such as proanthocyanidins and anthocyanins, and developmental processes such as trichome formation in many plant species. DkMYB2 and DkMYB4 (MYB-type), DkMYC1 (bHLH-type) and DkWDR1 (WD40-type) factors have been proposed by different authors to take part of persimmon MBW complexes for proanthocyanidin accumulation in immature fruit, leading to its characteristic astringent flavour with important agronomical and ecological effects. We have confirmed the nuclear localization of these proteins and their mutual physical interaction by bimolecular fluorescence complementation analysis. In addition, transient expression of DkMYB2, DkMYB4 and DkMYC1 cooperatively increase the expression of a persimmon anthocyanidin reductase gene (ANR), involved in the biosynthesis of cis-flavan-3-ols, the structural units of proanthocyanidin compounds. Collectively, these data support the presence of MBW complexes in persimmon fruit and suggest their coordinated participation in ANR regulation for proanthocyanidin production.


[Pancreaticoduodenectomy in the era of evidence based medicine].
The aim of this comprehensive literature review was to analyse evidence based data in the field of pancreaticoduodenectomy. Pylorus preserving does reduce mortality or morbidity of the standard procedure and could increase the risk of delayed gastric emptying. Pancreaticogastrostomy does not decrease the rate of postoperative pancreatic fistula and is not superior to the pancreaticojejunal anastomosis which is more physiological. No other procedure (chemical occlusion, octreotide, stenting) has been demonstrated to prevent pancreatic fistula. Octreotide injection could be advocated in centres where there is a high rate of pancreatic fistula, when pancreatic parenchyma is soft and the main pancreatic duct thin. Intra-abdominal drainage is not beneficial and could be associated with some morbidity. Its use needs to be further evaluated. When a resection is done for pancreatic cancer, less than 5% of patients are a live five years after surgery with postoperative mortality rate of 5% in expert centres and a high morbidity rate (25-50%). Extended lymphadenectomy does not increase survival. The first trials showed that adjuvant therapies could be beneficial for pancreatic cancers, but further trials did not confirm these findings. Adjuvant therapy is not validated for pancreatic cancers and needs to be considered only in the settings of clinical trials.


Association of ACO Shared Savings Success and Serious Illness Spending.
Accountable care organizations (ACOs) need confidence in their return on investment to implement changes in care delivery that prioritize seriously ill and high-cost Medicare beneficiaries. The objective of this study was to characterize spending on seriously ill beneficiaries in ACOs with Medicare Shared Savings Program (MSSP) contracts and the association of spending with ACO shared savings. The population included Medicare fee-for-service beneficiaries identified with serious illness (N = 2,109,573) using the Medicare Master Beneficiary Summary File for 100% of ACO-attributed beneficiaries linked to MSSP beneficiary files (2014-2016). Lower spending for seriously ill Medicare beneficiaries and risk-bearing contracts in ACOs were associated with achieving ACO shared savings in the MSSP. For most ACOs, the seriously ill contribute approximately half of the spending and constitute 8%-13% of the attributed population. Patient and geographic (county) factors explained $2,329 of the observed difference in per beneficiary per year spending on seriously ill beneficiaries between high- and low-spending ACOs. The remaining $12,536 may indicate variation as a result of potentially modifiable factors. Consequently, if 10% of attributed beneficiaries were seriously ill, an ACO that moved from the worst to the best quartile of per capita serious illness spending could realize a reduction of $1,200 per beneficiary per year for the ACO population overall. Though the prevalence and case mix of seriously ill populations vary across ACOs, this association suggests that care provided for seriously ill patients is an important consideration for ACOs to achieve MSSP shared savings.


Risk of recurrent gastrointestinal bleeding after aortic valve replacement in patients with Heyde syndrome.
We sought to evaluate the effectiveness of aortic valve replacement for reducing gastrointestinal bleeding in patients with Heyde syndrome, in whom gastrointestinal bleeding is associated with intestinal angiodysplasia and aortic valve stenosis. We conducted a retrospective review of patients treated at the Mayo Clinic between 1971 and 2007 for gastrointestinal bleeding and intestinal angiodysplasia who later underwent aortic valve replacement for severe aortic valve stenosis. We analyzed early and late outcomes, including recurrent gastrointestinal hemorrhage. Fifty-seven patients (39 men and 18 women) were identified. At operation, the median age of patients was 75 years. Intestinal angiodysplasia occurred most commonly in the duodenum and right side of the colon. Before aortic valve replacement, the mean number of bleeding episodes was 12 per patient-year; 48 patients (84%) required blood transfusions. Bioprosthetic valves were used in 47 patients. During follow-up extending to 15 years, 45 patients (79%) had no recurrence of bleeding. In patients who experienced recurrent bleeding, the episodes were reduced from a mean ± standard deviation of 4.7 ± 7 episodes per patient-year to 1.9 ± 2 per patient-year. Recurrent bleeding occurred only in patients with lesions of the duodenum or right colon. Among patients who received bioprostheses, the overall risk of recurrent bleeding was 15%, lower than the 50% risk of subsequent gastrointestinal bleeding with mechanical prostheses. Aortic valve replacement seems to decrease the risk of gastrointestinal bleeding in patients with Heyde syndrome and is curative in approximately 80%. Although rates of recurrent bleeding were not significantly different between the 2 prosthetic valve types, the higher risk of bleeding in patients receiving warfarin makes bioprosthetic valves the valve of choice for most patients.


Blood flow in mobilized nerves: results in a rabbit sciatic nerve model.
The purpose of this study was to evaluate the immediate effect on capillary blood flow of surgical mobilization of 15 cm of the rabbit sciatic and tibial nerve. Capillary nerve blood flow was determined with 16-micron radioactive microspheres. Thirty-seven rabbits were divided into six groups. In the control group A (n = 7), the in situ nerve blood flow was determined. In group B (n = 7), the nerve was mobilized, leaving only the proximal and distal endoneurial vascular supplies; blood flow increased compared with in situ values in most segments. In group C (n = 5), the nerve was mobilized as in group B, but also transected distally; blood flow was markedly decreased in the distal segments but was maintained up to a diameter-to-length ratio of 1:63. In group D (n = 6), the nerve was not mobilized, but was transected proximally and distally; blood flow increased in all segments. In group E (n = 5), the nerve was mobilized and transected proximally and distally, leaving only nerve branches intact; blood flow was significantly higher in segments of the nerve from which nerve branches originated with the nerve receiving blood flow through its branches. In group F (n = 6), the nerve was mobilized, all extrinsic vessels except one were transected, and the proximal and distal nerve was transected; flow was maintained to a diameter:length ratio of 1:41 from the source of blood flow. Therefore, it does appear that long lengths of nerve may be mobilized and transposed while maintaining sufficient blood flow.


Biomedical and bioimaging applications of 2D pnictogens and transition metal dichalcogenides.
Multifunctional platforms will play a key role and gain more prominence in the field of personalized healthcare worldwide in the near future due to the ever-increasing number of patients suffering from cancer. Along with the development of efficient techniques for cancer treatment, a considerable effort should be devoted toward the exploration of an emerging class of materials with unique properties that might be beneficial in this context. Currently, 2D post-carbon materials, such as pnictogens (phosphorene, antimonene), transition metal dichalcogenides, and boron nitride, have become popular due to their efficient photothermal behavior, drug-loading capability, and low toxicity. This review underlines the recent progresses made in the abovementioned 2D materials for photothermal/photodynamic cancer therapies and their applicability in bioimaging applications.


The Oregon Health Plan: predictors of office-based diabetic quality of care.
In 1994, the Oregon Health Plan (OHP) expanded basic Medicaid insurance to residents under the federal poverty limit, adopted a prioritized limited benefits package, and converted to managed care. The quality of care in predominantly Medicaid populations with diabetes has not been previously described. In OHP enrollees, we examined predictors of diabetes care based on American Diabetes Association guidelines and described OHP diabetes care compared with national benchmarks. Chart abstraction and Medicaid data for 1995-1996 yielded 996 nonpregnant diabetic patients who were 18-64 years of age. Using HbA1c, lipid panel, and urine protein/microalbumin documentation ordered during the study year, we constructed a standard care (SC) index: SC for all three tests, mixed care (MC) for one to two tests, or no tests documented (NTD). Our sample was predominantly white, 48 +/- 11 years of age, 63% women, with 8 +/- 5 provider visits. Providers ordered HbA1c (70%), urine microalbumin/protein (57%), and lipid panel (41%) tests. Patients distributed into SC (22%), MC (62%), or NTD (16%). Thirteen variables predicted SC. Patients had a higher likelihood of SC if they were 18-24 years of age, had more clinic visits, were on insulin daily, were in several comorbid groups, were enrolled in salaried or capitated health plans, or lived in counties with more hospital beds. Four studies were used as comparable national benchmarks. Care provided to OHP patients with diabetes compares favorably with national benchmarks. Yet, most OHP patients with diabetes are still not achieving optimal care. Examining predictors of SC may play an important role in further policy development.


Arsenic from community water fluoridation: quantifying the effect.
Community water fluoridation is a WHO recommended strategy to prevent dental carries. One debated concern is that hydrofluorosilicic acid, used to fluoridate water, contains arsenic and poses a health risk. This study was undertaken to determine if fluoridation contributes to arsenic in drinking water, to estimate the amount of additional arsenic associated with fluoridation, and compare this to the National Sanitation Foundation/American National Standards Institute (NSF/ANSI) standard and estimates from other researchers. Using surveillance data from Ontario drinking water systems, mixed effects linear regression was performed to examine the effect of fluoridation status on the difference in arsenic concentration between raw water and treated water samples. On average, drinking water treatment was found to reduce arsenic levels in water in both fluoridated and non-fluoridated systems by 0.2 μg/L. However, fluoridated systems were associated with an additional 0.078 μg/L (95% CI 0.021, 0.136) of arsenic in water when compared to non-fluoridated systems (P = 0.008) while controlling for raw water arsenic concentrations, types of treatment processes, and source water type. Our estimate is consistent with concentrations expected from other research and is less than 10% of the NSF/ANSI standard of 1 μg/L arsenic in water. This study provides further information to inform decision-making regarding community water fluoridation.


An Analysis and Comparison of Survival and Functional Outcomes in Oropharyngeal Squamous Cell Carcinoma Patients Treated with Concurrent Chemoradiation Therapy within City of Hope Cancer Center Sites.
Oropharyngeal squamous cell carcinoma (OPSCC) is a subset of head and neck cancers that can arise due to human papillomavirus (HPV) infection. We designed a retrospective analysis to determine differences in outcomes of OPSCC patients treated at City of Hope (COH) Cancer Center's main campus versus selected satellite sites with COH-associated faculty and facilities. Patients diagnosed with OPSCC and treated with concurrent chemoradiation therapy (n = 94) were identified and included in the study. Patients underwent treatment at the COH main campus site (n = 50) or satellite sites (n = 44). The majority of patients were Caucasian, male, and diagnosed with p16 positive stage IV locally advanced OPSCC by AJCC 7th edition. Most patients completed their prescribed cumulative radiation therapy dose and had a complete response to treatment. No significant difference in overall survival and progression-free survival was observed between the main campus and the satellite sites. Our study demonstrates successful treatment completion rates as well as comparable recurrence rates between the main campus and COH-associated satellite sites. A trend toward significant difference in feeding tube dependency at 6-months was observed. Differences in feeding tube placement and dependency rates could be addressed by the establishment of on-site supportive services in satellite sites.


Traumatic brain injury assessed with olfactory event-related brain potentials.
Olfactory event-related potentials (OERPs) were evaluated to develop an objective, quantitative assessment of sensory and cognitive olfactory loss following traumatic brain injury (TBI). Subjects included 25 TBI patients and 25 age/gender-matched healthy controls. Following standard clinical evaluation of smell function, TBI patients were divided into three groups: 12 anosmics (loss of smell), 6 hyposmics (reduced smell), and 7 normosmics (normal smell). Cognitive ability was assessed using the Trail Making Test (A and B). OERPs were recorded monopolarly from midline electrode sites using an amyl acetate stimulus with a 60-second interstimulus interval; subjects estimated the magnitude of each odor stimulus. Anosmic TBI patients were also tested with OERPs using ammonia to ensure trigeminal nerve function. Amyl acetate OERPs demonstrated that the sensory N1 and P2 amplitudes and the cognitive P3 amplitudes were absent in the anosmic TBI patients and greatly reduced in the hyposmic and normosmic TBI patients compared to healthy controls. The trigeminal OERPs from the anosmic TBI patients were within normal limits, indicating that the primary olfactory deficits were objectively measured with OERPs. The relationship between the OERPs and neuropsychologic test performance supports the cognitive loss associated with TBI. The present study lends support to the utility of OERPs as an objective tool for measuring sensory and cognitive loss after traumatic brain injury.


Mental health-care utilization in survivors of childhood cancer and siblings: the Swiss childhood cancer survivor study.
We aimed to (1) describe the utilization of mental health-care in survivors and siblings, the association with severity of distress, and visits to other professionals in distressed survivors not utilizing mental health-care; and (2) identify factors associated with utilization of mental health-care in distressed survivors. Within the Swiss Childhood Cancer Survivor Study, we sent postal questionnaires to all participants aged <16 years at diagnosis (1976-2003), who survived ≥5 years after diagnosis and were aged ≥16 years at study. Survivors and siblings could indicate if they utilized mental health-care in the past year. Psychological distress was assessed with the Brief Symptom Inventory-18 (BSI-18). Participants with scores T ≥ 57 on two of three scales or the Global Severity Index were considered distressed. We included 1,602 survivors and 703 siblings. Overall, 160 (10 %) and 53 (8 %), utilized mental health-care and 203 (14 %) and 127 (14 %) were considered distressed. Among these, 69 (34 %) survivors and 20 (24 %) siblings had utilized mental health-care. Participants with higher distress were more likely to utilize mental health-care. Distressed survivors not utilizing mental health-care were more likely to see a medical specialist than nondistressed. In the multivariable regression, factors associated with utilizing mental health-care were higher psychological distress and reporting late effects. Our results underline the importance of developing interventional programs and implementing psychological screening in follow-up of survivors. It is also important to systematically address siblings' needs. In follow-up, patients at risk should be informed about existing possibilities or advised to visit mental health professionals.


Blood transfusion: uses, abuses, and hazards.
Homologous blood transfusion without risk is an unobtainable goal. Infection with human immunodeficiency virus continues to occur at an average rate of one infection per 100,000 transfusions, in spite of the most sensitive and specific testing available. In the past 30 years, the number of red cell antigens identified have increased from primarily ABO and Rh to some 400 antigens, which has also contributed to the hazards of blood transfusion. These risks can be minimized by the judicious use of homologous blood in conjunction with technological advances in transfusion medicine therapy and changes in attitudes of transfusionists. In the operating theater, there has been a resurgence in intraoperative autologous transfusion therapy, and patients are individualized rather than held to an arbitrary hemoglobin standard prior to anesthesia. In the preoperative period, elective surgical candidates may predeposit autologous blood or select directed donors. The prospective recipient or the directed donor may be candidate for recombinant erythropoietin therapy as a prelude to blood donation. This article discusses the uses of blood and blood products, the hazards of blood transfusion, and precautions that can be taken to minimize risks to the patient.


Who leaves the emergency department without being seen? A public hospital experience in Georgetown, Guyana.
Left without being seen (LWBS) proportions are commonly used as quality control indicators, but little data is available on LWBS proportions in the developing world. This study sought to determine the proportion and characteristics of patients who LWBS from the emergency department (ED) of the main public hospital in Georgetown, Guyana. This is a retrospective cross-sectional analysis of an ED quality assurance database. Registration personnel collected demographic information on patients presenting to the ED over a 2-week period in July 2010. Both univariate and multivariate analysis were conducted to determine patient characteristics associated with LWBS. The LWBS proportion was 5.7%. In univariate analysis, patients 18 or older (OR 1.48, 95%CI 1.03-2.12), presenting during the 4PM-12AM shift (OR 2.15, 95%CI 1.53-3.01), with non-urgent triage classification (OR 1.88, 95%CI 1.76-4.66), with non-traumatic chief complaints (OR 1.70, 95%CI 1.14-2.55), or who were not transferred (OR 2.13, 95%CI 1.00-4.55) had significantly higher odds of LWBS. On multivariate analysis, only patients 18 or older (OR 1.54, 95%CI 1.02-2.33), presenting during the 4PM-12AM shift (OR 2.29, 95%CI 1.54-3.40), and with non-traumatic chief complaints (OR 2.39, 95%CI 1.43-4.02) were found to be significantly associated with LWBS. Sex, residence in the capital city, time to triage, transfer status, use of EMS, and triage classification were not statistically associated with LWBS. LWBS proportions are used as quality control indicators and this study determined the LWBS proportion at a public hospital in a developing country and some of the patient characteristics associated with LWBS. This can be helpful to develop strategies to decrease LWBS proportions and to assess progress over time.


Cytogenetic abnormalities in hematologic neoplasms with germline predisposition.
The number of predisposing genes is continuously growing with the widespread availability of DNA sequencing, increasing the prevalence of hematologic malignancies with germline predisposition. Cytogenetic analyses provide an effective approach for the recognition of these malignancies with germline predisposition, which is critical for proper diagnosis, optimal treatment and genetic counseling. Based on the World Health Organization and the international consensus classifications as well as the European LeukemiaNet recommendations, this review first presents an advanced classification of neoplasms with germline predisposition focused on the acquired cytogenetic alterations during leukemogenesis. The various genetic rescue mechanisms and the progression to transformation are then explained. The review also outlines the specific constitutional and somatic cytogenetic aberrations indicative of germline predisposition disorders in B-acute lymphoblastic leukemia (ALL), T-ALL, bone marrow failure syndrome and myeloid neoplasms. An emphasis is made on monosomy 7 in the predisposition field, its frequency and diagnosis impact as well as its various circumstances of occurrence. Lastly, we propose cytogenetic technical recommendations and guidelines for clinical reporting of these specific aberrations.


Soybean extracts facilitate bacterial agglutination and prevent biofilm formation on orthodontic wire.
Soybean is an essential food ingredient that contains a class of organic compounds known as isoflavones. It is also well known that several plant agglutinins interfere with bacterial adherence to smooth surfaces. However, little is known about the effects of soybean extracts or genistein (a purified isoflavone from soybean) on bacterial biofilm formation. We evaluated the effects of soybean (Glycine max) extracts, including fermented soybean and genistein, on streptococcal agglutination and attachment onto stainless steel orthodontic wire. After cultivating streptococci in biofilm medium containing soybean extracts and orthodontic wire, the viable bacteria attached to the wire were counted. Phase-contrast microscopy and scanning electron microscopy (SEM) analyses were conducted to evaluate bacterial agglutination and attachment. Our study showed that soybean extracts induce agglutination between streptococci, which results in bacterial precipitation. Conversely, viable bacterial counting and SEM image analysis of Streptococcus mutans attached to the orthodontic wire show that bacterial attachment decreases significantly when soybean extracts were added. However, there was no significant change in pre-attached S. mutans biofilm in response to soybean. A possible explanation for these results is that increased agglutination of planktonic streptococci by soybean extracts results in inhibition of bacterial attachment onto the orthodontic wire.


Legal liability for psychiatrists' decisions about involuntary inpatient status for mental health patients.
The decisions by the High Court in Hunter and New England Local Health District v McKenna [2014] HCA 44 and by the majority of the New South Wales Court of Appeal in Hunter Area Health Service v Presland (2005) 63 NSWLR 22 create a high level of immunity for psychiatrists and the institutions in which they provide services from tortious liability for failure to impose involuntary detention or maintain involuntary detention of persons who, after release, engage in violent conduct. This column scrutinises the development of Australian law in such matters, including the public policy issues. It argues that the law has gone too far in denying a duty of care on the basis of both the least restrictive principle that is inherent in the power (as against duty) to detain involuntarily and in seeking to avoid the creation of a defensive mindset in psychiatrists or a distortive influence upon their decision-making.


Identification of tamoxifen-induced coregulator interaction surfaces within the ligand-binding domain of estrogen receptors.
Tamoxifen is a selective estrogen receptor (ER) modulator that is clinically used as an antagonist to treat estrogen-dependent breast cancers but displays unwanted agonistic effects in other tissues. Previous studies on ERalpha have delineated a role of the N-terminal activation function AF-1 in mediating the agonistic effects of tamoxifen, while the mechanisms for how ERbeta mediates tamoxifen action remain to be elucidated. As peptides can be used to detect distinct receptor conformations and binding surfaces for coactivators and corepressors, we attempted in this study to identify previously unrecognized peptides that interact specifically with ERs in the presence of tamoxifen. We identified two distinct peptides among others that are highly selective for tamoxifen-bound ERalpha or ERbeta. Domain mapping and mutation analysis suggest that these peptides recognize a novel tamoxifen-induced binding surface within the C-terminal ligand-binding domain that is distinct from the agonist-induced AF-2 surface. Peptide expression specifically inhibited transcriptional ER activity in response to tamoxifen, presumably by preventing the binding of endogenous coactivators. Moreover, tamoxifen-responsive and ER subtype-selective coactivators were engineered by replacing the LXXLL motifs in the coactivator TIF2 with either of the two peptides. Finally, our results indicate that related coactivators may act via the novel tamoxifen-induced binding surface, referred to as AF-T, allowing us to propose a revised model of tamoxifen agonism.


Cross-cultural evaluation of the Autism Detection in Early Childhood (ADEC) in Mexico.
A Spanish translation of the Autism Detection in Early Childhood (ADEC-SP) was administered to 115 children aged 15-73 months in Mexico. In Phase 1, children with Autistic Disorder (AD), a non-Pervasive Developmental Disorder (PDD) diagnosis or typical development were assessed with the ADEC-SP by a clinician blind to the child's diagnostic status. In Phase 2, a referred sample of children was assessed with the ADEC-SP, Childhood Autism Rating Scale (CARS), Autism Diagnostic Interview - Revised (ADI-R) and Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), and typically developing children were assessed with the ADEC-SP and CARS. Psychometric properties relating to validity and reliability were addressed. Sensitivity and specificity levels for the ADEC-SP ranged from .79-.94 and .88-1.00 respectively. In a subgroup of toddlers aged 19 to 36 months the ADEC-SP correctly identified 17 of the 18 children with a diagnosis of a PDD, and no child without a PDD diagnosis was misdiagnosed. The ADEC-SP shows promise as a Level 2 screening instrument for use in Mexico.


Freeze-dried fecal samples are biologically active after long-lasting storage and suited to fecal microbiota transplantation in a preclinical murine model of Clostridioides difficile infection.
Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioides difficile infection. Recent studies have reported protocols using capsules of either frozen or freeze-dried stool allowing oral administration in in- and out-patient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti-Clostridioides difficile properties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance of Clostridioides difficile infection in a preclinical murine model with a survival rate of 70% versus 53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment of Clostridioides difficile infection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.


Do Metabolomics and Taxonomic Barcode Markers Tell the Same Story about the Evolution of Saccharomyces sensu stricto Complex in Fermentative Environments?
Yeast taxonomy was introduced based on the idea that physiological properties would help discriminate species, thus assuming a strong link between physiology and taxonomy. However, the instability of physiological characteristics within species configured them as not ideal markers for species delimitation, shading the importance of physiology and paving the way to the DNA-based taxonomy. The hypothesis of reconnecting taxonomy with specific traits from phylogenies has been successfully explored for Bacteria and Archaea, suggesting that a similar route can be traveled for yeasts. In this framework, thirteen single copy loci were used to investigate the predictability of complex Fourier Transform InfaRed spectroscopy (FTIR) and High-performance Liquid Chromatography-Mass Spectrometry (LC-MS) profiles of the four historical species of the Saccharomyces sensu stricto group, both on resting cells and under short-term ethanol stress. Our data show a significant connection between the taxonomy and physiology of these strains. Eight markers out of the thirteen tested displayed high correlation values with LC-MS profiles of cells in resting condition, confirming the low efficacy of FTIR in the identification of strains of closely related species. Conversely, most genetic markers displayed increasing trends of correlation with FTIR profiles as the ethanol concentration increased, according to their role in the cellular response to different type of stress.


Recalled sexual experiences in childhood with older partners: a study of Brazilian men who have sex with men and male-to-female transgender persons.
This study assessed the prevalence of recalled childhood sexual experiences with an older partner among men who have sex with men (MSM) and/or male-to-female transgender persons recruited in Campinas, Brazil. It also analyzed associations between such recalled experiences and sexual risk behavior in adulthood. Participants recruited using respondent driven sampling completed a self-administered, computer-based questionnaire, and underwent HIV testing. For data analysis, raw scores were weighted based on participants' reported network size. Of 575 participants (85% men and 15% transgender), 32% reported childhood sexual experiences with an older partner. Mean age at first experience was 9 years, partners being, on average, 19 years old, and mostly men. Most frequent behaviors were partners exposing their genitals, mutual fondling, child masturbating partner, child performing oral sex on partner, and child being anally penetrated. Only 29% of the participants who had had such childhood sexual experiences considered it abuse; 57% reported liking, 29% being indifferent and only 14% not liking the sexual experience at the time it happened. Transgender participants were significantly more likely to report such experiences and, compared with men, had less negative feelings about the experience at the time of the interview. No significant associations were found between sexual experiences in childhood and unprotected receptive or insertive anal intercourse in adulthood. Results highlight the importance of assessing participants' perception of abuse, regardless of researchers' pre-determined criteria to identify abuse. MSM and transgender people may experience childhood sexual experiences with older partners differently from other populations (e.g., heterosexuals), particularly in countries with different cultural norms concerning sexuality than those prevalent in Europe and the U.S.


Substitution of a heparin correlation value for activated partial thromboplastin time in heparin nomograms.
PURPOSE. Use of nomograms based on the "heparin correlation value" (HCV)-a value that corresponds to measured activated partial thromboplastin time (aPTT) and that removes the need to revise nomograms in response to a change in the aPTT reagent or coagulometer used-was evaluated as an alternative to traditional aPTT-based anticoagulation nomograms. SUMMARY. Data were collected on patients receiving heparin therapy for selected indications (thrombotic disorders, cardiac conditions, and acute coronary syndromes) during four-month periods before (n = 59) and after (n = 60) implementation of the HCV-based nomograms. The primary endpoints were the rate at which coagulation laboratory measurements were obtained at the appropriate time and the rate of appropriate dosage adjustment in response to reported laboratory values; secondary endpoints included the time to attainment of the first target anticoagulation value. After implementation of HCV-based nomograms, coagulation laboratory measurements were obtained at the appropriate time in (mean ± S.D.) 92.9% ± 12.8% of patients, compared with 80.1% ± 15.5% of patients who received aPTT-based monitoring (p < 0.0001). After implementation of HCV-based monitoring, the rate of correct heparin dosage adjustments was improved (mean ± S.D. 94.7% ± 7.8% versus 89.3% ± 14.0%, p = 0.01), and the time to attainment of the first target anticoagulation value was shorter (mean ± S.D. 16.4 ± 10.6 hours versus 21.5 ± 14.8 hours, p = 0.03). CONCLUSION. The HCV, which relates measured aPTT values to corresponding antifactor Xa concentrations, was substituted for aPTT in heparin nomograms and appeared to be a viable alternative to the aPTT.


Quality of anticoagulation and use of warfarin-interacting medications in long-term care: a chart review.
Maintenance of therapeutic International Normalized Ratio (INR) in the community is generally poor. The supervised environment in long-term care facilities may represent a more ideal setting for warfarin therapy since laboratory monitoring, compliance, dose adjustment, and interacting medications can all be monitored and controlled. The objectives of this study were to determine how effectively warfarin was administered to a cohort of residents in long-term care facilities, to identify the proportion of residents prescribed warfarin-interacting drugs and to ascertain factors associated with poor INR control. A chart review of 105 residents receiving warfarin therapy in five long-term care facilities in Hamilton, Ontario was performed. Data were collected on INR levels, warfarin prescribing and monitoring practices, and use of interacting medications. Over a 12 month period (28,555 resident-days, 78.2 resident years) 3065 INR values were available. Residents were within, below and above the therapeutic range 54%, 35% and 11% of the time, respectively. Seventy-nine percent of residents were prescribed at least one warfarin-interacting medication during the period in review. Residents receiving interacting medications spent less time in the therapeutic range (53.0% vs. 58.2%, OR = 0.93, 95% confidence interval 0.88 to 0.97, P = 0.002). Adequacy of anticoagulation varied significantly between physicians (time in therapeutic range 45.9 to 63.9%). In this group of long-term care residents, warfarin control was suboptimal. Both prescriber and co-prescription of interacting medications were associated with poorer INR control. Future studies should seek strategies to improve prescriber skill and decrease use of interacting medications.


Concepts and items in measuring social harm from drinking.
Social epidemiological traditions of asking about problems related to drinking are considered. The issue of the attribution of the problem to drinking, and variations in formulations concerning this, are discussed. Social problems from drinking are inherently properties of social interactions, so that they are composed both of behaviour deemed problematic and of a reaction by another. Most items measuring social harm asked of the drinker him/herself are concerned with major social roles, and problems in the particular life area of the role (work, family, friendships, etc.). Some ask the respondent to attribute the problems to alcohol, some ask about others' attributions to alcohol, and some ask about "objective" problem indicators, although these usually have the respondent's attribution to drinking built in. The possibility of a more systematic way of covering different aspects of interactional problems, as reported by the drinker, is considered. Traditions of questioning the person on the other side of the interaction--i.e., items about others' troubles with drinking, and the effect of these on the respondent--are also discussed, and possibilities for bringing questions asked of the drinker and questions asked of interacting others into the same frame are considered.


Targeted inhibition of sarcoplasmic reticulum CaMKII activity results in alterations of Ca2+ homeostasis and cardiac contractility.
Transgenic (TG) mice expressing a Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitory peptide targeted to the cardiac myocyte longitudinal sarcoplasmic reticulum (LSR) display reduced phospholamban phosphorylation at Thr17 and develop dilated myopathy when stressed by gestation and parturition (Ji Y, Li B, Reed TD, Lorenz JN, Kaetzel MA, and Dedman JR. J Biol Chem 278: 25063-25071, 2003). In the present study, these animals (TG) are evaluated for the effect of inhibition of sarcoplasmic reticulum (SR) CaMKII activity on the contractile characteristics and Ca2+ cycling of myocytes. Analysis of isolated work-performing hearts demonstrated moderate decreases in the maximal rates of contraction and relaxation (+/-dP/dt) in TG mice. The response of the TG hearts to increases in load is reduced. The TG hearts respond to isoproterenol (Iso) in a dose-dependent manner; the contractile properties were reduced in parallel to wild-type hearts. Assessment of isolated cardiomyocytes from TG mice revealed 40-47% decrease in the maximal rates of myocyte shortening and relengthening under both basal and Iso-stimulated conditions. Although twitch Ca2+ transient amplitudes were not significantly altered, the rate of twitch intracellular Ca2+ concentration decline was reduced by approximately 47% in TG myocytes, indicating decreased SR Ca2+ uptake function. Caffeine-induced Ca2+ transients indicated unaltered SR Ca2+ content and Na+/Ca2+ exchange function. Phosphorylation assays revealed an approximately 30% decrease in the phosphorylation of ryanodine receptor Ser2809. Iso stimulation increased the phosphorylation of both phospholamban Ser16 and the ryanodine receptor Ser2809 but not phospholamban Thr17 in TG mice. This study demonstrates that inhibition of SR CaMKII activity at the LSR results in alterations in cardiac contractility and Ca2+ handling in TG hearts.


A mutation in the 3'-UTR of the HDAC6 gene abolishing the post-transcriptional regulation mediated by hsa-miR-433 is linked to a new form of dominant X-linked chondrodysplasia.
A family with dominant X-linked chondrodysplasia was previously described. The disease locus was ascribed to a 24 Mb interval in Xp11.3-q13.1. We have identified a variant (c.*281A>T) in the 3' untranslated region (UTR) of the HDAC6 gene that totally segregates with the disease. The variant is located in the seed sequence of hsa-miR-433. Our data showed that, in MG63 osteosarcoma cells, hsa-miR-433 (miR433) down-regulated both the expression of endogenous HDAC6 and that of an enhanced green fluorescent protein-reporter mRNA bearing the wild-type 3'-UTR of HDAC6. This effect was totally abrogated when the reporter mRNA bore the mutated HDAC6 3'-UTR. The HDAC6 protein was found to be over-expressed in thymus from an affected male fetus. Concomitantly, the level of total alpha-tubulin, a target of HDAC6, was found to be increased in the affected fetal thymus, whereas the level of acetylated alpha-tubulin was found to be profoundly decreased. Skin biopsies were obtained from a female patient who presented a striking body asymmetry with hypotrophy of the left limbs. The mutated HDAC6 allele was expressed in 31% of left arm-derived fibroblasts, whereas it was not expressed in the right arm. Overexpression of HDAC6 was observed in left arm-derived fibroblasts. Altogether these results strongly suggest that this HDAC6 3'-UTR variant suppressed hsa-miR-433-mediated post-transcriptional regulation causing the overexpression of HDAC6. This variant is likely to constitute the molecular cause of this new form of X-linked chondrodysplasia. This represents to our knowledge the first example of a skeletal disease caused by the loss of a miRNA-mediated post-transcriptional regulation on its target mRNA.


Permeation studies and histological examination of sheep nasal mucosa following administration of different nasal formulations with or without absorption enhancers.
This study was designed to investigate the possible histological effects of different intranasal (IN) formulations of indomethacin (IND) on nasal mucosa in sheep. For this purpose, oil-in-water (O/W) emulsion (E) and solution (S) formulations including 3 mg/mL of IND were prepared. Penetration enhancers such as polyvinylpyrolidone (PVP), citric acid (CA) and sodium taurocholate (NaT) were added to emulsion (1%) at the final step into the formulations. First, the effect of penetration enhancers on permeation of IND was evaluated by in vitro permeation studies in which sheep nasal mucosa was used. According to the permeation studies PVP showed the highest enhancing effect on the permeation rate of IND from sheep nasal mucosa. Furthermore, the IND permeation from E containing PVP (1.624 +/- 0.045 mg) was significantly higher than that obtained from E (0.234 +/- 0.012 mg) (p < 0.05). For the histological studies, white Karaman sheep of approximately 20 +/- 5 kg, aged 4 to 8 months were used. They were randomly divided into eight groups, each including three sheep. Five experimental groups received different formulations of IND emulsion without/ with penetration enhancers (E-PVP, E-CA, E-NaT, E) and IND solution (S), respectively. Parallel controls were composed of either untreated groups and were given blank emulsion or isotonic sodium chloride solution (0.31 mg/kg). 2 mL of each experimental formulation was applied to both nostrils of sheep, and 1/3 central and lower regions of the nose were dissected and prepared for light microscopy. Specimens stained with hematoxylin and eosin and Gomori's trichrome were examined by light microscopy. No signs of inflammation or erosion were noticed in the nasal mucosa of the control groups. Widened epithelial intercellular spaces were noticed in E-CA, E-NaT, and E-PVP groups as well with the E-PVP group showing the largest intraepithelial separations. E-CA and E-NaT groups showed significant decrease in the amount of goblet cells, while hypoplasia was considerably moderate in the E-PVP group. Finally, intranasal administration of IND emulsion with PVP may be considered as an alternative to intravenous and per oral administrations of IND to overcome their adverse effects.


ORF5 of porcine reproductive and respiratory syndrome virus (PRRSV) is a target of diversifying selection as infection progresses from acute infection to virus rebound.
Genetic variation in both structural and nonstructural genes is a key factor in the capacity of porcine reproductive and respiratory syndrome virus (PRRSV) to evade host defenses and maintain within animals, farms and metapopulations. However, the exact mechanisms by which genetic variation contribute to immune evasion remain unclear. In a study to understand the role of host genetics in disease resistance, a population of pigs were experimentally infected with a type 2 PRRSV isolate. Four pigs that showed virus rebound at 42days post-infection (dpi) were analyzed by 454 sequencing to characterize the rebound quasispecies. Deep sequencing of variable regions in nsp1, nsp2, ORF3 and ORF5 showed the largest number of nucleotide substitutions at day 28 compared to days 4 and 42 post-infection. Differences were also found in genetic variations when comparing tonsil versus serum. The results of dN/dS ratios showed that the same regions evolved under negative selection. However, eight amino acid sites were identified as possessing significant levels of positive selection, including A27V and N32S substitutions in the GP5 ectodomain region. These changes may alter GP5 peptide signal sequence processing and N-glycosylation, respectively. The results indicate that the greatest genetic diversity occurs during the transition between acute and rebound stages of infection, and the introduction of mutations that may result in a gain of fitness provides a potential mechanism for persistence.


The dietary intake of wheat and other cereal grains and their role in inflammation.
Wheat is one of the most consumed cereal grains worldwide and makes up a substantial part of the human diet. Although government-supported dietary guidelines in Europe and the U.S.A advise individuals to eat adequate amounts of (whole) grain products per day, cereal grains contain "anti-nutrients," such as wheat gluten and wheat lectin, that in humans can elicit dysfunction and disease. In this review we discuss evidence from in vitro, in vivo and human intervention studies that describe how the consumption of wheat, but also other cereal grains, can contribute to the manifestation of chronic inflammation and autoimmune diseases by increasing intestinal permeability and initiating a pro-inflammatory immune response.


Loss of immunoreactivity for RTI40, a type I cell-specific protein in the alveolar epithelium of rat lungs with bleomycin-induced fibrosis.
After lung injury, the epithelial cells lining the alveolar surface in rat lung show an altered distribution of several membrane proteins. Pulmonary fibrosis was induced by intratracheal administration of bleomycin into the lung of rats and the distribution of RTI40, a recently detected alveolar epithelial type I cell antigen, was examined, as well as the relationship between RTI40 and a type I cell-specific antigen recognized by the monoclonal antibody MEP-1 and the type I cell-binding lectin Bauhinia purpurea in serial sections and double stainings. Loss of RTI40 protein was observed in fibrotic lungs, particularly in areas with obliteration of alveoli. Pre-embedding immunoelectron microscopy confirmed this observation by detection of RTI40 protein in the alveolar lumen. Western blot analysis revealed elevated levels of RTI40 in the bronchoalveolar fluid of bleomycin-treated rats with a maximum at day 7 after treatment. Twenty-eight days after bleomycin application, the bronchoalveolar fluid contained three times the amount of RTI40 x mg protein(-1) of control lungs, as determined by semiquantitative dot blot. These results suggest RTI40 as a tool for the evaluation of alveolar epithelial type I cell behaviour during re-epithelialization processes.


Comparison of von Willebrand factor antigen, von Willebrand factor-cleaving protease and protein S in blood components used for treatment of thrombotic thrombocytopenic purpura.
Replacement of normal levels of von Willebrand factor-cleaving protease (VWF:CP, ADAMTS13) activity from infused plasma is important in plasma exchange (PEX) for the treatment of thrombotic thrombocytopenic purpura (TTP) patients. We have studied the VWF:CP activity, VWF multimer distribution, VWF:Ag, protein S (PS) activity and free PS antigen levels in fresh frozen plasma (FFP), cryosupernatant (CSP) and virally inactivated components treated with methylene blue/light (MB) or solvent detergent (SD) processes. VWF:CP activity was normal in all components tested and was retained following overnight storage at room temperature. CSP and SD plasma contained reduced levels of the highest molecular weight VWF multimers. Protein S activity was reduced below the normal range in SD plasma, but within the normal range for the other components tested. Virally inactivated SD- and MB-treated plasma may be an effective alternative to FFP and CSP in PEX for TTP. Reduced PS activity in SD plasma may predispose to venous thromboembolism, especially if infused in large volumes.


In vivo measurement of swine endocardial convective heat transfer coefficient.
We measured the endocardial convective heat transfer coefficient h at 22 locations in the cardiac chambers of 15 pigs in vivo. A thin-film Pt catheter tip sensor in a Wheatstone-bridge circuit, similar to a hot wire/film anemometer, measured h. Using fluoroscopy, we could precisely locate the steerable catheter sensor tip and sensor orientation in pigs' cardiac chambers. With flows, h varies from 2500 to 9500 W/m2 x K. With zero flow, h is approximately 2400 W/m2 x K. These values of h can be used for the finite element method modeling of radiofrequency cardiac catheter ablation.


Postural constraints on movement variability.
Movements are inherently variable. When we move to a particular point in space, a cloud of final limb positions is observed around the target. Previously we noted that patterns of variability at the end of movement to a circular target were not circular, but instead reflected patterns of limb stiffness-in directions where limb stiffness was high, variability in end position was low, and vice versa. Here we examine the determinants of variability at movement end in more detail. To do this, we have subjects move the handle of a robotic device from different starting positions into a circular target. We use position servocontrolled displacements of the robot's handle to measure limb stiffness at the end of movement and we also record patterns of end position variability. To examine the effect of change in posture on movement variability, we use a visual motor transformation in which we change the limb configuration and also the actual movement target, while holding constant the visual display. We find that, regardless of movement direction, patterns of variability at the end of movement vary systematically with limb configuration and are also related to patterns of limb stiffness, which are likewise configuration dependent. The result suggests that postural configuration determines the base level of movement variability, on top of which control mechanisms can act to further alter variability.


Inkjet-printed PEDOT:PSS multi-electrode arrays for low-cost in vitro electrophysiology.
Multi-electrode arrays (MEAs) have become a key element in the study of cellular phenomena in vitro. Common modern MEAs are still based on costly microfabrication techniques, making them expensive tools that researchers are pushed to reuse, compromising the reproducibility and the quality of the acquired data. There is a need to develop novel fabrication strategies, able to produce disposable devices that incorporate advanced technologies beyond the standard metal electrodes on rigid substrates. Here we present an innovative fabrication process for the production of polymer-based flexible MEAs. The device fabrication exploited inkjet printing, as this low-cost manufacturing method allows for an easy and reliable patterning of conducting polymers. Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) was used as the sole conductive element of the MEAs. The physical structure and the electrical properties of the plastic/printed MEAs (pMEAs) were characterised, showing a low impedance that is maintained also in the long term. The biocompatibility of the devices was demonstrated, and their capability to successfully establish a tight coupling with cells was proved. Furthermore, the pMEAs were used to monitor the extracellular potentials from cardiac cell cultures and to record high quality electrophysiological signals from them. Our results validate the use of pMEAs as in vitro electrophysiology platforms, pushing for the adoption of innovative fabrication techniques and the use of new materials for the production of MEAs.


Primary care in Bosnia and Herzegovina. Health care and health status in general practice ambulatory care centres.
To assess the health care and health status of patients attending primary care clinics in Bosnia and Herzegovina. Assisted administration patient survey. Two ambulatory care clinics (ambulantas) in each of three cities in Bosnia and Herzegovina: Tuzla, Mostar, and Banja Luka. Patients attending the ambulantas during a 1-week period in March 1999; 885 answered questionnaires. Each patient listed demographic characteristics and answered questions on satisfaction with health care and with the physical and financial accessibility of health care services and medications. A validated health status questionnaire (EuroQoL), previously used in parts of the former Yugoslavia, was administered. Only 22% of patients were employed; 57% could not pay the nominal fee to see a physician; 71% walked to the clinic; mean distance from patients' homes to the clinics was 2.3 km; 63% could not get the medications prescribed (in 85% of cases because of cost, not availability); 80% to 90% of answers to satisfaction questions suggested high satisfaction with the care patients received from their doctors; 67% of the time patients were referred to a specialist by general practitioners; 33% had problems walking; 17% had problems with self-care; 36% had problems with usual daily activities; 72% had at least some pain or discomfort; and 62% described at least some anxiety or depression. The three cities showed significant differences; patients in Tuzla generally had lower health status and more problems with health care. Unemployment and financial considerations reduced health care access in Bosnia and Herzegovina. While only one third of patients had physical difficulties, two thirds had emotional problems or pain. Satisfaction with physicians' care was high.


Antifungal Activity of Phenolic and Polyphenolic Compounds from Different Matrices of Vitis vinifera L. against Human Pathogens.
Phenolic compounds, the most widely distributed class of natural products in the plants, show several biological properties including antifungal activity. Phenolics contained in grapes can be classified in two main groups, flavonoids and non-flavonoids compounds. Variability and yield extraction of phenolic and polyphenolic compounds from different matrices of Vitis vinifera depends of cultivar, climate, soil condition and process technology. Unripe grapes, berry skins and seeds, leaves, canes and stems and not-fermented and fermented pomaces represent large reusable and valuable wastes from agricultural and agro-industrial processes. This review summarizes studies that examine the extraction method, chemical characterization, and antifungal activity of phenolic and polyphenolic compounds from edible and non-edible V. vinifera matrices against human fungal pathogens. In the world, around one billion people have fungal diseases related to skin, nail or hair and around 150 million have systemic diseases caused by fungi. Few studies on antifungal activity of plant extracts have been performed. This review provides useful information for the application of V. vinifera phenolics in the field of antifungals for human use.


Validation of the functions and prognostic values of synapse-associated proteins in lower-grade glioma.
Synapse and synapse-associated proteins (SAPs) play critical roles in various neurodegeneration diseases and brain tumors. However, in lower-grade gliomas (LGG), SAPs have not been explored systematically. Herein, we are going to explore SAPs expression profile and its clinicopathological significance in LGG which can offer new insights to glioma therapy. In the present study, we integrate a list of SAPs that covered 231 proteins with synaptogenesis activity and post synapse formation. The LGG RNA-seq data were downloaded from GEO, TCGA and CGGA database. The prognosis associated SAPs in key modules of PPI (protein-protein interaction networks) was regarded as hub SAPs. Western blot, quantitative reverse transcription PCR (qRT-PCR) and immunochemistry results from HPA database were used to verify the expression of hub SAPs. There were 68 up-regulated SAPs and 44 down-regulated SAPs in LGG tissue compared with normal brain tissue. Data from function enrichment analysis revealed functions of differentially expressed SAPs in synapse organization and glutamatergic receptor pathway in LGGs. Survival analysis revealed that four SAPs, GRIK2, GABRD, GRID2 and ARC were correlate with the prognosis of LGG patients. Interestingly, we found that GABRD were up-regulated in LGG patients with seizures, indicating that SAPs may link to the pathogenesis of seizures in glioma patients. The four-SAPs signature was revealed as an independent prognostic factor in gliomas. Our study presented a novel strategy to assess the prognostic risks of LGGs, based on the expression of SAPs.


From Platelet-Rich Plasma to Mesenchymal Stem Cells: Cartilage, Tendon, and Bone Regeneration With Orthobiologics.
The use of orthobiologics such as platelet-rich plasma, bone marrow aspirate, and stem cells has been proposed as a biologic augmentation for treatment of various conditions of cartilage, tendon, and bone. Although the published evidence is not conclusive, the safety of these treatments and benefits in improving the biologic condition of treated tissues have been confirmed. Osteoarthritis, rotator cuff injuries, and osteonecrosis of the femoral head are three common musculoskeletal conditions associated with the use of orthobiologics in patients with cartilage, tendon, and bone injuries. When reviewing the use of platelet-rich plasma, bone marrow aspirate, and mesenchymal stem cells in patients with these conditions, there is evidence of high safety and positive, but variable, efficacy. Recent studies have shown promising results and have paved the way for research being conducted at many specialized centers around the world.


Creating a MEDPAR (Medicare provider analysis and review) analog to the RUG-III (Resource Utilization Groups, Version III) classification system.
As Medicare payments for post-acute institutional care continue to rise sharply, policy interest in the clinical characteristics of beneficiaries admitted to nursing homes and their variation across facilities has stimulated research into case mix. Measures of Medicare skilled nursing facility (SNF) case mix are important in relating payments to the care requirements of residents. The Resource Utilization Groups, Version III (RUG-III) classification system uses a new minimum data set that is not currently available nationally. In preparation for a multi-State demonstration, we needed to simulate at least the first-level splits at the national, State, and facility level. Therefore, we developed proxy measures using comparable data available on the National Claims History files. The analog is an easily programmed measure of the acuity/severity of beneficiaries' conditions across a Medicare Part A SNF stay in 75 percent of the SNF providers. This can be a method for estimating changes in case mix over the years, and differences across provider types and States.


Post orgasmic illness syndrome (POIS).
Men with post orgasmic illness syndrome (POIS) become ill rather immediately after ejaculation, whether spontaneously at night, during sexual intercourse or masturbation. Two subtypes are distinguished: primary and secondary POIS. It also occurs before or after a man has been sterilized. POIS is an invalidating most probably auto-immune disease leading to much distress in males and their partners. It is characterized by five criteria. Its symptoms are described by seven clusters. However, the manifestation of these symptoms varies from one male to the other but is relatively constant in the person himself. Among men the symptoms vary in intensity, durations and sort of symptoms. POIS is a chronic disorder that manifests itself in POIS "attacks" that occur within a few minutes to a few hours after ejaculation, and disappear spontaneously after 3 to 7 days. POIS is not associated with increased total serum IgE concentrations. On the contrary, there are indications that POIS is triggered by specific cytokines that are released by an auto-immune reaction to the man's seminal fluid. Indirect clinical evidence suggests that the antigen (Ag) triggering the POIS systemic reaction is not bound to spermatozoa but to seminal fluid produced by prostatic tissue. In addition, POIS may also occur-although rarely-in females. In those cases, it is hypothesized that the Ag is associated with female prostatic tissue around the vagina.


Heart rate behavior in children with atrial septal defect.
The aim of this study was to assess heart rate variability, a noninvasive parameter for studying the neurohumoral control of heart rate, in children with atrial septal defect. We examined five time-domain and three frequency-domain indices of heart rate variability determined from 24-hour Holter recordings in 20 children, aged 3-14 years, with secundum atrial septal defect who were about to undergo operation. The measures were compared to normal ranges and to the hemodynamic data of the preoperative cardiac catheterization. Most indices of heart rate variability were moderately depressed in children with atrial septal defect. Our data revealed negative correlations between indices and the mean right atrial pressure and the enddiastolic right ventricular pressure, respectively. The study demonstrates the importance of the right ventricular filling pressures for the autonomic control of the heart in children with atrial septal defect.


Growth-Regulating Chemicals Persist in Plants: Qualitative Bioassay.
Scions from untreated tomato plants were grafted on plants treated with 2,4-dichlorophenoxyacetic acid by dipping one leaf in a solution containing 1000 parts per million. Subsequent malformations of the scion shoot and leaves were used as criteria of the presence of this chemical. The chemical or a substance causing similar symptoms persisted in the plant in physiologically active amounts for approximately 60 days.


Research Trends and Hotspots of Q Fever Research: A Bibliometric Analysis 1990-2019.
Q fever is a worldwide distributed zoonosis caused by Coxiella burnetii, a Gram-negative bacterium. Despite existence of large amount of research data on the developments related to Q fever, no bibliometric analysis of this subject is available to our knowledge. Bibliometric studies are an essential resource to track scholarly trends and research output in a subject. This study is aimed at reporting a bibliometric analysis of publications related to Q fever (2,840 articles published in the period 1990-2019) retrieved from Science Citation Index Expanded, an online database of Clarivate Analytics Web of Science Core Collection. Data was retrieved using keywords "Q fever" or "Coxiella burnetii" in title, abstract, and author keywords to describe important research indicators such as the kind and language of articles, the most important publications, research journals and categories, authors, institutions, and the countries having the most significant contribution to this subject. Finally, the emerging areas in field of diagnosis, host range, and clinical presentation were identified. Word cluster analysis of research related to Q fever revealed that major focus of research has been on zoonosis, seroprevalence, laboratory diagnosis (mainly using ELISA and PCR), clinical manifestations (abortion and endocarditis), vectors (ticks), and hosts (sheep, goat, and cattle). This bibliometric study is intended to visualize the existing research landscape and future trends in Q fever to assist in future knowledge exchange and research collaborations.


Endotoxin removal: history of a mission.
One of the key molecules involved in the pathogenesis of severe sepsis and septic shock is lipopolysaccharide (LPS) or endotoxin, which is a component of the cellular wall of Gram-negative bacteria. Clinical studies have shown that the level of circulating LPS is correlated with illness severity (APACHE II), the onset and amount of organ dysfunction (SOFA) and intensive care unit mortality. Many therapeutic strategies have attempted to neutralize the pathogenic activity of endotoxin in order to interrupt the progression of a septic state towards a worsened clinical framework, i.e. severe sepsis of septic shock. Over the past decades the role of extracorporeal hemoperfusion by means of polymyxin B-based cartridges (PMX-DHP) to bind and neutralize LPS from whole blood has increased in clinical relevance. This is due to an increasing number of studies confirming that a directed therapy of endotoxic shock could significantly influence the course of the septic cascade. This review will outline the meaning of the targeted approach to endotoxin, both highlighting the specific immunologic effect of endotoxin removal by polymyxin B and the evidence of clinical improvements following this kind of therapy in terms of recovery of organ function.


The mycobiome in atopic diseases: Inducers and triggers.
Atopic diseases are characterized by type 2 inflammation, with high levels of allergen-specific TH2 cell immune responses and elevated production of IgE. These common disorders have increased in incidence around the world, which is partly explained by detrimental disturbances to the early-life intestinal microbiome. Although most studies have focused exclusively on bacterial members of the microbiome, intestinal fungi have started to be recognized for their impact on host immune development and atopy pathogenesis. From this perspective, we review recent findings demonstrating the strong interactions between members of the mycobiome and the host immune system early in life, leading to immune tolerance during eubiosis or inducing sensitization and overt TH2 cell responses during dysbiosis. Current evidence places intestinal fungi as central players in the development of allergic diseases and potential targets for atopy prevention and treatments.


Intensified follow-up in colorectal cancer patients using frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging: Results of the randomized "CEAwatch" trial.
The value of frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging for detecting recurrent disease in colorectal cancer (CRC) patients was investigated in search for an evidence-based follow-up protocol. This is a randomized-controlled multicenter prospective study using a stepped-wedge cluster design. From October 2010 to October 2012, surgically treated non-metastasized CRC patients in follow-up were followed in eleven hospitals. Clusters of hospitals sequentially changed their usual follow-up care into an intensified follow-up schedule consisting of CEA measurements every two months, with imaging in case of two CEA rises. The primary outcome measures were the proportion of recurrences that could be treated with curative intent, recurrences with definitive curative treatment outcome, and the time to detection of recurrent disease. 3223 patients were included; 243 recurrences were detected (7.5%). A higher proportion of recurrences was detected in the intervention protocol compared to the control protocol (OR = 1.80; 95%-CI: 1.33-2.50; p = 0.0004). The proportion of recurrences that could be treated with curative intent was higher in the intervention protocol (OR = 2.84; 95%-CI: 1.38-5.86; p = 0.0048) and the proportion of recurrences with definitive curative treatment outcome was also higher (OR = 3.12, 95%-CI: 1.25-6.02, p-value: 0.0145). The time to detection of recurrent disease was significantly shorter in the intensified follow-up protocol (HR = 1.45; 95%-CI: 1.08-1.95; p = 0.013). The CEAwatch protocol detects recurrent disease after colorectal cancer earlier, in a phase that a significantly higher proportion of recurrences can be treated with curative intent.


Novel Human NKCC1 Mutations Cause Defects in Goblet Cell Mucus Secretion and Chronic Inflammation.
Infections resulting from intestinal yeast and bacteria affect a large number of patients with deficits in absorptive or secretory epithelial transport mechanisms. The basolateral Na+-K+-2Cl- cotransporter (NKCC1) has been implicated in intestinal epithelial fluid secretion. Two patients with deleterious heterozygous (NKCC1-DFX, DFX for Asp-Phe-stop codon) or homozygous (Kilquist) mutations in SLC12A2 (NKCC1) suffered from gastrointestinal deficits. Because of chronic infections, the colon and the small intestine of the NKCC1-DFX patient were resected surgically. To investigate how NKCC1 affects the integrity and function of the gut epithelia, we used a mouse model recapitulating the NKCC1-DFX patient mutation. Electron microscopy and immunostaining were used to analyze the integrity of the colonic mucus layers and immune cell infiltration. Fluorescence in situ hybridization was performed on the distal colon sections to measure bacteria translocation to the mucosa and submucosa. Citrobacter rodentium was used to measure mouse ability to clear enteric infection. A multiplex cytokine assay was used to analyze mouse inflammatory response to infection. We show that NKCC1-DFX expression causes defective goblet cell mucus granule exocytosis, leading to secretion of intact granules into the lumen of the large intestine. In addition, NKCC1-DFX colon submucosal glands secrete mucus that remained attached to the epithelium. Importantly, expression of the mutant NKCC1 or complete loss of NKCC1 function leads to aggravated inflammatory response to C rodentium infection. Compared with wild-type, NKCC1-DFX mice showed decreased expression of claudin-2, a tight junction protein involved in paracellular Na+ and water transport and enteric infection clearance. Our data indicate that NKCC1-DFX impairs gut barrier function by affecting mucus secretion and immune properties.


Phylogeography of the pallid kangaroo mouse, Microdipodops pallidus: a sand-obligate endemic of the Great Basin, western North America.
AIM: Kangaroo mice, genus Microdipodops Merriam, are endemic to the Great Basin and include two species: M. pallidus Merriam and M. megacephalus Merriam. The pallid kangaroo mouse, M. pallidus, is a sand-obligate desert rodent. Our principal intent is to identify its current geographical distribution and to formulate a phylogeographical hypothesis for this taxon. In addition, we test for orientation patterns in haplotype sharing for evidence of past episodes of movement and gene flow. LOCATION: The Great Basin Desert region of western North America, especially the sandy habitats of the Lahontan Trough and those in south-central Nevada. METHODS: Mitochondrial DNA sequence data from portions of three genes (16S ribosomal RNA, cytochrome b, and transfer RNA for glutamic acid) were obtained from 98 individuals of M. pallidus representing 27 general localities sampled throughout its geographical range. Molecular sequence data were analysed using neighbour-joining, maximum-parsimony, maximum-likelihood and Bayesian methods of phylogenetic inference. Directional analysis of phylogeographical patterns, a novel method, was used to examine angular measurements of haplotype sharing between pairs of localities to detect and quantify historical events pertaining to movement patterns and gene flow. RESULTS: Collecting activities showed that M. pallidus is a rather rare rodent (mean trapping success was 2.88%), and its distribution has changed little from that determined three-quarters of a century ago. Two principal phylogroups, distributed as eastern and western moieties, are evident from the phylogenetic analyses (mean sequence divergence for cytochrome b is c. 8%). The western clade shows little phylogenetic structure and seems to represent a large polytomy. In the eastern clade, however, three subgroups are recognized. Nine of the 42 unique composite haplotypes are present at two or more localities and are used for the orientation analyses. Axial data from haplotype sharing between pairwise localities show significant, non-random angular patterns: a north-west to south-east orientation in the western clade, and a north-east to south-west directional pattern in the eastern clade. MAIN CONCLUSIONS: The geographical range of M. pallidus seems to be remarkably stable in historical times and does not show a northward (or elevationally upward) movement trend, as has been reported for some other kinds of organism in response to global climate change. The eastern and western clades are likely to represent morphologically cryptic species. Estimated times of divergence of the principal clades of M. pallidus (4.38 Ma) and between M. pallidus and M. megacephalus (8.1 Ma; data from a related study) indicate that kangaroo mice diverged much earlier than thought previously. The phylogeographical patterns described here may serve as a model for other sand-obligate members of the Great Basin Desert biota.


Domain-general biases in spatial localization: Evidence against a distorted body model hypothesis.
A number of studies have proposed the existence of a distorted body model of the hand. Supporting this hypothesis, judgments of the location of hand landmarks without vision are characterized by consistent distortions-wider knuckle and shorter finger lengths. We examined an alternative hypothesis in which these biases are caused by domain-general mechanisms, in which participants overestimate the distance between consecutive localization judgments that are spatially close. To do so, we examined performance on a landmark localization task with the hand (Experiments 1-3) using a lag-1 analysis. We replicated the widened knuckle judgments in previous studies. Using the lag-1 analysis, we found evidence for a constant overestimation bias along the mediolateral hand axis, such that consecutive stimuli were perceived as farther apart when they were closer (e.g., index-middle knuckle) versus farther (index-pinky) in space. Controlling for this bias, we found no evidence for a distorted body model along the mediolateral hand axis. To examine whether similar widening biases could be found with noncorporeal stimuli, we asked participants to localize remembered dots on a hand-like array (Experiments 4-5). Mean localization judgments were wider than actual along the primary array axis, similar to previous work with hands. As with proprioceptively defined stimuli, we found that this widening was primarily due to a constant overestimation bias. These results provide substantial evidence against a distorted body model hypothesis and support a domain-general model in which responses are biased away from the uncertainty distribution of the previous trial, leading to a constant overestimation bias. (PsycINFO Database Record


Habitat-related variation in the plasticity of a UV-sensitive photoreceptor over a small spatial scale in the palmate newt.
Plastic phenotypes are expected to be favoured in heterogeneous environments compared with stable environments. Sensory systems are interesting to test this theory because they are costly to produce and support, and strong fitness costs are expected if they are not tuned to the local environment. Consistently, the visual system of several species changes with the conditions experienced during early development. However, there is little information on whether the amplitude of the change, that is the reaction norm, differs between visual environments. Given the rapid change of many ecosystems, especially eutrophication for aquatic habitats, it is crucial to determine down to which spatial scale, change in the reaction norm occurs. We addressed this issue by quantifying the between-habitat variation in the expression of a UV-sensitive opsin in a newt. In western France, this species breeds in ponds of small forest patches, where water filters out UV, and in agricultural ponds where UV transmission is variable. We raised larvae from both habitats with or without exposure to UV. Opsin expression was reduced in larvae from agricultural habitats when raised without UV, whereas it was low in larvae from forest ponds under all lighting conditions. Thus, the variation in the reaction norm of opsin expression was lower in stable filtering environments and higher in heterogeneous environments. Its variation occurred between habitats across a small spatial scale. We discuss the hypotheses for this pattern and for the maintenance of residual opsin expression in forest populations.


Aureochrome 1 illuminated: structural changes of a transcription factor probed by molecular spectroscopy.
Aureochrome 1 from Vaucheria frigida is a recently identified blue-light receptor that acts as a transcription factor. The protein comprises a photosensitive light-, oxygen- and voltage-sensitive (LOV) domain and a basic zipper (bZIP) domain that binds DNA rendering aureochrome 1 a prospective optogenetic tool. Here, we studied the photoreaction of full-length aureochrome 1 by molecular spectroscopy. The kinetics of the decay of the red-shifted triplet state and the blue-shifted signaling state were determined by time-resolved UV/Vis spectroscopy. It is shown that the presence of the bZIP domain further prolongs the lifetime of the LOV390 signaling state in comparison to the isolated LOV domain whereas bound DNA does not influence the photocycle kinetics. The light-dark Fourier transform infrared (FTIR) difference spectrum shows the characteristic features of the flavin mononucleotide chromophore except that the S-H stretching vibration of cysteine 254, which is involved in the formation of the thio-adduct state, is significantly shifted to lower frequencies compared to other LOV domains. The presence of the target DNA influences the light-induced FTIR difference spectrum of aureochrome 1. Vibrational bands that can be assigned to arginine and lysine side chains as well to the phosphate backbone, indicate crucial changes in interactions between transcription factor and DNA.


Activin A regulation of gonadotropin-releasing hormone synthesis and release in vitro.
Activin is essential for the regulation of normal mammalian reproductive function at both the pituitary and gonadal levels. However, its central actions in the control of the hypothalamic-pituitary-gonadal axis remain largely unexplored. The present study aims to determine whether activin could regulate the reproductive axis at the level of the hypothalamus, through control of the GnRH neuroendocrine system. Using the GnRH-secreting GT1-7 neuronal cell line as a model system, we demonstrate expression of mRNAs encoding activin receptor types I, IB, and II. We examined the effects of activin A on GnRH protein secretion and mRNA levels in GT1-7 cells. Treatment with rh-activin A regulated both GnRH protein secretion and GnRH mRNA expression in the GT1-7 cells in a time-dependent fashion. Using transient transfection assays, we explored a potential transcriptional basis for these changes. Activin A increased reporter gene activity driven by minimal GnRH enhancer and promoter elements, suggesting that activin may regulate GnRH gene expression at the level of transcription. Lastly, activin A treatment of male rat hypothalami, in vitro, increased GnRH protein secretion. Collectively, molecular and physiological evidence support the presence of an activin system which might act at a hypothalamic site to regulate mammalian reproduction via activation of GnRH synthesis and release.


Cultural context and a critical approach to eliminating health disparities.
The science of eliminating racial health disparities requires a clear understanding of the underlying social processes that drive persistent differences in health outcomes by self-identified race. Understanding these social processes requires analysis of cultural notions of race as these are instantiated in institutional policies and practices that ultimately contribute to health disparities. Racism provides a useful framework for understanding how social, political and economic factors directly and indirectly influence health outcomes. While it is important to capture how individuals are influenced by their psychological experience of prejudice and discrimination, racism is more than an intrapersonal or interpersonal variable. Considerable attention has focused on race-based residential segregation and other forms of institutional racism but less focus has been placed on how cultural values, frameworks and meanings shape institutional policies and practices. In this article, we highlight the intersection of cultural and institutional racism as a critical mechanism through which racial inequities in social determinants of health not only develop but persist. This distinction highlights and helps to explain processes and structures that contribute to racial disparities persisting across time and outcomes. Using two historical examples, the National Negro Health Movement and hospital desegregation during the Civil Rights Era, we identify key questions that an analysis of cultural racism might add to the more common focus on overt policy decisions and practices.


[Synthesis in French of the 2022 global recommendations for the management and prevention of falls in the elderly].
Falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. To synthesize evidence-based and expert consensus-based 2022 world guidelines for the management and prevention of falls in older adults. These recommendations consider a person-centred approach that includes the preferences of the patient, caregivers and other stakeholders, gaps in previous guidelines, recent developments in e-health and both local context and resources. All older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for communitydwelling older adults. An algorithm is proposed to stratify falls risk and interventions for persons at low, moderate or high risk. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. The core set of recommendations provided will require flexible implementation strategies that consider both local context and resources.


[Ovarian torsion in early childhood].
Three cases of torsion of normal the uterine adnexa in premenarcheal girls are reported. The possible etiopathogenic mechanisms are commented, and the operative management is discussed. The value of ultrasonography in early diagnosis is pointed out.


Ethnobotanical Study of Medicinal Plants Used as Anti-Obesity Remedies in the Nomad and Hunter Communities of Burkina Faso.
Obesity is a global epidemic that affects both developed and developing countries. According to World Health Organization (WHO), in 2014, over 1.9 billion adults were overweight. Burkina Faso, like other countries, faces the problem of obesity, with a prevalence of 7.3%. The main cause is excessive intake of caloric foods combined with low physical activity, although genetic, endocrine and environmental influences (pollution) can sometimes be predisposing factors. This metabolic imbalance often leads to multiple pathologies (heart failure, Type II diabetes, cancers, etc.). Drugs have been developed for the treatment of these diseases; but in addition to having many side effects, locally these products are not economically accessible to the majority of the population. Burkina Faso, like the other countries bordering the Sahara, has often been confronted in the past with periods of famine during which populations have generally used anorectic plants to regulate their food needs. This traditional ethnobotanical knowledge has not been previously investigated. An ethnobotanical survey was conducted in Burkina Faso in the provinces of Seno (North) and Nayala (Northwest) to list the plants used by local people as an anorectic and/or fort weight loss. The survey, conducted in the two provinces concerned traditional healers, herbalists, hunters, nomads and resourceful people with knowledge of plants. It was conducted over a period of two months and data were collected following a structured interview with the respondents. The approach was based on dialogue in the language of choice of the respondent and the use of a questionnaire. The data have been structured and then statistically analyzed. The fifty-five (55) respondents of the survey were aged between 40 and 80 years. Sixty-one (61) plant species, belonging to thirty-one (31) families were listed as appetite suppressants and/or for their anti-obesity properties. The main families of plants are Mimosaceae, Rubiaceae, Asclepiadaceae and Cesalpiniaceae. Fruits are the most used part of the plant organs. Consumption in the raw state or as a decoction are the two main forms of preparation. The great diversity of plants cited by informants demonstrates the existence of rich local knowledge to address obesity in Burkina Faso. Evaluation of the biochemical activity of the extracts of the most cited species could allow the development of a phytomedicine economically accessible to the majority of the population. This could allow for the preservation of biodiversity in this region which is weakened by climate change because some of the species cited are in fragile state or are threatened with extinction.


Immunophenotypical characterization of monocytes in canine distemper virus infection.
Canine distemper virus (CDV) infection induces multifocal demyelination in the central nervous system (CNS). It is thought that the resident macrophages of the CNS, the microglia, as well as invading monocytes associated with the inflammatory reaction may play a central role in the demyelinating process. To evaluate changes in peripheral monocytes in CDV infection their immunophenotype was characterized by flow cytometry during the course of an experimental CDV infection in dogs. The highest number of CDV-infected monocytes was found in dogs developing demyelinating lesions. In CD18, CD45, CD44, and CD14 neither up- nor down-regulation was observed. Marked up-regulation occurred in a number of surface molecules including CD1c, B7-1 and B7-2, MHC I, and CD11b. Peak expression was found at 4-5 weeks post-infection (PI), regardless of clinical outcome. All these molecules play an important role in the host's immune response, notably antigen presentation and cell adhesion. These results demonstrate that CDV infection in vivo may enhance several macrophage functions. This could lead to more effective clearance of the virus but may also increase demyelination through a bystander effect in animals that accumulated significant amounts of CDV in the CNS.


[Cystic adenoid carcinoma of the larynx. Presentation of a case and review of the literature].
We present a case of Adenoid Cystic Carcinoma of the larynx. When we review the literature, we verify the rareness of this carcinoma in this localization. We were made use of this and we realize a exposition of these tumours, with special interest on the clinic study and the treatment carried out in our case.


Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation: A retrospective, single center study.
There is an abundant need to increase the availability of deceased donor kidney transplantation (DDKT) to address the high incidence of kidney failure. Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients; thus the identification of modifiable risk factors associated with poor outcomes is paramount. To identify risk factors associated with delayed graft function (DGF). Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients. The primary outcome was the occurrence of DGF. The incidence of DGF was 27%. Under logistic regression, eight independent risk factors for DGF were identified including recipient body mass index ≥ 30 kg/m2, baseline mean arterial pressure < 110 mmHg, intraoperative phenylephrine administration, cold storage time ≥ 16 h, donation after cardiac death, donor history of coronary artery disease, donor terminal creatinine ≥ 1.9 mg/dL, and a hypothermic machine perfusion (HMP) pump resistance ≥ 0.23 mmHg/mL/min. We delineate the association between DGF and recipient characteristics of pre-induction mean arterial pressure below 110 mmHg, metabolic syndrome, donor-specific risk factors, HMP pump parameters, and intraoperative use of phenylephrine.


Transfusion medicine in American undergraduate medical education.
Blood transfusion is the most common procedure performed in American hospitals, and transfusions are commonly ordered by physicians without formal training in transfusion medicine. Several transfusion medicine curricula have been proposed, including those developed through the Transfusion Medicine Academic Awards (TMAA). To our knowledge, no comprehensive study has assessed how transfusion medicine is incorporated into undergraduate medical education. We conducted an online survey to determine the manner in which transfusion medicine is incorporated into American undergraduate medical education. The survey was e-mailed to administrators of medical education at all of the 129 American medical schools accredited by the Association of American Medical Colleges. Eighty-six (67%) of the 129 identified medical school administrators responded. Seventy-one (83%) of the 86 administrators reported that their undergraduate medical education curriculum provides didactic lectures in transfusion medicine, with 48% of medical schools providing 1 or 2 hours of lecture-based instruction. A minority reported small group sessions devoted to transfusion medicine topics. While a slim majority reported the availability of transfusion medicine electives, only one of 84 administrators reported that such a rotation is required. Seventy-six of 83 (92%) administrators were unfamiliar with either the 1989 or the 1995 TMAA transfusion medicine curricula. Transfusion medicine content in American undergraduate medical education is variable and the influence of the TMAA program on contemporary medical school curricula is questionable. Future efforts in this area should focus on standardizing and improving undergraduate medical education in transfusion medicine.