Huckstep intramedullary nailing for non-union of humeral shaft fractures.
Various techniques of internal fixation for non-union of humeral shaft fractures have been attempted, leading to union rates of between 50 and 90% with persisting non-union causing pain and disability. Some of these techniques have led to shoulder and elbow dysfunction. Eight patients treated with Huckstep nail fixation for humeral shaft non-union were reviewed and the rate of union was determined. Elbow and shoulder function were assessed as well as the presence of pain or disability. Union was achieved in seven of the eight patients (87.5%). Four patients had occasional mild pain after union. All patients achieved good arm function. Average shoulder abduction was 157 degrees and flexion 151 degrees excluding one patient with antecedent advanced osteoarthrosis of the gleno-humeral joint. No patient experienced any permanent neurological deficit. Huckstep nail fixation achieved union rates comparable to or higher than the other techniques of internal fixation for non-union of humeral shaft fractures. Unlike the various methods of closed nailing, Huckstep nail fixation is not associated with shoulder and elbow dysfunction. It should be considered as a therapeutic option in humeral shaft fracture and non-union, especially where the fracture site needs to be opened.


[Confirmed Dengue, Chikungunya and Zika Cases during the Period 2014 to 2016 in Barcelona, Spain].
Arbovirus infections are a group of diseases whose incidence is increasing and that entail an important problem for public health. The aim of this study was to describe detected cases of arbovirosis in Barcelona, and surveillance and control actions performed in order to reduce the risk of transmission. Descriptive cross-sectional study of confirmed dengue, chikungunya and Zika cases in Barcelona during 2014-2016 (1st trimester). Suspected cases detected in the city were notified to the Epidemiology Department of the Barcelona Public Health Agency, where an epidemiological survey is undertaken and, if appropriate, Urban Pests Surveillance and Control Department is contacted. They perform an entomological inspection and implement control and monitoring actions. We collected sociodemographical, epidemiological, clinical and entomological variables. In 2014, 50 chikungunya and 20 dengue cases were detected; 25 entomological inspections were carried out in residences and 38 in the street. In 2015, 47 chikungunya, 51 dengue and 2 Zika cases were detected; 27 inspections were carried out in residences and 80 in the street. In 2016, 17 chikungunya, 52 dengue and 48 Zika cases were detected; 50 inspections were carried out in residences and 103 in the street. No autochtonous case was detected. We observed an increasing incidence of arbovirosis cases during the 3-year study period. There was a progressive intensification of vector surveillance and control actions (inspections, sample collection…).


A Rare Presentation of Psychotic Depression with Suicidality in a Case of Papillon-Lefèvre Syndrome.
Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder that presents with palmoplantar hyperkeratosis and childhood-onset progressive loss of all dentition. Mental retardation is the only neurodevelopmental disorder reported with this condition till date. We report the first ever case in the literature of PLS presenting with psychotic depression and suicidal intention. A 40-year-old, never married, unemployed woman presented for psychiatric consultation and was given an International Classification of Diseases version 10 diagnosis of severe depression with psychotic symptoms. Physical examination warranted dermatological and dental evaluation before electroconvulsive therapy (ECT) could be administered. She was diagnosed with PLS and pseudoainhum by the skin and dental specialists. Karyotyping study was normal, and histopathology of the palmar tissue showed hyperkeratinization. She was treated with ECT, duloxetine and olanzapine, and she achieved full remission of her depression. She was prescribed oral retinoids and emollients for the skin disorder, and there was a good improvement. The dental prosthesis was fixed, and she was able to eat and feel better than before. Early diagnosis of this condition and rehabilitation would be important in improving wellbeing.


An evaluation of trigger tool method for adverse drug reaction monitoring at a tertiary care teaching hospital.
Trigger tool method (TTM) is an active surveillance method for adverse drug reaction (ADR) monitoring. The study aimed to evaluate TTM for ADR monitoring in indoor patients of the surgery department. This prospective, observational study was conducted at the Department of Surgery of a Tertiary Care Teaching Hospital in Gujarat. Patients of either gender and more than 18 years of age admitted to two selected surgery units were enrolled with prior informed consent. Preliminary trigger tool list (PTTL) comprising 13 drug triggers (DTs), 13 patient triggers (PTs), 9 laboratory triggers (LTs), and 12 surgical module triggers (STs) were used. Patients were followed up till discharge to monitor the occurrence of triggers and adverse events. A total of 400 patients were included (male: female ratio of 2.3:1; mean age: 43.07 ± 16.4 years; and mean length of hospital stay: 5.75 ± 3.12 days). Of 400 patients, triggers were present in 359 patients (89.75%) and no trigger was observed in 41 patients (10.25%). Of the 47 triggers in PTTL, 24 triggers were observed 1155 times, of these 14 triggers lead to the detection of 49 ADRs in 43 patients. The rate of adverse drug events was 12.25/100 patients. DT was the most common trigger identified (81.64%). Positive predictive values (PPV) for PTs, STs, DTs, LTs were 26.88%, 23.07%, 10.3%, and 5.55%, respectively. The comprehensive PPV of PTTL was 11.97%. Modified trigger tool list consists of 14 triggers. TTM is an effective method of ADR monitoring in the surgery department. An awareness of TT helps better detection of ADRs.


Ticking the box of 'cultural safety' is not enough: why trauma-informed practice is critical to Indigenous healing.
It is critical that those working with Aboriginal and Torres Strait Islander communities acknowledge and understand the impacts of trauma in order to engage in culturally safe practice. Recognising the role that historical and other traumas play in Indigenous people's communities and lives is a prerequisite for respectful and safe practice. Culturally safe, trauma-informed practice training makes cultural safety more achievable. Organisations that are serious about working and partnering with Aboriginal and Torres Strait Islander peoples are becoming 'trauma informed'. Aboriginal and Torres Strait Islander peoples are drawing immense strength and hope from understanding trauma and its impact on their lives. Sharing this knowledge with Aboriginal and Torres Strait Islander populations also has the potential to create safe healing spaces and interrupt trauma being passed on through generations. Trauma-informed cultural safety can allow profound change for individuals and the systems within which they practice.


Mitochondrial matrix copper complex used in metallation of cytochrome oxidase and superoxide dismutase.
A mitochondrial matrix copper ligand (CuL) complex, conserved in mammalian cells, is the likely source of copper for assembly of cytochrome c oxidase (CcO) and superoxide dismutase 1 (Sod1) within the intermembrane space (IMS) in yeast. Targeting the copper-binding proteins human Sod1 and Crs5 to the mitochondrial matrix results in growth impairment on non-fermentable medium caused by decreased levels of CcO. This effect is reversed by copper supplementation. Matrix-targeted Crs5 diminished Sod1 protein within the IMS and impaired activity of an inner membrane tethered human Sod1. Copper binding by the matrix-targeted proteins attenuates levels of the CuL complex without affecting total mitochondrial copper. These data suggest that attenuation of the matrix CuL complex via heterologous competitors limits available copper for metallation of CcO and Sod1 within the IMS. The ligand also exists in the cytoplasm in an apparent metal-free state.


Identification of Potential Poly (ADP-Ribose) Polymerase-1 Inhibitors Derived from Rauwolfia serpentina: Possible Implication in Cancer Therapy.
Poly (ADP-ribose) polymerase-1 (PARP-1) has been recognized as a prospective target for the development of novel cancer therapeutics. Several PARP-1 inhibitors are currently being considered for anticancer drug development and clinical investigation. Lately, natural compounds seem to be excellent alternative drug candidates for cancer treatment. Rauwolfia serpentina is a medicinal plant traditionally used in Indian subcontinents to treat various diseases. This study has been designed to identify the bioactive compounds derived from R. serpentina for possible binding and inhibition of PARP-1 using the molecular docking approach. Thirteen compounds were found to interact with the target with a binding affinity greater than the value of -9.0 kcal/mol. After screening the physicochemical properties, only 5 ligands (ajmalicine, yohimbine, isorauhimbine, rauwolscine, and 1,2-dihydrovomilenine) were found to obey all the parameters of Lipinski's rule of five, showed maximum drug-likeness, and possess no significant toxicity. These ligands displayed strong interactions with target PARP-1 via several hydrogen bonds and hydrophobic interactions. Therefore, these identified compounds derived from R. serpentina can be considered for drug development against cancer-targeting PARP-1.


Drought-tolerant Pseudomonas sp. showed differential expression of stress-responsive genes and induced drought tolerance in Arabidopsis thaliana.
The growth and persistence of rhizobacteria in soils are highly impacted by moisture stress. In this study, we report the first transcript analysis of four Pseudomonas strains (PS1, PS2, PS3, and PS4) isolated from the root-soil interface of rice and maize associated with different moisture levels during water deprivation. Filtered Pseudomonas sp. cells incubated at low (RH10%) and high (RH85%) relative humidity showed decreased survival of all Pseudomonas sp. at RH10% when compared with RH85%. RT-PCR showed differential expression of treS (trehalose synthase), rpoS (sigma factor), mucA (alginate regulatory gene), and fliM (flagellar motor switch protein gene) in response to exposure to RH10%. However, molecular fingerprinting and nutrient assimilation profile of Pseudomonas strains demonstrated genetic and physiological variation between the four strains irrespective of water regime and host. In vitro testing of these strains showed ACC deaminase activity and gibberellic acid, abscisic acid, indole acetic acid, and exopolysaccharide production. We determined that 50 μl of 1.2 × 103 CFU ml-1 of these Pseudomonas strains was enough to protect Arabidopsis plants against drought stress in a pot experiment. Inoculated plants increased their root colonization ability and biomass; however, PS2 showed higher survival (95%), relative water content (59%), chlorophyll (30%), glycine betaine (38%), proline (23%), and reduced MDA (43%) in shoots than irrigated control under induced water deprivation. It can be concluded that all Pseudomonas strains were effective in mitigating drought stress, however, PS2 appears to impart more resistance to drought than the other strains by upregulating key defense mechanisms.


A tertiary care-primary care partnership model for medically complex and fragile children and youth with special health care needs.
To evaluate the impact of a tertiary care center special needs program that partners with families and primary care physicians to ensure seamless inpatient and outpatient care and assist in providing medical homes. Up to 3 years of preenrollment and postenrollment data were compared for patients in the special needs program from July 1, 2002, through June 30, 2005. A tertiary care center pediatric hospital and medical school serving urban and rural patients. A total of 227 of 230 medically complex and fragile children and youth with special needs who had a wide range of chronic disorders and were enrolled in the special needs program. Care coordination provided by a special needs program pediatric nurse case manager with or without a special needs program physician. Preenrollment and postenrollment tertiary care center resource utilization, charges, and payments. A statistically significant decrease was found in the number of hospitalizations, number of hospital days, and tertiary care center charges and payments, and an increase was found in the use of outpatient services. Aggregate data revealed a decrease in hospital days from 7926 to 3831, an increase in clinic visits from 3150 to 5420, and a decrease in tertiary care center payments of $10.7 million. The special needs program budget for fiscal year 2005 had a deficit of $400,000. This tertiary care-primary care partnership model improved health care and reduced costs with relatively modest institutional support.


Increased leptin expression in endometriosis cells is associated with endometrial stromal cell proliferation and leptin gene up-regulation.
Endometriosis is a polygenic disease with complex, multifactorial aetiologies affecting approximately 10% of women of reproductive age. Leptin is the product of the ob gene, which is related to reproductive function and immunological alteration. The angiogenic and mitogenic action of leptin may influence the formation of endometriosis. This study was aimed at determining whether leptin and leptin receptor expression differs in eutopic and ectopic endometria collected from laparoscopy and at investigating the pathophysiological role of leptin in the development of endometriosis. Leptin mRNA was undetectable in seven out of 14 eutopic endometria and only a minute amount was detected in the remaining samples. In contrast, there was a marked increase in leptin mRNA and protein expression in ectopic endometriotic lesions of patients with endometriosis (P < 0.05). Receptors for leptin were immunologically stained in eutopic endometrium as well as in ectopic endometriotic implants. However, the levels of mRNA for the long and total forms of leptin receptors were suppressed in association with the severity of endometriosis (P < 0.05). Administration of leptin stimulated its own mRNA expression in ectopic endometriotic stromal cells but decreased steady-state concentrations of mRNA encoding for leptin receptor (n = 6). In addition, leptin significantly enhanced both eutopic and ectopic endometrial stromal cell proliferation (P < 0.05). In conclusion, the differential distribution of mRNA for leptin and its receptor suggests an important autocrine and paracrine role for leptin in human endometriosis. The mitogenic and auto-augmentation effects of leptin may further contribute to the pathogenesis of endometriosis.


Shape-controlled synthesis of zinc oxide: a simple method for the preparation of metal oxide nanocrystals in non-aqueous medium.
A general and facile approach has been developed to prepare various metal oxide nanocrystals from commercially available metal acetate precursors using an amine-mediated reaction. The influence of temperature and capping agents on the yield and final morphology of the metal oxides nanocrystals was investigated. The approach was applied in the synthesis of shape-controlled ZnO nanocrystals. ZnO nanowires, nanorods, bullets and triangular nanocrystals were successfully prepared by tuning the molar ratio between amine to zinc acetate precursor. On the basis of FTIR and NMR spectroscopic studies, we propose that the amine could mediate the breakdown of the metal acetates through a nucleophilic attack mechanism. The results suggest that amine can play dual role as both the attacking agent and capping agent in this new methodology.


Psychosocial predictors of adherence to lymphedema risk minimization guidelines among women with breast cancer.
The effective management of lymphedema risk following breast cancer surgery and treatment requires enactment of simple behavioural strategies, including regularly checking for early lymphedema symptoms. Adopting a broad self-regulatory perspective, our aim for this study was to identify psychological factors associated with adherence to these risk management strategies. Women (N = 98) recently diagnosed with breast cancer and scheduled for breast and lymph node surgery completed questionnaires prior to surgery and at 3 months post-surgery. Variables assessed included demographics, cognitive belief variables in relation to lymphedema and its management (perceived negative consequences, perceived lymphedema controllability, self-efficacy, perceived personal risk, perceived self-regulatory ability to manage risk-related distress), lymphedema knowledge, trait anxiety and adherence to lymphedema risk management recommendations. Greater adherence was associated bivariately with greater beliefs in lymphedema controllability, self-efficacy, perceived consequences and perceived self-regulatory ability. Linear regression analyses revealed that only greater beliefs in the controllability of lymphedema and self-regulatory ability, as well as greater knowledge, were predictive of greater adherence to risk management strategies. This study highlights the importance of underlying beliefs as determinants of whether a woman who is informed and knowledgeable about lymphedema risk and its management will undertake the recommended risk management actions. Along with raising awareness of lymphedema and its risk management, health professionals should promote positive beliefs among women regarding the controllability of lymphedema through early-detection/early-treatment approaches. In addition, educational approaches should aim to enhance a woman's beliefs in her ability to adhere to these risk management recommendations over time.


[The cytokeratin skeleton of the human organ of Corti and its functional significance].
In the adult human organ of Corti cytokeratin (CK) is expressed by all supporting cells enclosing it like a shell. The pattern of immunoreactivity clearly demonstrates a quantitative gradient in the expression of CK, with more CK at the apex than at the base of the cochlea. Predominantly in the apical cochlear turns, the CK-shell separates the compartment of the inner hair cells from that of the outer hair cells. Ultrastructurally, the supporting cells contain a loose fibrillary network which apically is oriented toward the desmosome chain and which can be clearly distinguished from the well-known tubular filaments (microtubuli). Some supporting cells show centrioles. Both the expression of CK and the presence of centrioles indicate a possible potential for cell regeneration. Ultrastructurally, outer hair cells and Deiters' cells show features of a specialized contact zone which might be of functional significance regarding the contractile abilities of the outer hair cells. In the human organ of Corti, vimentin is expressed only by the inner and outer pillar cells. These cells thus express CK together with vimentin. The distinct shell configuration of the CK network in the organ of Corti gives it a tonotopically related difference in rigidity which not only must be of importance for cochlear perception of sound but also could explain the reduced vulnerability of the ear to low frequencies.


Chaperones and Proteostasis: Role in Parkinson's Disease.
Proper folding to attain a defined three-dimensional structure is a prerequisite for the functionality of a protein. Improper folding that eventually leads to formation of protein aggregates is a hallmark of several neurodegenerative disorders. Loss of protein homeostasis triggered by cellular stress conditions is a major contributing factor for the formation of these toxic aggregates. A conserved class of proteins called chaperones and co-chaperones is implicated in maintaining the cellular protein homeostasis. Expanding the body of evidence highlights the role of chaperones as central mediators in the formation, de-aggregation and degradation of the aggregates. Altered expression and function of chaperones is associated with many neurodegenerative diseases including Parkinson's disease. Several studies indicate that chaperones are at the center of the cause and effect cycle of this disease. An overview of the various chaperones that are associated with homeostasis of Parkinson's disease-related proteins and their role in pathogenicity will be discussed in this review.


Graphene Oxide by UV-Ozone Treatment as an Efficient Hole Extraction Layer for Highly Efficient and Stable Polymer Solar Cells.
The hole extraction layer has a significant impact on the achievement of high-efficiency polymer solar cells (PSCs). Here, we report an efficient approach to direct UV-ozone treatment by larger device performance enhancement employing graphene oxide (GO). The dramatic performance enhancement of PSCs with the P3HT:PCBM blend as an active layer was demonstrated by the UV-ozone treatment of GO for 30 min: best power conversion efficiency (PCE) of 4.18%, fill factor of 0.63, Jsc of 10.94 mA cm-2, and Voc of 0.61 V, which are significantly higher than those of the untreated GO (1.82%) and highly comparable PEDOT:PSS-based PSCs (3.73%). In addition, PSCs with UV-ozone-treated GO showed a longer stability than PSCs with PEDOT:PSS. The significant enhancement of PCEs of PSCs can be attributed to the fact that ozone molecules can oxidize GO into CO2 and leave highly conductive graphene particles. We suggest that this simple UV-ozone treatment can provide an efficient method for highly efficient GO hole extraction in high-performance PSCs.


Values, Norms, and Peer Effects on Weight Status.
This study uses data from the European Social Survey in order to test the Prinstein-Dodge hypothesis that posits that peer effects may be larger in collectivistic than in individualistic societies. When defining individualism and collectivism at the country level, our results show that peer effects on obesity are indeed larger in collectivistic than in individualistic societies. However, when defining individualism and collectivism with individual values based on the Shalom Schwartz universal values theory, we find little support for this hypothesis.


[Hyperthermia as a method for treating prostatic adenoma].
Local microwave hyperthermia was used in 15 patients aged 60 to 76 years with prostatic adenoma on an inpatient (n = 8) and outpatient (n = 7) basis. Severe clinical symptoms of prostatic adenoma was considered indication and urinary and prostatic stones were contraindications. Every patient received 6 hyperthermia treatments (41 to 42 degrees C) with a 915 or 460 MHz device. Adenoma of the prostate was treated twice a week. An interval of 3-4 days was used to avoid thermic tolerance. The treatments were well tolerated. Prostatic size was reduced by 15.2 cm2 in 11 patients and unchanged in 1 patient. Three patients required surgery 2 weeks after treatment withdrawal because of adenoma distension with residual urine and 3 patients were operated on for cystostomes. The overall effect of microwave hyperthermia on prostatic adenoma was induction of focal sclerosis in adenoma. This treatment improved uroflowmetric findings and abolished residual urine. Hyperthermia is a reasonably safe conservative option for inoperable patients with prostatic adenoma.


Identification of a novel intracellular cholesteryl ester hydrolase (carboxylesterase 3) in human macrophages: compensatory increase in its expression after carboxylesterase 1 silencing.
Cholesteryl ester (CE) hydrolysis is the rate-limiting step in the removal of free cholesterol (FC) from macrophage foam cells, and several enzymes have been identified as intracellular CE hydrolases in human macrophages. We have previously reported the antiatherogenic role of a carboxylesterase [carboxylesterase 1 (CES1)], and the objective of the present study was to determine the contribution of CES1 to total CE hydrolytic activity in human macrophages. Two approaches, namely, immune depletion and short hairpin (sh)RNA-mediated knockdown, were used. Immuneprecipitation by a CES1-specific antibody resulted in a 70-80% decrease in enzyme activity, indicating that CES1 is responsible for >70% of the total CE hydrolytic activity. THP1-shRNA cells were generated by stably transfecting human THP1 cells with four different CES1-specific shRNA vectors. Despite a significant (>90%) reduction in CES1 expression both at the mRNA and protein levels, CES1 knockdown neither decreased intracellular CE hydrolysis nor decreased FC efflux. Examination of the underlying mechanisms for the observed lack of effects of CES1 knockdown revealed a compensatory increase in the expression of a novel CES, CES3, which is only expressed at <30% of the level of CES1 in human macrophages. Transient overexpression of CES3 led to an increase in CE hydrolytic activity, mobilization of intracellular lipid droplets, and a reduction in cellular CE content, establishing CES3 as a bona fide CE hydrolase. This study provides the first evidence of functional compensation whereby increased expression of CES3 restores intracellular CE hydrolytic activity and FC efflux in CES1-deficient cells. Furthermore, these data support the concept that intracellular CE hydrolysis is a multienzyme process.


The feet in Pfeiffer's syndrome.
Broad toes are the classic clinical finding occurring in the feet in Pfeiffer's syndrome patients, but few cases undergo formal radiological assessment. However, the feet in other craniosynostosis syndromes resulting from mutations of the fibroblast growth factor receptor 2 gene have anomalies at many other sites within the feet, which raised the possibility that there may also be a wider range of anomalies other than broad big toes in the feet of those with Pfeiffer's syndrome. The object of this study was to assess prospectively the incidence and pattern of clinical and radiographic anomalies of the feet of patients with a confirmed diagnosis of Pfeiffer's syndrome. Twenty-two Pfeiffer's syndrome patients were examined both clinically and radiologically for anomalies of the feet. Clinical examination revealed broad big toes in 12 patients and syndactyly in 2. Radiographs of the feet were evaluated by a radiologist with an interest in skeletal dysplasia as well as by members of the Craniofacial team. A wider range of radiological than clinical anomalies involving the phalanges, metatarsals, and tarsals was seen. The severity of the anomalies observed ranged from normal to those resembling the feet of Apert's syndrome patients. Only 4 patients had radiologically normal feet. These radiographic findings suggest that there is a range of foot anomalies more extensive than the broad big toes, which are classically associated with Pfeiffer's syndrome.


Transient response method for evaluating the rate constants of reactions over immobilized enzymes.
The transient response method was utilized to evaluate the rate constants of reaction over immobilized enzyme. Glucose oxidation catalyzed by the immobilized glucose oxidase in a fixed-bed reactor was selected as an example. A theoretical model including the effects of axial dispersion, film diffusion, and intraparticle diffusion was established for the reactor. The individual rate constant of each elementary step of this enzymatic reaction was determined through direct fitting of the experimental response data to the model.


The first fatal case of yam bean and rotenone toxicity in Thailand.
The first fatal case of Yam bean and Rotenone toxicity in Thailand was studied at Forensic Medicine, Chiang Mai, Thailand. A Chinese Taiwan man, 59 years old, was found dead after Yam bean ingestion. Yam bean toxicity and death have been found very rarely in the world and has not been reported in Thailand The Yam bean plant is grown widely in Northern Thailand. But many people know that mature pods, seeds and filage of the Yam bean, except the tuberous root, are very toxic. The victim ate a lot of Yam bean seeds and died within 2 hours with respiratory failure. The authors detected Rotenone substance in Yam bean seeds, gastric content and 72 ng/ml blood by HPLC. Also generalized microscopic hemorrhage in the brain, lungs, liver and adrenal glands which were of characteristic pathology were detected. The authors concluded that the cause of death was asphyxia from Yam bean or Rotenone toxicity.


Association between Death or Hospitalization and Observable Variables of Eating and Swallowing Function among Elderly Residents in Long-Term Care Facilities: A Multicenter Prospective Cohort Study.
This 1-year multicenter prospective cohort study aimed to determine the association between observable eating and swallowing function factors and outcomes (death/hospitalization or survival) among elderly persons in long-term care insurance facilities in Japan. Baseline assessments of factors, such as language, drooling, halitosis, hypersalivation, tongue movement, perioral muscle function, coughing, respiration after swallowing, rinsing, and oral residue, among others, were conducted. A score of 0 was considered positive, and a score of 1 or 2 was considered negative. Patient age, sex, body mass index, Barthel index, and Clinical Dementia Rating were recorded. The death/hospitalization or survival rates over 1 year were recorded, and patients were allocated into groups depending on the respective outcome (death/hospitalization group or survival group) and baseline characteristics. A total of 986 residents from 32 facilities were included, with 216 in the death/hospitalization group and 770 in the survival group. Language, salivation, halitosis, perioral muscle, coughing, respiration after swallowing, rinsing, and oral residue were significantly associated with the outcomes (p < 0.05). Therefore, routine performance of these simple assessments by caregivers may allow early detection and treatment to prevent death, pneumonia, aspiration, and malnutrition in elderly persons.


Temporal and Triggered Evolution of Host-Guest Characteristics in Amphiphilic Polymer Assemblies.
An amphiphilic polymer with cleavable side chain and main chain functional groups has been designed and synthesized. Specific cleavage of either of its functional groups was found to have an effect on the morphology of the assembly. Degradation of the main chain is shown to cause morphology of the supramolecular assembly to evolve with time from a micelle-like assembly to a vesicular assembly. On the other hand, stimulus-induced cleavage of the side chains causes these nanoassemblies to disassemble. These temporal (main chain) and triggered (side chain) degradation processes have implications in the design of degradable polymers as supramolecular scaffolds for biological applications.


The Michigan Trauma Quality Improvement Program: Results from a collaborative quality initiative.
American College of Surgeons verified trauma centers and a third-party payer within the state of Michigan built a regional collaborative quality initiative (CQI). The Michigan Trauma Quality Improvement Program began as a pilot in 2008 and expanded to a formal program in 2011. Here, we examine the performance of the collaborative over time with regard to patient outcomes, resource utilization, and process measures. Data from the initial 23 hospitals that joined the CQI in 2011 were analyzed. Performance trends from 2011 to 2015 were evaluated for outcomes, resource utilization, and process measures using univariate analysis. Risk-adjustment was performed to confirm results observed in the unadjusted data. To calculate the potential number of patients impacted by the CQI program, the maximum absolute change was multiplied by the number of trauma patients treated in the 23 hospitals during 2015. Membership in a CQI program significantly reduced serious complications (8.5 vs. 7.3%, p = 0.002), decreased resource utilization, and improved process measure execution in trauma patients over 5 years time. Similar results were obtained in unadjusted and risk-adjusted analyses. The CQI program potentially avoided inferior vena cava filter placement in 167 patients annually. Decreased venous thromboembolism rates mirrored increased compliance with venous thromboembolism pharmacologic prophylaxis. This study confirms our hypothesis that participation in a regional CQI improves patient outcomes and decreases resource utilization while promoting compliance with processes of care. Economic/therapeutic care, level V.


Use of archived data to derive soil health and water quality indicators for monitoring shifts in natural resources.
Current gaps impeding researchers from developing a soil and watershed health nexus include design of long-term field-scale experiments and statistical methodologies that link soil health indicators (SHI) with water quality indicators (WQI). Land cover is often used to predict WQI but may not reflect the effects of previous management such as legacy fertilizer applications, disturbance, and shifts in plant populations) and soil texture. Our research objectives were to use nonparametric Spearman rank-order correlations to identify SHI and WQI that were related across the Fort Cobb Reservoir experimental watershed (FCREW); use the resulting rho (r) and p values (P) to explore potential drivers of SHI-WQI relationships, specifically land use, management, and inherent properties (soil texture, aspect, elevation, slope); and interpret findings to make recommendations regarding assessment of the sustainability of land use and management. The SHI values used in the correlation matrix were weighted by soil texture and land management. The SHI that were significantly correlated with one or more WQI were available water capacity (AWC), Mehlich III soil P, and the sand to clay ratio (S:C). Mehlich III soil P was highly correlated with three WQI: total dissolved solids (TDS) (0.80; P < 0.01), electrical conductivity of water (EC-H2 O) (0.79; P < 0.01), and water nitrates (NO3 -H2 O) (0.76; P < 0.01). The correlations verified that soil texture and management jointly influence water quality (WQ), but the size of the soils dataset prohibited determination of the specific processes. Adoption of conservation tillage and grasslands within the FCREW improved WQ such that water samples met the U.S. Environmental Protection Agency (EPA) drinking water standards. Future research should integrate current WQI sampling sites into an edge-of-field design representing all management by soil series combinations within the FCREW.


Conformational Dynamics in Ion Mobility Data.
The shape of the spectral features in arrival time distributions (ATDs) recorded by ion mobility spectrometry (IMS) can often be interpreted in terms of the coexistence of different isomeric species. Interconversion between such species is also acknowledged to influence the shape of the ATD, even if no general quantitative description of this effect is available. We present an analytical model that allows simulating ATDs resulting from interconverting species. This model is used to reproduce experimental data obtained on a bistable system and to interpret discrepancies between measurements on different types of instruments. We show that the proposed model can be further exploited to extract kinetic and thermodynamic data from tandem-IMS measurements.


Orphan nuclear receptor constitutive active/androstane receptor-mediated alterations in DNA methylation during phenobarbital promotion of liver tumorigenesis.
Altered DNA methylation is an epigenetic mechanism that plays a key role in the carcinogenesis process, and the nongenotoxic rodent hepatocarcinogen phenobarbital (PB) alters the methylation status of DNA in mouse liver. The constitutive active/androstane nuclear receptor (CAR) mediates half of the PB-induced hepatic gene expression changes and it is essential for liver tumor promotion in PB-treated mice. Here, a technique involving methylation-sensitive restriction digestion, arbitrarily primed PCR, and capillary electrophoresis was utilized to detect PB-induced regions of altered DNA methylation (RAMs) in CAR wildtype (WT) mice that are sensitive to promotion by PB and resistant CAR knockout (KO) mice. The CAR WT mice developed preneoplastic lesions after 23 weeks of PB treatment (precancerous) and liver tumors after 32 weeks, while the CAR KO mice did not develop tumors (Y. Yamamoto, et al., 2004, Cancer Res. 64, 7197-7200). Our goal was to discern those RAMs which are playing important roles in tumor formation by comparing the RAMs that form in sensitive and resistant groups of mice. Using this novel approach, 42 unique RAMs were identified in the precancerous as compared to the CAR KO, 23-week PB-treated tissue. Of these 42 RAMs, 14 carried forward to the tumor tissue, and additionally, 104 total unique RAMs were observed in the tumor tissue. These results indicate that there are unique RAMs occurring in the sensitive CAR WT mice and that a portion of these are seen in both the precancerous and tumor tissue. We hypothesize that these unique RAMs may be facilitating the tumorigenesis process, and these data support the view that DNA methylation plays a causative role in PB-induced tumorigenesis.


Fetal Medicine Foundation charts for fetal growth in twins.
To derive reference distributions of estimated fetal weight (EFW) in twins relative to singletons. Gestational age and chorionicity-specific reference distributions for singleton percentiles and EFW were fitted to data on 4,391 twin pregnancies with two liveborn fetuses from four European centres; there were 3,323 dichorionic (DC) and 1,068 monochorionic diamniotic (MCDA) twin pregnancies. Gestational age was derived using the larger of the two crown-rump length measurements obtained during the first trimester of pregnancy. The EFW was obtained from ultrasound measurements of head circumference, abdominal circumference, and femur length using the Hadlock formula. Singleton percentiles were obtained using the Fetal Medicine Foundation population weight charts for singleton percentiles. Hierarchical models were fitted to singleton z-scores with autoregressive terms for serial correlations within and between twins; separate models were fitted to DC and MCDA twins. Fetuses from twin pregnancies tended to be smaller than singletons at the earliest gestations; 16 weeks for MCDA and 20 weeks for DC twins. This was followed by a period of catch-up growth to around 24 weeks. After that, both DC and MCDA twins showed reduced growth. In DC twins, the EFW corresponding to the 50th percentile was on the 50th percentile of singleton pregnancies at 24 weeks, the 43rd percentile at 28 weeks, the 31st percentile at 32 weeks, and the 22nd percentile at 36 weeks. In MCDA twins, the EFW corresponding to the 50th percentile was on the 36th percentile of singleton pregnancies at 24 weeks, the 29th at 28 weeks, the 19th at 32 weeks, and the 12th at 36 weeks. In DC and, to a greater extent, MCDA twin pregnancies, fetal growth demonstrates a comparatively lower rate than that observed in singleton pregnancies. Furthermore, the divergence in growth trajectories between twin and singleton pregnancies becomes more pronounced as gestational age increases. This article is protected by copyright. All rights reserved.


A model of the ingroup as a social resource.
Drawing on theories of social comparison, realistic group conflict, and social identity, we present an integrative model designed to describe the psychological utility of social groups. We review diverse motivations that group membership may satisfy (e.g., the need for acceptance or ideological consensus) and attempt to link these particular needs to a global concern for self-worth. We then examine several factors hypothesized to influence an ingroup's utility in the eyes of its members. Attempting to unite our understanding of (a) why groups are needed and (b) what kinds of groups are useful in meeting those needs, a proposed model of the ingroup as a social resource (MISR) suggests that the dimensions of perceived value, entitativity, and identification interact to determine the overall psychological utility of an ingroup. We discuss empirical and theoretical support for this model, as well as its implications for intra- and intergroup attitudes.


High levels of FLT3-ligand in bone marrow and peripheral blood of patients with advanced multiple myeloma.
Multiple myeloma (MM) is still incurable due to resistance against various therapies. Thus, the identification of biomarkers predicting progression is urgently needed. Here, we evaluated four biomarkers in bone marrow and peripheral blood of MM patients for their prognostic significance. Bone marrow- and peripheral blood plasma levels of FLT3-L, soluble TIE2, endostatin, and osteoactivin were determined in patients with monoclonal gammopathy of undetermined significance (MGUS, n = 14/n = 4), patients with newly diagnosed MM (NDMM, n = 42/n = 31) and patients with relapsed/refractory MM (RRMM, n = 27/n = 16) by sandwich ELISA. Median FLT3-L expression increased from MGUS (58.77 pg/ml in bone marrow; 80.40 pg/ml in peripheral blood) to NDMM (63.15 pg/ml in bone marrow; 85.05 pg/ml in peripheral blood) and was maximal in RRMM (122 pg/ml in bone marrow; 160.47 pg/ml in peripheral blood; NDMM vs. RRMM p<0.001). A cut-off value of FLT3-L >92 pg/ml in bone marrow and >121 pg/ml in peripheral blood was associated with relapse or refractoriness in MM patients. FLT3-L was found to be a high predictive marker for discrimination between NDMM and RRMM as well in bone marrow as in peripheral blood (AUC 0.75 in bone marrow; vs 0.84 in peripheral blood). High levels of FLT3-L in bone marrow and peripheral blood of MM patients identify patients with progressive disease and are associated with relapse or refractoriness in MM patients. FLT3-L could be useful as a marker to identify RRMM patients and should be evaluated as target for future therapies.


Phospholipase A2 genes and their expressions in Thai Russell's viper venom glands.
Phospholipase A2 (PLA2) is a multi-functional enzyme found in many snake venoms and exists in several isoforms. PLA2 causes a variety of pathological effects including anticoagulant, edema, and platelet aggregation inhibition. Here, we reported the cDNA and gene sequences of PLA2 and their expressions in Thai Russell's viper (RV) Daboia russellii siamensis venom glands. We identified 3 PLA2 genes in the RV genome, 2 of which are actively transcribed in the venom gland. The deduced amino acids of these 2 PLA2 isoforms share 80% identity and are the same as PLA2s from Taiwan Russell's viper, Daboia russellii formosensis. A third PLA2 gene has no corresponding mRNA transcript from the venom gland suggesting a very low level of expression in the venom glands.


A new proposal for the action of vasopressin, based on studies of a complex synthetic membrane.
The total osmotic flow of water across cell membranes generally exceeds diffusional flow measured with labeled water. The ratio of osmotic to diffusional flow has been widely used as a basis for the calculation of the radius of pores in the membrane, assuming Poiseuille flow of water through the pores. An important assumption underlying this calculation is that both osmotic and diffusional flow are rate-limited by the same barrier in the membrane. Studies employing a complex synthetic membrane show, however, that osmotic flow can be limited by one barrier (thin, dense barrier), and the rate of diffusion of isotopic water by a second (thick, porous) barrier in series with the first. Calculation of a pore radius is meaningless under these conditions, greatly overestimating the size of the pores determining osmotic flow. On the basis of these results, the estimation of pore radius in biological membranes is reassessed. It is proposed that vasopressin acts by greatly increasing the rate of diffusion of water across an outer barrier of the membrane, with little or no accompanying increase in pore size.


The effect of subunit composition of rat brain GABAA receptors on channel function.
Different combinations of cloned rat brain subunit isoforms of the GABAA receptor channel were expressed in Xenopus oocytes. The voltage-clamp technique was then used to measure properties of the GABA-induced membrane currents and to study the effects of various modulators of the GABAA receptor channel (diazepam, DMCM, pentobarbital, and picrotoxin). This approach was used to obtain information on the minimal structural requirements for several functional properties of the ion channel. The combination alpha 5 beta 2 gamma 2 was identified as the minimal requirement reproducing consensus properties of the vertebrate GABAA receptor channel, including cooperativity of GABA-dependent channel gating with a Ka in the range of 10 microM, modulation by various drugs acting at the benzodiazepine binding site, picrotoxin sensitivity, and barbiturate effects.


Impact of Staff Localization on Turnover: The Role of a Foreign Subsidiary CEO.
Great resignation has become a critical issue in management discipline and retaining talents is one of the most important properties across the globe. Among them, local staff have been regarded as an essential competitive advantage for multinational companies and their sustainability. In this sense, staff localization has received considerable attention from scholars and professionals; however, few studies have examined the mechanisms underlying the relationship between staff localization and turnover. This study examines the macro-level relationship between the ratio of local staff in a subsidiary and the actual turnover rate of 89 multinational companies in 25 countries through their headquarters and subsidiary staff. Additionally, the aim of this study was to identify the moderating impact of a CEO's nationality. The results showed that local staff leave organizations in which there are more expatriates deployed from HQs. Furthermore, the CEO's nationality buffered the relationship between staff localization and the local staff turnover. This study can contribute to the academia and practice by revealing the effect of staff localization on staff turnover. In addition, a CEO staffing strategy focusing on nationality can be considered an important factor in retaining competitive local staff during the COVID-19 pandemic for multinational companies.


Recanalization of Total Occlusion of the Superficial Femoral Artery and Profunda Femoris Using the Transcollateral Approach.
Chronic total occlusions (CTOs) are seen in 30%-40% of symptomatic superficial femoral artery (SFA) disease. Despite advances in revascularization techniques, 10%-20% of these occlusions cannot be crossed. We report 1 case and review the literature on transcollateral retrograde crossing of the SFA from the profunda femoris. The procedural steps and devices (wires and crossing catheters) utilized by various operators are outlined. Based on an overview of current cases in the literature (19 cases, 21 CTOs), success rate was 95.2% with no complications reported. We conclude that transcollateral recanalization of chronically occluded SFA appears to be a viable technique when antegrade access is not feasible.


Case report on unusual tumor with synchronous cutaneous and gastrointestinal tract involvement.
Histiocytic sarcoma (HS) is an exceedingly rare lymphohematopoietic malignancy with morphological and immunophenotypic characteristics of mature tissue histiocytes. We report a unique case of a HS with synchronous skin and gastrointestinal tract involvement which has not been reported in literature till date to the best of our knowledge. A 70-year-old male farmer presented with multiple ulcerated skin lesions ranging from 0.5 to 10 cm all over the body. Autopsy revealed multiple transmural nodular deposits in stomach, intestines, head of pancreas, and peripancreatic tissue. Histopathology and immunohistochemistry profile was consistent with HS exhibiting positivity for CD68, CD163, and lysozyme. CD 163 identifies histiocytic malignancies with high degree of specificity and has become a promising marker for their diagnosis.


An update of Wnt signalling in endometrial cancer and its potential as a therapeutic target.
Endometrial cancer is the most common gynaecological malignancy in developed nations, and its prevalence is rising as women defer or decide not to have children and as obesity rises, both key risk factors. Despite this, treatment options remain limited, particularly for advanced or refractory disease. New genomic analyses have revealed distinct mutational profiles with therapeutic and prognostic potential. Wnt signalling, which is pivotal in embryogenesis, healing and homeostasis, is of importance in the endometrium and has been linked to carcinogenesis. This review aims to update and discuss the current evidence for the role of β-catenin dependent and independent Wnt signalling, including the ROR receptors in the endometrium and its potential as a therapeutic target, in light of recent trials of Wnt-targeted therapy in multiple tumour types.


Synthesis of novel mRNA 5' cap-analogues: dinucleoside P1, P3-tri-, P1, P4-tetra-, and P1, P5-pentaphosphates.
A series of new mRNA anti reverse cap analogues (ARCA) was designed to obtain a tool for studying the mechanism of protein translation. Dinucleoside P1, P3-tri-, P1, P4-tetra- and P1, P5-pentaphosphates, linked by a 5'-to-5' phosphate bridge and composed of modified 7-methylguanosine and guanosine, have been synthesized. The hydroxyl group (2'OH or 3'OH) in 7-metylguanosine moiety was replaced by -OCH3 or -H in order to obtain the cap analogues capable to be correctly incorporated into synthetic mRNA transcripts. Tri-, tetra-, and pentaphosphates were prepared by ZnCl2 catalyzed condensation in DMF of derivatives of the 7-methylguanosine diphosphates with the guanosine mono-, di- and triphosphate P-imidazolides, respectively. The structures of the novel compounds were established by means of 1H and 31P NMR spectra.


Motivating online learners using attention, relevance, confidence, satisfaction Motivational Theory and distributed scaffolding.
Learning online requires self-regulation, intrinsic motivation, and independence. Building an online classroom environment that fosters the development of these behaviors for students is key to their success. Use of ARCS (attention, relevance, confidence, satisfaction) Motivational Theory and distributed scaffolding can assist faculty in developing intentional support to help the online student achieve learning outcomes. The authors discuss development of teaching strategies in online, distance learning courses that will enhance student motivation and learning outcomes.


Application of a novel resorbable membrane in the treatment of calvarial defects in rats.
Diplen-Gam (DG) is a novel absorbable guided bone regeneration (GBR) membrane. This study was designed to evaluate the capacity of bone repair of DG compared with that of Bio-Gide (BG). Critical size defects were created in both sides of the calcarium of 36 Sprague-Dawley rats. Defects were assigned to six groups and each group was subjected to one of the following treatments: (A1) unfilled defects, (A2) Bio-Oss (BO) grafts, (B1) DG membrane, (B2) BG membrane, (C1) DG membrane + BO grafts and (C2) BG membrane + BO grafts. The animals were killed at 2, 4, 8 and 12 weeks after the operation. The defects and surrounding tissues were examined by gross observation and X-ray examination. The paraffin sections were subjected to HE (hematoxylin and eosin) staining and IHC (immunohistochemistry) for bone morphogenetic protein-2 (BMP-2). The X-rays showed that, at 12 weeks, the DG and BG group exhibited more new bone formation than CSD blank group did; the BG group exhibited more new bone formation than the DG group did (t = 5.240, P = 0.035), the BG + BO group showed no significant differences in bone formation compared with the DG + BO group (t = 1.246, P = 0.339). By IHC staining, BMP-2-positive results could be seen inside the DG membrane, on the surface of the new bone, and inside the new bone. It can be suggested that BG membrane achieved better effects in guided bone regeneration compared with DG membrane. No significant differences were found between the two membranes in their bone healing ability when they are used with BO. Therefore, DG membrane shows clinical effectiveness, but should be used in combination with bone substitute.


Systematic Review - Combining Neuroprotection With Reperfusion in Acute Ischemic Stroke.
Clinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective treatments. This systematic review provides an overview of efficacy of neuroprotective agents in combination with reperfusion therapy in AIS. A literature search was performed on the following databases, namely PubMed, Embase, Web of Science, Cochrane Library, Emcare. All databases were searched up to September 23rd 2021. All randomized controlled trials in which patients were treated with neuroprotective strategies within 12 h of stroke onset in combination with intravenous thrombolysis (IVT), endovascular therapy (EVT), or both were included. We screened 1,764 titles/abstracts and included 30 full reports of unique studies with a total of 16,160 patients. In 15 studies neuroprotectants were tested for clinical efficacy, where all patients had to receive reperfusion therapies, either IVT and/or EVT. Heterogeneity in reported outcome measures was observed. Treatment was associated with improved clinical outcome for: 1) uric acid in patients treated with EVT and IVT, 2) nerinetide in patients who underwent EVT without IVT, 3) imatinib in stroke patients treated with IVT with or without EVT, 4) remote ischemic perconditioning and IVT, and 5) high-flow normobaric oxygen treatment after EVT, with or without IVT. Studies specifically testing effects of neuroprotective agents in addition to IVT and/or EVT are scarce. Future neuroprotection studies should report standardized functional outcome measures and combine neuroprotective agents with reperfusion therapies in AIS or aim to include prespecified subgroup analyses for treatment with IVT and/or EVT.


Tumor-Suppression Mechanisms of Protein Tyrosine Phosphatase O and Clinical Applications.
Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development. Some reports have shown PTPRO over-expression in tumors can not only inhibit the frequency of tumor cell division and induce tumor cell death, but also suppress migration. However, the tumor-suppression mechanisms are very complex and understanding is incomplete, which in some degree blocks the further development of PTPRO. Hence, in order to resolve this problem, we here have summarized research findings to draw meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to be diverse, such as controlling G0/G1 of the tumor cell proliferation cycle, inhibiting substrate phosphorylation, down-regulating transcription activators and other activities. In clinical anticancer efforts, expression level of PTPRO in tumors can not only serve as a biomarker to monitor the prognosis of patients, but act as an epigenetic biomarker for noninvasive diagnosis. In addition, the re-activation of PTPRO in tumor tissues, not only can induce tumor volume reduction, but also enhance the susceptibility to chemotherapy drugs. So, we can propose that these research findings of PTPRO will not only support new study ideas and directions for other tumor- suppressors, importantly, but also supply a theoretical basis for researching new molecular targeting agents in the future.


Design, Synthesis, Pharmacological Activities, Structure-Activity Relationship, and In Silico Studies of Novel 5-Substituted-2-(morpholinoimino)-thiazolidin-4-ones.
This study is aimed to synthesize morpholine- and thiazolidine-based novel 5-(substituted)benzylidene)-2-(morpholinoimino)-3-phenylthiazolidin-4-ones (3-26) and characterized by molecular spectroscopy. The synthesized compounds were subjected to antioxidant activity with anticholinesterase, tyrosinase, and urease inhibition activities and evaluated the structure-activity relationship (SAR) of enzyme inhibition activities. Compound 11 was found to be the most active antioxidant. In anticholinesterase inhibition, compound 12 (IC50: 17.41 ± 0.22 μM) was the most active against AChE, while compounds 3-26 ( except 3, 8, and 17) showed notable activity against BChE. Compounds 17 (IC50: 3.22 ± 0.70 mM), 15 (IC50: 5.19 ± 0.03 mM), 24 (IC50: 7.21 ± 0.27 mM), 23 (IC50: 8.05 ± 0.11 mM), 14 (IC50: 8.10 ± 0.22 mM), 25 (IC50: 8.40 ± 0.64 mM), 26 (IC50: 8.76 ± 0.90 mM), and 22 (IC50: 9.13 ± 0.55 mM) produced higher tyrosinase inhibition activity. In urease inhibition activity, compounds 20 (IC50: 16.79 ± 0.19 μM), 19 (IC50: 18.25 ± 0.50 μM), 18 (IC50: 20.24 ± 0.77 μM), 26 (IC50: 21.51 ± 0.44 μM), 25 (IC50: 21.70 ± 0.06 μM), and 24 (IC50: 22.49 ± 0.11 μM) demonstrated excellent activities. Besides, the molecular docking study was applied to better understand the inhibitory mechanism between (1-26) compounds and enzymes at the molecular level. According to the results of this study, the synthesized compounds exhibited a better binding affinity toward these enzymes compared to the positive control. Further, molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) binding free energy and molecular dynamics (MD) simulation analyses were performed for AChE with compound 26, which showed high inhibitory activity in silico and in vitro studies. In conclusion, novel morpholine and thiazolidine-based derivative compounds may be pharmacologically effective agents for AChE, BChE, tyrosinase, and urease enzymes.


[Management of complications after angularly stable locking proximal humerus plate fixation].
In this prospective study, complications observed after angularly stable proximal humerus plate fixation (locking proximal humerus plate) were analysed by deriving specific therapies. Fifty patients (median age 65 years, range 25-84 years, 39 female, 11 male) with displaced proximal humerus fractures (seven single, 36 double, and seven triple fractures) were evaluated 3, 6, and 12 months after angularly stable plate fixation using a standard protocol. Age- and gender-matched median constant scores 12 months postoperatively showed for the three fracture types 86, 87, and 55 points and complication rates of 14, 19, and 100%, respectively. There were seven primary and seven secondary implant displacements, five humeral head necroses, four osseous malalignments, two nonunions, two deep infections, and one heterotopic ossification. Nine reoperations were required in six patients: implant removal (n=3), reosteosynthesis (n=2), revision because of nonunion (n=2), and deep infection (n=2). Differentiated analysis of complications and the development of specific prevention and therapeutic strategies considering surgical technique, implant, fracture morphology, and humeral head perfusion minimize the rate of complications observed after angularly stable locking proximal humerus plate fixation.


ER, p53 and MIB-1 are significantly associated with malignant phyllodes tumor.
Fibroadenomas (FA) are common while phyllodes tumors (PT) are rare and both tumors are composed of epithelial and stromal components. We evaluated the expression status of ER, Bc12, p53, and MIB-1 protein in these tumors. One hundred and ninety-three tumors comprising of 117 FAs and 76 PTs were examined using immunohistochemistry on tissue microarray. The mean age of patients with FA was 28.5 years while the mean ages of patients with benign, borderline and malignant PTs were 41.7, 48.6 and 42.1 years, respectively. Also all types of PTs were large (>Scm). ER showed a strong nuclear staining in the epithelial component of all tumors while ER/3 immunoreactivity was detected in both the epithelial and stromal components ofF A and PT. ER/β (p<0.001), and p53 (p=0.006) in the stromal component were associated with tumor size. p53 expression was significantly associated with both the epithelial and stromal components of malignant PTs (p<0.05). In the PT, the decreased expressions of p53 and MIB-1 were significantly different with positive Bc12 protein expression in the epithelial component (p=0.000). In addition, MIB-1 was also found to be associated with ER and ER/3 in the stromal component (p=0.000). The expression of p53 with tumor size and histological grade in PT may increase the risk for malignancy.


[Angiographical extravasation in the intracranial hemorrhage due to cerebrovascular moyamoya disease--autopsy study].
A 53-year-old, non-hypertensive farmer, who had sudden attack of severe headache, was transferred to our clinic. He presented comatous state and tetraparesis without extraocular movements nor reactive pupils to light. CT scan, 7 hours after the ictus showed intracerebral hematoma in the right temporo-parietal region with ventricular extension. The following bilateral carotid angiograms established the diagnosis of the intracerebral hemorrhage due to cerebrovascular moyamoya disease. In angiograms of the affected side, irregular spotty stains spread from the periphei of the right posterior choroidal artery was delineated. The repeated CT scan after that indicated increment of hematoma. Fifty-three hours from the ictus, the patient died and an autopsy study was performed. After the fixation, the coronal brain section was made, and the careful observation of them elucidated the formation of an organized dissecting aneurysm in the angiographically extravasated vessel. About seven hundreds of serial specimen, 4 micron in thickness, was then investigated adjacent to the aneurysm. The organized dissecting aneurysm seemed to initiate from the branch of it, where marked fraying and undulation of the fibroelastic intima and internal elastic laminae were observed. The concavity toward the true lumen was completely disrupted and communicated to the extravascular space. As a result, the continuous part of it obstructed the lumen of the branch. These findings suggested the newly-developed dissection and it seemed to correspond to the angiographical extravasated points.


Effects of alcoholism on acetaminophen pharmacokinetics in man.
As a nonspecific measure of increased metabolic clearance, the kinetics of acetaminophen was studied in a group of nondrinking controls and alcoholics who had ceased drinking within the previous 48 hours. After a single 1-Gm dose of acetaminophen, blood levels showed a significant increase in nondrinking controls over the alcoholics. The area under the curve for the alcoholics was smaller than that for the controls. Further studies are indicated to determine the quantities of the various metabolites of acetaminophen in both groups.


Unrelated umbilical cord blood transplantation and unrelated bone marrow transplantation in children with hematological disease: a meta-analysis.
UCB has been used as an alternative source of HSC. Both unrelated donor BM and UCB are available as potential options for transplantation. However, there have been limited comparisons of the outcomes of unrelated donor UCBT vs. UBMT in the unrelated setting. Our aim is to observe the therapeutic efficacy of UCBT and UBMT for treatment of pediatric hematological diseases. We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and critically appraised all relevant articles (1989.1-2008.5). Comparative studies were carried out on clinical therapeutic effect of UCBT and UBMT with research on stem cells engraftment, complications, earlier mortality, and survival rate. We performed a meta-analysis using review manager 5.0 software (RevMan, The Nordic Cochrane Center, The Cochrane Collaboration) and adopted funnel plot regression to assess the publication bias. We obtained 324 records. Seven trials totaling 1453 patients have been assessed. Pooled comparisons of studies of UCBT and UBMT in children found that the incidence of engraftment failure and earlier transplantation-related mortality were higher with UCBT because of its delay of hematological recovery [OR = 4.96, 95% CI (3.25, 7.59), p < 0.00001 and OR = 2.36, 95% CI (1.79, 3.11), p < 0.00001 respectively], but CMV infection didn't increase obviously. There was no difference in long disease-free survival rate [OR = 0.85, 95% CI (0.65, 1.01), p = 0.06] between UCBT and UBMT due to the decrease of GVHD in UCBT [OR = 0.45, 95% CI (0.34, 0.60), p < 0.0001]. Our meta-analysis confirmed that UCBT in children is also an effective way to treat children with hematological disease and has equivalent survival outcomes compared with UBMT.


A survival guide for endovascular declotting in dialysis access: procedures, devices, and a statistical analysis of 3,000 cases.
Thrombosis is the most important access-related complication. Several declotting procedures have been suggested falling mainly into two categories; thrombolysis-dependent and thrombectomy-dependent. Seventeen studies after 2001 have been published on percutaneous treatment of thrombosed vascular access. Authors performed a systematic review of these studies together with a parametric meta-analysis of data available investigating clinical success, postintervention assisted primary patency (PAPP) and independent factors that could influence outcome measures. A shift to thrombectomy-dependent procedures is observed with a view to diminishing complications from the use of thrombolytic agents. Arteriovenous fistulas provide significantly better PAPP, while newer studies show improved, non-significant results compared with older ones. The role of improvement of devices for subsequent angioplasty is of equal importance, if not more, for improved declotting results.


Biosorption and toxicity responses to arsenite (As[III]) in Scenedesmus quadricauda.
Toxicity and biosorption responses to arsenite (As[III]) were examined in a 96-h exposure study using Scenedesmus quadricauda, one of the most popular green algae distributed in freshwaters in China. Results indicated that the pH-dependent distribution of two arsenite species (H2AsO3(-) and H3AsO3) played an important role in biosorption and toxicity. The undissociated H3AsO3 was more toxic than its monoanionic H2AsO3(-) through comparison of algal cell numbers, chlorophyll-a contents, and algal ultrastructural changes observed with transmission electron microscopy. An effective biosorption of 89.0mgg(-1) at 100mgL(-1) As[III] was found in the treatments with an initial pH of 9.3 and 25.2μgg(-1) at 0.03mgL(-1) As[III] at an initial pH of 8.2 as a result of the predominant species of H2AsO3(-) under the ambient pH and Eh conditions. Our results imply that S. quadricauda may provide a new means for the removal of toxic arsenite species present in contaminated surface water.


Modified cellular automaton model for the prediction of dendritic growth with melt convection.
A modified cellular automaton (MCA) coupled with a momentum and species transport model has been developed in order to predict the evolution of dendritic morphology during solidification of alloys in the presence of melt convection. In the present model, the cellular automaton algorithm for dendritic growth is incorporated with the transport model, for calculating fluid flow and mass transfer by both convention and diffusion. The MCA model takes into account the effects of the constitutional undercooling and the curvature undercooling on the equilibrium interface temperature. It also considers the preferred growth orientation of crystals and solute redistribution during solidification. In the transport model, which is coupled with cellular automaton approach, the SIMPLE scheme is employed to solve the governing equations of momentum and species transfers. The present model was applied to model solutal dendritic growth of an Al-3mass%Cu alloy in a forced flow. The simulations reproduced the typical asymmetric growth features of convective dendrites with various preferred orientations. The effects of inlet flow velocity on the solute redistribution and the growth velocity of a dendritic tip were quantitatively investigated.


The melting of pulmonary surfactant monolayers.
Monomolecular films of phospholipids in the liquid-expanded (LE) phase after supercompression to high surface pressures (pi), well above the equilibrium surface pressure (pi(e)) at which fluid films collapse from the interface to form a three-dimensional bulk phase, and in the tilted-condensed (TC) phase both replicate the resistance to collapse that is characteristic of alveolar films in the lungs. To provide the basis for determining which film is present in the alveolus, we measured the melting characteristics of monolayers containing TC dipalmitoyl phosphatidylcholine (DPPC), as well as supercompressed 1-palmitoyl-2-oleoyl phosphatidylcholine and calf lung surfactant extract (CLSE). Films generated by appropriate manipulations on a captive bubble were heated from < or =27 degrees C to > or =60 degrees C at different constant pi above pi(e). DPPC showed the abrupt expansion expected for the TC-LE phase transition, followed by the contraction produced by collapse. Supercompressed CLSE showed no evidence of the TC-LE expansion, arguing that supercompression did not simply convert the mixed lipid film to TC DPPC. For both DPPC and CLSE, the melting point, taken as the temperature at which collapse began, increased at higher pi, in contrast to 1-palmitoyl-2-oleoyl phosphatidylcholine, for which higher pi produced collapse at lower temperatures. For pi between 50 and 65 mN/m, DPPC melted at 48-55 degrees C, well above the main transition for bilayers at 41 degrees C. At each pi, CLSE melted at temperatures >10 degrees C lower. The distinct melting points for TC DPPC and supercompressed CLSE provide the basis by which the nature of the alveolar film might be determined from the temperature-dependence of pulmonary mechanics.


Thymidine phosphorylase: a possible marker of cell maturation in acute myeloid leukaemia.
Thymidine Phosphorylase activity has been measured in two populations of human Acute Myeloid Leukaemia cells (AML) and in normal human macrophages. During short-term culture in vitro of AML cells the activity of this enzyme increases progressively and approaches that of normal non-dividing macrophages at a time when the leukaemia cells in culture show evidence of maturation as assayed by functional, enzymatic and morphological criteria. It is suggested that the level of Thymidine Phosphorylase activity may be a marker of maturation in AML.


Pharmacokinetic studies of mabuterol, a new selective beta 2-stimulant. I: Studies on the absorption, distribution and excretion in rats.
Pharmacokinetic studies on absorption, distribution, excretion and placental transfer of the beta-sympathomimetic 14C-labelled dl - 1 - (4 - amino - 3 - chloro - 5 - trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol hydrochloride (mabuterol) have been carried out in rats. Mabuterol was easily absorbed from the whole length of the small intestine in a study in situ with the gastro-intestinal ligated loop technique. The blood and tissue levels of radioactivity reached the maximum within 1 h after oral administration. Concerning tissue distribution (excluding the digestive tract) after oral administration, the radioactivity in the liver, lung, kidney and several secretory organs was considerably higher than that in the blood. The levels of radioactivity in these tissues continued at almost the same levels for 2-6 h after oral administration, resulting from a slow gastric emptying of the radioactivity. The whole-body autoradiograms obtained after intravenous administration revealed the secretion of the radioactivity into the stomach. The radioactive concentration in the CNS was much lower than that in the principal organs with either route of administration. About 60% and 26% were excreted into urine and feces, respectively, within 24 h after oral administration. Although about 22% was excreted into bile within 24 h after intravenous administration, no other evidence of enterohepatic circulation was observed. The multiple oral administration of 14C-mabuterol indicated no, appreciable accumulation in the tissues of rats. A placental transfer in the pregnant rats in the last stage of gestation was not significant.


Principles-based medical informatics for success--how Hong Kong built one of the world's largest integrated longitudinal electronic patient records.
Since 1994, the Hospital Authority has been developing and deploying clinical applications at its constituent 41 hospitals and 121 clinics. The Clinical Management System (CMS) is now used by over 4000 doctors and 20000 other clinicians on a daily basis to order, document and review care. The territory-wide Electronic Patient Record (ePR) has given clinicians an integrated, longitudinal, lifelong view of a patient's record. Today the CMS and ePR form an essential clinical and management tool to the Hospital Authority. The CMS handles two million clinical transactions per day, and the ePR has over 6TB of data covering 57 million episodes for 7.9 million patients. This paper describes how the HA has taken a principles-based approach to Medical Informatics to achieve its success in the enterprise-wide deployment and deep utilization of a comprehensive clinical information system.


[Highly active interferon in the combined treatment of patients with meningoencephalitis].
High-active interferon was used in the complex treatment of 49 patients with nervous system diseases of viral-bacterial etiology. A control group of 28 similar patients were also analyzed. A positive clinical effect was observed in early use of interferon. The clinical course of the disease was milder, the duration of clinical symptoms reduced, healing of the CSF was enhanced, the development of protracted forms of the disease was preventable, lethality reduced 2.9 times with interferon in the complex treatment of these patients.


The Potential of Pre-Exposure Prophylaxis for Women in Violent Relationships.
HIV and intimate partner violence (IPV) are significant intersecting threats to women's health. Women in violent relationships have few feasible HIV risk reduction options as traditional prevention methods are largely dependent on a partner's cooperation. The purpose of this review is to explore potential benefits and drawbacks of pre-exposure prophylaxis (PrEP) use among women in the United States experiencing IPV. Advantages of PrEP use in this population include the potential for covert or autonomous use, coital independence, dual protection against sexual and injection risk, and facilitated connections to social services. A number of barriers, however, may interfere with the effective use of PrEP, including partner resistance, cost, frequent medical visits, gendered norms regarding sexuality, and stigma. To realize its potential for women in violent relationships, it will be necessary to incorporate PrEP into behavioral and structural interventions that encourage uptake, facilitate adherence, ensure women's safety, and challenge existing gender norms.


Duration of hydralazine action in hypertension.
The effect on blood pressure of giving hydralazine orally, 300 mg per day divided into 2, 3, and 4 doses, was studied in 4 hypertensive patients. There was no significant difference in average mean arterial pressure for the 3 regimens. Fluctuations of mean arterial pressure with time were not significantly different for the regimens as indicated by coefficient of variation. The mean coefficient of variation for the 2 days prior to initiation of hydralazine dosing was 4.0% +/- 0.3 (SEM) and for the 3 dosing regimens ranged from 4.1% to 4.8%. Heart rate was used as an index of vasodilator-induced increase in sympathetic tone and therefore as a measure of possible side effects. Fluctuations in heart rate were small and were not associated with symptoms. After discontinuation of hydralazine, the time for blood pressure to return halfway between initial placebo value and end treatment value varied from 30 to 140 hr. A tracer dose of hydralazine 14C. HCl was administered intravenously to the patients. The urinary excretion of 14C showed a multiexponential pattern of elimination with a previously undescribed prolonged terminal phase. Under the conditions of the present study, a daily dose of 300 mg of hydralazine was as effective and free of side effects given in 2 as in 4 divided doses.


Growth Promotion Ethics and the Challenge to Resist Cosmetic Endocrinology .
The advancement of "human growth hormone (hGH)-for-height" - increasing height attainment in children short for reasons other than GH deficiency - arose from intuitive, deep-seated assumptions about the disability of short stature, its improvement with hGH-mediated height gain, and the safety of escalating dosages of hGH in healthy children. Evidence challenging these assumptions now strengthens criticism of hGH-for-height as cosmetic endocrinology. To counter this characterization, collective acceptance of guidelines is needed that advise nontreatment of the vast majority of short children, support strategies that minimize treatment duration and dosage, and restrain enhancement of normal adult stature. Through a clinical case analysis, ethical issues underlying these recommendations are explored. These include duties to provide informed assent and re-assent, protect children from unnecessary treatment, consider fairness to nontreated children, and allocate healthcare resources responsibly. Informed assent for hGH-for-height should ensure awareness of modest, variable height gain expectations, limited evidence for psychosocial benefit, ongoing studies for potential posttreatment adverse effects, and options for less expensive/invasive approaches, including nontreatment and counseling. Approaching growth pro-motion in this way fosters therapeutic restraint, resists the al lure of enhancement therapy, and minimizes contributions to society's perception that to be taller is to be better. .


Efficacy and Safety of Naloxegol in Patients with Chronic Non-Cancer Pain Who Experience Opioid-Induced Constipation: A Pooled Analysis of Two Global, Randomized Controlled Studies.
This study evaluates the onset, magnitude, and consistency of improvement of opioid-induced constipation (OIC) symptoms with naloxegol treatment. This was a pooled analysis of two Phase 3, double-blind, randomized, placebo-controlled studies (KODIAC-04/05, NCT01309841/NCT01323790) in patients with chronic non-cancer pain and OIC treated with naloxegol 25mg or 12.5mg daily. This analysis assessed improvements in response rates, frequency of spontaneous bowel movement (SBM) and complete SBMs (CSBM), OIC constipation symptoms (straining, stool consistency), time to first post-dose SBM and CSBM, and onset of adverse events over the 12-week period. The population of 1337 subjects had a mean age of 52 years and mean duration of opioid use of 3.6 years at baseline. Mean SBM frequency was 1.4/week. Naloxegol 25mg and 12.5mg demonstrated significantly higher response rates vs placebo (PBO) [41.9% (P < 0.001), 37.8% (P = 0.008), 29.4% respectively]. Rapid (within 1 week) and sustained (over 12 weeks) symptom improvement was significantly greater for naloxegol vs PBO (P < 0.05). Both doses showed statistically significant and clinically meaningful improvements in straining, stool consistency, number of SBMs and CSBMs/wk. Significantly shorter times to first post-dose SBM and CSBM were observed with naloxegol vs PBO (SBM HR: 25mg = 1.90, 12.5mg= 1.60; CSBM HR: 25mg = 1.42, 12.5mg = 1.36; P < 0.001 for each regimen). Adverse events occurred more frequently in the naloxegol 25mg group and were most frequently reported during the first week. In patients with chronic non-cancer pain, naloxegol 25mg and 12.5mg demonstrated significantly higher response rates and rapid and sustained improvements in OIC symptoms compared with PBO.


Self-assembly of carbon-nanotube-based single-electron memories.
We demonstrate the wafer-scale integration of single-electron memories based on carbon nanotube field-effect transistors (CNFETs) using a process based entirely on self assembly. First, a "dry" self-assembly step based on chemical vapor deposition (CVD) allows the growth and connection of CNFETs. Next, a "wet" self-assembly step is used to attach a single 30-nm-diameter gold bead in the nanotube vicinity via chemical functionalization. The bead is used as the memory storage node while the CNFET operating in the subthreshold regime acts as an electrometer exhibiting exponential gain. Below 60 K, the transfer characteristics of gold-CNFETs show highly reproducible hysteretic steps. Evaluation of the capacitance confirms that these current steps originate from the controlled storage of single electrons with a retention time that exceeds 550 s at 4 K.


Ultrastructural characteristics of spermiogenesis in the domestic duck (Anas platyrhynchos).
In this present study was observed that the spermatids underwent morphological differentiation and modifications, which primarily comprised nuclear elongation, during the process of spermiogenesis in the domestic duck. The acrosome was formed and the flagellum developed concomitantly with nuclear modifications. Thus, various modifications could be observed during this process, especially changes in the distribution of cytoplasmic organelles. Long cisternae of the rough endoplasmic reticulum present in the spermatid cytoplasm dissociated into vesicles and the distal centriole initiated the development of the flagellum in the cellular portion opposite to the acrosome. The ultrastructure of the spermatids of the domestic duck did not show the characteristic development of pre-acrosomal granules, but the acrosomal granule could be directly visualized in this species.


Novel Inhaled Combination Powder Containing Amorphous Colistin and Crystalline Rifapentine with Enhanced Antimicrobial Activities against Planktonic Cells and Biofilm of Pseudomonas aeruginosa for Respiratory Infections.
Colistin has been increasingly used for the treatment of respiratory infections caused by Gram-negative bacteria. Unfortunately parenteral administration of colistin can cause severe adverse effects. This study aimed to develop an inhaled combination dry powder formulation of colistin and rifapentine for the treatment of respiratory infections. The combination formulation was produced by spray-drying rifapentine particles suspended in an aqueous colistin solution. The combination dry powder had enhanced antimicrobial activities against planktonic cells and biofilm cultures of Pseudomonas aeruginosa, with both minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) values (2 and 4 mg/L, respectively) being half that of pure colistin (MIC 4 mg/L and MBIC 8 mg/L) and 1/16th that of pure rifapentine (MIC 32 mg/L and MBIC 64 mg/L). High aerosol performance, as measured via an Aerolizer device, was observed with emitted doses>89% and fine particle fraction (FPF) total>76%. The proportion of submicron particles of rifapentine particles was minimized by the attachment of colistin, which increased the overall particle mass and aerodynamic size distribution. Using the spray-drying method described here, stable particles of amorphous colistin and crystalline rifapentine were distributed homogeneously in each stage of the impinger. Unlike the colistin alone formulation, no deterioration in aerosol performance was found for the combination powder when exposed to a high relative humidity of 75%. In our previous study, surface coating by rifampicin contributed to the moisture protection of colistin. Here, a novel approach with a new mechanism was proposed whereby moisture protection was attributed to the carrier effect of elongated crystalline rifapentine particles, which minimized contact between hygroscopic colistin particles. This inhaled combination antibiotic formulation with enhanced aerosol dispersion efficiency and in vitro efficacy could become a superior treatment for respiratory infections.


A survey of management strategies for noncarious cervical lesions.
Both causation and management of noncarious cervical lesions (NCCLs) (abfractions, wedge-shaped defects, stress-induced cervical lesions, and cervical erosion) remain debatable. A survey of clinicians' perceptions was therefore conducted at a recent professional meeting to determine optimal approaches to NCCL management. Examples of lesions differing in depth (1, 2, and 3 mm) were presented as being either sensitive or nonsensitive, and participants recorded their responses to the presented individual scenarios. This report provides information regarding correlations between increases in lesion depth, lesion sensitivity, and professionals' willingness to restore them. It was also noted that decisions to ensure mechanical retention positively influenced estimates for restoration longevity.


Phenotypic debrisoquine 4-hydroxylase activity among extensive metabolizers is unrelated to genotype as determined by the Xba-I restriction fragment length polymorphism.
1. The major pathway for 4-hydroxylation of debrisoquine in man is polymorphic and under genetic control. More than 90% of subjects (extensive metabolizers, EMs) have active debrisoquine 4-hydroxylase (cytochrome P450IID6) while in the remainder (poor metabolizers, PMs), cytochrome P450IID6 activity is greatly impaired. 2. Within the EM group, cytochrome P450IID6-mediated metabolism of a range of substrates varies widely. Some of this intra-phenotype non-uniformity may be explained by the presence of two subsets of subjects with different genotypes (heterozygotes and homozygotes). 3. Cytochrome P450IID6 substrates have not differentiated between these two genotypes. However, a restriction fragment length polymorphism (RFLP) which identifies mutant alleles of cytochrome P450IID6 locus has been described and can definitively assign genotype in some heterozygous EM subjects. 4. In this study, we used RFLP analysis and encainide as a model substrate to determine if non-uniformity in cytochrome P450IID6 activity among EMs is related to genotype. We tested the hypothesis that heterozygotes exhibit intermediate metabolic activity and that homozygous dominants exhibit the highest activity. We proposed encainide as a useful substrate for this purpose since cytochrome P450IID6 catalyzes not only its biotransformation to O-desmethyl encainide (ODE) but also the subsequent metabolism of ODE to 3-methoxy-O-desmethyl encainide (MODE). 5. A single 50 mg oral dose of encainide was administered to 139 normal volunteers and 14 PMs were identified. Urinary ratios among encainide, ODE and MODE in the remaining 125 EM subjects revealed a wide range of cytochrome P450IID6 activity. However, Southern blotting of genomic DNA digested with XbaI identified obligate heterozygotes in both extremes of all ratio distributions.(ABSTRACT TRUNCATED AT 250 WORDS)


Hyphal differentiation in the exploring mycelium of Aspergillus niger.
Mycelial fungi play a central role in element cycling in nature by degrading dead organic material such as wood. Fungal colonization of a substrate starts with the invasion of exploring hyphae. These hyphae secrete enzymes that convert the organic material into small molecules that can be taken up by the fungus to serve as nutrients. Using green fluorescent protein (GFP) as a reporter, we show for the first time that exploring hyphae of Aspergillus niger differentiate with respect to enzyme secretion; some strongly express the glucoamylase gene glaA, while others hardly express it at all. When a cytoplasmic GFP was used, 27% of the exploring hyphae of a 5-day-old colony belonged to the low expressing hyphae. By fusing GFP to glucoamylase and by introducing an ER retention signal, this number increased to 50%. This difference is due to cytoplasmic streaming of the reporter in the former case, as was shown by using a photo-activatable GFP. Our findings indicate that a fungal mycelium is highly differentiated, especially when taking into account that hyphae in the exploration zone were exposed to the same nutritional conditions.


Autophagy pathway upregulation in a human iPSC-derived neuronal model of Cohen syndrome with VPS13B missense mutations.
Significant clinical symptoms of Cohen syndrome (CS), a rare autosomal recessive disorder, include intellectual disability, facial dysmorphism, postnatal microcephaly, retinal dystrophy, and intermittent neutropenia. CS has been associated with mutations in the VPS13B (vacuolar protein sorting 13 homolog B) gene, which regulates vesicle-mediated protein sorting and transport; however, the cellular mechanism underlying CS pathogenesis in patient-derived neurons remains uncertain. This report states that autophagic vacuoles accumulate in CS fibroblasts and the axonal terminals of CS patient-specific induced pluripotent stem cells (CS iPSC)-derived neurons; additionally, autophagic flux was significantly increased in CS-derived neurons compared to control neurons. VPS13B knockout HeLa cell lines generated using the CRISPR/Cas9 genome editing system showed significant upregulation of autophagic flux, indicating that VSP13B may be associated with autophagy in CS. Transcriptomic analysis focusing on the autophagy pathway revealed that genes associated with autophagosome organization were dysregulated in CS-derived neurons. ATG4C is a mammalian ATG4 paralog and a crucial regulatory component of the autophagosome biogenesis/recycling pathway. ATG4C was significantly upregulated in CS-derived neurons, indicating that autophagy is upregulated in CS neurons. The autophagy pathway in CS neurons may be associated with the pathophysiology exhibited in the neural network of CS patients.


Toxoplasma gondii Infection in Dustmen in Northeastern China: A Case-Control Seroprevalence Study.
Toxoplasmosis is caused by an intracellular parasite Toxoplasma gondii, which can infect many hosts including humans. In order to estimate whether dustmen are more susceptible to T. gondii, a case-control study was conducted containing 332 dustmen from Jilin and Heilongjiang in Northeastern China, as well as 332 general populations from the same regions as control subjects. Serum samples were tested IgG and IgM antibodies to T. gondii using the enzyme-linked immunosorbent assay (ELISA). The overall anti-T. gondii IgG was 15.06% (50/332) in dustmen compared with 9.64% (32/332) in the controls (P = 0.0337). Also, 5 (1.51%) dustmen had anti-T. gondii IgM antibodies compared with 2 (0.60%) control individuals (P = 0.2543). A significant association was only found between dustmen and level of T. gondii IgG in comparison with the control subjects. Seroprevalence of T. gondii IgG antibodies in male dustmen was significant higher than male control subjects (P = 0.0399). Dustmen from Jilin had the significant higher T. gondii IgG rate (P = 0.0143), in comparison with the control subjects from Jilin. Moreover, dustmen raising cat at home had the significant higher T. gondii IgG rate (P = 0.0097), in comparison with the control subjects. Risk factor analysis suggested that raising cat at home and not having habits of washing hand before eating were mainly related to the T. gondii infection in dustmen. This is the first record of seroprevalence of T. gondii infection in dustmen in Jilin and Heilongjiang provinces in Northeastern China. These findings also suggest that the government departments should pay close attention to the toxoplasmosis in dustmen in Northeastern China.


Coactivator-associated arginine methyltransferase 1 enhances transcriptional activity of the human T-cell lymphotropic virus type 1 long terminal repeat through direct interaction with Tax.
In this study, we demonstrate that the coactivator-associated arginine methyltransferase 1 (CARM1), which methylates histone H3 and other proteins such as p300/CBP, is positively involved in the regulation of Tax transactivation. First, transfection studies demonstrated that overexpression of CARM1 wild-type protein resulted in increased Tax transactivation of the human T-cell lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR). In contrast, transfection of a catalytically inactive CARM1 methyltransferase mutant did not enhance Tax transactivation. CARM1 facilitated Tax transactivation of the CREB-dependent cellular GEM promoter. A direct physical interaction between HTLV-1 Tax and CARM1 was demonstrated using in vitro glutathione S-transferase-Tax binding assays, in vivo coimmunoprecipitation, and confocal microscopy experiments. Finally, chromatin immunoprecipitation analysis of the activated HTLV-1 LTR promoter showed the association of CARM1 and methylated histone H3 with the template DNA. In vitro, Tax facilitates the binding of CARM1 to the transcription complex. Together, our data provide evidence that CARM1 enhances Tax transactivation of the HTLV-1 LTR through a direct interaction between CARM1 and Tax and this binding promotes methylation of histone H3 (R2, R17, and R26).


Isolated Persistent Left Superior Vena Cava Revealed by an Associated Asthma.
Persistent left superior vena cava (PLSVC) is a rare anomaly of the thoracic venous system. Case Report. We present a case of a patient with isolated asymptomatic PLSVC, who was diagnosed because of dyspnea revealing an associated asthma. An 18-year-old male patient complained of paroxystic sibilant dyspnea. He did not have any anomaly in physical examination. The chest X-ray revealed cardiomegaly with a widening of lower mediastinum. The electrocardiogram does not show any anomaly. Echocardiography showed the PLSVC. The thoracic contrast computed tomography of the chest showed ecstasies of the right cardiac cavities and a double superior vena cava. The patient did not have similar family cases. Respiratory functional explorations led to the diagnosis of an associated asthma. Currently, he is followed up periodically. Asthma was improved with inhaled corticosteroid treatment. PLSVC is rare but can have important clinical implications. Associated severe cardiac malformations must be systematically sought.


Hard x-ray telescopes to be onboard ASTRO-H.
The new Japanese x-ray astronomy satellite, ASTRO-H, will carry two identical hard x-ray telescopes (HXTs), which cover the energy range of 5 to 80 keV. The HXT mirrors employ tightly nested, conically approximated thin-foil Wolter-I optics, and the mirror surfaces are coated with Pt/C depth-graded multilayers to enhance the hard x-ray effective area by means of Bragg reflection. The HXT comprises foils 120-450 mm in diameter and 200 mm in length, with a focal length of 12 m. To obtain a large effective area, 213 aluminum foils 0.2 mm in thickness are tightly nested confocally. The requirements for HXT are a total effective area of >300 cm2 at 30 keV and an angular resolution of <1.7' in half-power diameter (HPD). Fabrication of two HXTs has been completed, and the x-ray performance of each HXT was measured at a synchrotron radiation facility, SPring-8 BL20B2 in Japan. Angular resolutions (HPD) of 1.9' and 1.8' at 30 keV were obtained for the full telescopes of HXT-1 and HXT-2, respectively. The total effective area of the two HXTs at 30 keV is 349 cm2.


Acinetobacter baumannii: no more a choosy intruder?
Acinetobacter baumannii, a non-fermenter, is fast coming up the list of pathogens causing nosocomial infections. Earlier considered to be a harmless colonizer, or at the most, a pathogen causing mostly respiratory tract infections, it has slowly but successfully emerged as a ubiquitous pathogen causing both community as well as health care associated infections. It has acquired multidrug resistance, and seems to be no more selective in mainly attacking any one or two body systems. According to recent reports, a shy selective bacterium has turned into a dangerous pathogen, capable of causing infections anywhere in the body, thereby adding extra furrows on the forehead of medical community worldwide. To determine the range of infections caused by A. baumannii, and the frequencies thereof, in our tertiary care hospital; and to study their resistance patterns. A total of 88 isolates of A. baumannii were found from a variety of clinical samples, from hospitalized patients as well as patients attending the outpatient departments. The isolates were subjected to disc-diffusion method for antibiotic sensitivity testing. Acinetobacter was mostly recovered from samples of pus, followed by endotracheal tube, urine, sputum samples, etc., Imipenem showed highest sensitivity, while other drugs with good sensitivity patterns were aminoglycosides and piperacillin-tazobactum. In this tertiary care institution of ours, A. baumannii isolates have shown a high frequency of drug resistance, with imipenem being the best sensitive drug. This non-fermenter is the cause of a variety of infections, irrespective of whether the individuals are hospitalized or are outdoor patients.


Anaphylaxis to piñon nuts.
A 21-year-old white male developed life threatening systemic anaphylaxis within seconds of ingesting a small amount of a cookie containing piñon nuts. Skin testing, ELISA, and basophil histamine release studies demonstrated piñon nut-specific IgE. Electrophoresis of the piñon nut extract demonstrated 30 bands, three of which (in the 66 to 68,000 dalton range) bound IgE in the patient's serum in an immunoblot. Ingestion challenge was not performed due to the severity of the patient's reaction. Although used for centuries in certain cultures, piñon nuts are now being eaten more frequently in the American diet. Physicians should be aware of the potential for anaphylactic reactions following ingestion of this food.