Impact of 2013 ACGME Minimum Case Requirements on Orthopedic Resident Operative Volume.
In 2013, the Accreditation Council for Graduate Medical Education (ACGME) mandated orthopedic surgery residents to perform at least 1000 surgical cases during residency and specified "case minimums" for 15 core procedure categories. We assessed trends in the volume and variability of graduating orthopedic surgery resident caseload since the implementation of these case minimums. We performed a retrospective linear regression analysis of ACGME-published case log data of US orthopedic residents graduating from 2014 to 2019, with trend analysis, comparison of case volume between residents in 10th and 90th percentiles, and comparison of logged cases vs case minimums for core procedures. Median total procedures performed increased from 1464 (range, 592-2842) in 2014 to 1709 (range, 870-3318) in 2019, representing a 17% increase in case volume (P<.001). Residents performing at the 90th percentile logged twice as many cases as residents performing at the 10th percentile. Of the core procedures, carpal tunnel release and total knee arthroplasty most greatly exceeded ACGME requirements (performed at 4.3 to 4.7 times the minimums, respectively). Graduating resident case volume increased significantly from 2014 to 2019. Variability in operative experience remains high and did not change significantly during the study period. [Orthopedics. 2022;45(1):25-30.].


[Comparison of vaginal lactobacilli and Lactobacillus species discrimination using classic methods and polymerase chain reaction].
The aim of this study was to identify the vaginal lactobacilli in the species level and to investigate the concordance between classical methods and polymerase chain reaction (PCR) for the typing of these isolates. Vaginal swab samples which have been collected from women who were admitted to the outpatient clinics of Gynecology Department of our hospital, were examined by standard microbiological methods and additionally were inoculated into selective lactobacilli media. Of 200 subjects, 59.5% have had normal vaginal flora, 31% were diagnosed as bacterial vaginosis and 9.5% as vaginal candidiasis. The lactobacilli isolation rates of these groups were found 76.5%, 45.2% and 78.9%, respectively. A total of 160 facultative anaerobic Lactobacillus strains were isolated from 134 (67%) of the swab samples. Of these, 90.6% were identified into species level by classical methods, and the most frequently isolated species in our study was found as L. gasseri (40%), followed by L. delbrueckii (18%). The comparative study was performed only for 66 isolates, and 58 of them (87.8%) were grouped into 7 species while 8 have not been identified by classical methods, however, all of 66 isolates were successfully grouped into 4 species by PCR. Fourty-five of 66 strains have been found to be identical by means of classical methods and PCR, and the concordance between the methods were found 68.2 percent.


Prognostic factors of hepatic decompensation and hepatocellular carcinoma in patients with transfusion-acquired HCV infection.
Aim of this study was to assess if host (immunogenetic traits, age, sex), exogenous (alcohol) or viral factors (viral type, past HBV infection) might affect the progression of chronic hepatitis C to liver decompensation or the development of HCC in a cohort of patients exposed to a single blood transfusion prior to the introduction of anti-HCV screening. Two hundred and forty-eight patients with a history of a single exposure to blood or blood products prior to 1990 were retrospectively considered. Patients were devoid of other risk factors of liver disease or immunosuppression and naïve to antiviral therapies. Eight baseline variables were assessed: age at transfusion, sex, HBV core antibody, immunogenetic profile (DRB1*11, DRB1*1104, DRB1*07), HCV genotype and alcohol consumption. The follow-up was 22 (SD: 11) years. Sixty-eight patients (27%) progressed to hepatic decompensation over a median period of 22.5 years (IQR: 14-30) and 41 patients (16%) developed HCC over a median period of 31 years (IQR: 24-38). The cumulative incidence of liver failure was 0.4% (95% CI: 0.1-3.1), 4.9% (95% CI: 2.6-9.3) and 16.2% (95% CI: 10.4-24.7) at 10, 20 and 30 years after blood transfusion respectively. By univariate analysis, only age at transfusion was correlated with the risk of decompensation. Stratifying the age of transfusion by tertiles, the incidence of hepatic decompensation was 0.7% per year in patients transfused at ≤24 years of age as compared to 1.2% and 1.9% per year in those transfused at 25-35 and >36 years of age respectively (HR: 5.5, 95% CI: 2.78-10.7, P<0.001). The risk of HCC development was correlated by univariate analysis with age at transfusion (as continuous variable, HR: 1.12, 95% CI: 1.08-1.16 per year of age, P<0.001, >36 compared to ≤24 years, HR: 10.3, 95% CI: 3.9-26.9, P<0.001) and male sex (HR: 4.2, 95% CI: 1.7-10, P=0.001). Multivariate analysis confirmed age at transfusion and male sex as independent predictors of HCC development [HR: 1.12 per year (95% CI: 1.08-1.16), P<0.001 and HR: 5.4 (95% CI: 2.2-13.2), P<0.001 respectively]. In patients with transfusion-acquired HCV infection, age at transfusion affects the risk for hepatic decompensation. Age at transfusion and male sex are independent risk factors for HCC development.


The Setting is the Service: How the Architecture of Sober Living Residences Supports Community Based Recovery.
The architecture of residential recovery settings is an important silent partner in the alcohol/drug recovery field. The settings significantly support or hinder recovery experiences of residents, and shape community reactions to the presence of sober living houses (SLH) in ordinary neighborhoods. Grounded in the principles of Alcoholics Anonymous, the SLH provides residents with settings designed to support peer based recovery; further, these settings operate in a community context that insists on sobriety and strongly encourages attendance at 12-step meetings. Little formal research has been conducted to show how architectural features of the recovery setting - building appearance, spatial layouts, furnishings and finishes, policies for use of the facilities, physical care and maintenance of the property, neighborhood features, aspects of location in the city - function to promote (or retard) recovery, and to build (or detract from) community support. This paper uses a case-study approach to analyze the architecture of a community-based residential recovery service that has demonstrated successful recovery outcomes for its residents, is popular in its community, and has achieved state-wide recognition. The Environmental Pattern Language (Alexander, Ishikawa, & Silverstein, 1977) is used to analyze its architecture in a format that can be tested, critiqued, and adapted for use by similar programs in many communities, providing a model for replication and further research.


Beam Diagnostics for High Energy Pulsed CO(2) Lasers.
To examine high energy CO(2) pulsed laser beams, reliable sampling and attenuation procedures were devised using the properties of coarse transmission gratings and diffuse scatter from specular metal mirrors. Details of measurements and alignment procedures are described including a single shot, nondisruptive method for effectively scanning the time integrated focal distribution of a high energy pulsed laser. In addition, it is shown that a simple multiple burn pattern technique can be used for the quantitative measurement of the integrated distribution. The data obtained demonstrate near diffraction-limited capability for large e-beam lasers with unstable resonators.


The Role of SH2 Domain-containing Leukocyte Phosphoprotein of 76 kDa in the Regulation of Immune Cell Development and Function.
Recent years have seen an explosion of new knowledge defining the molecular events that are critical for development and activation of immune cells. Much of this new information has come from a careful molecular dissection of key signal transduction pathways that are initiated when immune cell receptors are engaged. In addition to the receptors themselves and critical effector molecules, these signaling pathways depend on adapters, proteins that have no intrinsic effector function but serve instead as scaffolds to nucleate multimolecular complexes. This review summarizes some of what has been learned about one such adapter protein, SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76), and how it regulates and integrates signals after engagement of immunoreceptors and integrins on various immune cell lineages.


Study of image findings in rapid eye movement sleep behavioural disorder.
To elucidate the cause of idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), magnetic resonance imaging and single-photon emission computed tomography of the brain were conducted on 20 patients with RBD. Blood flow in the upper portion of both sides of the frontal lobe and pons was significantly lower in patients with RBD than in the normal elderly group. Among the patients with RBD, decreased blood flow in the frontal lobe showed no correlation with the extent of frontal lobe atrophy. Decreased blood flow in the upper portion of the frontal lobe and pons might be associated with the pathogenesis of idiopathic RBD.


Average Force of Deployment and Maximum Arrest Force of Energy Absorbers Lanyards.
Energy-absorbing lanyards (EAL) are part of fall arrest systems (FAS), their main mission is to dissipate the energy generated during the fall, ensuring that the arresting force does not cause injury to the user. For the design of FAS as set out in the American standard Z359.6 and the Canadian Z259.16 it is essential to know the deployment force or average arrest force (Fa). Fa is necessary to estimate the elongation that the absorber will suffer during the fall and therefore essential data to calculate the clearance distance. There is a lack of useful experimental data for the design of this personal protective equipment (PPE). This work provides empirical data required for the design of FAS with EAL in accordance with EN 355. This paper covers different types of EAL that are marketed internationally; different empirical data, average and maximum forces, required for improving safety design are researched. Six manufacturers, 10 models, and 2 samples of each model were selected, with total of 20 tests being performed. Dynamic performance tests were carried out, the free fall of a person was simulated using a 100 kg steel ballast from the maximum height allowed by the equipment, obtaining the maximum arrest force (Fm), average deployment force (Fa), and, by calculating the balance of forces, the maximum and average acceleration suffered by the ballast during its arrest. In light of the results, relevant conclusions for user safety are obtained. It is feasible to raise the safety requirements established by the different standards. The Fm can be established below 6 kN in the EAL, and the Fa can be estimated at 87.5% of the Fm. The categorization of the force-time curve in fall arrest with EAL has been obtained. Two EAL purchased on the market exceed the Fm permitted, therefore it is recommended to increase the quality controls of EAL.


Evaluation of transdermal delivery of nanoemulsions in ex vivo porcine skin using two-photon microscopy and confocal laser-scanning microscopy.
This study experimentally evaluates the self-targeting ability of asiaticoside-loaded nanoemulsions compared with nontargeted nanoemulsions in ex vivo experiments with porcine skin samples. Homebuilt two-photon and confocal laser-scanning microscopes were employed to noninvasively examine the transdermal delivery of two distinct nanoemulsions. Prior to the application of nanoemulsions, we noninvasively observed the morphology of porcine skin using two-photon microscopy. We have successfully visualized the distributions of the targeted and nontargeted nanoemulsions absorbed into the porcine skin samples. Asiaticoside-loaded nanoemulsions showed an improved ex vivo transdermal delivery through the stratum corneum compared with nonloaded nanoemulsions. As a secondary measure, nanoemulsions-applied samples were sliced in the depth direction with a surgical knife in order to obtain the complete depth-direction distribution profile of Nile red fluorescence. XZ images demonstrated that asiaticoside-loaded nanoemulsion penetrated deeper into the skin compared with nontargeted nanoemulsions. The basal layer boundary is clearly visible in the case of the asiaticoside-loaded skin sample. These results reaffirm the feasibility of using self-targeting ligands to improve permeation through the skin barrier for cosmetics and topical drug applications.


Endonasal endoscopy and posterior epistaxis.
The availability of a comprehensive range of endonasal telescopes facilitates systematic examination of the nasal cavity. Epistaxis is normally divided into anterior and posterior. Posterior epistaxis is diagnosed when anterior rhinoscopy fails to visualize anterior-located bleeding points. With the aid of endonasal endoscopy the exact location of bleeding points can be identified and diathermy applied under direct vision. Twenty-seven cases of the so-called posterior epistaxis were treated successfully by endonasal endoscopy. The technique is particularly useful during acute nose bleeds, it shortens hospital stay, and reduces the discomfort inflicted by the presence of nasal packing. The need for blood transfusion is reduced by using endonasal endoscopy in the acute stage of epistaxis.


Intra-Aortic Balloon Counterpulsation in Patients With Chronic Heart Failure and Cardiogenic Shock: Clinical Response and Predictors of Stabilization.
The aim of this work was to characterize the clinical response and identify predictors of clinical stabilization after intra-aortic balloon counterpulsation (IABP) support in patients with chronic systolic heart failure in cardiogenic shock before implantation of a left ventricular assist device (LVAD). Limited data exist regarding the clinical response to IABP in patients with chronic heart failure in cardiogenic shock. We identified 54 patients supported with IABP before LVAD implantation. Criteria for clinical decompensation after IABP insertion and before LVAD included the need for more advanced temporary support, initiation of mechanical ventilation or dialysis, increase in vasopressors/inotropes, refractory ventricular arrhythmias, or worsening acidosis. The absence of these indicated stabilization. Clinical decompensation after IABP occurred in 23 patients (43%). Both patients who decompensated and those who stabilized had similar hemodynamic improvements after IABP support, but patients who decompensated required more vasopressors/inotropes. Clinical decompensation after IABP was associated with worse outcomes after LVAD implantation, including a 3-fold longer intensive care unit stay and 5-fold longer time on mechanical ventilation (P < .01 for both). Although baseline characteristics were similar between groups, right and left ventricular cardiac power indexes (cardiac power index = cardiac index × mean arterial pressure/451) identified patients who were likely to stabilize (area under the receiver operating characteristic curve = 0.82). Among patients with chronic systolic heart failure who develop cardiogenic shock, more than one-half of patients stabilized with IABP support as a bridge to LVAD. Baseline measures of right and left ventricular cardiac power, reflecting work performed for a given flow and pressure, may allow clinicians to identify patients with sufficient contractile reserve who will be likely to stabilize with an IABP versus those who may need more aggressive ventricular support.


Analytical similarity as base for rituximab biosimilars in lymphoid malignancies in the clinic: a PF-05280586 case study.
The availability of biosimilars in oncology has provided an opportunity for increased patient access to biologic therapies. However, healthcare professional perceptions concerning the relatively limited clinical data sufficient to support their regulatory approval may contribute to varied uptake and use. We review key aspects of the development program for the rituximab biosimilar PF-05280586 (Ruxience™) that supported its approval for lymphoid malignancies, to illustrate the rationale for an abbreviated clinical program. In particular, we describe the extensive analytical assessment, comprising sensitive techniques that established similarity with the reference product in key product attributes, underlying structure, function, potency, safety and quality, which formed the foundation for a successful development program, culminating in a confirmatory comparative clinical trial in patients with follicular lymphoma.


Co-overexpression of folding modulators improves the solubility of the recombinant guinea pig liver transglutaminase expressed in Escherichia coli.
Transglutaminases (EC 126.96.36.199) catalyze the formation of epsilon-(gamma-glutamyl)lysine cross-links and the substitution of primary amines for the gamma-carboxamide groups of protein bound glutamine residues, and are involved in many biological phenomena. Transglutaminase reactions are also applicable in applied enzymology. Here, we established an expression system of recombinant mammalian tissue-type transglutaminase with high productivity. Overexpression of guinea pig liver transglutaminase in Escherichia coli, using a plasmid pET21-d, mostly resulted in the accumulation of insoluble and inactive enzyme protein. By the expression culture at lower temperatures (25 and 18 degrees C), however, a fraction of the soluble and active enzyme protein slightly increased. Co-overexpression of a molecular chaperone system (DnaK-DnaJ-GrpE) and/or a folding catalyst (trigger factor) improved the solubility of the recombinant enzyme produced in E. coli cells. The specific activity, the affinity to the amine substrate, and the sensitivity to the calcium activation and GTP inhibition of the purified soluble recombinant enzyme were lower than those of the natural liver enzyme. These results indicated that co-overexpression of folding modulators tested improved the solubility of the overproduced recombinant mammalian tissue-type transglutaminase, but the catalytic properties of the soluble recombinant enzyme were not exactly the same as those of the natural enzyme.


HMOs in the Medicare market. Part 1.
Final governmental regulations permitting all qualified health maintenance organizations and competitive medical plans to enter the Medicare market were published early last year. This action has created a significant need for information on marketing strategies and operational issues pertaining to this new area. Mathematica Policy Research was awarded a grant by HCFA to evaluate the Medicare Competition Demonstration program undertaken by 26 HMOs and CMPs between August 1982 and December 1984, with a focus on the marketing strategies and operational decisions and changes during the initial period of entering the Medicare market. In this first part of a two-part report, information is provided on the marketing approaches developed by the demonstration HMOs as they dealt with, in most cases, a large influx of elderly enrollees.


Calcitonin alters bone quality in beagle dogs.
Because of its antiresorptive properties, calcitonin is widely used to prevent and treat osteoporosis. A stimulatory effect of calcitonin on osteoblasts has also been reported; however, a recent histologic study points to a negative effect of calcitonin on mineralization of cancellous bone. The present experiment was performed to determine whether the observed histological signs of alterations in mineralization are also observed in cortical bone and whether this results in changes in mechanical properties, mineral densities, or mineral properties of canine bone. Sixteen female adult beagle dogs were randomly allocated to receive either human calcitonin at a dose of 0.25 mg/dog (50 IU, n = 8) or vehicle (mannitol, n = 8) every other day for 16 weeks. At the end of the study, the dogs were euthanized. Both tibiae, L1 and L5 vertebrae, and iliac crest bone samples were excised and defleshed. Torsional mechanical properties of tibial diaphyses and compressive strengths of vertebrae were measured. Bone mineral densities (BMD) of tibiae and vertebrae were measured by using dual-energy X-ray absorptiometry. Ultrastructural mineral characteristics of iliac crest bone were determined by gravimetry and Fourier transform infrared spectroscopy (FTIR). Bone histomorphometry was performed in the cortical envelope of the iliac crest. Tibiae from dogs treated with calcitonin withstood significantly less maximum torque until failure, required less torsional energy to reach the maximum torque, and had less torsional stiffness than the tibiae from dogs treated with vehicle (p < 0.05). Cancellous cores of vertebrae from calcitonin-treated dogs withstood less compressive mechanical loading than did vertebral cores from vehicle-treated animals (p < 0.05). Dogs treated with calcitonin had less BMD of both tibiae and vertebrae than vehicle-treated animals (p < 0.05). Bones from calcitonin-treated dogs had significantly less ash content, which correlated with the lower phosphate-to-amide I (detected by FTIR) and greater carbonate-to-phosphate ratios than did bones from vehicle-treated dogs (p < 0.05). Calcitonin-treated dogs exhibited a decrease in bone formation and mineralization rates and an increase in mineralization lag time. These results point to a negative effect of calcitonin on bone quality. These findings are intriguing and call for further studies addressing whether the observed abnormalities are transient or permanent.


[A multidirectional effect of metformin].
Diabetes as chronic civilization disease, very often occurs together with health disorders. One of the basic pharmaceuticals commonly used in her therapy is metformin. Many other positive effects, not related to diabetes, have been observed in tatients treated with metformin for a long time. These are: positive changes in diagnostiic parameters, protection against cancer development, less frequent occurrence of other pathologies and diseases, increased sensitivity to selected drugs (e.g. cytostatics), delayed aging processes of organism. In addition to the molecular changes resulting in a hypoglycemic effect, the most common modifications of gene expression have been described, indicated as the basis for the anti-aging, anti-atherosclerotic and anticancer effects of this drug and its effect on melanogenesis or the nervous system. The results presented in the study are very promising, but most of them relate to experiments carried out in cell cultures or animals. The possibility of obtaining similar effects in humans requires much more research.


Cardiac pacemaker registry--FDA, HCFA. Final rule.
The Food and Drug Administration (FDA) and the Health Care Financing Administration (HCFA) are issuing jointly a final rule to establish a national cardiac pacemaker registry, as required by the Deficit Reduction Act of 1984. This action is based on a proposed rule that was published in the Federal Register of May 6, 1986 (51 FR 16792). The final rule requires that certain information be submitted to FDA for inclusion in the registry from physicians and providers of services requesting or receiving Medicare payment for an implantation, removal, or replacement of permanent cardiac pacemaker devices and pacemaker leads. The final rule permits HCFA to deny Medicare payment to physicians and providers who fail to submit the required information to the registry.


Insect galls of Restinga de Marambaia (Barra de Guaratiba, Rio de Janeiro, RJ).
Thirty-one morphotypes of insect galls and two flower damages were found on 16 families, 22 genera and 24 plant species in Restinga de Marambaia (Barra de Guaratiba, Rio de Janeiro, RJ). Fabaceae and Myrtaceae were the plant families with the greatest richness of insect galls (4 and 6 morphotypes, respectively), and the greatest number of galled plants (four and three species, respectively). Galls were mostly found on leaves and stems (77% and 10%, respectively). The galling insects are represented by Diptera, Lepidoptera, and Hemiptera. The majority of the galls (81%) were induced by gall midges (Cecidomyiidae: Diptera).


Colistin as a potentiator of anti-TB drug activity against Mycobacterium tuberculosis.
The mycobacterial cell wall is an effective permeability barrier that limits intracellular concentrations of anti-TB drugs and hampers the success of treatment. We hypothesized that colistin might enhance the efficacy of anti-TB drugs by increasing mycobacterial cell wall permeability. In this study, we investigated the additional effect of colistin on the activity of anti-TB drugs against Mycobacterium tuberculosis in vitro. The concentration-dependent and time-dependent killing activity of isoniazid, rifampicin or amikacin alone or in combination with colistin against M. tuberculosis H37Rv was determined. Mycobacterial populations with both high and low metabolic activity were studied, and these were characterized by increasing or steady levels of ATP, respectively. With exposure to a single drug, striking differences in anti-TB drug activity were observed when the two mycobacterial populations were compared. The addition of colistin to isoniazid and amikacin resulted in sterilization of the mycobacterial load, but only in the M. tuberculosis population with high metabolic activity. The emergence of isoniazid and amikacin resistance was completely prevented by the addition of colistin. The results of this study emphasize the importance of investigating mycobacterial populations with both high and low metabolic activity when evaluating the efficacy of anti-TB drugs in vitro. This is the first study showing that colistin potentiates the activity of isoniazid and amikacin against M. tuberculosis and prevents the emergence of resistance to anti-TB drugs. These results form the basis for further studies on the applicability of colistin as a potentiator of anti-TB drugs.


Genetic analysis of gentamicin resistance in methicillin- and gentamicin-resistant strains of Staphylococcus aureus isolated in Dublin hospitals.
Methicillin- and gentamicin-resistant strains of Staphylococcus aureus isolated in Dublin hospitals have been classified into groups I, II, and III based on resistance to antimicrobial agents and plasmid profiles. Each group expresses a characteristic level of resistance to gentamicin, tobramycin, and sisomicin. Enzyme assays showed that resistant strains expressed 2"-aminoglycoside phosphotransferase-6'-aminoglycoside transferase activity by a determinant which is known to be chromosomally located. The gentamicin resistance (Gmr) determinants were transferred from group I, II, or III strains by transduction into a laboratory strain where each expressed the same low level of resistance. This finding suggests that high-level resistance in some clinical strains is due to a second, unlinked resistance mechanism. No evidence was obtained by hybridization experiments that clinical isolates or spontaneous mutants expressing high-level Gmr carried more than one copy of the Gmr determinant, thus eliminating the possibility that a gene dosage effect was responsible for high-level resistance. Hybridization experiments with transductants and wild strains suggested that the Gmr determinant was located at homologous sites in wild strains from different groups, although restriction site differences were observed in flanking sequences. Electron microscope analysis of a cloned Gmr determinant and genetic evidence suggested that a Dublin clinical isolate harbored a transposon very similar to Tn4001.


Treatment failure in malignant gestational trophoblastic disease.
One hundred and thirty-three patients with malignant gestational trophoblastic disease (GTD) were admitted. All patients (86/86) of the nonmetastatic and metastatic low-risk groups and 89.4% (42/47) of the metastatic high-risk group showed remission. The overall remission rate was 96.2%. Among 5 patients with brain metastases, however, only one (20%) survived. We arrived at two main conclusions. First, brain metastatic lesions did not successfully respond to therapy utilizing conventional chemotherapeutic regimens. Second, the key factors for successful outcome in brain metastases were early diagnosis and aggressive initial therapy. Therefore, early detection of brain metastases should be made with: (1) fine computerized tomography (CT) or magnetic resonance imaging (MRI), (2) measurement of the ratio of serum to cerebrospinal fluid hCG concentration, and (3) early recognition of their clinical features.


Extensive involvement of the myocardium and the cardiac conduction system in a case of Wegener's granulomatosis.
A 61-year-old female who had shown Raynaud's phenomenon and articular swelling for 10 years, was admitted to hospital because of fever of unknown origin (FUO) and dry cough. She was diagnosed by skin biopsy to have a collagen disease or overlap syndrome. Anemia developed rapidly and FUO persisted, but blood culture was negative. Although indomethacin and prednisolone were administered for the progression of clinical signs and symptoms, severe dyspnea developed, resulting in bradycardia, followed by recurrent episodes of ventricular tachycardia. In spite of extensive treatment for her arrhythmia she died on the 9th hospital day. An autopsy revealed generalized Wegener's granulomatosis with extensive cardiac involvement. Necrotizing angitis and severe granulomatous inflammatory foci affected characteristically the common bundle of His and right bundle branch in addition to the ordinary myocardium.


Educational needs in families of pediatric liver and kidney transplant recipients: A quality improvement project.
Parents of pediatric liver and kidney transplant recipients were surveyed regarding their current education plans (eg, Individualized Education Program, 504), satisfaction with these plans, and interest in educational support from the psychosocial transplant team. Survey results indicate high rates of IEP and 504 plans, academic and related services, and accommodations among this population. The majority of parents/guardians reported satisfaction with their child's current school plan and did not report need for additional transplant team support specific to school services on the survey measure. However, other information highlights the importance for pediatric transplant teams to consider other ways to support this population's educational needs.


Refractive index, dispersion, and birefringence of silicon carbide polytypes.
The refractive index of each of the four common silicon carbide polytypes has been measured over the visible range. The data were analyzed in an attempt to relate the birefringence to the relative hexagonal character of the polytype. A general relationship exists, namely, that the birefringence increases with increasing hexagonal character of the polytype. This relationship is not sufficiently precise to use for the identification of polytypes.


[Bilateral primary adrenal lymphoma: an unusual presentation].
A case of primary adrenal bilateral non-Hodgking lymphoma, with depressed adrenal reserve is presented. This rare neoplasm causes rapid evolution and fatal outcome in most cases. In our patient, lethal outcome was associated with severe hypercalcemia and refractary hypotension. Many other complications are due to tumoral lysis syndrome associated with high steroid doses in adrenal insufficiency. This rare entity must be included in the differencial diagnosis of adrenal masses, uni or bilateral, because early diagnostic is important for preventing complications, potentially lethals and for improving survival. Image thecnics and ultrasound-guided or computed-tomography-guided FNA, are best diagnostic methods, but in many cases, definitive diagnostic is obtained by necropsy.


Endothelial progenitor cells and colony-forming units in rheumatoid arthritis: association with clinical characteristics.
To compare levels of a range of endothelial progenitor cells (EPCs) and endothelial colony-forming units (CFUs) in control participants and RA patients, in addition to verifying whether levels of EPCs or CFUs are associated with clinical characteristics in RA patients. Peripheral blood mononuclear cells (PBMCs) from 36 RA patients and 30 control participants were analysed by flow cytometry for EPCs defined by the expression of CD34/CD133, CD34/CD117, CD34/CD31, CD34/KDR and CD34/CD133/KDR. Endothelial cell colonies derived from culture of PBMCs were also assessed by CFU assay. No differences in levels of EPCs were observed in RA patients compared with controls. However, levels of EPCs were negatively associated with prognostic markers of poor disease status, but not cardiovascular (CV)-related risk factors. Furthermore, the majority of EPCs examined were negatively correlated with levels of RF. In contrast, CFU number was significantly reduced in RA patients compared with controls and was negatively associated with CV risk factors only. These findings indicate that more informative than comparing changes in absolute levels of EPCs, the examination of their relationship with clinical characteristics of RA patients can reveal significant associations, which may provide important clinical insights.


U.S. Fruit and Vegetable Affordability on the Thrifty Food Plan Depends on Purchasing Power and Safety Net Supports.
The Supplemental Nutrition Assistance Program (SNAP) increases the food purchasing power of lower-income households so that they can better afford a nutritious diet. Benefit amounts are based in part on the cost for a household to follow the Thrifty Food Plan (TFP), a meal pattern designed to meet the Dietary Guidelines for Americans. In October 2021, the U.S. Department of Agriculture (USDA) reformulated the TFP and increased its cost by 21%. However, the TFP still does not account for differences in food prices across the country. This study examines: (1) how geographic variation in food prices affects fruit and vegetable affordability and (2) to what extent raising the cost of the TFP (and therefore the maximum SNAP benefit) has mitigated these effects. We use data on fruit and vegetable prices from the USDA and simulation techniques to create and cost out food baskets with a sufficient quantity and variety of fruits and vegetables for a representative household to satisfy guidelines over one week. We find that the increase in SNAP benefits will increase fruit and vegetable affordability for participating households. However, households facing food prices greater than national average food prices may still face tradeoffs to purchase a balanced diet.


The Friend of GATA proteins U-shaped, FOG-1, and FOG-2 function as negative regulators of blood, heart, and eye development in Drosophila.
Friend of GATA (FOG) proteins regulate GATA factor-activated gene transcription. During vertebrate hematopoiesis, FOG and GATA proteins cooperate to promote erythrocyte and megakaryocyte differentiation. The Drosophila FOG homologue U-shaped (Ush) is expressed similarly in the blood cell anlage during embryogenesis. During hematopoiesis, the acute myeloid leukemia 1 homologue Lozenge and Glial cells missing are required for the production of crystal cells and plasmatocytes, respectively. However, additional factors have been predicted to control crystal cell proliferation. In this report, we show that Ush is expressed in hemocyte precursors and plasmatocytes throughout embryogenesis and larval development, and the GATA factor Serpent is essential for Ush embryonic expression. Furthermore, loss of ush function results in an overproduction of crystal cells, whereas forced expression of Ush reduces this cell population. Murine FOG-1 and FOG-2 also can repress crystal cell production, but a mutant version of FOG-2 lacking a conserved motif that binds the corepressor C-terminal binding protein fails to affect the cell lineage. The GATA factor Pannier (Pnr) is required for eye and heart development in Drosophila. When Ush, FOG-1, FOG-2, or mutant FOG-2 is coexpressed with Pnr during these developmental processes, severe eye and heart phenotypes result, consistent with a conserved negative regulation of Pnr function. These results indicate that the fly and mouse FOG proteins function similarly in three distinct cellular contexts in Drosophila, but may use different mechanisms to regulate genetic events in blood vs. cardial or eye cell lineages.


Revising expectations from rapid HIV tests in the emergency department.
Expanded HIV screening efforts in the United States have increased the use of rapid HIV tests in emergency departments. The reported sensitivity and specificity of rapid HIV tests exceed 99%. To assess whether a reactive rapid oral HIV test result correctly identifies adults with HIV infection in the emergency department. Diagnostic test performance assessment within the framework of a randomized, clinical trial. Brigham and Women's Hospital emergency department (Boston, Massachusetts) from 7 February to 1 October 2007. 849 adults with valid rapid oral HIV test results. Rapid HIV testing with the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test (OraSure Technologies, Bethlehem, Pennsylvania). Patients with reactive rapid test results were offered enzyme-linked immunoassay, Western blot, and plasma HIV-1 RNA testing for confirmation. Specificity and positive likelihood ratio. 39 patients had reactive results (4.6% [95% CI, 3.2% to 6.0%]). On confirmation, 5 patients were HIV-infected (prevalence, 0.6% [CI, 0.1% to 1.1%]) and 26 were non-HIV-infected (8 patients declined confirmation). The estimated rapid test specificity was 96.9% (CI, 95.7% to 98.1%). Sensitivity analyses of the true HIV status of unconfirmed cases and test sensitivity resulted in a positive likelihood ratio of 8 to 32. Western blot alone as a confirmation test provided conclusive HIV status in only 50.0% (CI, 30.8% to 69.2%) of patients at first follow-up. The addition of HIV-1 RNA testing to the confirmation protocol improved this rate to 96.2% (CI, 88.8% to 100.0%). Test sensitivity cannot be assessed because nonreactive OraQuick test results were not confirmed. Although patients with a reactive oral OraQuick HIV screening test in the emergency department had an 8- to 32-fold increased odds of HIV infection compared with the pretest odds, the specificity of the test was lower than anticipated.


Characterization of the Major Protease Involved in the Soybean beta-Conglycinin Storage Protein Mobilization.
Protease C1, the protease responsible for the initial degradation of the alpha' and alpha subunits of the soybean beta-conglycinin storage protein (Glycine max [L.] Merrill), has been purified. The enzyme was found by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to have a molecular weight of 70,000 and a pH optimum of 3.5 to 4.5. Susceptibility to protease inhibitors indicates that protease C1 is a serine protease. Study of the proteolytic intermediates generated suggests that the cleavage of the alpha' and alpha subunits of beta-conglycinin by protease C1 results in intermediates that are 1 or 2 kilodaltons smaller than the native alpha' and alpha subunits. Following that, a succession of intermediates exhibiting molecular masses of 70.0 and 58.0 kilodaltons, then 63.0, 61.0, 55.0, and 53.5 kilodaltons, are observed. A 50.0- and a 48.0- kilodalton intermediate are the final products of protease C1 action. Comparison of these intermediates with the prominent anti-beta-conglycinin cross-reacting bands that increase during the first few days of germination and early growth show that protease C1 plays an important physiological role, but not an exclusive one, in the living plant.


Black bones following long-term minocycline treatment.
During a surgical procedure, black vertebrae were observed in a 42-year-old white woman. An undecalcified iliac crest bone biopsy specimen revealed intense fluorescence compatible with tetracycline labeling and osteoporosis. A urinary screening test was negative for amino acids. The patient had been treated with minocycline hydrochloride (100 to 300 mg/d) for at least 6 years. Since minocycline is known to discolor many body tissues, it is likely that the black discoloration of bone in our patient was caused by the long-term intake of the antibiotic.


The effects of a new alpha-2 adrenoceptor antagonist on sleep and nocturnal penile tumescence in normal male volunteers and men with erectile dysfunction.
The effects of a new alpha-2 adrenoceptor antagonist, RS 15385, on sleep and nocturnal penile tumescence (NPT) was assessed by intravenous infusion of the drug, in two doses (high and low), and of placebo through the night in 12 young normal volunteers and 24 men with erectile dysfunction. The drug reduced total sleep time in the younger normal volunteers only with the high dose and in the dysfunctional men with both doses. There was no selective effect on different sleep stages in the normal volunteers, except for an increase in the per cent of total sleep time in Stage 1 with the high dose. The dysfunctional men were divided into two age groups (< 47 years and > 47 years). There was an age-related increase in the proportion of total sleep in rapid eye movement (REM), which was only apparent in the older age group. In the volunteers, there was a curvilinear dose-response effect on NPT. The lower dose modestly increased erectile response, particularly during non-REM sleep, whereas the higher dose reduced erectile response, most noticeably during REM. The only positive effect of the higher dose was an increase in spontaneous erections after lights out before sleep onset. The older dysfunctional group showed no drug effects on NPT. The younger dysfunctional men showed increased erectile response during non-REM with the higher dose, an effect that was also significant in the interval between sleep onset (Stage 2) and first REM.


Artificial Intelligence for Personalized Medicine in Thyroid Cancer: Current Status and Future Perspectives.
Thyroid cancers (TC) have increasingly been detected following advances in diagnostic methods. Risk stratification guided by refined information becomes a crucial step toward the goal of personalized medicine. The diagnosis of TC mainly relies on imaging analysis, but visual examination may not reveal much information and not enable comprehensive analysis. Artificial intelligence (AI) is a technology used to extract and quantify key image information by simulating complex human functions. This latent, precise information contributes to stratify TC on the distinct risk and drives tailored management to transit from the surface (population-based) to a point (individual-based). In this review, we started with several challenges regarding personalized care in TC, for example, inconsistent rating ability of ultrasound physicians, uncertainty in cytopathological diagnosis, difficulty in discriminating follicular neoplasms, and inaccurate prognostication. We then analyzed and summarized the advances of AI to extract and analyze morphological, textural, and molecular features to reveal the ground truth of TC. Consequently, their combination with AI technology will make individual medical strategies possible.


Extramedullary plasmacytoma of the jejunum.
A case of extramedullary plasmacytoma (EMP) of the jejunum, an uncommon neoplasia, is reported. A 56-year-old Japanese woman who experienced intermittent upper abdominal pain and weight loss had a large movable mass in the upper abdomen. The mass was hypervascular in an angiographic study and positive for gallium-67 citrate scintigraphy. Immunoelectrophoresis showed the presence of an M-component of immunoglobulin (Ig) A-lambda in the serum. It was identified as an EMP immunohistochemically positive for IgA-lambda. This M-component disappeared after resection and chemotherapy. The clinical features of this rare neoplastic disorder are discussed.


Clinical characteristics and comparison of longitudinal qPCR results from different specimen types in a cohort of ambulatory and hospitalized patients infected with monkeypox virus.
The ongoing monkeypox virus outbreak includes at least 7553 confirmed cases in previously non-endemic countries worldwide as of July 2022. Clinical presentation has been reported as highly variable, sometimes lacking classically described systemic symptoms, and only small numbers of cutaneous lesions in most patients. The aim of this study was to compare clinical data with longitudinal qPCR results from lesion swabs, oropharyngeal swabs and blood in a well characterized patient cohort. 16 male patients (5 hospitalized, 11 outpatients) were included in the study cohort and serial testing for monkeypox virus-DNA carried out in various materials throughout the course of disease. Laboratory analysis included quantitative PCR, next-generation sequencing, immunofluorescence tests and virus isolation in cell culture. All patients were male, between age 20 and 60, and self-identified as men having sex with men. Two had a known HIV infection, coinciding with an increased number of lesions and viral DNA detectable in blood. In initial- and serial testing, lesion swabs yielded viral DNA-loads at, or above 106 cp/ml and only declined during the third week. Oropharyngeal swabs featured lower viral loads and returned repeatedly negative in some cases. Viral culture was successful only from lesion swabs but not from oropharyngeal swabs or plasma. The data presented underscore the reliability of lesion swabs for monkeypox virus-detection, even in later stages of the disease. Oropharyngeal swabs and blood samples alone carry the risk of false negative results, but may hold value in pre-/asymptomatic cases or viral load monitoring, respectively.


Maxillary tuberosity fracture and subconjunctival hemorrhage following extraction of maxillary third molar.
Extraction of teeth is the most common minor surgical procedure performed. Complication of extraction ranges from periodontal injury to fracture of jaw in the mandible and fracture of tuberosity and oroantral communication in the maxilla. Subconjunctival hemorrhage after extraction of maxillary molar is a very rare complication, and so far, only one case is reported in the literature. We report a case of subconjunctival hemorrhage with maxillary tuberosity fracture after maxillary third molar extraction.


[Satisfaction about physical appearance and teeth. Results of a nationwide study].
In a study involving a group of 907 randomly selected Dutch individuals, satisfaction about one's physical appearance and satisfaction about the appearance of one's teeth were assessed. Furthermore, the relationship between body esteem and happiness was explored. Three quarters of the respondents were satisfied about their physical appearance, while 70% was satisfied about the appearance of their teeth. Women and people with a non-Dutch background were significantly less likely to be satisfied about their physical appearance than men and those with a Dutch background. Individuals 30 years old and younger were more likely to be satisfied about their teeth than those who were older. Almost two third of the respondents (64%) reported that the appearance of their teeth contributed positively to their happiness. Women and people with a non-Dutch background were most likely to indicate that the appearance of their teeth contributed to their happiness. Satisfaction about general physical appearance and appearance of the teeth were significantly associated with happiness. Prospective studies are needed to examine to what extent esthetically motivated dental treatments make people happy and enhance their general well-being.


Practical considerations for postarrest targeted temperature management.
Out-of-hospital cardiac arrest remains a major challenge worldwide, with survival to discharge rates of <20% in the great majority of countries. Advancements in prehospital care, including increasing deployment of automated external defibrillators and improvements in bystander cardiopulmonary resuscitation, have led to more victims achieving return of spontaneous circulation (ROSC), yet the majority of patients with ROSC suffer in-hospital mortality or significant neurologic injuries that persist after discharge. This postarrest morbidity and mortality is largely due to a complex syndrome of mitochondrial dysfunction, inflammatory cascades and cellular injuries known as the postcardiac arrest syndrome (PCAS). The management of PCAS represents a formidable task for emergency and critical care providers. A cornerstone of PCAS treatment is the use of aggressive core body temperature control using thermostatically controlled devices, known as targeted temperature management (TTM). This therapy, demonstrated to be effective in improving both survival and neurologic recovery by several randomized controlled trials nearly 20 years ago, remains a major topic of clinical investigation. Important practical questions about TTM remain: How soon must providers initiate the therapy? What TTM goal temperature maximizes benefit while limiting potential adverse effects? How long should TTM therapy be continued in patients following resuscitation? In this review, we will address these issues and summarize clinical research over the past decade that has added to our fund of knowledge surrounding this important treatment of patients following cardiac arrest.


Synthesis and Properties of Silk Fibroin/Konjac Glucomannan Blend Beads.
Silk fibroin (SF) and konjac glucomannan (KGM) are promising materials in the biomedical field due to their low toxicity, biocompatibility, biodegradability and low immune response. Beads of these natural polymers are interesting scaffolds for biomedical applications, but their fabrication is a challenge due to their low stability and the necessary adaptation of their chemical and mechanical properties to be successfully applied. In that sense, this study aimed to synthesize a blend of silk fibroin and konjac glucomannan (SF/KGM) in the form of porous beads obtained through dripping into liquid nitrogen, with a post-treatment using ethanol. Intermolecular hydrogen bonds promoted the integration of SF and KGM. Treated beads showed higher porous size, crystallinity, and stability than untreated beads. Characterization analyses by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric (TGA), and X-ray diffraction (XDR) evidenced that ethanol treatment allows a conformational transition from silk I to silk II in SF and an increase in the KGM deacetylation. Those chemical changes significantly enhanced the mechanical resistance of SF/KGM beads in comparison to pure SF and KGM beads. Moreover, samples showed cytocompatibility with HaCaT and BALB/c 3T3 cells.


A national survey of epidural use and management in elderly patients undergoing elective and emergency laparotomy.
A postal questionnaire was sent to anaesthetic clinical tutors in the United Kingdom describing two hypothetical 75-year-old patients requiring abdominal surgery. Patient 1 (ASA 2) required elective anterior resection and patient 2 (ASA 3-4) required emergency laparotomy. There was a 65% response rate. For patient 1, 98.5% of respondents would insert an epidural, 93% inserting this awake and 50% placing it in the high-mid thoracic region. All respondents would use local anaesthesia (concentration varied four-fold) and 62% would use opioids. All respondents would place the epidural pre-operatively; although 36% would administer the epidural block pre-operatively and 3% postoperatively. For patient 2, 70% of respondents would insert an epidural (p < 0.0001), drug administration would be more frequently delayed until postoperatively (13%); p = 0.0005) and epidural opioid use decreased (57%); p = n/s. Epidural insertion influenced the postoperative destination in 42% of departments. Use of a critical care facility was anticipated for more than half of these patients; 60% reported difficulty accessing critical care beds.


Antenatal unilateral hydrocephalus.
Fetal ventriculomegaly usually involves both lateral ventricles. If dilatation of the dependent lateral ventricle is seen, it might be assumed that the condition is bilateral and symmetric and that reverberation artifact is obscuring the ventricle nearer to the transducer. However, unilateral hydrocephalus can occur, though rarely and usually as a result of unilateral obstruction of the foramen of Monro. Careful attention to visualization of the obscured hemisphere is emphasized. In the patient described here the condition was associated with frontoethmoidal encephalocele.


A cluster of patients with inferior rectus restriction following local anesthesia for cataract surgery.
During a 5-month period, four patients developed contracture of the inferior rectus muscle following local anesthesia for cataract surgery in the practice of one ophthalmologist. Two anesthesiologists administered retrobulbar anesthesia. All patients had persistent vertical diplopia caused by a large hypotropia of the operated eye. Forced duction testing revealed marked restriction to elevation of the eye. In two patients, MRI demonstrated segmental thickening of the inferior rectus muscle, just posterior to the globe. All patients had normal thyroid function tests. No patient had a previous history of strabismus. Three of the four have had strabismus surgery consisting of recession of the markedly restricted inferior rectus muscle on an adjustable suture. These three patients have regained fusion and are now asymptomatic.


Excited-State Intramolecular Proton Transfer-Based Multifunctional Solid-State Emitter: A Fluorescent Platform with "Write-Erase-Write" Function.
The excited-state intramolecular proton transfer (ESIPT)-based molecular probes have drawn significant attention owing to their environment-sensitive fluorescence properties, large Stokes shift, and emerged as building blocks for the development of molecular sensors and switches. However, most of the ESIPT-based fluorophores exhibit weak emission in the solid state limiting the scope of real-time applications. Addressing such issues, herein, we presented a C3 symmetric-like molecular architecture employing a simple one-step Schiff base condensation between triaminoguanidinium chloride and 3,5-di- tert-butyl-2-hydroxybenzaldehyde (TGHB). The temperature-dependent fluorescence studies including at 77 K indicated the strong emission from the keto tautomer compared to that of the enol tautomer. The facile ESIPT in TGHB in the solid-state led to a remarkable enhancement of fluorescence quantum yield of 1600 times compared to that of the solution (λem = 545 nm) by restricting the intramolecular rotation and subsequently suppressing the nonradiative deactivation. The excited-state processes were further elucidated through time-resolved fluorescence measurements. TGHB exhibited turn on-off fluorescence upon exposure to acid/base vapor in the form of a powder as well as a transparent, free-standing thin film. A rewritable and erasable fluorescent platform was demonstrated using TGHB as molecular ink, which offers a potential testbed for performing "write-erase-write" cycles multiple times. In addition, TGHB, possessing multiple binding sites (O and N donors) involving the central core of the triaminoguanidinium cation displayed selective turn-on fluorescence with Zn2+. The structure-property relationship revealed in the present study provides insight into the development of novel cost-effective multifunctional materials, which are promising for stimuli-responsive molecular switches.


Anatomical Variations of the First Dorsal Compartment in de Quervain Tenosynovitis.
De Quervain tenosynovitis of the wrist is a common pathology. The primary aim of this study is to determine the prevalence of extensor pollicis brevis and abductor pollicis longus (APL) anatomical variations in association with de Quervain tenosynovitis. The secondary aim was to compare additional patient-specific factors associated with de Quervain tenosynovitis. This retrospective study included 172 patients with de Quervain tenosynovitis who underwent first dorsal compartment release and 179 patients with thumb carpometacarpal (CMC) arthritis who underwent thumb CMC arthroplasty between August 1, 2007, and May 1, 2022. The CMC group was chosen as the control group because the study surgeons perform APL suspensionplasty as the primary procedure for thumb CMC arthritis, allowing for a comparison group without de Quervain tenosynovitis. Exclusion criteria included patients undergoing revision surgery, patients undergoing thumb CMC procedure other than APL suspensionplasty, and patients with both CMC and first dorsal compartment diagnoses. Demographics, clinical variables, and intraoperative findings were collected through retrospective chart reviews. Patients in the de Quervain tenosynovitis group tended to be younger (51 years, range: 23-92 years vs 63 years, range: 28-85 years), women (86.1% vs 77.1%), and more commonly of African American or black race (15.7% vs 3.9%) and Asian race (5.2% vs 0%). There was a higher prevalence of tendon subcompartments (79.1% vs 64.2%), but fewer number of APL slips (38.3% vs 20.7% 2 or fewer slips) seen in the de Quervain tenosynovitis group. Anatomical variation exists between patients with and without de Quervain tenosynovitis. The presence of tendon subcompartments but not an increased number of tendon slips is associated with de Quervain tenosynovitis.


Interactions of biomedical and environmental risk factors for cognitive development: a preliminary study of sickle cell disease.
Sickle cell disease (SCD) is associated with a number of biopsychosocial risk factors for cognitive development. Understanding how these risk factors may interact is important for developing interventions for cognitive functioning. The authors assessed the cognitive abilities of children with SCD (n = 50) and related their performance to anemia severity, socioeconomic status (SES), and their interaction. Demographically matched peers without SCD (n = 36) served as a comparison group. Four areas of cognitive weakness were identified among children with SCD: general cognitive ability, crystallized ability, short-term memory, and processing speed. Anemia severity predicted general cognitive ability, crystallized ability, and processing speed. Interactions between anemia severity and SES were found for general cognitive ability and short-term memory. Disease effects in SCD appear to vary depending on the child's level of socioenvironmental risk. Biomedical interventions to benefit cognitive functioning may have different effects depending on whether additional socioenvironmental risk factors are present.


Structure-activity relations of nanolipoblockers with the atherogenic domain of human macrophage scavenger receptor A.
Oxidized low density lipoprotein (oxLDL) uptake by macrophages is mediated by scavenger receptors and leads to unregulated cholesterol accumulation. Micellar nanolipoblockers (NLBs) consist of alkyl chains and polyethylene glycol on mucic acid. NLBs functionalized with anionic groups inhibit oxLDL uptake via the scavenger receptor A (SR-A). Molecular modeling and docking approaches were used to understand the structure-activity relationship (SAR) between NLBs and SR-A. Six NLB models were docked to the SR-A homology model to investigate charge placement and clustering. NLB models with the most favorable binding energy were also the most effective oxLDL inhibitors in THP-1 macrophages. Mutant SR-A models were generated by replacing charged residues with alanine. All charged residues in the region were necessary, with Lys60, Lys63, and Lys66 having the greatest effect on binding. We hypothesize that structural studies aided by theoretical modeling and docking can be used to design promising NLB candidates with optimal binding properties.


Exposure of Small-Scale Gold Miners in Prestea to Mercury, Ghana, 2012.
Small-scale gold miners in Ghana have been using mercury to amalgamate gold for many years. Mercury is toxic even at low concentration. We assessed occupational exposure of small-scale gold miners to mercury in Prestea, a gold mining town in Ghana. We conducted a cross-sectional study in which we collected morning urine samples from 343 small-scale gold miners and tested for elemental mercury. Data on small-scale gold miner's socio-demographics, adverse health effects and occupational factors for mercury exposure were obtained and analyzed using SPSS Version 16 to determine frequency and percentage. Bivariate analysis was used to determine occupational factors associated with mercury exposure at 95% confidence level. The mean age of the small-scale gold miners was 29.5 ±9.6 years, and 323(94.20%) were males. One hundred and sixty (46.65%) of the small-scale gold miners had urine mercury above the recommended exposure limit (<5.0ug/L). Complaints of numbness were significantly associated with mercury exposure among those who have previously worked at other small-scale gold mines (χ2=4.96, p=0.03). The use of personal protective equipment among the small-scale gold miners was low. Retorts, which are globally recommended for burning amalgam, were not found at mining sites. A large proportion of small-scale gold miners in Prestea were having mercury exposure in excess of occupational exposure limits, and are at risk of experiencing adverse health related complications. Ghana Environmental Protection Agency should organize training for the miners.


Organic Collaborative Research Partnership Building: Researchers, Needle and Syringe Program Providers, and People Who Inject Drugs.
(1) Background: People who inject drugs (PWID) and needle and syringe program (NSP) providers increasingly partner with researchers to explore harm reduction best practice. However, a paucity of research exists regarding how best to engage PWID and community NSP providers to generate the evidence for sustainable harm reduction services. (2) Aim: This study reports on our use of an organic community research partnership-building approach between researchers, NSP providers, and PWID in Canberra ACT, Australia. (3) Method: Survey participants included both PWID (n = 70) and NSP providers (n = 26) across primary (n = 2), secondary (n = 7), and outreach (n = 1) services in Canberra ACT. Applying an organic partnership-building strategy, we engaged with partners and adapted approaches according to information gained in the process of implementation. (4) Results: We found engaging in relationship building around partner priority activities created mutual understanding and trust premised in authenticity of the evolving partnership. Our organic approach, which included a partner audit of the research tools for relevance, resulted in high acceptance and enrolment into the research by NSP providers and PWID. Finally, we observed strong social capital building utilizing an organic approach for the sustainability of the partnership. (5) Conclusions: The results of this study provide evidence for the benefits of organic collaborative research partnership building with NSP providers and PWID for authentic service program implementation. Our approach to research partnership building resulted in strong relationships built on shared goals and objectives, mutual gains, and complementary expertise. We propose the wider use of organic approaches to developing collaborative research partnerships with NSP providers and PWID to enhance consumer responsiveness towards service provision.


A novel thermotropic elastomer based on highly-filled LDH-SSB composites.
Elastomeric composites are prepared based on solution styrene butadiene elastomer and zinc-aluminium layered double hydroxides (LDH), using a conventional sulphur cure system. Up to 100 parts per hundred rubber of LDH are incorporated into the elastomer matrix. The composites exhibit an interesting phenomenon of thermoreversible transparency, i.e. the transparent sample becomes opaque at warm condition and restores the transparency at room temperature. The transparency is found to be increased as the amount of LDH was increased. The addition of LDH gradually improved the mechanical, dynamic mechanical performance and thermal stability of the base elastomer. These developped elastomers could be utilised as smart materials in different applications.


[Chondroid hamartoma of the thoracic wall: apropos of a case treated by extensive surgical exeresis].
The Authors describe a case of chest wall hamartoma, very rare in infants and usually present at birth. This lesion, histologically, is benign. Surgical ablation is mandatory and curative, but the ablation of the tumor and the reconstruction of the large residual parietal defect are sometimes very difficult. In this case the surgical treatment was successful and the reconstruction of the thoracic cage was obtained with a particular surgical technique.


Association of TNFA promoter region haplotype in Behçet's Disease.
Although the etiology of Behçet's Disease (BD; MIM 109650) remains to be clearly elucidated, levels of tumor necrosis factor alpha (TNF-alpha) have been reported to be significantly elevated in BD patients, and TNF-alpha blockers have been demonstrated to exhibit some degree of therapeutic efficacy for a certain subset of BD sufferers. In this study, we have conducted an analysis of the TNFA haplotypes in the promoter response element that affect the binding affinity of specific transcription factors, in order to characterize their association with the clinical features of BD. Six polymorphisms in the promoter region of TNFA were genotyped in 254 BD patients and 344 control subjects, via the PCR-RFLP technique. TNFA -1031*C, -863*A and -308*G alleles were associated with an increased risk of BD (p=0.030, OR=1.4; p=0.008, OR=1.5; p=0.010, OR=1.8, respectively). The sole TNFA haplotype -1031C-863A-857C-376G-308G-238G, was associated with a 1.6 fold increase in the risk of BD, whereas the TNFA haplotype -1031T-863C-857C-376G-308A-238G was associated with a 0.6 decreased risk of BD. The TNFA -1031*C, -863*A, -857*C and -308*G alleles were significantly associated with BD. The findings of this study, collectively, indicate that TNFA haplotypes in the promoter response elements may exert significant influence on susceptibility to BD.


[Immunological indices in schizoaffective and affective psychoses].
Proliferative activity of peripheral blood lymphocytes has been studied in patients with schizoaffective (18) and affective (24) psychoses in 4 experimental variants: cultivation of blood lymphocytes isolated by centrifuging in the density gradient with fetal (1st variant) or autologic serum (2nd variant); cultivation of lymphocyte obtained in plasma sedimentation with fetal (3rd variant) and autologic serum (4th variant). A level of functional lymphocyte activity was significantly decreased in patients. The data obtained suggest that different mechanisms underlie this decrease. In schizoaffective psychosis, a disturbance of cell cooperative interaction in immune response was observed. In affective psychosis, the determining factors were a decrease of the ability of lymphocytes to respond to mytogenic stimulation and a presence of the factor inhibiting a functional activity of lymphoid cells in patient's blood. Besides, it was shown that in patients with schizoaffective psychosis, lymphocyte proliferative activity inversely correlates with the disease duration and in affective patients the direct correlation between these indices was detected.


EEG biomarkers in major depressive disorder: discriminative power and prediction of treatment response.
Major depressive disorder (MDD) has high population prevalence and is associated with substantial impact on quality of life, not least due to an unsatisfactory time span of sometimes several weeks from initiation of treatment to clinical response. Therefore extensive research focused on the identification of cost-effective and widely available electroencephalogram (EEG)-based biomarkers that not only allow distinguishing between patients and healthy controls but also have predictive value for treatment response for a variety of treatments. In this comprehensive overview on EEG research on MDD, biomarkers that are either assessed at baseline or during the early course of treatment and are helpful in discriminating patients from healthy controls and assist in predicting treatment outcome are reviewed, covering recent decades up to now. Reviewed markers include quantitative EEG (QEEG) measures, connectivity measures, EEG vigilance-based measures, sleep-EEG-related measures and event-related potentials (ERPs). Further, the value and limitations of these different markers are discussed. Finally, the need for integrated models of brain function and the necessity for standardized procedures in EEG biomarker research are highlighted to enhance future research in this field.


Self-care 3 months after attending chronic obstructive pulmonary disease patient education: a qualitative descriptive analysis.
The authors performed a qualitative descriptive analysis to explore how group patient education influences the self-care of patients with chronic obstructive pulmonary disease. In the period 2009-2010, eleven patients diagnosed with chronic obstructive pulmonary disease completed an 8-week group education program in a Danish community health center. The patients were interviewed 3 months after completion of the program. Patients reported that their knowledge of chronic obstructive pulmonary disease had increased, that they had acquired tools to handle their symptoms, and that the social aspect of patient education had motivated them to utilize their new habits after finishing the course. The data indicate that patients need a period of adjustment (a "ripening period"): it took time for patients to integrate new habits and competencies into everyday life. Talking to health care professionals focused the patients' attention on their newly acquired skills and the research interview made them more aware of their enhanced self-care. Patients' self-care may be enhanced through group education, even though the patients are not always able to see the immediate outcome. Some patients may require professional help to implement their newly acquired knowledge and skills in everyday life. A planned dialogue concentrating on self-care in everyday life 3 months after finishing the course may enhance patients' awareness and appraisal of their newly acquired competencies.


PHLPP1 splice variants differentially regulate AKT and PKCα signaling in hippocampal neurons: characterization of PHLPP proteins in the adult hippocampus.
Pleckstrin homology and leucine rich repeat protein phosphatases (PHLPPs) are a novel class of potent protein kinase B (AKT) inhibitors that have been intensely investigated in relation to AKT activity in cancer. Currently, our understanding of the role of PHLPP1α in the central nervous system is limited. In this study, we characterized PHLPP protein expression and target kinases in the adult hippocampus. We directly verify PHLPP1α inhibits AKT in hippocampal neurons and demonstrate a novel role for PHLPP1β/SCOP, to promote AKT activation. PHLPP1α expression changes dramatically in the hippocampus during development, constituting the most abundant PHLPP protein in adult neurons. Further, while all PHLPP proteins could be observed in the cytosolic fraction, only PHLPP1α could be localized to the nucleus. The results provide unique evidence for a divergence in the function of PHLPP1α and PHLPP1β/SCOP, and suggest that PHLPP1α plays a major role in regulating AKT signaling in neurons.


Pulsatile gonadotropin-releasing hormone therapy for ovulatory disorders.
Pulsatile GnRH remains a physiologic method of inducing ovulation that is effective and safer than other parenteral preparations. Its lower rate of acceptance in the United States stands in curious contrast to its widespread usage in other countries as a second-line (postclomiphene) technique of choice for ovulation induction. In a high-technology era such as ours, women who may benefit from pulsatile GnRH therapy should not be forgotten. By far the most favorable results are obtained in women with primary or secondary hypothalamic amenorrhea. In such women, pregnancy rates appear comparable to those achieved with exogenous gonadotropins with a much lower risk of multiple pregnancy and ovarian hyperstimulation. These positive aspects, combined with the decreased need for clinical monitoring and the increased sense of control imparted to the patient, lead to the conclusion that women with uncomplicated hypothalamic-pituitary disorders are the ideal patient group to consider for therapy. The application of pulsatile GnRH therapy to other groups of women relies on limited data. By all means, women with polycystic ovarian syndrome who have not ovulated or conceived after other forms of treatment should be considered because reasonable pregnancy salvage can be obtained. We have noted a first-cycle successful pregnancy after failure of exogenous gonadotropins, with or without a superimposed GnRH agonist, and even in vitro fertilization with multiple embryo transfers. Before such invasive, high-technology procedures are entertained, it would appear prudent to consider this simple alternative in women with an overactive hypothalamic-pituitary axis, as seen in polycystic ovarian syndrome. Other ovulatory defects also may be amenable to treatment with pulsatile GnRH, but their practical usefulness will await further clinical study.


Trends in neonatal resuscitation patterns in Queensland, Australia - A 10-year retrospective cohort study.
To describe the frequency of neonatal resuscitation interventions implemented for newborn babies in the state of Queensland over a 10-year period and determine if these changes suggest adherence to changes in Australian guidelines. A population-based retrospective cohort study utilising the Queensland Perinatal Data Collection dataset. All liveborn babies ≥23 + 0 weeks + days gestation born between 1 July 2007 and 30 June 2017 were included except those for whom resuscitation was not attempted and those babies <25 + 0 weeks for whom it was unsuccessful. Trends in resuscitation were demonstrated using Loess regression. Of 618,589 eligible newborns,182,260 received any resuscitation manoeuvre (29.5%). The proportion receiving oxygen without assisted ventilation declined from 19.3% in 2007-08 to 5.6% in 2016-17. Upper airway suctioning also decreased. Assisted ventilation increased from 7.9% to 10.0% of all babies with the largest contribution from late preterm and term babies. The rate of endotracheal suctioning for meconium and the rate of narcotic antagonist use also declined. A greater proportion of babies received chest compressions (1.9-3.2 per 1000 babies) and adrenaline (epinephrine). Mortality decreased from 1.9 to 1.5 per 1000 babies in the cohort. Ten-year trends showed reduced use of oxygen or upper airway suctioning without assisted ventilation, reduced intubation to suction meconium, reduced use of narcotic antagonists and greater use of assisted ventilation suggesting appropriate practice change in response to Australian neonatal resuscitation guidelines. The increase in the use of chest compressions and adrenaline was unexpected and the reasons for it are unclear.


Klebsiella pneumoniae endogenous endophthalmitis presenting as orbital cellulitis.
This report describes the first documented case of Klebsiella pneumoniae endogenous endophthalmitis with concurrent orbital cellulitis in a patient without a liver abscess. A 34-year-old, caucasian male with a history of intravenous drug abuse and type 1 diabetes mellitus was transferred from an outside hospital for progressively worsening pain and swelling in the right eye. Careful history, physical examination, and imaging were consistent with a diagnosis of endogenous endophthalmitis with concurrent orbital cellulitis. Vitreous cultures were positive for Klebsiella pneumoniae. Despite aggressive and early intervention with antibiotics and vitrectomy, the patient's condition continued to worsen and evisceration was required to adequately control the infection. Klebsiella pneumoniae endogenous endophthalmitis with concurrent orbital cellulitis is a rare and often blinding infection, despite appropriately aggressive intervention.


Mechanism of Spatial and Temporal Control in Precision Cyclic Vinyl Polymer Synthesis by Lewis Pair Polymerization.
In typical cyclic polymer synthesis via ring-closure, chain growth and cyclization events are competing with each other, thus affording cyclic polymers with uncontrolled molecular weight or ring size and high dispersity. Here we uncover a mechanism by which Lewis pair polymerization (LPP) operates on polar vinyl monomers that allows the control of where and when cyclization takes place, thereby achieving spatial and temporal control to afford precision cyclic vinyl polymers or block copolymers with predictable molecular weight and low dispersity (≈1.03). A combined experimental and theoretical study demonstrates that cyclization occurs only after all monomers have been consumed (when) via conjugate addition of the propagating chain end to the specific site of the initiating chain end (where), allowing the cyclic polymer formation steps to be regulated and executed with precision in space and time.


[Isoimmune haemolytic icterus in neonatal calves as a consequence of vaccination against piroplasmosis].
The article refers about several cases of isoimmunohaemolytic icterus in neonatal calves from different farms, whose dams had all been vaccinated against piroplasmosis. Clinical signs of immunomediated icterus neonatorum gravis, results of blood chemistry (with special regard to liver-specific parameters in the neonatal calf and results of haematology) as well as gross pathology and pathohistology are to be discussed. It is summarized, that the most relevant indicators for a hepatopathy in the newborn calf are total-bilirubin and the glutamate-dehydrogenase. Today, the production of piroplasmosis-vaccines out of blood of splenectomized animals is referred to as the only practicable method of harvesting sufficient amounts of vaccine-antigen.


Influence of Household Remittance on Childhood Stunting in Nepal.
Migration is a livelihood strategy for many poor households in Nepal. About 56% of the households receive remittances, the country also has high rates of undernutrition as 36% of children under five years of age are stunted. Remittance are known to increase household income, potentially contributing to improvements in health and nutrition of children, but few studies have examined it in the Nepalese context. We used data of 2,498 children under 5 years of age from the Nepal Living Standard Survey 2010/11 to investigate associations between childhood stunting and household remittances. Multiple logistic regression was used to evaluate the odds of child stunting by remittances received by the families in the 12 months preceding the survey. Guided by a conceptual framework, the model was adjusted for variables representing child, maternal and household level characteristics. Our investigation showed that the odds of a child being stunted decreased with increased levels of remittance received by households, 67% (OR: 0.33, 95% CI: 0.16, 0.67) lower for households receiving more than Nrs.60,000 remittance per year. However, there was no difference in the risk of stunting by gender of the household head and income categories. An increased household income could potentially reduce the burden of chronic undernutrition in poor families in Nepal, which in turn paves a path for the expansion of cash transfer programs. Further research is indicated to understand the threshold of remittance or cash transfer needed to estimate nutritional outcomes.


Early enhancement of successful breast-feeding.
Fifty-two healthy mother--infant pairs were referred to the paediatric clinic of Malmo General Hospital because of nursing problems. Observation of nursing behaviour showed that almost all these problems were connected to incorrect sucking technique. Only three of the infants sucked correctly, with mouth wide open and tongue under the areola. In a control group of 40 mother--infant pairs without nursing problems, 36 sucked correctly. The introduction of a bottle and the use of pacifiers seemed to interfere with the course of normal nursing.


[Instantaneous pressure-flow relations in a continuous flow in a collapsible tube: impact on the evaluation of urethral resistance].
The urethra is a collapsed tube in the absence of micturition. Consequently, the evaluation of instantaneous urethral resistance by the pressure/flow relation (R = P/Q2) derived from Bernoulli's equation has been criticised for not taking into account the opening pressure or at least the fact that flow must maintain patency of the urethra during voiding. The objective of this study was to determine whether such a criticism is justified in terms of fluid mechanics. A study of the pressure/flow relation was performed in a soft tube, collapsed by various peritubular pressures, which subsequently opened in response to flow. Experiments demonstrated that the pressure/flow relation, the instantaneous resistance to flow and the pressure drop were identical when the tube reached the same calibre, despite different peritubular pressures. The same pressure therefore propels the flow and maintains the patency of the tube. Consequently, it would be unreasonable to expect to improve the evaluation of instantaneous urethral resistance by subtracting an opening pressure from the maximal bladder pressure. The formula R = P/Q2 is valid, experimentally, and complies with the principles of fluid mechanics. In theory and in practice, it constitutes a good method of evaluation of instantaneous resistance.


Oxidation reaction of Scapharca inaequivalvis hemoglobins with nitrite.
The oxidation reaction with nitrite of the dimeric and tetrameric hemoglobins from the mollusc Scapharca inaequivalvis has been studied kinetically and at equilibrium. In line with previous findings obtained with ferricyanide as oxidant, in both proteins the stable oxidation product is a hemichrome, although the nitrite-methemoglobin complex is formed in significant amount when excess nitrite is employed. The reaction kinetics are characterized by a lag period followed by an autocatalytic phase, as in the case of human hemoglobin. However, with respect to human hemoglobin, in the two molluscan proteins the lag phase is prolonged significantly due to the instability of their met-form, an obligatory intermediate for the onset of autocatalysis. All the data obtained in spectrophotometric, EPR and sedimentation velocity experiments under a variety of experimental conditions conform to the reaction mechanism proposed for human hemoglobin (Spagnuolo et al., Biochim. Biophys. Acta 911 (1987) 59-63) provided hemichrome formation and nitrite binding are taken into account.


Possible involvement of CD10 in the development of endometriosis due to its inhibitory effects on CD44-dependent cell adhesion.
A reduced response to progesterone in the eutopic endometrium with endometriosis and in endometriotic tissues is considered to be the underlying factor for endometriosis. CD10 is known to be expressed by endometrial and endometriotic stromal cells and may be induced by progestins, although the function of CD10 is not fully revealed in endometrial or endometriotic tissues. In the current study, the expression of CD10 was significantly increased by treatment of the cells with progesterone, 17β-estradiol, and dibutyryl cyclic adenosine monophosphate (cAMP) in the endometrial stromal cells. On the other hand, the expression of CD10 following treatment with progesterone, 17β-estradiol, and dibutyryl cAMP was not significantly increased in endometriotic stromal cells. The adhesion assay for endometrial and endometriotic stromal cells to hyaluronan using 5- or 6-(N-succinimidyloxycarbonyl)-fluorescein 3', 6'-diacetate-labeled cells demonstrated that the CD44-dependent adhesion of stromal cells was inhibited by CD10. As far as the induction of CD10 is concerned, the effect of progesterone was different between endometrial stromal cells and endometriotic stromal cells. CD10 might be involved in the development of endometriosis due to its influence on CD44-dependent cell adhesion.


Pulmonary Micro-Ecological Changes and Potential Microbial Markers in Lung Cancer Patients.
The relationship between the microbiome and disease has been investigated for many years. As a highly malignant tumor, biomarkers for lung cancer are diverse. However, precision of these biomarkers has not yet been achieved. It has been confirmed that lung microecology changes in lung cancer patients compared with healthy individuals. Furthermore, the abundance of some bacterial species shows obvious changes, suggesting their potential use as a microbial marker for the detection of lung cancer. In addition, recent studies have confirmed that inflammation, immune response, virulence factors, and metabolism may be potential mechanisms linking the microbiome with carcinogenesis. In this review, microbiome studies of lung cancer, potential mechanisms, potential microbial markers, and the influence of the microbiome on the diagnosis and treatment of lung cancer are summarized, providing theoretical strategies for the diagnosis and treatment of lung cancer.


Prevention of hypertensive disorders of pregnancy.
A prospective randomised clinical trial comprising 510 pregnant patients was performed to determine whether supplementation with calcium, low-dose aspirin or a combination of calcium and low-dose aspirin can lower the incidence of hypertension in pregnancy. Greatest benefits were obtained with calcium. Perinatal mortality was lowest in the aspirin group.


[Changes in the contents of phosphoinositides in formed elements of blood and endometrial tissue in patients with hyperplastic processes and cancer of the endometrium].
The levels of phosphoinositides were measured in blood macrophages, platelets, lymphocytes, granulocytes, neutrophils, and red cells, as well as in endometrial tissue of 175 patients with glandular hyperplasia of the endometrium, atypical hyperplasia, endometrial polyps and cancer. A reliable reduction of the content of phosphatidyl inositides and phosphatidyl inositide-S-phosphates was observed in all formed elements of the blood, the most marked decrease being observed in endometrial cancer. On the contrary, the content of phosphatidyl inositide-4-phosphates and phosphatidyl inositide-4.5-diphosphates in the macrophages, lymphocytes, and granulocytes was reliably increased in the patients as against healthy women. The process of phosphatidylinositide phosphorylation run an absolutely different course in pathologically altered endometrial tissue than in comparison with that in blood cells. A new phosphatidyl inositide-signal mechanism was revealed, which is unrelated to inositol-1.4.5-triphosphate, as a result of which the potentiality of appearance of new secondary messengers actively participating in cell growth increases.


On the Shape-Selected, Ligand-Free Preparation of Hybrid Perovskite (CH3NH3PbBr3) Microcrystals and Their Suitability as Model-System for Single-Crystal Studies of Optoelectronic Properties.
Hybrid perovskite materials are one of the most promising candidates for optoelectronic applications, e.g., solar cells and LEDs, which can be produced at low cost compared to established materials. Although this field of research has seen a huge upsurge in the past decade, there is a major lack in understanding the underlying processes, such as shape-property relationships and the role of defects. Our aerosol-assisted synthesis pathway offers the possibility to obtain methylammonium lead bromide (MAPbBr3) microcrystals from a liquid single source precursor. The differently shaped particles are aligned on several substrates, without using a directing agent or other additives. The obtained particles show good stability under dry conditions. This allows us to characterize these materials and their pure surfaces at the single-crystal level using time- and spatially resolved methods, without any influences of size-dependent effects. By optimizing the precursor for the aerosol process, we were able to eliminate any purification steps and use the materials as processed. In addition, we performed theoretical simulations to deepen the understanding of the underlying processes in the formation of the different crystal facets and their specific properties. The model system presented provides insights into the shape-related properties of MAPbBr3 single crystals and their directed but ligand-free synthesis.


Orthopedic surgical infection prevention: host and environmental factors.
Postoperative infection has the potential to be a devastating and costly adverse outcome of major orthopedic joint reconstruction. There are numerous motivations to reduce surgical site infection. The impact of this impending epidemic can be reduced by focusing on preventive strategies that successfully can reduce the burden of perioperative infection. Surgeons and health systems must pay close attention to all factors that can affect the host and the environment of care. Preventing infection must be a top priority and a unifying concern when preparing for major orthopedic surgery. Increasing the attention given to these factors is paramount if health care organizations are to address this major threat to public health successfully.


A simple explanation for taxon abundance patterns.
For taxonomic levels higher than species, the abundance distributions of the number of subtaxa per taxon tend to approximate power laws but often show strong deviations from such laws. Previously, these deviations were attributed to finite-time effects in a continuous-time branching process at the generic level. Instead, we describe herein a simple discrete branching process that generates the observed distributions and find that the distribution's deviation from power law form is not caused by disequilibration, but rather that it is time independent and determined by the evolutionary properties of the taxa of interest. Our model predicts-with no free parameters-the rank-frequency distribution of the number of families in fossil marine animal orders obtained from the fossil record. We find that near power law distributions are statistically almost inevitable for taxa higher than species. The branching model also sheds light on species-abundance patterns, as well as on links between evolutionary processes, self-organized criticality, and fractals.


Genetic basis of drug sensitivity in human testis tumour cells.
Testicular germ cell tumours (TGCT) are cured in over 80% of patients by using combination chemotherapy. However, the mechanism regulating this sensitivity has not been defined. Because cells derived from patients with DNA repair syndromes are similar to TCGT in their sensitivity to certain DNA-damaging agents and some of the genes involved have been cloned by functional complementation, the purpose of our study was to determine whether drug sensitivity in TGCT also has a genetic basis. Three testis tumour cell lines (cisplatin-sensitive) and 3 bladder cancer cell lines (cisplatin-resistant) were fused with a cisplatin-sensitive cell line (D98orC1). The authenticity of the hybrids was confirmed by karyotyping and PCR analysis of locus-specific sites, and sensitivities to cisplatin were measured by colony forming assays. The hybrids between sensitive cell lines were more resistant to cisplatin than the parental cells, indicating that functional complementation had occurred. The hybrids between the cisplatin-resistant and sensitive cells were intermediate in their cisplatin sensitivity, indicating that resistance is incompletely dominant. We conclude that cisplatin sensitivity has a genetic basis in TGCT and that resistance to cisplatin can be conferred by somatic cell fusion. Our data indicate that gene(s) controlling sensitivity to chemotherapy in TGCT might be identified by expression cloning.


Research agendas: an invitation to readers.
Ethical problem solving in human research is a continuing dialectic. Each question that is investigated leads to new questions calling for research. Articles published in JERHRE include a research agenda, and questions raised elsewhere suggest research agendas publishable here. Pursuit of these research agendas will lead to a more comprehensive understanding of effective approaches to ethical problem solving. Readers are invited to propose agendas, form collaborations, and publish their findings.


Human genetic variation within neural crest enhancers: molecular and phenotypic implications.
Developmental gene expression programmes are coordinated by the specialized distal cis-regulatory elements called enhancers, which integrate lineage- and signalling-dependent inputs to guide morphogenesis. In previous work, we characterized the genome-wide repertoire of active enhancers in human neural crest cells (hNCC), an embryonic cell population with critical roles in craniofacial development. We showed that in hNCC, co-occupancy of a master regulator TFAP2A with nuclear receptors NR2F1 and NR2F2 correlates with the presence of permissive enhancer chromatin states. Here, we take advantage of pre-existing human genetic variation to further explore potential cooperation between TFAP2A and NR2F1/F2. We demonstrate that isolated single nucleotide polymorphisms affecting NR2F1/F2-binding sites within hNCC enhancers can alter TFAP2A occupancy and overall chromatin features at the same enhancer allele. We propose that a similar strategy can be used to elucidate other cooperative relationships between transcription factors involved in developmental transitions. Using the neural crest and its major contribution to human craniofacial phenotypes as a paradigm, we discuss how genetic variation might modulate the molecular properties and activity of enhancers, and ultimately impact human phenotypic diversity.


Cloning, tissue expression, and regulation of beagle dog CYP4A genes.
In addition to its function as a fatty acid hydroxylase, the peroxisome proliferator-activated receptor alpha (PPARalpha) target gene, CYP4A, has been shown to be important in the conversion of arachidonic acid to the potent vasoconstrictor 20-hydroxyeicosatetraenoic acid, suggesting a role for this enzyme in mediating vascular tone. In the present study, the cDNA sequence of beagle dog CYP4A37, CYP4A38, and CYP4A39 from the liver was determined. Open reading frame analysis predicted that CYP4A37, CYP4A38, and CYP4A39 each comprised 510 amino acids with approximately 90% sequence identity to one another, and approximately 71 and 78% sequence identity to rat CYP4A1 and human CYP4A11, respectively. PCR analysis revealed that the three dog CYP4A isoforms are expressed in kidney > liver >> lung >> intestine > skeletal muscle > heart. Treatment of primary dog hepatocytes with the PPARalpha agonists GW7647X and clofibric acid resulted in an increase in CYP4A37, CYP4A38, and CYP4A39 mRNA expression (up to fourfold), whereas HMG-CoA synthase mRNA expression was increased to a greater extent (up to 10-fold). These results suggest that dog CYP4A37, CYP4A38, and CYP4A39 are expressed in a tissue-dependent manner and that beagle dog CYP4A is not highly inducible by PPARalpha agonists, similar to the human CYP4A11 gene.


Blood Glucose Level Prediction: Advanced Deep-Ensemble Learning Approach.
Optimal and sustainable control of blood glucose levels (BGLs) is the aim of type-1 diabetes management. The automated prediction of BGL using machine learning (ML) algorithms is considered as a promising tool that can support this aim. In this context, this paper proposes new advanced ML architectures to predict BGL leveraging deep learning and ensemble learning. The deep-ensemble models are developed with novel meta-learning approaches, where the feasibility of changing the dimension of a univariate time series forecasting task is investigated. The models are evaluated regression-wise and clinical-wise. The performance of the proposed ensemble models are compared with benchmark non-ensemble models. The results show the superior performance of the developed ensemble models over developed non-ensemble benchmark models and also show the efficacy of the proposed meta-learning approaches.


Posterior sternoclavicular inveterate dislocation.
The authors report a case of posterior inveterate sternoclavicular dislocation, which came to their observation after tangential resection of the clavicle. They discuss the surgical technique of reduction and stabilization and clinical results. CT scan was the method most-suited to evaluate dislocation of the clavicle.


Seroepidemiology of human immunodeficiency virus infection in Borno State of Nigeria by sentinel surveillance.
A serosurvey for human immunodeficiency virus (HIV) infection was carried out in three well-separated population centers in Borno State of Nigeria in 1989-1990. The study subjects were 1,259 made up of sexually transmitted disease (STD) clinic attenders, pregnant women, female prostitutes, and blood donors. Sera were screened by enzyme-linked immunosorbent assay and confirmation was done by Western blotting. The overall seroprevalence was 1.67% (21/1,259), with no significant differences from one population center to another. There were, however, significant differences among the population groups studied: prostitutes, 4.24%; STD clinic attenders, 1.67%; blood donors, 0.71%; and pregnant women, 0.24%. Of the 21 seropositives, 18 were positive for HIV-1 only; 1 was positive for HIV-2 only; and 2 were positive for both HIV-1 and HIV-2. All three HIV-2-positive sera were from prostitutes. Prevalence rates found in this study showed marked increases from 2 to 3 years earlier. There is therefore the need for a vigorous and sustained intervention program.