Recent Advances in Encapsulation of Flexible Bioelectronic Implants: Materials, Technologies, and Characterization Methods.
Bioelectronic implantable systems (BIS) targeting biomedical and clinical research should combine long-term performance and biointegration in vivo. Here, recent advances in novel encapsulations to protect flexible versions of such systems from the surrounding biological environment are reviewed, focusing on material strategies and synthesis techniques. Considerable effort is put on thin-film encapsulation (TFE), and specifically organic-inorganic multilayer architectures as a flexible and conformal alternative to conventional rigid cans. TFE is in direct contact with the biological medium and thus must exhibit not only biocompatibility, inertness, and hermeticity but also mechanical robustness, conformability, and compatibility with the manufacturing of microfabricated devices. Quantitative characterization methods of the barrier and mechanical performance of the TFE are reviewed with a particular emphasis on water-vapor transmission rate through electrical, optical, or electrochemical principles. The integrability and functionalization of TFE into functional bioelectronic interfaces are also discussed. TFE represents a must-have component for the next-generation bioelectronic implants with diagnostic or therapeutic functions in human healthcare and precision medicine.


Use of extra-oral scanner for the study of arch form in a sample of Italian adolescents with ideal occlusion.
The aim of this study was to evaluate the shape and the average size of the maxillary and mandibular arch in an Italian adolescents' sample with correct occlusion, using the digital technology. The study sample was composed, after the use of an extra-oral scanner and after the application of inclusion and exclusion criteria, by the digitized dental casts of 79 Italian adolescents (39 females and 40 males), aged 14±1 years, with correct occlusion. On each model, both upper and lower, the reference points of the dental arches (FA), of the alveolar bone (WALA ridges) and of the incisal edge of the central incisors were identified. With these points, using a software, fourteen parameters were evaluated for each cast: basal and dental intermolar and inter-canine width, basal and dental molar and canine depth, basal and dental molar and canine ratio, overjet, overbite. Finally, the shape of the arches was assessed, dividing it into ovoid, triangular or square. Chi-square test and Student's T-test for each parameter were adopted with a p<0,05 significance level. The results showed that the ovoid form was the most frequent, followed by the triangular one for the upper arch and by the rectangular one for the lower arch. On the canine level, both upper and lower, both for dental and for basal references, the triangular shape showed the lowest width and ratio values and the highest depth values in comparison with the other two groups. The square one showed the opposite situation, and the ovoid one presented in the intermediate value. On the molar level the trend is quite similar to the canine one. The results obtained maybe suggest that on a significant percentage of the patients of the sample is expected to use a preformed ovoid arch wire, and the data found could be useful to study the adequacy of the arch wires currently on the market or to design new ones. .


[The synergistic antitumor effects of berberine alpha-hydroxy-beta-decanoylethyl sulfonate with hydroxycamptothecine and its effect on topoisomerase].
Synergistic antitumor effects of HB (berberine alpha-hydroxy-beta-decanoylethyl sulfonate, houttuyn berberine) with HCPT (hydroxycamptothecine), and its correlative mechanism were studied in vitro. MTT assay was employed to determine the cytotoxicity of HB combined with HCPT in tumor cells culture in vitro, IC50 and combination index (CI value) were used to evaluate the synergistic effects. The supercoiled DNA relaxation mediated by topoisomerase I & II was measured by agarose gel electrophoresis assay, and influence of HB was detected. The results showed that HB could inhibit the proliferation of tumor cells (SGC-7901, SW1116 and SW480) in vitro, and the inhibition ratio was increased, IC50 was reduced when combining with HCPT. CI value of the two drugs was less than 1 in HepG2, SW480, SGC-7901 and SW1116 cells. The lowest value was 0.447, 0.626, 0.161 and 0.178 in these tumor cells, respectively, further indicating HB has synergistic action with HCPT on suppressing tumor proliferation. The agarose gel electrophoresis assay showed HB can inhibit topoisomerase I & II activity of SW480 cells at the concentration of 2.0-8.0 mg x L(-1). HCPT is a typical inhibitor of topoisomerase I , the synergistic action between HCPT and HB on suppressing tumor proliferation is perhaps related to the congenerous inhibition of topoisomerase.


A role for the FtsQLB complex in cytokinetic ring activation revealed by an ftsL allele that accelerates division.
The cytokinetic apparatus of bacteria is initially formed by the polymerization of the tubulin-like FtsZ protein into a ring structure at midcell. This so-called Z-ring facilitates the recruitment of many additional proteins to the division site to form the mature divisome machine. Although the assembly pathway leading to divisome formation has been well characterized, the mechanisms that trigger cell constriction remain unclear. In this report, we study a 'forgotten' allele of ftsL from Escherichia coli, which encodes a conserved division gene of unknown function. We discovered that this allele promotes the premature initiation of cell division. Further analysis also revealed that the mutant bypasses the requirement for the essential division proteins ZipA, FtsK and FtsN, and partially bypasses the need for FtsA. These findings suggest that rather than serving simply as a protein scaffold within the divisome, FtsL may play a more active role in the activation of the machine. Our results support a model in which FtsL, along with its partners FtsB and FtsQ, function as part of a sensing mechanism that promotes the onset of cell wall remodeling processes needed for the initiation of cell constriction once assembly of the divisome complex is deemed complete.


[Bacteraemia due to Shigella flexneri serotype 6 in two patients with AIDS].
Infections due to Shigella usually remain localized to the digestive tract and are self-limited. Bacteremia is a potentially lethal complication that can occur in immunocompromised patients. We describe two episodes of bacteremia caused by Shigella in two adults with AIDS. In both patients, S. flexneri was recovered from stool and blood samples. The isolates belonged to serotype 6, were resistant only to trimethoprim-sulfamethoxazole and showed a similar band profile by pulsed-field gel electrophoresis. Patients received prolonged antimicrobial treatment with a favorable outcome. There were no cases of diarrhea in other individuals admitted to the emergency room. We hypothesized that patient No. 2 was infected at the hospital from patient No. 1. However, we could not establish the way of transmission. Although rare, it is important to take into account the possible occurrence of bacteremia due to Shigella or other bacterial enteropathogens in immunocompromised patients with diarrhea.


Cross-validation of best linear unbiased predictions of breeding values using an efficient leave-one-out strategy.
Empirical estimates of the accuracy of estimates of breeding values (EBV) can be obtained by cross-validation. Leave-one-out cross-validation (LOOCV) is an extreme case of k-fold cross-validation. Efficient strategies for LOOCV of predictions of phenotypes have been developed for a simple model with an overall mean and random marker or animal genetic effects. The objective here was to develop and evaluate an efficient LOOCV method for prediction of breeding values and other random effects under a general mixed linear model with multiple random effects. Conventional LOOCV of EBV requires inverting an (n-1)×(n-1) covariance matrix for each of n (= number of observations) data sets. Our efficient LOOCV obtains the required inverses from the inverse of the covariance matrix for all n observations. The efficient method can be applied to complex models with multiple fixed and random effects, but requires fixed effects to be treated as random, with large variances. An alternative is to precorrect observations using estimates of fixed effects obtained from the complete data, but this can lead to biases. The efficient LOOCV method was compared to conventional LOOCV of predictions of breeding values in terms of computational demands and accuracy. For a data set with 3,205 observations and a model with multiple random and fixed effects, the efficient LOOCV method was 962 times faster than the conventional LOOCV with precorrection for fixed effects based on each training data set but resulted in identical EBV. A computationally efficient LOOCV for prediction of breeding values for single- and multiple-trait mixed models with multiple fixed and random effects was successfully developed. The method enables cross-validation of predictions of breeding values and of any linear combination of random and/or fixed effects, along with leave-one-out precorrection of validation phenotypes.


Synergistic Effects of Oxygen on Phosphine and Ethyl Formate for the Control of Phthorimaea operculella (Lepidoptera: Gelechiidae).
Phosphine (PH3) and ethyl formate (EF) are two potentially powerful postharvest fumigant insecticides. We investigated the effectiveness of both PH3 and EF as fumigants at all developmental stages of the potato tuber moth Phthorimaea operculella Zeller, and we also studied the synergistic effects of these fumigants under controlled atmospheres of 50 and 80% oxygen (O2). The larval stage of P. operculella was the most susceptible to fumigation with PH3 at both 5°C and 20°C. All of the developmental stages showed greater susceptibility to PH3 at 20°C than at 5°C, whereas the susceptibility of adult P. operculella to this fumigant was not affected by temperature. The toxicity of EF did not differ with temperature for any of the P. operculella developmental stages. The atmospheric oxidation of PH3 increased the toxicity of this fumigant toward all developmental stages at both temperatures. In contrast, no differences in toxicity were observed for oxidized EF compared with EF alone at any developmental stage. In conclusion, using fumigation tests, we showed that atmospherically oxidized PH3 was much more effective against P. operculella than PH3 alone, demonstrating a synergistic effect for this fumigant and O2. Therefore, treatment with PH3 and high concentrations of O2, as described in this study, could be useful for managing the postharvest pest P. operculella.


Euthanasia, assisted suicide and AIDS.
Euthanasia is the termination of the life of a patient by a doctor at the request of the patient. Over the past 15 years AIDS has become the most common cause of death among men aged 20-50 years in Amsterdam. It follows from this that in Amsterdam euthanasia and assisted suicide among PWAs is seen relatively frequently, considerably more frequently than among patients with other diseases. This paper examines the existing data on suicide and euthanasia in relation to HIV. The calculated overall incidence of euthanasia/assisted suicide among PWAs in Amsterdam is about 26%. Reasons for the procedure, drugs used and outcomes are discussed, with specific reference to the Dutch context within which these occur.


Indigeneity of organic matter in fossils: a test using stable isotope analysis of amino acid enantiomers in Quaternary mollusk shells.
Comparison of the delta 13C values of D and L enantiomers of individual amino acids was used to evaluate the presence of amino acid contaminants in Quaternary land snails. Measurements of delta 13C values of amino acid D and L enantiomers determined by combined gas chromatography, combustion, isotope-ratio mass spectrometry are reported. Conventional combustion techniques, following separation of aspartic acid and glutamic acid enantiomers by liquid chromatography, were also used to determine delta 13C as well as delta 15N values. Thoroughly cleaned samples ranging in age from 7000 to > 100,000 yr B.P. are shown to have analytically identical delta 13C values for the D and L enantiomers of each amino acid, thus confirming that the amino acids are indigenous to the shells, even in Pleistocene samples. On the other hand, partially cleaned material shows divergence of isotopic values, thus indicating the presence of amino acid contaminants and emphasizing the importance of proper cleaning procedures. This approach provides a powerful method for assessing the indigeneity of amino acids in fossils.


Macrolides: present and future. An appraisal of in-vitro activity and pharmacokinetic behavior.
Macrolides belong to a large family of drugs called macrocyclic antibiotics, that can be divided into four groups: macrolactamas or ansamycins, polyene macrolides, macrolide-like compounds and macrolide antibiotics. Macrolide antibiotics comprise a large group of drugs, which are very much alike, characterized by large lactonic cycle with 12, 14, 15 or 16 atoms, to which are bound sugar and/or aminosugar. Although there are very large structural differences, macrolides represent a homogeneous group of drugs for which both a spectrum and a mode of action are similar. Macrolide antibiotics bind to the large subunit of prokaryotic ribosomes and perturb protein synthesis. The antimicrobial activity of macrolides is broad spectrum, being exhibited against gram-positive and gram-negative bacteria, including actinomyces and mycobacteria, as well as against treponemes, mycoplasmas, chlamydiae, rickettsias and also against some protozoa. Depending on the drug concentrations, bacterial species and phase of growth, macrolides may be bacteriostatic or bactericidal. Macrolides show high tissue/serum rations and greater concentrations of antibiotics are though to be achieved at the presumed site of infection. Such findings are in agreement with the apparent volumes of distribution for all the macrolide drugs, which are generally large. The worldwide resurgence of interest in macrolide antibiotics has yielded several semisynthetic derivatives of 14- and 16-membered macrolides which have progressed to clinical trials.


Overall Survival of Ovarian Cancer Patients Is Determined by Expression of Galectins-8 and -9.
The evaluation of new prognostic factors that can be targeted in ovarian cancer diagnosis and therapy is of the utmost importance. Galectins are a family of carbohydrate binding proteins with various implications in cancer biology. In this study, the presence of galectin (Gal)-8 and -9 was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC). Staining was evaluated using semi-quantitative immunoreactivity (IR) scores and correlated to clinical and pathological data. Different types of galectin expression were compared with respect to disease-free survival (DFS) and overall survival (OS). Gal-8 served as a new positive prognostic factor for the OS and DFS of ovarian cancer patients. Gal-9 expression determined the DFS and OS of ovarian cancer patients in two opposing ways-moderate Gal-9 expression was correlated with a reduced outcome as compared to Gal-9 negative cases, while patients with high Gal-9 expression showed the best outcome.


Treatment of asymptomatic left ventricular dysfunction.
Patients with abnormalities of left ventricular (LV) systolic or diastolic function may have no symptoms, especially in the early stages. These patients are not uncommon in the community, and the prevalence of this condition increases in the presence of risk factors such as diabetes, hypertension, and coronary artery disease. Patients with asymptomatic LV dysfunction have a significantly increased risk of overt heart failure and mortality. Therefore, it is of prime importance to identify and treat these patients to prevent progression of the disease. Echocardiography is an excellent tool to characterize systolic and diastolic properties of the left ventricle. However, its cost and lack of widespread availability have limited its usefulness in screening the general population. Careful clinical assessment coupled with electrocardiography and natriuretic peptide level assessment can identify higher-risk patients who should be referred for detailed evaluation of LV function. The goal of therapy is to halt and even reverse LV remodeling. Neurohormonal blockade, now the cornerstone of heart failure therapy, has been shown to have salutatory effects in patients with asymptomatic LV systolic dysfunction, both in reversing remodeling and reducing adverse clinical outcomes. Except for risk factor control, there is no evidence to advocate any specific therapy for asymptomatic patients with LV diastolic dysfunction.


State Licensing Board Requirements for Entry into the Dental Hygiene Profession.
Purpose: The purpose of this study was to identify current requirements for initial licensure and entry into the dental hygiene profession across state dental and dental hygiene licensing boards in the United States.Methods: A non-experimental study design was used to study dental and dental hygiene board licensing requirements in the United States, Puerto Rico and the Virgin Islands. Each regulatory board website was searched for requirements for entry-level dental hygiene licensure. Requirements were recorded on an Excel spreadsheet. State dental practice acts were reviewed to gather further information and 20 regulatory bodies were contacted to verify accuracy. Descriptive statistics were used to analyze data.Results: Information from a total of 52 dental boards (n=52) was examined for this study. Nearly all boards (n=51, 98.1%), with the exception of Alabama, required completion of entry-level education from a CODA accredited dental hygiene program and successful completion of the National Board Dental Hygiene Examination. Most states (n=51, 98.1%), except Delaware, also required a live-patient, a clinical board examination. Application fees ranged from $47.70 to $600. States varied considerably in terms of requirements for background checks, age, military status, and infection control training.Conclusion: Although the majority of regulatory bodies require completion of entry-level dental hygiene education from a CODA accredited program and successful completion of national board and a live-patient, clinical examination, there is considerable variation in other additional requirements for initial dental hygiene licensure.


Substitutions of glycine residues Gly100 and Gly147 in conservative loops decrease rates of conformational rearrangements of Escherichia coli inorganic pyrophosphatase.
Escherichia coli inorganic pyrophosphatase (PPase) is a one-domain globular enzyme characterized by its ability to easily undergo minor structure rearrangements involving flexible segments of the polypeptide chain. To elucidate a possible role of these segments in catalysis, catalytic properties of mutant variants of E. coli PPase Gly100Ala and Gly147Val with substitutions in the conservative loops II and III have been studied. The main result of the mutations was a sharp decrease in the rates of conformational changes required for binding of activating Mg2+ ions, whereas affinity of the enzyme for Mg2+ was not affected. The pH-independent parameters of MgPP(i) hydrolysis, kcat and kcat/Km, have been determined for the mutant PPases. The values of kcat for Gly100Ala and Gly147Val variants were 4 and 25%, respectively, of the value for the native enzyme. Parameter kcat/Km for both mutants was two orders of magnitude lower. Mutation Gly147Val increased pH-independent Km value about tenfold. The study of synthesis of pyrophosphate in the active sites of the mutant PPases has shown that the maximal level of synthesized pyrophosphate was in the case of Gly100Ala twofold, and in the case of Gly147Val fivefold, higher than for the native enzyme. The results reported in this paper demonstrate that the flexibility of the loops where the residues Gly100 and Gly147 are located is necessary at the stages of substrate binding and product release. In the case of Gly100Ala PPase, significant impairment of affinity of enzyme effector site for PP(i) was also found.


Nonlinear electrostatic emittance compensation in kA, fs electron bunches.
Nonlinear space-charge effects play an important role in emittance growth in the production of kA electron bunches with a bunch length much smaller than the bunch diameter. We propose a scheme employing the radial third-order component of an electrostatic acceleration field, to fully compensate the nonlinear space-charge effects. This results in minimal transverse root-mean-square emittance. The principle is demonstrated using our design simulations of a device for the production of high-quality, high-current, subpicosecond electron bunches using electrostatic acceleration in a 1 GV/m field. Simulations using the GPT code produce a bunch of 100 pC and 73 fs full width at half maximum pulse width, resulting in a peak current of about 1.2 kA at an energy of 2 MeV. The compensation scheme reduces the root-mean-square emittance by 34% to 0.4pi mm mrad.


Early recognition of potentially fatal necrotizing fasciitis. The use of frozen-section biopsy.
Necrotizing fasciitis is a rare, rapidly progressing soft-tissue infection. Early clinical recognition is difficult, and there is often a fatal delay in appropriate treatment. We evaluated the use of frozen-section biopsies for the rapid diagnosis of this disease in its early stages. Nineteen cases of necrotizing fasciitis were studied over a 13-year period. In all eight cases in which frozen-section biopsy was performed within zero to four days (average, 21 hours) after the onset of symptoms, histologic study confirmed the diagnosis, and surgical d ebridement was immediately performed. Only one patient died. In 11 patients, the diagnosis was made on clinical grounds, and surgical therapy was delayed for 1 to 15 days (average, 6) after the onset of symptoms because of failure to recognize the disorder immediately. Eight patients died (P less than 0.02). Our study indicates that rapid performance of frozen-section soft-tissue biopsy early in the evolution of a suspect lesion may provide a definitive and life-saving diagnosis.


Identifying multiple-target ligands via computational chemogenomics approaches.
Despite the rapidly growing knowledge of functional and structural information regarding pharmaceutically relevant targets during the past decade, target-based drug discovery has remained a high-cost and low-yield process. Particularly, single-target drugs often turn out to be less effective in treating complicated diseases such as cancers, metabolic disorders and CNS diseases. However, discovering compounds that are effective against multiple desired targets raises an enormous challenge to the current mode of drug innovation. Computational chemogenomics approaches aim at predicting all potential interactions between small molecular ligands and biomolecular targets, thus the derived information can be directly applied to "design in" (i.e. engineer desirable binding spectrum) and "design out" (i.e. eliminate the unwanted interactions) specific biological activities. The present review will focus on introducing the recent methodological development and successful applications of structure-based and ligand-based approaches on predicting the ligand binding profiles, which is the very first and essential step toward rationally designing the multiple-target ligands. Structure-based methods (e.g. binding site mapping and inverse molecular docking) generally require the structures of known targets to navigate the receptor-ligand binding space, while ligand-based approaches (e.g. chemical similarity analysis and pharmacophore search) can only rely on the series of active compounds to derive the structural characteristics for describing certain biological activities.


Brain mediation of Anolis social dominance displays. II. Differential forebrain serotonin turnover, and effects of specific 5-HT receptor agonists.
Serotonin (5-HT) functions are associated with social dominance status in diverse species, but to date the brain regions wherein 5-HT exerts such effects are uncertain. Here, we indexed 5-HT turnover in male Anolis carolinensis as the ratio of 5-HT to its metabolite, 5-hydroxy-indol-acetic acid, and also as the accumulation of the in vivo tracer 14C-alpha-methyl-tryptophan (14C-AMT). After patching one eye, displaying dominant animals increased both measures of 5-HT turnover in the forebrain hemisphere receiving display-evocative visual stimuli, compared to control, contralateral brain, whereas both 5-HT turnover indices were decreased when animals displayed submissively. In contrast, various non-displaying controls showed forebrain symmetry on both measures. Drugs that stimulate 5-HT(2C) receptors in mammals, and have 5-HT(2C)-like binding in A. carolinensis, evoked some elements of dominant display behaviors in non-dominant anole males and also activated dorsolateral basal ganglia as seen in non-medicated dominants when they display [Baxter et al., 2001]. Thus, acute changes in forebrain 5-HT output from baseline equilibrium, acting at 5-HT(2C)-like receptors, might effect some elements of the dominant vs. submissive male anoles' territorial displays. A mechanistic model of how this might occur is offered. Given similarities in 5-HT systems, forebrain functions, and territorial display routines, similar mechanisms might have similar functions in other amniotes, including primates.


A novel human biomonitoring study by semiconductor gas sensors in Exposomics: investigation of health risk in contaminated sites.
Two areas in central-southern Italy Land of Fires in Campania and Valley of Sacco river in Lazio are known to be contaminated sites, the first due to illegal fly-tipping and toxic fires, and the second due to an intensive industrial exploitation done by no-scruple companies and crooked public administration offices with dramatic consequences for environment and resident people. The work is intended to contribute to Human BioMonitoring (HBM) studies conducted in these areas on healthy young male population by a semiconductor gas sensor array trained by SPME-GC/MS. Human semen, blood and urine were investigated. The fingerprinting of the Volatile Organic Compounds (VOCs) by a gas sensors system allowed to discriminate the different contamination of the two areas and was able to predict the chemical concentration of several VOCs identified by GC/MS.


Development of a scale for measuring invasive plant environmentalism.
The ecological impact of invasive plant species is a serious concern among environmental scientists and conservationists. Educating the public about invasive plant issues is a major hurdle, given that several invaders come into the environment through ornamental gardening. An important first step in planning an educational program concerning invasive plant issues is to assess public knowledge and attitudes concerning these issues. This paper describes the development of an instrument that measures invasive plant environmentalism. Responses from 237 nursery customers from the southeastern U.S. to a 17-item standardized interview were scaled using the partial credit model, a member of the family of Rasch (1960) measurement models. Our results indicate that the instrument adequately measures this construct. Substantive interpretations of the results are also discussed.


Bisphenol A release from food and beverage containers - A review.
Dietary exposure was introduced as the primary way Bisphenol A (BPA) enters the human body. Although significant efforts have been made to analyze BPA's presence in different foodstuffs, less attention has been given to introducing the conditions that facilitate BPA release. This review aimed to mention possible factors affecting BPA release into foods and beverages. According to the results, the critical factors in BPA release are temperature, manufacturing process, food and packaging type, pH, mineral elements, repeated use, irradiation, washing, contact time, and using detergents. It showed that using PC containers, high temperature and pH, storage under solar irradiation, alkaline detergents, water hardness, and repeated use could increase the BPA release from containers into foodstuff. During various conditions, hydrolysis of the carbonate linkage and d-spacing will increase. Considering these parameters and limiting the use of PC containers, the potential risk of BPA exposure could be eliminated.


Active Binding Modes of Caffeine with Cytochrome P450 1A2 Determine Its Metabolite Profiles.
Caffeine is a very common kind of nervous stimulant, and it is primarily metabolized by Cytochrome P450 1A2 (CYP1A2) in the human body. Over the years, determining the interactions between caffeine and CYP1A2 has been a tough issue. The active binding modes and the catalytic regioselectivity of the metabolism between CYP1A2 and caffeine remain unclear. Here, to investigate the interactions between CYP1A2 and caffeine, we constructed the all-sequence CYP1A2-caffeine-membrane system using a multiple template approach. According to our simulation results, four active binding modes between CYP1A2 and caffeine that correspond to the four metabolic sites of caffeine are determined. What is more, a pre-reaction state for the CYP1A2-catalyzed reaction at caffeine's N3 site is identified. A more preponderant active binding mode might be the reason why the N3 site of caffeine becomes the primary metabolic site. Our findings could enhance our knowledge of the interactions between CYP1A2 and caffeine and help us better understand the regioselectivity of the metabolism between CYP1A2 and caffeine.


Casting and Splinting Management for Hand Injuries in the In-Season Contact Sport Athlete.
Upper extremity injuries are extremely common in contact sports such as football, soccer, and lacrosse. The culture of competitive athletics provides an environment where hand injuries are frequently downplayed in an effort to prevent loss of game time. However, studies have shown that many sport-induced hand injuries do not actually require immediate surgical attention and can be safely treated through immobilization so that the athlete may complete the athletic season. In these cases, appropriate casting and splinting measures should be taken to ensure protection of the injured player and the other competitors without causing loss of game time. Articles published between 1976 and 2015 were reviewed to capture historical and current views on the treatment of hand injuries in the in-season athlete. Clinical review. Level 5. Although traditionally many sports-induced traumatic injuries to the hand held the potential to be season-ending injuries, experience has shown that in-season athletes do not necessarily need to lose game time to receive appropriate treatment. A thorough knowledge of converting everyday splints and casts into game day, sport-approved protective immobilization devices is key to safely allowing athletes with select injuries to play while injured. Protective techniques allow for maximum functionality during gameplay while safely and effectively protecting the injury from further trauma while bony healing takes place.


High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways.
Advancing from gene discovery in autism spectrum disorders (ASDs) to the identification of biologically relevant mechanisms remains a central challenge. Here, we perform parallel in vivo functional analysis of 10 ASD genes at the behavioral, structural, and circuit levels in zebrafish mutants, revealing both unique and overlapping effects of gene loss of function. Whole-brain mapping identifies the forebrain and cerebellum as the most significant contributors to brain size differences, while regions involved in sensory-motor control, particularly dopaminergic regions, are associated with altered baseline brain activity. Finally, we show a global increase in microglia resulting from ASD gene loss of function in select mutants, implicating neuroimmune dysfunction as a key pathway relevant to ASD biology.


Ulcerative colitis: a genetically heterogeneous disorder defined by genetic (HLA class II) and subclinical (antineutrophil cytoplasmic antibodies) markers.
Newly described distinct associations of HLA class II genes with ulcerative colitis (UC) (DR2) and Crohn's disease (CD) (DR1/DQ5) provide strong evidence for genetic heterogeneity of susceptibility between these two forms of inflammatory bowel disease. A familial distribution of antineutrophil cytoplasmic antibodies (ANCAs, a subclinical marker of UC) in UC families has further implied the existence of heterogeneity within UC. To test the hypothesis that the heterogeneity within UC indicated by ANCAs has a genetic basis that resides within the HLA region, we studied 89 UC cases and an ethnically matched control group (n = 50). Serological and molecular typing techniques were applied to define HLA class II genes (DR, DQ). ANCAs were detected using an enzyme-linked immunosorbent assay, and positive values were confirmed by indirect immunofluorescence. We observed that ANCA-positive UC patients (n = 70) had a significantly increased frequency of DR2 compared with ANCA-negative controls (n = 46) (44% vs 22%, P = 0.01). In contrast, the frequency of DR2 in ANCA-negative UC cases (21%) was virtually identical to that in controls (22%, P = 0.9). Furthermore, the ANCA-negative UC patients had an increase in the DR4 allele compared with ANCA-positive UC (P = 0.004). Thus, with the combination of a subclinical marker (ANCAs) and molecular genetic markers, genetic heterogeneity has been demonstrated within UC: ANCA-positive UC associated with DR2, and ANCA-negative UC likely associated with DR4.


Influence on Learning of a Collaborative Learning Method Comprising the Jigsaw Method and Problem-based Learning (PBL).
Recently, the practice of active learning has spread, increasingly recognized as an essential component of academic studies. Classes incorporating small group discussion (SGD) are conducted at many universities. At present, assessments of the effectiveness of SGD have mostly involved evaluation by questionnaires conducted by teachers, by peer assessment, and by self-evaluation of students. However, qualitative data, such as open-ended descriptions by students, have not been widely evaluated. As a result, we have been unable to analyze the processes and methods involved in how students acquire knowledge in SGD. In recent years, due to advances in information and communication technology (ICT), text mining has enabled the analysis of qualitative data. We therefore investigated whether the introduction of a learning system comprising the jigsaw method and problem-based learning (PBL) would improve student attitudes toward learning; we did this by text mining analysis of the content of student reports. We found that by applying the jigsaw method before PBL, we were able to improve student attitudes toward learning and increase the depth of their understanding of the area of study as a result of working with others. The use of text mining to analyze qualitative data also allowed us to understand the processes and methods by which students acquired knowledge in SGD and also changes in students' understanding and performance based on improvements to the class. This finding suggests that the use of text mining to analyze qualitative data could enable teachers to evaluate the effectiveness of various methods employed to improve learning.


Accuracy of ultrasound estimates of urine volume.
Ultrascan and actual catheterization volumes were compared on 48 urology, general surgery, and rehabilitation patients. The findings suggest that mean scan and actual urine volumes can be considered equal. In clinical situations where it is necessary to determine residual urine volume, the bladder scan technology is a good alternative to an invasive catheterization procedure.


Jailed double-microcatheter technique following horizontal stenting for coil embolization of intracranial wide-necked bifurcation aneurysms: A technical report of two cases.
The horizontal stenting technique facilitates endovascular treatment of wide-necked bifurcation intracranial aneurysms. Previous literature shows, however, that subsequent coil embolization at initial treatment results in incomplete obliteration in many cases. The authors present two consecutive cases of wide-necked large bifurcation aneurysms to describe an additional coil embolization technique following horizontal stenting. The patients were a 53-year-old female with an unruptured internal carotid artery terminus aneurysm and a 57-year-old female with a recurrent basilar artery tip aneurysm. Both patients underwent endovascular treatment with horizontal stenting followed by coil embolization with jailed double-microcatheters. Immediate complete obliteration was achieved with no complications, and no recanalization was observed at the one-year follow-up in both cases. Coil embolization with jailed double-microcatheter technique following horizontal stenting is a safe and effective strategy for wide-necked bifurcation aneurysms.


Longitudinal volumetric and 2D assessment of cerebellar atrophy in a large cohort of children with phosphomannomutase deficiency (PMM2-CDG).
We aim to delineate the progression of cerebellar atrophy (the primary neuroimaging finding) in children with phosphomannomutase-deficiency (PMM2-CDG) by analyzing longitudinal MRI studies and performing cerebellar volumetric analysis and a 2D cerebellar measurement. Statistical analysis was used to compare MRI measurements [midsagittal vermis relative diameter (MVRD) and volume] of children with PMM2-CDG and sex- and age-matched controls, and to determine the rate of progression of cerebellar atrophy at different ages. Fifty MRI studies of 33 PMM2-CDG patients were used for 2D evaluation, and 19 MRI studies were available for volumetric analysis. Results from a linear regression model showed that patients have a significantly lower MVRD and cerebellar volume compared to controls (p < 0.001 and p < 0.001 respectively). There was a significant negative correlation between age and MVRD for patients (p = 0.014). The rate of cerebellar atrophy measured by the loss of MVRD and cerebellar volume per year was higher at early ages (r = -0.578, p = 0.012 and r = -0.323, p = 0.48 respectively), particularly in patients under 11 years (p = 0.004). There was a significant positive correlation between MVRD and cerebellar volume in PMM2-CDG patients (r = 0.669, p = 0.001). Our study quantifies a progression of cerebellar atrophy in PMM2-CDG patients, particularly during the first decade of life, and suggests a simple and reliable measure, the MVRD, to monitor cerebellar atrophy. Quantitative measurement of MVRD and cerebellar volume are essential for correlation with phenotype and outcome, natural follow-up, and monitoring in view of potential therapies in children with PMM2-CDG.


Structural-Level Racial-, Sexual Orientation-, and HIV-Related Discrimination and Subsequent Criminal Justice Involvement Among Young, Black, Men Who Have Sex With Men in North Carolina.
Multiple aspects of Black young men who have sex with men's (YMSM) identities cause them to be differentially targeted for arrest and incarceration. However, limited research has explored structural drivers of Black YMSM' criminal justice involvement, particularly co-occurring forms of discrimination. This article examines the temporal relationship between perceived racial discrimination, perceived sexual orientation discrimination, and community-level HIV discrimination and criminal justice involvement among Black YMSM in North Carolina. The study followed 465 Black YMSM from November 2013 to October 2016 who were recruited for a randomized controlled trial to test an internet-based intervention for Black YMSM living with, and at risk for HIV; participants completed online surveys at baseline, 3, 6, and 12 months. Logistic regression was used to explore the relationship between the three predictors at baseline (i.e., perceived racism and sexual orientation discrimination and community-level HIV discrimination) and criminal justice involvement at follow-up. All three predictor variables were significantly associated with subsequent criminal justice involvement in separate regression models that adjusted for other covariates: HIV discrimination (aOR = 1.06 [1.01-1.11]), perceived sexual orientation discrimination (aOR = 1.12 [1.00-1.27]), and perceived racism (aOR = 1.26 [1.12-1.42]). Perceived racism remained significant in the model with all three predictors (aOR = 1.29 [1.07-1.55]). Racism did not modify the relationship between HIV discrimination and perceived sexual orientation discrimination and criminal justice involvement. This study expands existing research by exploring racism as a structural driver of criminal justice involvement; we subsequently examined whether racism modified the effect of the two other predictors. It also contributes to research on co-occurring discrimination by examining their impact on an underrepresented population.


[Intra-cavity aspergilloma complicating necrotising sarcoid granulomatosis].
Necrotising sarcoid granulomatosis is a rare clinical entity, characterised by the development of nodular pulmonary opacities, the diagnosis if which is based on the identification of characteristic pathological lesions. A 44-years-old male smoker presented with cough and fever. With the exception of a few basal crepitations clinical examination was normal. The chest x-ray showed multiple areas of alveolar consolidation scattered throughout both lung fields, some of which were cavitated. The thoracic CT scan confirmed the presence of cavitating nodules and hilar and mediastinal lymphadenopathy. Samples for mycobacteria were negative. A search for anti-neutrophil cytoplasmic antibodies was negative. Fibreoptic bronchoscopy was normal but transbronchial biopsies revealed giant cells. Lung biopsies taken by video thoracoscopy showed non-caseating granulomata with areas of fibrinoid necrosis and perivascular infiltration with lymphocytes, histology characteristic of necrotising sarcoid granulomatosis. Resolution occurred without treatment. The parenchymal lesions regressed leaving residual cavities. Four years later, following an episode of haemoptysis, the patient was found to have a squamous cell carcinoma (T1N0M0) and aspergillomas in the pulmonary cavities. Our observation demonstrates that the cavities of necrotising sarcoid granulomatosis may be complicated by aspergillomas.


Cations in the rat pars distalis ultrastructural localization.
Pituitary glands of female Sprague Dawley rats were fixed using the potassium pyroantimonate-osmium tetroxide technique by immersion or vascular perfusion. Both fixation procedures resulted in similar patterns of cation localization visualized as electron-dense precipitate within cells of the pars distalis. Nuclei were prominent sites of localization. Cytoplasmic precipitate occurred in association with the endoplasmic reticulum, typically within the cisternal spaces, and also was localized within the mitochondrial matrix and cristae, as well as Golgi membranes, small Golgi-associated vesicles, and multivesicular bodies. Immature secretory granules often contained precipitate between the core material of the granule and the enclosing smooth membrane. Frequently small antimonate-containing vesicles bordered the immature secretory granules. Precipitate was variable in secretory granules of more mature appearance although precipitate was apparent occasionally just within a granule's enclosing membrane. Granules closest to the plasma membrane often contained increased amounts of precipitate and small vesicles containing precipitate were observed fusing with them. Instances of granule release by emiocytosis often revealed a clustering of precipitate behind the core material away from the emiocytotic stoma, as well as at the stoma, and frequently an increased electron density of filamentous material radiating from the granules' enclosing membranes or from the adjacent plasma membrane. Exposure of section material to the chelating agents EGTA and EDTA indicate that calcium is the primary cation localized within the cytoplasm of these secretory cells. These findings are consistent with a role for calcium as a facilitator in the processes of transport and release of secretory granules.


Aging and heart failure--similar syndromes of exercise intolerance? Implications for exercise-based interventions.
A classic hallmark of chronic heart failure (CHF) is exercise intolerance; however, the extent of exercise limitation is not correlated with the degree of left ventricular dysfunction. Over the past 2 decades it has become more and more evident that peripheral factors, such as skeletal muscle dysfunction, ventilatory abnormalities, and endothelial dysfunction, contribute the greater part to the limitation of exercise capacity. The molecular and pathophysiological changes observed in these organ systems are not always specific to the underlying CHF but rather represent a common pathway that is activated in several chronic disease processes, including severe chronic obstructive pulmonary disease, cancer, and in the normal aging process. A major contributing factor for skeletal muscle catabolism (i.e. elevated cytokine expression in the skeletal muscle) can be found in both normal healthy aging and in heart failure patients. It is reasonable to assume that the overlap of aging and CHF-associated changes in the skeletal muscle partially explains the disabling consequences of the CHF syndrome among elderly patients (nearly 80% of all patients hospitalized for CHF are >65 years old). Peripheral alterations in CHF are often not adequately treated in routine clinical care since standard pharmacological therapy is still focused on the cardiac function and neurohormonal alteration. Exercise training is a guideline-oriented adjuvant therapy with well-documented beneficial effects on exercise tolerance, skeletal muscle function, endothelial function, and respiration. In this review, the effects of exercise in aging and in CHF are compared and the parallel mechanisms are explored.


Emerging Coxsackievirus A6 Causing Hand, Foot and Mouth Disease, Vietnam.
Hand, foot and mouth disease (HFMD) is a major public health issue in Asia and has global pandemic potential. Coxsackievirus A6 (CV-A6) was detected in 514/2,230 (23%) of HFMD patients admitted to 3 major hospitals in southern Vietnam during 2011-2015. Of these patients, 93 (18%) had severe HFMD. Phylogenetic analysis of 98 genome sequences revealed they belonged to cluster A and had been circulating in Vietnam for 2 years before emergence. CV-A6 movement among localities within Vietnam occurred frequently, whereas viral movement across international borders appeared rare. Skyline plots identified fluctuations in the relative genetic diversity of CV-A6 corresponding to large CV-A6-associated HFMD outbreaks worldwide. These data show that CV-A6 is an emerging pathogen and emphasize the necessity of active surveillance and understanding the mechanisms that shape the pathogen evolution and emergence, which is essential for development and implementation of intervention strategies.


Suicide among men in Ghana: The burden of masculinity.
In Ghana, some studies have reported a high rate for both fatal and non-fatal suicidal behaviors among men. The current study aimed at understanding the psychosocial circumstances involved in male suicides. We interviewed between two to seven close relations of each of 12 men who died by suicide. Interpretative phenomenological analysis of data indicates that experiences of shame related to loss of economic control, breach of patriarchal norms, and threats to sexual competence contributed to the suicides. Addressing socioeconomic issues, creating opportunities for men to disclose their emotions, and identifying sources of these emotions may help prevent suicide among men.


Computerized tomographic prediction of flexor tendon injuries complicating hamate hook fractures.
We reviewed computerized axial tomography of 28 patients with hamate hook fractures who had surgical resection of the hook. We analysed the relationship between the fragment height ratio, fragment gap, and intraoperative findings of the tendons. We determined whether parameters in the images can predict complication of tear or disruption of the flexor tendons to the ring or little fingers. Of 28 patients, 16 had fragment height ratios between 50-74; ten among them had worn (eight patients) or ruptured (two patients) flexor tendons. Nine of the ten patients had fragment gaps greater than 2 mm. The remaining 12 patients had fragment height ratios between 75-100 and had intact tendons. We conclude that a fragment height ratio greater than 75 and fragment gap less than 2 mm in computer tomography may rule out tear or disruption of the flexor tendons of the ring and little fingers after hamate hook fractures, and a fragment height ratio between 50-74 with fragment gap greater than 2 mm indicates a high risk of flexor tendon tear or disruption. Level of evidence: IV.


Physical conditioning in the aging adult.
The benefits of exercise are well established but the impact of exercise on the older adult is not as clearly defined. Increasing numbers of people in the United States are over 65 years old. Thus health care providers will find themselves often involved with the older adult and will need an understanding of exercise in this age group. This article reviews the known benefits of exercise for the older adult, exercise-related age changes, and how to prescribe exercise for those 65 years and over. Selected case reports are used to provide examples of how specified guidelines can be incorporated into practice.


Complications of orbital and skull base phlebography.
Two complications, one in association with frontal vein phlebography and one in association with inferior petrosal sinus phlebography, are presented. Possible mechanisms for complications are discussed. It is concluded that a significant risk exists in association with inferior petrosal sinus phlebography, particularly in association with vascular disorders of the skull base, while the risk in association with orbital phlebography after frontal vein puncture is minimal if compression of the jugular veins is omitted.


Ceftolozane-tazobactam activity against drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa causing healthcare-associated infections in Australia and New Zealand: Report from an Antimicrobial Surveillance Program (2013-2015).
To evaluate the in vitro activity of ceftolozane-tazobactam and comparator agents tested against isolates of Enterobacteriaceae and Pseudomonas aeruginosa from patients in Australia and New Zealand with healthcare-associated infection. A total of 1459 gram-negative organisms (440 P. aeruginosa and 1019 Enterobacteriaceae) were consecutively collected from 11 medical centers located in Australia and New Zealand. The organisms were tested for susceptibility by broth microdilution methods as described by the CLSI M07-A10 document and the results interpreted according to EUCAST and CLSI breakpoint criteria. Ceftolozane-tazobactam (MIC50/90, 0.25/0.5μg/mL; 97.7/95.9% susceptible [CLSI/EUCAST]), meropenem (MIC50/90, ≤0.06/≤0.06μg/mL; 99.8/99.9% susceptible [CLSI/EUCAST]) and amikacin (MIC50/90, 2/4μg/mL; 99.8/99.6% susceptible [CLSI/EUCAST]) were the most active compounds tested against Enterobacteriaceae. Enterobacteriaceae isolates displayed susceptibility rates to other β-lactam agents ranging from 95.3/94.4% for cefepime, 94.1/91.4% for piperacillin-tazobactam, and 93.3/91.5% for ceftazidime using CLSI/EUCAST breakpoints. Among the Enterobacteriaceae isolates tested, 0.1% were CRE and 6.6% exhibited an ESBL non-CRE phenotype. Whereas ceftolozane-tazobactam showed good activity against ESBL non-CRE phenotype strains of Enterobacteriaceae (MIC50/90, 0.5/2μg/mL), it lacked useful activity (MIC, >32μg/mL) against the single isolate with a CRE resistant phenotype. Ceftolozane-tazobactam was the most potent (MIC50/90, 0.5/2μg/mL) β-lactam agent tested against P. aeruginosa isolates, inhibiting 95.7% at an MIC of ≤4μg/mL. Ceftolozane-tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than currently available cephalosporins and piperacillin-tazobactam when tested against Enterobacteriaceae.


ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues.
Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In diclofenac alone and nimesulide alone group, the sections from the gastric areas showed partial necrosis and mild chronic inflammation respectively. The study, therefore, has provided therapeutic rationale towards simultaneous administration of H2 receptor blocker ranitidine with diclofenac to be more beneficial as compared to ranitidine with nimesulide, to minimise the gastric intolerance of diclofenac in long term treatment of inflammatory conditions.


Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fc oligosaccharides: the high-mannose, hybrid, and complex types.
The structure of asparagine-linked oligosaccharides attached to the antibody constant region (Fc) of human immunoglobulin G1 (IgG1) has been shown to affect the pharmacokinetics and antibody effector functions of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, it is still unclear how differences in the N-linked oligosaccharide structures impact the biological activities of antibodies, especially those lacking core fucose. Here, we succeeded in generating core fucose-lacking human IgG1 antibodies with three different N-linked Fc oligosaccharides, namely, a high-mannose, hybrid, and complex type, using the same producing clone, and compared their activities. Cultivation of an alpha-1,6-fucosyltransferase (FUT8) knockout Chinese hamster ovary cell line in the presence or absence of a glycosidase inhibitor (either swainsonine or kifunensine) yielded antibody production of each of the three types without contamination by the others. Two of three types of nonnaturally occurring atypical oligosaccharide IgG1, except the complex type, reduced the affinity for both human lymphocyte receptor IIIa (FcgammaRIIIa) and the C1q component of the complement, resulting in reduction of ADCC and CDC. The bulky structure of the nonreducing end of N-linked Fc oligosaccharides is considered to contribute the CDC change, whereas the structural change in the reducing end, i.e. the removal of core fucose, causes ADCC enhancement through improved FcgammaRIIIa binding. In the pharmacokinetic profile, although no significant difference of human neonatal Fc receptor (FcRn)-binding affinity was observed among the three types, the complex type showed longer serum half-lives than the other types irrespective of core fucosylation in mice, which also suggests the contribution of the nonreducing end structure. The present study provides basic information on the effects of core fucose-lacking N-linked Fc oligosaccharides on antibody biological activities.


HiC-spector: a matrix library for spectral and reproducibility analysis of Hi-C contact maps.
Genome-wide proximity ligation based assays like Hi-C have opened a window to the 3D organization of the genome. In so doing, they present data structures that are different from conventional 1D signal tracks. To exploit the 2D nature of Hi-C contact maps, matrix techniques like spectral analysis are particularly useful. Here, we present HiC-spector, a collection of matrix-related functions for analyzing Hi-C contact maps. In particular, we introduce a novel reproducibility metric for quantifying the similarity between contact maps based on spectral decomposition. The metric successfully separates contact maps mapped from Hi-C data coming from biological replicates, pseudo-replicates and different cell types. Source code in Julia and Python, and detailed documentation is available at https://github.com/gersteinlab/HiC-spector . email@example.com or firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


The role of dietary sugars and de novo lipogenesis in non-alcoholic fatty liver disease.
Dietary sugar consumption, in particular sugar-sweetened beverages and the monosaccharide fructose, has been linked to the incidence and severity of non-alcoholic fatty liver disease (NAFLD). Intervention studies in both animals and humans have shown large doses of fructose to be particularly lipogenic. While fructose does stimulate de novo lipogenesis (DNL), stable isotope tracer studies in humans demonstrate quantitatively that the lipogenic effect of fructose is not mediated exclusively by its provision of excess substrates for DNL. The deleterious metabolic effects of high fructose loads appear to be a consequence of altered transcriptional regulatory networks impacting intracellular macronutrient metabolism and altering signaling and inflammatory processes. Uric acid generated by fructose metabolism may also contribute to or exacerbate these effects. Here we review data from human and animal intervention and stable isotope tracer studies relevant to the role of dietary sugars on NAFLD development and progression, in the context of typical sugar consumption patterns and dietary recommendations worldwide. We conclude that the use of hypercaloric, supra-physiological doses in intervention trials has been a major confounding factor and whether or not dietary sugars, including fructose, at typically consumed population levels, effect hepatic lipogenesis and NAFLD pathogenesis in humans independently of excess energy remains unresolved.


HIV risk among young Ghanaians in high school: validation of a multidimensional attitude towards condom use scale.
Condom use remains low among sexually active youth in sub-Saharan Africa. Theoretical and empirical evidence suggests that attitudes towards condom use are important predictors of actual condom use. However, few attempts have been made to systematically develop a valid scale that measures attitudes towards condom use among youth, particularly high school students in sub-Saharan Africa. Using the health belief model, we developed an instrument that measures such attitudes. We analysed survey data collected from 6252 Ghanaian junior high school students. We assessed construct validity using confirmatory factor analysis. Results indicate that attitudes towards condom use among young Ghanaians are best represented by a multidimensional construct. Young Ghanaians differentiate constructs related to perception of benefits and barriers to condom use, as well as perception of severity and susceptibility to HIV. This instrument offers a valid tool for assessing high school students' attitudes towards condom use and their HIV risk.


Delicate balance of hydrogen bonding forces in D-threoninol.
The seven most stable conformers of D-threoninol (2(S)-amino-1,3(S)-butanediol), a template used for the synthesis of artificial nucleic acids, have been identified and characterized from their pure rotational transitions in the gas phase using chirped-pulse Fourier transform microwave spectroscopy. D-Threoninol is a close analogue of glycerol, differing by substitution of an NH2 group for OH on the C(β) carbon and by the presence of a terminal CH3 group that breaks the symmetry of the carbon framework. Of the seven observed structures, two are H-bonded cycles containing three H-bonds that differ in the direction of the H-bonds in the cycle. The other five are H-bonded chains containing OH···NH···OH H-bonds with different directions along the carbon framework and different dihedral angles along the chain. The two structural types (cycles and chains of H-bonds) are in surprisingly close energetic proximity. Comparison of the rotational constants with the calculated structures at the MP2/6-311++G(d,p) level of theory reveals systematic changes in the H-bond distances that reflect NH2 as a better H-bond acceptor and poorer donor, shrinking the H-bond distances by ∼0.2 Å in the former case and lengthening them by a corresponding amount in the latter. Thus revealed is the subtle effect of asymmetric substitution on the energy landscape of a simple molecule, likely to be important in living systems.


Chronological association between increases in drug abuse and psychosis in Connecticut state hospitals.
Disagreement remains as to whether drug use can result in an autonomous psychotic disorder. If drug use can create new psychosis cases, an increase in the number of psychosis patients ought to be observable following periods of increased drug use by the general population. First admissions data for the categories of drug abuse and schizophrenia/paranoid disorders from all Connecticut state hospitals from 1965 to 1983 were examined to determine the prevalence of psychotic disorders before, during, and after a period of increased drug use by the general population. Affective disorders first admissions were examined for comparison. A rapid increase in new schizophrenia admissions coincided with a peak period for drug-related admissions. The data suggest that increased drug use of the late 1960s may have contributed to the increase noted 3 to 5 years later in first admissions of patients diagnosed with psychotic disorders.


The restorative rehabilitation of the severe loss of dental hard tissue due to dental erosion or abrasion is a challenging situation for the dentist. The following article presents the case of applying direct adhesive composite restorations as one possible approach to reconstruct erosively-induced severe dental hard tissue loss.


Cross-cultural validation of stool Based Colorectal cancer screening methods in the North West of Iran.
Globally, colorectal cancer (CRC) is the third most common cancer and the second leading cause of death from cancer. Incidence and mortality from CRCboth can be reduced and prevented using screening and early detection programs. The current study aimed to assess the feasibility of the colorectal cancer screening program in Northwest of Iran. The study designed as a cross-cultural analytic study, to evaluate the diagnostic accuracy of stool-based tests compared with colonoscopy, during 2016-2020. All individuals first were assessed with our CRC risk assessment tool, then eligible volunteers entered the study. Colonoscopy was performed on all participants, also stool-based tests including traditional guaiac, high-sensitivity guaiac-based, fecal immunochemical test (FIT), and multitarget stool DNA (Mt-sDNA) panel tests were performed. Mt-sDNA test panel had a sensitivity of 77.8% (95% CI: 40-97.2)for detecting colorectal cancer with a specificity of 91.2% (95% CI:85.4-95.2). The FIT test alone had a lower sensitivity (66.7%; 95% CI:29.9-92.5) and almost the same specificity of 93.9% (95% CI: 88.7-97.2) for cancer detection. Mt-sDNA test had better diagnostic accuracy than the FIT (AUC = 0.85 vs 0.80), and is a more useful screening test. Positive and negative predictive values for cancer detection for both Mt-sDNA and FIT tests were almost the same results, however Mt-sDNA test had better NPV results than the FIT test alone. Our results showed that both Mt-sDNA panel and the FIT test had acceptable cut-off points for cancer detection, however, Mt-sDNA test had better diagnostic accuracy.


Exploring Iranian β-Thalassemia major patients' perception of barriers and facilitators of adherence to treatment: A qualitative study.
Despite the clinical importance of adherence to treatment in β-Thalassemia Major (β-TM) patients, poor adherence remains a prevalent and persistent problem in these patients. The aim of this study was to explore Iranian β-TM patients' perception regarding the barriers and facilitators of adherence to their treatments. In this qualitative study, data were collected using purposeful sampling and semi-structured interviews with 18 β-TM patients, 3 family members and 5 healthcare professionals (total=26) in Sari, northern Iran, between August 2015 and May 2017. Data were analyzed using conventional content analysis with the support of MAXQDA software. All the interviews were transcribed verbatim. Data were coded and grouped under specific categories. We identified and classified the perceived barriers of patients' adherence to treatment into six main categories including: (I) long distance challenges, (II) delayed occurrence of complications, (III) fatigue of healthcare providers, (IV) staff workload, (V) insufficient follow-up of healthcare workers, and (VI) busy everyday life. Also, nine main categories emerged as facilitators including: (I) concern of appearance changing, (II) outcomes of treatment, (III) good awareness, (IV) parental monitoring, (V) fear of complications, (VI) social activity, (VII) marriage as a facilitator, (VIII) friendly interaction with the medical staff, and (IX) trusting the medical staff. Our findings provide a broad range of context-specific facilitators and barriers to treatment adherence perceived by Iranian β-TM patients. These factors improve our understanding of the complex and multifactorial nature of adherence to treatments. Health care providers can use these findings in designing and implementing appropriate interventions to promote β-TM patients' adherence to treatment.


Efficacy of enamel matrix protein applied to spontaneous periodontal disease in two dogs.
Enamel matrix protein (EMP) was applied for regeneration of periodontal tissue in 2 dogs with spontaneous periodontal disease. Case 1 had bony resorption around the root and root apex of the maxillary fourth premolars. Case 2 had vertical resorption of bone between the mandibular first and second molars. A flap was formed in the buccal gingiva, and EMP was applied onto the surface of the exposed root. One or 4 months postoperatively, increased bone level and clinical attachment were recognized. EMP was therefore suggested to be effective to induce regeneration of periodontal tissues in the cases with periodontal disease.


Repetitive ejaculation before intracytoplasmic sperm injection in patients with absolute immotile spermatozoa.
Cases with absolute immotile sperm syndrome are rare, and include the genetic defect of immotile cilia syndrome with the absence of dynein arms in the flagellum. We attempted to increase the percentage of viable spermatozoa to improve the outcome of intracytoplasmic sperm injection (ICSI). Three couples in whom repeated analysis of the male partners indicated 100% sperm immotility underwent an in-vitro fertilization (IVF) procedure in which ICSI was performed. On their first ICSI cycle the males produced a single ejaculation while in their successive ICSI cycles they were requested to repeatedly ejaculate (two to four times) and only the last ejaculation was used. The eosin-Y test was performed on each used sample. Following their first treatment, one couple had one repeated treatment cycle, another had two and the third couple had three repeated treatment cycles. The mean percentages of viable spermatozoa were 41+/-7.4 and 71+/-6.9% in the first and repeated cycles respectively (P < 0.01; t-test). Of the 39 oocytes injected in the first ICSI cycles only one (3%) was normally fertilized (2PN) compared with 41 (48%) of the 85 oocytes injected in the repeated ICSI cycles. One (3%) embryo in the first and 35 (41%) embryos in the repeated ICSI cycles respectively were obtained (P < 0.001), enabling their replacement into the uterine cavity in all the repeated cycles. One woman (in a repeated cycle) conceived a twin pregnancy and delivered two healthy babies. The use of spermatozoa from repeated ejaculation is recommended in men with absolutely immotile spermatozoa so as to obtain significantly better viability and fertilizing capacity.


Development of the first geldanamycin-based HSP90 degraders.
Despite the early clinical promise, adverse events such as acquired resistance and dose-limiting toxicities have barred the widespread use of HSP90 inhibitors as anticancer drugs. A new approach involving proteolysis-targeting chimeras (PROTACs) to degrade the protein instead of inhibiting it may overcome these problems. In this work, we describe the design, synthesis, and evaluation of cereblon-recruiting geldanamycin-based HSP90 degraders based on the PROTAC technology. Our best degrader, 3a, effectively decreased HSP90α and HSP90β levels in cells utilizing the ubiquitin-proteasome pathway.


Non-receptor-mediated inotropic drugs.
There has been an active search recently for non-glycoside, non-sympathomimetic positive inotropic agents. Phosphodiesterase inhibitors inhibit the breakdown of cyclic AMP, leading to an increase in intracellular cAMP concentration, and can be expected to enhance the force of myocardial contraction. The methylxanthines exert such an action in vitro; the situation in vivo is more complex, due to their manyfold actions. Phosphodiesterase F-III is relatively specific for cAMP degradation; the new phosphodiesterase inhibitors may act specifically by inhibiting this enzyme. Phosphodiesterase inhibitors with combined inotropic and vasodilatory action include amrinone, which is no longer in widespread use due to its pronounced side-effects, milrinone, which is much better tolerated and has shown promising results in recent large-scale trials, and sulmazole which has been withdrawn due to toxic effects in rodents. Other drugs are still under investigation. Of importance is the relative role of the inotropic versus dilatory action of these drugs. A salutory effect on resting haemodynamics, does not necessarily imply improved exercise haemodynamics. The pharmacokinetic profile of these drugs is also of interest. The clinical benefits should be sustained and the side-effects should not outweigh the beneficial actions of these drugs.


Reversibility of cadmium-induced health effects in rabbits.
Twenty-one male rabbits were divided into three groups: rabbits of two groups were given pelleted food containing cadmium chloride at a dose level of 300 micrograms Cd/g over periods of 44 or 19 weeks. Rabbits of the last group were given ordinary commercial pelleted food and served as controls. Cadmium increased urinary protein and amino acid by week 19 and increased it to a remarkably high level by week 44. After cessation of cadmium exposure, rabbits of the first group (44 weeks exposure group) showed only little recovery from cadmium health effects: proteinuria and aminoaciduria were slightly improved. Depressed hepatic functions were also slightly improved, but did not return to the control level in 24 weeks. Fat and bone metabolism also remained depressed below the control level. Anemia did not also readily recover. On the other hand, rabbits of the second group (19 weeks exposure) recovered from the effects of cadmium: proteinuria and aminoaciduria in most animals disappeared soon after the end of cadmium exposure, plasma GPT fell after 1 week, and hemoglobin and hematocrit returned to normal in 6-11 weeks. The above results show that after cessation of cadmium exposure, mild cadmium-induced health effects were reversible in a short period, while more severe effects were not readily reversible. High performance liquid chromatographic (HPLC) profiles of renal and hepatic cadmium-thionein (Cd-MT) during and after exposure to cadmium showed no correlation to the degree of cadmium health effects, and therefore, did not help to elucidate mechanisms of the recovery from cadmium-induced health effects, probably because cadmium not bound with metallothionein (non-MT-Cd) is responsible for inducing renal effects.


Assessment of pre-injury health-related quality of life: a systematic review.
Insight into the change from pre- to post-injury health-related quality of life (HRQL) of trauma patients is important to derive estimates of the impact of injury on HRQL. Prospectively collected pre-injury HRQL data are, however, often not available due to the difficulty to collect these data before the injury. We performed a systematic review on the current methods used to assess pre-injury health status and to estimate the change from pre- to post-injury HRQL due to an injury. A systematic literature search was conducted in EMBASE, MEDLINE, and other databases. We identified studies that reported on the pre-injury HRQL of trauma patients. Articles were collated by type of injury and HRQL instrument used. Reported pre-injury HRQL scores were compared with general age- and gender-adjusted norms for the EQ-5D, SF-36, and SF-12. We retrieved results from 31 eligible studies, described in 41 publications. All but two studies used retrospective assessment and asked patients to recall their pre-injury HRQL, showing widely varying timings of assessments (soon after injury up to years after injury). These studies commonly applied the SF-36 (n = 13), EQ-5D (n = 9), or SF-12 (n = 3) using questionnaires (n = 14) or face-to-face interviews (n = 11). Two studies reported prospective pre-injury assessment, based on prospective longitudinal cohort studies from a sample of initially non-injured patients, and applied questionnaires using the SF-36 or SF-12. The recalled pre-injury HRQL scores of injury patients consistently exceeded age- and sex-adjusted population norms, except in a limited number of studies on injury types of higher severity (e.g., traumatic brain injury and hip fractures). All studies reported reduced post-injury HRQL compared to pre-injury HRQL. Both prospective studies reported that patients had recovered to their pre-injury levels of physical and mental health, while in all but one retrospective study patients did not regain the reported pre-injury levels of HRQL, even years after injury. So far, primarily retrospective research has been conducted to assess pre-injury HRQL. This research shows consistently higher pre-injury HRQL scores than population norms and a recovery that lags behind that of prospective assessments, implying a systematic overestimation of the change in HRQL from pre- to post-injury due to an injury. More prospective research is necessary to examine the effect of recall bias and response shift. Researchers should be aware of the bias that may arise when pre-injury HRQL is assessed retrospectively or when population norms are applied, and should use prospectively derived HRQL scores wherever possible to estimate the impact of injury on HRQL.


Effect of sulfur sources on specific desulfurization activity of Rhodococcus erythropolis KA2-5-1 in exponential fed-batch culture.
The effects of sulfur sources on the desulfurization activity of Rhodococcus erythropolis KA2-5-1 were investigated by using an exponential fed-batch culture technique. The feed rate of a sulfur source was controlled independently of the feed rate of ethanol, which was used as a carbon and energy source. Among the sulfur sources examined were dibenzothiophene (DBT), ammonium sulfate, L-cysteine, L-methionine, and 2-amino-ethanesulfonic acid. When the fed-medium contained DBT as the sole sulfur source, KA2-5-1 cells showed a maximum desulfurization activity of approximately 130 mmol 2-HBP kg-cell(-1) h(-1). Similar levels of enzyme activity were also achieved with inexpensive ammonium sulfate by using the exponential fed-batch culture technique. In addition, higher levels of desulfurization activity were achieved by increasing the dosage of the DBT desulfurization (dsz) operon and dszD gene in R. erythropolis KA2-5-1. The recombinant strain showed a maximum desulfurization activity of approximately 250 mmol 2-HBP kg-cell(-1) h(-1) in the exponential fed-batch cultures.


Scanning the genome with 1772 microsatellite markers in search of a bipolar disorder susceptibility gene.
Bipolar disorder affects approximately 1% of the population and there is evidence that genetic factors play an important role in the production of symptoms. We undertook a genetic linkage study for the discovery of a major locus conferring susceptibility for bipolar illness in an Old Order Amish pedigree. Our study took advantage of publicly available phenotypic and genotypic information, the latter as a byproduct of the human genome project effort. We present a genomic scan using 1772 polymorphic genetic markers and we suggest candidate genetic regions for harboring a bipolar disorder susceptibility gene.


Etiologies and outcomes of pleural effusions in patients with systemic lupus erythematosus.
Pleuritis is the most common pulmonary manifestation in systemic lupus erythematosus (SLE). In Thailand, the incidence of tuberculosis (TB) is high; moreover, treatment with immunosuppressive agents increases the risk for TB infection. The objective of this study was to examine the clinical manifestations, etiology, management, and outcomes of patients with SLE and pleural effusion in an area for TB. We studied adults satisfying the American College of Rheumatology classification criteria for SLE who presented with pleuritis between 2002 and 2010. Pleuritis was defined as having 1 of 3 of the following criteria: typical pleuritic chest pain, pleural rub, and clinical or radiological evidence of pleural effusion. A total of 119 patients with 127 episodes of pleuritis/pleural effusion were included. Pleuritis was the first presentation in 47 episodes (37%) and was found accompanied with pericarditis for 16%. Most patients (81%) had active SLE in other systems. The causes of pleural effusion included lupus pleuritis (52%), tuberculous pleuritis (9%), parapneumonic effusion (7%), and transudate (15%). The diagnosis was inconclusive in 17%. The diagnosis of lupus pleuritis was made by a clinical diagnosis (47%) and by excluding other causes from pleural fluid analysis or biopsy (53%). Most patients with lupus pleuritic responded well to corticosteroid therapy. Lupus pleuritis is still the most common cause of pleural effusion in SLE and often reflects its disease activity. The diagnosis of lupus pleuritis is a clinical diagnosis or is performed by excluding other conditions. The treatment outcomes of lupus pleuritis are generally good.


[Microscopical identification of roots and rhizome of six species of plants from viola in the region of Nanjing].
Microscopical identification of 6 species of plants from Viola in Nanjing was made, and the distinguished microscopical characteristics of them were found. The key was also listed on, which can provide scientific data for identification and exploitation of Viola plants.


Clostridium difficile infection in Johannesburg, South Africa.
The incidence of Clostridium difficile infection is increasing, resulting in significant in-patient morbidity and mortality. We describe the characteristics of Clostridium difficile infection in patients admitted to a tertiary Academic Hospital in Johannesburg, South Africa. This was a retrospective record review of 154 adult in-patients with confirmed Clostridium difficile infection undertaken between 1 January 2013 and 30 June 2014. Overall, 83 (53.9%) patients were female and the median age was 39 years. The most common symptoms were watery diarrhea (92.9%) and fever (27.3%). Overall, 145 (97.9%) patients had been exposed to antibiotics in the last 30 days, 54 (35.1%) to immunosuppressives, 48 (31.2%) to gastric acid suppressants, and 65 (42.2%) patients had previous hospital admissions. Only two cases were community-acquired. In total, 73 (47.4%) patients died. There was no difference in outcomes of HIV-positive patients compared to HIV-negative patients; however, the clinical features were more marked in the HIV-negative patients. Non-survivors tended to have a greater number of severity indicators compared to the survivors. Patients with Clostridium difficile infection in this study were younger and had a higher mortality than that reported in the Western world. Most infections were hospital-acquired.


Field-based experimental acidification alters fouling community structure and reduces diversity.
Increasing levels of CO2 in the atmosphere are affecting ocean chemistry, leading to increased acidification (i.e. decreased pH) and reductions in calcium carbonate saturation state. Many species are likely to respond to acidification, but the direction and magnitude of these responses will be based on interspecific and ontogenetic variation in physiology and the relative importance of calcification. Differential responses to ocean acidification (OA) among species will likely result in important changes in community structure and diversity. To characterize the potential impacts of OA on community composition and structure, we examined the response of a marine fouling community to experimental CO2 enrichment in field-deployed flow-through mesocosm systems. Acidification significantly altered the community structure by altering the relative abundance of species and reduced community variability, resulting in more homogenous biofouling communities from one experimental tile to the next both among and within the acidified mesocosms. Mussel (Mytilus trossulus) recruitment was reduced by over 30% in the elevated CO2 treatment compared to the ambient treatment by the end of the experiment. Strong differences in mussel cover (up to 40% lower in acidified conditions) developed over the second half of the 10-week experiment. Acidification did not appear to affect the mussel growth, as average mussel sizes were similar between treatments at the end of the experiment. Hydroid (Obelia dichotoma) cover was significantly reduced in the elevated CO2 treatment after 8 weeks. Conversely, the percentage cover of bryozoan colonies (Mebranipora membranacea) was higher under acidified conditions with differences becoming apparent after 6 weeks. Neither recruitment nor final size of barnacles (Balanus crenatus) was affected by acidification. By the end of the experiment, diversity was 41% lower in the acidified treatment relative to ambient conditions. Overall, our findings support the general expectation that OA will simplify marine communities by acting on important ecological processes that ultimately determine the community structure and diversity.


Perisynaptic organization of plasma membrane calcium pumps in cerebellar cortex.
Calcium, a ubiquitous intracellular messenger, regulates numerous intracellular signaling pathways. To permit specificity of signal transduction and prevent unwanted cross-talk between pathways, sites of calcium entry in neurons are localized to specific membrane domains. To test whether Ca(2+) extrusion pumps might exhibit analogous compartmentalization, we used immunohistochemistry to determine the subcellular localization of the two main plasma membrane Ca(2+)-ATPase (PMCA) isoforms in the cortex of the rat cerebellum. We find that both PMCA2 and PMCA3 are targeted to distinct compartments within the plasma membrane. In the molecular layer, both isoforms were at highest levels within synaptic profiles, but PMCA2 was postsynaptic and PMCA3 was presynaptic. Moreover, inside these compartments, both pumps exhibited nonuniform distributions. These data imply that cerebellar neurons possess remarkably effective mechanisms to target and restrict PMCA2 and -3 to specific membrane domains, raising the possibility that calcium pumps contribute to local Ca(2+) signaling.


ANAPHYLACTOID OEDEMA PRODUCED IN RATS BY CERTAIN DEXTRINS.
The author has previously shown the conditioning role of the anaphylactoid reaction in the calcification of the snout and paws of the rat after the injection of certain metallic compounds. The present experiments show that it is the dextrin fraction of these compounds which causes these anaphylactoid phenomena before the calcifying response. This fact deserves special attention since dextrin is frequently used in the preparation of certain drugs.


Stability of Two Antifungal Agents, Fluconazole and Miconazole, Compounded in HUMCO RECURA Topical Cream to Determine Beyond-Use Date.
A novel compounding vehicle (RECURA) has previously been proven to penetrate the nail bed when compounded with the antifungal agent miconazole or fluconazole, providing for an effective treatment for onychomycosis. In this study, miconazole and fluconazole were compounded separately in RECURA compounding cream, and they were tested at different time points (0, 7, 14, 28, 45, 60, 90, and 180 days) to determine the beyond-use date of those formulations. The beyond-use date testing of both formulations (10% miconazole in RECURA and 10% fluconazole in RECURA) proved them to be physically, chemically, and microbiologically stable under International Conference of Harmonisation controlled room temperature (25°C ± 2°C/60% RH ±5%) for at least 180 days from the date of compounding. Stability-indicating analytical method validation was completed for the simultaneous determination of miconazole and fluconazole in RECURA base using high-performance liquid chromatography coupled with photodiode array detector prior to the study.


The human ubiquitin gene family: structure of a gene and pseudogenes from the Ub B subfamily.
An ubiquitin cDNA clone was isolated from a human liver cDNA library. This clone contained two complete, and a portion of a third, ubiquitin coding sequences joined head to tail with no spacer peptides. Screening a human genomic library with a probe derived from the coding region of this cDNA identified a large number of cross-hybridising clones. Differential screening of these genomic clones with the 3' non-coding region of the cDNA identified three different 3'-positive clones. Sequence analysis of these three clones revealed: a gene corresponding to the cDNA containing an intron in the 5' non-coding region and coding for three direct repeats of mature ubiquitin, and two related pseudogenes which appear to have arisen by reverse transcription and insertion into the genome. However, one pseudogene contains two repeats of the ubiquitin coding sequence, while the other contains only one. Hybridisation analysis of restricted human genomic DNA suggests the presence of one other closely related gene within the genome.


Peanut lectin binding as a marker for activated T-lineage lymphocytes.
A series of experiments was undertaken to ascertain the reliability of peanut agglutinin (PNA) binding as a means of distinguishing mouse pre-T cells from other cell types. Normal bone marrow, thymus and spleen cells were stained with graded doses of fluoresceinated lectin (FITC-PNA) and subsequently examined by fluorescence microscopy to determine the number of lectin-binding cells. In addition, the PNA binding properties of mitogenically activated lymphocytes were examined in a similar manner. The results of this study show that PNA binding does not define a fixed population of cells, as the percentage of PNA+ cells detected in normal mouse tissues varied directly with the concentration of PNS used for staining. Nor is PNA able to distinguish between pre-T cells and mature T cells after mitogenic stimulation, both of which are shown to bind PNA. This lectin may , however, have value as a general marker of lymphoid precursors and activated lymphocytes of the T lineage.


Targeting tumor suppressor networks for cancer therapeutics.
Cancer is a consequence of mutations in genes that control cell proliferation, differentiation and cellular homeostasis. These genes are classified into two categories: oncogenes and tumor suppressor genes. Together, overexpression of oncogenes and loss of tumor suppressors are the dominant driving forces for tumorigenesis. Hence, targeting oncogenes and tumor suppressors hold tremendous therapeutic potential for cancer treatment. In the last decade, the predominant cancer drug discovery strategy has relied on a traditional reductionist approach of dissecting molecular signaling pathways and designing inhibitors for the selected oncogenic targets. Remarkable therapies have been developed using this approach; however, targeting oncogenes is only part of the picture. Our understanding of the importance of tumor suppressors in preventing tumorigenesis has also advanced significantly and provides a new therapeutic window of opportunity. Given that tumor suppressors are frequently mutated, deleted, or silenced with loss-of-function, restoring their normal functions to treat cancer holds tremendous therapeutic potential. With the rapid expansion in our knowledge of cancer over the last several decades, developing effective anticancer regimens against tumor suppressor pathways has never been more promising. In this article, we will review the concept of tumor suppression, and outline the major therapeutic strategies and challenges of targeting tumor suppressor networks for cancer therapeutics.


Influence of the lower-hybrid drift instability on magnetic reconnection in asymmetric configurations.
Using fully kinetic 3D simulations of magnetic reconnection in asymmetric antiparallel configurations, we demonstrate that an electromagnetic lower-hybrid drift instability (LHDI) localized near the X line can substantially modify the reconnection mechanism in the regimes with large asymmetry, a moderate ratio of electron to ion temperature, and low plasma β. However, the mode saturates at a small amplitude in the regimes typical of Earth's magnetopause. In these cases, LHDI-driven turbulence is predominantly localized along the separatrices on the low-β side of the current sheet, in agreement with spacecraft observations.


[Prenatal diagnosis of enzymopathies of the urea cycle].
Seven defects of the urea cycle enzymes were obtained in 48 hours at-risk pregnancies. A new method for measuring ornithine transcarbamylase and carbamylphosphate synthetase-I was used for prenatal diagnosis of the related enzymopathies in chorionic villi.


Rate of condom use among sexually active adolescents: a nationwide cross-sectional study in Taiwan from 2012 to 2016.
Adolescents' sexual behaviours are associated with sexually transmitted infections and unwanted pregnancies. This study aimed to estimate the sexual intercourse and condom use rates at first and last sex among Taiwanese adolescents in grades 7-12. A secondary data analysis of the Taiwan Global School-Based Student Health Survey's 2012-2016 data. The survey was anonymous, cross-sectional and nationwide. Taiwan high school students (grades 7-12). The sample comprised 27 525 students from junior high schools (grades 7-9), and senior high schools, comprehensive schools, vocational high schools and night schools (grades 10-12). The rate of ever having had sexual intercourse; the rates and factors of condom use at first and last sex. The sexual intercourse rate in each school type (in ascending order) was junior high school (1.62%), senior high school (4.14%), comprehensive school (9.08%), vocational high school (14.03%) and night school (41.09%). Condom use rate decreased from 57.07% (95% CI=54.31% to 59.83%) at first sex to 25.72% (95% CI=23.34% to 28.10%) at last sex (p<0.0001). The condom use rate (in ascending order) was junior high school (first sex: 37.67%, last sex: 19.76%), night school (55.83%, 22.62%), vocational high school (61.13%, 25.78%), comprehensive school (62.83%, 28.61%) and senior high school (68.38%, 34.96%). Older age at sexual debut was associated with condom use at first and last sex, and having one sexual partner was associated with condom use at last sex, as revealed by logistic regression analysis. This study highlights an urgent need to instil a proper understanding of protected sex while adolescents are still in their formative years. Despite the low sexual intercourse rate (4.95%), there is lower condom use at last sex than at first sex, which indicates that many sexually active adolescents are not practising protected sex, especially among junior high school students.


Lutidyl Radical Photoelectron Spectra Reveal Additive Substituent Effects on Benzyl Derivatives' Ionization Energy.
Understanding how isomerism influences photoelectron spectra helps in the assignment and analysis of reactive mixtures, especially for heterocycles with numerous isomers. Threshold photoelectron spectra of lutidyl radical isomers, i. e., benzyl derivatives with a nitrogen heteroatom and a methyl substituent, are recorded using vacuum ultraviolet synchrotron radiation. The radicals are produced by flash pyrolysis from aminomethyl methylpyridine precursors. Experimental ionization energies are determined to be 7.54, 7.50, and 7.45 eV for 2,4-, 2,6- and 3,5-lutidyl, respectively, in excellent agreement with composite method calculations. Franck-Condon simulations aid the TPES assignment but are also shown to exhibit artifacts if large-amplitude motions, notably the methyl internal rotation are assumed to be active in the double harmonic approximation. Based on calculated adiabatic ionization energies (AIE) of benzyl, picolyl, and xylyl radicals, the N and CH3 substituent effects are found to be additive, position-dependent and decrease in the para>ortho≳meta order in magnitude with the nitrogen heteroatom increasing and the methyl substituent decreasing the AIE. These effects are discussed in light of the charge distribution upon ionization. The additivity of the substituent effects also helps predict the influence of substituents on the binding energy of the unpaired electron in analogous radicals.


Erythrocyte ion transport in rats subjected to acute and chronic hypobaric hypoxia.
Our study addresses selected parameters of rat erythrocyte ion transport (Na(+)-K(+) pump, Na(+)-K(+)-2Cl- cotransport, and passive cation fluxes) after acute or chronic hypoxia exposure. We did not find any significant change of ion transport after acute hypoxia. However, chronic hypoxia could modify ion transport because the affinity of Na(+)-K(+) pump for intracellular Na(+) seems to be decreased.


[Significance of soluble interleukin-2 receptor alpha chain in the management of patients with malignant lymphoma: a multi-center study].
A multi-center series of 117 patients with malignant lymphoma were analyzed to evaluate the clinical significance of soluble interleukin-2 receptor alpha chain (sIL-2R alpha). The initial levels of sIL-2R alpha ranged from 277 U/ml to 22,800 U/ml with a mean level of 3,451 +/- 4,268 U/ml and a median level of 1,600 U/ml. The sIL-2R alpha levels of the diffuse lymphoma/intermediate-grade subtypes defined by the LSG classification/Working Formulation were higher than those of the follicular lymphoma/low-grade subtypes. There was a tendency for B-cell lymphomas to show higher sIL-2R alpha levels than T-cell lymphomas. The sIL-2R alpha level was correlated with the Ann Arbor clinical stage (I, II versus III, IV), presence or absence of B symptoms, and performance status (0, 1 versus 2, 3, 4) of the patients. The sIL-2R alpha levels were in good accordance with the four risk groups defined by the International Prognostic Indices. Of 21 patients whose tumor burden was serially measured, the coefficients of correlation between sIL-2R alpha and tumor mass were > 0.6 in 18 cases. Sixty-two patients achieved complete remission (CR) during the study; the initial and minimum sIL-2R alpha levels were lower than those of the non-CR patients. This study confirmed that sIL-2R alpha is a convenient and useful marker in the management of malignant lymphoma.


Anomalous pressure dependence of the superconducting transition temperature of beta-pyrochlore AOs2O6 oxides.
High-pressure effects on the superconducting transitions of beta-pyrochlore oxide superconductors AOs(2)O(6) (A = Cs,Rb,K) are studied by measuring resistivity under high pressures up to 10 GPa. The superconducting transition temperature T(c) first increases with increasing pressure in every compound and then exhibits a broad maximum at 7.6 K (6 GPa), 8.2 K (2 GPa), and 10 K (0.6 GPa) for A = Cs, Rb, and K, respectively. Finally, the superconductivity is suppressed completely at a critical pressure near 7 GPa and 6 GPa for A = Rb and K and probably above 10 GPa for A = Cs. Characteristic changes in the coefficient A of the T(2) term in resistivity and residual resistivity are observed, both of which are synchronized with the corresponding change in T(c).