Bactericidal activity of orally available agents against methicillin-resistant Staphylococcus aureus.
The recent proliferation of community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) has led to a marked increase in the need for outpatient treatment of MRSA infections. Many oral agents active against MRSA have been available for years, and a paucity of literature compares them, leaving physicians with little guidance for choosing among them. The purpose of the present study was to compare the bactericidal effects of orally available antibiotics against MRSA and to determine whether there were differences in antimicrobial killing activity against CA-MRSA and hospital-acquired (HA) MRSA isolates. A total of 12 unique patient MRSA isolates were studied. Six strains were CA, carrying the staphylococcal chromosomal cassette (SCCmec) type IVa, while six were HA and carried SCCmec type II. Time-kill methods were used to study the bactericidal activity of the orally available antimicrobials linezolid, rifampicin, trimethoprim/sulfamethoxazole, clindamycin, minocycline, and moxifloxacin alone and in combination in vitro. Trimethoprim/sulfamethoxazole was rapidly bactericidal resulting in >2 log(10) cfu/mL decrease at 8 h and >3 log(10) cfu/mL decrease at 24 h in vitro. No antibiotic combination exhibited better killing than trimethoprim/sulfamethoxazole alone. Adding rifampicin to trimethoprim/sulfamethoxazole showed a trend towards antagonism in vitro. There were no differences in the bactericidal activity of any antimicrobial or antimicrobial combination against MRSA isolates carrying SCCmec type IVa versus those carrying SCCmec type II. Trimethoprim/sulfamethoxazole is rapidly bactericidal against MRSA in vitro when compared with most other orally available antimicrobials. No differences in bactericidal activity were detected when activities against CA-MRSA and HA-MRSA were compared.


Simultaneous algebraic reconstruction technique (SART): a superior implementation of the art algorithm.
In this paper we have discussed what appears to be a superior implementation of the Algebraic Reconstruction Technique (ART). The method is based on 1) simultaneous application of the error correction terms as computed by ART for all rays in a given projection; 2) longitudinal weighting of the correction terms back-distributed along the rays; and 3) using bilinear elements for discrete approximation to the ray integrals of a continuous image. Since this implementation generates a good reconstruction in only one iteration, it also appears to have a computational advantage over the more traditional implementation of ART. Potential applications of this implementation include image reconstruction in conjunction with ray tracing for ultrasound and microwave tomography in which the curved nature of the rays leads to a non-uniform ray density across the image.


Are GOLD ABCD groups better associated with health status and costs than GOLD 1234 grades? A cross-sectional study.
To investigate the association of the GOLD ABCD groups classification with costs and health-related quality of life (HR-QoL) and to compare this with the GOLD 1234 grades classification that was primarily based on lung function only. In a cross-sectional study, we selected patients diagnosed with chronic obstructive pulmonary disease (COPD) from electronic medical records of general practices. Multi-level analysis was used with costs (medication, primary care, healthcare, societal), diseasespecific and generic HR-QoL as independent variables. Either the new or the old GOLD stages were included in the analysis together with several covariates (age, gender, living situation, co-morbidity, self-efficacy, smoking, education, employment). 611 patients from 28 general practices were categorised as GOLD-A (n=333), GOLD-B (n=110), GOLD-C (n=80) and GOLD-D (n=88). Patients in the GOLD-B and GOLD-D groups had the highest prevalence of co-morbidities and the lowest level of physical activity, self-efficacy, and employment. The models with GOLD ABCD groups were more strongly related to and explained more variance in costs and in disease-specific and generic HR-QoL than the models with GOLD 1234 grades. The mean Clinical COPD Questionnaire score worsened significantly, with scores 1.04 (GOLD-B), 0.4 (GOLD-C) and 1.21 (GOLD-D) worse than for patients in GOLD-A. Healthcare costs per patient were significantly higher in GOLD-B (72%), GOLD-C (74%) and GOLD-D (131%) patients than in GOLD-A patients. The GOLD ABCD groups classification is more closely associated with costs and HR-QoL than the GOLD 1234 grades classification. Furthermore, patients with GOLD-C had a better HR-QoL than those with GOLD-B but the costs of the two groups did not differ.


Rivastigmine transdermal patch and physical exercises for Alzheimer's disease: a randomized clinical trial.
To determine the effects of rivastigmine patch associated with physical exercise versus rivastigmine patch alone in quality of life (QOL), cognition, activities of daily living (ADL) and functional mobility in Alzheimer's disease (AD)subjects. A randomized, controlled, single-blinded trial was conducted in 40 patients with mild to moderate stages of AD. All patients were daily treated with rivastigmine transdermal patch at a stable dose of 4.6 mg and randomized into two groups: physical exercises or control. The exercise program consisted of aerobic, flexibility, strength and balance movements, twice a week for 6 months. Main outcomes were Quality of Life in Alzheimer's disease scale (QOL), Activities of Daily Living Questionnaire (ADL), Mini-Mental State Examination (MMSE) and "Time Up and Go Test". Thirty-four patients completed the study. After 6 months, there was a significant improvement in QOL of patients randomized to physical exercise group (P< 0.05). In both groups, there was an improvement on caregivers QOL (P>0.05). When considering cognitive functions, there was no difference between groups. The ability to perform ADL worsened in the group enrolled to RTP alone. There was an improvement in functional mobility in the group treated with RTP. Our results suggest that the association between physical exercises and RTP improves QOL in patients with AD. Cognition remained unchanged in both groups. Regarding the effect of physical exercises in ADL, further trials are necessary to confirm these results.


Treatment with sodium benzoate leads to malformation of zebrafish larvae.
Sodium benzoate (SB) is a commonly used food preservative and anti-microbial agent in many foods from soup to cereals. However, little is known about the SB-induced toxicity and teratogenicity during early embryonic development. Here, we used zebrafish as a model to test the toxicity and teratogenicity because of their transparent eggs; therefore, the organogenesis of zebrafish embryos is easy to observe. After low dosages of SB (1-1000 ppm) treatment, the zebrafish embryos exhibited a 100% survival rate. As the exposure dosages increased, the survival rates decreased. No embryos survived after treatment with 2000 ppm SB. The 50% lethal dose (LD(50)) of zebrafish is found to be in the range of 1400-1500 ppm. Gut abnormalities, malformation of pronephros, defective hatching gland and edema in pericardial sac were observed after treatment with SB. Compared to untreated littermates (vehicle-treated control), SB-treated embryos exhibited significantly reduced tactile sensitivity frequencies of touch-induced movement (vehicle-treated control: 27.60+/-1.98 v.s. 1000 ppm SB: 7.89+/-5.28; N=30). Subtle changes are easily observed by staining with specific monoclonal antibodies F59, Znp1 and alpha6F to detect morphology changes in muscle fibers, motor axons and pronephros, respectively. Our data showed that the treatment of SB led to misalignment of muscle fibers, motor neuron innervations, excess acetyl-choline receptor cluster and defective pronephric tubes. On the basis of these observations, we suggest that sodium benzoate is able to induce neurotoxicity and nephrotoxicity of zebrafish larvae.


Industry perspectives on prenatal genetic testing.
Until recent years, prenatal genetic tests have been almost exclusively developed and implemented by academic physicians and laboratories. In the last several years, industry has led the development of novel prenatal genetic tests, funded clinical trials and implemented these tests into clinical practice. That these efforts have been driven by industry has raised questions about diagnostics development regulations, consistency in reporting of results, and management of potential conflicts of interest. In this article, these topics are addressed from an industry perspective. While commercial laboratories may have the resources to develop and offer novel genetic tests, collaboration with healthcare providers is crucial for appropriate, effective, and efficient utilization of such tests.


Radiation Therapy Oncology Group clinical trials for carcinoma of the cervix.
Grigsby PW. Radiation Therapy Oncology Group clinical trials for carcinoma of the cervix. The purpose of this paper is to review the primary data of the clinical trials performed by the Radiation Therapy Oncology Group (RTOG) for patients with carcinoma of the uterine cervix. The trials, their strengths, limitations, and the implications of the results are discussed. During the past 25 years there have been several clinical trials performed by the RTOG to test various hypotheses for improving local control and survival for patients with carcinoma of the uterine cervix. The major research themes that have been appraised are the use of hyperbaric oxygen, altered fractionation radiotherapy, hypoxic cell sensitization, chemo-sensitization, prophylactic paraaortic irradiation, and neutron radiotherapy. There are two general research themes. The initial RTOG trials for cervical cancer attempted to address the issues of tumor volume and hypoxic cells while the latter studies addressed these issues and the issue of micrometastatic disease. The phase III clinical trials performed by the RTOG have not demonstrated a local control or survival advantage in the experimental arm with the use of hyperbaric oxygen, split-course radiotherapy, hypoxic cell sensitization, or neutron radiotherapy. Acceptable toxicity and efficacy results were shown in phase II studies evaluating twice-daily irradiation and chemo-sensitization. The positive phase III trials were RTOG 79-20 which evaluated prophylactic paraaortic irradiation in patients with bulky stages IB, IIA, and IIB disease, and RTOG 90-01 which evaluated concurrent chemotherapy. Results of more recent clinical trials are pending their completion.


Sociobehavioral determinants of compliance with health and medical care recommendations.
Over the past two decades, hundreds of articles, editorials, and commentaries have been published describing the considerable disruptive effects on quality of care of individuals noncompliance with health and medical advice. While much research has been directed at determining factors responsible for poor compliance, past studies have tended to focus upon easily measured characteristics of the patients, regimen, or illness which, unfortunately, are usually neither predictive nor alterable. This paper systematically reviews the literature on patient acceptance of recommended health behaviors, attempting to find social-psychological and related variables which have proven to be consistent predictors of compliance. The review suggests that certain health beliefs (especailly personal estimates of vulnerability to, and seriousness of, the disease, and faith in the efficacy of care), health-related motivations, perceptions of psychological and other costs of the recommended action, various aspects of the doctor-patient relationship, and social influence are the most productive dimensions for present intervention and further exploration. Building upon an earlier formulation, an hypothesized model is presented which combines these elements for explaining and predicting compliance behavior. Further research should, with standardized questionnaires and analysis techniques, employ prospective, experimental designs for a variety of population groups, settings, and regimens, to evaluate the ability of practical attempts to modify the model variables and thus enhance compliance.


[Chemical composition of a preparation of the cell walls of Corynebacterium diphtheriae].
The chemical characteristics of 6 batches of the preparation, obtained from the cell wall of C. diphtheriae grown in liquid and solid culture media, with respect to their content of nitrogen, hexoses, pentoses, total amino sugars, lipids and to the possible admixture of nucleic acids are presented. From the results of the chemical analysis of these batches their standardization according to the ratio of total amino sugars and pentoses to total nitrogen in C. diphtheriae cell-wall preparation is proposed.


The Application of Liver Stiffness Measurement in Residents Without Overt Liver Diseases Through a Community-Based Screening Program.
The application of liver stiffness measurement (LSM) by transient elastography (TE) in general population remains to clarify. This cohort study aimed to examine the usefulness of TE and to identify factors associated with significant liver fibrosis in community-based population.We conducted a hepatitis screening program in 2 remote villages of Southern Taiwan. All residents participated voluntarily and received questionnaire evaluation, blood tests, abdominal sonography, and LSM by TE. Residents with any one of following criteria including hepatitis B virus infection, hepatitis C virus infection, more than moderate alcohol drinking, and failure to obtain valid or reliable LSM were excluded.There were 831 residents participated in program. The valid and reliable LSM were obtained in 98.3% and 96.3% of residents, respectively. Finally, a total of 559 residents including 283 residents with nonalcoholic steatotic fatty liver disease (NAFLD) were enrolled for analysis. The mean liver stiffness was 4.9 ± 1.9 kPa. The liver stiffness increased in residents with diabetes mellitus (DM), higher body mass index (BMI), hypertension, abnormal waist-hip circumference ration (WHR), higher waist circumference (WC), and presence of fatty liver. Higher body weight, higher BMI, higher WC, abnormal WHR, abnormal aspartate aminotransferase (AST), abnormal alanine aminotransferase (ALT), and DM were the factors associated with significant fibrosis (liver stiffness ≥7 kPa) in either all participants or NAFLD residents. As determined by multivariate analysis, abnormal AST values and DM were the 2 independent factors in all participants (abnormal AST: OR 3.648, 95% CI 1.134-11.740, P = 0.03; DM: OR 2.882, 95% CI 1.282-6.478, P = 0.01) and in residents with NAFLD (abnormal AST: OR 4.197, 95% CI 1.154-15.262, P = 0.03; DM: OR 3.254, 95% CI 1.258-8.413, P = 0.02).LSM by TE is a useful screening tool in community. In residents, who were absence of chronic hepatitis virus infection or consumed less than moderate alcohol drinking, exhibited DM or abnormal AST values may consider a substantial group with significant fibrosis in community.


Microearthquake imaging of the parkfield asperity.
Microearthquake data from a downhole seismometer network on the San Andreas fault appear to outline two aseismic asperities that may correspond to the locations of the foreshocks and main shocks of the Parkfield characteristic earthquakes. The source parameters of the microearthquakes show that a few of the earthquakes have significantly higher stress drops than most. Furthermore, the magnitude-frequency statistics suggest that at local magnitude 0.6, the cumulative number of small events begins to fall off the usual Gutenberg-Richter (b = -1) relation, in which the number of events increases exponentially with decreasing magnitude. The downhole seismometer data establish a baseline from which the evolution of the earthquake process at Parkfield can be monitored and suggest that different mechanical conditions than those that lead to the typical Gutenberg-Richter relation may be operating for the smallest of Parkfield microearthquakes.


Intrinsic ferroelectric coercive field
The Landau-Ginzburg theory of ferroelectricity predicts the intrinsic coercive field for polarization reversal, but the observed extrinsic coercive field is always much smaller as a result of nucleation, dynamic processes not covered by the static theory. We have realized the intrinsic coercive field for the first time, in two-dimensional Langmuir-Blodgett polymer films as thin as 1 nm. The measured coercive field is in good agreement with the theoretical intrinsic value, exhibits the expected dependence on temperature, and does not depend on thickness below 15 nm.


Regulation of glutamate-synthesizing enzymes by NMDA and potassium in cerebellar granule cells.
The presence of 25 mm potassium (KCl) or N-methyl-d-aspartate (NMDA) in cultured cerebellar granule neurons (CGN) induces a trophic effect, including a specific regulation of the enzymes involved in the glutamate neurotransmitter synthesis. In this study we explored the effect of these conditions on the cytosolic and mitochondrial isoenzymes of aspartate aminotransferase (AAT), and phosphate-activated glutaminase (PAG) in CGN. We found that NMDA and KCl increased the AAT total activity by 40% and 70%, respectively. This effect was mediated by an augmentation in the protein levels (68% by NMDA, 58% by KCl). NMDA raised the Vmax and KCl raised both the maximol velocity (Vmax) and Michaelis constant (Km) of AAT. NMDA increased cytosolic AAT activity by 30% and mitochondrial activity by 70%; KCl increased cytosolic and mitochondrial AAT activity by 60% and 100%, respectively. This activation was also related to an increase in the protein levels. The effect of both conditions on the activity and protein levels were more pronounced in mitochondrial than cytosolic AAT and the increment elicited by KCl was higher in both isoforms than that produced by NMDA. The PAG and AAT mRNA levels were also regulated by incubation with NMDA and KCl similarly to the observed changes in the protein levels. These results suggest that NMDA receptor stimulation during CGN development differentially regulates the two AAT isoenzymes involved in the maturation of CGN and that the regulation of both AAT and PAG occurs also at the mRNA expression level, suggesting the involvement of a mechanism of gene expression regulation.


Plasmonic behaviors of metallic AZO thin film and AZO nanodisk array.
Aluminum-doped zinc oxide (AZO) is well known as transparent conducting material for electro-optical devices, but is rarely used as plasmonic material, particularly on the localized surface plasmon resonance (LSPR) behavior of AZO nanostructure and its plasmonic devices. In this study, we systematically investigate the plasmonic behaviors of AZO thin films and patterned AZO nanostructures with various structural dimensions under different annealing treatments. We find that AZO film can possess highly-tunable, metal-like, and low-loss plasmonic property and the LSPR characteristic of AZO nanostructure is observed in the near-infrared (NIR) region under proper annealing conditions. Finally, environmental index sensing is performed to demonstrate the capability of AZO nanostructure for optical sensing application. High index sensitivity of 873 nm per refractive index unit (RIU) variation is obtained in experiment.


A study of the nature of the immediate precursor of the extracellular -amylase of Bacillus amyloliquefaciens. A reappraisal.
1. A defined medium was devised for use in washed-cell experiments with post-exponential-phase cultures of Bacillus amyloliquefaciens. The medium allowed alpha-amylase to be secreted, bacterial concentration to increase and l-[U-(14)C]valine to be incorporated into protein at a linear rate, which was the same as in a post-exponential-phase culture, for up to 6h. 2. Determination of the specific radioactivity of l-[U-(14)C]valine in the medium, the intracellular amino acid pool, the cellular protein and the isolated alpha-amylase, after a 3h incubation of washed cells in the defined medium, showed that at least 76% of the alpha-amylase secreted was synthesized de novo. 3. By isolating the alpha-amylase formed during a 6h incubation in the presence of l-[U-(14)C]valine it was shown that the specific radioactivity of the N-terminal valine, within the limits of experimental error, was the same as that of the total valine residues from the complete alpha-amylase molecule. 4. A consideration of these results in relation to the whole literature on the subject strongly supports the idea that there is no reason to suppose that extracellular alpha-amylase is formed from a high-molecular-weight precursor in B. amyloliquefaciens and closely related organisms with identical characteristics of exoenzyme secretion.


[HIV and related infections in Italian penal institutions: epidemiological and health organization note].
HIV and other infections represent an important health problem in Italian jails. In particular, HIV prevalence is high, due to the characteristics of the prison population, which is constituted by a large proportion of injecting drug users and foreigners. In addition, data from other countries suggest that risky behaviour are not uncommon during imprisonment, and transmission of HIV and other infection in this setting may also occur. Data from surveys conducted by the Penitentiary Authority in Italian jails show a decline of HIV seroprevalence from 9.7% in 1990 to 2.6% in 2001. However, these data are largely incomplete and do not account for possible biases due to self-selection of inmates toward HIV serological testing or to variations in the access to screening activities. More accurate data, possibly obtained through anonymous unlinked surveys, are needed in order to better plan health services and preventive measures.


Role of Regular Physical Activity in Neuroprotection against Acute Ischemia.
One of the major obstacles that prevents an effective therapeutic intervention against ischemic stroke is the lack of neuroprotective agents able to reduce neuronal damage; this results in frequent evolution towards a long-term disability with limited alternatives available to aid in recovery. Nevertheless, various treatment options have shown clinical efficacy. Neurotrophins such as brain-derived neurotrophic factor (BDNF), widely produced throughout the brain, but also in distant tissues such as the muscle, have demonstrated regenerative properties with the potential to restore damaged neural tissue. Neurotrophins play a significant role in both protection and recovery of function following neurological diseases such as ischemic stroke or traumatic brain injury. Unfortunately, the efficacy of exogenous administration of these neurotrophins is limited by rapid degradation with subsequent poor half-life and a lack of blood-brain-barrier permeability. Regular exercise seems to be a therapeutic approach able to induce the activation of several pathways related to the neurotrophins release. Exercise, furthermore, reduces the infarct volume in the ischemic brain and ameliorates motor function in animal models increasing astrocyte proliferation, inducing angiogenesis and reducing neuronal apoptosis and oxidative stress. One of the most critical issues is to identify the relationship between neurotrophins and myokines, newly discovered skeletal muscle-derived factors released during and after exercise able to exert several biological functions. Various myokines (e.g., Insulin-Like Growth Factor 1, Irisin) have recently shown their ability to protects against neuronal injury in cerebral ischemia models, suggesting that these substances may influence the degree of neuronal damage in part via inhibiting inflammatory signaling pathways. The aim of this narrative review is to examine the main experimental data available to date on the neuroprotective and anti-ischemic role of regular exercise, analyzing also the possible role played by neurotrophins and myokines.


Assisting physicians in decision-making.
The American Medical Association's long-standing commitment to improving the quality of medical care has been marked by a variety of efforts, from improvement of medical education and accreditation to technology assessment and peer review. But with increasing nationwide attention on evaluating quality of care, the AMA, as well as many other physician organizations, has focused on developing practice parameters that identify appropriate medical care.


[Biological testing of water with different structural states in rats and frogs].
The effect of water samples with different structural states on some physiological indices of white laboratory rats, 5 groups of 10 animals (5 females and 5 males) and frogs has been studied. The investigation was performed for 1 month. For the determination of the content of liquid crystal associates (LCA) in water samples there was used the dilatometric method, the performance of experimental animals was studied by the swimming test (up to total fatigue). The performed experiment on growing rats with the use of water with varying degrees of structuredness showed that according to the weight gain there were optimal water "Lekor" and tap water, treated with Bioptron (the content of the structured fraction is 5.06 +/- 0.09% and 6.9 +/- 0.23%, respectively). On physical performance the best indices were in animals consumed water treated with the Bioptron lamp. In performance of experiments on frogs it was found that cardiac function in animals under experimental conditions over time weakens spontaneously: heart rate and cardiac output decline. Therefore, the effect of different water samples on the cardiac function was assessed on the intensity of its decrease for 15 minutes. In the experimental study of the effect of water with different content of LCA on heart rate and cardiac output of the frog it was found that the optimum level of structuredness of water is within the range of 5.06 +/- 0.09% (in water "Lekor") - 6.9 +/- 0.23% (tap water treated with Bioptron). All the other water samples, the content of nanocrystals in which was below or above this range, has a pronounced inhibitory effect on the heart performance of the frog.


[Compensatory and adaptive changes in the heart after pulmonary resection (morphometric analysis)].
The experiment has been performed in 124 non-inbred dogs by means of a complex of morphometrical methods in order to study compensatory-adaptive processes in the heart after pulmonary resection various in its volume. After 58% resection, and especially after 67-75% resection of the lung mass, a stable pulmonary arterial hypertension appears; it results in development of a chronic cor pulmonale and terminates in its decompensation. Application of extrapulmonary arterio-venous anastomosis, before 67-75% of the pulmonary parenchyma is resected, decreases hypertension in the pulmonary circulation, improves adaptive changes of the heart in the newly formed conditions of hemodynamics, preventing development of its failure.


Development and Characterization of an Antimicrobial Polydopamine Coating for Conservation of Humpback Whales.
Migration patterns of humpback whales have been monitored using 316L stainless steel (SS) satellite telemetry tags. The potential for tissue infection and necrosis is increased if the bacteria, naturally a part of the diverse microbiome on the skin of humpback whales, can adhere to and colonize the surface of the tags. Polydopamine (pDA) has the potential to prevent the adhesion of one of the most prevalent bacterial strains on the surface of the skin of cetaceans (Psychrobacter) through the release of hydrogen peroxide. The release of hydrogen peroxide from the pDA coatings (40-100 μM) has the ability to induce a bacteriostatic response in E. coli, a commonly used bacteria strain in antimicrobial studies and potentially P. cryohalolentis, a common humpback associated bacteria. The H2O2 dose required to induce bacteriostatic conditions in E. coli is approximately 60 μM and in P. cryohalolentis is 100 μM. Bacterial adhesion on the surface of pDA coated SS coupons was measured first using E. coli. The coating successfully prevented adhesion of E. coli on the surface of SS coupons under certain conditions (60% reduction, p < 0.05) but the same was not seen with P. cryohalolentis. When coating conditions were altered (an increase in pH and temperature) the adhesion of P. cryohalolentis was reduced (80% reduction, p < 0.001). Overall, the pDA coatings have the capacity to generate varying amounts of hydrogen peroxide by altering the coating conditions and have the ability to reduce bacterial adhesion on the surface of satellite telemetry tags, and therefore the potential to increase tag functional service lifetime.


Students' perspectives on their skills acquisition and confidence.
To investigate students' perspectives on their skills acquisition and knowledge during the foundation year of their nursing programme, and whether this improved students' levels of competence and confidence. Two groups of nursing students (n=140) responded to a clinical acquisition skills survey (CASS) to elicit their perceptions of clinical skills acquisition. Additionally, students' competence levels were examined, drawing comparisons with the students' objective, structured clinical examination (OSCE) results. Students identified that the curriculum supported the acquisition of clinical skills, and clinical examination results confirmed that 95% of students were competent to pass their OSCE. Students' responses to items that related to perceived confidence and competence levels were positive. This indicates that the introduction of clinical skills teaching and assessment within a university's simulation suites augmented with structured assessment within the clinical environment improved the acquisition of clinical skills.


Rectal Culture-Guided Targeted Antimicrobial Prophylaxis Reduces the Incidence of Post-Operative Infectious Complications in Men at High Risk for Infections Submitted to Transrectal Ultrasound Prostate Biopsy - Results of a Cross-Sectional Study.
The role of rectal culture-guided antimicrobial prophylaxis (TAP) in reducing infectious complications (IC) after transrectal-ultrasound prostate biopsy (TRUSPBx) is conflicting. We assessed the prevalence of IC in a cohort of men at high risk for IC submitted to TRUSPBx and treated with either TAP or empirical prophylaxis (EAP). Data from 53 patients at high risk for IC undergoing TRUSPBx were collected. Patients who did not receive a rectal swab (RS) were treated with EAP with fluoroquinolones (FQs). Of those who received the RS, patients with FQ-susceptible organisms received ciprofloxacin while those with FQ-resistant organisms received TAP. Office visits were scheduled to investigate the rate of complication at day 7 and 30 after TRUSPBx. Comorbidities were scored with the Charlson Comorbidity Index (CCI). Descriptive statistics and logistic regression models detailed the association between clinical parameters and IC rate. Out of 53 men, 17 (32.1%) had RS while 36 (67.9%) did not. All RS cultures were positive for E. Coli and 4 (23.5%) reported FQ-resistant pathogens. Considering risk factors for IC, no difference was found in terms of CCI, rate of diabetes, UTIs or recent antibiotic utilization between groups. Overall, 12 (22.6%) men reported IC, with a greater proportion of them belonging to the group treated with EAP (30.6% vs 5.9%; p = 0.045). Of these, 9 (25.0%) patients, all treated with EAP, developed post biopsy UTIs. E. Coli sustained all UTIs and 7 (77.7%) were FQ resistant. At multivariable analysis, CCI≥1, a history of UTIs/prostatitis and recent antibiotic utilization (all p<0.04) were the most powerful predictors for ICs. In conclusion, we found that compared to EAP, TAP significantly reduces ICs, in men at high risk for post TRUSPBx IC. Patients at risk for IC, especially those with recent antibiotic utilization, CCI≥1 and a history of UTIs/prostatitis before biopsy, could benefit from TAP.


The charge carrier dynamics, efficiency and stability of two-dimensional material-based perovskite solar cells.
Perovskites have been firmly established as one of the most promising materials for third-generation solar cells. There remain several great and lingering challenges to be addressed regarding device efficiency and stability. The photovoltaic efficiency of perovskite solar cells (PSCs) depends drastically on the charge-carrier dynamics. This complex process includes charge-carrier generation, extraction, transport and collection, each of which needs to be modulated in a favorable manner to achieve high performance. Two-dimensional materials (TDMs) including graphene and its derivatives, transition metal dichalcogenides (e.g., MoS2, WS2), black phosphorus (BP), metal nanosheets and two-dimensional (2D) perovskite active layers have attracted much attention for application in perovskite solar cells due to their high carrier mobility and tunable work function properties which greatly impact the charge carrier dynamics of PSCs. To date, significant advances have been achieved in the field of TDM-based PSCs. In this review, the recent progress in the development and application of TDMs (i.e., graphene, graphdiyne, transition metal dichalcogenides, BP, and others) as electrodes, hole transporting layers, electron transporting layers and buffer layers in PSCs is detailed. 2D perovskites as active absorber materials in PSCs are also summarized. The effect of TDMs and 2D perovskites on the charge carrier dynamics of PSCs is discussed to provide a comprehensive understanding of their optoelectronic processes. The challenges facing the PSC devices are emphasized with corresponding solutions to these problems provided with the overall goal of improving the efficiency and stability of photovoltaic devices.


Preoperative false-negative transthoracic echocardiographic results in native valve infective endocarditis patients: a retrospective study from 2001 to 2018.
Infective endocarditis (IE) is a lethal disease that is difficult to diagnosis early. Although echocardiography is one of the most widely used diagnostic technique, it has limited sensitivity. This study surveyed the clinical features of IE patients who underwent surgery and compared transthoracic echocardiography and histological findings to explore the factors related to false-negative echocardiographic results. Medical records were extracted from IE patients consecutively hospitalized between June 2001 and June 2018. A total of 182 patients with native valve IE who underwent surgery were included. Compared to the non-surgery group, the surgery group was more likely to have pre-existing valvular lesions and more serious cardiac conditions and a relative lack of signs of infection and cerebrovascular events, leading to a lower proportion of "definite cases" before surgery. The false-negative rate of echocardiography was 14.5%. Echocardiography has significant disadvantages in diagnosing perivalvular abscesses, valve perforations, and left-sided endocarditis, especially for subjects with both aortic and mitral valve infections. The multivariate analysis identified congenital heart disease and small vegetations (< 10 mm) as independent predictors of false-negative echocardiography results. Conversely, fever and heart murmurs on admission served as protective factors. Under some circumstances, echocardiography provides inconsistent results compared with surgical findings, and negative echocardiography results do not rule out IE. The diagnosis of IE depends on comprehensive evaluations using multiple methods.


Psychometric Properties of Patient-Reported Outcome Measures Assessing Self-Efficacy in Patients with Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review.
This systematic review aimed to synthesize the evidence of the psychometric properties of self-efficacy patient-reported outcome measures (PROMs) in patients with chronic obstructive pulmonary disease (COPD). We conducted a systematic search of MEDLINE and other common databases from inception until September 2020. Studies that reported psychometric properties of self-efficacy outcome measures in COPD patients were included. We used the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) 2018 guidelines for data extraction and evidence synthesis. Eighteen studies that assessed nine self-efficacy PROMs were eligible for inclusion. The assessment of structural validity indicated sufficient results rating for the Exercise Self-Regulatory Efficacy Scale and the Self-Care-Self-Efficacy Scale, and insufficient rating for the COPD Self-Efficacy Scale and the Pulmonary Rehabilitation Adaptation Index for Self-Efficacy (PRAISE). Construct validity measures displayed sufficient results rating with correlations ranging from -0.48 to - 0.71 between self-efficacy PROMs and other PROMs such as St. George's Respiratory Questionnaire, Hospital Anxiety and Depression Scale and Chronic Respiratory Questionnaire. Internal consistency measures indicated sufficient rating for all self-efficacy PROMs with a Cronbach's alpha range of 0.71 - 0.98. Responsiveness was assessed for the PRAISE with an overall sufficient rating (effect sizes of 0.21 - 0.37). The evidence regarding the psychometric properties of self-efficacy PROMs in COPD is variable. The PRAISE is responsive to changes in self-efficacy in COPD patients attending a pulmonary rehabilitation program. When using self-efficacy PROMs in clinical practice or research, clinicians and researchers should consider the psychometric properties and choose the appropriate outcome measure based on the purpose.


One-Minute Fish Freshness Evaluation by Testing the Volatile Amine Gas with an Ultrasensitive Porous-Electrode-Capped Organic Gas Sensor System.
In this work, we successfully demonstrate a fast method to determine the fish freshness by using a sensing system containing an ultrasensitive amine gas sensor to detect the volatile amine gas from the raw fish meat. When traditional titration method takes 4 h and complicated steps to test the total volatile basic nitrogen (TVB-N) as a worldwide standard for fish freshness, our sensor takes 1 min to deliver an electrical sensing response that is highly correlated with the TVB-N value. When detecting a fresh fish with a TVB-N as 18 mg/100 g, the sensor delivers an effective ammonia concentration as 100 ppb. For TVB-N as 28-35 mg/100 g, a well-accepted freshness limit, the effective ammonia concentration is as 200-300 ppb. The ppb-regime sensitivity of the sensor and the humidity control in the sensing system are the keys to realizing fast and accurate detection. It is expected that the results in this report enable the development of on-site freshness detection and real-time monitoring in a fish factory.


Effect of β-Substitution and β,β'-Fusion on the Formation of Boron Complexes of Porphycenes.
Boron(III) complexation was investigated in a series of β-substituted porphycenes. Unlike meso-arylporphycenes, these macrocycles undergo a facile complexation reaction. Upon fusion of the β,β'-positions of the porphycene ligand, the complexation resulted in fast insertion of boron, forming the cisoid-B2OF2 complex. However, in the case of the other β-substituted porphycenes, only bis-BF2 complexes formed. The effect of these substituents on the core geometry and photophysical properties are elaborated here.


In vitro interaction of ceftazidime-avibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates.
Combination therapy has been recommended when using ceftazidime-avibactam (CAZ-AVI) for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal combination is unknown. Six common antimicrobial agents (ertapenem, imipenem, meropenem, gentamicin, tigecycline, and ciprofloxacin) were evaluated for synergy with the recently approved cephalosporin-β-lactamase inhibitor combination CAZ-AVI in this study. Different antimicrobial combinations were tested against 13 KPC-Kp, including CAZ-AVI-susceptible (n=11) and resistant (n=2) clinical isolates. In vitro interactions of CAZ-AVI with different antimicrobials were tested using the gradient synergy test. Changes in the minimum inhibitory concentration (MIC) value were interpreted using the fractional inhibitory concentration (FIC) index and susceptible breakpoint index (SBPI). The combination of CAZ-AVI with gentamicin or ciprofloxacin displayed no synergism against any of the KPC-Kp isolates, whereas synergistic activity was observed with imipenem and meropenem against all KPC-Kp isolates. Notably, CAZ-AVI reduced MICs for meropenem and imipenem below the resistance breakpoints against all strains. The SBPI analysis showed that CAZ-AVI in combination with imipenem achieved higher SBPI values than other CAZ-AVI-based combinations. These data suggest that combinations of CAZ-AVI with imipenem may be considered a useful therapeutic option for the treatment of KPC-Kp infections.


Evaluation of the measurement properties of the Perceived Stress Scale (PSS) in Hispanic caregivers to patients with Alzheimer's disease and related disorders.
The Perceived Stress Scale (PSS) is the most widely used measure of perceived stress; however, minimal psychometric evaluation has been performed among Hispanic respondents, and even less among Hispanic caregivers to persons with Alzheimer's disease and related disorders (ADRDs). Secondary data analysis. New York City, NY, USA. A sample of 453 community dwelling Hispanic caregivers to patients with ADRD. Latent variable models were used to evaluate the PSS. Exploratory and confirmatory factor analyses were used to examine unidimensionality. Differential item functioning (DIF) was examined for age, education, and language using the graded item response model. The factor and bifactor analyses results supported essential unidimensionality of the item set; however, positively worded items were observed using response item theory to be less informative than the negatively worded items. Reliability estimates were high. Salient DIF was not observed for age, education, or language of interview using the primary DIF detection method. Sensitivity analyses using a second DIF detection method identified uniform language-DIF for the item, "In the last month, how often have you felt that you were on top of things?" However, the non-compensatory DIF value was below the threshold considered salient. In summary, the 10-item PSS performed well in a sample of English- and Spanish-speaking Hispanic caregivers to patients with ADRD. Very little DIF, and none of high magnitude and impact, was observed. However, the negatively worded items, perhaps because they are more directly reflective of stress, were more informative. In the context of a short-form measure or computerized adaptive test, more informative items are those that would be selected for inclusion.


IgE antibodies in toxoplasmosis.
Toxoplasmosis is a worldwide infection caused by the intracellular parasite Toxoplasma gondii. At least a third of the world human population is infected with the parasite, making it one of the most successful parasitic infections. Primary maternal infection may cause health-threatening sequelae for the fetus, or even cause death of the uterus. Reactivation of a latent infection in immune deficiency conditions such as AIDS and organ transplantation can cause fatal toxoplasmic encephalitis. Toxoplasmosis is a major cause of chorioretinitis, especially in individuals with impaired immune systems. In the acute phase, directly after invading the body, T. gondii begins to multiply rapidly. In the majority of cases acquired toxoplasmosis is asymptomatic. In the second week of infection, specific IgM antibodies are present in the blood. IgE antibodies appear at the same time, slightly preceding specific IgA antibodies. The concentration of IgE can be one of the parameters used for diagnosing an infection with T. gondii. Laboratory diagnosis, i.e. IgE and serologic assays, plays the main role in the diagnosis of congenital infection and assists in the confirmatory diagnosis of toxoplasmic encephalitis and ocular toxoplasmosis. This article is a review of IgE in toxoplasmosis.


The impact of sociodemographic and health-service factors on breast-feeding in sub-Saharan African countries with high diarrhoea mortality.
The current study aimed to examine the impact of sociodemographic and health-service factors on breast-feeding in sub-Saharan African (SSA) countries with high diarrhoea mortality. The study used the most recent and pooled Demographic and Health Survey data sets collected in nine SSA countries with high diarrhoea mortality. Multivariate logistic regression models that adjusted for cluster and sampling weights were used to investigate the association between sociodemographic and health-service factors and breast-feeding in SSA countries. Sub-Saharan Africa with high diarrhoea mortality. Children (n 50 975) under 24 months old (Burkina Faso (2010, N 5710); Demographic Republic of Congo (2013, N 6797); Ethiopia (2013, N 4193); Kenya (2014, N 7024); Mali (2013, N 3802); Niger (2013, N 4930); Nigeria (2013, N 11 712); Tanzania (2015, N 3894); and Uganda (2010, N 2913)). Overall prevalence of exclusive breast-feeding (EBF) and early initiation of breast-feeding (EIBF) was 35 and 44 %, respectively. Uganda, Ethiopia and Tanzania had higher EBF prevalence compared with Nigeria and Niger. Prevalence of EIBF was highest in Mali and lowest in Kenya. Higher educational attainment and frequent health-service visits of mothers (i.e. antenatal care, postnatal care and delivery at a health facility) were associated with EBF and EIBF. Breast-feeding practices in SSA countries with high diarrhoea mortality varied across geographical regions. To improve breast-feeding behaviours among mothers in SSA countries with high diarrhoea mortality, breast-feeding initiatives and policies should be context-specific, measurable and culturally appropriate, and should focus on all women, particularly mothers from low socio-economic groups with limited health-service access.


Acute hemolytic anemia as an initial clinical manifestation of Wilson's disease.
Wilson's disease is an inherited disorder of copper transport in the organism, transmitted in autosomal recessive fashion. It is caused by dysfunction in homologous copper-transporting adenosine triphosphatases. The main clinical symptoms are usually due to hepatic (42%) or/and neurologic (34%) involvement, which is the reason for the name hepatolenticular degeneration. Described in this report are four cases--the first three demonstrate an unusual form of manifestation of Wilson's disease in clinical practice--glucose-6-phosphate dehydrogenase deficiency hemolytic anemia. The fourth case concerns acute intravascular hemolysis that was provoked by the disease and presented without erythrocyte enzyme disturbances. Hemolytic anemia is a recognized but rare (10-15%) complication of the disease. Most often Coombs' negative acute intravascular hemolysis occurs as a consequence of oxidative damage to the erythrocytes by the higher copper concentration. A literature review with discussion of the possible mechanisms for the development of this phenomenon is done.


Evaluating the undescended testis.
This problem is often associated with other anomalies which, if present, are usually evident on the initial examination. Therapy before age two is mandatory to preserve fertility. The malignant potential of undescended testes is well established. Placement of the testes into the scrotum facilitates frequent examinations. All postpubertal patients with intra-abdominal testes, as well as patients who have inguinal testes and are between puberty and age 50, should be referred for orchiectomy.


Chronic pain and analgesic use in CKD: implications for patient safety.
Chronic pain in predialysis CKD is not fully understood. This study examined chronic pain in CKD and its relationship with analgesic usage. Data include baseline visits from 308 patients with CKD enrolled between 2011 and 2013 in the Safe Kidney Care cohort study in Baltimore, Maryland. The Wong-Baker FACES Pain Rating Scale measured chronic pain severity. Analgesic prescriptions and over-the-counter purchases were recorded up to 30 days before visits, and were classified as a drug-related problem (DRP) based on an analgesic's nephrotoxicity and dose appropriateness at participants' eGFR. Participants were sorted by pain frequency and severity and categorized into ordinal groups. Analgesic use and the rate of analgesics with a DRP were reported across pain groups. Multivariate regression determined the factors associated with chronic pain and assessed the relationship between chronic pain and analgesic usage. There were 187 (60.7%) participants who reported chronic pain. Factors associated with pain severity included arthritis, taking ≥12 medications, and lower physical function. Use of nonsteroidal anti-inflammatory drugs was reported by seven participants (5.8%) with no chronic pain. Mild and severe chronic pain were associated with analgesics with a DRP, with odds ratios of 3.04 (95% confidence interval [95% CI], 1.12 to 8.29) and 5.46 (95% CI, 1.85 to 16.10), respectively. The adjusted rate of analgesics with a DRP per participant increased from the group with none to severe chronic pain, with rates of 0.07 (95% CI, 0.04 to 0.13), 0.12 (95% CI, 0.07 to 0.20) and 0.16 (95% CI, 0.09 to 0.27), respectively. Chronic pain is common in CKD with a significant relationship between the severity of pain and both proper and improper analgesic usage. Screening for chronic pain may help in understanding the role of DRPs in the delivery of safe CKD care.


Preserving condensate structure and composition by lowering sequence complexity.
Biological condensates play a vital role in organizing cellular chemistry. They selectively partition biomolecules, preventing unwanted cross-talk and buffering against chemical noise. Intrinsically disordered proteins (IDPs) serve as primary components of these condensates due to their flexibility and ability to engage in multivalent, nonspecific interactions, leading to spontaneous aggregation. Theoretical advancements are critical at connecting IDP sequences with condensate emergent properties to establish the so-called molecular grammar. We proposed an extension to the stickers and spacers model, incorporating non-specific pairwise interactions between spacers alongside specific interactions among stickers. Our investigation revealed that while spacer interactions contribute to phase separation and co-condensation, their non-specific nature leads to disorganized condensates. Specific sticker-sticker interactions drive the formation of condensates with well-defined structures and molecular composition. We discussed how evolutionary pressures might emerge to affect these interactions, leading to the prevalence of low complexity domains in IDP sequences. These domains suppress spurious interactions and facilitate the formation of biologically meaningful condensates. Biomolecular condensates serve as pivotal mechanisms in cellular organization, often characterized by an abundance of intrinsically disordered proteins (IDPs) that undergo frequent mutations in their sequences. Despite this, IDP sequences exhibit non-random patterns, yet the precise relationship between these sequences and the emergent properties of condensates remains unclear. To address this gap, we propose a molecular theory that delineates how various sequence features of IDPs contribute to the organization and composition of condensates. This theory not only sheds light on the evolution of IDPs but also elucidates the emergence of non-random sequence patterns as essential elements for the formation of functional condensates. Correspondingly, we posit that the prevalence of low-complexity regions within IDPs is a result of evolutionary selection.


CD8 T-cell regulation by T regulatory cells and the programmed cell death protein 1 pathway.
The primary function of the immune system is to protect the host from infectious microorganisms and cancers. However, a major component of the immune response involves the direct elimination of cells in the body and the induction of systemic inflammation, which may result in life-threatening immunopathology. Therefore, the immune system has developed complex mechanisms to regulate itself with a specialized subset of CD4 T lymphocytes (referred to as regulatory T cells) and immune checkpoint pathways, such as the programmed cell death protein 1 pathway. These immune regulatory mechanisms can be exploited by pathogens and tumours to establish persistence in the host, warranting a deeper understanding of how to fine-tune immune responses during these chronic diseases. Here, I discuss various features of immune regulatory pathways and what important aspects must be considered in the next generation of therapies to reverse immune exhaustion, understanding that this process is a natural mechanism to prevent the host from destroying itself.


Managed alcohol as a harm reduction intervention for alcohol addiction in populations at high risk for substance abuse.
Managed alcohol programmes (MAP) are a harm reduction strategy used to minimise the personal harm and adverse societal effects that alcohol dependence can lead to by providing an alternative to zero-tolerance approaches that incorporate drinking goals (abstinence or moderation) that are compatible with the needs of the individual, and promoting access to services by offering low-threshold alternatives. This enables clients to gain access to services despite continued alcohol consumption and works to help the patient understand the risks involved in their behaviour and make decisions about their own treatment goals. To assess the effectiveness of MAP treatment regimens (serving limited quantities of alcohol daily to alcoholics) on their own or as compared to moderate drinking (self-controlled drinking), screening and brief intervention using a harm reduction approach, traditional abstinence-based interventions (12 step programmes) and no intervention. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO up to March 2012. This search was expanded by handsearching of high-yield journals and conference proceedings that had not already been handsearched on behalf of The Cochrane Collaboration, searching reference lists of all papers and relevant reviews identified, references to ongoing and recently completed clinical trials in the National Research Register and IFPMA Clinical Trials Database (which contains ClinicalTrials.gov, Centerwatch, Current Controlled Trials and ClinicalStudyResults.gov, and Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali). Trials registers, grey literature and reference lists were also searched. Individuals, organisations and experts in the field were contacted. Randomised control trials (RCT), controlled clinical trials (CCT), interrupted time series (ITS) studies, and control before and after (CBA) studies involving vulnerable people aged 18 years or older who were at high risk for alcohol abuse attending MAP, defined as a structured programme that provided clients with controlled amounts of alcohol on a daily schedule, comparing no treatment, moderate drinking, brief intervention or 12-step variants. All study citations were collated into a single database. Two review author independently screened titles and abstracts and selected references potentially relevant to the review. Differences between selection lists were resolved by discussion. Two review authors independently evaluated whether studies should be included or excluded according to the eligibility criteria. In the event of a disagreement, a third author was consulted. No studies were included in the review. This systematic review was intended to assess the effectiveness of a brief MAP on the reduction of incidence of harmful behaviour; however, no evidence was available to make this comparison; 22 articles were considered possibly relevant and all were excluded. Most articles were excluded because they failed to compare or consider managed alcohol as the experimental or control intervention, as well as one study (Baker 2010), which was also excluded because study participants were under 18 years of age. No study reviewed offered an intervention that was compared with managed alcohol or considered it as the intervention of interest, providing insufficient evidence to address the objectives of the review. Four studies (Aalto 2001; Baker 2010; Bertholet 2005; Tracy 2007) considered alcohol reduction as an outcome of interest, while four engaged interventions in a shelter setting or targeted vulnerable people (Baker 2010; Bradford 2005; Lapham 1993; McGlynn 1993); only one study (Kidd 2011) offered a qualitative assessment of a participant being admitted to MAP, but offered no analysis of the programme itself. These results accurately reflect the use of MAPs in current practice as existing programmes are ongoing only in a small number of sample pilot projects that target individuals with severe alcohol dependence or who consume non-beverage alcohol. The lack of evidence does not allow for a conclusion regarding the efficacy of MAP on their own, or as compared to brief intervention, moderate drinking, no intervention or 12-step variants. It is the review authors' opinion that it is likely to be the objective of MAPs that reduce their reportability and use in current practice, rather than a failure to provide an intervention that reduces the effects of alcohol dependence. Aiming to reduce harmful or antisocial behaviour in vulnerable individuals through the regulation of daily alcohol intake, rather than reducing harmful alcohol intake over time, provides considerable difficulty in developing measures of success from self-reported data (low treatment thresholds), monitoring long-term efficacy or establishing causal links between programme admission and a reduction in targeted behaviours, owing to the fact that prolonged participation in the programme is likely to indicate a willingness in the individual to change their behaviour patterns. More effort is needed to develop reporting measures, as well as methodologies, which address these specific challenges.


Effects of L-arginine on flow mediated dilatation induced by atrial pacing in diseased epicardial coronary arteries.
To examine the effects of L-arginine on basal coronary tone and flow mediated dilatation induced by atrial pacing in patients with coronary artery disease and stable angina. Atrial pacing was performed during intracoronary infusions of normal saline and L-arginine (150 micromol/min) in 8 patients with coronary artery disease and stable angina. The luminal diameter of epicardial coronary arteries was assessed by quantitative angiography. L-arginine administration significantly increased the diameter of all the coronary segments and stenoses. During atrial pacing with saline infusion, luminal diameter of the proximal, distal, and stenosis reference segments increased significantly (p < 0.01 versus saline) but stenosis diameter did not change. L-arginine administration did not change the magnitude (NS) of atrial pacing induced dilatation in proximal and distal segments and in coronary stenoses and their reference segments. Non-stenotic segments of diseased coronary arteries dilate in response to atrial pacing but stenoses do not. L-arginine dilates coronary segments and stenoses but does not increase the magnitude of the response to atrial pacing in proximal and distal segments and in coronary stenoses and their reference segments. These findings provide evidence that the shear stress responsive mechanism is absent at stenoses but present in non-stenotic segments of diseased coronary arteries. They also indicate a relative deficiency of L-arginine, except in the shear response mechanism.


Does neuroticism in adolescents moderate contextual and explicit threat cue modulation of the startle reflex?
This study evaluated the relationship between neuroticism (N), a probable risk factor for emotional disorders, and modulation of startle reflexes (SRs). One hundred thirty-two adolescents with varying levels of N but without anxiety or depressive disorders were evaluated in contextual cue and explicit threat cue paradigms. Within the explicit threat cue paradigm, N potentiated SRs more in conditions that were intermediately associated with threat of an aversive biceps contraction than conditions that were the furthest from and conditions that were the closest to the same threat. Also, N potentiated SRs across the entire experiment, regardless of experimental conditions, in male and not in female subjects. These results suggest that adolescents with high levels of N show greater sensitivity to contexts intermediately associated with threat. Results are discussed in comparison with other studies of groups at risk for anxiety and depressive disorders.


[Effect of infectious factors on human and animal cytogenetic structures].
The analysis of blood leucocyte chromosomes has been carried out on 60 patients with different infectious diseases (influenza, measles, scarlet fever, and disentery), and on 47 patients immunized against measles, tick-born encephalitis, typhoid fever and brucellosis. The mutagenic influence of viruses on the genital cells of mice and on the human somatic cells in vitro was studied. Both viruses and bacteria appeared to be able to bring about different breaks in human and animal cells.


[Arteriosinus anastomoses of the posterior cranial fossa (pathologic anatomy)].
Postmortem examination of the brain of 10 patients with occipito-sinus anastomoses showed that the morphological basis of this vascular pathology is an anatomical developmental defect of vessels of the system of the external and internal carotid arteries and dura mater sinuses with disturbed histological structure of their walls. Severe abnormality of calcium metabolism of the type of systemic calciphilaxis with involvement of the brain and viscera is encountered simultaneously in some cases. The combination of these pathological processes leads finally to gradually increasing circulatory disorders, brain hypoxia, and severe damage to the brain matter.


Activities of key enzymes in sucrose-to-starch conversion in wheat grains subjected to water deficit during grain filling.
This study tested the hypothesis that a controlled water deficit during grain filling of wheat (Triticum aestivum) could accelerate grain-filling rate through regulating the key enzymes involved in Suc-to-starch pathway in the grains. Two high lodging-resistant wheat cultivars were field grown. Well-watered and water-deficit (WD) treatments were imposed from 9 DPA until maturity. The WD promoted the reallocation of prefixed 14C from the stems to grains, shortened the grain-filling period, and increased grain-filling rate or starch accumulation rate (SAR) in the grains. Activities of Suc synthase (SuSase), soluble starch synthase (SSS), and starch branching enzyme (SBE) in the grains were substantially enhanced by WD and positively correlated with the SAR. ADP Glc pyrophosphorylase activity was also enhanced in WD grains initially and correlated with SAR with a smaller coefficient. Activities of granule-bound starch synthase and soluble and insoluble acid invertase in the grains were less affected by WD. Abscisic acid (ABA) content in the grains was remarkably enhanced by WD and very significantly correlated with activities of SuSase, SSS, and SBE. Application of ABA on well-watered plants showed similar results as those by WD. Spraying with fluridone, an ABA synthesis inhibitor, had the opposite effect. The results suggest that increased grain-filling rate is mainly attributed to the enhanced sink activity by regulating key enzymes involved in Suc-to-starch conversion, especially SuSase, SSS, and SBE, in wheat grains when subjected to a mild water deficit during grain filling, and ABA plays a vital role in the regulation of this process.


Thiazolidinediones: a new class of drugs for the therapy of ischemia-reperfusion injury.
Synthetic peroxisome proliferator-activated receptor gamma (PPAR-gamma) ligands shown to induce adipocyte differentiation and increase insulin sensitivity, thiazolidinediones have recently been implicated as regulators of cellular inflammatory and ischemic responses. Thiazolidinediones inhibit the activity of a number of transcriptional factors, including nuclear factor-gammaB, activating protein 1, signal transducers and activated T cells, and early response gene 1 by either PPAR-gamma-dependent or -independent mechanisms. Recent experimental studies demonstrated a dramatic protection by thiazolidinediones against cardiac, gastrointestinal and lung injury after ischemia-reperfusion, in addition to a significant reduction in infiltrating neutrophils. These reports have hypothesized that the inhibition of neutrophil-mediated inflammation by thiazolidinediones is involved in the reduction of ischemia-reperfusion-induced tissue injury. Altogether, recent findings suggest that thiazolidinediones could represent a novel therapeutic approach to reducing or preventing reperfusion injury.


Botulinum toxin A injection into corrugator muscle for frontally localised chronic daily headache or chronic tension-type headache.
To describe our results with botulinum toxin type A injection for headache in carefully selected patients, and to present the rationale behind this therapy. Tertiary referral centre. This article describes a case series of 10 consecutive patients with frontally localised headache, whose pain worsened when pressure was applied at the orbital rim near the supratrochlear nerve. The patients received a local anaesthetic nerve block with Xylocaine 2 per cent at this site. If this reduced the pain, they were then offered treatment with botulinum toxin. Injection with 12.5 IU of botulinum toxin A into the corrugator supercilii muscle on both sides (a total of 25 IU). Pain severity scoring by the patients, ranging from zero (no pain) to 10 (severe pain) on a verbal scale. Following injection, all patients had less pain for approximately two months. This treatment did not appear to have lasting side effects. Xylocaine injection is a good predictor of the effectiveness of botulinum toxin injection into the corrugator muscle as treatment of frontally localised headache. We hypothesise that this pain is caused by entrapment of the supratrochlearis nerve in the corrugator muscle. Furthermore, we found botulinum toxin injection to be a safe and effective means of achieving pain relief in this patient group.


E3 Ligase cIAP2 Mediates Downregulation of MRE11 and Radiosensitization in Response to HDAC Inhibition in Bladder Cancer.
The MRE11/RAD50/NBS1 (MRN) complex mediates DNA repair pathways, including double-strand breaks induced by radiotherapy. Meiotic recombination 11 homolog (MRE11) is downregulated by histone deacetylase inhibition (HDACi), resulting in reduced levels of DNA repair in bladder cancer cells and radiosensitization. In this study, we show that the mechanism of this downregulation is posttranslational and identify a C-terminally truncated MRE11, which is formed after HDAC inhibition as full-length MRE11 is downregulated. Truncated MRE11 was stabilized by proteasome inhibition, exhibited a decreased half-life after treatment with panobinostat, and therefore represents a newly identified intermediate induced and degraded in response to HDAC inhibition. The E3 ligase cellular inhibitor of apoptosis protein 2 (cIAP2) was upregulated in response to HDAC inhibition and was validated as a new MRE11 binding partner whose upregulation had similar effects to HDAC inhibition. cIAP2 overexpression resulted in downregulation and altered ubiquitination patterns of MRE11 and mediated radiosensitization in response to HDAC inhibition. These results highlight cIAP2 as a player in the DNA damage response as a posttranscriptional regulator of MRE11 and identify cIAP2 as a potential target for biomarker discovery or chemoradiation strategies in bladder cancer. Cancer Res; 77(11); 3027-39. ©2017 AACR.


The dynamics of Enterococcus transmission from bacterial reservoirs commonly encountered by anesthesia providers.
Enterococci, the second leading cause of health care-associated infections, have evolved from commensal and harmless organisms to multidrug-resistant bacteria associated with a significant increase in patient morbidity and mortality. Prevention of ongoing spread of this organism within and between hospitals is important. In this study, we characterized Enterococcus transmission dynamics for bacterial reservoirs commonly encountered by anesthesia providers during the routine administration of general anesthesia. Enterococcus isolates previously obtained from bacterial reservoirs frequently encountered by anesthesiologists (patient nasopharynx and axilla, anesthesia provider hands, and the adjustable pressure-limiting valve and agent dial of the anesthesia machine) at 3 major academic medical centers were identified as possible intraoperative bacterial transmission events by class of pathogen, temporal association, and phenotypic analysis (analytical profile indexing). They were then subjected to antibiotic disk diffusion sensitivity for transmission event confirmation. Isolates involved in confirmed transmission events were further analyzed to characterize the frequency, mode, origin, location of transmission events, and antibiotic susceptibility of transmitted pathogens. Three hundred eighty-nine anesthesia reservoir isolates were previously identified by gross morphology and simple rapid tests as Enterococcus. The combination of further analytical profile indexing analysis and temporal association implicated 43% (166/389) of those isolates in possible intraoperative bacterial transmission events. Approximately, 30% (49/166) of possible transmission events were confirmed by additional antibiotic disk diffusion analysis. Two phenotypes, E5 and E7, explained 80% (39/49) of confirmed transmission events. For both phenotypes, provider hands were a common reservoir of origin proximal to the transmission event (96% [72/75] hand origin for E7 and 89% [50/56] hand origin for E5) and site of transmission (94% [16/17] hand transmission location for E7 and 86% [19/22] hand transmission location for E5). Anesthesia provider hand contamination is a common proximal source and transmission location for Enterococcus transmission events in the anesthesia work area. Future work should evaluate the impact of intraoperative hand hygiene improvement strategies on the dynamics of intraoperative Enterococcus transmission.


Reduction of acrylamide in whole-wheat bread by combining lactobacilli and yeast fermentation.
This study mainly focuses on a strategy for reducing acrylamide content in whole-wheat bread by combining lactobacilli and yeast in sourdough breadmaking. Combinations of sourdough (fermented dough using different Lactobacillus strains including Lactobacillus plantarum PTCC 1896 [probiotic], L. sakei DSM 20,017, L. rhamnosus DSM 20,021, and L. delbrueckii DSM 20,081) and yeast, in comparison with yeast alone, were used for breadmaking. The results showed that acrylamide levels in breads fermented using sourdough+yeast were in all cases much lower (6.9-20 μg/kg on a dry weight basis [d.b.]) than those in the yeast-only fermented bread (47.6 μg/kg d.b.). Significant (p < 0.05) correlations were also found between pH, total titratable acids (TTA) and lactic acid, and acrylamide content. Furthermore, the obtained results showed that the moisture content of dough directly influenced the formation of acrylamide in bread (r = 0.925, p < 0.0001). In addition, no significant correlations were observed between acrylamide content in breads and either the reducing sugar or free amino acid contents in dough samples. According to the different effects of Lactobacillus strains, it could be concluded that the acrylamide reducing potential of lactobacilli was strain-specific, with L. rhamnosus being the most effective. This suggests that sourdough fermentation with appropriate Lactobacillus strains can be used as an advantageous technology to reduce the acrylamide content of whole-wheat breads.


Prenatal ultrasonographic diagnosis of generalized arterial calcification of infancy.
A healthy 19-year-old nulliparous pregnant woman was referred to our clinic because of fetal pericardial effusion and ascites. The sonographic examination performed at 28 weeks' gestation revealed scalp edema, severe skin edema, bilateral hydrocele, ascites, and pleural and pericardial effusion. Fetal echocardiographic examination showed that both ventricles were dilated with severely depressed contractility. The aortic annulus, ascending aorta, aortic arch, descending aorta, common iliac arteries, main pulmonary artery, tricuspid valve, and mitral chordae tendinae were hyperechogenic. Right ventricular outflow tract was narrow with decreased blood flow. There was tricuspid and mitral valve regurgitation and tricuspid valve stenosis. On the basis of these findings, we made the diagnosis of generalized arterial calcification, which is characterized by extensive calcification of internal elastic lamina and intimal proliferation of medium-sized and large arteries. This diagnosis was confirmed histologically after the termination of pregnancy.


[Epilepsy and learning: a neuropsychological approach].
The quality of life of an epileptic patient largely depends on the interplay of the control of the convulsive crises and the degree to which higher mental functions are affected. Some types of epilepsy lead to mental retardation during development and with others the basic cerebral mechanisms for processing data are damaged and this may lead to transient or permanent cogniscitive deterioration. There are certain important clinical factors such as the site of the discharge regarding the lobe, hemisphere, type of cerebral area involved and the age of the patient. We describe the clinical features of each type of epilepsy with respect to focal or generalized involvement. The subclinical effects of continuous discharges affects processing in the areas involved and therefore intellectual function, thus leading to a secondary learning disorder. The neuropsychological tests used in investigation of higher cerebral functions in epilepsy include, in general, tests to assess speed of processing, attention, memory, reasoning and visuospacial ability and frontal executive functions. These tests should be sufficiently sensitive so as to detect minimal changes in the state of the illness, the time elapsed and the medication given. Anticonvulsant drugs may themselves cause changes in mental functions. There may often be mixed neurocognitive behaviour depending on the drug used. There may also be transient cognitive deterioration.


C-reactive protein concentration as a significant correlate for metabolic syndrome: a Chinese population-based study.
Increasing evidence suggests that chronic, low-grade inflammation may be a common soil involving the pathogenesis of metabolic syndrome (MetS) and cardiovascular disease. We examined the association between C-reactive protein (CRP) concentration, an extensively studied biomarker of low-grade inflammation, and the MetS in a representative sample of Chinese adults in Taiwan. We performed a cross-sectional analysis of data from 4234 subjects [mean (±SD) age, 47.1 (±18.2) years; 46.4 % males] who participated in a population-based survey on prevalences of hypertension, hyperglycemia, and hyperlipidemia in Taiwan. CRP levels were measured by the immunoturbidimetric CRP-latex high-sensitivity assay. The MetS was defined by an unified criteria set by several major organizations. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated with logistic regression model. Overall, there were 938 subjects with MetS among 4,234 participants, resulting in a prevalence rate of 22.1 %. A significantly progressive increase in the prevalence of MetS across quartiles of CRP was observed (p for trend <0.001). Participants in the second, third, and upper quartiles of CRP had significantly higher risk of having MetS when compared with those in the lowest quartile [adjusted ORs (95 % CIs) were 2.18 (1.62-2.94), 4.39 (3.31-5.81), and 7.11 (5.39-9.38), respectively; p for trend <0.001]. Furthermore, there was a strong stepwise increase in CRP levels as the number of components of the MetS increased. The prevalence of MetS showed a graded increase according to CRP concentrations. The possible utility of CRP concentration as a marker for MetS risk awaits further evaluation in prospective studies.


Histopathological Analysis in Testicular Tumors: 10 Years of Experience.
Introduction. This study aims to review the morphological and immunohistochemical features of testicular tumors and compare them with prognostic parameters. Methods. Testicular tumors diagnosed between January 2011 and September 2021 were reviewed. Patient age, tumor subtype, size, spread, lateralization, number of foci, and immunohistochemical results were recorded. Results. A total of 121 tumors were detected, of which 108 (89%) were germ cell tumors (GCTs). Of the germ cell tumors, 70 (65%) were found to be pure type, and 38 (35%) were mixed germ cell tumors. The ratio of pure seminoma among GCTs was 56/108 (52%). Lymphatic/vascular invasion (LVI) was detected in 48/121 (40%), rete testis invasion in 32/121 (26%), hilar soft tissue invasion in 10/121 (8%), epididymal invasion in 5/121 (4%), and spermatic cord invasion in 5/121 (4%) patients. Lymphatic/vascular invasion was observed in 6 (22%) of 27 germ cell tumors smaller than 3 cm in size, and rete testis invasion was observed in 2 (7%), while in 40 (55%) of the 73 germ cell tumors of 3 cm and above, lymphatic/vascular invasion was seen, and 26 (36%) of them had rete testis invasion. Immunohistochemical results contributed significantly to the determination of tumor components and rates, especially in mixed germ cell tumors. Conclusion. Most of the tumors were germ cell tumors, and the majority were seminomas. Lymphatic/vascular invasion and rete testis invasion rates increase as the tumor diameter increases, which is more evident when the 3 cm cut-off value is taken into account (P < 0.005).


Transmissible Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in saliva of men with a history of Kaposi's sarcoma.
We have evaluated the physical state and infectious nature of Kaposi's sarcoma-associated herpesvirus (KSHV) in the saliva of nine persons with past or current Kaposi's sarcoma (KS). KSHV DNA in saliva had the physical characteristics of DNA present in virions. Inoculation of 293 cells with cell-free saliva fluid resulted in the persistence of KSHV DNA in culture for at least 13 passages of the cells. The addition of tetradecanoyl phorbol acetate to KSHV-infected 293 cells led to increased viral DNA. Two virus-specific RNAs were detected by reverse transcriptase PCR in 293 cells infected with cell-free saliva fluid and in cells present in saliva from subjects with KSHV salivary shedding. These results indicate that infectious KSHV can be present in saliva of patients with KS.


Current research on the treatment of primary sclerosing cholangitis.
Primary sclerosing cholangitis (PSC) is a progressive disease of the liver characterized by inflammation and destruction of the intra- and/or extra-hepatic bile ducts, leading to fibrosis and ultimately liver failure, cirrhosis and an increased risk of malignancy. The etiology of PSC is unclear. It is often associated with the inflammatory bowel diseases (IBD), particularly Ulcerative Colitis (UC); up to 75% of PSC patients have UC. PSC is more prevalent in men than in women. Ursodeoxycholic acid (UDCA) has been extensively studied in PSC in randomized clinical trials but failed to show a positive impact on the natural course of the disease. Currently, there is no effective medical therapy for PSC, and the majority of patients will eventually require liver transplantation. PSC is one of the leading indications for liver transplantation. In this paper, we review the current research on the potential therapeutic agents for the treatment of PSC.


Localization of vascular response to VEGF is not dependent on heparin binding.
The major vascular endothelial growth factor (VEGF) isoforms are splice variants from a single gene that differ in their extent of heparin affinity due to the absence of the heparin binding domain in the smallest isoform (mouse VEGF120, human VEGF121). A long-held assumption that has guided the use of VEGF isoforms clinically has been that their differences in heparin binding dictate their ability to diffuse through tissue, with VEGF121 moving most freely and that the distribution of recombinant VEGF would have therapeutically relevant consequences. To test this assumption, we delivered the genes encoding these isoforms by myoblast-mediated gene transfer, a means of delivering genes to highly localized sites within muscle. Surprisingly, all isoforms induced comparable extremely localized physiological effects. Significantly, irrespective of the isoform delivered, the vessels passing within several micrometers of muscle fibers expressing VEGF displayed sharply delineated changes in morphology. The induction of capillary wrapping around VEGF-producing fibers, and of vascular malformations in the muscle at high levels, did not differ among isoforms. These results indicate that heparin binding is not essential for the localization of VEGF in adult tissue and suggest that the preferential delivery of VEGF121 cDNA for clinical applications may not have a physiological basis.


[Expression of Twist1, SIRT1, FGF2 and TGF-β3 genes and its regulatory effect on the proliferation of placenta, umbilical cord and dental pulp mesenchymal stem cells].
To compare the mRNA level of cell proliferation-related genes Twist1, SIRT1, FGF2 and TGF-β3 in placenta mesenchymal stem cells (PA-MSCs), umbilical cord mensenchymals (UC-MSCs) and dental pulp mesenchymal stem cells (DP-MSCs). The morphology of various passages of PA-MSCs, UC-MSCs and DP-MSCs were observed by microscopy. Proliferation and promoting ability of the three cell lines were detected with the MTT method. Real-time PCR (RT-PCR) was used to determine the mRNA levels of Twist1, SIRT1, FGF2, TGF-β3. The morphology of UC-MSCs and DP-MSCs was different from that of PA-MSCs. Proliferation ability and promoting ability of the PA-MSCs was superior to that of UC-MSCs and DP-MSCs. In PA-MSCs, expression level of Twist1 and TGF-β3 was the highest and FGF2 was the lowest. SIRT1 was highly expressed in UC-MSCs. With the cell subcultured, different expression levels of Twist1, SIRT1, FGF2, TGF-β3 was observed in PA-MSCs, UC-MSCs and DP-MSCs. Up-regulated expression of the Twist1, SIRT1 and TGF-β3 genes can promote proliferation of PA-MSCs, UC-MSCs and DP-MSCs, whilst TGF-β3 may inhibit these. The regulatory effect of Twist1, SIRT1, FGF2 and TGF-β3 genes on PA-MSCs, UC-MSCs and DP-MSCs are different.


Neonatal opioid exposure: public health crisis and novel neuroinflammatory disease.
Substance use, specifically the use of prescription and non-prescription opioids among pregnant women, is a major public health issue and chief contributor to the opioid crisis. The prevalence of Neonatal Opioid Withdrawal Syndrome has risen 5-fold in the past decade, and is a well-recognized consequence of perinatal opioid exposure. By contrast, the long-term damage to the developing brain from opioid medications is just beginning to be recognized as a serious concern. Published data suggest that opioid exposure commencing in utero negatively affects the maturation of the neural-immune system, and trajectory of central nervous system development. Methadone induces peripheral immune hyper-reactivity, lasting structural and microstructural brain injury, and significant deficits in executive function and cognitive control in adult animals following in utero exposure. Thus, to address the cascading public health crisis stemming from the multitude of infants with in utero opioid exposure who will grow up with altered neurodevelopmental trajectories, rigorous preclinical, mechanistic studies are required. Such studies will define the long-term sequelae of prenatal opioid exposure in an effort to develop appropriate and targeted interventions. Specifically, the development of novel fluid, neuroimaging and biobehavioral biomarkers will be the most useful to aid in early identification and treatment of opioid exposed infants with the greatest risk of poor clinical outcomes. These studies will be essential to understand how in utero insults determine brain structure and function in adulthood, and what targeted interventions will be required to improve long-term outcomes in the countless children being born exposed to opioids each year.


Indirect costs of depression and other mental and behavioural disorders for Australia from 2015 to 2030.
The impact of mental disorders has been assessed in relation to longevity and quality of life; however, mental disorders also have an impact on productive life-years (PLYs). To quantify the long-term costs of Australians aged 45-64 having lost PLYs because of mental disorders. The Survey of Disability, Ageing and Carers 2003, 2009 formed the base population of Health&WealthMOD2030 - a microsimulation model integrating output from the Static Incomes Model, the Australian Population and Policy Simulation Model, the Treasury and the Australian Burden of Disease Study. For depression, individuals incurred a loss of AU$1062 million in income in 2015, projected to increase to AU$1539 million in 2030 (45% increase). The government is projected to incur costs comprising a 22% increase in social security payments and a 45% increase in lost taxes as a result of depression through its impact on PLYs. Effectiveness of mental health programmes should be judged not only in terms of healthcare use but also quality of life and economic well-being. None.


Effect of food matrix microstructure on stomach emptying rate and apparent ileal fatty acid digestibility of almond lipids.
Almond lipids can be consumed in different forms such as nuts, oil-in-water emulsions or oil. The stomach emptying rate (SER) of almond lipids (0.2 g of fat per 2 mL of almond lipid suspension) as a function of the food matrix was studied using magnetic resonance spectroscopy based on the stomach emptying of a marker (AlCl3-6H2O) in the growing rat. Chyme and digesta samples were collected following serial gavaging (0.2 g of fat per 2 mL of almond lipid suspension) to study microstructural changes and determine the apparent ileal digestibility of almond fatty acids as a function of the native food matrix. The T(1/2) for the stomach emptying of crushed whole almonds and almond cream (194 ± 17 min and 185 ± 19 min, respectively) were not different (P > 0.05) from that of a gastric-stable Tween-oil emulsion (197 ± 19 min). The T(1/2) values for a sodium caseinate (NaCas)-oil emulsion (145 ± 11 min) and a gastric-unstable Span-oil emulsion (135 ± 7 min) were different (P < 0.05) from those for crushed whole almonds, almond cream and Tween-oil emulsion, while almond milk and oil emptied at an intermediate rate (157 ± 9 min and 172 ± 11 min, respectively). Extensively coalesced emulsions under gastric conditions (almond oil, almond cream and Span-oil) had lower (P < 0.05) overall apparent ileal fatty acid digestibility (85.8%, 75.8% and 74.3%, respectively) than crushed whole almonds, almond milk, NaCas-oil and Tween-oil emulsions (91.0%, 92.2%, 92.1% and 88.7%, respectively). The original food matrix and structural changes occurring within the gastrointestinal tract had an impact on SER and ileal fatty acid digestibility of the almond preparations.


Immunolocalization of myosin I heavy chain kinase in Acanthamoeba castellanii and binding of purified kinase to isolated plasma membranes.
The actin-activated Mg(2+)-ATPase activities of Acanthamoeba myosins I are known to be maximally expressed only when a single threonine (myosin IA) or serine (myosins IB and IC) is phosphorylated by myosin I heavy chain kinase. The purified kinase is highly activated by autophosphorylation and the rate of autophosphorylation is greatly enhanced by the presence of acidic phospholipids. In this paper, we show by immunofluorescence and immunoelectron microscopy of permeabilized cells that myosin I heavy chain kinase is highly concentrated, but not exclusively, at the plasma membrane. Judged by their electrophoretic mobilities, kinase associated with purified plasma membranes may differ from the cytoplasmic kinase, possibly in the extent of its phosphorylation. Purified kinase binds to highly purified plasma membranes with an apparent KD of approximately 17 nM and a capacity of approximately 0.8 nmol/mg of plasma membrane protein, values that are similar to the affinity and capacity of plasma membranes for myosins I. Binding of kinase to membranes is inhibited by elevated ionic strength and by extensive autophosphorylation but not by substrate-level concentrations of ATP. Membrane-bound kinase autophosphorylates to a lesser extent than free kinase and does not dissociate from the membranes after autophosphorylation. The co-localization of myosin I heavy chain kinase and myosin I at the plasma membrane is of interest in relation to the possible functions of myosin I especially as phospholipids increase kinase activity.


[The use of trimethine dye to stain proteins following cellulose acetate electrophoresis].
The synthetic trimethine stain PK-144 is recommended for staining the biological fluid proteins after electrophoresis in cellulose acetate films. A good correlation of the values of protein fraction composition determined with the use of this stain and Ponso S stain was observed. The trimethine stain is highly sensitive and may be used in serial electrophoresis analyses in laboratory studies.


Assessment of text documentation accompanying uncoded diagnoses in computerized health insurance claims in Japan.
Uncoded diagnoses in health insurance claims (HICs) may introduce bias into Japanese health statistics dependent on computerized HICs. This study's aim was to identify the causes and characteristics of uncoded diagnoses. Uncoded diagnoses from computerized HICs (outpatient, inpatient, and the diagnosis procedure-combination per-diem payment system [DPC/PDPS]) submitted to the National Health Insurance Organization of Kumamoto Prefecture in May 2010 were analyzed. The text documentation accompanying the uncoded diagnoses was used to classify diagnoses in accordance with the International Classification of Diseases-10 (ICD-10). The text documentation was also classified into four categories using the standard descriptions of diagnoses defined in the master files of the computerized HIC system: 1) standard descriptions of diagnoses, 2) standard descriptions with a modifier, 3) non-standard descriptions of diagnoses, and 4) unclassifiable text documentation. Using these classifications, the proportions of uncoded diagnoses by ICD-10 disease category were calculated. Of the uncoded diagnoses analyzed (n = 363 753), non-standard descriptions of diagnoses for outpatient, inpatient, and DPC/PDPS HICs comprised 12.1%, 14.6%, and 1.0% of uncoded diagnoses, respectively. The proportion of uncoded diagnoses with standard descriptions with a modifier for Diseases of the eye and adnexa was significantly higher than the overall proportion of uncoded diagnoses among every HIC type. The pattern of uncoded diagnoses differed by HIC type and disease category. Evaluating the proportion of uncoded diagnoses in all medical facilities and developing effective coding methods for diagnoses with modifiers, prefixes, and suffixes should reduce number of uncoded diagnoses in computerized HICs and improve the quality of HIC databases.


Hemoglobin adduct and hepatic- and urinary bladder-DNA adduct levels in rapid and slow acetylator Syrian inbred hamsters administered 2-aminofluorene.
The levels of covalently bound arylamine-hemoglobin and DNA adduct formation were used as dosimeters to measure the effect of acetylator genotype and sex on the metabolic conversion of the carcinogen, 2-aminofluorene, to reactive intermediates. A single high dose of 2-aminofluorene (60 mg/kg b.wt. i.p.) was administered to male and female homozygous rapid (Patr/Patr) acetylator hamsters (MHA/SsLaK) and homozygous slow (Pats/Pats) acetylator hamsters (Bio. 82.73/H). By using 32P-postlabeling assay methodology, a sole nonacetylated DNA adduct, which cochromatographed with authentic N-(deoxyguanosin-8-yl)-2-aminofluorene was detected at 3, 6, 12, 18 or 24 hr postdosing in liver and urinary bladder DNA of both rapid and slow acetylator hamsters. The highest levels were detected at 18 hr post 2-aminofluorene injection at which time the average levels of hepatic 2-aminofluorene-DNA adducts were similar between male and female rapid and slow acetylators. By comparison, the levels of 2-aminofluorene-DNA adducts in the urinary bladder at 18 hr were about 4-fold lower than in the liver, and were significantly greater in homozygous rapid than in homozygous slow acetylator counterparts (P less than .01). In both the liver and urinary bladder, the levels of 2-aminofluorene-DNA adducts were independent of sex. In contrast to the DNA adduct data, the levels of 2-aminofluorene-hemoglobin adducts, evaluated by capillary gas chromatography-mass spectrometry, were significantly higher in the homozygous slow acetylators than in homozygous rapid acetylators. However, there again were no differences between males and females.(ABSTRACT TRUNCATED AT 250 WORDS)


Retrovirus promoter-trap vector to induce lacZ gene fusions in mammalian cells.
A retrovirus promoter-trap vector (U3LacZ) has been developed in which Escherichia coli lacZ coding sequences were inserted into the 3' long terminal repeat (LTR) of an enhancerless Moloney murine leukemia virus. The U3LacZ virus contains the longest reported LTR (3.4 kbp); nevertheless, lacZ sequences did not interfere with the ability of the virus to transduce a neomycin resistance gene expressed from an internal promoter. Duplication of the LTR placed lacZ sequences in the 5' LTR just 30 nucleotides from the flanking cellular DNA. Approximately 0.4% of integrated proviruses expressed beta-galactosidase as judged by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining, and individual clones expressing lacZ were isolated by fluorescence-activated cell sorting. In all clones examined, beta-galactosidase expression resulted from the fusion of lacZ sequences to transcriptional promoters located in the flanking cellular DNA. Furthermore, by differential sorting of neomycin-resistant cell populations, clones were isolated in which lacZ expression was induced and repressed in growth-arrested and log phase cells, respectively.


The coverage and challenges of increasing uptake of non-National Immunization Program vaccines in China: a scoping review.
Non-National Immunization Program (NIP) vaccines have played an important role in controlling vaccine-preventable diseases (VPDs) in China. However, these vaccines are paid out of pocket and there is room to increase their coverage. We focused on four selected non-NIP vaccines in this study, namely Haemophilus influenzae type b (Hib) vaccine, human papillomavirus (HPV) vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine. We aimed to conduct a scoping review of their vaccination rates and the major barriers faced by health systems, providers, and caregivers to increase coverage. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). We searched five English databases (PubMed, Web of Science, EMBASE, Scopus, and WHO IRIS) and four Chinese databases using the search strategy developed by the study team. Two independent reviewers screened, selected studies, and examined their quality. We summarized the non-NIP vaccine coverage data by vaccine and applied the 5A framework (Access, Affordability, Acceptance, Awareness, Activation) to chart and analyze barriers to increasing coverage. A total of 28 articles were included in the analysis (nine pertaining to vaccine coverage, and another 19 reporting challenges of increasing uptake). Among the four selected vaccines, coverage for the Hib vaccine was the highest (54.9-55.9% for 1 dose or more from two meta-analyses) in 2016, while the coverage of the other three vaccines was lower than 30%. Eight of the nine included articles mentioned the regional disparity of coverage, which was lower in under-developing regions. For example, the three-dose Hib vaccination rate in eastern provinces was 38.1%, whereas the rate in central and western provinces was 34.3% and 26.2%, respectively in 2017. Within the 5A framework, acceptance, awareness, and affordability stood out as the most prominent themes. Among the 12 identified sub-themes, high prices, low vaccine awareness, concerns about vaccine safety and efficacy were the most cited barriers to increasing the uptake. There is an urgent need to increase coverage of non-NIP vaccines and reduce disparities in access to these vaccines across regions. Concerted efforts from the government, the public, and society are required to tackle the barriers and challenges identified in this study, both on the demand and supply side, to ensure everybody has equal access to life-saving vaccines in China. Particularly, the government should take a prudent approach to gradually incorporate non-NIP vaccines into the NIP step by step, and make a prioritizing strategy based on key factors such as disease burden, financial resources, and market readiness, with special attention to high-risk populations and underdeveloped regions.