[Symptomatic benign prostate hyperplasia affects the quality of life of the patients' wives].
Symptomatic benign prostate hyperplasia (BPH) affects both the patients' and their wives' quality of life (QOL) due to lower urinary tract symptoms (LUTS) and related events. This study was to investigate the QOL of the wives of symptomatic BPH patients being evaluated for surgical treatment. We included 50 couples in this study, in which the husbands were symptomatic BPH patients referred for surgical treatment. The patients were asked to fill in the forms of IPSS and BPH impact index ( BPHII), while their wives investigated with a 7-item questionnaire. The data obtained were subjected to statistic analyses. LUTS of the BPH patients caused sleep disturbance in 12% of their wives, decreased social activity in 12%, inadequate sexual life in 20%, psychological stress in 38%, fear of prostate cancer in 68%, fear of surgery in 40% and insufficiency for essential tasks in 14%. The decrease in the QOL of the patients' wives was not correlated with the patients' scores on IPSS and BPHII (P > 0.05). LUTS and related events of symptomatic BPH patients obviously decrease the QOL of their wives, but the severity of the patients' symptoms is not correlated with the decrease of their wives' QOL.


Leptin Gene and Leptin Receptor Gene Polymorphisms in Alcohol Use Disorder: Findings Related to Psychopathology.
Comorbidity between alcohol use disorder (AUD) and other addictive and psychiatric disorders is highly prevalent and disabling; however, the underlying biological correlates are not fully understood. Leptin is a peptide hormone known for its role in energy homeostasis and food intake. Furthermore, leptin plays a key role in the activity of the hypothalamic-pituitary-adrenal (HPA) axis and of several neurotransmitter systems that regulate emotionality and behavior. However, human studies that have investigated circulating leptin levels in relation to AUD and affective disorders, such as anxiety and depression, are conflicting. Genetic-based analyses of the leptin gene (LEP) and leptin receptor gene (LEPR) have the potential of providing more insight into the potential role of the leptin system in AUD and comorbid psychopathology. The aim of the current study was to investigate whether genotypic variations at LEP and LEPR are associated with measures of alcohol use, nicotine use, anxiety, and depression, all of which represent common comorbidities with AUD. Haplotype association analyses were performed, using data from participants enrolled in screening and natural history protocols at the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Analyses were performed separately in European Americans and African Americans due to the variation in haplotype diversity for most genes between these groups. In the European American group, one LEP haplotype (EB2H4) was associated with lower odds of having a current AUD diagnosis, two LEPR haplotypes (EB7H3, EB8H3) were associated with lower cigarette pack years and two LEPR haplotypes (EB7H2, EB8H2) were associated with higher State-Trait Anxiety Inventory (STAI-T) scores. In the African American group, one LEP haplotype (AB2H8) was associated with higher cigarette pack years and one LEP haplotype (AB3H2) was associated with lower Fagerström Test for Nicotine Dependence (FTND) scores. Overall, this study found that variations in the leptin and leptin receptor genes are associated with measures of alcohol use, nicotine use, and anxiety. While this preliminary study adds support for a role of the leptin system in AUD and psychopathologies, additional studies are required to fully understand the underlying mechanisms and potential therapeutic implications of these findings.


[Met-enkephalin in the cerebrospinal fluid as an indicator of central nervous system injury in meningitis and encephalitis].
Assessment of met-enkephalin level in the cerebrospinal fluid (CSF) of patients with inflammatory process of the central nervous system (CNS) was performed to estimate the role of opioid system in viral and bacterial meningitis, and encephalitis. The met-enkephalin level, protein concentration and pleocytosis were analysed in the CSF of 53 patients with viral or bacterial meningitis, encephalitis, and in the control group of patients without inflammatory disease of the CNS. The biggest differences have been observed between the groups of patients with bacterial meningitis and those without inflammatory disease of the CNS, but they were statistically insignificant. There was a lack of correlation between met-enkephalin level and some factors of inflammatory process in CSF, such as pleocytosis and protein concentration. We have not revealed any correlation between etiological agent of CNS infection and opioid system of the brain. Despite the fact that, we observed in the study statistically insignificant changes, we suggest to continue investigations, including additional parameters which are characteristic for the CNS diseases.


An iterative procedure for deriving selection indexes with constant restrictions.
The objective of this study was to present an iterative procedure for deriving selection indexes with constant restrictions. Constant restriction means that the genetic responses of the restricted traits are preset to actual amounts for a given selection intensity (ī). Results of this study show that an index with constant restriction alone or in combination with other types of restrictions possesses three distinctive characteristics: 1) the coefficient matrix of the index equations is not symmetric and is nonlinear; 2) the coefficient matrix contains unknown ī, indicating that the index coefficients (b) to be derived depends on the value of ī predetermined before selection; and 3) the coefficient matrix contains unknown b, thus requiring iterative methods to solve the index equations. As a result of these unique characteristics, the index coefficients, genetic responses of the index traits, and overall genetic gain in net merit change nonlinearly with varying levels of ī, which is in sharp contrast to both unrestricted and restricted indexes reported in the literature. The construction of a constant-restricted index requires predetermining the value of ī intended for a selection program to derive the corresponding b. An index with constant restrictions has no meaning unless it is associated with a specific value of ī. Numerical examples are given to illustrate the construction of the index with constant restrictions and to validate the theoretical development proposed. The derived equations have yielded an index that maximized the total merit and fulfilled constant restriction at the same time.


pSTAT3/pSTAT5 Signaling Patterns in Molecularly Defined Subsets of Myeloproliferative Neoplasms.
BCR/ABL1-negative myeloproliferative neoplasms (MPNs) are characterized by recurrent mutations in JAK2, CALR, and MPL, each of which has been reported to alter JAK/STAT signaling pathways. This report characterizes JAK/STAT signaling patterns in molecularly defined subsets of MPN utilizing immunohistochemistry for pSTAT3 and pSTAT5. Analysis of 30 BCR/ABL1-negative, nonpolycythemia vera MPN identified 15 (50%) with JAK2 V617F, 2 with MPL mutations (7%), and 8 with CALR mutations (27%). All mutations were mutually exclusive, except for 1 case with concurrent JAK2 V617F and CALR mutations. pSTAT3 staining in megakaryocyte nuclei was found in 4 cases (13%) and was not significantly associated with mutation status. pSTAT5 staining in megakaryocyte nuclei was found in 16 cases (53%), as was significantly associated with JAK2 V617F versus CALR mutation (P=0.009). Erythroid staining for pSTAT5 was seen exclusively in "triple-negative (TN)" cases lacking JAK2 V617F, MPL, and CALR mutations (P=0.006, TN vs. other genotypes), and pSTAT5 staining in megakaryocyte nuclei was seen in 2 TN cases. pSTAT5 staining in TN MPN suggests that other unknown abnormalities in this pathway may contribute to the pathogenesis of these cases. Furthermore, the demonstration of distinct STAT staining patterns in molecularly defined MPN suggests that these mutations result in divergent signaling events that may contribute to the biological and prognostic differences in these molecular subsets of MPN.


Participant Experiences of Transcranial Direct Current Stimulation (tDCS) as a Treatment for Antipsychotic Medication Induced Weight Gain.
Background: Despite the growing number of studies on the use of non-invasive brain stimulation in people with schizophrenia, there is limited research on participant views of such treatment methods. Aim: Explore participant experiences and perceptions of transcranial direct current stimulation (tDCS). Methods: Twelve people with schizophrenia took part in semi-structured interviews after having completed 5 sessions of tDCS. Thematic analysis was used to identify codes and themes. Results: Five themes were identified: (1) motivation for study enrolment; (2) concerns about tDCS; (3) factors reducing the fear of tDCS; (4) experience of tDCS; (5) perceived effects of tDCS. Conclusions: The study provides insight into the perceptions and experiences of each individual. Participants were concerned about the safety of tDCS and associated it with invasive procedures such as electroconvulsive therapy and lobotomy. Educational materials and a good relationship with the researcher played an important role in reducing the fear of brain stimulation. All participants described tDCS as uncomfortable, however, agreed that unpleasant sensations only lasted for a short while (20 s-5 min). After the first session, participants no longer felt anxious about the remaining ones. Strategies to improve treatment experience and study recruitment have been identified.


Long-term fatigue after perimesencephalic subarachnoid haemorrhage in relation to cognitive functioning, mood and comorbidity.
To study relationships between fatigue and objective and subjective cognitive functioning, mood and comorbidity in the long term after perimesencephalic subarachnoid haemorrhage (PM-SAH). Cross-sectional study. Objective cognitive functioning was measured with: Trail Making Test; Symbol Substitution; D2; Verbal and Semantic Fluency; Tower Test; Digit Span; 15-Words Test; Rey Complex Figure. Subjective cognitive functioning: Cognitive Failure Questionnaire. Fatigue: Fatigue Severity Scale. Mood: Hospital Anxiety and Depression Scale. Forty-six patients, mean age 50.4 (SD = 9.4), mean time after PM-SAH 4.7 (SD = 1.6) years participated. Patients with fatigue (33%) had significantly lower scores than patients without fatigue on most objective cognitive functioning tests (p < 0.05). Fatigue score was significantly associated with subjective and objective cognitive functioning, mood and comorbidity. After adjustment for mood and comorbidity, fatigue remained associated with attention and executive functioning. This study supports our previous findings that a third of patients with PM-SAH experience fatigue and problems of cognitive functioning, also in the long term. Future research should investigate whether these patients would benefit from long-term follow-up and/or cognitive rehabilitation programmes. Implications for Rehabilitation Consequences for patients with PM-SAH are underestimated. One in every three patients suffered from fatigue in the long term after onset of PM-SAH. Patients with PM-SAH should be screened for problems of cognitive functioning, fatigue and mood in outpatient clinic just as patients with aneurysmal SAH.


Even modest prediction accuracy of genomic models can have large clinical utility.
Whole Genome Prediction (WGP) jointly fits thousands of SNPs into a regression model to yield estimates for the contribution of markers to the overall variance of a particular trait, and for their associations with that trait. To date, WGP has offered only modest prediction accuracy, but in some cases even modest prediction accuracy may be useful. We provide an illustration of this using a theoretical simulation that used WGP to predict weight loss after bariatric surgery with moderate accuracy (R (2) = 0.07) to assess the clinical utility of WGP despite these limitations. Prevention of Type 2 Diabetes (T2DM) post-surgery was considered the major outcome. Treating only patients above predefined threshold of predicted weight loss in our simulation, in the realistic context of finite resources for the surgery, significantly reduced lifetime risk of T2DM in the treatable population by selecting those most likely to succeed. Thus, our example illustrates how WGP may be clinically useful in some situations, and even with moderate accuracy, may provide a clear path for turning personalized medicine from theory to reality.


Potential involvement of the AML1-MTG8 fusion protein in the granulocytic maturation characteristic of the t(8;21) acute myelogenous leukemia revealed by microarray analysis.
The AML1 (RUNX1)-MTG8 (ETO) fusion transcription factor generated by the t(8;21) translocation is believed to deregulate the expression of genes that are crucial for normal differentiation and proliferation of hematopoietic progenitors, resulting in acute myelogenous leukemia. To elucidate the role of AML1-MTG8 in leukemogenesis, we used oligonucleotide microarrays to detect alterations in gene expression caused by ectopic expression of AML1-MTG8 in a murine myeloid progenitor cell line, L-G. Microarray analysis of approximately 6500 genes identified 32 candidate genes under the downstream control of AML1-MTG8. Among the 32 genes, 23 were not known to be regulated by AML1-MTG8. These included many granule protein genes and several cell surface antigen genes. Interestingly, AML1-MTG8 enhanced the expression of several genes that are usually induced during granulocytic differentiation, particularly those encoding azurophil granule proteins, including cathepsin G, myeloperoxidase and lysozyme. This indicates that AML1-MTG8 induces partial differentiation of myeloid progenitor cells into promyelocytes in the absence of the usual differentiation signals, while it inhibits terminal differentiation into mature granulocytes. Thus, AML1-MTG8 itself may play a crucial role in defining a unique cytologic type with abnormal maturation, characteristic of t(8;21) acute myelogenous leukemia.


Precise and accurate compound specific carbon and nitrogen isotope analysis of atrazine: critical role of combustion oven conditions.
Compound-specific stable isotope analysis by gas chromatography-isotope ratio mass spectrometry (GC-IRMS) is increasingly used to assess origin and fate of organic substances in the environment. Although analysis without isotopic discrimination is essential, it cannot be taken for granted for new target compounds. We developed and validated carbon isotope analysis of atrazine, a herbicide widely used in agriculture. Combustion was tested with reactors containing (i) CuO/NiO/Pt operating at 940 degrees C; (ii) CuO operating at 800 degrees C; (iii) Ni/NiO operating at 1150 degrees C and being reoxidized for 2 min during each gas chromatographic run. Accurate and precise carbon isotope measurements were only obtained with Ni/NiO reactors giving a mean deviation delta delta(13)C from dual inlet measurements of -0.1-0.2% per hundred and a standard deviation (SD) of +/- 0.4% per hundred. CuO at 800 degrees C gave precise, but inaccurate values (delta delta(13)C = -1.3% per hundred, SD +/- 0.4% per hundred), whereas CuO/NiO/Pt reactors at 940 degrees C gave inaccurate and imprecise data. Accurate (delta delta(15)N = 0.2% per hundred) and precise (SD +/- 0.3% per hundred) nitrogen isotope analysis was accomplished with a Ni/NiO-reactor previously used for carbon isotope analysis. The applicability of the method was demonstrated for alkaline hydrolysis of atrazine at 20 degrees C and pH 12 (nucleophilic aromatic substitution) giving epsilon(carbon) = -5.6% per hundred +/- 0.1% per hundred (SD) and epsilon(nitrogen) = -1.2% per hundred +/- 0.1% per hundred (SD).


UV-induced squamous cell carcinomas in the hairless mouse. Morphological characteristics and transplantation in the syngenic and nude mouse.
Squamous cell carcinomas were induced by UVB in the hairless mouse HRO hr/hr. Twelve mice were irradiated three times a week at a dose of 0.19 J/cm2. The average latency period for the appearance of the first tumour is 16 weeks and by the 21st week, tumour incidence is 100%. Further observation of these tumours shows that their growth is independent of irradiation dose and that the tumours continue to appear even after cessation of irradiation. Histological and cytological examination of these tumours show them to have characteristics of malignancy. Transplantation in athymic mice suggests that UVB provokes immune deficiencies in hairless mice similar to those seen in conditioned nude mice.


Total synthesis of clavilactone B: a radical cyclization-fragmentation strategy.
A new synthetic route to clavilactone B, a naturally occurring inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is disclosed. The route features a sequential samarium-mediated radical cyclization-fragmentation of an indanone derivative, which provides rapid access to a 10-membered carbocyclic motif fused to an aromatic ring.


Factors affecting family satisfaction with inpatient end-of-life care.
Little data exists addressing satisfaction with end-of-life care among hospitalized patients, as they and their family members are systematically excluded from routine satisfaction surveys. It is imperative that we closely examine patient and institution factors associated with quality end-of-life care and determine high-priority target areas for quality improvement. Between September 1, 2010 and January 1, 2012 the Canadian Health care Evaluation Project (CANHELP) Bereavement Questionnaire was mailed to the next-of-kin of recently deceased inpatients to seek factors associated with satisfaction with end-of-life care. The primary outcome was the global rating of satisfaction. Secondary outcomes included rates of actual versus preferred location of death, associations between demographic factors and global satisfaction, and identification of targets for quality improvement. Response rate was 33% among 275 valid addresses. Overall, 67.4% of respondents were very or completely satisfied with the overall quality of care their relative received. However, 71.4% of respondents who thought their relative did not die in their preferred location favoured an out-of-hospital location of death. A common location of death was the intensive care unit (45.7%); however, this was not the preferred location of death for 47.6% of such patients. Multivariate Poisson regression analysis showed respondents who believed their relative died in their preferred location were 1.7 times more likely to be satisfied with the end-of-life care that was provided (p = 0.001). Items identified as high-priority targets for improvement included: relationships with, and characteristics of health care professionals; illness management; communication; and end-of-life decision-making. Nearly three-quarters of recently deceased inpatients would have preferred an out-of-hospital death. Intensive care units were a common, but not preferred, location of in-hospital deaths. Family satisfaction with end-of-life care was strongly associated with their relative dying in their preferred location. Improved communication regarding end-of-life care preferences should be a high-priority quality improvement target.


Performance of computer-assisted continuous infusion at low concentrations of intravenous sedatives.
We studied the performance of a target-controlled drug infusion device, computer-assisted continuous infusion (CACI). Forty-one volunteers received one of midazolam (n = 11), propofol (n = 10), thiopental (n = 10), or fentanyl (n = 10) in sedative concentrations. Concentrations were kept constant for 45-70 min at five sequential target concentrations in each subject. Twenty-six subjects had arterial sampling and 15 had venous sampling to determine drug concentrations. Median performance errors, median absolute performance error (MDAPE), wobble, divergence, and median absolute constancy error (MDACE), defined as error around mean actual concentration at each target, were calculated. CACI demonstrated significant performance errors, which were different among drugs. MDAPE (5%-95% confidence interval) ranged from 22.9% (12.1%-39.6%) for propofol to 82.2% (36.0%-183.0%) for midazolam. Although performance errors could be large, CACI was able to maintain a constant serum concentration over time very successfully. The MDACE ranged from 5.6% (3.9%-17.3%) for fentanyl to 11.2% (8.9%-20.4%) for propofol. Few differences occurred between arterial and venous sampling, although when they occurred, arterial samples indicated larger errors. It is concluded that CACI is very successful at maintaining constant serum concentrations of these drugs at sedative concentrations. Arterial sampling should be used when the performance characteristics of an infusion device are being tested. However, venous sampling may be adequate to determine serum concentrations when a pseudo-steady state has been achieved.


Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation.
Homo-oligomerization via a coiled-coil (C-C) domain has been shown to be necessary for the promyelocytic leukemia (PML)-retinoic acid receptor-alpha (RARalpha) fusion protein to acquire oncogenic potential in acute promyelocytic leukemia. We show here that PML(DeltaC-C)-RARalpha, which contains a deletion in its C-C domain, is neither localized as characteristic microspeckles nor modified by small ubiquitin-like modifiers (SUMO). The absence of sumoylation of the DeltaC-C mutant was due to the lack of binding to Ubc9, a SUMO conjugation enzyme. The integrity of RING finger domain was also needed for both sumoylation and microspeckle formation. In GAL4-DNA tethering assays, the DeltaC-C mutant completely lost the inhibitory effect on retinoic acid (RA)-mediated transactivation. Furthermore, the expression of CD14 in U937 cells expressing the DeltaC-C mutant in response to vitamin D3 was markedly higher than in cells expressing PML-RARalpha. However, the RA-mediated induction of C/EBPbeta in cells expressing the DeltaC-C mutant was comparable to that of control cells. Thus, our results suggest that the C-C domain-associated functions of sumoylation, localization as microspeckles, and the inhibition of monocyte differentiation all contribute to the oncogenic activity of PML-RARalpha.


Different strategies and cost-effectiveness in the treatment of primary open angle glaucoma.
Glaucoma is the second highest cause of blindness worldwide with an estimated half of the glaucoma population unaware of their disease. To date, intraocular pressure is the most important modifiable risk factor and lowering it has been proven to reduce progression of visual field loss associated with glaucoma. Different strategies are available to lower intraocular pressure and include medical, laser, or surgical treatment in the form of topical or systemic medications, argon or selective laser trabeculoplasty, and glaucoma drainage surgery such as trabeculectomy, deep sclerectomy, or other drainage devices. The effectiveness of these treatments has been well documented however their cost-effectiveness between the developed world and third world remains unclear.


Beyond the 'tick and flick': facilitating best practice falls prevention through an action research approach.
To examine residential aged care facility staff views on using falls risk assessment tools and the implications for developing falls prevention practices in the context of an action research project. Falls risk assessments play an important role in care planning by identifying and monitoring aged care facility residents most at risk of falls. Yet while such assessments are recommended in falls prevention best practice guidelines, there is little published research that examines staff procedures and views related to conducting falls risk assessments. Falls risk assessments were undertaken in the context of an action research project. Twelve staff members from two residential aged care facilities (RACFs) in Tasmania formed a single Falls Action Research Group, which met 22 times over a year, providing the study's qualitative data. During this time, key group members assessed 178 residents using a new falls risk assessment tool (FROP-Resi). According to group members, facilities evolved from a 'tick-and-flick' approach to falls risk assessment to a more individualised, face-to-face assessment process. Group members perceived the process to be more meaningful and enjoyable for staff involved in the assessment process resulting in higher quality of assessments and leading to improved levels of falls awareness among staff, residents and family caregivers. An action research process is useful for facilitating a new approach to falls risk assessments, engaging aged care facility staff with falls prevention and prompting improvements in falls prevention practices. RACFs need to provide opportunities for staff to meet regularly to discuss practice, identify issues and take action. By doing so, staff can engage meaningfully with best practice activities such as optimising falls risk assessment processes.


The intraluminal thrombus as a source of proteolytic activity.
Most abdominal aortic aneurysms (AAAs) with a diameter indicating need for surgical repair contain intraluminal thrombus (ILT). The development of AAA is linked to degradation of elastin and collagen. These changes are more pronounced in the aneurysm wall covered by the ILT, which also shows more signs of inflammation and is thinner compared to the aneurysm wall exposed to flowing blood. The rate of increase in diameter of AAA correlates with increased thrombus growth and rupture. CT examinations of patients with rupture have demonstrated contrast appearing in the thrombus suggesting bleeding into it. Studies using gene array of human aneurysm specimens have shown that most matrix metalloproteinases (MMP) were upregulated in the thrombus-free wall. Analyses by zymography, however, demonstrate gelatinase activity in the interface between the thrombus and the underlying wall and in the media of the wall not covered by a thrombus. The thrombus contains large amounts of neutrophils. Neutrophil gelatinase associated lipocalin (NGAL) is involved in the regulation of MMP-9 activity and prevents its inactivation, thus augmenting the proteolytic effect. It has been identified in all layers of the ILT. The presence of NGAL/MMP-9 complexes throughout the thrombus and in the thrombus-covered wall may contribute to the increased proteolytic degradation seen in this wall segment. In conclusion, the presence, growth, and thickness of the ILT have been shown to be associated with growth and risk of rupture. The wall underlying the thrombus is thinner and shows more signs of proteolytic degradation. Increased proteolytic activity by MMP-9 may be mediated by binding to NGAL.


Hydroconductive and silver-impregnated foam dressings: a comparison.
As the number of commercially available wound dressings is increasing rapidly, it is important for clinicians to understand the strengths and limitations of each and to recognise relationships between wound type and dressing properties to obtain optimal healing results. Our aim is to test the antimicrobial activity of two dressings. A hydroconductive (HC) dressing and a silver-impregnated foam (SIF) dressing were compared for their potential to reduce the levels meticillin-resistant Staphylococcus aureus (MRSA). We also assessed MRSA-derived biologically active components in liquid or agar matrices, simplified models for heavily exuding or dry wounds respectively, and in an in vivo animal model with MRSA infected wounds. In the agar model (dry wounds) both dressings showed a strong reduction in MRSA activities within 24 hours post-application. The antibacterial effects of the SIF dressing were more pronounced in the liquid model, however, at an increasing cytotoxic cost. In agreement with these in vitro results, assessment of dressings using an MRSA-infected wound in an rat model showed a decrease in MRSA which was significant 7 days post-burn and inoculation, with more compromised viability of MRSA. Dressings showed a similar capability to reduced and eliminate toxic shock syndrome toxin (TSST-1) at day 7 post-burn in the animal model but not at day 4, where the SIF dressing was more potent Conclusion: These results confirm the advantages of using silver in reducing bacterial load in wound treatment, except for conditions of highly exuding wounds where the cytotoxic properties of silver may offset these advantages and HC dressing use is more suitable.


[Development and evaluation of the reliability and validity of a scale for basic actions relevant to public health].
The purpose of this study was to develop a Scale for Basic Action for Public Health (hereinafter referred to as the BAPH scale) to assess and improve the ability of public health nurses (PHNs) to contribute to the health and well-being of Japanese people. The present study was carried out to assess the reliability and validity of the BAPH scale. One hundred and thirty-five prefectural public health centers and 115 municipal health centers in Japan were randomly chosen. Full-time PHNs working at the selected health centers were selected as the subjects of this study. Questionnaires were sent to the directors of the health centers and then distributed to the subjects. The questionnaire survey included some provisional questions formulated taking into account the assessment items derived from the existing literature as well as questions related to the respondent's age, years of experience as a PHN, academic background, and job title. Of a total of 250 health centers, 184 (73.6%) responded. The questionnaire was completed and returned by 1,261 (70.1%) PHNs, 1,112 of whom provided valid responses and were thus included in the analysis. 1) Based on the results obtained from the factor analysis performed on the 18 provisional BAPH questions, 12 BAPH scale items were chosen for inclusion in the scale. These items consisted of three sub-scales, namely "promotion of accessibility and fairness" (five items), "assessment of quality and quantity of service" (four items), and "prevention action for health risk" (three items). 2) The Cronbach's coefficient alpha for the BAPH scale and its three sub-scales were 0.91, 0.84, 0.86, and 0.82, respectively. 3) As respondents experience become longer, their scores on the BAPH scale become higher. In addition, respondents who had given either presentations or speeches at academic conferences and those who subscribed to academic journals were significantly more likely than others to score high on the scale. The results of the present study revealed that the BAPH scale is a reliable and valid method to evaluate the ability of PHNs to contribute to the health and well-being of people. Hitherto, there has been no method that can be used to evaluate the job performance of PHNs. The use of the BAPH scale to assess the effectiveness of basic education and in-service training for PHNs may not only improve the content of training/education offered but also help them fulfill their duties as providers of health care and welfare services.


Newer applications of the histological stain prepared from Pterocarpus santalinus.
A histological stain prepared from the heartwood of Pterocarpus santalinus Linn. has been found to be an excellent nuclear stain for various cells of animal and plant origin. As an elastic tissue stain, the results are comparable to standard elastic tissue stains. The striations of voluntary muscle fibers are well shown. The Nissl granules and fibers of cranial nerves in the pons are visualized. When counterstained with light green, it differentially stains muscle and fibrous tissue. The stain can be used as counterstain with certain histochemical procedures with satisfactory results. The preparation and use of this versatile stain are described.


Copper(I)-promoted cycloalkylation-peroxidation of unactivated alkenes via sp(3) C-H functionalisation.
A copper(I)-promoted cycloalkylation-peroxidation strategy has been developed via a three-component reaction involving cycloalkanes, tert-butyl hydroperoxide (TBHP) and internal conjugated alkenes possessing electron-withdrawing groups (EWGs). This process installs C-O and C-C bonds via sp(3) C-H functionalisation with concomitant generation of two stereocentres. This regioselective radical addition of coumarin system is opposite to that of styrene.


Microphase versus macrophase separation in the square-well-linear fluid: A theoretical and computational study.
Due to the presence of competing interactions, the square-well-linear fluid can exhibit either liquid-vapor equilibrium (macrophase separation) or clustering (microphase separation). Here we address the issue of determining the boundary between these two regimes, i.e., the Lifshitz point, expressed in terms of a relationship between the parameters of the model. To this aim, we carry out Monte Carlo simulations to compute the structure factor of the fluid, whose behavior at low wave vectors accurately captures the tendency of the fluid to form aggregates or, alternatively, to phase separate. Specifically, for a number of different combinations of attraction and repulsion ranges, we make the system go across the Lifshitz point by increasing the strength of the repulsion. We use simulation results to benchmark the performance of two theories of fluids, namely, the hypernetted chain (HNC) equation and the analytically solvable random phase approximation (RPA); in particular, the RPA theory is applied with two different prescriptions as for the direct correlation function inside the core. Overall, the HNC theory proves to be an appropriate tool to characterize the fluid structure and the low-wave-vector behavior of the structure factor is consistent with the threshold between microphase and macrophase separation established through simulation. The structural predictions of the RPA theory turn out to be less accurate, but this theory offers the advantage of providing an analytical expression of the Lifshitz point. Compared to simulation, both RPA schemes predict a Lifshitz point that falls within the macrophase-separation region of parameters: in the best case, barriers roughly twice higher than predicted are required to attain clustering conditions.


Prediction of lithium response in first-episode mania using the LITHium Intelligent Agent (LITHIA): Pilot data and proof-of-concept.
Individualized treatment for bipolar disorder based on neuroimaging treatment targets remains elusive. To address this shortcoming, we developed a linguistic machine learning system based on a cascading genetic fuzzy tree (GFT) design called the LITHium Intelligent Agent (LITHIA). Using multiple objectively defined functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1 H-MRS) inputs, we tested whether LITHIA could accurately predict the lithium response in participants with first-episode bipolar mania. We identified 20 subjects with first-episode bipolar mania who received an adequate trial of lithium over 8 weeks and both fMRI and 1 H-MRS scans at baseline pre-treatment. We trained LITHIA using 18 1 H-MRS and 90 fMRI inputs over four training runs to classify treatment response and predict symptom reductions. Each training run contained a randomly selected 80% of the total sample and was followed by a 20% validation run. Over a different randomly selected distribution of the sample, we then compared LITHIA to eight common classification methods. LITHIA demonstrated nearly perfect classification accuracy and was able to predict post-treatment symptom reductions at 8 weeks with at least 88% accuracy in training and 80% accuracy in validation. Moreover, LITHIA exceeded the predictive capacity of the eight comparator methods and showed little tendency towards overfitting. The results provided proof-of-concept that a novel GFT is capable of providing control to a multidimensional bioinformatics problem-namely, prediction of the lithium response-in a pilot data set. Future work on this, and similar machine learning systems, could help assign psychiatric treatments more efficiently, thereby optimizing outcomes and limiting unnecessary treatment.


Benign sebaceous neoplasm with prominent epidermal component.
A 65-year-old woman presented with a solitary nodule within an erythematous plaque in her right groin. Histopathologic examination showed central lobular proliferation of basaloid cells admixed with mature sebaceous cells and a lateral extensive intraepidermal component composed mostly of lobules of mature sebocytes consistent with intraepidermal epithelioma with sebaceous differentiation and focal invasion. Although various cutaneous neoplasms may show an intraepidermal growth pattern, extensive sebaceous differentiation in such a neoplasm, as seen in this case, has not been described. Electron-microscopic study revealed that the basaloid cells have features of pluripotential cells. This observation supports the previously reported concept that intraepidermal epithelioma may be composed of a group of heterogeneous tumors with various degrees and lines of differentiation. Additionally, sebaceous epithelioma/adenoma should be considered in the differential diagnosis of the cutaneous neoplasms with an intraepidermal growth pattern.


[Role of dynamic penile color Doppler echography in the evaluation of the patient with La Peyronie's disease].
From March 1995 to February 1996, sixteen consecutive patients with Peyronie's Disease (PD) were routinely submitted to penile dynamic colour-coded doppler ultrasonography (CCDU). The test yielded normal results in 6 patients who had no erectile problems and in other 4 patients who conversely complained of reduced erectile function. In the other 6 patients who complained of reduced erectile function, the test pointed out pure arteriogenic failure in 1 case, pure venogenic failure in 4, and mixed arteriogenic and venogenic failure in 1. CCDU enables a precise assessment of erectile function as well of the site, kind and entity of the penile curvature to be corrected. These data are very useful when planning the surgical approach for each patient.


Inter-cycle and inter-observer variability of the antral follicle count in routine clinical practice.
Antral follicle count (AFC) is a reliable predictor of ovarian response to stimulation and its inter-cycle and inter-observer variability has been extensively studied on in vitro fertilization (IVF), mostly in highly selected populations within studies not originally designed for this purpose. In this retrospective cohort study, we assess the inter-cycle variation of AFC in a setting similar to that of the daily practice. We included only patients undergoing mild stimulation for intrauterine insemination (IUI). One hundred and forty-eight patients had two (62 patients, group A), three (49 patients, group B) or four (37 patients, group C) IUI cycles and AFC was measured on early follicular phase of each cycle by one of the members of the medical team within daily practice. Intra-class correlation coefficients were used to estimate variability. Inter-cycle variability rendered ICCs above 0.70 in all groups improving along with the number of cycles [Group A ICC 0.78 (95%CI 0.66-0.86), Group B ICC 0.87 (95%CI 0.80-0.92) and Group C ICC 0.91 (95%CI 0.85-0.95)]. Inter-observer variability showed a high degree of concordance with ICCs above 0.95. We provide the closest approximation to real inter-cycle and inter-observer AFC variability expected in routine clinical practice.


[Use of three-dimensional conformal radiation system in radiotherapy of solid tumours in children].
Three - dimensional treatment planning system using CT is the most modern tool in the radiotherapy of children. It is most useful in treatment of solid tumours when the neoplasm is very close to the vital organs. In our work we have presented three cases of small children in whom owing to conformal radiotherapy it was possible to give the treatment dose to the planning target volume (PTV) and spare adjacent critical organs.


Speciation in the genus Cloacina (Nematoda: Strongylida): species flocks and intra-host speciation.
Sequences of the first and second internal transcribed spacers (ITS1 + ITS2) of nuclear ribosomal DNA were employed to determine whether the congeneric assemblages of species of the strongyloid nematode genus Cloacina, found in the forestomachs of individual species of kangaroos and wallabies (Marsupialia: Macropodidae), considered to represent species flocks, were monophyletic. Nematode assemblages examined in the black-striped wallaby, Macropus (Notamacropus) dorsalis, the wallaroos, Macropus (Osphranter) antilopinus/robustus, rock wallabies, Petrogale spp., the quokka, Setonix brachyurus, and the swamp wallaby, Wallabia bicolor, were not monophyletic and appeared to have arisen by host colonization. However, a number of instances of within-host speciation were detected, suggesting that a variety of methods of speciation have contributed to the evolution of the complex assemblages of species present in this genus.


Peripheral sympatholytic actions of four AT1 antagonists: are they relevant for long-term antihypertensive efficacy?
Angiotensin II causes hypertension not only by direct constriction of vascular smooth muscle, but also by facilitating the release of noradrenaline from sympathetic terminals and by enhancing vascular noradrenaline sensitivity. AT1 receptor antagonists attenuate all these actions, but display some evidence of substance-related selectivities. The contribution of pre- or postsynaptic impairment of sympathetic transmission to long-term antihypertensive efficacy should be determined for four structurally different, clinically approved AT1 antagonists. Spontaneously hypertensive rats were treated with candesartan, eprosartan, irbesartan, or losartan via osmotic minipumps for 4 weeks at doses yielding identical reductions of blood pressure. Maximum efficacy was obtained with a tripled dose of candesartan. In the pithed rat model, stimulus/response dependencies were determined for vasopressor effectivity of preganglionic electrical stimulation, and of intravenous bolus applications of noradrenaline and angiotensin II. Losartan, irbesartan, eprosartan, and candesartan at doses of 5, 40, 20, and 0.05 mg/kg per day, were equally effective in reducing basal systolic blood pressure (-42 mmHg), and the vasopressor potency of angiotensin II (approximately 10-fold). The efficacies of preganglionic stimulation and exogenous noradrenaline were unaltered, with the exception of irbesartan, which reduced vascular noradrenaline sensitivity. The tripled dose of candesartan further reduced basal and angiotensin II-stimulated blood pressures, and significantly attenuated vascular noradrenaline sensitivity. AT1 antagonists at doses that effectively reduce blood pressure in chronic therapy do not generally suppress peripheral sympathetic function. A potential interaction consists in a reduction of vascular noradrenaline sensitivity, which can be considered as a class effect of AT1 antagonists at high dosage.


Distribution of calcitonin gene-related peptide immunoreactivity in relation to the rat central somatosensory projection.
The distribution of the neuropeptide calcitonin gene-related peptide (CGRP) was studied in relation to the known subcortical somatosensory pathways and contiguous systems in the central nervous system (CNS) of rats by using peroxidase histochemical methods in order to relate zones of immunoreactivity (IR) to cytoarchitecture. CGRP is the most ubiquitous peptide found to date in sensory ganglion cells: principally small and medium-size neurons emitting thin axons inferred to be largely nociceptive in function on the basis of the peripheral distribution of their terminals. Its apparent absence in sympathetic axons provides an especially useful sensory marker. The distribution of CGRP-IR axons displays remarkable selectivity at each level of the CNS. The trigeminal root distributes axons primarily to the pericornual layers (laminae I and II) of spinal V nucleus caudalis and to subnucleus oralis, evading the subnucleus interpolaris and contributing only few axons to principal V. Although there are only a few CGRP-IR somata at each level, heavily labeled axon trajectories can be traced to the nuclei of the solitary tract, the parabrachial nuclei, several sectors of the caudal medial thalamus, and the central nucleus of the amygdala. A sector of labeled neuron somata lies contiguous to each of these axon terminal zones, the largest of which is a thalamic nucleus containing cells of distinctive dendritic architecture extending from the periaqueductal gray across the posterior group nuclei to the peripeduncular nucleus, forming a linear array at the mesodiencephalic junction. The relation of CGRP-IR axonal distribution to spinothalamic, visceral, and gustatory systems is discussed in the context of a specialized "chemosensory" component of the thin-fiber somatosensory system.


The block of elongation in c-myc exon 1 is abolished in Burkitt's lymphoma cell lines with variant translocation.
Dimethylsulfoxide (DMSO) induces a block of c-myc RNA elongation in the human B cell line BJAB. In Burkitt's lymphoma cell lines with variant translocations, which are characterized by mutations in and around the first c-myc exon, DMSO is not capable of inducing the RNA elongation block. The action of DMSO is, however, not restricted to regulation at the level of RNA elongation. In the cell line BL2 with a t(8;22) translocation c-myc steady-state RNA decreased about 20 fold 1 and 2 h after DMSO treatment, followed by an increase to approximately initial levels after 4 h. During the time course of the experiment the usage of the dual promoter P1/P2 shifted from the ratio 3:1 in untreated cells to the ratio of 1:5 in BL2 cells treated with DMSO for 4 h. This promoter shift is presumably regulated at the transcriptional level. In BJAB cells an isolated intragenic transcription was detected at the boundary of intron 1 and exon 2. This transcription appeared 2 to 4 h after addition of DMSO when expression of the c-myc gene was downregulated by blocking RNA elongation at the end of exon 1.


Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy.
In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3O4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity (r 2) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity (r 1) (r 2/r 1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T2-weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy.


Occupational health in Poland.
Globalization and Poland's pending membership in the European Union have created a need for reappraisal of the country's occupational health and safety (OHS) programs. The current trend of industrial growth is likely to follow observed historical patterns in other parts of the world: the manufacturing sector will shrink, and the service sector will increasingly play a dominant role. Poland's OHS structure must be tailored accordingly. This article outlines the current state of OHS in Poland and indicates priorities for future research and special attention.


Scaled Model Tests Investigating Deformation Characteristics of Geosynthetic Reinforced Soil (GRS) Abutments under Vertical Loads.
This study conducted plane-strain scaled model tests to investigate the deformation characteristics of geosynthetic reinforced soil (GRS) abutments subjected to vertical loads. Setback distance, i.e., the distance between the back of the abutment facing and the front of the loading plate, was chosen as the investigated influencing factor since it is one of the most frequently used variables by engineers for the design of GRS abutments. This study analyzed the settlements at the top of the abutment, the lateral displacements of the abutment facing, and the volumetric deformations of the abutment under the applied vertical loads. Test results showed that increasing the setback distance could effectively reduce the deformations of the GRS abutment. There existed an optimum setback distance and further increasing the setback distance beyond this optimum value did not have a significant effect on reducing the abutment deformations. The vertical, lateral, and total volumetric deformations of the GRS abutment showed an approximately linear increase with the increase of the applied vertical loads. The lateral volumetric deformations of the GRS abutment were larger than its vertical volumetric deformations and therefore the total volumetric strains of the GRS abutment were not zero based on the test results. However, the theory of zero volume change may still be suitable for the deformation calculation of the GRS abutment since the values of the volumetric strains were minimal. The measured maximum lateral facing displacements were compared with the calculated values using the US Federal Highway Administration (FHWA) method, which assumes zero volume change of the GRS abutment under vertical loads. Comparison results indicated that the FHWA method overestimated the maximum lateral facing displacements of the GRS abutment under vertical loads. An improved method was proposed in this study to calculate the maximum lateral facing displacements under vertical loads based on the theory of zero volume change and a revised distribution of the settlements at the top of the GRS abutment. Results showed that the improved method could better predict the maximum lateral facing displacements as compared to the FHWA method.


Pattern of CSF glucose concentration after induced hyperglycaemia in patients with acute meningitis and evidence of cerebrospinal canal obstruction.
The pattern of glucose CSF concentration after induced hyperglycaemia was studied in 14 patients suffering from acute meningitis and 10 having meningism, as judged by normal CSF. Four out of the first group of patients had symptoms and signs likely to be due to cerebrospinal canal obstruction after the acute phase of the disease was over. When the patterns of CSF glucose concentration of the two groups were compared it was noted that patients suffering from acute meningitis showed generally a quicker and more profound rise of glucose levels after induced hyperglycaemia than patients with meningism. In four cases CSF glucose levels showed a partial or complete failure to rise, despite adequate increase of blood glucose concentration. Subsequent investigation revealed permanent obstruction of the cerebrospinal canal in three of the cases. The usefulness of serial CSF glucose estimations after induced hyperglycaemia as an early screening test for cases with possible obstruction is discussed.


Insulin resistance as a therapeutic target for chronic kidney disease.
Insulin resistance (IR) is a prevalent metabolic feature in chronic kidney disease (CKD). Postreceptor insulin-signaling defects have been observed in uremia. A decrease in the activity of phosphatidylinositol 3-kinase appears critical in the pathophysiology of CKD-associated IR. Lipotoxicity due to ectopic accumulation of lipid moieties has recently emerged as another mechanism by which CKD and/or associated metabolic disorders may lead to IR through impairment of various insulin-signaling molecules. Metabolic acidosis, anemia, excess of fat mass, inflammation, vitamin D deficiency, adipokine imbalance, physical inactivity, and the accumulation of nitrogenous compounds of uremia all contribute to CKD-associated IR. The clinical impacts of IR in this setting are numerous, including endothelial dysfunction, increased cardiovascular mortality, muscle wasting, and possibly initiation and progression of CKD. This is why IR may be a therapeutic target in the attempt to improve outcomes in CKD. General measures to improve IR are directed to counteract causal factors. The use of pharmaceutical agents such as inhibitors of the renin-angiotensin system may improve IR in hypertensive and CKD patients. Pioglitazone appears a safe and promising therapeutic agent to reduce IR and uremic-associated abnormalities. However, interventional studies are needed to test if the reduction and/or normalization of IR may actually improve outcomes in these patients.


Amplification of RNA for Microarrays.
Gene expression profiling typically requires microgram quantities of mRNA, which can be difficult to obtain. In such cases, RNA must be amplified to have enough material for microarray labeling and hybridization. This protocol generates amplified antisense RNA (aRNA) from limited quantities of total RNA. It is designed around maximizing yield and product length while minimizing template-independent side reactions. Template-independent reactions compete with the desired template-dependent reaction, an undesirable situation that becomes more severe as less RNA template is used. Amplification products dominated by template-independent product result in greatly reduced sensitivity and compression of differences in microarray hybridization experiments. Most notably, the oligo(dT) primer used in reverse transcription (RT) yields a high-molecular-weight product in the in vitro transcription (IVT) reaction independent of any cDNA template. This protocol therefore limits the amount of primer used by using small cDNA synthesis volumes. In addition, high-molecular-weight, template-independent product is generated in the presence of biotinylated NTPs and the absence of any polymer when excessive amounts of T7 RNA polymerase activity are used. Template-dependent product of questionable molecular weight and limited functionality in downstream reactions can also be produced with excessive T7 RNA polymerase activity. Essentially, more yield is not always better. Here, a single round of amplification typically results in a fivefold to 20-fold mass conversion of starting material. If the first-round aRNA is used as a template for a second round of amplification, 200- to 400-fold amplification is typical.


Minimally Invasive Retrograde Method of Harvesting the Flexor Hallucis Longus Tendon: A Cadaveric Study.
Use of the flexor hallucis longus (FHL) tendon is well described for several tendon augmentation procedures. Harvesting the FHL through an open medial approach is commonly done, but is associated with anatomic risks. Recently, several authors have described a minimally invasive (MI) technique to harvest the FHL tendon utilizing a hamstring tendon stripper commonly used in ACL reconstruction. The purpose of this study was to evaluate the safety and effectiveness of harvesting the FHL tendon using this novel minimally invasive retrograde approach. The FHL tendon was harvested through a transverse plantar incision over the interphalangeal joint of the great toe in 10 fresh-frozen cadaver lower extremities. A lateral-based incision for peroneal tendon repair was made and the FHL was retrieved. Tendon length, complications, and interconnections between the FHL and flexor digitorum longus (FDL) were recorded and classified. The specimens were then dissected by a single surgeon in a standardized fashion, and damage to any surrounding structures was recorded. The average length of the FHL tendon from the distal stump to the first intertendinous connection was 13.3 cm (range 8.8-16 cm, SD 2.3 cm). Eight cadavers demonstrated Plaass type 1 interconnections whereas 2 demonstrated type 3. There was no injury to the medial and lateral plantar arteries and nerves, plantar plate, or FDL tendons. One FHL tendon was amputated at the level of the sustentaculum during graft harvest. No injury of the medial neurovascular structures occurred with retrieval of the FHL tendon through the lateral incision. We found that care must be taken when approaching the sustentaculum with the tendon harvester in order to avoid amputation of the graft against a hard bony endpoint. Additionally, flexion and extension of the lesser toes could aid in successful tendon harvest when tendon interconnections were encountered. Using this MI technique appears to be a safe and effective way to obtain a long FHL tendon graft for tissue augmentation.


Attitudes toward abortion, social welfare programs, and gender roles in the U.S. and South Africa.
Public abortion attitudes are important predictors of abortion stigma and accessibility, even in legal settings like the U.S. and South Africa. With data from the U.S. General Social Survey and South African Social Attitudes Survey, we used ordinal logistic regressions to measure whether abortion acceptability (in cases of poverty and fetal anomaly) is related to attitudes about social welfare programs and gender roles, then assessed differences by race/ethnicity and education. Social welfare program attitudes did not correlate with abortion acceptability in the U.S., but in South Africa, greater support for income equalization (OR: 0.59, 95% CI: 0.41-0.85) and increased government spending on the poor (OR: 0.66, 95% CI: 0.49-0.91) correlated with lower abortion acceptability in circumstances of poverty. This was significant for Black African and higher educated South Africans. In the U.S., egalitarian gender role attitudes correlated with higher acceptability of abortion in circumstances of poverty (OR: 1.18, 95% CI: 1.03-1.36) and fetal anomaly (OR: 1.15, 95% CI: 1.01-1.31). This was significant for White and less educated Americans. In South Africa, egalitarian gender role attitudes correlated with higher abortion acceptability for fetal anomaly (OR: 1.12, 95% CI: 1.01-1.25) overall and among Black and less educated respondents, but among non-Black South Africans they correlated with higher abortion acceptability in circumstances of poverty. These results suggest abortion attitudes are distinctly related to socioeconomic and gender ideology depending one's national context, race/ethnicity, and socioeconomic status. Reducing abortion stigma will require community-based approaches rooted in intersectional reproductive justice frameworks.


Competition of electrons to enter the respiratory chain: a new regulatory mechanism of oxidative metabolism in Saccharomyces cerevisiae.
In the yeast Saccharomyces cerevisiae, the most important systems for conveying excess cytosolic NADH to the mitochondrial respiratory chain are the external NADH dehydrogenases (Nde1p and Nde2p) and the glycerol-3-phosphate dehydrogenase shuttle. In the latter system, NADH is oxidized to NAD+ and dihydroxyacetone phosphate is reduced to glycerol 3-phosphate by the cytosolic Gpd1p. Subsequently, glycerol 3-phosphate donates electrons to the respiratory chain via mitochondrial glycerol-3-phosphate dehydrogenase (Gut2p). At saturating concentrations of NADH, the activation of external NADH dehydrogenases completely inhibits glycerol 3-phosphate oxidation. Studies on the functionally isolated enzymes demonstrated that neither Nde1p nor Nde2p directly inhibits Gut2p. Thus, the inhibition of glycerol 3-phosphate oxidation may be caused by competition for the entrance of electrons into the respiratory chain. Using single deletion mutants of Nde1p or Nde2p, we have shown that glycerol 3-phosphate oxidation via Gut2p is inhibited fully when NADH is oxidized via Nde1p, whereas only 50% of glycerol 3-phosphate oxidation is inhibited when Nde2p is functioning. By comparing respiratory rates with different respiratory substrates, we show that electrons from Nde1p are favored over electrons coming from Ndip (internal NADH dehydrogenase) and that when electrons come from either Nde1p or Nde2p and succinodehydrogenase, their use by the respiratory chain is shared to a comparable extent. This suggests a very specific competition for electron entrance into the respiratory chain, which may be caused by the supramolecular organization of the respiratory chain. The physiological consequences of such regulation are discussed.


Successful multiresistant community-associated methicillin-resistant Staphylococcus aureus lineage from Taipei, Taiwan, that carries either the novel Staphylococcal chromosome cassette mec (SCCmec) type VT or SCCmec type IV.
Methicillin-resistant Staphylococcus aureus (MRSA) isolates carry the methicillin resistance gene (mecA) on a horizontally transferred genetic element called the staphylococcal chromosome cassette mec (SCCmec). Community-acquired MRSA (CAMRSA) isolates usually carry SCCmec type IV. We previously reported that 76% of 17 CAMRSA isolates (multilocus sequence type 59) obtained from pediatric patients with skin and soft tissue infections (SSTI) from Taipei did not carry SCCmec types I to IV. We used DNA sequence analysis to determine that the element harbored by these nontypeable isolates is a novel subtype of SCCmec V called SCCmec V(T.) It contains a ccrC recombinase gene variant (ccrC2) and mec complex C2. One SSTI isolate contained molecular features of SCCmec IV but also contained ccrC2 (a feature of SCCmec V(T)), suggesting that it may harbor a composite SCCmec element. The genes lukS-PV and lukF-PV encoding the Panton-Valentine leukocidin (PVL) were present in all CAMRSA SSTI isolates whether they contained SCCmec type IV or V(T). SCCmec V(T) was also present in 5 of 34 (14.7%) CAMRSA colonization isolates collected from healthy children from Taipei who lacked MRSA risk factors. Four (80%) of the these isolates contained lukS-PV and lukF-PV, as did 1 of 27 (3.7%) SCCmec IV-containing colonization isolates. A total of 63% (10 of 16) of the SSTI isolates and 61.7% (21 of 34) of the colonization isolates tested were resistant to at least four classes of non-beta-lactam antimicrobials. SCCmec V(T) is a novel SCCmec variant that is found in multiply resistant CAMRSA strains with sequence type 59 in Taipei in association with the PVL leukotoxin genes.


Life style and cardiovascular risk factors in the Japanese population--from an epidemiological survey on serum lipid levels in Japan 1990 part 1: influence of life style and excess body weight on HDL-cholesterol and other lipid parameters in men.
Low HDL-cholesterol (HDL-C) has long been used as an important predictor of coronary artery disease (CAD), although HDL-C values themselves are influenced by various factors including serum triglyceride (TG) levels, obesity, and life style. In view of the importance of the metabolic syndrome as a risk factor of CAD, changes in HDL-C and other lipid parameters in the Japanese population associated with life style, especially in males, were analyzed in this study based on data obtained in an epidemiological survey carried out in 1990. Smokers had higher TG and lower HDL-C levels than non-smokers, while BMI and LDL-C were slightly decreased by smoking in middle-aged men (40-59 years old). Increases in both HDL-C and TG due to alcohol consumption were associated with an increase in BMI in younger men aged 20-39. In middle-aged men, significant increases in HDL-C were seen in every quintile of BMI, while the increase in TG levels due to alcohol was small. Middle-aged men engaged in occupations requiring greater physical activity also had higher HDL-C levels in every quintile of BMI. The influence of life style on serum lipid parameters appeared to be mostly expressed as a function of BMI in younger men, while it appeared to be independent of BMI in older men.


Michelin tire baby syndrome: a review of the literature and a proposal for diagnostic criteria with adoption of the name circumferential skin folds syndrome.
The term Michelin tire baby (MTB), named for the cartoon mascot of the Michelin Tire Company, has been used to describe babies with multiple symmetric circumferential rings of folded skin. In those reported with this phenotype who had skin biopsies, pathology has shown nevus lipomatosis, smooth muscle hamartoma, degenerative collagen, and scarring. Others did not undergo biopsy or had normal skin. Many individuals with the MTB phenotype have had a variety of other congenital anomalies. I review the literature on MTB and the history of the designation Michelin tire baby Syndrome (MTBS). Because the term MTBS has been poorly defined or not defined at all, I propose strict criteria for diagnosis. In doing so, it is recommended that the syndrome be renamed to avoid further confusion.


Influence of phase transformation on stress evolution during growth of metal thin films on silicon.
In situ stress measurements during two-dimensional growth of low mobility metal films on amorphous Si were used to demonstrate the impact of interface reactivity and phase transformation on stress evolution. Using Mo1-xSix films as examples, the results show that the tensile stress rise, which develops after the film has become crystalline, is correlated with an increase in lateral grain size. The origin of the tensile stress is attributed to the volume change resulting from the alloy crystallization, which occurs at a concentration-dependent critical thickness.


Acute meningoencephalitis in chronic human immunodeficiency virus (HIV) infection: putative central nervous system escape of HIV replication.
We describe 3 patients with chronic human immunodeficiency virus (HIV) infection who presented with syndromes compatible with acute meningoencephalitis secondary to HIV; these syndromes were characterized by elevated cerebrospinal spinal fluid (CSF) HIV viral loads and T2-weighted signal abnormalities on magnetic resonance imaging of the brain. After the initiation of or a change in highly active antiretroviral therapy (HAART), each of the patients had significant and rapid improvement in neurologic symptoms and dramatic reductions in CSF HIV viral loads. Although further investigation is needed, these findings suggest that measurement of CSF HIV viral load and treatment with central nervous system-penetrating HAART should be considered for patients with acute neurologic complaints, chronic HIV infection, and no other identifiable cause of neurologic illness.


[Community requirements relating to drugs derived from human blood and plasma].
Since the adoption of the first pharmaceutical directive in 1965, the pharmaceutical legislation of the European Community has constantly pursued two objectives: the protection of public health and the free movement of products. Directive 89/381/EEC covers stable industrially prepared blood derivatives, intended for a large number of patients, namely albumin, coagulation factors and immunoglobulins. Whole blood, plasma and cellular components are excluded from the scope of the directive. As a consequence of the inclusion of blood derivatives in Community pharmaceutical legislation, these products are now subject to its general provisions regarding manufacturing and marketing authorization. The principles of good manufacturing practice laid down in Directive 91/356/EEC and detailed in a guide for manufacturers have become mandatory, as well as the tests in Directive 91/507/EEC aimed at demonstrating quality, safety and efficacy for the purpose of marketing authorization. The European format for the application file as well as the Community procedures for marketing authorization are applicable. In addition to these general provisions, which are applicable to all medicinal products, Directive 89/381/EEC contains several elements which are specific to medicinal products derived from human blood or plasma. The measures for selection and control of blood donors recommended by the Council of Europe and the World Health Organization have become compulsory. Moreover, for these particularly sensitive products, the Council has explicitly demanded the application of validated manufacturing and purification processes, in order to guarantee, insofar as the state of technology permits, the absence of specific viral contamination. For new medicinal products, the Directive entered into force on 1 January 1992. For products already on the market, a transitional period of one year was provided, during which the Member States had to proceed with the review of these products. The objective of Community self-sufficiency in blood and blood derivatives by voluntary unpaid donations is clearly expressed in the text of the Directive and the Member States have to inform the Commission on measures taken in this area. Thus, in adopting the Directive, the 12 Member States established as an objective that self-sufficiency be attained through voluntary unpaid blood donation. But, in addition to the Directive, the general rules of the EC Treaty are applicable, namely with regard to free movement of products, public procurement and monopolies.


ACOG Practice Bulletin No. 99: management of abnormal cervical cytology and histology.
Recent evidence has shown that the risk of malignant and premalignant cervical disease and human papillomavirus (HPV) infections varies significantly with age (1,2). Furthermore, evidence now shows that treatment for cervical disease carries significant risk for future pregnancies (3-7). These factors have led to a re-evaluation of the guidelines for the management of premalignant cervical disease. The purpose of this document is to define strategies for diagnosis and management of abnormal cervical cytology and histology results. In this document, HPV refers to high-risk oncogenic forms of the virus.


Hospital factors associated with discharge bias in ICU performance measurement.
Performance assessments based on in-hospital mortality for ICU patients can be affected by discharge practices such that differences in mortality may reflect variation in discharge patterns rather than quality of care. Time-specific mortality rates, such as 30-day mortality, are preferred but are harder to measure. The degree to which the difference between 30-day and in-hospital ICU mortality rates-or "discharge bias"-varies by hospital type is unknown. The aim of this study was to quantify variation in discharge bias across hospitals and determine the hospital characteristics associated with greater discharge bias. Retrospective cohort study. Nonfederal Pennsylvania hospital discharges in 2008. Eligible patients were 18 years old or older and admitted to an ICU. None. We used logistic regression with hospital-level random effects to calculate hospital-specific risk-adjusted 30-day and in-hospital mortality rates. We then calculated discharge bias, defined as the difference between 30-day and in-hospital mortality rates, and used multivariable linear regression to compare discharge bias across hospital types. A total of 43,830 patients and 134 hospitals were included in the analysis. Mean (SD) risk-adjusted hospital-specific in-hospital and 30-day ICU mortality rates were 9.6% (1.3) and 12.7% (1.5), respectively. Hospital-specific discharge biases ranged from -1.3% to 6.6%. Discharge bias was smaller in large hospitals compared with small hospitals, making large hospitals appear comparatively worse from a benchmarking standpoint when using in-hospital mortality instead of 30-day mortality. Discharge practices bias in-hospital ICU mortality measures in a way that disadvantages large hospitals. Accounting for discharge bias will prevent these hospitals from being unfairly disadvantaged in public reporting and pay-for-performance.


Electrospun TiO2 nanofiber integrated lab-on-a-disc for ultrasensitive protein detection from whole blood.
ELISA-based devices are promising tools for the detection of low abundant proteins in biological samples. Reductions of the sample volume and assay time as well as full automation are required for their potential use in point-of-care diagnostic applications. Here, we present a highly efficient lab-on-a-disc composed of a TiO2 nanofibrous mat for sensitive detection of serum proteins with a broad dynamic range, with only 10 μL of whole blood within 30 min. The TiO2 nanofibers provide high specific surface area as well as active functional groups to capture large amounts of antibodies on the surface. In addition, the device offers efficient mixing and washing for improving the signal-to-noise ratio, thus enhancing the overall detection sensitivity. We employ the device for the detection of cardiac biomarkers, C-reactive protein (CRP) and cardiac troponin I (cTnI), spiked in phosphate-buffered saline (PBS) as well as in serum or whole blood. The device exhibited a wide dynamic range of six orders of magnitude from 1 pg mL(-1) (~8 fM) to 100 ng mL(-1) (~0.8 pM) and a low detection limit of 0.8 pg mL(-1) (~6 fM) for CRP spiked in CRP-free serum and a dynamic range of 10 pg mL(-1) (~0.4 pM) to 100 ng mL(-1) (~4 nM) with a detection limit of 37 pg mL(-1) (~1.5 pM) for cTnI spiked in whole blood.


ACE gene polymorphism in premature neonates with respiratory distress syndrome.
The purpose of this study was to investigate the relationship between angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism and respiratory distress syndrome (RDS) in premature neonates. The patient group consisted of 101 premature neonates born before 37 weeks of gestation and diagnosed as RDS. The control group consisted of 100 premature neonates born before 37 weeks of gestation, but was not diagnosed as RDS. Genomic DNA from patients and controls was analyzed by polymerase chain reaction. D/D genotype was significantly higher in patient group (60.4% patients vs. 37.0% controls, p<0.05), whereas in the controls I/D genotype was markedly higher (33.7% patients vs. 61.0% controls, p<0.05). However, no marked change was observed with I/I genotype (5.9% patients vs. 2.0% controls). A significant increase of D alleles was observed in patients, whereas I allele was higher in controls (p<0.05). These results demonstrated the existence of higher frequency of the D/D genotype and D allele in premature neonates with RDS. These data may suggest that carriers of the D/D genotype and D allele are at increased risk of RDS development in premature neonates.


Bortezomib Maintenance for the Treatment of Monoclonal Gammopathy of Renal Significance.
Monoclonal gammopathy of renal significance (MGRS) defines renal diseases resulting from the nephrotoxic effects of monoclonal proteins secreted from non-malignant clonal B cells or plasma cells, that do not meet criteria for multiple myeloma, Waldenstrom's macroglobulinemia, chronic lymphocytic leukemia, or lymphomas. Renal disease in MGRS can result from monoclonal immunoglobulin deposition to different parts of the kidney and includes a wide spectrum of glomerular, tubulointerstitial and vascular renal diseases. Recognizing MGRS is important because renal outcomes are poor and treatments targeting the underlying clonal disease have been associated with improved renal survival. In this case report, we present a case of a patient with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) subtype of MGRS who underwent a phased clone directed treatment of induction and extended maintenance therapy to achieve renal response.


Structural and Sequence Similarity Makes a Significant Impact on Machine-Learning-Based Scoring Functions for Protein-Ligand Interactions.
The prediction of protein-ligand binding affinity has recently been improved remarkably by machine-learning-based scoring functions. For example, using a set of simple descriptors representing the atomic distance counts, the RF-Score improves the Pearson correlation coefficient to about 0.8 on the core set of the PDBbind 2007 database, which is significantly higher than the performance of any conventional scoring function on the same benchmark. A few studies have been made to discuss the performance of machine-learning-based methods, but the reason for this improvement remains unclear. In this study, by systemically controlling the structural and sequence similarity between the training and test proteins of the PDBbind benchmark, we demonstrate that protein structural and sequence similarity makes a significant impact on machine-learning-based methods. After removal of training proteins that are highly similar to the test proteins identified by structure alignment and sequence alignment, machine-learning-based methods trained on the new training sets do not outperform the conventional scoring functions any more. On the contrary, the performance of conventional functions like X-Score is relatively stable no matter what training data are used to fit the weights of its energy terms.


Nothing Else Matters! Trade-Offs Between Perceived Benefits and Barriers of AAL Technology Usage.
Ambient assisted living (AAL) technologies present one approach to counter the challenges of demographic change in terms of an aging population, rising care needs, and lacking care personnel by supporting (older) people in need of care and enabling a longer and more independent staying at own home. Although the number of studies focusing on AAL users' acceptance and perception has increased in the last years, trade-off decisions-the weighing of perceived benefits and barriers of technology usage-have not been studied so far. Nevertheless, this is of high relevance: A realistic evaluation of adoption behaviors in different stakeholders (patients, care personnel) requires an understanding of exactly the weighing process of benefits against the barriers in line with the decision of the final willingness to use AAL technology. The current study applied a conjoint analysis approach and investigates people's decision behavior to use an AAL system for a family member in need of care. Study participants (n = 140) had to decide between realistic care scenarios consisting of different options of two benefits (increase in safety, relief of caring burden of relatives) and two barriers (access to personal data and data handling) of technology usage. Results revealed data access and privacy to be most relevant for the decision to use AAL technology at home. However, care experience essentially influenced the decision patterns. For the care experienced group, data access should be limited to most trusted persons and close relatives, rather than to medical professionals. The most important reasons to use AAL are the emotional relief and the felt safety for the person in care. For care novices, in contrast, data access should be in the exclusive responsibility of medical professionals. The reasons that militate in favor of using AAL technology are the increase in process efficiency and medical safety. The results are useful to develop user-tailored technology concepts and derive user-specific communication guidelines within and across clinical and home care contexts.


Fueling innovation in medical devices (and beyond): venture capital in health care.
Innovation in health care requires new ideas and the capital to develop and commercialize those ideas into products or services. The necessary capital is often "venture capital," but the link between public policy and the venture capital industry has not been well examined. In this paper we explore the link between venture capital and innovation in health care, and we present new descriptive data from a survey of health care venture capital fund managers. Respondents generally viewed policy levers (for example, reimbursement and regulations) as important risks to venture capital investments, potentially affecting their ability to raise capital for early-stage investment funds.


Methicillin-resistant Staphylococcus aureus infections in correctional facilities---Georgia, California, and Texas, 2001-2003.
Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are common in hospitals and nursing homes. Because MRSA is resistant to all commonly prescribed beta-lactam antibiotics (e.g., penicillins and cephalosporins), these infections require treatment with alternative antimicrobial drugs. In addition, because antimicrobial drugs usually must be selected before identifying MRSA as the cause of infection, treatment presents a challenge for clinicians. MRSA has emerged recently as a more frequent cause of skin and soft tissue infections in the community, particularly in correctional facilities such as prisons, jails, and detention centers. This report summarizes recent investigations of MRSA transmission among inmates of correctional facilities in Georgia, California, and Texas. Inadequate personal hygiene, barriers to medical care, and other factors contributed to transmission. Information from these investigations has been used in the development of recently released Federal Bureau of Prisons guidance for control of MRSA, which recommends improvements in inmate hygiene, infection control, and targeted antimicrobial treatment.


Brain nonapeptide and gonadal steroid responses to deprivation of heterosexual contact in the black molly.
Fish may respond to different social situations with changes in both physiology and behaviour. A unique feature of fish is that social interactions between males and females strongly affect the sexual characteristics of individuals. Here we provide the first insight into the endocrine background of two phenomena that occur in mono-sex groups of the black molly (Poecilia sphenops): masculinization in females and same-sex sexual behaviour, manifested by gonopodial displays towards same-sex tank mates and copulation attempts in males. In socially controlled situations, brain neurohormones impact phenotypic sex determination and sexual behaviour. Among these hormones are the nonapeptides arginine vasotocin (AVT) and isotocin (IT), counterparts of the well-known mammalian arginine vasopressin and oxytocin, respectively. To reveal potential hormone interactions, we measured the concentrations of bioactive AVT and IT in the brain, along with those of the sex steroids 17β-estradiol and 11-ketotestosterone in the gonads, of females, masculinized females, males displaying same-sex sexual behaviour and those who did not. These data were supplemented by morphological and histological analyses of the gonads. Correlations between brain nonapeptides and gonadal steroids strongly suggest a cross talk between hormonal systems. In the black molly, the masculinization process was associated with the production of brain AVT and gonadal steroids, whereas same-sex sexual behaviour involves both brain nonapeptides, but neither of the sex steroids. This study extends current knowledge of endocrine control of phenotypic sex and sexual behaviour in fish and for the first time links brain nonapeptides with the occurrence of male-male sexual behaviour in lower vertebrates.


[Two Cases of Small Bowel Obstruction Due to Postoperative Adhesions Treated with Laparoscopic Adhesiolysis].
We occasionally require surgical treatment for postoperative adhesion ileus. One patient had adhesion ileus 14 times in 14 years after distal gastrectomy and Billroth-Ⅰreconstruction for gastric cancer. He underwent laparoscopic adhesiolysis for a small bowel obstruction that adhered to the entire surface. Another patient experienced adhesion ileus 7 times in 1.5 years after distal gastrectomy and Billroth-Ⅰreconstruction for gastric cancer. He underwent laparoscopic adhesiolysis for a small bowel obstruction adhering to the scar and the retroperitoneum. After laparoscopic treatment, he underwent an open operation for ischemic colitis but no small bowel obstruction was found. Laparoscopic adhesiolysis was found to be useful in both cases.


Glucagon-Like Peptide-1 Modulates Cholesterol Homeostasis by Suppressing the miR-19b-Induced Downregulation of ABCA1.
Abnormal regulation of cholesterol homeostasis is associated with type 2 diabetes mellitus (T2DM) and multiple other diseases. Glucagon-like peptide-1 (GLP-1) has unique effects on modulating hepatic lipid metabolism. However, the mechanism behind these is largely unknown. The aim of this study was to investigate the effects of GLP-1 on cholesterol-induced lipotoxicity in hepatocytes and examine the underlying mechanisms. Cell viability was determined by CCK-8. Caspase-3 detection was used to assess the effects of GLP-1 on cholesterol-induced apoptosis. TNF-α and IL-6 as the inflammatory markers were measured by ELISA. The alterations of miR-19b and ATP-binding cassette transporter A1 (ABCA1) resulting from high-fat diet/cholesterol incubation or GLP-1 were detected by real-time PCR and western blot. GLP-1 markedly up-regulated the expression of ABCA1 protein, but didn't affect peroxisome proliferator-activated receptor α (PPAR-α) protein. The miR-19b levels were significantly down-regulated in GLP-1-treated groups. The inhibition and overexpression of miR-19b were established to explore the effects of a GLP-1-mediated alteration in miR-19b. Cholesterol transport assays revealed that treatment with GLP-1 alone or together with miR-19b inhibitor significantly enhanced ABCA1-dependent cholesterol efflux, resulting in reduced total cholesterol. Further, histological examination was used to detect lipid accumulation. Cholesterol significantly attenuated cell viability, promoted hepatic cell apoptosis, and facilitated lipid accumulation, and these effects could be reversed by GLP-1. GLP-1 may affect cholesterol homeostasis by regulating the expression of miR-19b and ABCA1.


[Vascular changes in postmastectomy "thick arm"].
The authors, after shortly outlining some pathogenetic theories about postmastectomy "big arm", especially dwell upon the theory of the hindered venous discharge. They, subsequently, through a clear and interesting phlebographic iconography, illustrate ten of the 41 cases suffering from such syndrome, they recently had the opportunity to observe. On the basis of their own experience, and according to part of the literature thereabout, the authors think very probably the postmastectomy "big arm" is to be ascribed to the hindered venous reflux of upper limb (for thrombosis or compression), due to the operation of mastectomy. As a conclusion, they suggest the improvement or recovery of this syndrome by stepping over the stenosed venous tract through a by-pass.


Complex communication signals: the case of the Blue-black Grassquit Volatinia jacarina (Aves, Emberizidae) song. Part I--a structural analysis.
The song of the Blue-black Grassquit Volatinia jacarina is different for every individual and the structural differences between individuals are quite complex. Samples of songs from different Brazilian localities, as well as from Venezuela and Mexico, were studied through a comparative analysis of their sonograms. From the structural point of view, the results show a song composed of a single note that is compacted in a "window" between 2 and 13 kHz and rarely occupying more than half of a second. The note is essentially pure and is repeatedly uttered with a high level of fidelity. A global frequency modulation decreases from the beginning to the end of the song. The main song components are referred to as "Blocks" and are of three types: "Vibrations" (Buzzes or Vibratos), "Arabesques" (complex notes) and "Isolated Modulations" (simple syllables). Among other characteristics are double voices, which are quite diverse and probably function as codes for individual recognition. This song is considered a special case where a signature system has been developed to a high level of inter-individual variability.


Portable devices and mobile instruments for infectious diseases point-of-care testing.
Rapidity, simplicity, and portability are highly desirable characteristics of tests and devices designed for performing diagnostics at the point of care (POC), either near patients managed in healthcare facilities or to offer bioanalytical alternatives in external settings. By reducing the turnaround time of the diagnostic cycle, POC diagnostics can reduce the dissemination, morbidity, and mortality of infectious diseases and provide tools to control the global threat of antimicrobial resistance. Areas covered: A literature search of PubMed and Google Scholar, and extensive mining of specialized publications, Internet resources, and manufacturers' websites have been used to organize and write this overview of the challenges and requirements associated with the development of portable sample-to-answer diagnostics, and showcase relevant examples of handheld devices, portable instruments, and less mobile systems which may or could be operated at POC. Expert commentary: Rapid (<1 h) diagnostics can contribute to control infectious diseases and antimicrobial resistant pathogens. Portable devices or instruments enabling sample-to-answer bioanalysis can provide rapid, robust, and reproducible testing at the POC or close from it. Beyond testing, to realize some promises of personalized/precision medicine, it will be critical to connect instruments to healthcare data management systems, to efficiently link decentralized testing results to the electronic medical record of patients.


Human nonsyndromic sensorineural deafness.
Given the unique biological requirements of sound transduction and the selective advantage conferred upon a species capable of sensitive sound detection, it is not surprising that up to 1% of the approximately 30,000 or more human genes are necessary for hearing. There are hundreds of monogenic disorders for which hearing loss is one manifestation of a syndrome or the only disorder and therefore is nonsyndromic. Herein we review the supporting evidence for identifying over 30 genes for dominantly and recessively inherited, nonsyndromic, sensorineural deafness. The state of knowledge concerning their biological roles is discussed in the context of the controversies within an evolving understanding of the intricate molecular machinery of the inner ear.


The retinoid-inducible gene I: effect on apoptosis and mitogen-activated kinase signal pathways.
The retinoid-inducible gene I (RIG1), belonging to the family of type II tumor suppressor genes, was isolated from human gastric cancer cells treated with all-trans retinoic acid. The activity of the RIG1 gene was investigated in this study. HtTA cervical and TSGH9201 gastric cancer cells were transiently transfected with expression vectors that synthesized RIG1-myc or RIG1-EGFP fusion protein. Cell growth was analyzed by measuring the incorporation of bromodeoxyuridine. Apoptosis was evaluated by the formation of in situ DNA breakage. The activities of mitogen-activated kinase signal pathways were analyzed using signal pathway trans-reporting systems. Expression of the RIG1-myc fusion protein resulted in decreased cell growth. Both RIG1-EGFP and RIG1-myc fusion proteins induced cellular apoptosis that was characterized by the presence of apoptotic bodies and in situ DNA breakage. The transactivation activities of Elk1, c-Jun and CHOP proteins were suppressed by 80, 50 and 88%, respectively, in HtTA cells expressing the RIG1-myc fusion protein for two days. Similarly, the transactivation activities of the CHOP protein was suppressed in TSGH9201 and HtTA cells transiently expressing RIG1-myc and RIG1-EGFP, respectively. The RIG1 fusion proteins exhibited growth suppressive and apoptosis-inducing activity. The protein negatively-regulated signal pathways of extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38 mitogen-activated kinase.


How I treat smoldering multiple myeloma.
Smoldering myeloma is a heterogeneous clinical entity where a subset of patients has an indolent course of disease that mimics monoclonal gammopathy of undermined significance, whereas others have a more aggressive course that has been described as "early myeloma." It is defined as either serum M-protein ≥ 3 g/L or ≥ 10% monoclonal plasma cells in the bone marrow. There are currently no molecular factors to differentiate risks of progression for these patients. Current recommendations of therapy continue to be patient observation or patient enrollment in clinical trials. However, new definitions of active multiple myeloma recently agreed upon by the International Myeloma Working Group may alter the timing of therapy. On the basis of emerging data of therapy in these patients, it seems reasonable to believe that future recommendations for therapy of patients with smoldering myeloma will become an increasingly important topic. In this article, we review the current knowledge of this disease and risk factors associated with progression. We also examine biological insights and alterations that occur in the tumor clone and the surrounding bone marrow niche. Finally, we review clinical trials that have been performed in these patients and provide recommendations for follow-up of patients with this unique disease entity.


Levetiracetam for the treatment of status epilepticus.
Status epilepticus (SE) is a common, severe neurological disorder, and prolonged seizures in SE may result in irreversible brain damage in association with high disability and mortality rates. Thus, termination of seizures as soon as possible is vital for the successful treatment of this disease. Levetiracetam, a new broad-spectrum anti-epileptic drug, can be used to rapidly and effectively control SE episodes with few side effects. Thus, an understanding of the use of this drug to treat SE will help clinicians to more effectively control SE and improve patient prognosis.


Factors related to standing balance in patients with knee osteoarthritis.
To assess factors related to standing balance in patients with knee osteoarthritis (OA). In total, 37 female patients with painful knee OA were included. Pain, knee alignment, and Kellgren and Lawrence grade were evaluated accordingly. Static standing balance was measured with a force-platform system under two different conditions: static standing with eyes open (EO) and eyes closed (EC) for 30 seconds. The mean speed (mm/s) of movement of the center of pressure in the anteroposterior (AP) and mediolateral directions and the mean velocity moment (mm(2)/s) were analyzed for assessment of static balance. In the univariate regression analysis, age and knee alignment showed statistically significant relationships with the mean speed in the AP directions with EO. In the multiple linear regression model, age and knee alignment were positively associated and disease severity was negatively associated with mean speed in the AP directions with EO. However, the variables for EC static measurements were not significantly correlated with age, pain, knee alignment, or radiographic severity (p>0.05). These findings show that the worse balance was associated with advanced age, less varus knee malalignment, and mild radiographic changes. Pain was not associated with standing balance.


Counselling risk figures for fragile X carrier females of varying band sizes for use in predicting the likelihood of retardation in their offspring.
We have derived risk figures for fra(X) syndrome carrier mothers based on their DNA status. Clinical and molecular information was analysed in 200 carrier mothers and their offspring. Individuals were classified as affected by a requirement for special education. Risk figures were calculated using the genotype of the intellectually normal offspring in order to reduce ascertainment bias. Analysis was made on women with differing mutation size to predict the proportion of affected offspring. Using this method the following risk figures were derived: 1. For carrier women with an increase (delta) of 0.06-0.14 Kb, the risk for having an affected son was 29% (1 in 3.5) and 25% for daughters (1 in 4). This predicts an overall 73% chance of a normal child. 2. For delta size 0.15-0.24 Kb, the risk of having an affected son was 46% (1 in 2.2) and 32% for daughters (1 in 3.1), predicting a 61% chance of a normal child. 3. For delta size > 0.24 Kb, normal transmitting male offspring were not seen, i.e., the risk for males was 50% (1 in 2) and for females 32% (1 in 3.1) which predicts a 59% chance of a normal child.


Testicular cancer: innovations in diagnosis and treatment.
We are fortunate at this point in time that testicular cancer is probably the most successfully treated solid tumor. Although many diagnostic tools are available, successful diagnosis still relies on suspicion, and to a great extent, physical findings. Staging techniques have greatly improved but they still have limitations. Through advances in the treatment of disease, the toxicity of the treatment regimens and the morbidity from surgery and chemotherapy have been much reduced. Recently, advances have been made that will most likely allow the majority of patients to maintain their fertility even though they require surgical staging and perhaps chemotherapy for their disease. We are fortunate that we are truly in the time where the emphasis can be placed on finding less extensive treatments and still maintaining the high success rates that are enjoyed in the treatment of this tumor. However, one note of caution needs to be sounded, that continued long-term observation and tabulation of the results will be necessary in order to monitor the efficacy of our reduced treatment schemes.