A TEAM approach to NICU care.
The NICU can be a very stressful place not only for the infants who need intensive care, but also for their parents. By implementing family-centered care using the TEAM model described here, nurses can make baby's stay less upsetting, promote bonding between parents and child, and help improve postpartum care.


Combined granular-lattice ('Avellino') corneal dystrophy.
In 1988, a report was published describing the histopathologic examination of corneal buttons of 4 patients who had undergone unilateral keratoplasty because of decreased vision caused by what had been diagnosed clinically as granular dystrophy. But on pathologic examination, lesions characteristic of both granular dystrophy and lattice dystrophy were found in each of the 4 corneal buttons. The patients came from 3 different families, each of which traced its origin to the Italian province of Avellino. We studied the clinical and histopathological features of 4 corneas affected by combined granular-lattice dystrophy, adding thereby to the total of 12 other corneas that have been so-described in the literature. Two women underwent bilateral penetrating keratoplasty for what was diagnosed clinically as Reis-Bücklers dystrophy in the first patient, and as granular dystrophy in the second patient. We studied all 4 corneas pathologically, using both conventional hematoxylin and eosin stains as well as special histochemical techniques. All 4 corneas contained lesions characteristic of both granular dystrophy and lattice dystrophy, a circumstance that has given rise to the name "combined granular-lattice dystrophy." The patients are not known to be of Italian ancestry. Three clinical signs characterize combined granular-lattice dystrophy: (1) anterior stromal discrete, grayish-white deposits; (2) lattice lesions located in mid-stroma to posterior stroma; and (3) anterior stromal haze. Both clinically and histopathologically, the lattice lesions are of greater diameter than are those that occur in lattice dystrophy type I. In the past few years, striking advances have been made in understanding the genetics of combined granular-lattice dystrophy. The most recent of these was published just 2 months before the 1997 meeting of the American Ophthalmological Society, and establishes a common molecular origin for granular dystrophy, lattice dystrophy type I, Avellino dystrophy, and Reis-Bücklers dystrophy.


Speech outcomes at 5 and 10 years of age after one-stage palatal repair with muscle reconstruction in children born with isolated cleft palate.
The aim of this study was to investigate speech outcomes in children with clefts in the hard and/or soft palate only (CPH/CPS), in order to determine the prevalence of cleft speech characteristics, the change between 5 and 10 years of age, and the difference in occurrence between CPH and CPS. A consecutive series of 88 children born with CPH or CPS were included in a retrospective cohort. All participants were treated with one-stage palatal repair using a minimal incision technique with muscle reconstruction (mean age 13 months). Twelve children (14%) received a velopharyngeal flap. Cleft speech variables were rated at 5 and 10 years of age independently by three experienced external speech-language pathologists. Inter- and intra-rater agreements were determined, and the prevalence of cleft speech characteristics was calculated. Moderate-to-severe hypernasality and weak pressure consonants were present in 5%-10% of the children at 5 years, with marginal but statistically significant improvement at 10 years of age. Frequently or always occurring audible nasal air leakage was detected in 20% of children at age 5, and increased to ∼35% of the children at 10 years. Ten per cent had compensatory articulation at age 5, and 25% demonstrated s-distortions, whereas few had these problems at age 10. The results demonstrate low occurrence of compensatory articulation problems in this cohort, even by 5 years of age. The high presence of symptoms of velopharyngeal insufficiency at 10 years of age suggests a need for additional secondary velopharyngeal surgery.


[Giant traumatic diaphragmatic hernia as a complication after laparoscopic liver surgery].
Laparoscopic surgery is now one of the main options for patients with surgical diseases of abdominal cavity, pelvis and retroperitoneal space. Postoperative complications are known, and methods for their prevention after such interventions are well developed. However, there are rare complications, and their management deserves a special attention. The authors present a patient with giant traumatic hernia in long-term period after laparoscopic liver surgery. Clinical manifestations of disease are retrospectively analyzed. The authors discuss surgical aspects of treatment, i.e. choice of access, repair of diaphragmatic defect and peculiarities of postoperative period associated with non-anatomic return of abdominal organs through the diaphragmatic defect. This report will be useful for radiologists, thoracic and abdominal surgeons, anesthesiologists and intensive care specialists.


Dimensional accuracy of 3 silicone dental impression materials.
This study was carried out to measure the dimensional changes in silicone impression material, which can affect the fitness of the prosthesis. Using both single and double mix techniques, 20 impression samples for each of 3 different proprietary silicones, Xantopren-H, President and Fulldent, were made. Selected measurements were made on the stone casts made from each impression. In all 3 cases, the single mix gave more accurate casts than the double mix technique. The Xantopren-H impressions had the most accurate dimensions.


Changes in the Distance Between the Distal Rectal Pouch and Perineum From the Birth Day to the Next Day in Neonates With an Imperforate Anus.
To evaluate changes in the distance between the distal rectal pouch and the perineum (pouch-perineum distance) from the birth day to the next day and to determine which day is better for diagnosis of a low-type imperforate anus in neonates. We reviewed medical records at our hospital from May 2003 to August 2015 and identified 9 neonates with a radiographically and surgically proven low-type imperforate anus and 9 with high/intermediate types of imperforate anus who had undergone sonography on both the birth day and the next day before the first surgical treatment. The sonograms were reviewed to measure the pouch-perineum distance at both examinations. The Wilcoxon signed rank sum test and a receiver operating characteristic curve analysis were used for the statistical analyses. The pouch-perineum distance on the next day (mean ± SD, 9.37 ± 4.89 mm; range, 2.1-20.9 mm) was significantly shorter than on the birth day (15.75 ± 6.67 mm; range, 8.1-37.2 mm; P = .001). The receiver operating characteristic analysis showed significantly better diagnostic performance (P < .001) of the pouch-perineum distance on the next day (area under the curve, 0.864) versus the birth day (0.420) for the low-type imperforate anus. The pouch-perineum distance was shorter on the next day than on the birth day, and the diagnostic performance of the pouch-perineum distance on the next day was significantly superior to that on the birth day for the diagnosis of a low-type imperforate anus. We recommend sonography on the next day in neonates with an imperforate anus when possible.


Do guidelines for the diagnosis and monitoring of diabetes mellitus fulfill the criteria of evidence-based guideline development?
Although the methodological quality of therapeutic guidelines (GLs) has been criticized, little is known regarding the quality of GLs that make diagnostic recommendations. Therefore, we assessed the methodological quality of GLs providing diagnostic recommendations for managing diabetes mellitus (DM) and explored several reasons for differences in quality across these GLs. After systematic searches of published and electronic resources dated between 1999 and 2007, 26 DM GLs, published in English, were selected and scored for methodological quality using the AGREE Instrument. Subgroup analyses were performed based on the source, scope, length, origin, and date and type of publication of GLs. Using a checklist, we collected laboratory-specific items within GLs thought to be important for interpretation of test results. The 26 diagnostic GLs had significant shortcomings in methodological quality according to the AGREE criteria. GLs from agencies that had clear procedures for GL development, were longer than 50 pages, or were published in electronic databases were of higher quality. Diagnostic GLs contained more preanalytical or analytical information than combined (i.e., diagnostic and therapeutic) recommendations, but the overall quality was not significantly different. The quality of GLs did not show much improvement over the time period investigated. The methodological shortcomings of diagnostic GLs in DM raise questions regarding the validity of recommendations in these documents that may affect their implementation in practice. Our results suggest the need for standardization of GL terminology and for higher-quality, systematically developed recommendations based on explicit guideline development and reporting standards in laboratory medicine.


Significance of the timing of ureteral ligation on prognosis during radical nephroureterectomy for upper urinary tract urothelial cancer.
To investigate the impact on intravesical recurrence and prognosis according to the ureteral ligation timing during radical nephroureterectomy for upper urinary tract urothelial carcinoma. We carried out a retrospective chart review of 664 patients with non-metastatic upper urinary tract urothelial carcinoma who underwent radical nephroureterectomy with ureteral ligation (supplementary analysis of JCOG1110A). We excluded patients with previous and/or synchronous bladder cancer, clinically node-positive disease, no ureteral ligation data, those without ureteral ligation and those with any missing data. We investigated the cumulative incidence of intravesical recurrence and cancer-specific mortality, and overall survival between patients with ureteral ligation before renovascular ligation (early ureteral ligation), or ureteral ligation after renovascular ligation (late ureteral ligation). Early and late ureteral ligation was carried out in 243 patients (36.6%) and 421 patients (63.4%), respectively. Intravesical recurrence occurred in 218 patients (32.8%) during follow up (median 3.9 years). No significant difference in the intravesical recurrence was found between early and late ureteral ligation groups. Meanwhile, survival in the early ureteral ligation group was significantly worse compared with the late ureteral ligation group. Multivariable analysis showed that early ureteral ligation was an independent prognostic factor for overall survival (hazard ratio 1.88, 95% confidence interval 1.24-2.85, P = 0.003) and cancer-specific mortality (hazard ratio 1.93, 95% confidence interval 1.14-3.25, P = 0.014). Our findings suggest that the incidence of intravesical recurrence is not affected by the timing of ureteral ligation during radical nephroureterectomy. However, early ureteral ligation might have a negative impact on survival outcomes.


Yeast-recombinant hepatitis B vaccine. Efficacy with hepatitis B immune globulin in prevention of perinatal hepatitis B virus transmission.
A yeast-recombinant hepatitis B vaccine was licensed recently by the Food and Drug Administration and is now available. To assess the efficacy of the yeast-recombinant vaccine, we administered the vaccine in combination with hepatitis B immune globulin to high-risk newborns. If infants whose mothers were positive for both hepatitis B surface antigen and the e antigen receive no immunoprophylaxis, 70% to 90% become infected with the virus, and almost all become chronic carriers. Among infants in this study who received hepatitis B immune globulin at birth and three 5-micrograms doses of yeast-recombinant hepatitis B vaccine, only 4.8% became chronic carriers, a better than 90% level of protection and a rate that is comparable with that seen with immune globulin and plasma-derived hepatitis B vaccine. These data suggest that, in this high-risk setting, the yeast-recombinant vaccine is as effective as the plasma-derived vaccine in preventing hepatitis B virus infection and the chronic carrier state.


Indirect pulp therapy in a symptomatic mature molar using calcium enriched mixture cement.
Dental pulp has the ability of repair/regeneration. Indirect pulp therapy (IPT) is recommended for pulp preservation in asymptomatic teeth with extremely deep caries as well as teeth with clinical symptoms of reversible pulpitis. In this case study, we performed IPT with calcium enriched mixture (CEM) cement on a symptomatic permanent molar. After clinical/radiographic examinations the tooth was diagnosed with irreversible pulpitis and associated apical periodontitis. IPT involved partial caries removal, the placement of CEM cement pulp cap and overlying adhesive permanent restoration. At the 1 week follow-up, patient's spontaneous symptoms had resolved. One-year follow-up demonstrated pulp vitality, clinical function, as well as the absence of pain/tenderness to percussion/palpation/cold sensitivity tests; periapical radiograph showed a healing periradicular lesion with newly formed bone, that is normal pulp with normal periodontium. These favorable results indicate that IPT/CEM may be a good treatment option in comparison to endodontic treatment in young patients. IPT of deep-caries lesion is an easier, more practical and valuable treatment plan than complete caries removal.


[Correlation between the EEG coherence and recognition of emotions in speech].
Analysis of the EEG in 2 extreme groups: subjects with high and low indexes of identification of emotional intonation, was carried out. The number of pairs of electrode sites with significant differences in coherence was compared at rest and during the emotion identification task in 6 standard frequency bands. The data revealed that, in general, coherence is higher in the group with low identification rates.


The wandering mood: psychological and neural determinants of rest-related negative affect.
Rest related negative affect (RRNA) has gained scientific interest in the past decade. However, it is mostly studied within the context of mind-wandering (MW), and the relevance of other psychological and neural aspects of the resting state to its' occurrence has never been studied. Several indications associate RRNA with internally directed attention, yet the nature of this relation remains largely unknown. Moreover, the role of neural networks associated with rest related phenomenology - the default mode (DMN), executive (EXE), and salience (SAL) networks, has not been studied in this context. To this end, we explored two 5 (baseline) and 15-minute resting-state simultaneous fMRI-EEG scans of 29 participants. As vigilance has been shown to affect attention, and thus its availability for inward allocation, EEG-based vigilance levels were computed for each participant. Questionnaires for affective assessment were administered before and after scans, and retrospective reports of MW were additionally collected. Results revealed increased negative affect following rest, but only among participants who retained high vigilance levels. Among low-vigilance participants, changes in negative affect were negligible, despite reports of MW occurrence in both groups. In addition, in the high-vigilance group only, a significant increase in functional connectivity (FC) levels was found between the DMN-related ventral anterior cingulate cortex (ACC), associated with emotional processing, and the EXE-related dorsal ACC, associated with monitoring of self and other's behavior. These heightened FC levels further correlated with reported negative affect among this group. Taken together, these results demonstrate that, rather than an unavoidable outcome of the resting state, RRNA depends on internal allocation of attention at rest. Results are discussed in terms of two rest-related possible scenarios which defer in mental and neural processing, and subsequently, in the occurrence of RRNA.


Interventional Radiology: Indications and Best Practices.
Interventional radiology employs image-guided techniques to perform minimally invasive procedures for diagnosis and treatment. Interventional radiology is often used to place central venous catheters and subcutaneous ports, with some evidence of benefit over surgical placement. Arterial embolization procedures are used to manage many types of hemorrhage and are highly effective for severe postpartum hemorrhage. Vascular interventions, such as endovascular treatment of varicosities, acute limb ischemia, and pulmonary embolism, are superior to surgical interventions. For chronic limb ischemia and deep venous thrombosis, the choice of therapy is not as clear. Inferior vena cava filters can be placed and removed endovascularly, but there is a significant risk of complications that increases over time. Vascular interventions can be effective for scrotal varicocele and uterine fibroids, although fibroid treatment is limited by high recurrence rates. Image-guided percutaneous drainage and biopsy have become standard of care. Interventional approaches are being used in oncology for local diagnosis and treatment. Percutaneous ablation and targeted delivery of chemotherapy and radiation therapy are being developed as alternatives when surgery is not practical. Vertebroplasty and kyphoplasty provide significant pain and functional improvement in patients with spinal metastases.


[Analysis of risk factors related to mortality of patients with community-acquired pneumonia due to methicillin-resistant Staphylococcus aureus].
To describe the clinical features of reported cases of community-acquired pneumonia (CAP) due to methicillin-resistant Staphylococcus aureus (MRSA), and to evaluate the risk factors related to outcome. A systematic search of databases from January 1995 to December 2009 was performed. Baseline characteristics of survivors and non-survivors in the hospital were compared with the chi2 test for categorical variables. Variables with P<0.2 were entered in Logistic regression. Survival analysis was estimated by the Kaplan-Meier method according to use of antimicrobials inhibiting toxin production. Fifty-two articles were identified reporting data on 74 patients, with 41.1% of total mortality, short duration of symptom onset to death [(6.1+/-11.0) days], and prolonged hospital admissions [(28.6+/-29.1) days]. Logistic regression analysis showed that influenza like symptoms (P=0.04), hemoptysis (P<0.01), leucopenia (P<0.01) were the risk factors associated with death, and using clindamycin or linezolid which could inhibit the Panton-Valentine leukocidin (PLV, P<0.01) was the factor associated with survival. Kaplan-Meier analysis indicated that the antibiotic therapies inhibiting toxin production were associated with improved outcome in these cases (chi2=21.59, P<0.01). CAP due to MRSA is a severe disease with significant lethality. Empiric therapy of severe CAP with flu-like symptoms, hemoptysis and leucopenia should include coverage for MRSA. Targeted treatment with antimicrobials inhibiting toxin production appear to be more appropriate selection.


CT colonography with fecal tagging after incomplete colonoscopy.
The objective of this study was to evaluate dietary fecal tagging (FT) as a cleansing method prior to CT colonography (CTC) in patients with incomplete conventional colonoscopy (CC). After written informed consent was obtained, 24 patients had standard colonoscopic preparation (ScCl), and 25 patients had FT as cleansing method. Segmental distention, fluid levels, fecal residues, tagged appearance of fluid levels, and residual stool were evaluated. Mann-Whitney U test was used to test for significant differences between FT and ScCl groups. Compared with ScCl, FT improved distention (p=0.001), reduced the amount of fluid (p=0.043), but suffered from residual stool (p=0.046). A clear correlation was found between distention and fluid. No differences were found in stool size between FT and ScCl. FT showed a good labeling of fecal residues, and acceptable labeling of fluid levels. Compared with ScCl, FT reduces fluid, favors distention, but suffers from fecal residues. The tagged nature of these residues, however, allows differentiation from polyps.


Intraluminal exfoliated cancer cells and effectiveness of bowel ligatures during sigmoidectomy for sigmoid colon cancer.
To establish the efficiency of bowel ligatures in colon cancer surgery, focusing on the extent to which exfoliated cancer cells are shed in the colonic lumen during sigmoidectomy. Twenty consecutive patients who underwent sigmoidectomy for sigmoid colon cancer were prospectively randomized into two groups: the "ligatures group", in which bowel ligatures were placed, 3, 5, 10 cm from the tumor proximally and distally before dissection; and the "no ligatures group", in which the corresponding sites were ligated only immediately before taking the specimen out. Each colonic segment ligated was irrigated with saline and samples were sent for blind cytological examination. Cancer cells were found in the colonic segment where the tumor was located, in 18 of 20 samples. The frequency of free cancer cells decreased from 50 to 0 % (p < 0.04) in the distal 3-5 cm colonic segment and from 80 to 20 % (p < 0.03) in the proximal colonic segment after performing bowel ligatures. Free cancer cells were confirmed in 1 of 10 samples at both colonic segments 5-10 cm from the tumor, even after bowel ligatures. Intraluminal exfoliated cancer cells could be eliminated by placing bowel ligatures during sigmoidectomy. Measures should be considered to eliminate exfoliated cancer cells during colectomy, even after placing bowel ligatures.


Short-Term Comfort Responses Associated With the Use of Eyelid Cleansing Products to Manage Demodex folliculorum.
To quantify the discomfort over time of various eyelid cleansers against Demodex. This was a prospective, randomized, controlled, crossover, open-label study that enrolled 26 participants. The cleansers used in this study were Biotissue Cliradex (CD), OCuSOFT Lid Scrubs Plus (OP), OCuSOFT OUST Demodex Swabstix (ODS), TheraTears Theralid (TT), NovaBay Avenova (NA). Bausch+Lomb Sensitive Eyes Plus saline was used as a control. Participants were asked to close their eyes as the product was gently rubbed (10 cycles of gentle lateral motion) into the eyelashes. Participants verbally rated their discomfort (0 = no discomfort, 10 = maximum tolerable discomfort) every 15 sec for the first 5 min, and every 30 sec for 5 min after, for a total of 10 min. The order of products used was randomized, and washout period between cleansing was 48 hr. Twenty-five participants completed the study (mean age=26±6). There was no significant difference in discomfort scores at pre-application. The discomfort levels of saline, OP, and NA over the 10-min period were not significantly different than their pre-application discomfort at all time points (all P≥0.99). The discomfort of CD was significantly higher than pre-application levels between t=15 sec and t=180 sec (all P≤0.01), with maximum median (interquartile range [IQR]) discomfort of 3.0 (5.0) occurring at t=45 sec. The discomfort of TT was significantly higher than pre-application levels between t=45 and t=90 (all P<0.02), with maximum median (IQR) discomfort of 1.0 (1.5) occurring at t=75 sec. The discomfort of ODS was significantly higher than pre-application levels starting from t=60 sec and onward, with maximum median (IQR) discomfort of 6.0 (5.0) occurring at t=300 sec. Of the cleansers used in this study, the ones that induced significant discomfort were CD, TT, and ODS. The results from this study may help clinicians educate patients about what to expect when approaching the topic of eyelid Demodex treatment.


Gambling Patterns and Problem Gambling Among Youth in Sub-Saharan Africa: A Systematic Review.
Mounting evidence suggests that youth in sub-Saharan Africa (SSA) find themselves increasingly drawn to gambling related activities; an issue, that if left unchecked, can lead to adverse consequences including financial difficulties, crime and mental health problems. To better understand the psychosocial mechanisms underlying problem gambling, there is a pressing need to conduct more research on gambling related disorders amongst this vulnerable stratum of society. Against this background, the present review explores gambling patterns, attitudes and behaviors among youth in SSA-in a manner aligning with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We systematically searched 8 databases including PubMed, Science Direct, Scopus, ProQuest, Wiley Online, Google Scholar, PsycINFO and PsycARTICLES for published research articles up until July 2019. A total of 1624 articles were screened, of which, only 13 studies met inclusion criteria. All of these studies were cross-sectional in nature and the quality of each study was evaluated using the Newcastle-Ottawa Scale. Studies varied considerably ranging from neuropsychological and personality trait assessment to application of item response theory. Due to this study heterogeneity we could not conduct a meta-analysis. The results presented here suggest that the existing body of evidence pertaining to patterns of gambling-related harm among youth in SSA is weak. This study highlights the need for additional good quality studies focusing on gambling related behaviors and prevalence levels among the continent's youth. Additionally, the findings reported herein emphasise the need for implementing social policies alongside effective public health interventions to tackle gambling addiction.


Excellent Survival Rate of Cemented Modular Stems in One-Stage Revision for Periprosthetic Hip Infections With Massive Femoral Bone Loss: A Retrospective Single-Center Analysis of 150 Cases.
With the increasing incidence of total hip arthroplasty (THA) there is also an expected concurrent increase in revision THA (rTHA), which is known to have a high complication and re-revision rate. In the setting of infection, radical debridement is essential and options for femoral bone loss are limited. One viable solution is cemented modular stems, but limited evidence exists on their use in septic revision. This study aimed to analyze survival and complication related to the use of cemented modular stems in one-stage septic rTHA with severe femoral bone loss. The institutional database of patients who underwent rTHA for septic one-stage revision with cemented modular stems was reviewed. Exclusion criteria were patients under 18 years, and non-septic or two stage revisions. Outcomes measured were complication, re-infection, re-operation, and survivorship of the implant. A total of 150 patients were included. The mean age was 68 years (range, 30 to 91), and the mean follow-up was 105 months (range, 1 to 150). Treatment was considered successful in 81.3 % of cases. Patients who underwent multiple prior surgeries demonstrated a lower rate of treatment success (P<0.001). The main cause of failure was re-infection (11 out of 28). Among cases failed for aseptic reasons (17 out of 28), loosening of the cemented modular stem was the cause of re-revision in two patients (1.3%). The use of modular cemented stems is a viable option in case of septic one-stage rTHA associated with severe femoral bone loss. However, surgeons and patients should be aware that this treatment is still characterized by a high rate of complications, which may lead to further surgeries.


Performance of Clinical Algorithms for Smear-Negative Tuberculosis in HIV-Infected Persons in Ho Chi Minh City, Vietnam.
Background. Tuberculosis (TB) disease diagnosis in Vietnam relies on symptom screening, chest radiography (CXR), and acid fast bacilli (AFB) sputum smear which have a poor sensitivity in HIV patients. We evaluated the performance of clinical algorithms in screening and diagnosing AFB smear-negative TB in HIV patients. Methods. We enrolled 399 HIV-positive patients seeking care at a HIV clinic in Ho Chi Minh City (HCMC), Vietnam. Participants' demographics, medical history, common TB symptoms, CXR, and laboratory tests were collected. Results. Of 399 HIV patients, 390 had initial AFB-negative smears and 22/390 patients had positive cultures. Symptom screening missed 54% (12/22) of smear-negative pulmonary TB (PTB) cases. Multivariate analysis found CD4+ cell level and CXR were significant PTB predictors. An algorithm combining four TB symptoms and TST presented a high sensitivity (100%), but poorly specific (24%) diagnostic performance for smear-negative PTB. Conclusion. Up to 54% of PTB cases in the HIV-infected population may be missed in the routine screening and diagnostic procedures used in Vietnam. Symptom screening was a poor overall diagnostic measure in detecting smear-negative TB in HIV patients. Our study results suggest that routine sputum cultures should be implemented to achieve a more accurate diagnosis of TB in HIV patients.


Degranulation status of airway tissue eosinophils in mouse models of allergic airway inflammation.
Eosinophil degranulation is a characteristic feature of asthma and allergic rhinitis. However, degranulated eosinophils have not been convincingly demonstrated in the common mouse models of these airway diseases. This study uses eosinophil peroxidase (EPO) histochemistry and transmission electron microscopy (TEM) analysis to assess eosinophil degranulation in the airways of ovalbumin (OVA)-sensitized and challenged BALB/c and C57BL/6 mice. Using TEM we also examined mouse and human blood eosinophils after in vitro incubation with formyl-Met-Leu-Phe (fMLP) or phorbol myristate acetate (PMA). Although OVA exposure induced significant nasal and lung eosinophilia, we did not observe any of the known cellular processes by which eosinophils release their granule products, i.e., eosinophil cytolysis, piecemeal degranulation, and exocytosis. The occurrence of other allergen-induced degranulation events was ruled out because no difference in granule morphology was observed between lung-tissue eosinophils and blood or bone-marrow eosinophils from control animals. Accordingly, there was no detectable extracellular EPO in lung tissues of allergic mice. Similarly, mouse blood eosinophils remained nondegranulated in vitro in the presence of fMLP and PMA, whereas the same treatment of human eosinophils resulted in extensive degranulation. This investigation indicates that OVA-induced airway inflammation in the present mouse strains does not involve significant eosinophil degranulation. It is speculated that this dissimilarity from the human disease may be due to a fundamental difference in the regulation of mouse and human eosinophils.


Improving the repeat prescribing process in a busy general practice. A study using continuous quality improvement methodology.
A need to improve service to patients by reducing the time wasted by reception staff so that the 48 hour target for processing repeat prescription requests for patient collection could be achieved. An interprofessional team was established within the practice to tackle the area of repeat prescribing which had been identified as a priority by practice reception staff. The team met four times in three months and used continuous quality improvement (CQI) methodology (including the Plan-Do-Study-Act cycle) with the assistance of an external facilitator. A seven partner practice serving the 14,000 patients on the northern outskirts of Bournemouth including a large council estate and a substantial student population from Bournemouth University. The repeat prescribing process is computerised. Reducing turn around times for repeat prescription requests. Reducing numbers of requests which need medical records to be checked to issue the script. Feedback to staff about the working of the process. Using a Plan-Do-Study-Act cycle for guidance, the team decided to (a) coincide repeat medications and to record on the computer drugs prescribed during visits; (b) give signing of prescriptions a higher priority and bring them to doctors' desks at an agreed time; and (c) move the site for printing prescriptions to the reception desk so as to facilitate face to face queries. Prescription turnaround within 48 hours increased from 95% to 99% with reduced variability case to case and at a reduced cost. The number of prescriptions needing records to be looked at was reduced from 18% to 8.6%. This saved at least one working day of receptionist time each month. Feedback from all staff within the practice indicated greatly increased satisfaction with the newly designed process. The team's experience suggests that a combination of audit and improvement methodology offers a powerful way to learn about, and improve, practice. The interventions used by the team not only produced measurable and sustainable improvements but also helped the team to learn about the cost of achieving the results and provided them with tools to accomplish the aims. The importance of feedback to all staff about CQI measures was also recognised.


Effect of penetration modifiers on the dermal and transdermal delivery of drugs and cosmetic active ingredients.
In this study the effect of 2 penetration modifiers, dimethyl isosorbide (DMI) and diethylene glycol monoethyl ether (DGME) on the skin delivery of hydroquinone (HQ), salicylic acid (SA) and octadecenedioic acid (DIOIC) was investigated. Ten percent DMI and DGME were separately formulated into oil-in-water emulsions containing 1.8% HQ, SA and DIOIC, respectively. Skin delivery and the flux across split-thickness human skin of the active ingredients were determined using Franz diffusion cells. An emulsion with 10% water incorporated instead of the water-soluble penetration modifiers served as a control. The study showed that neither 10% DMI nor 10% DGME significantly enhanced the skin permeation of the various lipophilic active ingredients or the uptake into the skin. It was hypothesized that the addition of the penetration modifiers to the emulsions not only enhanced the solubility of the various active ingredients in the skin but also in the formulation, resulting in a reduced thermodynamic activity and hence a weaker driving force for penetration. Therefore, the effect of DMI and DGME on the solubility of the active ingredients in the skin was counteracted by a simultaneous reduction in the thermodynamic activity in the formulation.


Change and technology in nursing education.
In 1989, the Faculty of Health Science (FHS) within the University of Central Queensland (UCQ, now the Central Queensland University) committed itself to a major instructional development project--eventually partly funded by an Australian government National Priority Reserve Fund (NPRF) grant--to develop computer-based learning materials for a new nursing education program. This study, extracted from Zelmer (1993), reports on the management of change within that project.


Ethical challenges in conducting research in humanitarian crisis situations.
Research is vital to accurately describe phenomena in humanitarian emergency situations and to evaluate the effectiveness and appropriateness of interventions. Although the ethical principles of justice, beneficence and respect for autonomy respect for persons should be upheld in research, their application in emergency situations may differ from non-emergency situations. Just like in non-emergency situations, research in emergency situations should be conducted in the best interest of the victims or future victims. The research should not unnecessarily expose human subjects and the researcher to careless harm, and should be of adequate scientific rigor. Victims of emergency situations are vulnerable populations that need special protection from exploitation. Technical competency to conduct research in emergency situations should include the ability to conduct a fair risk-benefit assessment in order to come up with a risk management plan, and being culturally sensitive to the needs of the victims of the humanitarian crisis. In emergency situations, the roles of Institutional Review Boards (IRBs) may have to be modified without compromising the ethical standards that health researchers have globally attempted to achieve.


[Egas Moniz and the leukotomy debate with special reference to Portuguese literature].
Although the practice of psychosurgery had already been introduced in 1888 by the Swiss psychiatrist Gottlieb Burckhardt, the most widely practiced form of psychiatric surgery--the so-called, lobotomy'--was first performed in 1935 by the Portuguese neurologist Egas Moniz (1874-1955). Although the reaction to his intervention was mixed, Moniz was awarded the Nobel Price for his work in 1949. The present article concentrates on both the Portuguese and the international perception of Moniz' lobotomy and its apparent ethical implications. One particularly important question that Moniz's work brings to the fore concerns the role of psychosurgery in contemporary psychiatry and--consequently--the role of the spirit of the age in judging psychosurgical interventions. Therefore the early reactions to lobotomy are opposed to recent and actual statements in and outside Iberia.


Understanding Challenges, Strategies, and the Role of Support Networks in Medication Self-management Among Patients With Type 2 Diabetes.
Purpose The purpose of this qualitative study was to investigate the challenges and strategies of patients with type 2 diabetes mellitus (T2DM) regarding daily management of their medication regimen focusing on the role of their support networks. Methods A purposeful sample of 25 patients with T2DM was recruited from local self-help groups, general practitioner practices, and a university hospital in southwestern Germany. Four semi-structured focus groups were conducted to identify the challenges patients experienced, the strategies they used, and their collaboration with support networks to assist them in self-managing their medication regimen. Sessions were audio- and video-recorded, fully transcribed, and subjected to computer-aided qualitative content analysis, guided by the Self- and Family Management Framework (SFMF). Results Patients with T2DM experienced numerous challenges affecting medication self-management arising from their personal situation, health status and resources, characteristics of their regimen, and how health care is currently organized. Patients' self-initiated strategies included activating health care, community, social, and online resources; taking ownership of medication-related needs; and integrating medication-taking into daily life. Patients drew on self-help groups, family, and friends to discuss concerns regarding medication safety and receive experience-based information and advice for navigating within the health care system as well as practical hands-on support with daily medication self-management. Conclusions Understanding the challenges and building on strategies patients with T2DM devised help diabetes educators to better address patients' needs and priorities and guide patient-centered interventions to support patients' self-management activities. Community and social support networks operating in patients' lives need to be engaged in the self-management support.


The Current Role of Cardiopulmonary Exercise Test in the Diagnosis and Management of Pulmonary Hypertension.
Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis if left untreated. Despite remarkable achievements in understanding disease pathophysiology, specific treatments, and therapeutic strategies, we are still far from a definitive cure for the disease, and numerous evidences have underlined the importance of early diagnosis and treatment to improve the prognosis. Cardiopulmonary exercise testing (CPET) is the gold standard for assessing functional capacity and evaluating the pathophysiological mechanisms underlying exercise limitation. As effort dyspnea is the earliest and one of the main clinical manifestations of PAH, CPET has been shown to provide valid support in early detection, differential diagnosis, and prognostic stratification of PAH patients, being a useful tool in both the first approach to patients and follow-up. The purpose of this review is to present the current applications of CPET in pulmonary hypertension and to propose possible future utilization to be further investigated.


Case Study: Unfavorable But Transient Physiological Changes During Contest Preparation in a Drug-Free Male Bodybuilder.
Extreme body composition demands of competitive bodybuilding have been associated with unfavorable physiological changes, including alterations in metabolic rate and endocrine profile. The current case study evaluated the effects of contest preparation (8 months), followed by recovery (5 months), on a competitive drug-free male bodybuilder over 13 months (M1-M13). Serum testosterone, triiodothyronine (T3), thyroxine (T4), cortisol, leptin, and ghrelin were measured throughout the study. Body composition (BodPod, dualenergy x-ray absorptiometry [DXA]), anaerobic power (Wingate test), and resting metabolic rate (RMR) were assessed monthly. Sleep was assessed monthly via the Pittsburgh Sleep Quality Index (PSQI) and actigraphy. From M1 to M8, testosterone (623-173 ng∙dL-1), T3 (123-40 ng∙dL-1), and T4 (5.8-4.1 mg∙dL-1) decreased, while cortisol (25.2-26.5 mg∙dL-1) and ghrelin (383-822 pg∙mL-1) increased. The participant lost 9.1 kg before competition as typical energy intake dropped from 3,860 to 1,724 kcal∙day-1; BodPod estimates of body fat percentage were 13.4% at M1, 9.6% at M8, and 14.9% at M13; DXA estimates were 13.8%, 5.1%, and 13.8%, respectively. Peak anaerobic power (753.0 to 536.5 Watts) and RMR (107.2% of predicted to 81.2% of predicted) also decreased throughout preparation. Subjective sleep quality decreased from M1 to M8, but objective measures indicated minimal change. By M13, physiological changes were largely, but not entirely, reversed. Contest preparation may yield transient, unfavorable changes in endocrine profile, power output, RMR, and subjective sleep outcomes. Research with larger samples must identify strategies that minimize unfavorable adaptations and facilitate recovery following competition.


Analysis and generalized correction of the effect of spatial gradient field distortions in diffusion-weighted imaging.
Nonuniformities of magnetic field gradients can cause serious artifacts in diffusion imaging. While it is well known that nonlinearities of the imaging gradients lead to image warping, those imperfections can also cause spatially dependent errors in the direction and magnitude of the diffusion encoding. This study shows that the potential errors in diffusion imaging are considerable. Further, we show that retrospective corrections can be applied to reduce these errors. A general mathematical framework was formulated to characterize the contribution of gradient nonuniformities to diffusion experiments. The gradient field was approximated using spherical harmonic expansion, and this approximation was employed (after geometric distortions were eliminated) to predict and correct the errors in diffusion encoding. Before the corrections were made, the experiments clearly revealed marked deviations of the calculated diffusivity for fields of view (FOVs) generally used in diffusion experiments. These deviations were most significant farther away from the magnet's isocenter. For an FOV of 25 cm, the resultant errors in absolute diffusivity ranged from approximately -10% to +20%. Within the same FOV, the diffusion-encoding direction and the orientation of the calculated eigenvectors can be significantly altered if the perturbations by the gradient nonuniformities are not considered. With the proposed correction scheme, most of the errors introduced by gradient nonuniformities can be removed.


Neuroradiologic correlates of cognitive impairment in adult Moyamoya disease.
MMD has been shown to result in impairment of executive functioning in adults. The purpose of this study was to correlate presurgical neuropsychological assessments with the severity of primary MMD as measured by CBF and CVR and with secondary damage from MMD as estimated by cortical stroke and WMD. A retrospective analysis of 31 adult patients with MMD was performed. Xe-CT was used to obtain CBF and CVR, and MRI was reviewed to grade cortical stroke and WMD. Two tests of executive functioning (FAS and TMT-B) were correlated with imaging findings. A multiple regression analysis was performed. There was a significant overall positive relationship between mean CBF and FAS (P = .038) and TMT-B scores (P = .014). A significant negative relationship was present between the WMD score and the FAS (P = .009) and TMT-B scores (P = .015). Per-region analysis demonstrated that FAS and TMT-B scores were significantly decreased by the presence of a posterior stroke (P < .0001 and P = .001) or WMD (P = .006 and P = .004). All patients with posterior parieto-occipital WMD or stroke also had secondary disease in the anterior regions. Impaired executive functioning in adults with MMD is most strongly associated secondary damage in the form of WMD or cortical stroke. The effect is most profound with parieto-occipital lobe involvement, likely a reflection of overall disease severity. Increasing global WMD burden may be a better indicator of cognitive decline than cortical infarction. Patients with higher baseline CBF seem to have better cognitive functioning.


Efficacy and Clinical Value of Negative-Pressure Wound Therapy with Instillation (NPWTi) of Compound Phellodendron Liquid in the Treatment of Diabetic Foot Ulcer: A Prospective Cohort Study.
To evaluate the efficacy and application value of compound Phellodendron liquid (CPL) for negative-pressure wound therapy with instillation (NPWTi) in the treatment of diabetic foot ulcers by observing the improvement of diabetic foot ulcers. Sixty patients with diabetic foot ulcers who met the inclusion criteria were admitted to the Department of Peripheral Blood Vessels (Wound Repair) of Chongqing Hospital of Traditional Chinese Medicine from August 2020 to August 2021. The random number table method divided it into the CPL NPWTi group and normal saline NPWTi group, with 30 cases in each group. The experimental group adopted FufangHuangbaiye for NPWTi, and the control group used normal saline for NPWTi. The treatment effect was evaluated by baseline index, wound healing observation index, inflammatory factor index, pain scores during dressing change, and the number of days in hospital. After 10 days of treatment, the symptom integration, procalcitonin (PCT), and C reactive protein (CRP) of the CPL NPWTi group were significantly reduced compared with the normal saline NPWTi group, while there was no obvious difference between wound area and erythrocyte sedimentation rate (ESR). The wound area, symptom integral, PCT, ESR, and CRP of the CPL NPWTi group were significantly reduced compared with the normal saline NPWTi group after treatment for 20 days and 30 days. The positive proportion of bacterial culture in the CPL NPWTi group was significantly reduced compared with the normal saline NPWTi group after treatment for 10 days, 20 days, and 30 days. After treatment, the pain scores during dressing change and the number of days in hospital in normal saline NPWTi group were significantly lower than those in the CPL NPWTi group. Compound Phellodendron liquid NPWTi therapy can improve diabetic foot ulcers, providing a safe and effective method for treating diabetic foot ulcers.


Very small mobile repeated elements in cyanobacterial genomes.
Mobile DNA elements play a major role in genome plasticity and other evolutionary processes, an insight gained primarily through the study of transposons and retrotransposons (generally approximately 1000 nt or longer). These elements spawn smaller parasitic versions (generally >100 nt) that propagate through proteins encoded by the full elements. Highly repeated sequences smaller than 100 nt have been described, but they are either nonmobile or their origins are not known. We have surveyed the genome of the multicellular cyanobacterium, Nostoc punctiforme, and its relatives for small dispersed repeat (SDR) sequences and have identified eight families in the range of from 21 to 27 nucleotides. Three of the families (SDR4, SDR5, and SDR6), despite little sequence similarity, share a common predicted secondary structure, a conclusion supported by patterns of compensatory mutations. The SDR elements are found in a diverse set of contexts, often embedded within tandemly repeated heptameric sequences or within minitransposons. One element (SDR5) is found exclusively within instances of an octamer, HIP1, that is highly over-represented in the genomes of many cyanobacteria. Two elements (SDR1 and SDR4) often are found within copies of themselves, producing complex nested insertions. An analysis of SDR elements within cyanobacterial genomes indicate that they are essentially confined to a coherent subgroup. The evidence indicates that some of the SDR elements, probably working through RNA intermediates, have been mobile in recent evolutionary time, making them perhaps the smallest known mobile elements.


[An analysis of the survival of 120 male patients with systemic lupus erythematosus].
The aim of the study was to evaluate survival rates and causes of death of a large group of male patients with systemic lupus erythematosus (SLE). The group consisted of 120 patients with evident SLE that were observed at the Institute of Reanimatology from 1976 to 1989; the mean age was 31.3 years; the mean age for the disease onset was 29.6 years; the mean follow-up duration was 9.1 years. The survival pattern was obtained with the method of the life table analysis. Maximum lethality was observed during the first years of the disease: in 1-4 years 11 patients died, in 5-6 years--6 patients, and in 8-12 years--7 patients; 27 patients died during the follow-up period, 17--died of lupus nephritis, 4--of neurological involvement, one patient--of heart insufficiency, one--of lung tuberculosis, one--of ischemic heart disease, one--of amyloidosis, one--of sepsis and one patient died of chronic lung insufficiency.


Genetic diagnosis of immune dysregulation can lead to targeted therapy for interstitial lung disease: A case series and single center approach.
In recent years, a growing number of monogenic disorders have been described that are characterized by immune dysregulation. A subset of these "primary immune regulatory disorders" can cause severe interstitial lung disease, often recognized in late childhood or adolescence. Patients presenting to pulmonary clinic may have long and complex medical histories, but lack a unifying genetic diagnosis. It is crucial for pulmonologists to recognize features suggestive of multisystem immune dysregulation and to initiate genetic workup, since targeted therapies based on underlying genetics may halt or even reverse pulmonary disease progression. Through such an approach, our center has been able to diagnose and treat a cohort of patients with interstitial lung disease from gene defects that affect immune regulation. Here we present representative cases related to pathogenic variants in three distinct pathways and summarize disease manifestations and treatment approaches. We conclude with a discussion of our perspective on the outstanding challenges for diagnosing and managing these complex life-threatening and chronic disorders.


Long-term virologic and immunologic responses in human immunodeficiency virus type 1-infected children treated with indinavir, zidovudine, and lamivudine.
Virologic and immunologic responses were examined for 33 human immunodeficiency virus (HIV)-infected children who participated for > or = 96 weeks in a phase 1/2 protocol of 16 weeks of indinavir monotherapy, followed by the addition of zidovudine and lamivudine. At week 96, a median increase of 199 CD4+ T cells/microL and a median decrease of 0.74 log(10) HIV RNA copies/mL were observed. The relationship between control of viral replication and CD4) T cell count was examined. Patients were categorized into 3 response groups on the basis of duration and extent of control of viral replication. Of 21 children with a transient decrease in virus load of > or = 0.7 log(10) HIV RNA copies/mL from baseline, 7 experienced sustained increases in CD4+, CD4+ CD45RA+, and CD4+ CD45RO+ T cell counts. CD4+ CD45RA+ (naive) T cells were the major contributor to CD4+ T cell expansion. Continued long-term immunologic benefit may be experienced by a subset of children, despite only transient virologic suppression.


Associations between concentrations of uric acid with concentrations of vitamin A and beta-carotene among adults in the United States.
Our objective was to examine the cross-sectional associations between concentrations of vitamin A and beta-carotene, a major source of vitamin A, with concentrations of uric acid in a nationally representative sample of adults from the United States. We conducted a cross-sectional study using data from up to 10893 participants aged ≥ 20 years of National Health and Nutrition Examination Survey from 2001 to 2006. Concentrations of uric acid adjusted for numerous covariates increased from 305.8 μmol/L in the lowest quintile of vitamin A to 335.3 μmol/L in the highest quintile (p for linear trend <0.001). The prevalence ratio for hyperuricemia also increased progressively across quintiles of serum vitamin A reaching 1.82 (95% confidence interval [CI]: 1.52, 2.16; p for linear trend <0.001) in the top quintile in the maximally adjusted model. Adjusted mean concentrations of uric acid decreased progressively from quintile 1 (333.8 μmol/L) through quintile 4 of concentrations of beta-carotene and were similar for quintiles 4 (313.5 μmol/L) and 5 (313.8 μmol/L). Concentrations of beta-carotene were inversely associated with hyperuricemia (adjusted prevalence ratio comparing highest with lowest quintile = 0.61; 95% CI: 0.52, 0.72; p for linear trend <0.001). Concentrations of uric acid were significantly and positively associated with concentrations of vitamin A and inversely with concentrations of beta-carotene. These cross-sectional findings require confirmation with experimental studies of vitamin A and beta-carotene supplementation.


Early feedback on the use of the internal medicine reporting milestones in assessment of resident performance.
The educational milestones were designed as a criterion-based framework for assessing resident progression on the 6 Accreditation Council for Graduate Medical Education competencies. We obtained feedback on, and assessed the construct validity and perceived feasibility and utility of, draft Internal Medicine Milestones for Patient Care and Systems-Based Practice. All participants in our mixed-methods study were members of competency committees in internal medicine residency programs. An initial survey assessed participant and program demographics; focus groups obtained feedback on the draft milestones and explored their perceived utility in resident assessment, and an exit survey elicited input on the value of the draft milestones in resident assessment. Surveys were tabulated using descriptive statistics. Conventional content analysis method was used to assess the focus group data. Thirty-four participants from 17 programs completed surveys and participated in 1 of 6 focus groups. Overall, the milestones were perceived as useful in formative and summative assessment of residents. Participants raised concerns about the length and complexity of some draft milestones and suggested specific changes. The focus groups also identified a need for faculty development. In the exit survey, most participants agreed that the Patient Care and Systems-Based Practice Milestones would help competency committees assess trainee progress toward independent practice. Draft reporting milestones for 2 competencies demonstrated significant construct validity in both the content and response process and the perceived utility for the assessment of resident performance. To ensure success, additional feedback from the internal medicine community and faculty development will be necessary.


[Interaction of human blood plasma proteins with glycosaminoglycans].
Binding of human blood plasma proteins with hyaluronic acid, chondroitin-4-SO4 and heparin was studied. Chondroitin-4-SO4 was not involved in the reaction, whereas heparin and hyaluronic acid formed complexes with the proteins at very low concentrations. The intensity of binding correlated with concentration of carbohydrates in blood plasma proteins. Heparin displaced hyaluronic acid in the complexes. Biological importance of the interactions between glycosaminoglycans and glycoproteins, incorporated into blood plasma as well as into cell membranes of various tissues, is discussed.


Swiss Prison Suicides Between 2000 and 2010.
Background: Suicide is the leading cause of death in Swiss prisons. The Federal Statistics Office provides numbers but no further details. Previous studies worldwide have focused on identifying suicide risk factors in prisoners, but very few have looked at the methods used in relation to prevention strategies. Aims: To obtain details of Swiss prison suicides, determine new findings in an international context, and establish prevention strategies based on the information acquired. Method: Retrospective data analysis of prison suicides extracted from the database of all suicides investigated by Swiss institutes of legal medicine between 2000 and 2010, using a standardized assessment sheet. Results: Out of 4,885 suicides investigated in the institutes of legal medicine in Switzerland, we identified 50 (1.02%) inmate suicides. Most were unmarried Swiss men, with a median age of 32 years. The two most common methods used were hanging and tricyclic antidepressant overdose. Two died due to self-immolation. Conclusion: Swiss prison suicides do not differ from those in other countries regarding sociodemographic details and the most common method of hanging. Anchoring devices, even low ones, should be avoided to prevent hanging and medication intake should be monitored. As prisoners use tricyclic antidepressants to die by suicide, we recommend the general monitoring of intake.


Retinopathy in Egyptian patients with sickle cell disease: A cross-sectional study.
Sickle cell disease (SCD) is a disorder that causes red blood cells to become sticky and rigid. Sickle cells can block blood flow in small blood vessels depriving the eye of oxygen and cause damage. This is called sickle retinopathy that can progress to severe proliferative sickle cell retinopathy, bleeding into the eye, detachment of the retina or even loss of vision.To assess ocular manifestations and detect frequency of retinopathy in patients with SCD.Cross-sectional study was conducted on 32 patients with SCD. They were 22 males and 10 females with mean age of 12 years. Routine investigations as well as ophthalmological examination including visual acuity, fluorescein angiography and optical coherence tomography were done.We found that 8 patients (25%) suffered from proliferative retinopathy, 10 patients (31%) showed tortuous retinal veins, while 14 patients (44%) were normal. All patients showed macular thinning on optical coherence tomography examination.We concluded that frequency of retinopathy in patients with SCD is more than expected and it was higher in patients who started transfusion at a later age. More attention should be paid for this problem and close observations and follow up is strongly needed.


Theoretical and practical knowledge of nursing professionals on indirect blood pressure measurement at a coronary care unit.
To determine and to analyze the theoretical and practical knowledge of Nursing professionals on indirect blood pressure measurement. This cross-sectional study included 31 professionals of a coronary care unit (86% of the Nursing staff in the unit). Of these, 38.7% of professionals were nurses and 61.3% nurse technicians. A validated questionnaire was used to theoretical evaluation and for practice assessment the auscultatory technique was applied in a simulation environment, under a non-participant observation. To the theoretical knowledge of the stages of preparation of patient and environment, 12.9% mentioned 5-minute of rest, 48.4% checked calibration, and 29.0% chose adequate cuff width. A total of 64.5% of professionals avoided rounding values, and 22.6% mentioned the 6-month deadline period for the equipment calibration. On average, in practice assessment, 65% of the steps were followed. Lacks in knowledge were primary concerning lack of checking the device calibration and stethoscope, measurement of arm circumference to choose the cuff size, and the record of arm used in blood pressure measurement. Knowledge was poor and had disparities between theory and practice with evidence of steps taken without proper awareness and lack of consideration of important knowledge during implementation of blood pressure measurement. Educational and operational interventions should be applied systematically with institutional involvement to ensure safe care with reliable values.


Oncological imaging: tumor surveillance in children.
As the need for accurate diagnostic imaging often continues throughout a cancer survivor's life, imaging methods with the least toxicity must be used so as to provide needed information without contributing to long-term sequelae that might compound toxicities inherent with the primary disease and its treatment. In this regard, the costs, benefits and potential risks of post-therapy monitoring for disease recurrence warrant periodic review. Unfortunately, few analyses are available regarding the impact of surveillance imaging on the detection of disease recurrence, salvage rates of relapse disease and long-term survival outcomes for pediatric cancer survivors. This review will examine the role and limitations of surveillance imaging in pediatric oncology.


The involvement of Cav3.2/alpha1H T-type calcium channels in excitability of mouse embryonic primary vestibular neurones.
Ca2+ influx through voltage-gated calcium channels probably influences neuronal ontogenesis. Many developing neurones transiently express T-type/Cav3 calcium channels that contribute to their electrical activity and potentially to their morphological differentiation. Here we have characterized the electrophysiological properties and the functional role of a large T-type calcium current that is present in mouse developing primary vestibular neurones at embryonic day E17. This T-type current showed fast activation and inactivation, as well as slow deactivation kinetics. The overlap of activation and inactivation parameters produced a window current between -65 and -45 mV. Recovery from short-term inactivation was slow suggesting the presence of the Cav3.2 subunit. This T-type current was blocked by micromolar concentrations of Ni2+ and was inhibited by fast perfusion velocities in a similar fashion to recombinant Cav3.2 T-type channels expressed in HEK-293 cells. More importantly, current clamp experiments have revealed that the T-current could elicit afterdepolarization potentials during the repolarization phase of action potentials, and occasionally generate calcium spikes. Taken together, we demonstrate that the Cav3.2 subunit is likely to be the main T-type calcium channel subunit expressed in embryonic vestibular neurones and should play a key role in the excitability of these neurones during the ontogenesis of vestibular afferentation.


Fine mapping and analysis of candidate genes for qBT2 and qBT7.2 locus controlling bolting time in radish (Raphanus sativus L.).
Two major QTLs for bolting time in radish were mapped to chromosome 02 and 07 in a 0.37 Mb and 0. 52 Mb interval, RsFLC1 and RsFLC2 is the critical genes. Radish (Raphanus sativus L.) is an important vegetable crop of Cruciferae. The premature bolting and flowering reduces the yield and quality of the fleshy root of radish. However, the molecular mechanism underlying bolting and flowering in radish remains unknown. In YZH (early bolting) × XHT (late bolting) F2 population, a high-density genetic linkage map was constructed with genetic distance of 2497.74 cM and an average interval of 2.31 cM. A total of nine QTLs for bolting time and two QTLs for flowering time were detected. Three QTLs associated with bolting time in radish were identified by QTL-seq using radish GDE (early bolting) × GDL (late bolting) F2 population. Fine mapping narrowed down qBT2 and qBT7.2 to an 0.37 Mb and 0.52 Mb region on chromosome 02 and 07, respectively. RNA-seq and qRT-PCR analysis showed that RsFLC1 and RsFLC2 were the candidate gene for qBT7.2 and qBT2 locus, respectively. Subcellular localization exhibited that RsFLC1 and RsFLC2 were mainly expressed in the nucleus. A 1856-bp insertion in the first intron of RsFLC1 was responsible for bolting time. Overexpression of RsFLC2 in Arabidopsis was significantly delayed flowering. These findings will provide new insights into the exploring the molecular mechanism of late bolting and promote the marker-assisted selection for breeding late-bolting varieties in radish.


Efficacy of Noninvasive Brain Stimulation on Unilateral Neglect After Stroke: A Systematic Review and Meta-analysis.
Unilateral neglect (UN) is a common debilitating consequence of stroke. This review focused on the effect of noninvasive brain stimulation (NIBS) techniques in the recovery of UN in poststroke patients. Relevant databases were comprehensively searched, including Cochrane Central Register of Controlled Trials, Medline, Embase, the Web of Knowledge, and relevant websites. All randomized controlled trials were identified which used NIBS for poststroke UN. The methodological quality and risk of bias were systematically evaluated. Twelve studies were included, and 11 randomized controlled trials were made further meta-analysis. Participants who were randomized to active transcranial direct current stimulation (effect size [ES], -0.51; 95% confidence interval [CI], -1.02 to -0.01; P = 0.04) and repetitive transcranial magnetic stimulation (ES, -1.76; 95% CI, -2.40 to -1.12; P < 0.00001) decreased UN severity after intervention compared with the control group. Nonsignificant pooled effect size presented for continuous theta burst stimulation results (ES, -0.77; 95% CI, -1.90 to 0.37; P = 0.18). No participants experienced serious adverse events. This review found evidence for the efficacy of repetitive transcranial magnetic stimulation in the remediation of poststroke UN, but the efficacy of transcranial direct current stimulation and continuous theta burst stimulation was uncertain. Large-sample randomized controlled clinical trials are needed to understand effects of NIBS on poststroke UN.


Leucine content of dietary proteins is a determinant of postprandial skeletal muscle protein synthesis in adult rats.
Leucine (Leu) regulates muscle protein synthesis (MPS) producing dose-dependent plasma Leu and MPS responses from free amino acid solutions. This study examined the role of Leu content from dietary proteins in regulation of MPS after complete meals. Experiment 1 examined 4 protein sources (wheat, soy, egg, and whey) with different Leu concentrations (6.8, 8.0, 8.8, and 10.9% (w/w), respectively) on the potential to increase plasma Leu, activate translation factors, and stimulate MPS. Male rats (~250 g) were trained for 14 day to eat 3 meals/day consisting of 16/54/30% of energy from protein, carbohydrates and fats. Rats were killed on d14 either before or 90 min after consuming a 4 g breakfast meal. Experiment 2 compared feeding wheat, whey, and wheat + Leu to determine if supplementing the Leu content of the wheat meal would yield similar anabolic responses as whey. In Experiment 1, only whey and egg groups increased post-prandial plasma Leu and stimulated MPS above food-deprived controls. Likewise, greater phosphorylation of p70 S6 kinase 1 (S6K1) and 4E binding protein-1 (4E-BP1) occurred in whey and egg groups versus wheat and soy groups. Experiment 2 demonstrated that supplementing wheat with Leu to equalize the Leu content of the meal also equalized the rates of MPS. These findings demonstrate that Leu content is a critical factor for evaluating the quantity and quality of proteins necessary at a meal for stimulation of MPS.


Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases.
Ghrelin and its synthetic analog hexarelin are specific ligands of growth hormone secretagogue (GHS) receptor. GHS have strong growth hormone-releasing effect and other neuroendocrine activities such as stimulatory effects on prolactin and adrenocorticotropic hormone secretion. Recently, several studies have reported other beneficial functions of GHS that are independent of GH. Ghrelin and hexarelin, for examples, have been shown to exert GH-independent cardiovascular activity. Hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) in macrophages and adipocytes. PPAR-γ is an important regulator of adipogenesis, lipid metabolism, and insulin sensitization. Ghrelin also shows protective effects on beta cells against lipotoxicity through activation of phosphatidylinositol-3 kinase/protein kinase B, c-Jun N-terminal kinase (JNK) inhibition, and nuclear exclusion of forkhead box protein O1. Acylated ghrelin (AG) and unacylated ghrelin (UAG) administration reduces glucose levels and increases insulin-producing beta cell number, and insulin secretion in pancreatectomized rats and in newborn rats treated with streptozotocin, suggesting a possible role of GHS in pancreatic regeneration. Therefore, the discovery of GHS has opened many new perspectives in endocrine, metabolic, and cardiovascular research areas, suggesting the possible therapeutic application in diabetes and diabetic complications especially diabetic cardiomyopathy. Here, we review the physiological roles of ghrelin and hexarelin in the protection and regeneration of beta cells and their roles in the regulation of insulin release, glucose, and fat metabolism and present their potential therapeutic effects in the treatment of diabetes and diabetic-associated heart diseases.


Androgen-dependent atypical fibromas spontaneously arising in the skin of Djungarian hamsters (Phodopus sungorus).
Spontaneous atypical fibromas that arose in the thoracoabdominal skin of one aged female and 31 aged male Djungarian hamsters (Phodopus sungorus) were examined histologically, immunohistochemically, and ultrastructurally. The normal skin from both sexes obtained at various intervals until the age of 12 months was examined, as were the tumors. These tumors were composed of ganglion cell-like (GL) cells that had one or two ovoid nuclei, basophilic foamy cytoplasm, and various amount of collagen fibers between the cells. The tumor cells had positive reaction to vimentin and androgen receptor (AR); the stromal collagen fibers reacted positively with the antibody against collagen type I or III. Ultrastructurally, the tumor cells had abundant rough endoplasmic reticulum in the cytoplasm. On the other hand, small nests of the cells mimicking tumor GL cells were present in the dermal layer to the panniculus of the normal thoracoabdominal skin of adult males, but were seldom found in adult females. The morphologic and immunohistochemical features of these tumor GL cells were basically similar to those of normal skin GL cells, although the former had a certain degree of atypia. These results suggest that atypical skin fibroma in the Djungarian hamster is an androgen-dependent tumor and originates from skin GL cells.


Liver transplantation in Asia: Problems and practice.
Liver transplantation in Asia has been difficult to establish due to: a reluctance in Asians to donate organs; a lack of financial support; and the predominance of hepatitis B in the population, which effectively reduces the number of cadaveric organs. To overcome the problem of organ shortage, living-related liver transplantation for paediatric patients was rapidly established initially at Kyoto University, Japan, and then in several centres in Asia. Living-related liver transplantation was extended to adults using the left lobe in 1994 and using the right lobe in 1996. Up to May 1998, 785 liver transplantations had been performed in major centres in Asia with a patient survival rate approaching 80%. To overcome the problem of hepatitis B viral infection, lamivudine is now used peri-operatively. Lamivudine is shown to be very effective in preventing graft reinfection. Of the 15 patients who received lamivudine and liver transplantation at Queen Mary Hospital, hepatitis B surface antigen (HBsAg) disappeared in 11 patients and hepatitis B virus DNA was not detectable in any of them. Two patients had a reappearance of HBsAg after an initial loss, but their liver grafts were not affected by hepatitis. Compared with hepatitis B immunoglobulin, lamivudine is definitely cheaper and more convenient. In conclusion, even though there are major obstacles to liver transplantation in Asia, steady progress is being made. Hopefully, when the number of cadaveric grafts increases in future, an increasing number of patients can benefit.


FHL2 mediates podocyte Rac1 activation and foot process effacement in hypertensive nephropathy.
RAAS inhibition has been the standard treatment for CKD for years because it can reduce proteinuria and hence retard renal function decline, but the proteinuria reduction effect is still insufficient in many patients. Podocyte foot process and slit diaphragm are the final barrier to prevent serum proteins leak into urine, and podocyte foot process effacement is the common pathway of all proteinruic diseases. Cell structure are regulated by three evolutionarily conserved Rho GTPases, notably, Rac1 activation is sufficient and necessary for podocyte foot process effacement, however, Rac1 inhibition is not an option for kidney disease treatment because of its systemic side effects. Four-and-a-half LIM domains protein 2 (FHL2) is highly expressed in podocytes and has been implicated in regulating diverse biological functions. Here, we used micro-dissected human kidney samples, in vitro podocyte culture experiments, and a hypertension animal model to determine the possible role of FHL2 in hypertensive nephropathy. FHL2 was abundantly upregulated in hypertensive human glomeruli and animal kidney samples. Genetic deletion of the FHL2 did not alter normal renal structure or function but mitigated hypertension-induced podocyte foot process effacement and albuminuria. Mechanistically, angiotensin II-induced podocyte cytoskeleton reorganization via FAK-Rac1 axis, FHL2 binds with FAK and is an important mediator of Ang II induced Rac1 activation, thus, FHL2 inhibition can selectively block FAK-Rac1 axis in podocyte and prevent proteinuria. These results provide important insights into the mechanisms of podocyte foot process effacement and points out a promising strategy to treat kidney disease.


Profiling the in vitro drug-resistance mechanism of influenza A viruses towards the AM2-S31N proton channel blockers.
The majority of human influenza A viruses currently in circulation carry the amantadine-resistant AM2-S31N channel mutation. We previously discovered a series of AM2-S31N inhibitors with potent antiviral activity against both oseltamivir-sensitive and -resistant influenza A viruses. To understand the drug-resistance mechanism of AM2-S31N inhibitors, we performed serial viral passage experiments using the influenza virus A/California/07/2009 (H1N1) to select drug-resistant AM2 mutations against two representative AM2-S31N channel blockers (1 and 2). Unlike amantadine, which gives rise to resistance after a single passage, compounds 1 and 2 selected for partially resistant viruses at passages 05 and 04 with a V27I and L26I mutation, respectively. This appears to suggest compounds 1 and 2 have a higher genetic barrier to resistance than amantadine at least in cell culture. Passage with a higher drug concentration of compound 2 selected higher level resistant viruses with a double mutant L26I + A30T. The mechanism of resistance and replication fitness for mutant viruses were evaluated by electrophysiology, reverse genetics, growth kinetics, and competition assays. AM2-S31N/V27I and AM2-S31N/L26I channels achieved similar specific proton conductance as AM2-S31N, but the AM2-S31N/L26I/A30T triple mutant had drastically reduced specific proton conductance. Viral replication fitness of AM2-S31N/V27I and AM2-S31N/L26I double mutant viruses were similar to AM2-S31N containing viruses in cell culture. However, AM2-S31N/L26I/A30T viruses displayed attenuated growth as well as inability to compete with AM2-S31N viruses. The results herein offer insight regarding the resistance mechanism of AM2-S31N inhibitors, and may help guide the design of the next-generation of AM2-S31N inhibitors with a higher genetic barrier to drug resistance.


Scavenger receptor CD36 is essential for the cerebrovascular oxidative stress and neurovascular dysfunction induced by amyloid-beta.
Increasing evidence indicates that cerebrovascular dysfunction plays a pathogenic role in Alzheimer's dementia (AD). Amyloid-β (Aβ), a peptide central to the pathogenesis of AD, has profound vascular effects mediated, for the most part, by reactive oxygen species produced by the enzyme NADPH oxidase. The mechanisms linking Aβ to NADPH oxidase-dependent vascular oxidative stress have not been identified, however. We report that the scavenger receptor CD36, a membrane glycoprotein that binds Aβ, is essential for the vascular oxidative stress and neurovascular dysfunction induced by Aβ1-40. Thus, topical application of Aβ1-40 onto the somatosensory cortex attenuates the increase in cerebral blood flow elicited by neural activity or by endothelium-dependent vasodilators in WT mice but not in CD36-null mice (CD36(0/0)). The cerebrovascular effects of infusion of Aβ1-40 into cerebral arteries are not observed in mice pretreated with CD36 blocking antibodies or in CD36(0/0) mice. Furthermore, CD36 deficiency prevents the neurovascular dysfunction observed in transgenic mice overexpressing the Swedish mutation of the amyloid precursor protein Tg2576 despite elevated levels of brain Aβ1-40. CD36 is also required for the vascular oxidative stress induced by exogenous Aβ1-40 or observed in Tg2576 mice. These observations establish CD36 as a key link between Aβ1-40 and the NADPH oxidase-dependent vascular oxidative stress underlying the neurovascular dysfunction and suggest that CD36 is a potential therapeutical target to counteract the cerebrovascular dysfunction associated with Aβ.


Targeting cyclin-dependent kinases in human cancers: from small molecules to Peptide inhibitors.
Cyclin-dependent kinases (CDK/Cyclins) form a family of heterodimeric kinases that play central roles in regulation of cell cycle progression, transcription and other major biological processes including neuronal differentiation and metabolism. Constitutive or deregulated hyperactivity of these kinases due to amplification, overexpression or mutation of cyclins or CDK, contributes to proliferation of cancer cells, and aberrant activity of these kinases has been reported in a wide variety of human cancers. These kinases therefore constitute biomarkers of proliferation and attractive pharmacological targets for development of anticancer therapeutics. The structural features of several of these kinases have been elucidated and their molecular mechanisms of regulation characterized in depth, providing clues for development of drugs and inhibitors to disrupt their function. However, like most other kinases, they constitute a challenging class of therapeutic targets due to their highly conserved structural features and ATP-binding pocket. Notwithstanding, several classes of inhibitors have been discovered from natural sources, and small molecule derivatives have been synthesized through rational, structure-guided approaches or identified in high throughput screens. The larger part of these inhibitors target ATP pockets, but a growing number of peptides targeting protein/protein interfaces are being proposed, and a small number of compounds targeting allosteric sites have been reported.


Principles of a new treatment algorithm in multiple sclerosis.
We are entering a new era in the management of patients with multiple sclerosis (MS). The first oral treatment (fingolimod) has now gained US FDA approval, addressing an unmet need for patients with MS who wish to avoid parenteral administration. A second agent (cladribine) is currently being considered for approval. With the arrival of these oral agents, a key question is where they may fit into the existing MS treatment algorithm. This article aims to help answer this question by analyzing the trial data for the new oral therapies, as well as for existing MS treatments, by applying practical clinical experience, and through consideration of our increased understanding of how to define treatment success in MS. This article also provides a speculative look at what the treatment algorithm may look like in 5 years, with the availability of new data, greater experience and, potentially, other novel agents.


The contractile strength of vascular smooth muscle myocytes is shape dependent.
Vascular smooth muscle cells in muscular arteries are more elongated than those in elastic arteries. Previously, we reported changes in the contractility of engineered vascular smooth muscle tissue that appeared to be correlated with the shape of the constituent cells, supporting the commonly held belief that elongated muscle geometry may allow for the better contractile tone modulation required in response to changes in blood flow and pressure. To test this hypothesis more rigorously, we developed an in vitro model by engineering human vascular smooth muscle cells to take on the same shapes as those seen in elastic and muscular arteries and measured their contraction during stimulation with endothelin-1. We found that in the engineered cells, actin alignment and nuclear eccentricity increased as the shape of the cell elongated. Smooth muscle cells with elongated shapes exhibited lower contractile strength but greater percentage increase in contraction after endothelin-1 stimulation. We analysed the relationship between smooth muscle contractility and subcellular architecture and found that changes in contractility were correlated with actin alignment and nuclear shape. These results suggest that elongated smooth muscle cells facilitate muscular artery tone modulation by increasing its dynamic contractile range.


[Health litigation and new challenges in the management of pharmaceutical services].
Health litigation spurs many challenges in the management of pharmaceutical services. Performance of health managers and decisionmakers must be adjusted to new administrative and legal boundaries. Their actions must also be efficient in responding to ongoing lawsuits, as well as in avoiding additional litigation and in upholding principles and directives of the Brazilian Health System (SUS). This paper proposes to better understand one of the aspects of health litigation, namely the growing use of lawsuits demanding medicines, and the relationship between this phenomenon and pharmaceutical services management in SUS. Through review and analysis of available published research on the subject, from various Brazilian states, the main elements of "medicines litigation" are presented and examined in light of their interference on the activities of the pharmaceutical services cycle. The analysis points to possible mechanisms to be adopted by decision-makers in management and in the Judicial System, since the right to health can only be effectively established when management and Justice are predominantly aware and committed to the safety and the protection of patients and users.


Asiatic acid abridges pre-neoplastic lesions, inflammation, cell proliferation and induces apoptosis in a rat model of colon carcinogenesis.
The utmost aim of this present study was to investigate the anti-inflammatory, antiproliferative and proapoptotic potential of Asiatic acid (AA) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in experimental rats. Rats were divided into six groups and received modified pellet diet for 32 weeks. Group 1 served as control rats. Group 2 received AA (4 mg/kg b.w. p.o.). Group 3-6 rats received 15 DMH (20 mg/kg b.w., s.c.) injections once a week starting from the 4th week. Besides DMH, rats received AA (4 mg/kg b.w. p.o.) in group 4 starting 2 weeks before carcinogen treatment till the end of the last DMH; group 5 starting 2 days after last DMH till the end of the experiment; and group 6 throughout the experiment. Pre-neoplastic lesions, xenobiotic metabolizing enzymes, inflammation, cell proliferation and apoptotic markers were analysed in our study. Our results ascertained AA supplementation to DMH-exposed rats significantly decreased the incidence of aberrant crypt foci (ACF) and phase I xenobiotic enzymes; and increased the phase II xenobiotic enzymes and mucin content as compared to DMH-alone-exposed rats. Moreover the increased expressions of mast cells, argyrophilic nucleolar organizer regions (AgNORs), proliferating cell nuclear antigen (PCNA) and cyclin D1 observed in the DMH-alone-exposed rats were reverted and were comparable with those of the control rats, when treated with AA. Concordantly AA also induced apoptosis by downregulating the expression of Bcl-2 and upregulating Bax, cytochrome c, caspase-3 and -9 in the DMH-alone-exposed rats. Thus AA was able to inhibit DMH-induced colon carcinogenesis by detoxifying the carcinogen, decreasing the preneoplastic lesions by virtue of its anti-inflammatory, antiproliferative and proapoptotic effects. Therefore our findings suggest that AA could be used as an effective chemopreventive agent against DMH induced colon carcinogenesis.


Plant species richness and functional traits affect community stability after a flood event.
Climate change is expected to increase the frequency and magnitude of extreme weather events. It is therefore of major importance to identify the community attributes that confer stability in ecological communities during such events. In June 2013, a flood event affected a plant diversity experiment in Central Europe (Jena, Germany). We assessed the effects of plant species richness, functional diversity, flooding intensity and community means of functional traits on different measures of stability (resistance, resilience and raw biomass changes from pre-flood conditions). Surprisingly, plant species richness reduced community resistance in response to the flood. This was mostly because more diverse communities grew more immediately following the flood. Raw biomass increased over the previous year; this resulted in decreased absolute value measures of resistance. There was no clear response pattern for resilience. We found that functional traits drove these changes in raw biomass: communities with a high proportion of late-season, short-statured plants with dense, shallow roots and small leaves grew more following the flood. Late-growing species probably avoided the flood, whereas greater root length density might have allowed species to better access soil resources brought from the flood, thus growing more in the aftermath. We conclude that resource inputs following mild floods may favour the importance of traits related to resource acquisition and be less associated with flooding tolerance.


High-fat diet induces cognitive impairment through repression of SIRT1/AMPK-mediated autophagy.
Recent evidence suggests an association between a high-fat diet (HFD) and cognitive decline. HFD may reduce synaptic plasticity and cause tau hyperphosphorylation, but the mechanisms involved remain unclear. The purpose of this study was to explore whether Sirtuin1 (SIRT1)/AMP-activated protein kinase (AMPK) pathway was involved in this pathogenic effect in the HFD exposed mice. C57BL/6 mice at 12 months of age were fed a standard (9% kcal fat) or high-fat (60% kcal fat) diet for 22 weeks, and Neuro-2a (N2a) cells were treated with normal culture medium or a palmitic acid (PA) medium (100uM) for 40 h. After that, cognitive function was tested by Morris water maze (MWM). The levels of proteins involved in SIRT1/AMPK pathway and autophagy were measured using western blotting and immunofluorescence. We also assessed the phosphorylation of tau protein and synapse. The mice presented impaired learning and memory abilities. We further found decreased levels of synaptophysin (Syn) and brain-derived neurotrophic factor (BDNF), increased tau46 and phosphorylated tau protein, and damaged neurons in mice after HFD or in N2a cells treated with PA medium. Moreover, HFD can also reduce the expression of SIRT1, inhibit AMPK phosphorylation, and block autophagic flow in both mice and cells. After treating the cells with the SIRT1 agonist SRT1720, SIRT1/AMPK pathway and autophagy-related proteins were partially reversed and the number of PA-induced positive cells was alleviated in senescence-associated β-galactosidase (SA-β-gal) staining. HFD may inhibit the expression of SIRT1/AMPK pathway and disrupt autophagy flux, and result in tau hyperphosphorylation and synaptic dysfunction during aging, which ultimately lead to cognitive decline.


Optical polarization grating induced liquid crystal micro-structure using azo-dye command layer.
We create planar-periodic alignment in nematic liquid crystal (LC) cell by using a command layer of azo-dye molecules directly deposited on the cell substrates and exposed with two interfering laser beams of opposite circular polarizations. Permanent high efficiency polarization gratings are thus created. The diffraction efficiency of those gratings is controlled by a uniform electric field applied across the cell. The electro-optical properties of such polarization gratings are studied. Obtained gratings can be used for electrically controlled discrimination and detection of polarized components of light.


Association of CYP2D6 and CYP2C19 polymorphisms and disease-free survival of Thai post-menopausal breast cancer patients who received adjuvant tamoxifen.
To investigate the impact of CYP2D6 and CYP2C19 polymorphisms in predicting tamoxifen efficacy and clinical outcomes in Thai breast cancer patients. Polymorphisms of CYP2D6 and CYP2C19 were genotyped by the AmpliChip™ CYP450 Test (Roche Molecular Diagnostics, Branchburg, NJ, USA) for 57 patients, who were matched as recurrent versus non-recurrent breast cancers (n = 33 versus n = 24, respectively, with a 5-year follow-up). Based on the genotype data, five CYP2D6 predicted phenotype groups were identified in this study including homozygous extensive metabolizer (13 of 57, 22.80%), extensive/intermediate metabolizer (23 of 57, 40.40%), extensive/poor metabolizer (3 of 57, 5.30%), homozygous intermediate metabolizer (14 of 57, 24.50%), and intermediate/poor metabolizer (4 of 57, 7.00%), and three CYP2C19 genotype groups including homozygous extensive metabolizer (27 of 57, 47.40%), extensive/intermediate metabolizer (27 of 57, 47.40%), and homozygous poor metabolizer (3 of 57, 5.30%). The CYP2D6 variant alleles were *10 (52 of 114, 45.60%), *5 (5 of 114, 4.40%), *41 (2 of 114, 1.80%), *4 (1 of 114, 0.90%), and *36 (1 of 114, 0.90%); the CYP2C19 variant alleles were *2 (27 of 114, 23.70%) and *3 (6 of 114, 5.30%). Kaplan-Meier estimates showed significantly shorter disease-free survival in patients with homozygous TT when compared to those with heterozygous CT or homozygous CC at nucleotides 100C>T and 1039C>T (CYP2D6*10) post-menopausal (log-rank test; P = 0.046). They also had increased risk of recurrence, but no statistically significant association was observed (hazard ratio 3.48; 95% confidence interval 0.86-14.07; P = 0.080). The CYP2D6 and CYP2C19 polymorphisms were not involved in tamoxifen efficacy. However, in the subgroup of post-menopausal women, the polymorphisms in CYP2D6 and CYP2C19 might be useful in predicting tamoxifen efficacy and clinical outcomes in breast cancer patients receiving adjuvant tamoxifen treatment. As the number of breast cancer patients was relatively small in this study, results should be confirmed in a larger group of prospective patients.


Comparative trial of six methods for the detection of CMV antibody in blood donors.
Six techniques were compared to find the most suitable method for determining the cytomegalovirus (CMV) antibody status of blood donors. Five hundred and ninety-six random sera were tested by immunofluorescence (IF), complement fixation (CFT), two enzyme linked immunosorbent assays (ELISA), a commercial indirect haemagglutination test (IHA)--used as supplied, and a locally devised micromodification of the same IHA test. Five hundred and thirty-five sera shared total agreement of results by all tests. The ELISA tests were the most discordant with other methods (10.5% discordancies both positive and negative). IF and CFT correlated well with other tests (0.8% discordances each) but for different reasons are unsatisfactory for donor screening. The IHA test used as supplied and its micromodification gave the most consistent results (0.8% and 0.5% discordancies respectively). The micromodification is easy to perform and read; it compares very favourably with CFT and IF for material costs and expertise required, and readily lends itself to the testing of large numbers of sera in a reasonable time. Within certain provisos the micro-IHA technique described is recommended as the most suitable test for blood donor screening.


Polysulfides (H2Sn) produced from the interaction of hydrogen sulfide (H2S) and nitric oxide (NO) activate TRPA1 channels.
Hydrogen sulfide (H2S) exerts synergistic effects with another gaseous signaling molecule nitric oxide (NO) on ion channels and vasculature. However, the mechanism of the synergy is not well understood. Here, we show that the interaction between H2S and NO generates polysulfides (H2Sn), which activate transient receptor potential ankyrin 1 (TRPA1) channels. High performance liquid chromatography with tandem mass spectrometry analysis, along with the imaging of intracellular Ca2+ and H2Sn, showed that H2Sn and their effects were abolished by cyanolysis and by reducing substances such as dithiothreitol (DTT), cysteine, and glutathione (GSH). However, the effects of nitroxyl or nitrosopersulfide, other potential products of H2S and NO interaction, are not affected by cyanolysis or reducing substances. This study demonstrates that H2Sn are products of synergy between H2S and NO and provides a new insight into the signaling mechanisms.


[Morphology and histogenesis of so-called fibrous mesothelioma (submesothelial fibroma)].
Clinico-morphological characteristics of a tumor (6 observations) designated in the literature as fibrous mesothelioma are presented. This benign slowly growing tumor appears as an incapsulated dense nodule connected with the visceral layer of the pleura by a thin fibrous "pedicle". Microscopical structure of the tumor consists of outgrowths of monomorphic spindle-shaped cells, hyalinosis foci and abundance of blood vessels in some of its areas. Tumor cells ultrastructurally correspond to fibroblast indicating the connective tissue genesis of the so-called fibrous mesothelioma. This tumor should be distinguished from the group of mesotheliomas and be better called submesothelial fibroma.


F-Seq: a feature density estimator for high-throughput sequence tags.
Tag sequencing using high-throughput sequencing technologies are now regularly employed to identify specific sequence features, such as transcription factor binding sites (ChIP-seq) or regions of open chromatin (DNase-seq). To intuitively summarize and display individual sequence data as an accurate and interpretable signal, we developed F-Seq, a software package that generates a continuous tag sequence density estimation allowing identification of biologically meaningful sites whose output can be displayed directly in the UCSC Genome Browser. The software is written in the Java language and is available on all major computing platforms for download at http://www.genome.duke.edu/labs/furey/software/fseq.


Perspectives from the Society for Pediatric Research: contaminants of water and children's health: Can we do better?
Children are uniquely susceptible to the health consequences of water contamination. In this review, we summarize the existing, robust literature supporting the importance of examining specific water contaminants (i.e., lead, pesticides, nitrates, arsenic, perchlorate) and the routes of contamination in the United States and globally. We also discuss the health effects of exposure to contaminated water and significant disparities related to access to clean water. Lastly, we offer strategies for prevention and intervention-including those focused on the individual patient level-and review the current US policy framework pertaining to regulation of these toxicants. IMPACT: A key message in this article is that exposure to water contaminants have serious and long-lasting consequences on children's health. This review summarizes current existing literature and adds policy recommendations supporting clean water for children. Information from this review has two potential impacts: Guide health professionals in screening and/or treating children's health problems resulting from water contaminant exposure. Guide policy makers in using evidence-based approaches to improve water quality and clean water access.