Effects of aldosterone on biosynthesis, traffic, and functional expression of epithelial sodium channels in A6 cells.
The collecting duct regulates Na(+) transport by adjusting the abundance/activity of epithelial Na(+) channels (ENaC). In this study we have investigated the synthesis, degradation, endocytosis, and activity of ENaC and the effects of aldosterone on these processes using endogenous channels expressed in the A6 cell line. Biochemical studies were performed with a newly raised set of specific antibodies against each of the three subunits of the amphibian ENaC. Our results indicate simultaneous transcription and translation of alpha, beta, and gamma subunits and enhancement of both processes by aldosterone: two- and fourfold increase, respectively. The biosynthesis of new channels can be followed by acquisition of endoglycosidase H-resistant oligosacharides in alpha and beta subunits and, in the case of alpha, by the appearance of a form resistant to reducing agents. The half-life of the total pool of subunits (t(1/2) 40-70 min) is longer than the fraction of channels in the apical membrane (t(1/2) 12-17 min). Aldosterone induces a fourfold increase in the abundance of the three subunits in the apical membrane without significant changes in the open probability, kinetics of single channels, or in the rate of degradation of ENaC subunits. Accordingly, the aldosterone response could be accounted by an increase in the abundance of apical channels due, at least in part, to de novo synthesis of subunits.


Molecular probes and endocrine diseases.
This presentation reviews the use of in situ hybridization in the study of endocrine diseases. The basic techniques used, technical problems and pitfalls in interpretation and the application of in situ hybridization in the practice of diagnostic endocrine pathology are discussed. Finally, future directions for this technique and related molecular biological methods and their potential applications are presented.


Changes in correlation coefficients of exposure markers as a function of intensity of occupational exposure to toluene.
This study was initiated to identify a marker of choice to monitor occupational exposure to toluene through quantitative evaluation of changes in correlation coefficients (CCs), taking advantage of a large database. Six known or proposed exposure markers in end-of-shift blood (B) and urine (U) were studied, i.e., toluene in blood (Tol-B) and benzyl alcohol, benzylmercapturic acid, o-cresol, hippuric acid and toluene in urine (BeOH-U, BMA-U, o-CR-U, HA-U, and Tol-U, respectively). To construct a database, data on 8-h time-weighted average intensity of occupational exposure to toluene and resulting levels of the six exposure markers in blood or urine were cited for 901 cases from previous four publications of this study group and combined with 146 new cases. In practice, 874 cases (all men) were available when extremely dilute or dense urine samples were excluded. The 874 cases were classified taking the upper limit (from 120 ppm to 1 ppm) of the toluene exposure concentration, and the CCs for the six markers with TWA toluene exposure intensity were calculated. For further evaluation, the 874 cases were divided into 10 per thousand in terms of TWA toluene exposures, and several 10 per thousand were combined so that sufficient numbers of cases were available for calculation of the CCs at various levels of toluene exposure. Perusal was made to know whether or not and which one of the six makers gave significant CC even at low level of toluene exposure. The CCs for BMA-U, o-CR-U and HA-U with TWA toluene exposure were well >0.7 when toluene exposure was intense (e.g., up to 60-100 ppm as the upper limit of the exposure range), but were reduced when the upper limit of toluene exposure was less than 50 ppm, and the CCs were as small as <==0.2 when the upper limit was about 10 ppm or less. In contrast, Tol-U and Tol-B were correlated with exposure to toluene down to the <or=3 ppm range. The CC for BeOH-U was <0.1 almost throughout the exposure ranges. Further analyses showed that the CCs for all markers (except the CC for BeOH-U) were >0.4 when the cases in the 60th-100th per thousand were examined. The CCs for Tol-U and Tol-B were >0.3 also for cases in the 0th-60th or 30th-70th per thousand, whereas the CCs for other four markers were <0.3. In over-all evaluation, it was concluded that HA and o-CR are among the markers of choice to monitor occupational toluene exposure at high levels, and that only un-metabolized toluene in urine or in blood is recommended when toluene exposure level is low (e.g., 10 ppm or less). Toluene in urine may be preferred rather than that in blood due to practical reasons, such as non-invasiveness.


Incidence and predictors of rebleeding after band ligation of oesophageal varices.
Variceal bleeding is a severe complication in patients with portal hypertension. Early rebleeding occurs frequently in the first few weeks after band ligation, and the mortality associated with each bleeding episode ranges from 30% to 50%. Our aims were to study the rate of early rebleeding oesophageal varices after band ligation in the Sohag University Hospital, Egypt, and to assess different clinical, biochemical, ultrasonographic, and endoscopic parameters that may predict the risk factors of rebleeding. In the period from December 2011 to December 2012, we performed endoscopic variceal ligation (EVL) for 146 cirrhotic patients (105 male and 41 female) with a mean age of 51.77±10.47years; the patients were divided into rebleeding and non-rebleeding groups. Complete history taking, clinical examination, laboratory investigations, abdominal ultrasound (US), and upper gastrointestinal (GI) endoscopy were performed for all patients. The incidence of early rebleeding after EVL was 20.54%, and it was significantly associated with male gender (p=0.013), older age (p=0.009), infection with spontaneous bacterial peritonitis (SBP) (p<0.0007), reduced liver size (p=0.017), a coarser echo pattern (p=0.03), the presence of hepatic focal lesions (p<0.001), splenomegaly (p=0.02), the presence of portosystemic collaterals (p=0.006), a low haemoglobin (HB) level (p<0.0001), prothrombin concentration (p=0.017), high aspartate aminotransferase (AST) level (p=0.01), Child-Pugh B and C (p=0.02, 0.003), large oesophageal varices F3 in the two endoscopies (p=0.002; p<0.0001), varices extending to the superior third Ls (p<0.001), and the presence of massive red colour signs (RC+++) (p<0.0001). By multivariate analysis, SBP and low HB level were found to be independent predictors of rebleeding. The following conclusions were drawn from this study: (1) The incidence of rebleeding after EVL in our centre is about 20%. (2) Early rebleeding after EVL is affected by many clinical, laboratory, ultrasonographic, and endoscopic parameters. The most prominent of them are SBP, splenomegaly, the presence of collaterals, anaemia, more decompensated cirrhosis, and the presence of large varices with red signs. (3) SBP and low HB level were found to be independent predictors of rebleeding.


Morphological changes from silica tubules to hollow spheres controlled by the intermolecular interactions within block copolymer micelle templates.
The morphological changes from tubules to large hollow spheres to (micelle-sized) small hollow-spherical silica were realized by polystyrene-block-poly(vinylpyridine) (PS-b-PVP) block copolymer micelle templates by controlling the intermolecular interactions with the corona chains. PS-b-PVP with weak intermolecular interactions among PVP corona chains yields the coexistence of tubules, large hollow spheres, and small hollow spheres. The coexistence of the three phases arises from the direct aggregation of block copolymer micelles during hydrolytic condensation of a silica precursor (tetraethylorthosilicate), as evidenced by transmission electron microscopy. When the degree of intermolecular interactions within the PVP corona blocks is increased by a change in either the degree of quaternization of the PVP blocks or the dielectric constant of the medium, small hollow spherical silica, with size equivalent to the block copolymer micelles, were solely obtained. We believe that this morphological change is due to the fact that the dipole-dipole interactions among quaternized PVP blocks physically cross-link the PVP coronas in micelles resisting the curvature change during the silica condensation.


High b-value diffusion-weighted imaging in normal and malignant peripheral zone tissue of the prostate: effect of signal-to-noise ratio.
To determine whether the apparent diffusion coefficient (ADC) obtained using a high b-value (2,000 s/mm2) is superior to that using a standard b-value (1,000 s/mm2) for discriminating malignant from normal peripheral tissue in the prostate. Twenty-six patients with biopsy-proven prostate cancer underwent 1.5T magnetic resonance (MR) imaging including single-shot, echo-planar diffusion-weighted imaging (DWI) with repetition time/echo time, 3500/88 ms; 4-mm slice thickness; 1-mm interslice gap; 144x128 matrix; field of view, 250x250 mm; number of excitations, 10; and b-values, 0, 1,000, and 2,000 s/mm2. For each patient, ADC values were obtained for malignant and normal tissue using b=1,000 and 2,000 in a monoexponential model. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios in DWI were also evaluated. At b=1,000, the mean ADC (x10(-3) mm2/s) for malignant tissue was 0.82+/-0.27 (range 0.43-1.29) and for normal tissue, 1.69+/-0.23 (1.31-2.18). At b=2000, the mean ADC for malignant tissue was 0.61+/-0.19 (0.30-0.94) and for normal tissue, 1.01+/-0.14 (0.73-1.35). Significant ADC overlap between the malignant and normal tissue was recognized at b=2000. As b-value increased, the mean SNR within malignant tissue decreased by 21.6%, and mean CNR decreased 17.3%. Under the same imaging conditions, measuring ADC using a high b-value (2,000 s/mm2) in a monoexponential model has little diagnostic advantage over using the standard b-value (1,000 s/mm2) in discriminating malignant from normal prostate tissue.


Routine orthostatic LVOT gradient assessment in patients with basal septal hypertrophy and LVOT flow acceleration at rest: please stand up.
A 70-year-old female with exertional dyspnoea was found to have basal septal hypertrophy (BSH), or a 'basal septal bulge', with evidence of mild left ventricular outflow tract obstruction (LVOT) at rest on her initial echocardiogram. She was usually fit and well with no significant past medical history. She had no history of hypertension. She had never smoked. There was no family history of hypertrophic cardiomyopathy (HCM). A cardiac MRI did not demonstrate any typical features of HCM. ECG showed sinus tachycardia with a rate of 101 bpm but was otherwise unremarkable. She was referred for exercise echocardiography to assess for latent LVOT obstruction. Prior to commencing exercise, her LVOT gradient was re-assessed at rest. Her LVOT gradients were 30 mmHg at rest, 49 mmHg during Valsalva and 91 mmHg on standing. A diagnosis of significant latent LVOT obstruction was made and the patient was started on bisoprolol, a cardioselective beta-blocker. Bisoprolol was slowly uptitrated from 1.25 mg to 5 mg once daily, following which the patient reported a significant improvement in her symptoms with an improved exercise capacity. Follow-up echocardiography demonstrated a dramatic reduction in LVOT gradient, with a maximum of 11 mmHg assessed both with Valsalva and on standing. This case is a reminder that patients with a 'common' basal septal bulge can develop significant LVOT obstruction, the symptoms of which may respond to pharmacological therapy. Orthostatic assessment of LVOT gradient using echocardiography should be considered during standard LVOT obstruction provocation manoeuvres such as a Valsalva. Learning points: Differentiation between basal septal hypertrophy (BSH) and hypertrophic cardiomyopathy (HCM) may be challenging. Key factors favouring HCM include a positive family history of HCM or sudden cardiac death, septal thickness >15 mm/posterior wall thickness >11 mm, systolic anterior motion of the anterior mitral valve (SAM), late gadolinium enhancement on cardiac MRI, a causative genetic mutation associated with HCM and an abnormal ECG. Significant LVOT obstruction may develop in patients with BSH and is potentially responsive to pharmacotherapy. Standing reduces venous return, resulting in decreased LV volume. Compensatory mechanisms to maintain cardiac output involve sympathetic nervous system activation leading to increased LV contractility and subsequent increased LVOT gradient. Significant LVOT obstruction may be unmasked by an orthostatic posture. Orthostatic LVOT gradient assessment should be part of the routine echocardiographic assessment of all patients with an increased LVOT gradient at rest. The post-prandial state has been associated with increased LVOT gradient due to splanchnic dilatation and the consequent increased cardiac output required to maintain blood pressure. Post-prandial status should therefore be considered when assessing LVOT gradient.


Face validity vs. item subtlety in the MMPI D scale.
The distinction between item subtlety and face validity ( Holden & Jackson, 1979) provided the basis to reevaluate findings for subtle items in the MMPI D scale (N = 214). Results indicated that the inclusion of nonpathological items in the D scale did not lead to greater predictive validity of depression criteria. The need for substantive considerations in scale construction was emphasized further.


[Squamous cell carcinoma of the bladder--report of two cases].
Two cases of squamous cell carcinoma of the urinary bladder are presented. Initial pathologic diagnosis was based on biopsy findings; it was confirmed by findings on resected specimens. Since aggressive surgical therapy has been reported to be successful, we attempted radical surgery in both of our patients. A 76-year-old woman underwent total cystectomy with resection of segments of rectal and vaginal walls with ureterocutaneostomy and colostomy. The other patient, a 66-year-old woman was inoperable due to wide tumor invasion. She died two months later of cerebrovascular accident apparently unrelated to original disease. The ultrastructural findings, which typically show numerous tonofilaments, ribosomes and desmosomes, are presented and discussed.


[Prognostic significance of selected oncogene and suppressor gene expression in follicular thyroid carcinoma].
Oncogene and suppressor gene expression (cyclin D, p21WAF1, nm23-H1, Rb1, p16INK4A, and p53) was evaluated in 23 follicular thyroid carcinomas diagnosed in 20 women and 3 men operated or reoperated in Institute of Oncology in Gliwice in years 1992-1999. Positive reaction with p16INK4A, Rb1 and cyclin D1 antibodies was observed in all tumors, with nm23-H1 in 22 cases. The presence of p21WAF1 was stated in 8 cases (34.8%) and p53 in 7 cases (30.4%). A simultaneous presence of expression of p53 and lack of expression of p21WAF1 was stated three times and in two cases were accompanied by distant metastases. This pattern of expression was only rarely observed in minimally invasive follicular cancer. The prognostic significance of simultaneous immunohistochemical analysis of p53 and p21WAF1 in follicular thyroid carcinoma is suggested and has to be proved in further studies.


Fractal model of light scattering in biological tissue and cells.
The K-distribution, widely used for investigation of fractal scattering in the atmosphere and from surfaces, is applied as a model for light propagation in biological tissue and cells. This leads to simple expressions for the scattering function, anisotropy function, phase function, reduced scattering coefficient, and scattering power. Compared with an alternative previously published model [Opt. Lett.30, 3051 (2005)], the range of allowable power laws is extended into the subfractal regime.


The effects of two combinations of a beta-blocker and a diuretic on diuresis in normal subjects.
Combinations of a beta-blocker and a diuretic often produce a greater fall in blood pressure than does either drug alone. Furthermore, beta-blockers prevent an increase in plasma renin activity, thereby attenuating diuretic-induced potassium excretion and also the reduction in hypotensive response to the diuretic. This study was designed to compare the effects of the two fixed-dose combinations atenolol 100 mg plus chlorthalidone 25 mg (Tenoretic; ICI) and sotalol 320 mg plus hydrochlorothiazide 50 mg (Sotazide; B-M) on the pattern of diuresis and the biochemical composition of the urine in normal subjects. These preparations differ mainly in that the plasma half-lives of chlorthalidone and hydrochlorothiazide are 60 hours and 6 hours respectively; the former therefore accumulates when given once daily while the latter does not. These two preparations were found to have similar effects on the pattern of diuresis and the biochemical values. It is therefore concluded that the relationship between the serum chlorthalidone level and the fall in serum potassium level is in keeping with the flat dose-response curves for the thiazide and phthalimide diuretics.


Evaluation of the effectiveness of treatment with erythropoietin on anemia, cognitive functioning and functions studied by comprehensive geriatric assessment in elderly cancer patients with anemia related to cancer chemotherapy.
The primary aim of the present study was to examine the relationship of changes in hemoglobin levels following recombinant human erythropoietin (rHuEPO) treatment to changes in cognitive functioning studied by Mini Mental State Examination (MMSE) in elderly cancer patients undergoing chemotherapy treatment. The secondary aim was that to assess the relationship of changes in hemoglobin levels following rHuEPO treatment to changes in functions studied by Comprehensive Geriatic Assessment (CGA), such as Activity of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Geriatric Depression Scale (GDS) and the Mini Nutritional Assessment (MNA). To this end, hemoglobin levels and cognitive functioning were evaluated in a sample of cancer patients prior to the start of chemotherapy treatment and again after 4, 8 and 12 weeks of treatment with chemotherapy plus rHuEPO. Ten elderly patients (mean age 71.4 years) were enrolled. At baseline, enrolled patients had a mean Hb value of 10.3g/dl. After 4 weeks of rHuEPO treatment, Hb values increased significantly (p<0.0001), with a mean increase of 1.2g/dl (range: 0.2-2.1). Remarkably, 8 out of 10 (80%) showed an increase of Hb levels >or=1g/dl in comparison to baseline and therefore were considered responders. At baseline, four patients (40%) showed a moderate cognitive impairment, whilst six patients (60%) showed a normal cognitive function. After 4 weeks of rHuEPO treatment nine patients (90%) showed a significant improvement of cognitive functions in comparison to baseline (p<0.005): eight of them were responders also to rHuEPO in terms of correction of anemia. The Spearman's rank correlation test showed a statistical significant correlation between Hb increase and increase in cognitive functioning assessed by MMSE after 4 weeks (p=0.049), 8 weeks (p=0.044) and 12 weeks (p=0.031) of rHuEPO treatment. Therefore, the findings of this study provide support for the hypothesis that significant increases in hemoglobin over the course of chemotherapy supplemented with rHuEPO administration would be accompanied by significant improvement in cognitive performance over the same interval.


Japanese dietary protein allowance is sufficient for moderate physical exercise in young men.
The sufficiency of the dietary protein allowances recommended by the Ministry of Health and Welfare of Japan for various physical exercises has not been examined. We investigated the protein requirement for moderate-intensity physical exercise using nitrogen balance in the isoenergetic state. Seventeen healthy college students exercised for 10 days with an adaptation period of three days and non-exercise control period of 10 days. They were given a maintenance level of energy and 1.08 g/kg per day of high quality mixed proteins recommended by the Ministry of Health and Welfare of Japan throughout the experimental period. They performed treadmill running during the exercise period at about 65% of VO2max for 25, 41 or 48 min/day, which required 200, 300 or 400 kcal of extra energy, respectively. Although the exercise increased dermal nitrogen loss, urinary nitrogen excretion tended to decrease. Consequently, the exercise ranging from 200 to 400 kcal/day did not significantly alter the nitrogen balance. Thiobarbituric acid-reactive substances and glutathione disulfide were not increased after exercise, suggesting that the moderate exercise, recommended for health promotion by the Ministry of Health and Welfare of Japan, does not cause oxidative damage to healthy subjects. These findings demonstrate that a protein intake of 1.08 g/kg per day is enough for moderate exercise.


Identification, sequencing, and localization of a new carbonic anhydrase transcript from the hydrothermal vent tubeworm Riftia pachyptila.
The vestimentiferan annelid Riftia pachyptila forms dense populations at hydrothermal vents along the East Pacific Rise at a depth of 2600 m. It harbors CO(2)-assimilating sulfide-oxidizing bacteria that provide all of its nutrition. To find specific host transcripts that could be important for the functioning of this symbiosis, we used a subtractive suppression hybridization approach to identify plume- or trophosome-specific proteins. We demonstrated the existence of carbonic anhydrase transcripts, a protein endowed with an essential role in generating the influx of CO(2) required by the symbionts. One of the transcripts was previously known and sequenced. Our quantification analyses showed a higher expression of this transcript in the trophosome compared to the branchial plume or the body wall. A second transcript, with 69.7% nucleotide identity compared to the previous one, was almost only expressed in the branchial plume. Fluorescent in situ hybridization confirmed the coexpression of the two transcripts in the branchial plume in contrast with the trophosome where only one transcript could be detected. An alignment of these translated carbonic anhydrase cDNAs with vertebrate and nonvertebrate carbonic anhydrase protein sequences revealed the conservation of most amino acids involved in the catalytic site. According to the phylogenetic analyses, the two R. pachyptila transcripts clustered together but not all nonvertebrate sequences grouped together. Complete sequencing of the new carbonic anhydrase transcript revealed the existence of two slightly divergent isoforms probably coded by two different genes.


"Micromere" formation and expression of endomesoderm regulatory genes during embryogenesis of the primitive echinoid Prionocidaris baculosa.
Blastomere composition and expression profiles of wnt8 and hox11/13b orthologues were examined in the primitive indirect-developing echinoid Prionocidaris baculosa. We found that blastomere composition in the 16-cell-stage Prionocidaris embryos was different from that of the indirect-developing echinoids belonging to Euechinoidea, a derived group of the echinoids. The sizes of the blastomeres in the 16-cell-stage embryo varied, and no embryos formed a "micromere quartet," a group of four equal-sized micromeres. The smallest blastomere was usually located around the vegetal pole. We also found significant differences in early expression profiles of wnt8 orthologues of the Prionocidaris and euechinoids. Unlike euechinoids, the expression of wnt8 orthologue of Prionocidaris was not detected at the 16-cell stage; it began at the 32-cell stage in the broad area containing the vegetal pole. However, in later stages, the expression profiles of hox11/13b and wnt8 orthologues of Prionocidaris were similar to that of euechinoid orthologues. The present study suggests that there are considerable differences between Prionocidaris and euechinoids in early developmental mechanisms in the vicinity of the vegetal pole.


Endoluminal management of arterioportal fistulae in liver transplant recipients: a single-center experience.
Transcatheter embolization of arterioportal fistulae in liver transplant recipients is restricted to symptomatic arterioportal fistulae. Angiograms of liver transplant recipients from a single university medical center were retrospectively reviewed. Hemodynamically significant arterioportal fistulae were defined as those exhibiting opacification of the main portal vein of the transplanted hepatic graft or its first order branch with or without portal venous changes by Doppler ultrasound imaging. Six arterioportal fistulae were found. Doppler ultrasound imaging detected 50% of all arterioportal fistulae and all 3 hemodynamically significant arterioportal fistulae. Three successful embolizations were performed. Follow-up (37 to 67 months) demonstrated patent hepatic arteries and no parenchymal ischemic changes with graft preservation. High-throughput arterioportal fistulae may require larger intrahepatic artery branch embolization. There is a window of opportunity for embolizing significant arterioportal fistulae before their progression to large symptomatic, high through-put arterioportal fistulae with their added risk of ischemic changes before and after embolization.


Lessons learned from inter-laboratory studies of carbon isotope analysis of honey.
Forensic application of carbon isotope ratio measurements of honey and honey protein to investigate the degree of adulteration with high fructose corn syrup or other C4 plant sugars is well established. These measurements must use methods that exhibit suitable performance criteria, particularly with regard to measurement uncertainty and traceability - low levels of adulteration can only be detected by methods that result in suitably small measurement uncertainties such that differences of 1‰ or less can be reliably detected. Inter-laboratory exercises are invaluable to assess the state-of-the art of measurement capabilities of laboratories necessary to achieve such performance criteria. National and designated metrology institutes from a number of countries recently participated in an inter-laboratory assessment (CCQM-K140) of stable carbon isotope ratio determination of bulk honey. The same sample material was distributed to a number of forensic isotope analysis laboratories that could not participate directly in the metrological comparison. The results from these studies have demonstrated that the majority of participants provided isotope delta values with acceptable performance metrics; that all participants ensured traceability of their results; and that where measurement uncertainties were reported; these were fit-for-purpose. A number of the forensic laboratories only reported precision rather than full estimates of measurement uncertainty and this was the major cause of the few instances of questionable performance metrics. Reporting of standard deviations in place of measurement uncertainties is common practice outside metrology institutes and the implications for interpretations of small differences in isotopic compositions are discussed. The results have also highlighted a number of considerations that are useful for organisers of similar inter-laboratory studies in the future.


Effects of fatigue on kinematical parameters during submaximal and maximal 100-m butterfly bouts.
We aimed to analyze the effects of fatigue on kinematical parameters during submaximal and maximal butterfly. Seven female swimmers performed two randomized 100-m butterfly bouts, at submaximal velocity and at maximal velocity in 25-m pool. During the 1st and 4th laps of each 100 m, kinematic data were recorded by two video cameras (above and below water) on the sagittal plane. Velocity, stroke length, stroke frequency, intracyclic horizontal velocity variation, horizontal and vertical displacements of the hand and foot and stroke phases' duration were computed for each stroke cycle. Velocity, stroke length, stroke frequency were lower for 4th than 1st lap, at both intensities. Dropped elbow and foot vertical amplitude of 1st and 2nd downbeats were higher for 4th than 1st lap, at both intensities. At submaximal and maximal intensity, swimmers spent more time during push and recovery phases. At submaximal intensity, swimmers experienced fewer difficulties to cope with fatigue between 1st and 4th lap, which allowed the maintenance of intracyclic velocity variation. However, at maximal intensity, swimmers were probably more fatigued and, as a consequence, less mechanically efficient, showing an increase in intracyclic velocity variation.


The effects of low-high doses of dexmedetomidine on erythrocyte deformability in rats.
Dexmedetomidine is an anesthetic agent frequently used for sedation, intensive care units, and general anesthesia. The purpose of our study was to investigate the effect of two different doses of dexmedetomidine on erythrocyte deformability in rats. The study was performed on 21 male rats, with 7 rats in each study group and the control group. The rats in the study groups were administered dexmedetomidine (low dose 5 µg.kg-, high dose 10 µg.kg-) intraperitoneally, and the rats in the control group were administered physiological saline. Erythrocyte packs were prepared using heparinized total blood samples. Deformability measurements were done by erythrocyte suspensions in phosphate buffered saline (PBS) buffer. A constant flow filtrometer system was used to measure erythrocyte deformability, and the relative resistance was calculated. Use of a high dose dexmedetomidine resulted in an increase in relative resistance, which is an indicator for erythrocyte deformability in control rats (p=0.014). High dose dexmedetomidine via negative change in erythrocyte deformability may cause a functional deterioration in blood flow and tissue perfusion. Our results showed that low dose dexmedetomidine protects erythrocyte deformability better than the high dose (Fig. 1, Ref. 23).


Work resumption after invasive heart procedures, rehabilitation and ergonomic evaluation: from the hospital to the workplace.
Our Institute adopts a multidisciplinary protocol named "CardioWork" for work resumption after invasive cardiac procedures and subsequent rehabilitation: after evaluation of the cardiac functional profile, the occupational physician analyses the work activity prior to the cardiopathological event, identifies the presumed task energy requirement (from specific, published tables), and compares it with the exercise test results. Indications regarding timing and modality of returning to work are formulated accordingly. To verify the reliability of the indications thus provided, we carried out a clinical-functional follow-up study in the workplace, with Holter ECG and Armband measurement of actual energy expenditure. Over the course of two years, we enrolled 36 patients (mostly males, aged between 30 and 70 years), hospitalized after coronary revascularization, valve replacement or cardiac defibrillator implant. After rehabilitation, instrumental diagnostics (Holter ECG, echocardiography, exercise test) showed discrete functional conditions, with better values with regard to cardiac function than exercise capacity and effort tolerance. All subjects were judged fit for the job, in most cases with limitations concerning ergonomic factors, working timetable and/or stress. They returned to work quickly, with good adherence to the indications provided. Workplace Holter ECG did not show appreciable differences compared to the hospital evaluation. In one case, the average energy expenditure measured while working was higher than that inferred from the tables; in the remaining subjects, the actual expenditure coincided with what was expected or was lower. In a minority of cases (39%), the measured average expenditure slightly exceeded the optimal value (35% of the maximal value at the exercise test) recommended at the time of hospital discharge. At the end of the workplace evaluation, it was not necessary to formulate new indications. The study provides further evidence of the effectiveness of the CardioWork protocol in promoting return to work after invasive heart procedures. Though they need continuous updating, the published estimates of presumed task energy requirement remain reliable. In particularly complex cases, it is however advisable to carry out a field check of the ergometric assessments performed at the end of rehabilitation.


The chimeric GaaR-XlnR transcription factor induces pectinolytic activities in the presence of D-xylose in Aspergillus niger.
Aspergillus niger is a filamentous fungus well known for its ability to produce a wide variety of pectinolytic enzymes, which have many applications in the industry. The transcriptional activator GaaR is induced by 2-keto-3-deoxy-L-galactonate, a compound derived from D-galacturonic acid, and plays a major role in the regulation of pectinolytic genes. The requirement for inducer molecules can be a limiting factor for the production of enzymes. Therefore, the generation of chimeric transcription factors able to activate the expression of pectinolytic genes by using underutilized agricultural residues would be highly valuable for industrial applications. In this study, we used the CRISPR/Cas9 system to generate three chimeric GaaR-XlnR transcription factors expressed by the xlnR promoter by swapping the N-terminal region of the xylanolytic regulator XlnR to that of the GaaR in A. niger. As a test case, we constructed a PpgaX-hph reporter strain to evaluate the alteration of transcription factor specificity in the chimeric mutants. Our results showed that the chimeric GaaR-XlnR transcription factor was induced in the presence of D-xylose. Additionally, we generated a constitutively active GaaR-XlnR V756F version of the most efficient chimeric transcription factor to better assess its activity. Proteomics analysis confirmed the production of several pectinolytic enzymes by ΔgaaR mutants carrying the chimeric transcription factor. This correlates with the improved release of D-galacturonic acid from pectin by the GaaR-XlnR V756F mutant, as well as by the increased L-arabinose release from the pectin side chains by both chimeric mutants under inducing condition, which is required for efficient degradation of pectin. KEY POINTS: • Chimeric transcription factors were generated by on-site mutations using CRISPR/Cas9. • PpgaX-hph reporter strain allowed for the screening of functional GaaR-XlnR mutants. • Chimeric GaaR-XlnR induced pectinolytic activities in the presence of D-xylose.


Instability-Induced Pattern Formations in Soft Magnetoactive Composites.
Elastic instabilities can trigger dramatic microstructure transformations giving rise to unusual behavior in soft matter. Motivated by this phenomenon, we study instability-induced pattern formations in soft magnetoactive elastomer (MAE) composites deforming in the presence of a magnetic field. We show that identical MAE composites with periodically distributed particles can switch to a variety of new patterns with different periodicity upon developments of instabilities. The newly formed patterns and postbuckling behavior of the MAEs are dictated by the magnitude of the applied magnetic field. We identify the particular levels of magnetic fields that give rise to strictly doubled or multiplied periodicity upon the onset of instabilities in the periodic particulate soft MAE. Thus, the predicted phenomenon can be potentially used for designing new reconfigurable soft materials with tunable material microstructures remotely controlled by a magnetic field.


Is osteoporosis a peculiar association with primary biliary cirrhosis?
(1) To compare the prevalence of osteoporosis (t-score < or =-2.5 SD) between stage IV PBC patients, and two groups of age- and sex-matched controls: one with hepatitis C virus (HCV)-related cirrhosis, and the other one consisting of a group of healthy subjects from the general population; (2) to identify the main risk factors for the development of bone loss. Thirty-five stage IV PBC patients (mean age 52.5+/-10 years), 49 females with HCV-related cirrhosis (mean age 52.9+/-5.8 years) and 33 healthy females (mean age 51.8+/-2.22 years) were enrolled in the study. Bone metabolism was evaluated by measuring serum calcium corrected for serum albumin (Ca corr.), 25-hydroxy vitamin D (25-OH vit D), parathyroid hormone, osteocalcin. Bone mineral density (BMD) was assessed at the lumbar spine by dual-photon X-ray absorptiometry. Osteoporosis was present in 5/35 PBC patients (14.2%) and in 7/49 HCV-related cirrhotic patients (14.3%), without any statistical difference between the two groups. Among healthy control subjects, none had osteoporosis. No difference was found between the three groups in serum parameters of bone metabolism. Univariate analysis showed that menopausal state and low BMI were significantly correlated with osteoporosis. Multivariate regression analysis showed that menopausal status, BMI <23, and old age were independent variables significantly correlated with osteoporosis. PBC in itself has no negative influence on BMD. End-stage liver disease patients carry a disease-specific risk for osteoporosis, but have an effective risk of bone loss in relation to individual potential risk for each patient. A practical message should be taken into account, that is, every effort should be made to prevent osteoporosis when a patient has simple osteopenia, or if it is a woman in or near menopausal age.


Rpb4/7 facilitates RNA polymerase II CTD dephosphorylation.
The Rpb4 and Rpb7 subunits of eukaryotic RNA polymerase II (RNAPII) participate in a variety of processes from transcription, DNA repair, mRNA export and decay, to translation regulation and stress response. However, their mechanism(s) of action remains unclear. Here, we show that the Rpb4/7 heterodimer in Saccharomyces cerevisiae plays a key role in controlling phosphorylation of the carboxy terminal domain (CTD) of the Rpb1 subunit of RNAPII. Proper phosphorylation of the CTD is critical for the synthesis and processing of RNAPII transcripts. Deletion of RPB4, and mutations that disrupt the integrity of Rpb4/7 or its recruitment to the RNAPII complex, increased phosphorylation of Ser2, Ser5, Ser7 and Thr4 within the CTD. RPB4 interacted genetically with genes encoding CTD phosphatases (SSU72, FCP1), CTD kinases (KIN28, CTK1, SRB10) and a prolyl isomerase that targets the CTD (ESS1). We show that Rpb4 is important for Ssu72 and Fcp1 phosphatases association, recruitment and/or accessibility to the CTD, and that this correlates strongly with Ser5P and Ser2P levels, respectively. Our data also suggest that Fcp1 is the Thr4P phosphatase in yeast. Based on these and other results, we suggest a model in which Rpb4/7 helps recruit and potentially stimulate the activity of CTD-modifying enzymes, a role that is central to RNAPII function.


Cholinesterase inhibitors as Alzheimer's therapeutics (Review).
Alzheimer's disease (AD) is one of the most common forms of dementia. AD is a chronic syndrome of the central nervous system that causes a decline in cognitive function and language ability. Cholinergic deficiency is associated with AD, and various cholinesterase inhibitors have been developed for the treatment of AD, including naturally‑derived inhibitors, synthetic analogues and hybrids. Currently, the available drugs for AD are predominantly cholinesterase inhibitors. However, the efficacy of these drugs is limited as they may cause adverse side effects and are not able to completely arrest the progression of the disease. Since AD is multifactorial disease, dual and multi‑target inhibitors have been developed. The clinical applications and the limitations of the inhibitors used to treat AD are discussed in the present review. Additionally, this review presents the current status and future directions for the development of novel drugs with reduced toxicity and preserved pharmacological activity.


A Pilot Randomized Controlled Trial of Cognitive-Behavioral Therapy for Insomnia in Adolescents With Persistent Postconcussion Symptoms.
Cognitive-behavioral therapy for insomnia (CBT-I) is an effective insomnia treatment but has yet to be applied to adolescents with sleep disruption following concussion. This pilot study evaluated CBT-I to improve insomnia in adolescents with protracted concussion recovery. Tertiary pediatric hospital. Participants (N = 24) were 12 to 18 years old (M = 15.0, SD = 1.4), 15.1 weeks (SD = 9.2) postinjury, and presenting with sleep disruption and persistent postconcussion symptoms. A single-blind, parallel-group randomized controlled trial (RCT) design comparing 6 weeks of CBT-I and a treatment-as-usual control group. Outcomes were measured before treatment, at treatment completion, and 4 weeks after completion. Primary outcome was Insomnia Severity Index. Secondary outcomes included Pittsburgh Sleep Quality Index, Dysfunctional Beliefs and Attitudes about Sleep Scale, 7-night sleep diary, PROMIS Depression, PROMIS Anxiety, and Health and Behavior Inventory. Adolescents who received CBT-I demonstrated large and clinically significant improvements in insomnia ratings at posttreatment that were maintained at follow-up. They also reported improved sleep quality, fewer dysfunctional beliefs about sleep, better sleep efficiency, shorter sleep-onset latency, and longer sleep time compared with those with treatment as usual. There was also a modest reduction in postconcussion symptoms. In this pilot RCT, 6 weeks of CBT-I produced significant improvement in sleep in adolescents with persistent postconcussion symptoms. A larger trial is warranted.


Exercise Thermoregulation in Prepubertal Children: A Brief Methodological Review.
Prepubertal children (6-12 yr) differ from adults in various morphological and physiological factors that may influence thermoregulatory function; however, experimental evidence of meaningful child-adult differences in heat strain during exercise-heat stress is sparse, despite numerous studies. Although we appreciate the challenges associated with performing such comparisons, part of that discrepancy may be due to the methods used. Nonetheless, a focused discussion of these methodological considerations and their implications for current understanding remains unavailable. This is an important knowledge gap given the threat to health posed by rising global temperatures and the ongoing focus on improving physical activity levels in children. The aims of this methodological review were, therefore, to (i) review the theoretical basis for child-adult differences in thermoregulatory function, (ii) describe previous comparisons of exercise thermoregulation between prepubertal children and adults, (iii) discuss two methodological issues associated with that research, which, in our view, make it difficult to present empirical evidence related to child-adult differences in thermoregulatory function and associated heat strain, (iv) provide potential solutions to these issues, and (v) propose pertinent areas for further research.


[Baseline analysis of refractory primary biliary cirrhosis].
To summarize the clinical characters of refractory primary biliary cirrhosis (PBC) versus typical ones and explore the risk factors of prognosis. From 2009 to 2011, 60 PBC patients on the therapy of ursodeoxycholic acid (UDCA) over 1 year at our clinic were recruited. According to the response to UDCA by the Paris criteria, they were divided into refractory group (n = 23) and typical group (n = 37) to analyze the basic clinical conditions, biochemical markers, antibodies and liver biopsies. (1) Compared with the typical patients, the refractory ones had more fatigue (73.9% vs 45.9%), pruritus (60.9% vs 40.5%) and jaundice (43.4% vs 18.9%); (2) the serum level of biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL) and immunoglobulin M (IgM)) were higher in the refractory group (P < 0.05); (3) no differences existed between two groups in age, gender, antibodies (antinuclear antibody (ANA), antimitochondrial antibody (AMA), AMA-M2, anti-GP210, anti-SP100 and anti-centromere antibody (ACA)) or liver biopsies. Some clinical severe manifestation (fatigue, pruritus and jaundice) and higher biochemical markers levels (ALT, AST, ALP, GGT, TBIL, DBIL and IgM) seem to predict a worse response to UDCA and a rapid progression of disease in PBC patients.


CDK9/CYCLIN T1 expression during normal lymphoid differentiation and malignant transformation.
CDK9 is a member of the CDC2-like family of kinases. Its cyclin partners are members of the CYCLIN T family (T1, T2a, and T2b) and CYCLIN K. The CDK9/CYCLIN T1 complex is very important in the differentiation programme of several cell types, controlling specific differentiation pathways. Limited data are available regarding the expression of CDK9/CYCLIN T1 in haematopoietic and lymphoid tissues. The aim of this study was to analyse the expression of the CDK9/CYCLIN T1 complex in lymphoid tissue, in order to assess its role in B- and T-cell differentiation and lymphomagenesis. CDK9/CYCLIN T1 expression was found by immunohistochemistry in precursor B and T cells. In peripheral lymphoid tissues, germinal centre cells and scattered B- and T-cell blasts in interfollicular areas expressed CDK9/CYCLIN T1, while mantle cells, plasma cells, and small resting T-lymphocytes displayed no expression of either molecule. CDK9/CYCLIN T1 expression therefore appears to be related to particular stages of lymphoid differentiation/activation. CDK9 and CYCLIN T1 were highly expressed in lymphomas derived from precursor B and T cells, from germinal centre cells, such as follicular lymphomas, and from activated T cells (ie anaplastic large cell lymphomas). Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma also showed strong nuclear staining. Diffuse large B-cell, Burkitt's lymphomas, and peripheral T-cell lymphomas, among T-cell lymphoproliferative disorders, showed a wide range of values. No expression of CDK9 or CYCLIN T1 was detected in mantle cell and marginal zone lymphomas. However, at the mRNA level, an imbalance in the CDK9/CYCLIN T1 ratio was found in follicular lymphoma and diffuse large B-cell lymphomas with germinal centre phenotype, and in the cell lines of classical Hodgkin's lymphomas, Burkitt's lymphomas, and anaplastic large cell lymphoma, in comparison with reactive lymph nodes. These results suggest that the CDK9/CYCLIN T1 complex may affect the activation and differentiation programme of lymphoid cells. The molecular mechanism through which the CDK9/CYCLIN T1 complex is altered in malignant transformation needs to be elucidated.


[Efficacy and safety of vandetanib on advanced medullary thyroid carcinoma: single center result from a phase Ⅲ study].
Objective: There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib,a novel multitargeted receptor tyrosine kinase inhibitor, has previously shown antitumor activity in phase Ⅱ studies of patients with advanced MTC. This study was to evaluate the efficacy and the safety of vandetanib on advanced MTC. Methods: This study was an open, international multi-center phase Ⅲ clinical trial and the study number was NCT01298323. The single-center study was a sub-group analysis of the international study, which was conducted on 9 pathologically confirmed advanced MTC patients by Cancer Hospital Chinese Academy of Medical Sciences between March 2012 and October 2017. Vandetanib (300 mg) was orally administered daily till death or withdrawal. The efficacy was evaluated according to RECIST criteria and the adverse events were evaluated according to NCI criteria. Results: The objective response rate was 3/9,and the disease control rate was 4/9. The median progression-free survival was 44 months. All patients who had the elevated levels of calcitonin (CTN) and carcino-embryonic antigen (CEA) before treatment began to show the decreases in the level of CTN and CEA after 3 months and later showed again the increases in the levels of both tumor markers with tumor progression. By ROC curve analysis, CTN was of statistically significance(P<0.05, 95%CI 0.558-0.834), but CEA was not(P>0.05). Adverse events were generally mild (grade 1 or 2),including hypertension (9 cases),skin rash (9 cases), and diarrhea (6 cases). Two patients developed grade 3 elevation of serum glutamate pyruvate transaminase and one patient developed grade 3 elevation of drug-related bowel disease. No grade 4 drug-related adverse event occurred. Conclusions: Vandetanib is effective and well tolerated for patients with locally advanced or metastatic MTC who have no chance for surgery. This indicates the increase of CTN is clinically relevant to disease progression, but the number of patients are extremely low, and, therefore further research is needed. Long-term use of vandetanib may cause resistance.


2-Phenyl-8,9,10,11-tetra-hydro-1-benzo-thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine.
In the title compound, C(17)H(14)N(4)S, the benzothieno moiety is fused at one end of the pyramidine ring while the triazole ring with a phenyl substituent is fused at the other side. The triazole ring is almost planar [maximum deviation = 0.0028 (3) Å] while the cyclo-hexane ring adopts a half-chair conformation. In the crystal, pairs of inter-molecular C-H⋯N hydrogen bonds form centrosymmetric head-to-head dimers, corresponding to an R(2) (2)(8) graph-set motif. Further C-H⋯N inter-actions generate a zigzag chain of mol-ecules along the c axis. The supra-molecular assembly is consolidated by π-π stacking inter-actions [centroid-centroid distance = 3.445 (4) Å].


Kainate-induced apoptosis correlates with c-Jun activation in cultured cerebellar granule cells.
We have investigated the involvement of c-Jun in cell death induced by exposure of primary cultures of murine cerebellar granule cells to the glutamate receptor agonist kainate (KA) and evaluated its possible use as a marker for apoptosis. Using cerebellar granule cell neurones from postnatal day 7 mice, we found that 1 hr exposure to KA (1-1000 microM) induced a concentration-dependent neuronal cell death with characteristic apoptotic morphology, including cell shrinkage, neurite blebbing and DNA fragmentation. In addition KA-induced a concentration-dependent expression of c-Jun mRNA and protein as determined by in situ hybridization and immunocytochemistry respectively. DNA fragmentation was detected using terminal transferase-mediated nick-end (TUNEL) labelling and agarose gel electrophoresis. KA-induced cell death was significantly attenuated by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM), which shifted the concentration-response curve significantly rightward. The number of apoptotic cell bodies, determined by TUNEL, was also reduced by CNQX (50 microM), with only 15-20% of neurones staining positive after exposure to 1mM KA. In addition, the number of positively stained cells for c-Jun protein and mRNA was substantially reduced by CNQX (50 microM) as determined by random and representative cell counts. These results show for the first time that KA induced apoptotic neuronal death in cultured murine cerebellar granule cells involves the induction of c-Jun mRNA and protein, suggesting the involvement of this immediate early gene in excitotoxic receptor-mediated apoptosis and its potential use as a marker for apoptotic cell death.


Crisis intervention and social work practice in hospitals.
Crisis intervention, with its emphasis on focused treatment in a limited time frame, is adaptable to social work practice in hospitals. The author discusses the crisis intervention model in relation to the hospitalized patient and his or her family and examines three kinds of crises: those caused by illness or injuries, by hospitalization itself, and by treatment procedures.


Poly(ADP-ribosyl)ation enzyme-1 as a target for neuroprotection in acute central nervous system injury.
Poly(ADP-ribose) polymerase 1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network. In response to stresses that are toxic to the genome, PARP-1 activity increases substantially, an event that appears crucial for maintaining genomic integrity. Massive PARP-1 activation, however, can deplete the cell of NAD(+) and ATP, ultimately leading to energy failure and cell death. The discovery that cell death may be suppressed by PARP inhibitors or by deletion of the parp-1 gene has prompted a great deal of interest in the process of poly(ADP-ribosyl)ation. Suppression of PARP-1 is capable of protecting against cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes. The secondary damage of initially surviving neurons in brain stroke accounts for most of the volume of the infarcted area and the subsequent loss of brain function. Microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may therefore be a promising strategy in protecting neurons from this secondary damage, as well. As PARP-1 is now recognised as playing a role also in the regulation of gene transcription, this further increases the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenges the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death. PARP(s) might regulate cell fate as essential modulators of death and survival transcriptional programs with relation to NF-kappaB and p53, proposing that inhibitors of poly(ADP-ribosyl)ation could therefore prevent the deleterious consequences of neuroinflammation by reducing NF-kappaB activity.


Exposure to furry pets and the risk of asthma and allergic rhinitis: a meta-analysis.
Exposure to pets has been implicated as a risk factor for asthma. However, this relation has been difficult to assess in individual studies because of the large potential of selection bias. We sought to examine the association between exposure to furry pets and asthma and allergic rhinitis by means of a meta-analysis. We retrieved studies published in any language by searching systematically Medline (1966-March 2007), Embase, LILACS and ISI Proceedings computerized databases, and by examining manually the references of the original articles and reviews retrieved. We included cohort and case-control studies reporting relative risk estimates and confidence intervals of exposure to cats, dogs and unspecified furry animals and subsequent asthma and allergic rhinitis. We excluded cross-sectional studies and those studies that did not measure exposure but rather sensitization to pets. Thirty-two studies were included. For asthma, the pooled relative risk related to dog exposure was 1.14 (95% CI 1.01-1.29), that related to exposure to any furry pet was 1.39 (95% CI 1.00-1.95). Among cohort studies, exposure to cats yielded a relative risk of 0.72 (95% CI 0.55-0.93). For rhinitis, the pooled relative risk of exposure to any furry pet was 0.79 (95% CI 0.68-0.93). Exposure to cats exerts a slight preventive effect on asthma, an effect that is more pronounced in cohort studies. On the contrary, exposure to dogs increases slightly the risk of asthma. Exposure to furry pets of undermined type is not conclusive. More studies with exact measurement of exposure are needed to elucidate the role of pet exposures in atopic diseases.


The teaching of case formulation in Canada.
Prompted by the Council on Education and Professional Liaison of the Canadian Psychiatric Association, the authors surveyed the program directors and senior residents of departments of psychiatry on the teaching of case formulation skills in Canada. The results showed that case formulation is taught formally in most departments and that students are expected to demonstrate these skills throughout their training. However, less than one-half of the teaching programs provide guidelines for case formulation. The residents, who expected case formulation skills to be assessed in the oral examinations of the Royal College, were unanimous in their view that the process should be standardized and that guidelines be provided. Both the program directors and the residents favoured a biopsychosocial format for recording case formulation, but they did not agree on the content of an ideal formulation.


[Surgical technique of lateral unicompartmental knee arthroplasty and discussion of the maximum correction value in the treatment of knee valgus deformity].
To investigate the surgical technique and the short-term effectivenss of lateral unicompartmental knee arthroplasty (LUKA) through lateral approach in the treatment of valgus knee and to calculate the maximum value of the theoretical correction of knee valgus deformity. A retrospective analysis was performed on 16 patients (20 knees) who underwent LUKA and met the selection criteria between April 2021 and July 2022. There were 2 males and 14 females, aged 57-85 years (mean, 71.5 years). The disease duration ranged from 1 to 18 years, with an average of 11.9 years. Knee valgus was staged according to Ranawat classification, there were 6 knees of type Ⅰ, 13 knees of type Ⅱ, and 1 knee of type Ⅲ. All patients were assigned the expected correction value of genu valgus deformity by preoperative planning, including the correction value of lateral approach, intra-articular correction value, and residual knee valgus deformity value. The actual postoperative corrected values of the above indicators were recorded and the theoretical maximum correctable knee valgus deformity values were extrapolated. The operation time, intraoperative blood loss, incision length, hospital stay, hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibia angle (mMPTA), joint line convergence angle (JLCA), posterior tibial slope (PTS), range of motion (ROM), Hospital for Special Surgery (HSS) score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were also recorded for effectiveness evaluation. The patients' incision length averaged 13.83 cm, operation time averaged 85.8 minutes, intraoperative blood loss averaged 74.9 mL, and hospital stay averaged 6.7 days. None of the patients suffered any significant intraoperative neurological or vascular injuries. All patients were followed up 10-27 months, with a mean of 17.9 months. One patient with bilateral knee valgus deformities had intra-articular infection in the left knee at 1 month after operation and the remaining patients had no complication such as prosthesis loosening, dislocation, and infection. The ROM, HSS score, and WOMAC score of knee joint significantly improved at each time point after operation when compared to those before operation, and the indicators further improved with time after operation, the differences were all significant ( P<0.05). Imaging measurement showed that HKA, mLDFA, JLCA, and PTS significantly improved at 3 days after operation ( P<0.05) except for mMPTA ( P>0.05). Postoperative evaluation of the knee valgus deformity correction values showed that the actual intra-articular correction values ranged from 0.54° to 10.97°, with a mean of 3.84°. The postoperative residual knee valgus deformity values ranged from 0.42° to 5.30°, with a mean of 3.59°. The actual correction values of lateral approach ranged from 0.21° to 12.73°, with a mean of 4.26°. LUKA through lateral approach for knee valgus deformity can achieve good early effectiveness. Preoperative planning can help surgeons rationally allocate the correction value of knee valgus deformity, provide corresponding treatment strategies, and the maximum theoretical correction value of knee valgus deformity can reach 25°.


Phainanoids A-F, a new class of potent immunosuppressive triterpenoids with an unprecedented carbon skeleton from Phyllanthus hainanensis.
Phainanoids A-F (1-6), six highly modified triterpenoids with a new carbon skeleton by incorporating two unique motifs of a 4,5- and a 5,5-spirocyclic systems, were isolated from Phyllanthus hainanensis. Their structures with absolute configurations were determined by spectroscopic data, chemical methods, and X-ray crystallography. Compounds 1-6 exhibited exceptionally potent immunosuppressive activities in vitro against the proliferation of T and B lymphocytes. The most potent one, phainanoid F (6), showed activities against the proliferation of T cells with IC50 value of 2.04 ± 0.01 nM (positive control CsA = 14.21 ± 0.01 nM) and B cells with IC50 value of <1.60 ± 0.01 nM (CsA = 352.87 ± 0.01 nM), which is about 7 and 221 times as active as CsA, respectively. The structure-activity relationships of 1-6 are discussed.


[Effect of Safflor injection on the intestine ultrastructure characteristics following intestine ischemia/reperfusion injury in rabbits].
To explore effects of Safflor (Chinese Tradional Medicine) on the intestine ultrastructure characteristics during intestine ischemia/ reperfusion injury (I/RI) in rabbits. Thirty rabbits were randomly divided into three groups: control group (group S), ischemia/reperfusion group (group I/R) and Safflor injection group (group SI). Morphological changes of intestine ischemia/reperfusion in rabbits and the protective effects of Safflor were observed under electric telescope. The intestine ultrastructure was badly injured in group I/R. Mitochondria and intestinal mucosal cells were swellen and endoplasmic reticulum expanded, however, in the SI group the ultrastructural injury of the ischemia greatly ameliorated. The ultrastructure injury occurrted after intestine I/RI and Safflor has protective effects on the intestine ultrastructure.


Formation of novel bioactive metabolites from the reactions of pro-inflammatory oxidants with polyphenolics.
Dietary polyphenolics such as those in soy or red wine can have beneficial effects on the development of chronic human diseases. The mechanisms of action of isoflavones have been diverse and include their roles as weak estrogens, inhibitors of tyrosine kinase-dependent signal transduction processes and as antioxidants. Recent insights into the oxidative stress model of atherosclerosis suggest an interesting synthesis of these concepts. Sites of inflammation are associated with the formation of complex mixtures of reactive oxygen, nitrogen and halogenating species capable of modifying both endogenous biomolecules and polyphenolics. Of particular significance are the halogenation reactions mediated by myeloperoxidase that can modify key amino acids such as arginine and polyphenolics such as genistein. Hypochlorite, the reaction product of myeloperoxidase can halogenate polyphenolics to form stable derivatives with modified biological activity. Thus the in situ metabolism at sites of inflammation is unique and generates novel pharmacophores with potentially distinct modes of action from the parent compounds.


Elastomeric hydrogels by polymerizing silicone microemulsions.
Robust, transparent elastomeric hydrogels encoded with a bicontinuous structure result from the sequential photopolymerization of the aqueous hydroxyethyl methacrylate phase and crosslinking of the silicone phase of a silicone microemulsion stabilized with an acrylate-functional silicone-poly(ethylene glycol) surfactant.


Experience of sport stacking in Korean older adults.
Today sedentary lifestyles are a major public health concern and there are many evidences related to physical inactivity. The well-documented evidence is that regular physical activity is an essential part for improving overall health with advancing aging and the most efficient means playing roles of rehabilitation and prehabilitation. However, there are few activity programs which could motivate older adults to continue and maintain their active lifestyles. The purpose of the current study was to describe experience of sport stacking which applied to Korean older adults in the first time. Eighteen older adults living in the community in Seoul which was the capital and largest metropolis of the Republic of Korea participated in the study. A qualitative interview and a survey were conducted and data were analyzed by interpretive content analysis. Individual, semistructured, face-to-face interviews were recorded, transcribed, condensed and coded to find themes. The main themes were identified regarding older adults' experience of sport stacking: enjoyment of sport stacking, attitudes toward sport stacking as a physical activity program, and benefits from sport stacking. In conclusions, Korean older adults had positive experience of sport stacking and it was necessary for developing strategies to spread it as the physical activity program for older persons in Korea to improve their health and quality of life.


Hispidulin suppresses tumor growth and metastasis in renal cell carcinoma by modulating ceramide-sphingosine 1-phosphate rheostat.
Sphingosine 1-phosphate (S1P) rheostat is considered as a key signal that determines cell fate. This study aimed to report that hispidulin, a polyphenolic flavonoid, exerted anti-growth and anti-metastasis effects against renal cell carcinoma (RCC) by modulating the balance of ceramide-S1P. In vitro studies showed that hispidulin could effectively inhibit cell proliferation, cell migration, cell invasion, and epithelial-mesenchymal transition, and promote cell apoptosis in Caki-2 and A498 cell lines. Moreover, it also increased the ceramide/S1P ratio. Consistent with the in vitro findings, the efficacy of hispidulin in vivo showed that it effectively suppressed tumor growth and lung metastasis. Furthermore, the results revealed that hispidulin significantly suppressed the activity of sphingosine kinase 1 (Sphk1) in RCC cells; however, no significant change was observed in the mRNA or protein expression of Sphk1. The overexpression of Sphk1 could significantly abrogate the anti-growth and anti-metastasis effects of hispidulin, whereas the siRNA-targeting Sphk1 or Sphk1 inhibitor was able to augment the anticancer effects of hispidulin against RCC. Moreover, hispidulin interfered with the phosphorylation and translocation of Sphk1, leading to inhibitory effects of Sphk1 activity. In summary, the findings suggested that hispidulin suppressed tumor growth and metastasis by inhibiting the Sphk1 activity and consequently modulating ceramide-S1P rheostat. It also presented a new explanation for the antitumor mechanisms of hispidulin against RCC.


Lack of effects of tetracaine in rat nucleus paragigantocellularis (PGC) on analgesia from periqueductal gray (PAG) met-enkephalin (ME) injections (in raphe magnus-blocking doses), and on baseline tail-flick latency.
We showed previously that (1 microgram) tetracaine block of PAG prevents the analgesic effect of PGC-ME injections, and also produces hyperalgesia regarding baseline tail-flick latencies. In the present study we injected PGC (unilaterally and bilaterally) with tetracaine so as to study its possible role in tonic descending inhibition of pain, as well as its necessity for analgesia due to PAG opiate injection. Two micrograms of tetracaine in PGC unilaterally or bilaterally failed to affect baseline tail-flick latencies and failed to attenuate at all the distinct analgesic effect of 2 micrograms ME injected into PAG. This analgesic effect was seen as a change in mean tail-flick latency from about 5.5 to 7.0 seconds 8-12 minutes post-injection, recovering to 5.5 second baseline by 25 minutes. Two micrograms tetracaine in nucleus raphe magnus (RM) was however sufficient to block the analgesic effect of RM stimulation. Thus PGC does not appear to participate in tonic descending pain inhibition (as PAG appears to do) nor is its functional integrity necessary for PAG ME analgesia (though PAG is necessary for PGC analgesia).


Topical ketoconazole: a systematic review of current dermatological applications and future developments.
Introduction: Although labeling changes and market withdrawal have been implemented for oral ketoconazole (KTZ) due to serious adverse effects (AEs), topical KTZ is generally thought to be effective and safe for the treatment of superficial fungal infections. New dermatologic indications for the use of topical KTZ have arisen such as onychomycosis, blepharitis, and hair loss. This article aims to review the literature on topical KTZ's efficacy and AEs, as well as provide an overview on current insights regarding its mechanism of action and upcoming developments. Methods: A PubMed search was done to include randomized controlled trials (RCTs) focusing on the use of topical KTZ in human subjects. Results: Forty studies with 4566 patients were included in this review. Topical KTZ is clinically effective for the treatment of Malassezia-related conditions such as seborrheic dermatitis (SD) and pityriasis versicolor (PV) with a reported efficacy of 63-90% and 71-89%, respectively. Conclusions: Topical KTZ demonstrates high clinical efficacy for Malassezia-related conditions. More efficacious alternatives are now available for Tinea and Candida. Although topical KTZ is safe, clinicians should be aware that allergic contact dermatitis may occur. Further studies should be completed to investigate the use of topical KTZ for hair loss and inflammatory dermatoses.


Metabolic adaptation is associated with a greater increase in appetite following weight loss: a longitudinal study.
Weight loss is associated with a disproportionate reduction in energy expenditure, along with increases in hunger feelings and ghrelin concentrations. These changes are presumed to be homeostatic mechanisms to counteract the energy deficit. The possibility that these 2 components of the energy balance equation are mechanistically linked has never been examined. This study aimed to determine if the disproportionate reduction in resting metabolic rate (RMR) seen with weight loss is associated with changes in the plasma concentration of gastrointestinal hormones involved in appetite regulation and subjective appetite ratings. This was a longitudinal study with repeated measurements. Fifty-six individuals with obesity (body mass index [BMI]: 34.5±0.5 kg/m2; age: 47±1 y; 26 males) underwent an 8 wk low-energy diet, followed by 4 wk of refeeding and weight stabilization. The RMR, respiratory quotient (RQ), body composition, plasma concentrations of ghrelin, glucagon-like peptide 1, peptide YY, cholecystokinin, insulin, and appetite ratings in the fasting and postprandial states were measured at baseline, Wk9 and 13. Metabolic adaptation was defined as significantly lower when measured versus the predicted RMR (pRMR) (from own regression model using baseline data). A 14.2±0.6 kg weight loss was seen at Wk9 and maintained at Wk13. RQ was significantly reduced at Wk9 (0.82±0.06 vs. 0.76±0.05, P< 0.001) but returned to baseline at Wk13. Metabolic adaptation was seen at Wk9, but not Wk13 (-341±58, P <0.001 and -75±72 kJ/d, P = 0.305, respectively). The larger the difference between measured and predicted RMR at both timepoints, the greater the increase in hunger, desire to eat, and composite appetite score (fasting and postprandial at Wk9, postprandial only at Wk13), even after adjusting for weight loss and RQ. A larger metabolic adaptation during weight loss is accompanied by a greater drive to eat. This might help explain the interindividual differences in weight loss outcomes to dietary interventions.


Role of the MHC2TA gene in autoimmune diseases.
Expression of major histocompatibility complex (MHC) class II genes is almost exclusively regulated by the class II transactivator. A promoter polymorphism (-168A/G, rs3087456) in the MHC2TA gene was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction in a northern European population. However, no evidence of association of this MHC2TA variant with the two autoimmune diseases could be subsequently detected in independent cohorts. To test the aforementioned single nucleotide polymorphism and another G-->C change (nt1614 from coding sequence, rs4774) to analyse the haplotype pattern in this MHC2TA gene. A case-control study was performed with 350 patients with rheumatoid arthritis, 396 patients with multiple sclerosis, 663 patients with inflammatory bowel disease (IBD) and 519 healthy controls from Madrid. Genotyping was ascertained by using TaqMan assays-on-demand on a 7900HT analyser, following the manufacturer's suggestions (Applied Biosystems, Foster City, California, USA). Haplotypes were inferred with the expectation-maximisation algorithm implemented by the Arlequin software. No independent association with these autoimmune diseases was found for either polymorphism in the Spanish cohorts tested. However, when haplotypes were compared between patients with rheumatoid arthritis and controls, a significant difference in their overall frequency distribution was observed, evidencing a protective haplotype (-168A/1614C, p = 0.006; odds ratio (OR) 0.7) and a risk haplotype (-168G/1614C, p = 0.019; OR 1.6). Patients with multiple sclerosis mirrored these results, but no effect on IBD was identified. The MHC2TA gene influences predisposition to rheumatoid arthritis and multiple sclerosis, but not to IBD. The -168G allele is not an aetiological variant in itself, but a genetic marker of susceptibility/protection haplotypes.


Toward a Molecular Understanding of Abscisic Acid Actions in Floral Transition.
The transition from the vegetative growth phase to flowering is a crucial checkpoint for plant reproduction and survival, especially under environmental stress conditions. Numerous factors regulate flowering time, including exogenous environmental cues such as day length and temperature, as well as salt and drought stresses, and endogenous phytohormone signaling cascades. Gibberellins and ABA are one classic combination of phytohormones which antagonistically regulate several biological processes, including seed dormancy and germination, primary root growth and seedling development. As regards control of flowering time, gibberellin exhibits a positive role, and represents an important pathway in the regulation of floral transition. However, over the past decades, numerous investigations have demonstrated that the contribution of the stress hormone ABA to floral transition is still controversial, as both positive and negative effects have been documented. It is important to determine why and how ABA shows this contradictory effect on flowering time. In this up to date review, primarily based on recent publications and emerging data, we summarize the distinct and contrasting roles of ABA on floral transition, while the detailed molecular mechanisms underlying these roles are discussed. Finally, the remaining challenges and open questions in this topic are presented.


Report of validation study of assessment of direct immunotoxicity in the rat. The ICICIS Group Investigators. International Collaborative Immunotoxicity Study.
The International Collaborative Immunotoxicity Study (ICICIS) was established in 1986 as a joint activity of the International Programme on Chemical Safety (a cooperative programme of the United Nations Environment Programme, the International Labour Office and the World Health Organization), the Commission of the European Union and the United Kingdom Department of Health. The objectives were to examine whether various experimental techniques could be used in the rat to indicate toxic effects on the immune system, and so to suggest their possible value as general indicators of immunotoxicity. For this purpose scientists in a number of laboratories in different countries agreed to do joint studies, first of azathioprine (AZA) and then of cyclosporin A (CYA), as potent immunosuppressive compounds. The general experimental procedures and the detailed techniques employed were selected to explore whether the limited pathological investigations in the conventional 28-day subacute toxicity test in the rat (OECD, 1995), or 'Enhanced Pathology' tests (weight determination and examination of additional lymphoid organs and application of structured assessment and semiquantitative grading of changes in the principal compartments of lymphoid tissues) would suffice to indicate ('flag') the occurrence of immunotoxicity due to a chemical, or whether specific tests of immune function would be required. When the second chemical, CYA, was studied, standardisation of the protocol for the test, and of all the investigations, and prior training of the toxicological pathologists in the structured assessment scheme, were shown to greatly reduce interlaboratory variation in the results. The initial investigation of AZA had shown that the indicative power of the experiments had been diminished by the use of diverse experimental procedures. The studies were done as toxicity tests, in which three dose levels, including the maximum tolerated dose, and a vehicle control group were employed. The prime objective was to detect any immunotoxic effect of the test compound. It was shown that the limited, basic 'Pathology' investigations specified in Guideline 407 (OECD, 1981) were not able to reveal the effects on the immune system of AZA and CYA, but that several of the additional 'Enhanced Pathology' investigations did so. Of the immune function assays, the most reliable and useful was the 'Antibody Forming Cell' technique. Other immunological evaluations, such as examination of proliferation induced by selected mitogens and NK cell assay, showed promise. The methods employed have the potential to reveal an 'immunotoxic' effect, without necessarily indicating its mechanism, although the changes in different lymphoid compartments can afford a valuable guide to the detailed nature of the toxic action on the immune system. Function tests, being inherently quantitative in nature may well suggest the nature or mechanism of any effect seen, in addition to indicating the occurrence of the effect. However, they may be less convenient to do as part of a routine toxicity test. Overall, the work in ICICIS has shown that the immunotoxic actions of two chemicals were detectable within a 28-day subacute oral toxicity test in the rat, provided that the conventional laboratory procedures were extended to include extra investigations. Both additional selected pathology investigations and immune function tests 'flagged' the immunotoxicity.


Exploration of the Fire-Retardant Potential of Microencapsulated Ammonium Polyphosphate in Epoxy Vitrimer Containing Dynamic Disulfide Bonds.
Epoxy vitrimers appear as a promising alternative to common epoxy thermoset composites. Nevertheless, the possibilities of applying these materials are limited due to their high flammability which may cause high fire risks. To date, the flame-retardant epoxy vitrimer systems reported in the literature almost all rely on intrinsic flame retardancy to achieve high fire safety; however, the complex and expensive synthesis process hinders their large-scale application. In this work, disulfide-based epoxy vitrimer (EPV) was fabricated with 4, 4'-dithiodianiline as the curing agent, and microencapsulated ammonium polyphosphate (MFAPP) was employed as a potential additive flame retardant to improve their fire retardancy. As a comparative study, common epoxy (EP) composites were also prepared using 4,4'-diaminodiphenylmethane as the curing agent. The results showed that the introduction of dynamic disulfide bonds led to a reduction in the initial thermal decomposition temperature of EPV by around 70 °C compared to EP. Moreover, the addition of 7.5 wt.% of MFAPP endowed EP with excellent fire performance: the LOI value was as high as 29.9% and the V-0 rating was achieved in the UL-94 test (3.2 mm). However, under the same loading, although EPV/MFAPP7.5% showed obvious anti-dripping performance, it did not reach any rating in the UL-94 test. The flame-retardant mechanisms in the condensed phase were evaluated using SEM-EDS, XPS, and Raman spectroscopy. The results showed that the residue of EPV/MFAPP7.5% presented numerous holes during burning, which failed to form a continuous and dense char layer as a physical barrier resulting in relatively poor flame retardancy compared to EP/MFAPP7.5%.


Histopathological changes caused by the nymph stage of Linguatula serrata in the mesenteric lymph nodes of goats.
Linguatula serrata (Fröhlich, 1789) is a ubiquitous parasite species belonging to pentastomids, which has been reported frequently from domestic herbivores of Iran. This study was carried out to elucidate the pathological changes caused by the nymphal stage of L. serrata in the mesenteric lymph nodes (MLNs) of goats. Jejunal and ileal MLNs of slaughtered goats infected with L. serrata were collected and fixed in 10% neutral formal saline. Histopathological changes included follicular necrosis accompanied by a loss of lymphocytes and oedematous cystlike spaces. Granulomatous lesions were formed by mononuclear cell infiltration and necrotic tissue. Some lymphocytes were apoptotic with chromatolysis. A more frequent vascular abnormality was vasculitis. These findings show that larval migration is the main factor to initiate trauma and cause irritation in the MLNs of goats. Since goats are habitual intermediate hosts in Iran, rigorous inspection of the MLNs of slaughtered goats is recommended in order to decrease the chance of human infection through the consumption of raw visceral organs of goats.


Another case of "shopping bag" tremor: a difficult to classify action tremor.
This letter was written in response to: Zesiewicz T, Vu T, Carranza MA, et al. Unusual wrist tremor: unilateral isometric tremor? Tremor Other Hyperkinet Mov. 2014; 4: http://tremorjournal.org/article/view/194.


Osmotic and thermal control of magnocellular neurosecretory neurons--role of an N-terminal variant of trpv1.
The release of vasopressin (antidiuretic hormone) plays a key role in the osmoregulatory response of mammals to changes in salt or water intake and in the rate of water loss through evaporation during thermoregulatory cooling. Previous work has shown that the hypothalamus encloses the sensory elements that modulate vasopressin release during systemic changes in fluid osmolality or body temperature. These responses depend in part on a synaptic regulation of vasopressin neurons by afferent inputs arising from osmosensory and thermosensory neurons in the preoptic area. However, recent studies in rats and mice have shown that vasopressin neurons in the supraoptic nucleus also display intrinsic osmosensory and thermosensory properties. Isolated vasopressin neurons exposed to increases in perfusate temperature or osmolality generate increases in non-selective cation channel activity that cause membrane depolarization and increase neuronal excitability. These channels are calcium-permeable and can be blocked by ruthenium red. Moreover, intrinsic responses to osmotic and thermal stimuli are absent in magnocellular neurosecretory cells isolated from mice lacking the transient receptor potential vanilloid-1 (trpv1) gene, which encodes the capsaicin receptor. Immunostaining of vasopressin-releasing neurons with anti-TRPV1 antibodies reveals the presence of amino acids present in the carboxy terminus of the protein, but not those lying in the amino terminal domain. Thus, magnocellular neurosecretory neurons appear to express an N-terminal variant of trpv1 which lacks sensitivity to capsaicin, but which enables osmosensing and thermosensing.


Two phosphorylated subclasses of polyomavirus large T antigen that differ in their modes of association with the cell nucleus.
Two classes of polyomavirus large T antigen were distinguished, differing in their modes of association with the cell nucleus. A weakly associated class, the nucleoplasmic T antigen, representing 30 to 40% of the total, was solubilized when cells were lysed isotonic buffer at pH 7.2. A more tightly bound class retained in isolated nuclei, the retained T antigen, was extractable either at pH 9.0 or in 2 M NaCl. The retained T antigen contained an additional mole of phosphate, 4 mol of PO4 per mol of T antigen, compared with the nucleoplasmic T antigen (3 mol of PO4 per mol of T antigen). Limit digestion with staphylococcal V8 protease yielded equivalent amounts of five peptides ranging in size from 7.5 to 20 kilodaltons. Additional phosphorylation within a 12-kilodalton peptide accounted for most of the difference in phosphate content between retained and nucleoplasmic T-antigen classes.


Morbid Obesity Is Associated With Adverse Clinical Outcomes in Acute Pancreatitis: A Propensity-Matched Study.
Morbid obesity may adversely affect the clinical course of acute pancreatitis (AP); however, there are no inpatient, population-based studies assessing the impact of morbid obesity on AP-related outcomes. We sought to evaluate the impact of morbid obesity on AP-related clinical outcomes and health-care utilization. The Nationwide Inpatient Sample (2007-2011) was reviewed to identify all adult inpatients (≥18 years) with a principal diagnosis of AP. The primary clinical outcomes (mortality, renal failure, and respiratory failure) and secondary resource outcomes (length of stay and hospital charges) were analyzed using univariate and multivariate comparisons. Propensity score-matched analysis was performed to compare the outcomes in patients with and without morbid obesity. Morbid obesity was associated with 3.9% (52,297/1,330,302) of all AP admissions. Whereas the mortality rate decreased overall (0.97%→0.83%, P<0.001), it remained unchanged in those with morbid obesity (1.02%→1.07%, P=1.0). Multivariate analysis revealed that morbid obesity was associated with increased mortality (odds ratio (OR) 1.6; 95% confidence interval (CI) 1.3, 1.9), prolonged hospitalization (0.4 days; P<0.001), and higher hospitalization charges ($5,067; P<0.001). A propensity score-matched cohort analysis demonstrated that the primary outcomes, acute kidney failure (10.8 vs. 8.2%; P<0.001), respiratory failure (7.9 vs. 6.4%; P<0.001), and mortality (OR 1.6, 95% CI 1.2, 2.1) were more frequent in morbid obesity. Morbid obesity negatively influences inpatient hospitalization and is associated with adverse clinical outcomes, including mortality, organ failure, and health-care resource utilization. These observations and the increasing global prevalence of obesity justify ongoing efforts to understand the role of obesity-induced inflammation in the pathogenesis and management of AP.


[Comparison of the expression profile of surface molecular markers on mesenchymal stromal cell cultures isolated from human endometrium and umbilical cord].
Endometrial mesenchymal stromal cells (eMSCs), along with mesenchymal stromal cells (MSCs) isolated from other tissues, are promising for use in regenerative medicine. The benefits of eMSCs include their presence in adults, simplicity of isolation, high proliferative and differentiation capacity. In this study, we have employed the flow cytometry technique to assess expression of 28 molecular markers on the surface of two eMSCs cultures. The culture of MSCs isolated from Wharton's jelly of the umbilical cord (uMSCs) was used as a reference, because uMSCs were studied in details earlier and demonstrated their effectiveness in vivo. Both types of MSCs demonstrated similar expression profiles. They included stem cells surface molecules, cell adhesion molecules and their ligands, some receptor molecules responsible for cell metabolism and proliferation, as well as immunological response molecules.


[The month of birth as factor of child survival].
Season of birth may influence considerably children's survival. This study extends the analysis that the authors have already carried out on the Italian regions and Savoy to other countries: Russia, Low Countries, Belgium and Switzerland. The data refer to the second half of the 19th century. It is in Italy that differential mortality according to season of birth is larger (maximum differential in the Venetia region), followed by Russia and Switzerland. Climate's influence (cold in winter and heat in the summer) combine its effects with social customs typical of each country, age and weaning, other customs concerning children's survival. These different combinations determine some unexpected results in the various countries. In the final part of the paper, data derived from family reconstitution of two Tuscan villages (1790-1916) are analysed in order to build a simple model measuring the net impact of climate on mortality during the first two years of life.


Transport properties of valsartan, sacubitril and its active metabolite (LBQ657) as determinants of disposition.
1. The potential for drug-drug interactions of LCZ696 (a novel, crystalline complex comprising sacubitril and valsartan) was investigated in vitro. 2. Sacubitril was shown to be a highly permeable P-glycoprotein (P-gp) substrate and was hydrolyzed to the active anionic metabolite LBQ657 by human carboxylesterase 1 (CES1b and 1c). The multidrug resistance-associated protein 2 (MRP2) was shown to be capable of LBQ657 and valsartan transport that contributes to the elimination of either compound. 3. LBQ657 and valsartan were transported by OAT1, OAT3, OATP1B1 and OATP1B3, whereas no OAT- or OATP-mediated sacubitril transport was observed. 4. The contribution of OATP1B3 to valsartan transport (73%) was appreciably higher than that by OATP1B1 (27%), Alternatively, OATP1B1 contribution to the hepatic uptake of LBQ657 (∼70%) was higher than that by OATP1B3 (∼30%). 5. None of the compounds inhibited OCT1/OCT2, MATE1/MATE2-K, P-gp, or BCRP. Sacubitril and LBQ657 inhibited OAT3 but not OAT1, and valsartan inhibited the activity of both OAT1 and OAT3. Sacubitril and valsartan inhibited OATP1B1 and OATP1B3, whereas LBQ657 weakly inhibited OATP1B1 but not OATP1B3. 6. Drug interactions due to the inhibition of transporters are unlikely due to the redundancy of the available transport pathways (LBQ657: OATP1B1/OAT1/3 and valsartan: OATP1B3/OAT1/3) and the low therapeutic concentration of the LCZ696 analytes.


Interpreting the relation between force and cross-sectional area in human muscle.
The maximum force a muscle can produce depends on its cross-sectional area (CSA). However, the exact interpretation of this relationship has been a matter of controversy. Recently, the controversy has centered on whether the measurements are best correlated using regression analysis or ratio standards. Applying regression analysis to this problem implies that all the experimental error is in the measurement of force. Thus, confusion may arise by failure to take account of errors in the measurement of CSA. Using a statistical model, we show how regression analysis can be misleading as error is introduced into the measurement of CSA as well as that of force. Because neither the errors in force nor CSA can be quantified in the experimental situation, we conclude that ratio standards are less likely to mislead although the accuracy of the result depends on the degree of correlation between force and CSA in the muscle measured.


Content of medical information and unpredictable results in Spanish law.
In this study we consider the problem of content of medical information the patient must receive before a medical treatment. Specifically, Spanish law doesn't clarify if doctors must inform patients about every known risk or consequence inherent to an operation, or only about the most probable ones. There have been several contradictory judicial decisions of the Supreme Court about this, and in some cases it's been affirmed that the duty of information is not absolute, while in other decisions it's been affirmed just the opposite.


Arthroscopic distal clavicle resection for isolated atraumatic osteolysis in weight lifters.
Ten consecutive patients with isolated atraumatic osteolysis of the distal clavicle who had failed results with conservative treatment were treated with arthroscopic resection of the involved distal clavicle (average, 4.5 mm). All patients were men with an average age of 30.4 years, had unilateral involvement, and were considered aggressive amateur to elite weight lifters or bodybuilders. Postoperative symptoms consisted of pain at the incision and discomfort from extravasation of the irrigation fluid. At an average followup of 18.7 months, all patients had returned to their sport (average, 3.2 days) and to their preoperative weight training program (average, 9.1 days). They continued to be asymptomatic throughout the follow-up period and were able to increase both their training volume and strength from preoperative levels. Limited arthroscopic resection of the distal clavicle for isolated atraumatic osteolysis is a viable alternative for the weight lifter or bodybuilder. The ability to continue training without significant interruption as well as a more acceptable cosmetic appearance are benefits for these patients. Limited arthroscopic resection of the distal clavicle may be sufficient for this entity in this patient population, rather than the 1 to 2 cm previously reported. A sport-specific functional outcome questionnaire has been developed for this patient population.


Nonthyroidal illness syndrome or euthyroid sick syndrome?
To characterize the nonthyroidal illness syndrome (NTIS) and to discuss various underlying potential biochemical mechanisms for this condition. The pertinent medical literature was reviewed, and studies of thyroid function in systemic non-thyroidal illnesses were summarized. Abnormalities of thyroid function in the NTIS have been classified into four major categories: (1) low triiodothyronine (T3) syndrome, (2) a combination of low T3 and low thyroxine (T4), (3) high T4 syndrome, and (4) other abnormalities. The NTIS has been noted in essentially all severe systemic illnesses and after caloric deprivation, major operations, and administration of some drugs. Some mechanisms that may contribute to low serum T3 in the NTIS are decreased type I 5 -monodeiodinase in tissues, decreased uptake of T4 by tissues, decreased serum binding, increased reverse T3, alterations in selenium status, cytokines, and a decrease in thyrotropin. Decreased thyrotropin may also contribute to low T4 levels in NTIS, as may decreased serum T4-binding proteins, abnormalities in T4-binding globulin, and circulating inhibitors of binding of T4 to serum proteins. Although T4 treatment of patients with NTIS has yielded little improvement, administration of T3 has produced some beneficial effects. Further studies should be conducted to determine appropriate patient populations, dose-response ratios, and possible adverse effects of treatment of the NTIS with T3.


Sleep disturbances at the time of a new diagnosis: a comparative study of human immunodeficiency virus patients, cancer patients, and general population controls.
Sleep disturbances are a prevalent and troubling symptom of patients with highly stressful illnesses, such as human immunodeficiency virus (HIV) and cancer. The aim of this study was to compare the prevalence and incidence of sleep disturbances among persons with HIV, those with cancer, and the general population of Taiwan. A matched cohort study design was used to compare the risk of sleep disturbances among three groups using reimbursement claims recorded in Taiwan's National Health Insurance Research Database (NHIRD). A total of 14,531 HIV-infected persons were compared with 1493 cancer patients and 1373 general population controls matched by gender and age. Cox proportional hazard regression models were used to test the hazard risk of sleep disturbances among the groups. The mean durations between the date of the initial HIV/cancer diagnosis and onset of sleep disturbances of HIV-infected persons, cancer patients, and controls were 1.7, 2.3, and 1.8 years, respectively. The risk of developing sleep disturbances was significantly higher in HIV-infected persons (adjusted hazard ratio [AHR] = 3.74, p < 0.001) and cancer patients (AHR = 2.72, p < 0.001) than in controls. HIV-infected persons had a 20% higher risk of sleep disturbances than cancer patients (AHR = 1.20, p < 0.001). HIV-infected persons exhibited a higher risk of developing sleep disturbances than cancer patients and general population controls. With efficacious treatments for sleep disturbances, we should focus on training and research programs for health care providers to intervene and treat earlier for the present and future health of cancer patients and HIV-infected persons.