The structure of tick-borne encephalitis (TBE) foci in Central Europe.
The investigations on the structure of TBE foci were carried out in the localities Jívová (northern Moravia), Topolčianky and Žírany (Tribeč Mountains), and environs of Debreczén (Pannonian lowland, Hungary). The biphasic activity curve of Ixodes ricinus, characteristic for the central European conditions was confirmed in all three types.In some localities two or three tick species as vectors come into consideration and the unequal seasonal occurrence of individual species results in a permanent presence of virus-harbouring ticks in nature throughout the year.The average population density of ticks per hectare in a focus near topolčianky in mid-April, 1969, reached 46,000 nymphae and 50,000 adults. About 1% of the tick population were found to be viruliferous.Great differences were found in the composition of plant communities, mammalian synusies and in the population density of small mammals and ticks within the regions studied.Each elementary focus consists of many "microfoci" where the territories of individual host species overlap in space and time. Nests in tree holes and underground probably also belong to these microfoci. The maintenance hosts and indicators in each type of focus are mentioned. Free-living Carnivora can be considered as incidental hosts in each type of focus.


Oncogene-induced senescence as an initial barrier in lymphoma development.
Acute induction of oncogenic Ras provokes cellular senescence involving the retinoblastoma (Rb) pathway, but the tumour suppressive potential of senescence in vivo remains elusive. Recently, Rb-mediated silencing of growth-promoting genes by heterochromatin formation associated with methylation of histone H3 lysine 9 (H3K9me) was identified as a critical feature of cellular senescence, which may depend on the histone methyltransferase Suv39h1. Here we show that Emicro-N-Ras transgenic mice harbouring targeted heterozygous lesions at the Suv39h1, or the p53 locus for comparison, succumb to invasive T-cell lymphomas that lack expression of Suv39h1 or p53, respectively. By contrast, most N-Ras-transgenic wild-type ('control') animals develop a non-lymphoid neoplasia significantly later. Proliferation of primary lymphocytes is directly stalled by a Suv39h1-dependent, H3K9me-related senescent growth arrest in response to oncogenic Ras, thereby cancelling lymphomagenesis at an initial step. Suv39h1-deficient lymphoma cells grow rapidly but, unlike p53-deficient cells, remain highly susceptible to adriamycin-induced apoptosis. In contrast, only control, but not Suv39h1-deficient or p53-deficient, lymphomas senesce after drug therapy when apoptosis is blocked. These results identify H3K9me-mediated senescence as a novel Suv39h1-dependent tumour suppressor mechanism whose inactivation permits the formation of aggressive but apoptosis-competent lymphomas in response to oncogenic Ras.


Clinical utility of ursodeoxycholic acid in preventing flutamide-induced hepatopathy in patients with prostate cancer: a preliminary study.
The present study was designed to ascertain retrospectively the validity of ursodeoxycholic acid (UDCA) in the treatment of prostate cancer in terms of prophylactic effects on the occurrence of flutamide-induced hepatopathy in a large number of patients surveyed in a multi-center cooperative study. One hundred and eighty-one patients (74.1 +/- 4.9 years) with prostate cancer treated with flutamide with (n = 70) or without (n = 111) UDCA were retrospectively evaluated and the occurrence of hepatopathy was compared between these two patient groups. Between patients treated with UDCA and those without it, no significant differences were noted in age, clinical stage, grade, duration of flutamide administration and serum prostate-specific antigen (PSA) levels before treatment. However, there were significant differences in the presence or absence of previous treatments and treatments used together with flutamide. The incidence of hepatopathy was 11.4% (8/70) in patients with UDCA and 32.4% (36/111) in those without it, showing a statistically significant difference (P < 0.05). The hepatopathy-free rate obtained by the Kaplan-Meier method was also significantly higher in patients with UDCA (88.4% 1 year following flutamide administration) than that in those without it (59.6%) (P < 0.005). These results suggest that UDCA has a prophylactic effect against flutamide-induced hepatopathy in patients with prostate cancer.


Transoral vertebroplasty for the treatment of C2 painful metastatic lesions; evaluation and outcome.
A small number of studies supports vertebroplasty at the C2 vertebral body due to the documented technical challenges, the rarity of C2 osteolytic metastatic lesions, and the existence of potentially serious consequences linked to this particular anatomical area. Vertebroplasty, in such a situation, can be performed through a transoral, an anterolateral, or an open approach. All are supported by a limited number of studies with absence of a significant clinical trial assessing the efficacy, safety, and feasibility of vertebroplasty for the C2 vertebral body. We, herein, summarize a single-institution experience on C2 transoral vertebroplasty. This is a retrospective analysis of the records of a single tertiary institute hospital and the clinical visits of nine patients with C2 osteolytic metastatic lesions treated by transoral fluoroscopically guided vertebroplasty between May 2016 and May 2021. The median period of the last clinical follow-up was 23 months (range, 9-60 months). The intraoperative amount of polymethyl methacrylate (PMMA) injected and recorded in the surgical report was 2 mL (1.5-2.5 mL). Postoperative immediate imaging showed that the cement filling percentage in relation to the C2 mass was 70% (40-85%). The PMMA leakage through the needle track and into the paravertebral spaces was observed in only one patient (11.1%), without significant vascular and neurological consequences. Stability was maintained during the follow-up period. The postoperative median pain rating scale (PRS) score was 1 (0-2) immediately after the end of the operation and 0 (0-2) at the last visit. The recorded postoperative Pain Rating Scale (PRS) score was correlated with the cement filling percentage (rs= -0.9, p = 0.0008; Spearman correlation). Transoral vertebroplasty is considered feasible and efficient technique in the treatment of secondary osteolytic lesions in the C2 vertebra. Further long-term and larger comparative randomized studies are required to perform a more comprehensive analysis of this technique.


Production of fast-dissolving low-density powders for improved lung deposition by spray drying of a nanosuspension.
We combined high-energy wet media milling and spray drying to engineer dry powders for inhalation consisting of geometrically large, low-density particles with superior aerodynamic properties and fast dissolution. Peclet number proved to be a useful instrument to guide choice of the additives and process conditions for generating low-density powders by spray drying. Composite dry powders consisted of milled and stabilized budesonide nanoparticles, leucine or albumin as matrix formers, and ammonium carbonate as a pore former. Powders of different composition showed fairly large and comparable geometric particle sizes (de,50 > 4.4 µm) with effective densities strongly depending on the present matrix former. Powders with lowest density reached an aerosol performance of up to 60%, which is well above most commercial, carrier-based products. It was also demonstrated that the nanomilling step was indispensable to yield such good aerosol performance. Dissolution of aerodynamically classified particle fractions showed a very fast onset and was largely completed within 30 min irrespective of the formulation and the impactor stage. Mathematical kinetic modeling was used to deduce the API dissolution rate coefficient from the results obtained using a modified USP 2 apparatus. Dissolution rate was found to be determined by the properties of the API nanoparticles rather than those of the composite particles. The employment of industrially established, solely water-based processes allows introducing the presented approach as a platform technology for the development of well-performing pulmonary formulations.


HDL particle functionality as a primary pharmacological target for HDL-based therapies.
Despite all existing pharmaceuticals aiming at effectively reducing LDL cholesterol, the steadily increasing prevalence of coronary heart disease (CHD) worldwide shifted focus on HDL as an alternative therapeutic target for the treatment of CHD. Indeed, based on the results from epidemiological studies, high HDL cholesterol (HDL-C) levels have been traditionally associated to atheroprotection. Therefore, current drug design considers plasma HDL-C levels as a primary pharmacological target for combating CHD. However, this approach does not take into consideration the fact that HDL is a rather heterogeneous mixture of lipoprotein particles with distinct apolipoprotein and lipid composition that dictate their atheroprotective or proatherogenic function. This may explain why simply raising HDL-C levels by pharmacological means has yet to yield the expected atheroprotection in recent clinical trials. In this review we argue that HDL particle functionality rather than HDL-C levels should be the primary target in the rational design of new HDL-based pharmaceuticals aiming at successfully treating CHD.


Intravascular papillary endothelial hyperplasia: report of 2 cases and immunohistochemical study.
Intravascular papillary endothelial hyperplasia (IPEH) is a benign, nonneoplastic, vascular lesion. The main significance of the lesion lies in the fact that it may be mistaken for angiosarcoma. Oral lesions are uncommon and the present paper reports 2 cases of oral IPEH, in different sites. Histologically, the tissue was characterized by papillary fronds lined by proliferating endothelium. Immunohistochemically (IHC), the lesion was positive for CD34, smooth muscle actin (SMA), type I and IV collagen, vimentin, and laminin, but it was negative for CD105. Local excision was the treatment of choice. No recurrence was observed during a 1-year and 6-month follow-up period, respectively. The clinical, histological, and immunohistochemical characteristics are discussed.


Antigenic relationships between the serotypes of Pasteurella haemolytica demonstrable by enzyme-linked immunosorbent assay (ELISA).
Mice and rabbits were immunised with sodium salicylate extracts (SSE) prepared from each of 12 serotypes of Pasteurella haemolytica, and the antisera to each were used in cross-indirect haemagglutination (IHA) tests and cross-enzyme-linked immunosorbent assays (ELISA) to study antigenic relationships between the serotypes. An indirect micro-ELISA demonstrated common antigenic relationships which were not apparent by IHA. Antisera from both species revealed considerable shared antigenicity between all the serotypes. Rabbit antisera presented clearer differences between the A biotypes on one hand and the T biotypes on the other, the T biotypes exhibiting much less cross-relatedness than that shown between the A serotypes.


Moderate to high intensity statin in dialysis patients after acute myocardial infarction: A national cohort study in Asia.
Statin is not beneficial for dialysis patients but moderate to high intensity statin is beneficial for patients after acute myocardial infarction (MI). The aim of this study was to evaluate the effect of moderate to high intensity statin on mortality, cardiovascular outcomes in dialysis patients after acute MI. Data on dialysis patients were retrieved from the National Health Insurance Research Database in Taiwan. Dialysis patients admitted for MI were selected and divided into two groups according to statin prescription or not after MI. All-cause mortality and cardiovascular outcomes after a 4-year follow-up were analyzed after propensity score matching (PSM). We identified 790 patients who received moderate to high intensity statin therapy and 1788 patients who did not receive any statins after acute MI and clinical outcomes were analyzed after 1:1 PSM. The benefit of statin on mortality therapy appeared from 1 year to the end of the 4-year follow-up period after hospitalization (statin group versus non-statin group: 22.9% vs. 31.1% at 1 year (HR: 0.70; 95% CI: 0.58-0.85); 48.0% vs. 55.1% at the end of the 4 years (HR: 0.76; 95% CI: 0.67-0.88)). In addition, the impact of statin therapy was stronger in patients with shock at admission (p = 0.035). There were no differences in any individual cardiovascular outcome or adverse event. Moderate to high intensity statin therapy might lower all-cause mortality in dialysis patients after acute MI, especially those with shock, but not influence cardiovascular outcomes and any adverse events.


Formation and microstructural characterization of scallop (Patinopecten yessoensis) male gonad hydrolysates/sodium alginate coacervations as a function of pH.
Studying the noncovalent interactions between proteins and polysaccharides is quite important mainly due to the wide number of applications such as developing pH-responsive complexes. Scallop Patinopecten yessoensis male gonad hydrolysates‑sodium alginate (SMGHs-SA) was investigated as noncovalent complexes at pH from 1 to 10. The critical pH values pHC (around 6) and pHφ (around 4) were independent of the SMGHs-SA ratio, indicating the formation of soluble and insoluble complexes. The pH response of SMGHs-SA complexes was evaluated by investigating the rheological behavior, moisture distribution, functional group change and microstructure. Compared to the co-soluble and soluble complexes phases, the SMGHs-SA complexes had a higher storage modulus and viscosity as well as a lower relaxation time (T23) in the insoluble complexes phase (pHφ>3). Additionally, the amide I band and COO- stretching vibration peaks were redshifted and the amide A band vibration peaks were blueshifted by acidification. Electrostatic interactions and intermolecular/intramolecular hydrogen bonding led to SMGHs-SA agglomeration at pH 3, forming a uniform and dense gel network structure with strong gel strength and water-retention capacity. This study provides a theoretical and methodological basis for the design of novel pH-responsive complexes by studying SMGHs-SA complex coacervation.


The fine structural organization of the locus coeruleus in the rat with reference to noradrenaline contents.
Combination of glyoxylic acid perfusion and postfixation in permanganate was used in an electron microscopic study of the locus coeruleus (LC) of the rat to give good preservation of fine structure and a reproducible demonstration of noradrenaline (NA) storage granules. Medium-sized LC cells (18 x 30 microns) contained a moderate number of small granular vesicles (SGV) and a few large granular vesicles (LGV), mainly near the Golgi apparatus. Dendritic branches were identified by their SGV content up to the tip. Dendrites were occasionally in close contact with each other or with the soma of LC cells, forming dendro-dendritic or dendro-somatic contacts. Numerous axon terminals containing many SGV and some LGV were observed in the neuropil, and they tended to contact dendrites and somata of LC cells or dendrites of unknown origin. These neuronal contacts were devoid of synaptic specializations except for an array of dense perpendicular lines between the juxtaposed membranes. Small oval cells (10 x 15 microns) devoid of SGV occurred frequently in the peripheral part of the nucleus, and they were occasionally in direct contact with LC cells.


Photoperiodic effects on pubertal maturation of spermatogenesis, pituitary responsiveness to exogenous GnRH, and expression of boar taint in crossbred boars.
Forty-eight weaned, winter-born crossbred males (average age of 42 days) were exposed to either a natural photoperiod (January-June at 60 degrees N, Control) or one of two artificial photoperiods (1400 lx) in light-sealed rooms. The Spring/Summer group was exposed to an artificial photoperiod simulating conditions from the vernal equinox (mid-March) to August at 60 degrees N and the Autumn/Winter group to a photoperiod, simulating conditions from the autumnal equinox (mid-September) to February at 60 degrees N. Plasma samples were collected biweekly until the pigs were slaughtered, after reaching 115 kg, and analysed for testosterone, estrone sulfate, thyroxine and prolactin. Additionally, three animals per treatment (n = 9) were injected with gonadotropin-releasing hormone (GnRH) and plasma samples were collected every 15 min and analysed for luteinizing hormone and testosterone. Boar taint, carcass composition and reproductive traits were measured at slaughter. Live-weight gain from start to slaughter was lower among the Control animals compared with the Autumn/Winter and Spring/Summer animals. There was a peak in plasma testosterone in both the Spring/Summer and Autumn/Winter groups at 71 days of age, whereas plasma testosterone in the Control group remained at prepubertal levels. At 113 and 127 days of age, the Control group had somewhat higher testosterone levels than the Spring/Summer group, but at 141 days of age and on the day before slaughter, the Autumn/Winter group had a higher mean plasma testosterone concentration. There were no differences between treatments in the endocrine response to the GnRH challenge. Bulbourethral gland weight at slaughter was lower in the Spring/Summer group than in the Autumn/Winter group. The percentage of proximal cytoplasmic droplets was higher in the Spring/Summer group than in both the Control and Autumn/Winter groups. Spermatogenesis at the time of slaughter was clearly more mature in animals in the Autumn/Winter group than in those in the Spring/Summer and Control groups. Fat androstenone was lower in the Spring/Summer group than in the Control group. In the sensory evaluation, the Spring/Summer group had less boar taint than the Autumn/Winter group. Artificial short days with moderate initial changes in photoperiod, stimulated spermatogenesis compared with long days, in accordance with the pattern seen in European Wild Boars (Sus scrofa). Boar taint was also affected with higher scores in the Autumn/Winter group than in the Spring/Summer group, although this was not clearly indicated by the traditional measurements of boar taint-fat contents of androstenone and skatole.


Eosinophilic gastroenteritis with esophageal involvement.
A patient with a lifelong history of asthma and hay fever was investigated because of symptoms of esophageal spasm. Esophageal biopsies revealed elongated papillae and basal zone hyperplasia of the epithelial layer with eosinophilic infiltration of the lamina propria and muscularis mucosae. There was no evidence of reflux. Small bowel biopsies revealed a flat mucosal pattern with absent or blunted villi, tall columar surface epithelium, and eosinophilic infiltration of the lamina propria. He did not respond to a gluten-free diet. This patient is thought to have eosinophilic gatroenteritis with esophageal involvement, the first such case reported.


Endoscopic-assisted achilles tendon reconstruction with free hamstring tendon autograft for chronic rupture of achilles tendon: clinical and isokinetic evaluation.
To evaluate the clinical and functional outcome of endoscopic-assisted reconstruction of chronic ruptures of the Achilles tendon using free hamstring tendon autograft. We present a case series of 15 patients who had chronic ruptures of the Achilles tendon (>6 weeks earlier) and underwent endoscopic-assisted reconstruction with a free hamstring autograft. The graft loop was passed through and fixed to the proximal stump of the tendon. The graft was then passed through suture to the distal stump and finally inserted into a tunnel in the anterior calcaneus to the Achilles tendon insertion and fixed with an bioabsorbable interference screw. The mean follow-up period was 27 months (SD, 3 months; range, 24 to 33 months). All patients underwent magnetic resonance imaging preoperatively, immediately postoperatively, and at follow-up 2 years postoperatively. All patients were functionally evaluated with the American Orthopaedic Foot & Ankle Society (AOFAS) score for the hindfoot preoperatively and postoperatively. Calf muscle power was evaluated by isokinetic strength testing at 2 years' follow-up. The mean size of the gap on preoperative magnetic resonance imaging was 49 mm (SD, 9 mm). The mean preoperative AOFAS score was 32.6 (SD, 7.5). There was a statistically significant improvement in the postoperative AOFAS score after 2 years to 90.8 (SD, 3.54) (P < .05). The mean time of return to all daily activities (except running and other sports) was 12.6 weeks (SD, 1.39 weeks). Isokinetic testing showed a nonsignificant deficit (<10%) between the involved and uninvolved plantar flexors and dorsiflexors with regard to peak torque, average power, and total work. Endoscopic-assisted Achilles tendon reconstruction with free hamstring tendon autograft for chronic ruptures of the Achilles tendon showed good to excellent results in all patients. Isokinetic testing showed a nonsignificant deficit between the involved and uninvolved sides at 2 years' follow-up. Level IV, therapeutic cases series.


E6 hijacks KDM5C/lnc_000231/miR-497-5p/CCNE1 axis to promote cervical cancer progression.
Emerging evidence suggests that long non-coding RNA (lncRNA) plays an important role in disease development, particularly in cancers. Recent studies with genome-wide sequencing on cervical squamous cell carcinoma and matched adjacent non-tumour tissues showed that a newly identified lncRNA-lnc_000231 was highly expressed in cervical cancers. However, the underlying mechanism through which it is activated and its role in cervical cancer progression is still unclear. In this study, first, we confirmed that lnc_000231 is up-regulated in cervical cancer cells and tumour tissues. Mechanically, we demonstrated that E6 up-regulates lnc_000231 expression through promoting its promoter region H3K4me3 modification by destabilizing KDM5C. In vitro and in vivo results showed that lnc_000231 promotes cervical cancer cell proliferation and tumour formation by acting as miR-497-5p sponge and maintaining cyclin E1 (CCNE1) expression. Thus, our studies identified a new signalling pathway through which E6 promotes cervical cancer progression. E6 hijacked KDM5C/lnc_000231/miR-497-5p/CCNE1 signalling pathway is a promising target for cervical cancer treatment in the future.


Overexpression of AQP5 Was Detected in Axillary Sweat Glands of Primary Focal Hyperhidrosis Patients.
The expression of aquaporin 5 (AQP5) in human axillary sweat glands has never been studied so far. To detect the expression of AQP5 in axillary sweat glands of patients with primary focal hyperhidrosis (PFH) relative to control subjects. The morphological characteristics and the number of sweat coils in axillary sweat glands were compared between two groups by using transmission electron microscopy. The expression of AQP5 was detected by immunohistochemistry, Western blot analysis, and real-time transcription polymerase chain reaction. There were no significant differences between the two groups in terms of morphological characteristics and the number of sweat coils in axillary sweat glands. The expressions of AQP5 protein and AQP5 mRNA were significantly higher in the patient group than in the control group. AQP5 is involved in the secretion of human axillary sweat glands. The overexpression of AQP5 in sweat glands is probably one pathogenetic mechanism underlying PFH.


Decisional conflict, caregiver mastery, and depression among Chinese parental caregivers of children with leukemia.
Informal caregivers of children with leukemia can be emotionally and psychiatrically vulnerable when facing difficult treatment decisions (e.g., chemotherapy, targeted therapy, radiation, transplantation). A common behavioral manifestation of decisional conflict is the verbalized expression of uncertainty about which medical treatment plan to take. The study aims to examine the associations between decisional conflict, mastery, and depressive symptoms among parental caregivers of children with leukemia in China. It explored the mediating role of mastery in the relationship. A cross-sectional survey design was adopted. A total of 386 parental caregivers were recruited, and 325 valid questionnaires remained. The mean age of caregivers was 37.7 years, and 61.5% caregivers were female. We used Question Format Decisional Conflict Scale to assess decisional conflict, Pearlin's Mastery Scale to assess mastery, and Center for Epidemiological Studies Depression 10 to assess depressive symptoms. We used mediation analyses to test the mediating effect of mastery. The total score of decisional conflict scale, along with its dimensions of uncertainty, support, and effective decision were found negatively associated with depressive symptoms. In contrast, the dimension of information and value were not significantly associated with depressive symptoms. Mediation analyses demonstrated the direct effects of overall decisional conflict and uncertainly were fully mediated by mastery, while the direct effect of support and effective decision were partially mediated. Efforts should be made to alleviate parental caregivers' decisional conflict and enhance sense of mastery. Particular attention should be paid to the psycho-social support to relieve uncertainties and ineffectiveness in decision making.


Unusual renal manifestations of Wegener's granulomatosis. Report of two cases.
Two patients with previously undescribed renal manifestations of Wegener's granulomatosis are described. A 24 year old man, who presented with typical necrotizing granulomatous sinus disease and cavitary pulmonary lesions, had multiple bilateral renal arterial aneurysms demonstrated angiographically. One of these aneurysms ruptured, leading to a massive perinephric hematoma. The bleeding artery was successfully occluded with Gelfoam embolization, thereby obviating the need for nephrectomy. A 60 year old woman presented with glomerulonephritis and mononeuritis multiplex two years before the development of classic necrotizing granulomatous inflammation of her sinuses and nose, along with pulmonary nodules. In addition, her left ureter became obstructed due to necrotizing vasculitis of the periureteral vessels. Both patients responded dramatically to cyclophosphamide therapy. The diagnosis of Wegener's granulomatosis should be considered in patients who present with multiple renal aneurysms, a spontaneous perinephric hematoma, necrotizing glomerulitis or ureteral obstruction due to vasculitis, even though the characteristic granulomatous respiratory involvement may be absent at that time. It is important to recognize these unusual renal manifestations as features of Wegener's granulomatosis because of the therapeutic efficacy of cytotoxic immunosuppressive agents in this disease.


A first insight into the genetic diversity of Mycobacterium Tuberculosis in Veracruz, Mexico.
Tuberculosis (TB) remains one of the most important infectious diseases. Although Mexico is one of the Latin American countries with the largest contribution to these statistics, there are few reports that describe the genotypic characteristics of TB. The aim of this study was to use the MIRU-VNTR-24 loci to analyze the genetic diversity of M. tuberculosis circulating in the state of Veracruz, Mexico. Here, we analyze by MIRU-VNTR-24 loci 80 clinical isolates from individuals with confirmed TB from Veracruz México, also clinical and epidemiological variables were recovered and analyzed. Of the individuals included in the analyses 65% were from men with an average age of 42 (± 17) years, 17% and 6% were drug and multi-drug resistant. 88% of the isolates were included in 20 clusters, of which 52% were classified into twelve orphan clusters and the remaining 37% were distributed among eight lineages: LAM (10%), EAI (9%), Haarlem (8%), H37Rv (4%), S (4%) and TUR (2%). An important diversity of lineages and unknown genotypes was identified; however, more studies are necessary in order to understand the characteristics of the genotypes displayed in the region. There is no doubt regarding the need for a molecular epidemiological surveillance system that can help to evaluate the dynamics of genotypes circulating in the country and support strategies for the prevention and management of populations affected by TB.


Percutaneous acetabuloplasty for metastatic acetabular lesions.
Osteolytic metastases around the acetabulum are frequent in tumour patients, and may cause intense and drug-resistant pain of the hip. These lesions also cause structural weakening of the pelvis, limping, and poor quality of life. Percutaneous acetabuloplasty is a mini-invasive procedure for the management of metastatic lesions due to carcinoma of the acetabulum performed in patients who cannot tolerate major surgery, or in patients towards whom radiotherapy had already proved ineffective. We report a retrospective study in 25 such patients (30 acetabuli) who were evaluated before and after percutaneous acetabuloplasty, with regard to pain, mobility of the hip joint, use of analgesics, by means of evaluation forms: Visual Analog Scale, Harris Hip Score, Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC), Eastern Cooperative Oncology Group (ECOG). The results obtained were analysed using the chi2 Test and Fisher's exact test. Significance was sent at P < 0.05. Marked clinical improvement was observed in all patients during the first six post-operative months, with gradual a worsening thereafter from deterioration of their general condition. Complete pain relief was achieved in 15 of our 25 (59%) of patients, and pain reduction was achieved in the remaining 10 (41%) patients. The mean duration of pain relief was 7.3 months. Pain recurred in three patients (12%) between 2 weeks to 3 months. No major complications occurred. There was transient local pain in most cases, and 2 cases of venous injection of cement without clinical consequences. Percutaneous acetabuloplasty is effective in improving the quality of life of patients with osteolytic bone tumours, even though the improvement is observed during the first 6 months only. It can be an effective aid to chemo- and radiotherapy in the management of acetabular metastases.


Utility of infertile male models for contraception and conservation.
Epididymal defects in infertile domestic species and transgenic mice demonstrate the role of the epididymis in influencing sperm function. Spermatozoa from these males cannot negotiate the female tract as they fail to regulate their volume. The latter is necessary to counter the osmotic stresses encountered in the female tract. Reduced epididymal provision of osmolytes or their premature loss is discussed as probable causes of failed volume regulation. Measuring cell volume regulation for diagnosis of male infertility and blocking it as a means to male contraception are briefly considered. Unchecked human population growth is destroying habitats supporting vulnerable and endangered species. Genome resource banks have been established to preserve spermatozoa of genetically valuable individuals. As cryopreservation stresses spermatozoa osmotically, this process could jeopardise volume regulation with consequences for fertility. Knowledge of sperm volume regulation and the uptake of organic solutes may permit improvement in sperm storage and prevent osmolyte-related cryodamage.


Characteristics of ACS-verified Level I and Level II trauma centers: A study linking trauma center verification review data and the National Trauma Data Bank of the American College of Surgeons Committee on Trauma.
The Trauma Quality Improvement Project of the American College of Surgeons (ACS) has demonstrated variations in trauma center outcomes despite similar verification status. The purpose of this study was to identify structural characteristics of trauma centers that affect patient outcomes. Trauma registry data on 361,187 patients treated at 222 ACS-verified Level I and Level II trauma centers were obtained from the National Trauma Data Bank of ACS. These data were used to estimate each center's observed-to-expected (O-E) mortality ratio with 95% confidence intervals using multivariate logistic regression analysis. De-identified data on structural characteristics of these trauma centers were obtained from the ACS Verification Review Committee. Centers in the lowest quartile of mortality based on O-E ratio (n = 56) were compared to the rest (n = 166) using Classification and Regression Tree (CART) analysis to identify institutional characteristics independently associated with high-performing centers. Of the 72 structural characteristics explored, only 3 were independently associated with high-performing centers: annual patient visits to the emergency department of fewer than 61,000; proportion of patients on Medicare greater than 20%; and continuing medical education for emergency department physician liaison to the trauma program ranging from 55 and 113 hours annually. Each 5% increase in O-E mortality ratio was associated with an increase in total length of stay of one day (r = 0.25; p < 0.001). Very few structural characteristics of ACS-verified trauma centers are associated with risk-adjusted mortality. Thus, variations in patient outcomes across trauma centers are likely related to variations in clinical practices. Therapeutic study, level III.


[Construction and identification of a vector inserted with complete genome of poliovirus strain Sabin I].
To develop a vector inserted with complete genome of poliovirus strain Sabin I. The 3 fragments of the complete genome of Sabin I was amplified and cloned to pEASY-T3 by molecular biological technology. These cloned pEASY-T3 were then digested by Restriction enzymes and ligated to pWSK29 step by step and identified. The complete genome of poliovirus strain Sabin I was successfully cloned into vector pWSK29 with 9 nucleotide mutations. The complete genome plasmid was constructed and it provided a basis for further research of the function of Sabin I.


Sidewinder gait in horses.
Sidewinder gait in horses is poorly understood and characterized by walking with the trunk and pelvic limbs drifting to 1 side. To report causes, clinical and diagnostic features. Horses examined at 2 institutions. Retrospective study (2000-2019). Cases with sidewinder gait, neurological and orthopedic examination, and diagnostic work up or postmortem evaluation were included. Descriptive statistics were performed. Twenty-four horses (mean age 18.9 years) of various breeds and both sexes were included. Onset was acute (N = 10), subacute (N = 6), and insidious (N = 8). Electromyography and muscle biopsy supported neurologic disease and further aided in localizing site of lesion (N = 9/9). Neurologic causes included dynamic thoracolumbar spinal cord compression (N = 5), equine protozoal myeloencephalitis (N = 4, confirmed and presumed [2 each]), thoracic myelopathy of unknown etiology (N = 4), gliosis (N = 2), and thrombosis of thoracic spinal cord segments (N = 1). Non-neurologic causes included osteoarthritis of the coxofemoral joint (N = 4), multiple displaced pelvic fractures (N = 2), bilateral rupture of the ligamentum capitis ossis femoris (N = 1), and severe myonecrosis of multiple pelvic limb muscles (N = 1). Case fatality was 79%. Sidewinder gait is usually observed in older horses and can have neurologic or musculoskeletal etiologies. Electromyography can be used as a diagnostic aid to determine neurologic versus non-neurologic disease and further localize those of neurologic origin. The condition often has a poor prognosis for function and life.


Expression of a soluble IL-10 receptor enhances the therapeutic effects of a papillomavirus-associated antitumor vaccine in a murine model.
The presence of IL-10, produced either by tumor cells or immunosuppressive cells, is frequently associated with a poor prognosis for cancer progression. It may also negatively impact anticancer treatments, such as immunotherapies, that otherwise would promote the activation of cytotoxic T cells capable of detecting and destroying malignant cells. In the present study, we evaluated a new adjuvant approach for anticancer immunotherapy using a plasmid vector encoding a soluble form of the IL-10 receptor (pIL-10R). pIL-10R was coadministered to mice with a DNA vaccine encoding the type 16 human papillomavirus (HPV-16) E7 oncoprotein genetically fused with glycoprotein D of herpes simplex virus (HSV) (pgDE7h). Immunization regimens based on the coadministration of pIL-10R and pgDE7h enhanced the antitumor immunity elicited in mice injected with TC-1 cells, which express HPV-16 oncoproteins. The administration of the DNA vaccines by in vivo electroporation further enhanced the anticancer effects of the vaccines, leading to the activation of tumor-infiltrating polyfunctional E7-specific cytotoxic CD8+ T cells and control of the expansion of immunosuppressive cells. In addition, the combination of immunotherapy and pIL-10R allowed the control of tumors in more advanced growth stages that otherwise would not be treatable by the pgDE7h vaccine. In conclusion, the proposed treatment involving the expression of IL-10R enhanced the antitumor protective immunity induced by pgDE7h administration and may contribute to the development of more efficient clinical interventions against HPV-induced tumors.


The maze of myocardial perfusion imaging protocols in 1994.
A confusing multitude of different myocardial perfusion imaging protocols have been proposed during the last few years. The impetus for this development was new insights in imaging with thallium 201 and the challenge to perform efficient imaging with the newly developed technetium 99m-labeled imaging agents. The practicing nuclear cardiologist is confronted with a true maze of options. This review describes in detail the various protocols, discusses advantages and disadvantages of each, and states, when appropriate, the personal preference of the author.


Patient safety concept for multichannel transmit coils.
To propose and illustrate a safety concept for multichannel transmit coils in MRI based on finite-differences time-domain (FDTD) simulations and validated by measurements. FDTD simulations of specific absorption rate (SAR) distributions in a cylindrical agarose phantom were carried out for various radio frequency (RF) driving conditions of a four-element coil array. Additionally, maps of transmit amplitude, signal phase, and temperature rise following RF heating were measured by MRI. Quantitative agreement was achieved between simulated and measured field distributions, thus validating the numerical modeling. When applying the same RF power to each element of the coil array but systematically varying the RF phase between its elements, the maximum of the SAR distribution was found to vary by a factor of about 15. Our results demonstrate that current RF safety approaches are inadequate to deal with the new challenge of multichannel transmit coils. We propose a new concept based on a systematic investigation of the parameter space for RF phases and amplitudes. In this way the driving conditions generating the highest local SAR values per unit power can be identified and appropriately considered in the RF safety concept of a given MRI system.


A self-administered Short Michigan Alcoholism Screening Test (SMAST).
The Michigan Alcoholism Screening Test and a shortened 13-item version can reliably be used as self-administered questionnaires.


Tetramethylbenzidine method for monitoring the free available chlorine and microbicidal activity of chlorite-based sanitizers under organic-matter-rich environments.
Chlorine is a principal disinfectant for food and environmental sanitation. Monitoring of free available chlorine (FAC) is essential for ensuring the efficacy of food disinfection processes that rely on chlorine. N,N-diethyl-p-phenylenediamine (DPD) is commonly used for FAC monitoring. However, here, we show that upon contact with bovine serum albumin (BSA) or broiler carcasses, chlorite (HClO2 )-based sanitizers acquire a pink colour, which can interfere with measurement of oxidized DPD absorbance at 513-550 nm. Alternatively, the pink colour did not interfere with 3,3',5,5'-tetramethylbenzidine (TMB)-based FAC monitoring. The FAC levels of NaClO and weakly acidified chlorous acid water (WACAW) were first adjusted by the TMB method and the killing activity of these sanitizers towards methicillin-resistant Staphylococcus aureus (MRSA) and feline calicivirus (FCV) was compared in the presence or absence of 0·5% BSA. At 200 ppm FAC, NaClO lost its bactericidal activity against MRSA after 10-min incubation with 0·5% BSA. Meanwhile, under the same conditions WACAW reduced the number of bacteria to below the detection limit. Similar results were obtained with FCV, indicating that the chlorite-based WACAW sanitizer is relatively stable under organic-matter-rich conditions. Moreover, TMB is suitable for in situ FAC monitoring of chlorite-based sanitizers in food and environmental disinfection processes. For practical applications of chlorine in food processing, monitoring of FAC is critical to validate disinfection efficacy. In this study we found that chlorite-based sanitizers acquired a pink colour upon contact with BSA or broiler carcasses. This pink colour interfered with FAC monitoring by methods that measure oxidized N,N-diethyl-p-phenylenediamine absorbance between 513-550 nm. Alternatively, FAC levels of chlorite-based sanitizers could be monitored using the absorbance of 3,3',5,5'-tetramethylbenzidine at 650 nm, which does not overlap with the acquired pink colour. These data provide valuable information for safety management of disinfection processes that use chlorite-based sanitizers.


Case-control association study of 14 variants of CREB1, CREBBP and CREM on diagnosis and treatment outcome in major depressive disorder and bipolar disorder.
Some evidence suggests an association between genetic variants within the cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), CREB binding protein (CREBBP) and cAMP response element-modulator (CREM) and several psychiatric disorders. The present study investigated whether some single nucleotide polymorphisms (SNPs) within these genes could be associated with major depressive disorder (MDD) and bipolar disorder (BD) and whether they could predict clinical outcomes in Korean in-patients treated with antidepressants and mood stabilizers, respectively. The sample comprised 145 patients with MDD, 132 patients with BD and 170 psychiatrically healthy controls. Participants were genotyped for 14 SNPs within CREB1, CREBBP and CREM. Baseline and final clinical measures, including the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale for patients with MDD and BD, respectively, were recorded. All p-values were 2-tailed, and statistical significance was conservatively set at the 0.006 level in order to reduce the likelihood of false positive results. We failed to observe any association of the 14 SNPs genotypes or alleles with clinical improvement, response and remission rates as well as final outcomes in any of such disorders. Our findings suggest that the 14 SNP under investigation in our study do not influence diagnosis and treatment response in patients with MDD and BD. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions.


On the explanation of short REM latencies in depression.
Sleep in depression is characterized by the occurrence of episodes of rapid eye movement (REM) sleep at sleep onset. The empirical foundations of three hypotheses about the origin of this phenomenon are examined: A circadian rhythm hypothesis stating that sleep onset REM episodes (SOREMs) are the result of an abnormal phase-position of the REM sleep production cycle. A REM sleep-slow wave sleep interaction hypothesis that attributes SOREMs to a low non-REM sleep propensity. A circadian amplitude hypothesis, in which a flattening of the circadian arousal cycle is thought to be causally related to SOREMs. None of the hypotheses are found to be supported by firm empirical evidence.


The Rieger syndrome: orofacial manifestations. Case report of a rare condition.
Rieger syndrome is a rare, autosomal dominant disorder due to developmental arrest of tissues derived from neural crest ectoderm in the third trimester. It is characterized by abnormalities of the anterior chamber of the eye coincident with dental and craniofacial anomalies. Early recognition of dental anomalies aids in detection of the syndrome and prevents progressive loss of vision. This case report discusses the ocular, dental, and craniofacial findings and the overall management of the patient.


Chemical form of selenium-containing metabolite in small intestine and liver of mice following orally administered selenocystine.
The chemical form of a selenium-containing metabolite in the small intestine following a single oral administration of selenocystine was investigated with ICR male mice. Selenium content in the small intestine of animals treated with 50 mg/kg selenocystine significantly increased 15 min, 1 h and 6 h after treatment. In contrast, selenocystine significantly depressed the intestinal reduced glutathione (GSH) level at 1 h after administration. A significant negative correlation between the selenium level and the level of GSH in the small intestine was observed (r = -0.83, p < 0.001). Analysis of the intestinal metabolite of selenocystine showed that selenium-containing metabolites elute in two fractions from a Sephadex G-25 column: the low-molecular fraction (peak I) contained the selenocystine, while the high-molecular fraction (peak II) contained selenocysteine-containing metabolite. An in vitro experiment was performed to gain insight into the mechanism for selenocysteine-containing metabolite production in the intestinal cytosol. When selenocystine or selenocysteine reacted with excess GSH in the presence of intestinal homogenate, the peak II fraction which involved the selenocysteine-containing metabolite was recognized in the Sephadex G-25 chromatogram. From an examination of the distribution of the selenocysteine-containing metabolite, it was recognized that this metabolite exists in plasma and liver cytosol of mice after oral administration of selenocystine. These results suggested that the mice treated with selenocystine produce selenocysteine-containing metabolite by reaction of selenocystine with excess GSH in the small intestine, and the metabolite is then transported to the liver through blood plasma.


Effect of ochratoxin A and ochratoxin C on the monocyte and lymphocyte function.
The effect of practically relevant mycotoxin concentrations on functions of immune cells was studied in in vitro experiments. Porcine mononuclear cells were exposed to a crudeAspergillus-ochraceus toxin containing OTA, a HPLC fraction identical with OTC derived from the crude toxin (RE2), as well as pure OTA and OTC in a concentration range from 0.46 to 3000 ng/ml. The influence of mycotoxin exposure on metabolic activity, mitogen induced proliferation, expression of the activation marker CD25 and the cell cycle of lymphocytes and on the formation of free oxygen radicals as well as the production of the cytokines IL-6 and TNF-α by monocytes was determined. Exposure to high concentrations of all mycotoxin preparations lead to non-specific suppression of the immune cell functions, which was related to cytotoxic effects. Low concentrations caused ambivalent reactions, especially on monocyte function. In general, the HPLC fraction RE2 had an up to 100-fold stronger effect than pure OTA. Ochratoxin-induced suppression of lymphocyte proliferation was not abrogated by phenylalanine or aspartame. The results indicate that immunomodulation can be caused by very low mycotoxin concentrations which are not related to clinical symptoms or loss of performance.


Dynamics of electron transfer pathways in cytochrome C oxidase.
Cytochrome c oxidase mediates the final step of electron transfer reactions in the respiratory chain, catalyzing the transfer between cytochrome c and the molecular oxygen and concomitantly pumping protons across the inner mitochondrial membrane. We investigate the electron transfer reactions in cytochrome c oxidase, particularly the control of the effective electronic coupling by the nuclear thermal motion. The effective coupling is calculated using the Green's function technique with an extended Huckel level electronic Hamiltonian, combined with all-atom molecular dynamics of the protein in a native (membrane and solvent) environment. The effective coupling between Cu(A) and heme a is found to be dominated by the pathway that starts from His(B204). The coupling between heme a and heme a(3) is dominated by a through-space jump between the two heme rings rather than by covalent pathways. In the both steps, the effective electronic coupling is robust to the thermal nuclear vibrations, thereby providing fast and efficient electron transfer.


Digital tomosynthesis as a new diagnostic tool for evaluation of spine damage in patients with ankylosing spondylitis.
We aimed to compare digital tomosynthesis (DTS) with radiographs for the assessment of spinal bone damage in patients with ankylosing spondylitis (AS). The study comprised 68 patients with AS who underwent both DTS and radiographs of the cervical and lumbar spine on the same day. Spinal bone damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and the presence of facet joint damage. The Wilcoxon signed-rank test and McNemar's test were used to compare spinal bone damage between the two modalities. In 68 AS patients with mean 4.5 years of disease duration, the mean mSASSS was 11.7 ± 11.3 with radiographs and 13.1 ± 11.5 with DTS (p = 0.001). A grade 1 (erosion, sclerosis, or squaring) score in the mSASSS system was higher with DTS than with radiographs (p = 0.001), but grade 2 (syndesmophyte) and grade 3 (bridge) scores (p > 0.005 each) were not. In particular, the grade 1 score was higher with DTS than with radiographs at the cervicothoracic (p < 0.001) and thoracolumbar (p = 0.003) junctions. With regard to facet joint damage, erosion/sclerosis of facet joints was better depicted by DTS than by radiographs in the cervical (54.4 vs. 22.1%, p < 0.001) and lumbar spine (72.1 vs. 11.8%, p < 0.001). DTS depicted more subtle damage of spinal vertebrae in patients with AS than radiographs did. Moreover, erosion/sclerosis of facet joints was better detected with DTS than with radiographs.


Fall-related injuries for three ages groups - Analysis of Swedish registry data 1999-2013.
The objective of this study was to analyze which factors (including factors pertaining to the individual, the household, and the local area) increase the risk of fall injuries for the three age groups with the highest risk for fall injuries in Sweden. The study combined longitudinal data covering the period 1999-2013 from several different official registries from Statistics Sweden as well as from the Swedish health care system and fitted the models to data using mixed model regressions. Three age groups had a markedly heightened risk for fall injuries: 1-3-year olds, 12-14 year olds, and the elderly (65+). The home was the most common location for fall injuries, as about 40% of all fall injuries occur in the home. Only for the elderly strong predictors for fall injuries were found, and these were: age, single household, and special housing. There is preventive potential in the special residences for the elderly and disabled. People living in these special residences make up a strongly selected group that needs extra safe environments. Our findings indicate that their needs are currently not meet. Practical applications: Design of special residences for the elderly and disabled should aim at reducing the consequences of falling.


Unrevealing the role of metal oxide nanoparticles on biohydrogen production by Lactobacillus delbrueckii.
The positive interaction between Clostridium sp. and lactic acid-producing bacteria (Lactobacillus sp) is commonly seen in various high-rate hydrogen production systems. However, the exact role of the hydrogen production ability of Lactobacillus sp in a dark fermentation production system is rarely studied. Lactobacillus delbrueckii was herein used for the first time, to the best of the author's knowledge, to demonstrate biohydrogen production under anaerobic conditions. At first, the pH condition was optimized, followed by the addition of nanoparticles for enhanced biohydrogen production. Under optimized conditions of pH 6.5, substrate concentration 10 g/L, and 100 mg/L of NiO/Fe2O3, the maximum hydrogen yield (HY) of 1.94 mol/mol hexose was obtained, which is 18 % more than the control. The enhanced H2 production upon the addition of nanoparticles is supported via the external electron transfer (EET) mechanism, which regulates the metabolic pathway regulation with increased production of acetate and butyrate and reduced formation of lactate.


Mast cells rescue implantation defects caused by c-kit deficiency.
Various physiologically relevant processes are regulated by the interaction of the receptor tyrosine kinase (c-Kit) and its ligand stem cell factor (SCF), with SCF known to be the most important growth factor for mast cells (MCs). In spite of their traditional role in allergic disorders and innate immunity, MCs have lately emerged as versatile modulators of a variety of physiologic and pathologic processes. Here we show that MCs are critical for pregnancy success. Uterine MCs presented a unique phenotype, accumulated during receptivity and expanded upon pregnancy establishment. Kit(W-sh/W-sh) mice, whose MC deficiency is based on restricted c-Kit gene expression, exhibited severely impaired implantation, which could be completely rescued by systemic or local transfer of wild-type bone marrow-derived MCs. Transferred wild-type MCs favored normal implantation, induced optimal spiral artery remodeling and promoted the expression of MC proteases, transforming growth factor-β and connective tissue growth factor. MCs contributed to trophoblast survival, placentation and fetal growth through secretion of the glycan-binding protein galectin-1. Our data unveil unrecognized roles for MCs at the fetomaternal interface with critical implications in reproductive medicine.


Production of tripeptide from gelatin using collagenase-immobilized porous hollow-fiber membrane.
Tripeptide was produced during the permeation of a gelatin solution through the pore of a collagenase-immobilized porous hollow-fiber membrane. Gelatin was obtained via hydrolysis of fish collagen. First, an epoxy-group-containing monomer was graft-polymerized onto an electron-beam-irradiated porous hollow-fiber membrane. Second, the 2-hydroxyethylamino group was introduced into the epoxy group to bind collagenase on the basis of electrostatic interaction. Third, adsorbed collagenase was cross-linked with glutaraldehyde to prevent leakage of the enzyme. Gelatin solution (10-50 g/L) was forced to permeate across the collagenase-immobilized porous hollow-fiber membrane with a density of immobilized collagenase of 52 mg/g at various residence times of the gelatin solution ranging from 0.13 to 20 min. Fourteen percent in weight of 10 g/L gelatin solution was hydrolyzed into tripeptide at a residence time of 20 min.


Manifestation of familial porphyria cutanea tarda after childbirth.
We report the case of a woman with hereditary porphyria cutanea tarda which manifested 3 weeks after she gave birth to her second child. The mother of the patient had also been diagnosed and treated for porphyria cutanea tarda. Reduced red cell uroporphyrinogen decarboxylase activity was found in the patient, the new-born child and the patient's mother. Normal enzyme activity was found in the patient's first child.


The Wily and Courageous Red Fox: Behavioural Analysis of a Mesopredator at Resource Points Shared by an Apex Predator.
The red fox (Vulpes vulpes) is a widespread and ecologically significant terrestrial mesopredator, that has expanded its range with human globalisation. Despite this, we know relatively little about their behaviour under the wide range of ecological conditions they experience, particularly how they navigate the risk of encounters with apex predators. We conducted the first ethological study of foxes outside their historic native range, in Australia, where both the foxes and their main predator were protected from human hunting. Using remote camera traps, we recorded foxes visiting key resource points regularly utilised by territorial dingoes (Canis dingo), their local apex predator, in the Painted Desert, South Australia. We constructed an ethogram sensitive to a range of behaviours and attitudes. Since foxes are suppressed by dingoes, we expected that the foxes would primarily be in a cautious state. In contrast, we found that foxes were in a confident state most of the time. Where human hunting is absent, social stability of predators may increase predictability and therefore decrease fear.


[The effect of malnutrition during milk feeding on the enzyme activity of the initial and final stages of carbohydrate hydrolysis in the small intestine of growing rats].
Malnutrition in the period from 10 to 17 days of postnatal life causes in young rats an early increase of intestinal alpha-glucosidase activity. However, this rise in the enzyme activity is soon changed by its decrease during normal nutrition. The decreased level of the enzyme activity remains stable during 2-3 weeks after the reduction of normal nutrition.


Malignant transformation of fibrous dysplasia into chondroblastic osteosarcoma.
A case of malignant transformation of polyostotic fibrous dysplasia into maxillary chondroblastic osteosarcoma is presented. The clinical, radiographic, CT, MR imaging features and pathological findings of polyostotic fibrous dysplasia and its malignant transformation are described. Malignant transformation of fibrous dysplasia is rare and has not previously been described in the English literature in this location in McCune-Albright syndrome and in the absence of radiation treatment.


Effect of cytosine arabinoside on cerebellar neurofilaments during development: A sexual dimorphism.
Previous reports suggest that the resistance of neuronal cytoskeleton to drug toxicity may vary with age and gender. The aim of the present study was to assess the impact of cytosine arabinoside (AraC) treatment on neurofilament (NF) levels and phosphorylation status in the developing cerebellum of male, female and testosterone propionate (1.25 mg/rat)-androgenized female rats. AraC (200 mg/kg bw) was administered from postnatal day (PND) 14-16 and changes in the level and phosphorylation of NFs were detected at PND 16 by Western blot analysis. The drug had no effect in male pups, while it increased the non-phosphorylated NF subunits of medium and low molecular weight in females. Androgenization of females prevented the AraC-induced increase in NF subunits. The levels of estrogen receptor beta (ER-β), known to mediate neuroprotective actions of estrogens in the brain, were significantly higher in the developing female cerebellum, as compared to males and androgenized females. These data show that the neurofilament cytoskeleton in the developing rat cerebellum exhibits resistance to AraC that appears sexually dimorphic. In young males the resistance is exemplified by a lack of responsiveness, whereas in juvenile females it is presented by an androgenization-sensitive NF upregulation.


On the effect of basic and acidic additives on the separation of the enantiomers of some basic drugs with polysaccharide-based chiral selectors and polar organic mobile phases.
This article reports the systematic study of the effect of basic and acidic additives on HPLC separation of enantiomers of some basic chiral drugs on polysaccharide-based chiral columns under polar organic mobile-phase conditions. In contrary to generally accepted opinion that the basic additives improve the separation of enantiomers of basic compounds, the multiple scenarios were observed including the increase, decrease, disappearance and appearance of separation, as well as the reversal of the enantiomer elution order of studied basic compounds induced by the acidic additives. These effects were observed on most of the studied 6 chiral columns in 2-propanol and acetonitrile as mobile phases and diethylamine as a basic additive. As acidic additives formic acid was used systematically and acetic acid and trifluoroacetic acid were applied for comparative purposes. This study illustrates that the minor acidic additives to the mobile phase can be used as for the adjustment of separation selectivity and the enantiomer elution order of basic compounds, as well as for study of chiral recognition mechanisms with polysaccharide-based chiral stationary phases.


Anterior approach versus posterior approach for the open reduction of displaced pediatric supracondylar humerus fracture.
This study's objective was to compare the results and adverse outcomes of the anterior approach and posterior approach in patients with a type 3 Gartland pediatric supracondylar fracture who failed close treatment and indicated open reduction. in this retrospective study patients with Gartland type 3 fracture who failed close reduction and required open reduction were enrolled in the study. Eligible patients underwent open reduction via anterior and posterior triceps sparing approaches. Patients were followed up 3, 6, and 12 months after the surgery. Study variables included age, sex, Bauman's angle, pin site infection, nerve injury, osteonecrosis, and elbow arc of motion. The study included a total of 83 patients. Surgery was performed on 49 patients using the posterior technique and 34 patients using the anterior approach. The mean age of patients was 6.78 ± 1.40 years. The mean age and the relative frequency of sex didn't differ significantly between study groups (P > 0.05). Two-way repeated measures ANOVA test showed that there was a statistically significant difference in elbow arc of motion in the anterior approach in comparison with the posterior approach, however, this increase was not clinically significant. In terms of adverse events including pin site infection, nerve injury, osteonecrosis, and cubitus varus, there was no statistically significant difference between the two approaches. There was no clinically significant difference in elbow arc of motion and adverse events between the anterior approach and the posterior approach. Therefore, surgeons should choose the approach with which they are more familiar and comfortable.


Antibody capture haemadherence tests for parvovirus B19-specific IgM and IgG.
In the absence of serum inhibitor human parvovirus B19 agglutinates primate red cells. Agglutination of baboon erythrocytes by inhibitor free baculovirus expressed VP1/VP2 proteins of B19 virus was enhanced by low pH. To avoid interference from inhibitor(s) present in serum specimens microtitre tests with an antibody capture configuration were designed and optimised. Antigen binding was demonstrated by the adherence of baboon erythrocytes. These tests (MACHAT, GACHAT) detected IgM or IgG anti-B19 in 1032 serum specimens with an overall sensitivity of 99%, specificity of 98.2% and positive predictive value of 96.8% with reference to the radioimmunoassays currently in diagnostic use. MACHAT and GACHAT are straightforward, and well suited to large scale research and seroepidemiological investigations. They are without the risks from infectious antigen and radiation associated with existing radioimmunoassays and allow the phenomenon of B19 virus haemagglutination to be put to practical advantage.


Effects of rosiglitazone on plasma brain natriuretic peptide levels and myocardial performance index in patients with type 2 diabetes mellitus.
Thiazolidinediones (TZD) have become a powerful tool for lowering insulin resistance. The problem of cardiovascular adverse events including fluid retention and risk of heart failure should be well known and recognised. We aimed to evaluate the long-term effects of rosiglitazone on cardiac function and fluid dynamics. Forty-six type 2 diabetic patients were randomised to treatment with rosiglitazone or metformin or to a control group. There are no significant differences between the groups in the duration of diabetes, HbA1c, plasma brain natriuretic peptide (BNP) levels, body mass index and myocardial performance indexes (MPIs) before the treatment. After three and six months all these parameters were repeated. Rosiglitazone increased plasma BNP levels and worsened MPIs 3 months after the start of treatment. Also left ventricular end-systolic volume increased and weight gain was observed. But these results were statistically non-significant (all p>0.05). When we continued rosiglitazone treatment to six months the increase in BNP levels became soft and statistically significant improvements were seen in MPIs (p<0.01). Also left ventricular end-systolic volume decreased significantly (p=0.004) and weight gain was stopped. In patients with type 2 diabetes, TZD treatment might have slight adverse effects on ventricular contractility and fluid dynamics at the beginning of the therapy. However, these changes seem to stabilise in the long term.


Characterization of a nonenzymatic component in the isomerization of 5-pregnene-3,20-dione catalyzed by human placental microsomes in vitro.
When human placental microsomes were heated in boiling water or exposed to trypsin, 30 to 40% of the 5-ene,3-ketosteroid isomerase activity was stable. Aqueous suspensions of chloroform:methanol extracts of microsomes also catalyzed isomerization of 5-pregnene-3,20-dione, activity being associated with the polar lipid fraction. The trypsin- and heat-stable activities, as well as that of resuspended microsomal lipids, showed a dependence on buffer composition and concentration. Little activity was detected in water at pH 7.0. Relative activities in various buffers were Hepes (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) greater than Pipes (1,4-piperazinediethanesulfonic acid) greater than potassium phosphate greater than Mes(4-morpholineethanesulfonic acid). The data suggest that the occurrence of membrane lipid-dependent nonenzymatic catalysis could contribute to the isotope exchange with solvent observed in previous studies of the mechanism of isomerization catalyzed by placental microsomes. The ability of the membrane lipid phase to catalyze steroid isomerization under certain conditions and the fact that this activity is subject to modifications by exogenous agents may have more general implications for an understanding of possible effects of xenobiotics on steroid hormone formation and action in vivo.


Efficacy of Cicuta virosa medicinal preparations against pentylenetetrazole-induced seizures.
Epileptic seizures are characterized by imbalanced inhibition-excitation cycle that triggers biochemical alterations responsible for jeopardized neuronal integrity. Conventional antiepileptic drugs (AEDs) have been the mainstay option for treatment and control; however, symptomatic control and potential to exacerbate the seizure condition calls for viable alternative to these chemical agents. In this context, natural product-based therapies have accrued great interest in recent years due to competent disease management potential and lower associated adversities. Cicuta virosa (CV) is one such herbal remedy that is used in traditional system of medicine against myriad of disorders including epilepsy. Homeopathic medicinal preparations (HMPs) of CV were assessed for their efficacy in pentylenetetrazole (PTZ)-induced acute and kindling models of epilepsy. CV HMPs increased the latency and reduced the duration of tonic-clonic phase in acute model while lowering the kindling score in the kindling model that signified their role in modulating GABAergic neurotransmission and potassium conductance. Kindling-induced impairment of cognition, memory, and motor coordination was ameliorated by the CV HMPs that substantiated their efficacy in imparting sustained neuronal fortification. Furthermore, biochemical evaluation showed attenuated oxidative stress load through reduced lipid peroxidation and strengthened free radical scavenging mechanism. Taken together, CV HMPs exhibited promising results in acute and kindling models and must be further assessed through molecular and epigenomic studies.


A density functional theory based tight-binding study on the water effect on nanostructuring of choline chloride + ethylene glycol deep eutectic solvent.
The effect of water on the properties of an archetypical type III deep eutectic solvent [choline chloride : ethyleneglycol (1:2)] is analyzed using ab initio molecular dynamics simulations in the 0 to 60 wt. % water content range. The properties of the mixed fluids are studied considering nanostructuring, intermolecular forces (hydrogen bonding), the energy of interactions, dynamic properties, and domain analysis. The reported results confirm that the change in the properties of the studied deep eutectic solvent is largely dependent on the amount of water. The competing effect of water molecules for the available hydrogen bonding sites determines the evolution of the properties upon water sorption. The main structural features of the considered deep eutectic were maintained even for large water contents; thus, its hydrophilicity could be used for tuning fluid physicochemical properties.


Cloning and expression of the cyclophilin Bet v 7, and analysis of immunological cross-reactivity among the cyclophilin A family.
Allergic symptoms in sensitized individuals are caused by proteins named allergens. We report here the cloning and the production of the cyclophilin Bet v 7, one of the birch pollen allergens. Recombinant Bet v 7 was produced in bacteria and used to raise a rabbit anti-Bet v 7 antiserum. With this antiserum we detected cyclophilin A in several pollen species and we demonstrated immunological cross-reactivity among those plant cyclophilins A by immunoblot and ELISA inhibition experiments. However, we could not detect cyclophilins in extracts of animal or mould origin with our anti-Bet v 7 antiserum. By inhibition experiments with purified mould cyclophilins, we confirmed the absence of cross-reactivity between plant cyclophilins and non-plant cyclophilins. In addition, our results indicate that the level of immunological cross-reactivity correlates with the level of sequence identity among the cyclophilin A family. This allowed us to define the plant cyclophilin A sub-family as being immunologically distinct, which might have implications at the clinical level in the allergy practice.


A clinicopathologic analysis of 54 cases of cutaneous myxoma.
Cutaneous myxoma (CM) is an uncommon benign neoplasm of skin, which may be sporadic or arise in association with syndromes such as Carney complex. There has been only one large case series describing CM. We report 54 additional cases of CM; patients had a mean age of 55 years (range = 7-91), with a female-to-male ratio of 1.3. Most occurred on the trunk (n = 19), with the back being the most common site. The remainder presented on the lower extremity (n = 18), head and neck (n = 10), and arm (n = 7). Histopathologically, they were relatively circumscribed, nodular, and centered in the dermis. All had abundant myxoid stroma, a thin, arborizing vascular network, and spindled to stellate cells with no to mild atypia without mitotic activity. Follicular induction, stromal neutrophils, and intranuclear inclusions were present in 35%, 25%, and 61% of cases, respectively. Collagen trapping, splitting of collagen fibers, and encircling of hair follicles or eccrine glands were encountered in a subset. Thirty-nine cases were treated with shave excision, whereas 12 cases underwent wide local excision. Follow-up data were available for 28 of 54 cases (mean = 50 months). Only one case recurred at 36 months. This study suggests CM has a lower risk of local recurrence than previously reported.


Urinary excretion of deoxypyridinoline in 24-hour and first-void samples in healthy Turkish children.
Collagen cross-links are formed during the maturation process of bone matrix. They have been considered as valuable markers in some metabolic, endocrinologic, and neoplastic bone disorders. As an advantage, it can be measured in urine as well as in serum samples. However, the excretion characteristics remains controversial. We investigated urinary free deoxypyridinoline (f-Dpd) excretion in first-void urine samples and in 24-hour collections in healthy Turkish children. We also evaluated the possible correlations and gender-related differences in Dpd excretion between these sampling methods. Both urine samples of 62 subjects (aged from 31 to 120 months) were analyzed by Immulite chemiluminescent technique. There were no remarkable differences in f-Dpd excretion between first-void and 24-hour urine samples, although f-Dpd values of the first-void samples were slightly higher (Dpd: creatinine, mean +/- SD, 20.5 +/- 5.8 nmol/mmol vs. 19.6 +/- 5.6 nmol/mmol, respectively, p > 0.05). A strong linear correlation was found between 24-hour and first-void urine f-Dpd excretions (r = 0.77, p < 0.05). In addition, f-Dpd showed no gender-related differences between boys and girls in either 24-hour or first-void urine samples (p > 0.05). Because of difficulties in long-time urine collection in infants and young children, f-Dpd assessment in first-void single urine samples is an easy, safe, and non-invasive method.


Internal fixation of complex fractures of the tarsal navicular with locking plates. A report of 10 cases.
Tarsal navicular fractures are rare and treatment of comminuted fractures is especially difficult. Since 2007, the authors have had access to 3D reconstruction from CT scan images and specific locking plates, and they decided to evaluate whether these elements improved management of these severe cases. Between 2007 and 2011, 10 comminuted tarsal navicular fractures were treated in a prospective study. All of the fractures were evaluated by 3D reconstruction from CT scan images, with suppression of the posterior tarsal bones. The surgical approach was chosen according to the type of lesion. Reduction was achieved with a mini-distractor when necessary, and stabilized by AO locking plate fixation (Synthes™). Patient follow-up included a clinical and radiological evaluation (Maryland Foot score, AOFAS score). Eight patients underwent postoperative CT scan. All patients were followed up after a mean 20.5 months. Union was obtained in all patients and arthrodesis was not necessary in any of them. The mean Maryland Foot score was 92.8/100, and the AOFAS score 90.6/100. One patient with an associated comminuted calcaneal fracture had minimal sequella from a compartment syndrome of the foot. The authors did not find any series in the literature that reported evaluating tarsal navicular fractures by 3D reconstruction from CT scan images. The images obtained after suppression of the posterior tarsal bones systematically showed a lateral plantar fragment attached to the plantar calcaneonavicular ligament, which is essential for stability, and which helped determine the reduction technique. Locking plate fixation of these fractures has never been reported. Comminuted fractures of the tarsal navicular were successfully treated with specific imaging techniques in particular 3D reconstructions of CT scan images to choose the surgical approach and the reduction technique. Locking plate fixation of the navicular seems to be a satisfactory solution for the treatment of these particularly difficult fractures. Level IV.


[Melanoma and atopy].
331 melanoma patients (206 females; 125 males) and 380 control subjects (205 females; 175 males) were questioned about symptoms of atopy (eczema, allergic rhinitis, allergic asthma). Among the melanoma patients there were 14 (10 females, 4 males; 4.2%) with atopy, while in the control group there were 38 (23 females, 15 males; 10%). The influence of age, sex, socio-economic status and other risk factors for melanoma were analysed with the Mantel-Haenszell test, which indicated that melanoma patients had fewer atopic symptoms than subjects in the control group (p less than 0.05). The role of fever may be an explanation of this finding. Among melanoma patients there were fewer feverish infections, while patients with atopy had more feverish complications of their symptoms.


Floor of mouth haemorrhage and life-threatening airway obstruction during immediate implant placement in the anterior mandible.
A majority of the procedures performed in the dental office setting are considered safe and minimally invasive. Despite this fact, as healthcare providers it is our responsibility to be able to anticipate, recognize and manage life-threatening emergencies that may occur. In the following report, the authors will describe a life-threatening complication that resulted from the placement of mandibular implants.


1 alpha,25-dihydroxyvitamin D3-induced changes in intracellular pH in osteoblast-like cells modulate gene expression.
1 alpha,25-Dihydroxyvitamin D3 exerts rapid nongenomic effects on rat osteoblast-like cells independent of the classic nuclear receptor. These effects include changes in phospholipid metabolism and cell calcium. Intracellular calcium itself has been proposed to regulate intracellular pH in osteoblast cell lines. The purpose of this study was to determine the effect of 1 alpha,25-dihydroxyvitamin D3 on intracellular pH, the relationship of changes in calcium to changes in pH, and the role of pH changes in genomic activation. 1 alpha,25-Dihydroxyvitamin D3 increased intracellular pH within 10 min in rat osteoblast-like cells, an effect that was inhibited by removal of extracellular sodium and by the biologically inactive epimer 1 beta,25-dihydroxyvitamin D3. The hormone increased intracellular calcium in Quin 2 loaded cells in the presence and absence of extracellular sodium. The 1 alpha,25-dihydroxyvitamin D3-induced increments in osteocalcin and osteopontin mRNA levels were abolished in sodium-free medium. The results indicate that 1 alpha,25-dihydroxyvitamin D3-induced increments in cellular calcium precede cell alkalinization and that these changes in intracellular pH may modulate steady-state mRNA levels of genes induced by vitamin D.


Multi-country investigation of factors influencing breeding decisions by smallholder dairy farmers in sub-Saharan Africa.
Artificial insemination (AI) and selective bull mating are considered as robust methods for dairy cattle breeding. Globally, these methods have been used to enhance productivity and realize rapid genetic gains. However, these technologies have had low adoption rates in sub-Saharan Africa (SSA). Even though available evidence suggests that this is due to various infrastructural and technical challenges. There is limited information about what drives this low uptake of AI from a farmer's perspective. Therefore, the main objective of this study was to determine and characterize factors that influence the choice by smallholder farmers between bull service and AI for dairy cow breeding. Further, the relationships between the breeding choices and the bio-physical elements of dairy farming, mainly, farmer characteristics, household income levels, farm management practices, and institutional support structures, were investigated. Data were collected through face-to-face interviews from a total of 16,308 small-scale dairy farmers in Ethiopia (n = 4679), Kenya (n = 5278), Tanzania (n = 3500), and Uganda (n = 2851). The questionnaire was coded in an electronic form using Open Data Kit (ODK) platform to allow for real-time data entry and management. Descriptive statistics, chi-square test, and a t-test were used to evaluate the independent and dependent variables, while logistic regression and factor analysis were used to identify factors that influenced farmers' breeding decisions. Results showed that there was a significant difference in animal husbandry practices between farmers who used artificial insemination (AI) and those who practiced bull mating. The majority of farmers who used AI kept records, purchased more animal feeds, had more labor by hiring workers whose average wages were higher than those of bull service farmers. However, farmers who used AI pay more for services such as water access and breeding while their service providers had to cover long distances compared to farmers who used bulls. This indicates limited access to services and service providers for AI farmers. The ratio of AI to bull service users was even for Ethiopia and Kenya, while in Uganda and Tanzania, more farmers preferred bull service to AI. It was established that the factors that influence farmers' breeding decision were not the same across the region. Factors such as farmer's experience in dairy farming, influence of the neighbor, farmer's ability to keep records, and management practices such as water provision and availability of feeds had a significant association (p < 0.001) with AI adoption among dairy farmers. In contrast, large herd and large land size negatively influenced AI adoption. Institutional settings including cost of AI service and the distance covered by the service provider negatively affected (p < 0.001) the choice of AI as a breeding option. There was a high probability of continued use of a specific breeding method when there was a previous conception success with that same method. Based on the results obtained, we recommend that improvement of institutional settings such as the availability of AI service providers, as well as better access to services such as water, animal feed, and animal health provision, be treated as critical components to focus on for enhanced AI adoption. Most importantly, there is a need to avail training opportunities to equip farmers with the necessary skills for best farm management practices such as record keeping, proper feeding, and selective breeding.


A new cholesterol biosynthesis and absorption disorder associated with epilepsy, hypogonadism, and cerebro-cerebello-bulbar degeneration.
Cholesterol is one of the main components of human cell membranes and constitutes an essential substance in the central nervous system, endocrine system, and its hormones, including sex hormones. A 19-year-old male patient presented with failure to thrive, psychomotor deterioration, intractable epilepsy, hypogonadism, and cerebro-cerebello-bulbar degeneration. His serum level of cholesterol was low, ranging from 78.7 to 116.5 mg/dL. The serum concentrations of intermediates in the cholesterol biosynthesis pathway, such as 7-dehydrocholesterol, 8-dehydrocholesterol, desmosterol, lathosterol, and dihydrolanosterol, were not increased. In addition, the levels of the urinary cholesterol biosynthesis marker mevalonic acid, the serum cholesterol absorption markers, campesterol and sitosterol, and the serum cholesterol catabolism marker, 7α-hydroxycholesterol, were all low. A serum biomarker analysis indicated that the patient's basic abnormality differed from that of Smith-Lemli-Opitz syndrome and other known disorders of cholesterol metabolism. Therefore, this individual may have a new metabolic disorder with hypocholesterolemia because of decreased biosynthesis and absorption of cholesterol.


Metabolomic Analysis of the Improvements in Insulin Secretion and Resistance After Sleeve Gastrectomy: Implications of the Novel Biomarkers.
Large neutral amino acids (LNAAs) and gut microbial metabolites have been linked to insulin secretion and resistance. We investigated whether baseline LNAAs and kynurenine pathway metabolites and changes in tryptophan-derived gut microbial metabolites (TDGMs), such as indole compounds, were associated with improvements in insulin secretion and resistance after sleeve gastrectomy. In this prospective single-arm longitudinal study, 23 patients with type 2 diabetes underwent sleeve gastrectomy. Twelve diabetes-related amino acid metabolites were quantified before surgery, and the following three indices were assessed as outcome measures: insulinogenic index, homeostasis model assessment-insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI). We also measured changes in TDGMs, including four indole compounds, 3 months after bariatric surgery. A linear regression model and receiver operating characteristic curves were assessed. The mean age and body mass index of study participants were 41.8 years (standard deviation (SD), 13.1 years) and 38.9 kg/m2 (SD, 5.2 kg/m2), respectively. Several baseline amino acid metabolites were significantly associated with a change in insulin secretion or resistance 3 months after bariatric surgery. Phenylalanine and LNAAs showed superior performance for predicting improvements in insulin secretion and resistance. Among the TDGMs, Δindole-3-propionic acid was significantly associated with the Δinsulinogenic index, and Δindole-3-acetic acid was significantly associated with the ΔHOMA-IR and ΔQUICKI. Our findings underscore the importance of baseline amino acid profiles, especially those of LNAAs and phenylalanine, and alterations in TDGMs for improving insulin secretion and resistance in the early postoperative period after sleeve gastrectomy.


European Society of Sexual Medicine consensus statement on the use of animal models for studying Peyronie's disease.
Animal models are frequently used for translational research in Peyronie's disease (PD). However, due to lack of availability of guidelines, there is some heterogeneity in study design, data reporting, and outcome measures. This European Society for Sexual Medicine consensus statement aims to provide guidance in utilization of animal models in PD research in a standardized and uniform fashion. PubMed was searched for studies using animal models for PD. The following search terms were used: ("Peyronie's disease" OR "penile fibrosis" OR "penile curvature" OR "induration penis plastica" OR "erectile dysfunction") AND ("rodent" OR "mouse" OR "mice" OR "rat" OR "rabbit"). This European Society for Sexual Medicine statement describes best practice guidelines for utilization of animals in PD research: power calculation, details of available models, surgical procedures, and measurement techniques, while highlighting possible pitfalls and translational limitations of the models. In total, 2490 studies were retrieved and 2446 articles were excluded. A total of 44 studies were included, of which 40 studies used rats, 1 study used both rats and mice, 1 study used a genetic mouse model, and 2 studies used rabbits. A significant number of the studies (70.5%) used transforming growth factor β 1 for induction of fibrosis. Oxford 2011 Levels of Evidence criteria could not be applied due to the nature of the studies. Despite certain limitations of PD animal models presented, we aimed to provide guidance for their appropriate use in translational research, with the purpose of improving study quality and reproducibility as well as facilitating interpretation of reported results and conclusions.


Tetrathiafulvalenes as anchors for building highly conductive and mechanically tunable molecular junctions.
The interface between molecules and electrodes has great impact on charge transport of molecular devices. Precisely manipulating the structure and electronic coupling of electrode-molecule interface at a molecular level is very challenging. Here, we develop new molecular junctions based on tetrathiafulvalene (TTF)-fused naphthalene diimide (NDI) molecules which are anchored to gold electrodes through direct TTF-Au contacts formed via Au-S bonding. These contacts enable highly efficient orbital hybridization of gold electrodes and the conducting π-channels, yielding strong electrode-molecule coupling and remarkably high conductivity in the junctions. By further introducing additional thiohexyl (SHe) anchors to the TTF units, we develop molecular wires with multiple binding sites and demonstrate reversibly switchable electrode-molecule contacts and junction conductance through mechanical control. These findings show a superb electrode-molecule interface and provide a new strategy for precisely tunning the conductance of molecular devices towards new functions.


Trace element accumulation in fishes collected from coastal waters of the Caspian Sea.
Concentrations of 13 trace elements (V, Mn, Cr, Co, Cu, Zn, Se, Mo, Ag, Cd, Hg, Tl and Pb) were determined in muscle of bony fishes collected from coastal areas of the Caspian Sea (Kazakhstan, Azerbaijan, Turkmenistan and Iran). In all the fishes, Zn concentration was highest, followed by Cu, Se, Mn and Co, while levels of toxic elements (Ag, Cd, Cd, Tl and Pb) were relatively low. Concentrations of several elements were significantly varied between the species in each sampling area. For most of the trace elements examined, the concentrations decreased significantly with body weight of fishes. In contrast, a positive correlation with body weight was found for Co, Se and Pb concentrations in one fish species, and Hg in 2 fish species. Geographical difference in the concentrations of trace elements was examined using the Caspian roach collected from five stations of Iranian coastal waters. The concentrations of Co, Mo, Ag, Cd and Tl were higher in fishes from western stations than those from eastern stations, whereas the opposite trend was observed for Hg, indicating that local sources of trace metal pollution may be present in the Iranian coastal areas of the Caspian Sea. Levels of trace elements in Caspian fishes were relatively low in comparison to those of other regions, but Zn and Hg levels in some specimens exceeded the guideline values for food.


Impaired circulating CD56dim NK cells are associated with decompensation of HBV-related cirrhosis.
NK cells play an important role in immune regulation and defense of infection, but their characteristics in patients with decompensated cirrhosis and their relationship with liver function remain unclear. We studied the functional properties of NK cells (including CD56dim NK and CD56bright NK cells) in patients with HBV-related decompensated liver cirrhosis (HBV-DLC) and analyzed their relationship with decompensation of liver function. Thirty patients with HBV-DLC and 25 patients with HBV-related compensated liver cirrhosis (HBV-CLC) were recruited in this study. Twenty five age- and sex-matched healthy individuals were recruited as healthy controls (HCs). The phenotypical and functional characteristics of NK cell subsets were detected by flow cytometry, and the correlation between NK cells and decompensation of liver function was analyzed. The frequency of circulating CD56bright NK cells was significantly increased while circulating CD56dim NK cells was significantly decreased in HBV-DLC patients as compared with HCs and HBV-CLC patients. Peripheral activated-CD56bright NK cells from HBV-DLC patients might express lower levels of inhibitory receptor CD158b1/2 and higher levels of activating receptor NKG2D and their expression of perforin and granzyme A/B also increased significantly compared with HCs, suggesting a high immune activation status of peripheral CD56bright NK cells in HBV-DLC patients. In HBV-DLC patients, the expression of CD107a and perforin in circulating CD56dim NK cells was positively correlated with cytolytic capacity while CD107a and perforin expression in circulating CD56dim NK cells were significantly decreased, suggesting an impaired cytolytic capacity of circulating CD56dim NK cells. Besides, we found that the perforin expression of circulating CD56dim NK cells correlated negatively with child-pugh classification in HBV-DLC patients. The functional properties of circulating NK cell subsets in HBV-DLC patients have changed significantly, especially of CD56dim NK cells which closely related to decompensation of liver function. These findings may help provide new perspectives and theoretical basis for the treatment of patients with HBV-DLC.


Draft Genome Sequence of Ralstonia sp. MD27, a Poly(3-Hydroxybutyrate)-Degrading Bacterium, Isolated from Compost.
Ralstonia sp. strain MD27, a novel biopolymer-degrading betaproteobacterium, was isolated from compost samples. This organism has been shown to utilize the biopolymer poly(3-hydroxybutyrate) [P(3HB)] as a carbon source for growth. We report the draft genome sequence of MD27 with an estimated total sequence length of 5.9 Mb.


Oral reduced B-nicotinamide adenine dinucleotide (NADH) affects blood pressure, lipid peroxidation, and lipid profile in hypertensive rats (SHR).
A gradual increase in blood pressure (BP), often attaining hypertensive levels, is common during aging--"age-related hypertension." Therefore, means to prevent or ameliorate this elevated BP safely are important. Although oral B-nicotinamide adenine dinucleotide (NADH), a natural coenzyme, is used principally to treat various neurologic disorders, we wished to investigate whether this agent had the same potential to lower BP and benefit the cardiovascular system as does coenzyme Q10, a similar-type agent. As a first approximation, spontaneously hypertensive rats (SHR) were used to determine effects of oral NADH. In a blinded, placebo-controlled study, ten rats received placebo; and ten, NADH for ten weeks. Systolic BP was measured by tail plethysmography. Blood was collected terminally, and chemistries were performed by routine methodologies. Thiobarbituric acid reactive species (TBARS) (an estimate of lipid peroxidation/free radical formation) was measured in renal and hepatic tissues. The following was noted: water and food intake were comparable, and the steady weight gain of young SHR were similar in the placebo and NADH groups. Although systolic BP did not differ between the two groups over the first month, it decreased and stayed markedly lower for the remainder of study in SHR receiving oral NADH. At the end of 60 days, SBP in NADH-treated SHR was 184 mm Hg +/- 2.8 (SEM) compared to 201 mm Hg +/- 2.1 (SEM) in control SHR (p < 0.001). No significant differences were seen in blood levels of glucose, insulin, triglyceride, and HDL levels but NADH intake lowered total cholesterol (p < 0.002) and LDL (p < 0.02). Renal TBARS were also significantly lower in SHR receiving NADH (P < 0.001). Accordingly, supplementation with the natural coenzyme NADH theoretically could prove to be useful in preventing age-related increases in BP and, thus, various cardiovascular maladies.


Molecular modelling of human CYP2D6 and molecular docking of a series of ajmalicine- and quinidine-like inhibitors.
3D-models were created and refined for CYP2D6 and for its complexes with ajmalicine and quinidine. The influence of the conformation of the enzyme active site on its interaction with ligands was evaluated by performing three series of molecular docking on selected ajmalicine- and quinidine-like inhibitors. The results suggested that the experimental binding values of ajmalicine- and quinidine-like inhibitors better fit with the energetic terms derived from their interaction with structures of CYP2D6 obtained by, respectively, optimizing the ajmalicine/CYP2D6 and the quinidine/CYP2D6 complexes, rather than exploiting the 3D-strucure of the enzyme not subjected to a ligand-induced conformational change. It suggests the relevance of induced-fit phenomena in the biological system of interest.


Variables affecting long-term usage rate of sperm samples cryopreserved for fertility preservation in cancer patients.
Previous evidence highlighted that only a minority of men who banked their semen before cancer therapies subsequently used their frozen samples. This may question the economical validity of sperm cryopreservation programmes. However, in most contributions, the duration of follow-up was insufficient to draw robust information on the real rate of use. To shed more light on the potential benefits of cryopreservation programmes. Men who cryopreserved their semen in a public hospital for a diagnosis of cancer between 1986 and 2009 were retrospectively reviewed. The rate of use as well as the possible determinants was investigated. The median time of follow-up was 12 [IQR: 7-16] years. One hundred forty-four patients out of 1,524 (9.4%, 95%CI: 8.1%-11.0%) used their frozen samples of whom 64% were azoospermic. The rate of men achieving parenthood with frozen semen was 46%. Predictive factors of use were older age at the time of storage, lower sperm count at the time of storage and a diagnosis of testicular cancer. The impact of this latter factor was also supported by the lower frequency of azoospermia after cancer treatment in these patients. Cost-beneficial studies are warranted to assess and possibly improve the economical validity of sperm banking. The usage rate of frozen sperm in cancer patient is low, even extending the duration of follow-up.