Denosumab for the treatment of osteoporosis.
Being a connective tissue, bone can increase or decrease its mass through the process of remodeling. Using a discovery in the mid-1980s-that tumor necrosis factor (TNF) could dramatically increase formation of osteoclasts (the cells that break down bone)-researchers at Amgen (Thousand Oaks, CA) discovered a TNF-like molecule that regulated bone resorption. Elevations in the expression of this molecule, receptor activator of nuclear factor-κB ligand (RANKL), can cause excessive bone destruction. A blocking antibody to RANKL named denosumab inhibits osteoclast formation and bone degradation. In a large multicenter clinical trial, known as the FREEDOM trial (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months), the effects of denosumab were tested in 60- to 90-year-old women over 3 years. Statistically significant reductions in fracture risk at the vertebral column, hip, and nonvertebral sites were associated with increases in bone mineral density (BMD) and reciprocal decreases in markers of bone resorption. However, the FREEDOM trial did not test the most beneficial use of a resorption blocking drug-to target the rapid bone loss that occurs in late perimenopause and early postmenopause. One adverse effect from denosumab is cellulitis, and research in animals suggests that RANKL/RANK interaction is needed for Langerhans cell (LC) survival in the skin. Further mechanistic and clinical studies on the role of RANKL in the skin are needed.


Isolated bone marrow non-Hodgkin's lymphoma: a clinicopathologic study.
Isolated bone marrow non-Hodgkin's lymphoma (NHL) is rare, and determining the diagnosis is difficult. We describe four patients with apparent isolated bone marrow NHL. The features they had in common included fever, abnormal liver function, pancytopenia, polyserositis, neurologic symptoms, opportunistic infections, and a short, fatal course. Routine cytologic and histologic studies showed intermediate and large lymphomatous cells in the bone marrow, with a predominantly interstitial pattern. Immunophenotyping revealed three cases of T-cell and one case of B-cell NHL. Cytogenetic analysis demonstrated an abnormal clone in two patients. The diagnosis of isolated bone marrow NHL should be based on the examination of both bone marrow aspirates and biopsy specimens.


White matter and nigral alterations in multiple system atrophy-parkinsonian type.
Multiple system atrophy (MSA) is classified into two main types: parkinsonian and cerebellar ataxia with oligodendrogliopathy. We examined microstructural alterations in the white matter and the substantia nigra pars compacta (SNc) of patients with MSA of parkinsonian type (MSA-P) using multishell diffusion magnetic resonance imaging (dMRI) and myelin sensitive imaging techniques. Age- and sex-matched patients with MSA-P (n = 21, n = 10 first and second cohorts, respectively), Parkinson's disease patients (n = 19, 17), and healthy controls (n = 20, 24) were enrolled. Magnetization transfer saturation imaging (MT-sat) and dMRI were obtained using 3-T MRI. Measurements obtained from diffusion tensor imaging (DTI), free-water elimination DTI, neurite orientation dispersion and density imaging (NODDI), and MT-sat were compared between groups. Tract-based spatial statistics analysis revealed differences in diffuse white matter alterations in the free-water fractional volume, myelin volume fraction, and intracellular volume fraction between the patients with MSA-P and healthy controls, whereas free-water and MT-sat differences were limited to the middle cerebellar peduncle in comparison with those with Parkinson's disease. Region-of-interest analysis of white matter and SNc revealed significant differences in the middle and inferior cerebellar peduncle, pontine crossing tract, corticospinal tract, and SNc between the MSA-P and healthy controls and/or Parkinson's disease patients. Our results shed light on alterations to brain microstructure in MSA.


Effective polyethylenimine-mediated gene transfer into human endothelial cells.
The major advantage in choosing non-viral vectors such as cationic polymers for in vitro and in vivo transfection is their higher biosafety than viral ones. Among the cationic polymers, polyethylenimines (PEIs) are promising molecules for gene delivery to a variety of cells. Efficient transfection of primary endothelial cells using PEIs could be regarded as an interesting strategy of treatment in some ischemic cardiovascular diseases. Efficacies of a 22-kDa linear PEI (L-PEI) and its glucose-grafted derivative (L-PEI-Glc(4)) were compared for gene transfer into human umbilical vein endothelial cells (HUVEC) using the reporter gene luciferase. Cells were incubated for 2, 4 and 24 h with PEI/DNA complexes made in 150 mM sodium chloride (NaCl) or in 5% glucose solution. Luciferase activity was measured 24 h after the onset of transfection. The effects of low (2%) and high (30%) concentrations of serum on transfection efficacy were assessed as well. We then studied the intracellular fate of the PEI/DNA complexes labelled with the DNA intercalator YOYO-1 using flow cytometry analysis (FACS) and confocal microscopy. PEI/DNA complexes formed in NaCl led to a higher transfection efficacy than those made in glucose. The optimal formulation, depending on the incubation time and the presence of serum in the medium, was obtained using DNA complexed to L-PEI-Glc(4) and incubated for 4 h with the cells. This condition led to 50% fluorescent cells after GFP transfection. A high serum concentration diminished the L-PEI associated toxicity but decreased L-PEI-Glc(4) transfection efficiency. FACS analysis using both vectors showed that almost 90% of the cells had internalized the DNA complexes. Confocal microscopic observations showed a fast attachment of the complexes to the cell surface followed by inclusion into vesicles that migrated to the perinuclear region. In this work, we defined the optimal conditions for gene delivery in HUVEC. These conditions were obtained when using derivatives L-PEI and L-PEI-Glc(4) complexed with DNA in 150 mM NaCl and added to cells for 2 and 4 h, respectively. Cellular trafficking of the complexes suggested that cell entry was not a limiting factor for gene delivery using PEI. This study underlined the interest in PEIs as efficient vectors for gene transfer into human endothelial cells.


Is HCV transmitted by the vertical/perinatal route?
Hepatitis type C is the major aetiological cause of both parenterally transmitted and cryptogenic, sporadic or community acquired nonAnonB hepatitis. The lack of known parenteral risk factors in a consistent number of cases with nonAnonB hepatitis has stimulated the search of other possible modes of viral transmission. The aim of this report is to review the evidence both for and against vertical/perinatal transmission of HCV from anti-HCV positive mothers to infants.


Selection of cord blood unit(s) for transplantation.
Selection of cord blood (CB) units for transplantation involves combining both cell dose and HLA matching as independent yet overlapping variables. Cell dose and cell yield at the time of transplant are critical given that the transplants are being performed with minimal cells for reliable engraftment. In transplants for malignant disorders, the greater allogenicity and lower relapse rate associated with the less well-matched units balance any benefit of better HLA matching on TRM. The only factor that has repeatedly been associated with improved outcome post CB transplant is cell dose. The CB inventories are rapidly increasing in size and the quality of CB units being banked (larger, better characterized) is improving. With this, some of our current limitations in CB availability will soon become moot. Explorations into CB expansion and multiple CB unit transplants are addressing the limited cell doses attainable with a single CB collection. At this point, one must conclude that bigger is better when selecting CB units for transplantation.


Molecular evolution of antioxidant and hypoxia response in long-lived, cancer-resistant blind mole rats: The Nrf2-Keap1 pathway.
The Nrf2-Keap1 pathway is crucial for the cellular antioxidant and hypoxia response in vertebrates. Deciphering its modifications in hypoxia-adapted animals will help understand its functionality under environmental stress and possibly allow for knowledge transfer into biomedical research. The blind mole rat Spalax, a long-lived cancer-resistant rodent, lives in burrows underground and is adapted to severely hypoxic conditions. Here we have conducted a bioinformatical survey of Spalax core genes from the Nrf2-Keap1 pathway on the coding sequence level in comparison to other hypoxia-tolerant and -sensitive rodents. We find strong sequence conservation across all genes, illustrating the pathway's importance. One of the central players however, Spalax Keap1, shows a non-conservative amino acid substitution from tyrosine to cysteine in its intervening region (IVR) domain. Cysteines in this location have been shown to be of high functional relevance to the binding and degradation of Nrf2. Therefore, this peculiar substitution could influence the cellular Nrf2 levels in Spalax and, thereby, downstream gene expression in the antioxidant pathway, contributing to the special adaptive phenotype of the blind mole rat.


Steamed root of Rehmannia glutinosa Libosch (Plantaginaceae) alleviates methotrexate-induced intestinal mucositis in rats.
Intestinal mucositis induced by chemotherapy is a severe clinical problem in cancer patients that currently lack effective interventions. In traditional Chinese medicine, chemotherapeutic toxicity is diagnosed as Qi and Yin deficiency, and steamed rehmannia root (SRR) is frequently prescribed to these patients. Whether SRR can prevent the adverse effects remains to be confirmed experimentally. The present study used a rat model to investigate potential efficacy and action mechanisms of SRR in attenuating the adverse effects caused by chemotherapy. Intraperitoneal injection of a single dose of anti-metabolite methotrexate (MTX, 25mg/kg) was given to adult Wistar rats, which also received oral gavage of water or SRR (1.08g/kg twice daily 3 days before and 4 days after MTX treatment), or calcium folinate (CF, a clinically used MTX antidote as a comparison, at 1mg/kg twice daily 36h after MTX treatment), or SRR and CF in combination. Animals were sacrificed 4 days after MTX treatment. Complete blood cell counting was carried out. Jejunum was analyzed histologically for mucosal damage, immunohistochemically for proliferating cell nuclear antigen (PCNA), and biochemically for thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH), as well as for tumor necrosis factor alpha (TNF-α). MTX treatment led to weight loss, leucopenia, polycythemia, increase in large thrombocyte ratio, intestinal villus atrophy, crypt loss and reduction in PCNA positive crypt cells, increases in mucosal TBARS and TNF-α and decrease in GSH. All these alterations were inhibited by SRR administration except leucopenia, and the effects of CF or CF plus SRR supplementation were found to be inferior to those of SRR. SRR can alleviate MTX-induced gut mucositis, which may be achieved by inhibiting MTX-induced oxidative stress and inflammatory response. These findings support the application of SRR in chemotherapy but not the combined application of SRR and CF.


Mortality prediction models for severe burn patients: Which one is the best?
For prediction of mortality and clinical course, various scoring systems had been developed. We choose four well known burn specific scoring systems and a general scoring system that using in Intensive Care Units. The primary outcome of this study was evaluate the predictive performances of this models and define the optimal one for our patient population. Variables analyzed were age, gender, burn type, total burned surface area (TBSA), total partial thickness burn area, total full thickness burn area, inhalation injuries, mechanical ventilation supports, blood products usage, total scores of Abbreviated Burn Severity Index (ABSI), revised Baux, Belgian Outcome in Burn Injury, Fatality by Longevity, Acute Physiology and Chronic Health Eval-uation II (APACHE II) score, Measured Extent of burn and Sex (FLAMES) and APACHE II, and their relations with mortality. In our study, a statistically significant relationship was found with mortality between age, TBSA, full thickness burn percent-age, inhalation injury, burn type, and it was similar to literature. Female gender was found to be a significant risk factor for mortality. We compared several burn mortality scoring systems and their predictional mortality rates. ABSI scores of patients for estimated mortality rates were similar to our mortality rate. Consequently, it was thought that ABSI was included all mortality-re-lated parameters.


Biolayer interferometry-SELEX for Shiga toxin antigenic-peptide aptamers & detection via chitosan-WSe2 aptasensor.
We report biolayer interferometry based in-vitro selection technique (BLI-SELEX) for fishing out specific aptamers against E. coli Shiga toxin subtypes viz., stx1 & stx2 via epitopic peptides. BLI-SELEX is a one-step technique for rapidly generating aptamers against protein biomarkers in a microtiter plate format, obliterating the need for multiple enrichment rounds to harvest high-affinity aptamers as in conventional SELEX. Two unique aptamers selected against stx1 & stx2 with picomolar Kd (~47 pM & ~29 pM, respectively) were successfully used to fabricate voltammetric diagnostic assay via immobilization onto chitosan exfoliated 2D tungsten diselenide (WSe2) nanosheet platform. These aptamers modified nanosensors showed high sensitivity of ~ 5.0 μA ng-1 mL, a dynamic response range from 50 pg mL-1 to 100 ng mL-1, with a detection limit of 44.5 pg mL-1 & 41.3 pg mL-1 for stx subtypes, respectively and showed low cross-reactivity in spiked urine, serum and milk samples. The synergistic effect of selective aptamers & high sensitivity imparted by 2D transition metal dichalcogenide (TMD) highlights the superior potential of a fabricated nanosensor for bacterial toxin detection.


Cyclodextrin-based sustained and controllable release system of insulin utilizing the combination system of self-assembly PEGylation and polypseudorotaxane formation.
Sustained and controllable release of insulin is strongly required to achieve the ideal treatment of diabetes. We previously developed "self-assembly PEGylation retaining activity (SPRA) technology" via a host-guest interaction between PEGylated β-cyclodextrin and adamantane-appended insulin, and resulting PEGylated insulin was termed SPRA-insulin. So far, we also demonstrated that covalently PEGylated insulin forms polypseudorotaxanes (PPRXs) with cyclodextrins (PPRX technology). In the present study, we designed and evaluated the combination system of SPRA technology and PPRX technology to achieve a sustained and controllable release system of insulin. SPRA-insulin formed PPRXs with α-cyclodextrin and γ-cyclodextrin. In addition, SPRA-insulin/cyclodextrin PPRXs provided sustained and controllable release of insulin beyond the each single technology both in vitro and in vivo. These results suggest that the combination system of SPRA technology and PPRX technology is useful for design of a sustained and controllable release system of insulin.


Intra- and interobserver variability of a fast on-line quantitative coronary angiographic system.
To evaluate intra- and interobserver variability of an on-line quantitative coronary angiographic system, 2 independent observers measured 166 primary lesions excluding total occlusions before and after coronary angioplasty. Each observer repeated his measurement 3 times at 14 days interval. The average percent diameter stenosis results obtained by observer 1 and 2 were almost identical, before (62.2% +/- 12.0% and 62.6% +/- 11.4%, NS) and after (27.1% +/- 12.0% and 26.9% +/- 11.3%, NS) angioplasty. Variability was expressed as 95% limits of agreement (mean difference +/- 2 x SD). The intra-observer variability of observer 1 ranged from -6.6% to 6.6% before angioplasty and from -9.6% to 9.6% after angioplasty. The corresponding limits of observer 2 were -8.0% to 7.5% and -8.3% to 8.5%, respectively. The interobserver variability ranged from -10.4% to 9.6% before versus -12.5% to 13.1% after angioplasty. This variability was not influenced by vessel size. The widening of the limits observed after angioplasty was largely due to an increased variability in the measurements of the absolute minimal luminal diameter but not of the reference segment. We conclude that the intra- and interobserver variability of measurements obtained with an on-line quantitative angiographic system used for guiding coronary interventions is acceptable and without systematic bias in any direction for a wide range of primary coronary stenoses. However, the variability increases when images are acquired immediately after angioplasty.


Omics AnalySIs System for PRecision Oncology (OASISPRO): a web-based omics analysis tool for clinical phenotype prediction.
Precision oncology is an approach that accounts for individual differences to guide cancer management. Omics signatures have been shown to predict clinical traits for cancer patients. However, the vast amount of omics information poses an informatics challenge in systematically identifying patterns associated with health outcomes, and no general purpose data mining tool exists for physicians, medical researchers and citizen scientists without significant training in programming and bioinformatics. To bridge this gap, we built the Omics AnalySIs System for PRecision Oncology (OASISPRO), a web-based system to mine the quantitative omics information from The Cancer Genome Atlas (TCGA). This system effectively visualizes patients' clinical profiles, executes machine-learning algorithms of choice on the omics data and evaluates the prediction performance using held-out test sets. With this tool, we successfully identified genes strongly associated with tumor stage, and accurately predicted patients' survival outcomes in many cancer types, including adrenocortical carcinoma. By identifying the links between omics and clinical phenotypes, this system will facilitate omics studies on precision cancer medicine and contribute to establishing personalized cancer treatment plans. This web-based tool is available at http://tinyurl.com/oasispro; source codes are available at http://tinyurl.com/oasisproSourceCode. Supplementary data are available at Bioinformatics online.


Effect of different zinc sources and levels on inhibition of the apoptosis induced by glucocorticoid of thymocytes in vitro.
This experiment was conducted to investigate the effects of zinc sulfate and zinc methionine (Zn-Met) and their levels on apoptosis induced by glucocorticoid of thymocytes and the possible mechanism. Dexamethasone was used to make the apoptosis model of thymocytes; zinc sulfate and zinc methionine were supplemented to the medium at levels of 0, 50, 100, 500, and 1000 microM. The activity of cells, Cu,Zn superoxide dismutase (Cu,Zn-SOD), DNA ladder pattern, intracellular calcium concentration, and the percentage of apoptosis nuclei were determined. Both ZnSO4 and Zn-Met could modulate apoptosis; they inhibited apoptosis and decreased DNA fragmentation. The regulation was concentration dependent. At levels of 50 and 100 microM, the effect of Zn-Met on inhibiting apoptosis was less efficient than that of ZnSO4 (p<0.05), but the activity of the cells cultured with Zn-Met was higher than those cultured with ZnSO4; they showed no difference in modulating apoptosis when added at levels of 500 and 1000 microM to the medium (p>0.05). Intracellular calcium concentrations of cells cultured with Zn-Met were higher than those cultured with ZnSO4 at the same levels. Zinc supplementation decreased the concentration of intracellular calcium significantly (p<0.05) and increased the activity of Cu,Zn-SOD in the extract of the cells (p<0.05). Both zinc sulfate and Zn-Met could modulate apoptosis of thymocytes induced by glucocorticoid; the mechanism might involve the exchange of intracellular calcium, the redox of cells, and the two forms of zinc might go different ways in the regulations.


2-deoxy-d-ribose induces apoptosis by inhibiting the synthesis and increasing the efflux of glutathione.
Oxidative stress is caused by imbalance between the production of reactive oxygen species (ROS) and biological system ability to readily detoxify the reactive intermediates or repair the resulting damage. 2-deoxy-D-ribose (dRib) is known to induce apoptosis by provoking an oxidative stress by depleting glutathione (GSH). In this paper, we elucidate the mechanisms underlying GSH depletion in response to dRib treatment. We demonstrated that the observed GSH depletion is not only due to inhibition of synthesis, by inhibiting gamma-glutamyl-cysteine synthetase, but also due to its increased efflux, by the activity of multidrug resistance associated proteins transporters. We conclude that dRib interferes with GSH homeostasis and that likely cellular oxidative stress is a consequence of GSH depletion. Various GSH fates, such as direct oxidation, lack of synthesis or of storage, characterize different kinds of oxidative stress. In the light of our observations we conclude that dRib does not induce GSH oxidation but interferes with GSH synthesis and storage. Lack of GSH allows accumulation of ROS and cells, disarmed against oxidative insults, undergo apoptosis.


[The diagnosis of phaeochromocytoma: sensitivity of vanillylmandelic acid and urinary catecholamine determination and the Katecult test (author's transl)].
Tumour weight was compared with maximal vanillylmandelic acid and catecholamine excretion in 24-hour urine in 21 patients with phaeochromocytoma. The tumour weight correlated both with vanillylmandelic acid (r = 0.805, P less than 0.001) as well as urinary catecholamine levels (r = 0.725, P less than 0.001). Normal vanillylmandelic acid excretion was found in seven patients; urinary catecholamine levels were abnormal in all patients. The Katecult test was additionally performed in ten patients, with nine positive results.


A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family.
A 1.4-kb full-length cDNA was isolated from a library constructed from activated human T-cell leukemia virus type 1-transformed human T-lymphocytes. Sequence analysis identified this cDNA as a new member of the human nerve-growth-factor receptor/tumor-necrosis-factor receptor family and as the potential human homologue of the murine sequence, 4-1BB. The gene encodes three cysteine-rich motifs in the extracellular domain which are characteristic of this receptor family, a transmembrane region and a short N-terminal cytoplasmic portion which contains potential phosphorylation sites.


Age-dependent Changes in Skeletal Muscle Mass and Visceral Fat Area in a Chinese Population.
The present study was conducted to demonstrate the age-dependent changes in skeletal muscle mass and visceral fat area in a population of Chinese adults aged 30-92 years old. A total of 6669 healthy Chinese men and 4494 healthy Chinese women aged 30-92 years old were assessed for their skeletal muscle mass and visceral fat area. The results showed age-dependent decreases in the total skeletal muscle mass indexes in both men and women aged 40-92 years old as well as age-dependent increases in the visceral fat area in men aged 30-92 years old and in women aged 30-80 years old. Multivariate regression models showed that the total skeletal muscle mass index was positively associated with the body mass index and negatively associated with the age and visceral fat area in both sexes. The loss of skeletal muscle mass becomes obvious at approximately 50 years of age, and the visceral fat area commences to increase at approximately 40 years of age in this Chinese population.


Pancreatic lipoma with a solid nodule mimicking invasion from adjoining intraductal papillary mucinous neoplasm.
A 74-year-old man was referred to our hospital for a mass in the pancreatic head found during screening chest computed tomography. Contrast computed tomography showed a 5-cm multicystic mass with an irregular border containing a solid component showing contrast enhancement. Caudal to this mass, a 5-cm solid mass of fat density with a nodular soft-tissue component was found. Cytology of the aspirated pancreatic fluid revealed malignant cells, and surgery was performed for suspected intraductal papillary mucinous carcinoma. Pathologic analysis of the resected specimen revealed a collision tumor of intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia and pancreatic lipoma. The soft-tissue component within the lipoma was a nodule consisting of pancreatic tissue with inflammatory infiltration and hyalinization and was not associated with IPMN invasion.


Chemical Synthesis and Oxide Dispersion Properties of Strengthened Tungsten via Spark Plasma Sintering.
Highly uniform oxide dispersion-strengthened materials W-1 wt % Nd₂O₃ and W-1 wt % CeO₂ were successfully fabricated via a novel wet chemical method followed by hydrogen reduction. The powders were consolidated by spark plasma sintering at 1700 °C to suppress grain growth. The samples were characterized by performing field emission scanning electron microscopy and transmission electron microscopy analyses, Vickers microhardness measurements, thermal conductivity, and tensile testing. The oxide particles were dispersed at the tungsten grain boundaries and within the grains. The thermal conductivity of the samples at room temperature exceeded 140 W/m·K. The tensile tests indicated that W-1 wt % CeO₂ exhibited a ductile-brittle transition temperature between 500 °C and 550 °C, which was a lower range than that for W-1 wt % Nd₂O₃. Surface topography and Vickers microhardness analyses were conducted before and after irradiations with 50 eV He ions at a fluence of 1 × 1022 m-2 for 1 h in the large-powder material irradiation experiment system. The grain boundaries of the irradiated area became more evident than that of the unirradiated area for both samples. Irradiation hardening was recognized for the W-1 wt % Nd₂O₃ and W-1 wt % CeO₂ samples.


The size structure of a lacustrine zoobenthic community.
Data from Mirror Lake, New Hampshire, are used to construct the first quantitative description of the size structure of a freshwater benthic animal community. Size spectra of the benthic animal community, whether expressed as animal density, biomass, species richness, or assimilation, are generally unimodal. These spectra are strikingly different from the characteristically bimodal size spectra reported for marine benthic communities. There is no indication in these size spectra that the meiofauna and macrofauna are distinct ecological entities in Mirror Lake, as has been suggested for marine benthic communities.


Non-seminomatous germ cell tumors of the testis: morphology of retroperitoneal lymph node metastases after chemotherapy.
Gross and histological examination of residual retroperitoneal mature teratoma revealed different findings in patients treated with PVB remission-induction chemotherapy with maintenance chemotherapy followed by an RLND 4-6 months after PVB chemotherapy (group I) as compared to patients who received PVB chemotherapy only and underwent an RLND after 4-6 weeks (group II). RLND specimens in group I predominantly contained mature teratoma with organoid differentiation, whereas the specimens in group II often consisted of small mature teratoma areas with less-differentiated structures next to large areas of fresh tumor necrosis. Our findings suggest that, either due to maintenance chemotherapy or due to a prolonged time interval between PVB remission-induction chemotherapy and RLND, mature teratoma grows and differentiates further from tissue level to organoid level.


Twisted molecule-based hyper-crosslinked porous polymers for rapid and efficient removal of organic micropollutants from water.
Organic micropollutants have become serious threats to human health and the environment over the past years. Novel materials and technologies are urgently needed to remove environmental contaminants. Herein, spirobifluorene (SBF) and triptycene (TP) were crosslinked to produce four hierarchically porous organic polymers (NHCPs). The twisted spatial structures of the monomers endow the NHCPs with high surface areas and abundant pores, which make them suitable for removal of pollutants in aqueous solution through adsorption. According to the results from adsorption experiments, the NHCPs exhibited high removal efficiency and adsorption capacities for pollutants in solution. Particularly, NHCP-3 could remove 99.4% of bisphenol A (BPA) in a few seconds with a maximum adsorption capacity of 562 mg g-1. Furthermore, the NHCPs could be easily recovered by immersion in ethanol and recycled at least five times without a loss in efficiency.


Treatment of neuropathic unstable knee osteoarthritis by a condylar, rotating-hinge prosthesis with cementless pentagonal stem: a case series.
Total knee arthroplasty (TKA) in the neuropathic unstable knee (NUK) setting is classically a challenging orthopedic problem due to intraoperative technical difficulties and a higher frequency of periprosthetic complications. More recently, satisfactory results have been reported using improved constraints, stems and revision-type TKA components. The study aims to present long-term results of a small case series with NUK osteoarthritis reconstructed by a condylar, semi-constrained prosthesis with a polygonal, hydroxyapatite-coated (HA-coated) press-fit stem. From 2009 through 2010, three knees in three patients with advanced NUK arthropathy underwent TKAs in our institution using the PENTA® prosthesis. The average age at surgery was 44 years (32-58). The patients were followed up for a mean period of 124 months (120-128). The etiology of NUK was determined to be poliomyelitis sequela in 2 cases and spinal cord injury in one case. Functional outcomes were assessed with Knee Society (KS) Knee and Function Scores, and radiological outcomes were evaluated with ISOLS radiographic implant scores. Patients were monitored for complications clinically and radiologically. KS knee scores improved from a mean of 12,3 (0-37) preoperatively to 71,3 (65-77) and KS function scores improved from a mean of 1,7 (0-5) preoperatively to 68,3 (55-80) at the latest follow-up. Radiological outcomes were excellent according to ISOLS scores, and no complications were observed. Although this is a small case series, the significant improvement in functional scores, excellent radiological outcome, and implant survival at the end of a long follow-up period warrants TKA with a semi-constrained hinged implant in the setting of NUK. PENTA® prosthesis offers a good choice of implant with its hydroxyapatite-coated, press-fit, pentagonal stem and precisely designed rotating hinge.


Monitoring alendronate and estradiol therapy with quantitative ultrasound and bone mineral density.
Few studies have compared quantitative ultrasound with bone mineral density (BMD) in monitoring response to therapy in osteoporosis. The aim of our study was to compare finger ultrasound variables and BMD for monitoring alendronate and estradiol therapy in postmenopausal women. We recruited 26 women aged 50 to 79 yr (mean: 65 yr) with osteoporosis; 18 patients received 10 mg/d of alendronate and 500 mg/d of calcium carbonate and 8 patients received 500 mg/d of calcium carbonate only. We recruited 21 hysterectomized postmenopausal women who were randomized to treatment or control. The treatment group received a 25-mg estradiol implant, which was replaced every 6 mo. The control group had a sham procedure. In the alendronate group, there were significant changes at 1 yr at the lumbar spine (p<0.05), bone transmission time (p<0.01), and pure speed of sound (p<0.001) and the changes continued into the second year. In the estradiol implant group, there were significant changes at 1 yr at the lumbar spine (p<0.001), the femoral neck (p<0.05), and the pure speed of sound (p<0.01). For alendronate, the signal-to-noise ratio was similar between the lumbar spine and bone transmission time (1.8 and 1.4) and greater than for the pure speed of sound and femoral neck (0.8 and 0.7); for estradiol, the signal-to-noise ratio was similar between the lumbar spine and femoral neck (2.0 and 1.5) and greater than for the pure speed of sound and bone transmission time (1.1 and 0.6). These results indicated that changes in finger ultrasound are similar in clinical utility to dual-energy X-ray absorptiometry measurements at the femoral neck for the monitoring of antiresorptive treatments for osteoporosis.


Acute scrotum due to edidymo-orchitis associated with vasal anomalies in children with anorectal malformations.
Epididymo-orchitis, an uncommon cause of acute scrotum in prepubertal boys, is infection or inflammation of epididymis and testis. Epididymo-orchitis may be associated with urinary tract infections or reflux of urine predisposed by an underlying vasal anomaly. Two infants with anorectal malformations who presented with acute scrotum are reported. The surgical exploration of the testes showed findings consistent with epididymo-orchitis. Further radiological investigations of urinary tract showed vasal anomalies in both patients. If a patient with anorectal malformation presents with acute scrotum, epididymo-orchitis should be suspected initially. Evaluations should be directed toward defining predisposing vasal anomaly, and appropriate therapeutic measures should be undertaken to prevent recurrences.


Genomic structure and assessment of the retinally expressed RFamide-related peptide gene in dominant cystoid macular dystrophy.
Computer-assisted sampling of EST data contained within the UniGene human sequences collection is being used to establish a catalog of novel genes that are expressed exclusively or predominantly in the human retina. This provides a valuable source for candidate genes possibly involved in retinal degeneration. In this report we present the characterization of the C7orf9 gene locus encoding RFamide-related peptides (RFRPs) and its evaluation in dominant cystoid macular dystrophy (CYMD). Bioinformatics and cDNA library screening were used to isolate the full-length cDNA sequence and to determine the genomic organization of C7orf9. Expression profiling was done by RT-PCR and Northern blot analysis. C7orf9 was evaluated as a candidate gene for CYMD by DNA sequencing and Southern blot analysis in two affected individuals from an extended Dutch CYMD family. The C7orf9 cDNA transcript consists of 1190 bp and is organized into 3 exons on the short arm of chromosome 7 within the critical region for CYMD. The transcript is specifically expressed in the retina but not in a large range of other human tissues. No disease-causing mutations or larger gene rearrangements were found. We provide the genomic organization of the RFamide-related peptide gene, C7orf9, which encodes a precursor protein for at least two small neuropeptides, referred to as NPSF (alias RFRP-1) and NPVF (alias RFRP-3) and show that it is abundantly expressed in the human retina. Results of our comprehensive mutation analysis suggests that C7orf9 is not the CYMD gene.


State-level response to gabapentin misuse in the United States: Implications and future direction.
Gabapentin misuse is on the rise and has forced many US states to mobilize policies to address this public health concern. The purpose of this manuscript is to update state-level gabapentin misuse-related policies in the US through September 1, 2021, discuss the benefits and risks of current measures, and highlight gaps in national response. Identification of state and federal district policy changes and deliberations related to gabapentin were searched via internet for all 50 states and 1 federal district (n = 51). Only results from state regulatory bodies, such as the board of pharmacy, or state legislative bodies, such as the senate, were considered for inclusion. Results showed that 22 states and federal districts (43.1%) tightened regulation, while another 2 (3.9%) are considering doing so. Of the 22 states and federal districts with policy changes, 15 (68.2%) enrolled gabapentin into their prescription drug monitoring program, while 7 (31.8%) reclassified gabapentin as a Schedule V controlled substance (C-V). Absent of federal guidance surrounding gabapentin misuse, the onus has fallen on individual states; thus, approaches have ranged from no intervention to reclassification as a C-V. These measures aim to reduce medication supply but fall short of addressing patient outcomes and reducing harm. Therefore, harm reduction-informed public health policies must be implemented to positively impact patient outcomes and enhance safety.


A nomogram to predict short-term outcome of radiotherapy or chemoradiotherapy based on pre/post-treatment inflammatory biomarkers and their dynamic changes in esophageal squamous cell carcinoma.
We initially aimed to investigate pre/post-treatment inflammatory biomarkers (pre/post-IBs) and their dynamic changes (delta-IBs) on the short-term outcome (STO) of radiotherapy or chemoradiotherapy in esophageal squamous cell carcinoma (ESCC). Furthermore, a nomogram was built to provide an accurate prediction of STO. The STO using the treatment response evaluation was assessed according to RECIST 1.1 at 1 month after radiotherapy or chemoradiotherapy. The IBs (absolute lymphocyte counts (ALC), neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), and lymphocyte/monocyte (LMR)) and clinical variables were collected and analyzed from 398 ESCC patients at Shandong Cancer Hospital between 2015 and 2019. The nomogram was then established for predicting STO. Pre-ALC and pre-LMR significantly increased, pre-NLR and pre-PLR significantly decreased during radiotherapy or chemoradiotherapy (all P < 0.001). Meanwhile, there was a positive correlation between delta-NLR as well as delta-PLR (r = 0.621) and delta-LMR (r = 0.613), whereas a negatively correlated between delta-LMR and delta-PLR (r = -0.573). Multivariate analysis indicated that gender [OR, 0.473; 95%CI, 0.274-0.816; P = 0.007], pre-ALC [OR, 0.554; 95%CI, 0.335-0.915; P = 0.021], pre-NLR [OR, 3.176; 95%CI, 1.733-5.823; P < 0.001], post-NLR [OR, 2.418; 95%CI, 1.271-4.600; P = 0.007] and delta-NLR [OR, 1.929; 95%CI, 1.035-3.595; P = 0.039] were statistically significant with STO. And c-index of the nomogram established by combining all independent predictors for STO was 0.770 [95%CI, 0.719-0.820]. Pre-NLR, pre-ALC, post-NLR, and delta-NLR were significant with STO in ESCC patients treated with radiotherapy or chemoradiotherapy. Further, pre-NLR had the best predictive value, and the developed nomogram with superior prediction ability for STO could assist in patients counseling and guide to make individual treatments.


The IMPACT-III (HR) questionnaire: a valid measure of health-related quality of life in Croatian children with inflammatory bowel disease.
To assess the reliability and validity of IMPACT-III (HR), a disease-specific, health-related quality of life instrument in Croatian children with inflammatory bowel disease. In a multicenter study, 104 children participated in a validation study of IMPACT-III (HR) cross-culturally adapted for Croatia. Factor analysis was used to determine optimal domain structure for this cohort, analysis of Cronbach's alpha coefficients to test internal reliability, ANOVA to assess discriminant validity, and correlation with Pediatric Quality of Life Inventory, Version 4.0 (PedsQL) using Pearson correlation coefficients to assess concurrent validity. Cronbach's alpha for the IMPACT-III (HR) total score was 0.92. The most robust factor solution was a 5-domain structure: Symptoms, Concerns, Socializing, Body Image, and Worry about Stool, all of which demonstrated good internal reliability (α=0.60-0.89), but two items were dropped to achieve this. Discriminant validity was demonstrated by significant differences (P<0.001) in mean IMPACT-III (HR) scores between quiescent and mild or moderate-severe disease activity groups for total (148 vs. 139 or 125) and following factor scores: Symptoms (84 vs. 71 or 61), Socializing (91 vs. 83 or 76), and Worry about Stool (significant only between quiescent and moderate-severe groups, 90 vs. 62, respectively). Concurrent validity of IMPACT-III (HR) with PedsQL showed significant correlation, which was strongest when similar domains were compared. IMPACT-III (HR) appears to be useful tool to measure health-related quality of life in Croatian children with Crohn's disease and ulcerative colitis.


Phagocytic activity in stressed mice: effects of alprazolam.
Mice exposed to a chronic auditory stressor and daily injected with alprazolam (1 mg/kg/day, s.c.) showed a reduction in stress-induced suppression of the in vitro and in vivo activity of phagocytosis, measured using the zymosan particle uptake method and the carbon clearance test, respectively. Pretreatment with Ro-15-1788 (10 mg/kg, s.c.), a central nervous system benzodiazepine antagonist, resulted in suppression of the effects of alprazolam in stressed mice.


Left ventricular diastolic dysfunction in patients with COPD in the presence and absence of elevated pulmonary arterial pressure.
Increased right ventricular afterload leads to left ventricular diastolic dysfunction due to ventricular interdependence. Increased right ventricular afterload is frequently present in patients with COPD. The purpose of this study was to determine whether left ventricular diastolic dysfunction could be detected in COPD patients with normal or elevated pulmonary artery pressure (PAP). Twenty-two patients with COPD and 22 matched control subjects underwent pulsed Doppler echocardiography. Left ventricular systolic dysfunction and other causes of left ventricular diastolic dysfunction (eg, coronary artery disease) were excluded in all patients and control subjects. PAP was measured invasively in 13 patients with COPD. The maximal atrial filling velocity was increased and the early filling velocity was decreased in patients with COPD compared to control subjects. The early flow velocity peak/late flow velocity peak (E/A) ratio was markedly decreased in patients with COPD compared to control subjects (0.79 +/- 0.035 vs 1.38 +/- 0.069, respectively; p < 0.0001), indicating the presence of left ventricular diastolic dysfunction. The atrial contribution to total left diastolic filling was increased in patients with COPD. This was also observed in COPD patients with normal PAP, as ascertained using a right heart catheter. The atrial contribution to total left diastolic filling was further increased in COPD patients with PAP. PAP correlated with the E/A ratio (r = -0.85; p < 0.0001). Left ventricular diastolic dysfunction is present in COPD patients with normal PAP and increases with right ventricular afterload.


Injuries in male professional football: A prospective comparison between individual and team-based exposure registration.
Methodological considerations of football injury epidemiology have only scarcely been described. The aim of this study was to evaluate the inter-rater agreement in injury capture rate and injury categorization for data registered in two different prospective injury surveillance audits studying the same two Norwegian male professional football clubs for two consecutive seasons, 2008-2009. One audit used team-based exposure (TBE) recording and the other individual-based exposure (IBE). The number of injuries recorded and corresponding injury rates (injuries/1000 h exposure) were compared between audits. Cohen's kappa and prevalence-adjusted bias-adjusted kappa (PABAK) coefficients were calculated for injury variables. Of 323 injuries included, the IBE audit captured 318 (overall capture rate 98.5%, training 98.9%, match 97.8%) and the TBE audit 303 injuries (overall capture rate 93.8%, training 91.4%, match 97.1%). Agreement analysis showed kappa and PABAK coefficients regarded as almost perfect (> 0.81) for 8 of 9 injury variables, and substantial (ƙ 0.75) for the variable injury severity. In conclusion, the capture rate for training injuries was slightly higher with IBE recording, and inter-agreement in injury categorization was very high.


Radiation therapy potentiates effective oncolytic viral therapy in the treatment of lung cancer.
Replication-competent oncolytic herpes simplex viruses with deletion of the gamma(1)34.5 gene preferentially replicate in and kill malignant cells. The gamma(1)34.5 gene codes for ICP 34.5, a protein that enhances viral replication, and is homologous to growth arrest and DNA damage protein 34 (GADD34), a radiation-inducible DNA repair gene. We hypothesized that radiation therapy may potentiate efficacy of oncolytic viral therapy by upregulating GADD34 and promoting viral replication. The A549 and H1299 lung cancer cell lines were infected with NV1066, an oncolytic herpes simplex virus, at multiplicities of infection (number of viral particles per tumor cell) of 0.1 to 0.5 in vitro with radiation (2 to 10 Gy) or without radiation. Viral replication was determined by plaque assay, cell-to-cell spread was determined by flow cytometry, cell kill was determined by lactate dehydrogenase assay, and GADD34 induction was determined by real-time reverse transcription-polymerase chain reaction and Western blot method. Evidence of synergistic cytotoxicity dependence with GADD34 induction is further confirmed by small inhibitory RNA inhibition of GADD34 expression. Using both the isobologram method and combination index method of Chou and Talalay, significant synergism was demonstrated between radiation therapy and NV1066 both in vitro and in vivo. As a result of such synergism, a dose reduction for each agent (2- to 6,000-fold) can be accomplished for a wide range of therapeutic effect levels without sacrificing tumor cell kill. This effect is correlated with increased GADD34 expression and inhibited by transfection of small inhibitory RNA directed against GADD34. These data provide the cellular basis for the clinical investigation of combined use of radiation therapy with oncolytic herpes simplex virus therapy in the treatment of lung cancer to achieve synergistic efficacy while minimizing dosage and toxicity.


Noninvasive beat-to-beat stroke volume computation during acute hydrostatic pressure changes in parabolic flight.
A three-element model of the cardiovascular system was used to monitor stroke volume (SV) changes during parabolic flight. Aortic blood flow was estimated from continuous arterial finger pressure and SV computed by integrating simulated aortic flow during each systole. SV was significantly higher in microgravity (microgravity) compared to 1 G whereas in hypergravity (hG), SV was significantly lower. Exponential SV transients were observed after the transitions to and from microgravity and the succeeding or preceeding hG phases. These SV transients present different time constants, which reflect two different mechanisms of cardiovascular adaptation to sudden gravitational changes. These results show that beat-to-beat computation of SV provides noninvasive information on circulatory adaptation to acute hydrostatic pressure changes.


Cross-cultural adaptation, reliability, and validity of the Turkish version of PedsQL 3.0 Arthritis Module: a quality-of-life measure for patients with juvenile idiopathic arthritis in Turkey.
The aim of this study was to describe the cultural adaptation, validity, and reliability of a Turkish version of the pediatric quality-of-life inventory (PedsQL) 3.0 Arthritis Module in a population with juvenile idiopathic arthritis (JIA). A total of 169 patients with JIA and their parents were enrolled in the study. The Turkish version of the childhood health assessment questionnaire (CHAQ) was used to evaluate the validity of related domains in the PedsQL 3.0 Arthritis Module. Both the PedsQL 3.0 Arthritis Module and CHAQ were filled out by children over 8 years of age and by the parents of children 2-7 years of age. Internal reliability was poor to excellent (Cronbach's alpha coefficients 0.56-0.84 for self-reporting and 0.63-0.82 for parent reporting), and interobserver reliability varied from good to excellent (intraclass correlation coefficient (ICC) 0.79-0.91 for self-reporting and 0.80-0.88 for parent reporting) for the total scores of the PedsQL 3.0 Arthritis Module. Parent-child concordance for all scores was moderate to excellent (ICC 0.42-0.92). The PedsQL 3.0 Arthritis Module and CHAQ were highly positively correlated, with coefficients from 0.21 to 0.76, indicating concurrent validity. We demonstrated the reliability and validity of quality-of-life measurement using the Turkish version of the PedsQL 3.0 Arthritis Module in our sociocultural context. The PedsQL 3.0 Arthritis Module can be utilized as a tool for the evaluation of quality of life in patients with JIA aged 2-18 years.


Interstitial hyperthermia using 27 MHz wire antennas and interstitial photodynamic therapy in a rat rhabdomyosarcoma: phantom and animal studies.
This paper deals with the interaction of interstitial hyperthermia (HT) and interstitial photodynamic therapy (PDT). Its main focus, however, is on a newly developed heating system; phantom studies as well as temperature-response data obtained from the in vivo experiments are presented. Heat was delivered by thin, flexible wire antennas operating at a frequency of 27 MHz. Measurements in muscle-equivalent phantom with infrared thermography were performed. Uniform heating over the inserted length of the antenna was obtained and impedance matching appears possible by simple variable air coils, thereby minimizing the reflected power to less than 20%. Light was obtained from an Argon-Dye laser system tuned to a wavelength of 625 nm at a dose rate of 75-100 mW per fiber to a total incident dose of 900 J from four linear light applicators. An experimental murine tumor (Rhabdomyosarcoma, type R-1) was transplanted in WAG/Rij rats and, after reaching an average diameter of 2 cm, the active component of haematoporphyrin derivative (HPD), Photofrin II, was injected intravenously. The tumors were subsequently implanted with four flexible catheters, through which either light or heat could be applied. Dose-response relationships for PDT alone, HT alone and PDT followed by HT were established with cure as endpoint. The animal experiments showed that with the use of low-frequency wires a good localized heat distribution in the tumors can be obtained. Moreover, this study showed that PDT and HT, in the proper sequence and only when optimal temperatures are reached, result in an augmented cytotoxicity on the tumor cells in vivo; i.e. a cure rate of 41% was obtained.


Effect of IGF-I on DNA, RNA, and protein loss associated with brain atrophy and impaired learning in diabetic rats.
Brain atrophy in diabetic dementia (DD) may be due to a catabolic state with DNA loss. Insulin-like growth factor (IGF) levels are reduced in diabetes, and IGF replacement may ameliorate brain protein loss. Subcutaneous minipumps released vehicle (Db + Veh) or IGF-I (Db + IGF-I) in diabetic rats. Brain wet, dry, and water weights as well as DNA, rRNA, poly(A)+ RNA, and protein contents per brain were significantly reduced in diabetic rats. In the remaining brain cells, there was a significant decline in ratios of (rRNA/DNA) and (protein/DNA). IGF-I administration partially prevented the loss of brain protein content independently of hyperglycemia (P < 0.03). This is the first demonstration of a severe disturbance in the brain protein regulatory pathway together with DNA loss in diabetes. Because Alzheimer's Disease (AD) is associated with a diabetes-like brain environment, a catabolic state may contribute to brain atrophy in sporadic AD as well as DD.


Regulation of neurotensin secretion in a mammalian C cell line: effect of dexamethasone.
We established in culture two colony clones of rMTC 44-2 cells, rMTC 44-2B and 44-2C which secrete substantially greater quantities of neurotensin (NT) than the parent cell line. We describe here the effects of the synthetic glucocorticoid, dexamethasone, on NT and cAMP release. Medium and intracellular levels of NT and cAMP were measured by specific RIAs. Long-term release experiments were performed in Dulbecco's Modified Eagle's Medium supplemented with 15% horse serum (DMEM). Short-term release experiments were performed in Krebs-Ringer-bicarbonate-glucose buffer (KRBG) supplemented with 1.0 mm Ca2+. Dexamethasone stimulated NT release and increased intracellular NT levels. The ED50 values for stimulation of NT release following 24 or 48 h incubation of cells in DMEM with dexamethasone were 5 X 10(-9) and 7 X 10(-9) M, respectively. Dexamethasone markedly enhanced intracellular levels of NT in rMTC 44-2 cells while it decreased cell growth. Cells pretreated with dexamethasone for 48 h released greater amounts of NT in response to Ca2+ (1.0 mM) with or without K+ (50 mM) or NE (10(-6) M) following a 10 min incubation with these substances in KRBG. This experimental paradigm was also used to measure the efflux of cAMP following a brief (10 min) exposure of cells to NE. We conclude that the rMTC 44-2B and 44-2C cells are useful tools for studying the effects of dexamethasone on the regulation of cell growth, as well as the secretion of NT and cAMP.


Density Functional Theory Study of the Formation of Naphthalene and Phenanthrene from Reactions of Phenyl with Vinyl- and Phenylacetylene.
Reaction pathways for polycyclic aromatic hydrocarbon growth from reactions of either vinyl- or phenylacetylene with a phenyl radical are proposed and investigated using density functional theory (DFT). B3LYP/TZVP calculations are performed to obtain structures of minima and saddle points as well as kinetic data, supplemented with BMK/TZVP single-point energy calculations. The pathways include a cis-trans isomerization via a radicalic four-membered ring intermediate, which has so far not been considered in the literature. The DFT approach is validated against coupled-cluster calculations of a model system representing this intermediate. The coupled-cluster calculations include single and double excitations as well as perturbative corrections for connected triples and are performed in a correlation-consistent cc-pVTZ basis.


A nanoelectromechanical biosensor based on precise quantification and control of DNA orientation.
We utilize spectral self-interference fluorescent microscopy (SSFM) to measure fluorophore height with sub-nm precision to precisely quantify DNA orientation. A novel polymeric 3D scaffold is used to functionalize the sensor surface and to control orientation of the surface anchored DNA.


Statistics, not memories: what was the standard of care for administering antenatal steroids to women in preterm labor between 1985 and 2000?
We determined the frequency of antenatal corticosteroid use for mothers with threatened premature delivery in 1985, 1990, 1995, and 2000. We next compared published data to the surveyed recollections of 302 obstetricians who were practicing during these years. Two points emerged. First, published reports reveal that the use of antenatal corticosteroids increased steadily, from 8% in 1985 to 20% in 1990, 52% in 1995, and 75% in 2000 (P <.001). Second, "expert" opinions derived from the recollections of practicing obstetricians consistently overestimated the actual use of antenatal corticosteroids during the year in question-31% versus 8% for 1985, 56% versus 20% for 1990, 78% versus 52% for 1995, and 92% versus 72% for 2000 (all Ps <.001). The use of antenatal corticosteroids by obstetricians in the past 15 years reveals a phenomenon that is widely recognized elsewhere-retrospective memories are often wrong, and when they are wrong they are not randomly wrong. Rather, recollections are systematically skewed toward an outcome that, in hindsight, is considered desirable (the "Monday morning quarterback" phenomenon). We offer a simple proposal. In determining the "standard of medical care," the legal system should rely on statistical data about doctors' performance rather than the recollections of experts about doctors' performance. The fallible memories of isolated experts are a crude second-best, far inferior to the data that they approximate. Widespread adoption of this view by professional physician organizations would dramatically increase the rationality of expert testimony in medical malpractice tort law.


Premarital hemoglobinopathy screening in Kayseri: a city in Middle Anatolia region of Turkey.
The aim of the present study was to report the frequency of β-thalassemia trait and other hemoglobinopathies in Kayseri province, which is located in Middle Anatolia of Turkey, as part of the premarital screening program. The study included subjects admitted to Family Planning Center for premarital screening test between January 2009 and March 2010. Blood samples of the couples were obtained during admission to the marriage office. Complete blood counts and hemoglobin (Hb) variant analysis were performed with automatic counter and capillary electrophoresis. A total of 10,261 people were screened. The prevalence of patients with the β-thalassemia trait was 1.71% (175/10261). Moreover, HbD Punjab and HbO Arab were the most common Hb variants after β-thalassemia trait with the frequencies of 0.36% and 0.09%, respectively. Only 2 HbS were detected in 15 months of screening time. In 2 couples both partners were found to be carriers of β-thalassemia trait, and both partners of 1 couple to be carrier of HbD. Kayseri is not a high-risk region according to Mediterranean parts of Turkey, but the city takes migrations apart from neighbor cities, migrations from East and South provinces because of its geographic and industrial situation. For that reason detecting carrier couples with premarital screening program is an effective way of controlling thalassemia major.


Comparison of seven phenotyping methods for Candida albicans.
Seven different phenotyping methods for strain differentiation of Candida albicans (auxonotyping, enzymotyping, resistotyping, Phongpaichit's morphotyping, Hunter's morphotyping and Odds and Abbott's biotyping method-1980 and 1983 versions) were compared on a single population of 94 strains. 77.6% of the strains belonged to auxonotyping 1, 59.6% to enzymotyping A, 34% to resistotyping B and 30.8% to BC, 40.4% to Phongpaichit's morphotyping 000,000 and 40.4% to Hunter's morphotyping 'No fringe/Smooth surface'. Using biotyping systems (1980 and 1983 versions), the most frequent biotypes were 145 (29.8%) and 147 (31.9%) respectively. The Discriminatory Index of Hunter and Gaston was employed to carry out comparisons among the different systems. The best discriminatory results, although far from ideal, were found using Phongpaichit's morphotyping (DI = 0.827) and Odds and Abbott's method (DI = 0.815 and 0.831--1980 and 1983 versions). A good discriminatory result was also found using Hunter's morphotyping method together with the biotyping of Odds and Abbott (1983 version). These approximated the ideal (DI = 0.950) and showed minimal difficulty in interpretation. The proposed combined method revealed high discrimination among the vulvovaginal strains, and suggested the absence of transmissible pathogenic strains.


Phylogenetic analysis and reconfiguration of genera in the cestode order Diphyllidea.
The generic boundaries of the Diphyllidea are reassessed based on parsimony and likelihood phylogenetic analyses of 28S rDNA (ribonucleic acid large subunit), 18S rDNA (ribonucleic acid small subunit), and COI (cytochrome oxidase subunit I) sequence data for 31 species representing morphological variation across the order. Trees resulting from these analyses yielded a number of well-supported clades that are congruent with unique morphological features mandating generic revision of the order and erection of at least two new genera. Species originally assigned to Echinobothriumvan Beneden, 1849 but bearing a corona of spines on the region of the scolex anterior to the bothria and posterior to the apical organ armature are transferred to Coronocestus n. gen.; members of this genus typically parasitize triakid sharks, although one report from a hemiscylliid shark exists. Species with lateral hooklets arranged in continuous bands, rather than in two distinct clusters, are transferred to Halysioncum n. gen.; all species parasitize batoids, mostly myliobatids and rhinopterids, but a few records also exist from arhynchobatids, rhinobatids, platyrhinids and urotrygonids. Our analyses support transfer of the five species originally assigned to MacrobothridiumKhalil and Abdul-Salam, 1989 owing to their lack of cephalic peduncle spines to Echinobothrium. As a consequence, Echinobothrium sensu stricto includes species both with and without spines on the cephalic peduncle, but all members of the genus possess lateral hooklets arranged in clusters on either side of the dorsal and ventral apical hooks. With respect to diphyllideans parasitizing catsharks, AhamulinaMarques, Jensen and Caira, 2012 is unique in possessing apical hooks but lacking lateral hooklets and DitrachybothridiumRees, 1959 is unique in entirely lacking scolex armature. By far the majority of species of Echinobothrium sensu stricto parasitize skates of the family Rajidae, guitarfish of the family Rhinobatidae, and stingrays of the dasyatid genera Taeniura Müller and Henle, Dasyatis Rafinesque, and Himantura Müller and Henle, although a single species each has been reported from Anacanthobatidae, Rhynchobatidae, Platyrhinidae and Myliobatidae. It now seems clear that while by far the majority of diphyllideans parasitize batoids, the diphyllideans parasitizing sharks, and catsharks in particular, remain problematic. Additional collections from these carcharhiniform hosts are likely to be particularly illuminating.


Effects of dietary lipid composition and inulin-type fructans on mineral bioavailability in growing rats.
This study reports the effects of feeding with a combination of inulin-type fructans (ITF) and fish oil (FO) on mineral absorption and bioavailability as part of a semipurified diet offered to rats. Male Wistar rats (n = 24) were fed a 15% lipid diet (soybean oil [SO] or a 1:0.3 fish:soybean oil mixture [FSO]) and diets containing the same sources of lipids supplemented with 10% ITF (Raftilose Synergy 1) ad libitum for 15 d. Feces and urine were collected for mineral analyses during the last 5 d of the test period. Fatty acid composition was determined in liver and cecal mucosa homogenates. Liver and bone mineral analyses were performed by atomic absorption spectrophotometry. Bone biomechanical analyses were evaluated by a 3-point bending test. Compared with the controls, ITF-fed rats had enlarged ceca and a significant decrease in cecal content pH (P < 0.001). The apparent mineral absorption was improved in these rats, and this effect was enhanced by dietary combination with FO for all minerals except for magnesium. Addition of ITF to the diet resulted in higher bone mineral content (calcium and zinc) and bone strength, but increased bone mineral content was only statistically significant in FO-fed animals. A decrease in liver iron stores (P = 0.015) was observed in rats fed FO, considering that ITF consumption returned to levels comparable to the SO control group. These findings confirm the positive influence of ITF on mineral bioavailability, which was potentiated by addition of FO to the diet.


Seed production and predispersal seed predation in the biennial composite species, Arctium minus (Hill) Bernh. and A. lappa L.
Comparison was made of the seed production of two species of burdock, Arctium minus (Hill) Bernh. and A. lappa L., which are found in a variety of recently disturbed habitats throughout Waterloo County, Ontario. The mean number of seeds per plant of A. minus was significantly greater, 13,400 compared with 8,200 seeds in A. lappa. The mean number of heads per plant was also greater for A. minus than for A. lappa, 338 versus 112 heads respectively. Above-ground biomass allocated to reproductive heads was similar in A. minus (44.2%) and A. lappa (43.7%). Significant variation in the mean number of seeds per head was observed in A. minus, ranging from 29.0 to 47.1. The between-plant variation in this character is significantly greater than the variation between populations from various sites.Predispersal seed predation by the microlepidopteran Metzneria lappella (Fam. Gelechiidae) resulted in 28% to 71% loss of seeds of A. minus at different sites. The observed loss in A. lappa was dramatically lower at 15.5%. The number of seeds attacked by one larval predator varied from 2 to 15 with means from 7 to 9. In addition, great variation in the number of seeds and the number of predators per head was observed. Larvae were randomly distributed among the heads at 4 of 7 sites and aggregated at the other sites. Seed predation per head greater than 60% was found with the aggregated larval distributions. Only rarely was the number of seeds attacked by a larva associated with the number of larvae in the head. The winter dispersal of heads of A. minus was much lower than that for A. lappa, 62.2% and 21.0% respectively. Also, the dispersal of seeds from heads differed between the two species. Only 21.8% of the seeds of A. minus were lost compared with a seed dispersal rate of 56.5% for A. lappa.


Arsenic entrapment by nanocrystals of Al-magnetite: The role of Al in crystal growth and As retention.
The nature of As-Al-Fe co-precipitates aged for 120 days are investigated in detail by High Resolution Transmission Electron Microscopy (HRTEM), Scanning TEM (STEM), electron diffraction, Energy Dispersive X-Ray Spectroscopy (EDS), Electron Energy-Loss Spectroscopy (EELS), and Energy Filtered Transmission Electron Microscopy (EFTEM). The Al present in magnetite is shown to favour As incorporation (up to 1.10 wt%) relative to Al-free magnetite and Al-goethite, but As uptake by Al-magnetite decreases with increasing Al substitution (3.53-11.37 mol% Al). Arsenic-bearing magnetite and goethite mesocrystals (MCs) are formed by oriented aggregation (OA) of primary nanoparticles (NPs). Well-crystalline magnetite likely formed by Otswald ripening was predominant in the Al-free system. The As content in Al-goethite MCs (having approximately 13% substituted Al) was close to the EDS detection limit (0.1 wt% As), but was below detection in Al-goethites with 23.00-32.19 mol% Al. Our results show for the first time the capacity of Al-magnetite to incorporate more As than Al-free magnetite, and the role of Al in favouring OA-based crystal growth under the experimental conditions, and therefore As retention in the formed MCs. The proposed mechanism of As incorporation involves adsorption of As onto the newly formed NPs. Arsenic is then trapped in the MCs as they grow by self-assembly OA upon attachment of the NPs. We conclude that Al may diffuse to the crystal faces with high surface energy to reduce the total energy of the system during the attachment events, thus favouring the oriented aggregation.


Correction to: Age-related differences in the attentional white bear.
This article was originally published with errors in the graphs. It has been republished with corrections.


Massive plexiform neurofibroma with associated meningo-encephalocoele and occipital bone defect presenting as a cervical mass.
The commonest skull manifestations in neurofibromatosis involve the orbit, with very few reports about occipital defects. We report a rare case of a 54-year-old lady with a massive plexiform neurofibroma extending from the auricular region down her left neck and into her shoulder, with an associated large left occipital and left petrous bone defect and extensive cerebellar meningo-encephalocoele, which presented with a relatively asymptomatic cervical mass and was treated with resection of the neurofibroma and advancement and rotational skin flaps.


Increased Lower Extremity Injury Risk Associated With Player Load and Distance in Collegiate Women's Soccer.
There is limited research regarding the impact of workload on injury risk specific to women's soccer. Wearable global positioning system (GPS) units can track workload metrics such as total distance traveled and player load during games and training sessions. These metrics can be useful in predicting injury risk. To examine the relationship between injury risk and player workload as collected from wearable GPS units in National Collegiate Athletic Association (NCAA) Division I women's soccer players. Case-control study; Level of evidence, 3. Lower extremity injury incidence and GPS workload data (player load, total distance, and high-speed distance) for 65 NCAA Division I women's soccer players were collected over 3 seasons. Accumulated 1-, 2-, 3-, and 4-week loads and acute-to-chronic workload ratios (ACWR) were classified into discrete ranges by z-scores. ACWR was calculated using rolling averages and exponentially weighted moving averages (EWMA) models. Binary logistic regression models were used to compare the 7:28 rolling average and EWMA ACWRs between injured and noninjured players for all GPS/accelerometer variables. The prior 1-, 2-, 3-, and 4-week accumulated loads for all GPS/accelerometer variables were compared between the injured and uninjured cohorts using 2-sample t tests. There were a total of 53 lower extremity injuries that resulted in lost time recorded (5.76/1000 hours "on-legs" exposure time; 34 noncontact and 19 contact injuries). The prior 2-week (7242 vs 6613 m/s2; P = .02), 3-week (10,533 vs 9718 m/s2; P = .02), and 4-week (13,819 vs 12,892 m/s2; P = .04) accumulated player loads and 2-week (62.40 vs 57.25 km; P = .04), 3-week (90.97 vs 84.10 km; P = .03), and 4-week (119.31 vs 111.38 km; P = .05) accumulated total distances were significantly higher for injured players compared with noninjured players during the same time frames. There were no significant differences in player load, total distance, or high-speed distance ACWR between injured and noninjured players for both the rolling averages and EWMA calculations. Higher accumulated player load and total distance, but not ACWR, were associated with injury in women's soccer players.


Screening of xenobiotic compounds degrading microorganisms using biosensor techniques.
A screening device based on microorganisms immobilised onto a Clark-type oxygen electrode was used to monitor the potential of these microorganisms for the degradation and detection of xenobiotic compounds especially their chlorinated derivatives. The sensitivity and specificity of various species of Pseudomonas, Sphinomonas, Ralstonia, Rhodococcus were characterised in relation to xenobiotic compounds by using biosensor techniques. The following groups of xenobiotics were subjects of investigation: chlorophenols, chlorobenzoates, 2,4-D, PCB, dibenzofurane and their putative intermediates. Using this simple setup it proved possible to screen microbial strains for their potential to catabolize aromatic and chloroaromatic compounds under oxygen consumption. In a kinetic regime, a reproducible signal was obtained within minutes. Based on these results the sensor technique was a suitable method for the rapid characterization of microorganisms and allowed to gather information about the substrate spectrum.


Modification of the BrdU/H33258 technique for flow cytometry based on the pH-dependence of the fluorescence of H33258 stained DNA.
A simple analytical method is described for the evaluation of cell cycle progression data by modification of the BrdU/H33258 technique for flow cytometry. This procedure allows to obtain quenched and unquenched DNA-histograms of cells containing BrdU-substituted DNA by staining with one dye only, namely H33258. Quenched histograms are obtained at pH = 7 and give information about how far cells have passed the cell cycle since the beginning of the incubation. The unquenched ones obtained at pH less than or equal to 4 of the staining solution give information about the actual position of the cells in the cell cycle.


Biotechnological advances on penicillin G acylase: pharmaceutical implications, unique expression mechanism and production strategies.
In light of unrestricted use of first-generation penicillins, these antibiotics are now superseded by their semisynthetic counterparts for augmented antibiosis. Traditional penicillin chemistry involves the use of hazardous chemicals and harsh reaction conditions for the production of semisynthetic derivatives and, therefore, is being displaced by the biosynthetic platform using enzymatic transformations. Penicillin G acylase (PGA) is one of the most relevant and widely used biocatalysts for the industrial production of β-lactam semisynthetic antibiotics. Accordingly, considerable genetic and biochemical engineering strategies have been devoted towards PGA applications. This article provides a state-of-the-art review in recent biotechnological advances associated with PGA, particularly in the production technologies with an emphasis on using the Escherichia coli expression platform.


The role of sexual minority stress and community involvement on disordered eating, dysmorphic concerns and appearance- and performance-enhancing drug misuse.
Prior research has established that sexual minority (SM) individuals are more likely to experience disordered body image behaviors and concerns than heterosexual individuals. This increased risk may be explained by minority stress theory - that SM individuals are subject to SM-specific stressors, leading to health disparities - but this has not yet been fully examined. Furthermore, this theory states that SM community involvement may mitigate negative outcomes. The current study examines whether minority stress is associated with screening positive for an eating disorder, screening positive for body dysmorphic disorder, and appearance- and performance-enhancing drug misuse in a sample of SM individuals (483 women and 479 men) in the US. This study also examines whether the effect of minority stress is moderated by SM community involvement. Logistic regressions were conducted for each type of minority stress (internalized homophobia, sexual orientation concealment, and heterosexist discrimination) interacting with community involvement. After correction for multiple comparisons, all minority stressors and community involvement were positively associated with increased odds of disordered body image behaviors and concerns, with no evidence of a buffering effect for community involvement. The lack of a buffering effect is contrary to minority stress theory and may inform future prevention efforts.


Simulating the impacts of ship emissions on coastal air quality: Importance of a high-resolution emission inventory relative to cruise- and land-based observations.
This work studied the impacts of ship emissions at a high temporal resolution on the real-time concentrations of PM2.5, NO2, and SO2 in urban harbors and coastal sea areas, taking the Yangtze River Delta (YRD) as an example. The WRF-Chem model with 3 nested grids and ship emissions derived from an automatic identification system (AIS) were combined to simulate the air quality. The AIS data showed significant temporal fluctuations in ship emissions, with hourly mean fluxes of approximately 1082.41 ± 444.41 and 593.55 ± 404.95 g/h/km2 near ports and in the channel waters of the YRD, respectively. The monthly mean contributions of shipping emissions reached 80.72% (2.15 ppbv) and 81.79% (8.79 ppbv) to ambient SO2 and NO2 in Ningbo Port, and 10.61% (6.96 μg/m3) to PM2.5 in Shanghai Port, respectively, regions with dense ship traffic. The relative differences in the PM2.5, SO2, and NO2 concentrations modeled using monthly and hourly ship emissions accounted for -10-15%, -10-30%, and - 5-30%, respectively. Compared with cruise- and land-based measurements, the simulations using hourly emissions were in much better agreement with the observations than those using monthly emissions and appropriately captured some air pollutant concentration peaks. Simulations during shipping-related periods with hourly ship emissions improved the normalized mean bias (NMBs) from -43.03%, 301.49%, and 223.02% to -27.28%, 90.45%, and 167.52%, respectively, for PM2.5, SO2, and NO2, highlighting the importance of using ship emissions with a fine temporal resolution. Our study showed that ignoring hourly fluctuations in ship emissions during air quality modeling leads to considerable uncertainties, especially in coastal urban areas and harbors with high ship activities. These results imply that data with a high temporal resolution, such as hourly ship emissions, are necessary to understand the realistic impacts of shipping traffic and to implement more precise control policies to improve coastal air quality.


Trajectories of Depressive Symptoms in Canadian Emerging Adults.
We identified courses of depressive symptoms in an epidemiological sample of emerging adults. We used latent class growth modeling to identify trajectories of depressive symptoms measured by the 12-item Center for Epidemiological Studies Depression Scale (CES-D) during a 14-year follow-up of 2825 Canadian youths aged 10 to 25 years enrolled in the National Longitudinal Survey of Children and Youth between 1994 and 2009. After adjustment for youth, parent, and family factors, the 3 distinct trajectories of depressive symptoms were minimal (55%; CES-D < 6), subclinical (39%; CES-D = 9-13), and clinical (6%; CES-D > 18). All trajectories exhibited a parallel course, with peak symptoms at 15 to 17 years of age. Subclinical and clinical symptoms were more common than minimal symptoms in female youths and in respondents with lower self-concept, lower socioeconomic status, poorer interpersonal relations, and chronic health conditions (P < .01). Among emerging adults, trajectories of depressive symptoms do not trend upward or downward, and variables associated with identified trajectories demonstrated dose-response effects that agreed with vulnerability-stress theories of depression.


Upper Urinary Tract Tumors: Variant Histology Versus Urothelial Carcinoma.
To evaluate stage at presentation and cancer-specific mortality (CSM) in upper urinary tract tumors according to histologic subtype. Within the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2016), we identified patients with upper urinary tract tumors with pure variant histology (UTVH) and pure upper urinary tract urothelial carcinoma (UTUC). Cumulative incidence plots, after propensity score matching for tumor and patient characteristics, addressed CSM. Subgroup analyses addressed efficacy of radical nephroureterectomy (RNU) in stage T1-2 and of chemotherapy in metastatic UTVH patients. Of all 11,809 upper urinary tract tumor patients, 154 (1.3%) harbored squamous cell carcinoma (SCC), 86 (0.7%) adenocarcinoma, 39 (0.3%) neuroendocrine carcinoma, 38 (0.3%) other UTVH, and 11,492 (97.3%) UTUC. UTVH patients were more likely to exhibit metastatic stage disease at diagnosis than UTUC (odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P < .01). After detailed matching for performance status, only SCC showed significantly higher CSM than UTUC (multivariate HR = 1.71; P < .01). Subgroup analyses in stage T1-2 RNU patients showed, relative to UTUC patients, no CSM differences for SCC or adenocarcinoma patients. No significant survival benefit for chemotherapy administration was identified in patients with metastatic SCC or metastatic adenocarcinoma. This study is limited by its sample size and the missing centralized pathologic review. Disease stage at diagnosis is more advanced in UTVH patients than UTUC. Across all stages, CSM is higher for SCC than for UTUC. However, in T1-2 stage disease, RNU results in similar survival in SCC or adenocarcinoma versus UTUC.


Human colonic intraepithelial lymphocytes regulate the cytokines produced by lamina propria mononuclear cells.
Using an in vitro autologous human system, the immunomodulatory function of colonic intraepithelial lymphocytes (IEL) on cytokine production by lamina propria mononuclear cells (LPMNC) has been investigated. In contrast to LPMNC, colonic IEL produced only low amounts of IL-10, interferon-gamma and interleukin-2. However, co-culture experiments (IEL + LPMNC) have shown that IEL can enhance the PHA-induced synthesis of IL-2 and interferon-gamma, but not IL-10 by LPMNC. Using a transwell filter culture system apparatus, this effect was shown not to require a cell-to-cell interaction. Thus, IEL in vitro may modulate the cytokine synthesis of LPMNC, through the production of soluble factors. This may prove highly relevant in the in vivo immune activation of the gastrointestinal mucosa.


Involvement of transforming growth factor-beta and thrombopoietin in the pathogenesis of myelodysplastic syndrome with myelofibrosis.
We investigated the cause of myelofibrosis and proliferation of megakaryocytes in myelodysplastic syndrome with myelofibrosis (MDS-MF (+)). Plasma-transforming growth factor-beta1 (PTGF-beta1) concentrations closely correlated with myelofibrosis grade in MDS-MF (+) and were higher than those in idiopathic myelofibrosis (IMF), essential thrombocythemia (ET), idiopathic thrombocytopenic purpura (ITP), MDS-without MF (MDS-MF (-)) or healthy volunteers (HV). Peripheral blood mononuclear cells from MDS-MF (+) patients expressed more TGF-beta1 mRNA than those from IMF, MDS-MF (-) or HV. When we immunostained bone marrow specimens of MDS-MF (+) for TGF-beta, the intensity of blasts was apparently higher than that of megakaryocytes, while in MDS-MF (-), megakaryocytes were immunostained with a similar intensity as that in MDS-MF (+), but blasts were negative for staining. In IMF, megakaryocytes, monocytes and small mononuclear cells representing CD34+ cells were all similarly stained with a much lower intensity than that of blasts in MDS-MF (+). The number of bone marrow megakaryocytes were increased the most in MDS-MF (+), followed by ET, ITP, MDS-MF (-) and NHL and correlated with plasma thrombopoietin (TPO) levels or with plasma TGF-beta1 levels, respectively, in each disease. Thus, in MDS-MF (+), both myelofibrosis and the increased megakaryocytes were ascribed to overproduction of TGF-beta1 from blasts.


Subarachnoid hemorrhage as a presentation of basilar artery dissection.
Subarachnoid hemorrhages caused by intracranial dissections are rare. The management of dissections in these cases not clear. Case report. An 82-year-old woman presented with acute drowsiness and vomiting. CT scan demonstrated extensive subarachnoid hemorrhage and hydrocephalus that subsequently required placement of ventriculoperitoneal shunt. Angiography revealed extensive basilar artery dissection and no aneurysms. The dissection did not produce a critical stenosis and, taking into consideration that the patient had a previous occlusion of her distal left vertebral artery, it was decided to manage the patient conservatively. On a 3-month follow-up, the patient was free of recurrent events. Basilar artery dissection can present with subarachnoid hemorrhage. No guidelines are available for management of basilar artery dissections and treatment should be tailored to the individual patient.


The effects of sodium bicarbonate supplementation at individual time-to-peak blood bicarbonate on 4-km cycling time trial performance in the heat.
The purpose of this study was to explore the effect of individualised sodium bicarbonate (NaHCO3) supplementation according to a pre-established individual time-to-peak (TTP) blood bicarbonate (HCO3-) on 4-km cycling time trial (TT) performance in the heat. Eleven recreationally trained male cyclists (age: 28 ± 6 years, height: 180 ± 6 cm, body mass: 80.5 ± 8.4 kg) volunteered for this study in a randomised, crossover, triple-blind, placebo-controlled design. An initial visit was conducted to determine TTP HCO3- following 0.2 g.kg-1 body mass (BM) NaHCO3 ingestion. Subsequently, on three separate occasions, participants completed a 4-km cycling TT in the heat (30 degrees centigrade; °C) (relative humidity ∼40%) following ingestion of either NaHCO3 (0.2 g.kg-1 body mass), a sodium chloride placebo (0.2 g.kg-1 BM; PLA) at the predetermined individual TTP HCO3-, or no supplementation (control; CON) . Absolute peak [HCO3-] prior to the 4-km cycling TT's was elevated for NaHCO3 compared to PLA (+2.8 mmol.l-1; p = 0.002; g = 2.2) and CON (+2.5 mmol.l-1; p < 0.001; g = 2.1). Completion time following NaHCO3 was 5.6 ± 3.2 s faster than PLA (1.6%; CI: 2.8, 8.3; p = 0.001; g = 0.2) and 4.7 ± 2.8 s faster than CON (1.3%; CI: 2.3, 7.1; p = 0.001; g = 0.2). These results demonstrate that NaHCO3 ingestion at a pre-established individual TTP HCO3- improves 4-km cycling TT performance in the heat, likely through enhancing buffering capacity.Highlights This is the first time NaHCO3 ingestion has been shown to improve 4-km cycling TT performance in conditions of high ambient heat.A smaller dose of NaHCO3 (0.2 g.kg-1 BM) is ergogenic in the heat, which is smaller than the dose typically ingested for sports performance (0.3 g.kg-1 BM). This is important, as gastrointestinal discomfort is typically lower as the dose reduces.This study suggests that the individualised time-to-peak HCO3- ingestion strategy with lower doses of NaHCO3 is an ergogenic strategy in conditions of high ambient heat.


Cardiac and pulmonary involvement in leptospirosis.
The clinico-pathological features of cardiac and pulmonary involvement were studied in seven cases of fatal leptospirosis. Petechial haemorrhages occurred in the heart and pericardium in all cases with blood-stained pericardial effusions in five. Interstitial myocarditis was noted in five patients and probably caused the changing electrocardiographic abnormalities and clinical cardiovascular effects during the illness. Sub-pleural and intrapulmonary haemorrhages occurred in all seven cases with pleural effusions in four. Pulmonary oedema was a striking feature during the early stages of the illness, while in patients surviving the first week of the disease infiltrative and proliferative lesions were common. The latter type of pulmonary changes occurred at a stage when acute renal failure was improving and were not related to the presence and severity of jaundice. The clinico-pathological profile of pulmonary involvement in leptospirosis appears to fall into an adult respiratory distress syndrome and, when present, carries a serious prognosis and would then be a prime factor in mortality. As clinical manifestations of pulmonary involvement appear late during the clinical illness and may be of abrupt onset, auscultatory and radiological surveillance becomes mandatory in severe leptospiral infections.


Adiponectin increases macrophages cholesterol efflux and suppresses foam cell formation in patients with type 2 diabetes mellitus.
Low levels of blood adiponectin contribute to an increased risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). To determine the mechanism through which adiponectin deficiency mediates accelerated cardiovascular disease in patients with diabetes, we investigated the effects of adiponectin on macrophage cholesterol deposition. 35 diabetic patients and 35 nondiabetic healthy subjects were recruited in this study. Macrophages from patients with diabetes mellitus were cultured in adiponectin-free or adiponectin-supplemented media and exposed to oxidized low-density lipoprotein cholesterol (OxLDL). Adiponectin treatment markedly suppressed foam cell formation in OxLDL-treated macrophages from diabetic subjects only, which was mainly attributed to an increase in cholesterol efflux. Adiponectin treatment significantly increased ATP-binding cassette transporter (ABC) ABCG1 mRNA and protein levels but not ABCA1, without affecting protein expression of scavenger receptors, including scavenger receptor-A (SR-A) and CD36 in diabetics. Pharmacological or genetic inhibition of liver X receptor α (LXRα) blocks the adiponectin-mediated ABCG1 expression, suggesting that LXRα activation is necessary for the attenuation of lipid accumulation of macrophages by adiponectin. In addition, deletion of the adiponectin receptor (adipoR1) in macrophages from diabetic patients accelerated foam cell formation induced by OxLDL. Finally, a strong positive correlation was noted between decreased serum adiponectin levels and impaired cholesterol efflux capacity both before and after adjustment for HDL-C and ApoAI in diabetic patients (both P < 0.001). The present study identifies reduced adiopoR signaling as a critical mechanism underlying increased foam cell formation and accelerated cardiovascular disease in diabetic subjects.


Immunoregulatory gene polymorphisms in Japanese women with preterm births and periodontitis.
Many studies have reported an association between periodontal disease and preterm birth, although this remains controversial. Cytokines and antibodies produced to give resistance to infection can enter the bloodstream and cause preterm labor. We analyzed maternal genetic polymorphisms in various immunoregulatory genes that could affect both preterm birth and periodontitis. A total of 1099 women referred to the Department of Obstetrics and Gynecology, Niigata University Medical and Dental Hospital were candidates for participation, 424 of whom refused, and 553 were excluded. The final number of subjects was 122 (51 with preterm birth, 71 with term birth). Genomic DNA was isolated from venous blood, and 22 polymorphisms were determined: IL-1A, IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, TNFA, TNFRI, TNFRII, FcγRIIA, FcγRIIB, FcγRIIIA, FcγRIIIB, and FcαR. Within five days of labor, periodontal parameters were evaluated, and bacteria from subgingival plaque were detected using real-time PCR. There was no difference in the prevalence and degree of periodontitis between term and preterm births. Chi-squared tests showed that an age <33 years and FcαR(+56)T/C alleles were associated with preterm birth. Multiple logistic regression analysis represented a model with significant fitness in which four variables were associated with preterm birth: maternal age, number of Aggregatibacter actinomycetemcomitans, IL-6(-572)G/C, and FcαR(+56)T/C. In conclusion, there was no association between preterm birth and periodontitis in this study. A. actinomycetemcomitans, IL-6, and FcαR were suggested to be associated with preterm birth. Multiple logistic regression models with both genetic and environmental factors would be useful for evaluating susceptibility to preterm birth.


Toxicology of isoproturon to the food crop wheat as affected by salicylic acid.
Isoproturon, a herbicide belonging to the phenylurea family, is widely used to kill weeds in soils. Recent study indicated that isoproturon has become a contaminant in ecosystems due to its intensive use, thus bringing environmental risks to crop production safety. Salicylic acid (SA) is one of the components in plant defense signaling pathways and regulates diverse physiological responses to biotic and environmental stresses. The purpose of the study is to help to understand how SA mediates the biological process in wheat under isoproturon stress. Wheat seeds (Triticum aestivum, cv. Yangmai 13) were surface-sterilized and placed on moist filter paper for germination. After 24 h, the germinating seeds were placed on a plastic pot (1 L) containing 1,120 g soil mixed with isoproturon at 4 mg kg(-1) soil. After 4 days, wheat leaves were sprayed with 5 mg L(-1) SA. The SA treatment was undertaken once a day and lasted for 6 days, when the third true leaf was well developed. For control seedlings, only water was sprayed. Seedlings were grown under a light intensity of 300 µmol m(-2) s(-1) with a light/dark cycle of 12/12 h at 25°C, and watered to keep 70% relative water content in soils. We investigated the role of SA in alleviating isoproturon-induced toxicity in the food crop wheat (T. aestivum). Plants exposed to 4 mg kg(-1) isoproturon showed growth stunt and oxidative damage, but concomitant treatment with 5 mg L(-1) SA was able to attenuate the toxic effect. Isoproturon in soils was readily accumulated by wheat, but such accumulation can be blocked significantly by SA application. Treatment with SA decreased the abundance of O(2) (.-) and H(2)O(2), as well as activities of antioxidant enzymes, and increased activities of catalase in isoproturon-exposed plants. The enzyme activities were confirmed by the native polyacrylamide gel electrophoresis. Further, an RT-PCR-based assay was performed to show that several transcripts coding antioxidant enzymes were increased with isoproturon but decreased by SA. The present results indicate that exogenous SA is able to improve the wheat tolerance to isoproturon toxicity.


Adverse reactions to tick-borne encephalitis vaccine: FSME-Immun.
Vaccination against tick-borne encephalitis with FSME-Immun vaccine was started in the Department of Infectious Diseases, University Medical School of Białystok, Poland, in 1992. No serious adverse reactions after vaccine administration were observed. Post-vaccine side effects were reported in 242 (11.3%) persons after the first dose (n = 2,135) and only in 14 patients (1.2%) after the second one (n = 1,183). These effects were mild and transitory. No relationship was observed between the frequency of adverse reactions, general or local, and the initial anti-TBE virus antibody titres or the age of the immunized individuals. Post-vaccine side effects were reported significantly more frequently among people not bitten by ticks.


Florence Nightingale bicentennial: 1820-2020. Her contributions to health care improvement.
In 2020 we celebrate the bicentennial of the birth of Florence Nightingale and 110 years from her death (1820-1910). This gives us the opportunity to remember her life and her achievements. She is mainly known for her contribution to the foundation of modern nursing in the British Empire and subsequently to the world. Besides her personal engagement in the Crimean War, she organized a professional training for nurses, wrote the first textbook on nursing ("Notes on Nursing") and took public positions in favor of health care and philanthropic funding. She was a militant for the rights of the women and for social justice. She was a pioneer of medical statistics and hospital management. Her activity is acknowledged worldwide.


Differential diagnosis of serous papillary carcinoma of the gynaecological tract and basal breast carcinoma: an immunohistochemical approach.
There is a high frequency of serous gynaecological and basal breast cancers in patients with germline BRCA1 mutations. These patients often undergo prophylactic salpingo-oophorectomies, where small tumours may be identified in which morphological distinction between primary serous and metastatic basal breast cancer may be problematic. These two cancer types share similar molecular genetics and have immunophenotypic overlap. We aimed to develop an immunohistochemical panel which could differentiate between these two tumour types. Immunohistochemistry was performed on a training set of 20 serous gynaecological and 20 basal breast cancers, from which a small differential panel was developed. This differential panel was tested in an additional validation set of serous and basal cancers. WT1, ER and CK5/6 expression successfully differentiated serous gynaecological and basal breast cancers. WT1 and ER expression was significantly more common in serous cancers and CK5/6 expression more common in basal cancers. There is considerable genetic, morphological and immunophenotypic overlap between serous gynaecological and basal breast cancers. A limited panel of WT1, ER and CK5/6 was found to optimally differentiate these tumour types. Differences in the expression of these proteins appear to reflect the expression pattern of their cell of origin, rather than identify aberrant oncogenic pathways.


Hepatotoxicity and Drug/Chemical Interaction Toxicity of Nanoclay Particles in Mice.
Nanomaterials are relatively new and unconventional materials with many useful properties, but their effects on biological systems are poorly understood. Nanoclay is a general term for layered mineral silicate nanoparticles that are ideally suited for use in clay-based nanocomposites. The potential biological hazards of nanoclays have not been addressed, however. Therefore, we investigated the in vivo effects and drug interactions of nanoclays. In mice, administration of nanoclay particles via the tail vein led to acute liver injury. Co-administration of nanoclay and carbon tetrachloride, paraquat, or cisplatin resulted in both liver and kidney injury. Our findings thus indicate that nanoclay particles are potentially hepato- and nephrotoxic.


Design and validation of high-density SNP array of goats and population stratification of Indian goat breeds.
Goats are the supporting pillars of rural economy contributing significantly to meat and milk production in India. It is a species targeted for fulfilling the interdependent goals of poverty reduction and creation of employment for supporting the rural income. The increased demand for goat products necessitates their genetic characterization and improvement to augment the production of native breeds. Bi-allelic, genome wide, densely placed single nucleotide polymorphism (SNP) markers are most suitable for this purpose. This paper describes the design and validation of an Affymetrix Axiom-based high-density (HD) SNP chip for goats. The array was designed using a panel of 225 samples from 15 diverse goat breeds of India. In total, more than 38 million high quality SNPs were subjected to stringent filtering and 626,975 SNPs were finally tiled on the array. The average coverage of SNPs in our chip is one SNP per four kilobase (kb), providing a denser coverage of the goat genome than previously available arrays. The HD chip (Axiom_Cahi) was validated by genotyping 443 samples from 26 indigenous goat breeds/populations. The results revealed 95.83% markers to be highly informative and polymorphic in Indian goats. Multivariate analysis indicated population structuring, as 15 breeds could be segregated using the designed array. Phylogenetic analysis suggested stratification of breeds by geographic proximity. This HD SNP chip for goats is a valuable resource for genomic selection, genome wide association as well as population genetic studies in goats.