[Certification in the healthcare system. What happens when the certificate is not awarded?].
A quality certification is nowadays an important competitive factor for clinics and other institutions in Germany. The best known procedures are certification according to the norm DIN EN ISO, the German certification procedure in the healthcare system KTQ (Cooperation for Quality and Transparency in Healthcare) and the procedures of the German Cancer Society or medical professional societies. The majority of German clinics, centers, practices and nursing institutions are certified according to one of these procedures. In some areas certification is mandatory and a prerequisite for patient care, e.g. for rehabilitation institutions. But even in the field of acute medicine certification is an important proof that quality requirements have been fulfilled and has an effect on the economic situation. The aim of a visitation or audit is always to check whether the requirements of the appropriate certification procedure have been fulfilled. The actual procedure and the course can however, be organized differently. The failure to obtain certification is a very unpleasant situation for all concerned and can have negative effects on the image of the institution. Such a failure can most probably be avoided by good preparation and if necessary external consultation or internal qualification by colleagues. In most cases the certificate can be successfully obtained at least by the second attempt. Appropriate regulations are made by all procedures. Basically a thorough cost-benefit analysis should be carried out before deciding to apply for certification.


Outcomes of two-step haploidentical allogeneic stem cell transplantation in elderly patients with hematologic malignancies.
Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the best curative option for the majority of patients with hematologic malignancies (HM); however, many elderly patients are excluded from transplant and outcome data in this population is still limited. The novel two-step graft engineering approach has been the main platform for allo-SCT at Thomas Jefferson University since 2006. Following administration of the preparative regimen, we infuse donor lymphocytes, followed by cyclophosphamide to induce bidirectional tolerance, then infusion of CD34-selected cells. A total of 76 patients ≥ 65 years old with HM underwent haploidentical (haplo) allo-SCT on the two-step transplant platform between 2007 and 2021. The median time to neutrophil engraftment was 11 days and platelet engraftment was 18 days. With a median follow up of 44 months, the 3-year overall survival (OS) and progression-free survival (PFS) were 36.3% and 35.6%, respectively. The cumulative incidences of non-relapse mortality (NRM) and relapse at 3 years were 43.5% and 21.0% at 3 years, respectively. The cumulative incidence of grade III-IV acute graft-versus-host-disease (GVHD) was 11.1% at 6 months, and chronic GVHD requiring treatment was 15.1% at 2 years. The two-step haplo allo-SCT is a novel alternative platform for high-risk older HM patients, achieving fast engraftment, low relapse rates and promising survival.


A water-soluble derivative of prazosin prazosinamine hydrochloride [1-(4'-amino-6',7'-dimethoxyquinazolin-2'-yl)-4-(6''-aminohexanoyl) piperazine hydrochloride], reversibly inhibits the calcium-mobilizing action of alpha 1-adrenergic agonists in the perfused rat liver.
A newly-synthesized derivative of prazosin, prazosinamine hydrochloride, was examined for its ability to antagonize the interaction of the alpha 1-adrenergic agonist phenylephrine with liver cells. Using a Ca2--selective electrode to measure changes in perfusate Ca2+ concentration, prazosinamine was found to be as effective as prazosin in inhibiting the phenylephrine-induced efflux of Ca2+ from the perfused liver. Maximal and half-maximal inhibition occurred at 150 nM and 25 nM prazosinamine, respectively. Prazosinamine appears to share the alpha 1-specificity of prazosin, but has other unique and desirable properties. Its solubility in aqueous media is about three orders of magnitude higher than that of prazosin. Also, its antagonistic effects are rapid in onset, and are reversed within seconds of terminating its infusion into the liver. These attributes seem to make this agent more useful than prazosin for adrenergic receptor studies in perfused tissues. The molecule can also be readily coupled to other ligands.


Stable oxygen and hydrogen isotope composition of leaf water in C3 and C4 plant species under field conditions.
In this paper we make comparisons between the observed oxygen and hydrogen stable isotope composition of leaf water and the predictions of the Craig-Gordon model of evaporative isotopic enrichment. Comparisons were made among two C3 species (Chenopodium album and Helianthus annuus) and two C4 species (Amaranthus retroflexus and Kochia scoparia), when plants were exposed to natural environmental conditions in the field. There were significant differences among the species for the hydrogen and oxygen isotopic composition of leaf water at mid-day. The Amaranthus and Helianthus plants had lower leaf water δD and δ18O values than did Kochia and Chenopodium. The observed leaf water δ values were significantly lower than those predicted by the evaporative enrichment model for all the species. The degree of discrepancy between the observed and modelled leaf water isotopic compositions differed among species. There was a strong linear relationship between the oxygen and hydrogen isotopic compositions of stem water, observed leaf water and the modelled leaf water for all species. The observed leaf water isotopic composition for the different species occurred at different points along the line connecting the stem water isotopic composition and the modelled leaf water isotopic composition in a plot of δD and δ18O. We interpret these linear relationships as mixing lines between the unfractionated source or stem water isotopic composition and the isotopic composition of water at the evaporation sites within leaves (as defined by the evaporative enrichment model).


Gut Epithelial-derived CXCL9 Maintains Gut Homeostasis Through Preventing Overgrown E. coli.
Increased E. coli in the colon are related to the occurrence and development of multiple diseases. Chemokines are shown to possess potential antimicrobial activity, including against Gram-positive and -negative bacterial pathogens. We here investigated function[s] of chemokine CXCL9 expressed in the gut epithelial cells, and mechanism[s] of CXCL9 by which to kill E. coli. We generated CXCL9fl/flpvillin-creT mice [pvillin-cre positive mice] and their control CXCL9fl/flpvillin-crewmice [pvillin-cre negative mice], and then employed a dextran sulphate sodium [DSS]-mediated colitis model to determine the sensitivity of CXCL9fl/flpvillin-creT mice. We analysed the composition of the gut microbiota by using 16S ribosomal RNA [V3-V4 variable region] sequencing and shotgun metagenomic analyses. We generated E. coli ΔFtsX [FtsX-depleted E. coli] and E. coli ΔaceE [aceE-depleted E. coli] by using a bacterium red recombining system to investigate the mechanism[s] of CXCL9 by which to kill E. coli. CXCL9 fl/flpvillin-creTmice were more sensitive to chemically induced colitis than their control littermates, CXCL9fl/flpvillin-crewmice. After DSS treatment, there were markedly increased gut E. coli [Escherichia-Shigella] in the colonic contents of CXCL9fl/flpvillin-creT mice as compared with control CXCL9fl/flpvillin-crew mice. The increased E. coli could promote colitis through NLRC4 and caspase 1/11-mediated IL-18, which was derived from gut epithelial cells. We finally demonstrated that CXCL9 expressed in gut epithelial cells could kill the overgrown E. coli. E. coli expressed Ftsx and PDHc subunits aceE. E.coliΔaceE but not E. coliΔFtsX were resistant to CXCL9-mediated killing. Gut epithelial cells-derived CXCL9 can kill the expanded E. coli through aceE, to remain gut homeostasis.


Enhancement of pentobarbital-induced sleep by apigenin through chloride ion channel activation.
This experiment was performed to investigate whether apigenin has hypnotic effects and/or enhances pentobarbital-induced sleep behaviors through the GABAergic systems. Apigenin prolonged sleep time induced by pentobarbital similar to muscimol, a GABA(A) receptors agonist. Apigenin also increased sleep rate and sleep time in the combined administration with pentobarbital at the sub-hypnotic dosage, and showed synergic effects with muscimol in potentiating sleep onset and enhancing sleep time induced by pentobarbital. In addition, both of apigeinin and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Apigenin increased glutamate decarboxylase (GAD) and had no effect on the expression of GABA(A) receptor α-, β-, γ-subunits in n hippocampus of mouse brain, showing different expression of subunits from pentobarbital treatment group. In conclusion, it is suggested that apigenin augments pentobarbital-induced sleep behaviors through chloride ion channel activation.


Commentary on: "Randomized phase III trial of temsirolimus and bevacizumab versus interferon alfa and bevacizumab in metastatic renal cell carcinoma: INTORACT trial." Rini BI, Bellmunt J, Clancy J, Wang K, Niethammer AG, Hariharan S, Escudier B. Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Joaquim Bellmunt, University Hospital del Mar-IMIM, Barcelona, Spain; Jill Clancy, Kongming Wang, Andreas G. Niethammer, Subramanian Hariharan, Pfizer, New York, NY; and Bernard Escudier, Institut Gustave Roussy, Villejuif, France.: J Clin Oncol. 2014 Mar 10;32(8):752-9; doi: 10.1200/JCO.2013.50.5305. [Epub 2013 Dec 2].
To prospectively determine the efficacy of combination therapy with temsirolimus plus bevacizumab versus interferon alfa (IFN) plus bevacizumab in metastatic renal cell carcinoma (mRCC). In a randomized, open-label, multicenter, phase III study, patients with previously untreated predominantly clear cell mRCC were randomly assigned, stratified by prior nephrectomy and Memorial Sloan-Kettering Cancer Center prognostic group, to receive the combination of either temsirolimus (25mg intravenously, weekly) or IFN (9MIU subcutaneously thrice weekly) with bevacizumab (10mg/kg intravenously, every 2weeks). The primary end point was independently assessed progression-free survival (PFS). Median PFS in patients treated with temsirolimus/bevacizumab (n = 400) versus IFN/bevacizumab (n = 391) was 9.1 and 9.3 months, respectively (hazard ratio [HR] = 1.1; 95% CI: 0.9 to 1.3; P = .8). There were no significant differences in overall survival (25.8 ν 25.5 months; HR = 1.0; P = .6) or objective response rate (27.0% ν 27.4%) with temsirolimus/bevacizumab versus IFN/bevacizumab, respectively. Patients receiving temsirolimus/bevacizumab reported significantly higher overall mean scores in the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI)-15 and FKSI Disease-Related Symptoms subscale compared with IFN/bevacizumab (indicating improvement); however, no differences in global health outcome measures were observed. Treatment-emergent all-causality grade≥3 adverse events more common (P<.001) with temsirolimus/bevacizumab were mucosal inflammation, stomatitis, hypophosphatemia, hyperglycemia, and hypercholesterolemia, whereas neutropenia was more common with IFN/bevacizumab. Incidence of pneumonitis with temsirolimus/bevacizumab was 4.8%, mostly grade 1 or 2. Temsirolimus/bevacizumab combination therapy was not superior to IFN/bevacizumab for first-line treatment in clear-cell mRCC.


Heat shock factor OsHsfB2b negatively regulates drought and salt tolerance in rice.
Expression of OsHsfB2b was strongly induced by heat, salt, ABA and PEG treatments. Drought and salt tolerances were significantly decreased by OsHsfB2b overexpression, but were enhanced by RNA interference. Plants have more than 20 heat shock factors (Hsfs) that were designated class A, B, and C. Many members of Class A Hsfs were characterized as activators of transcription, but the functional roles of class B and C Hsfs have not been fully recognized. OsHsfB2b is a member of class B Hsfs in rice (Oryza sativa). Expression of OsHsfB2b was strongly induced by heat, salt, abscisic acid (ABA) and polyethylene glycol (PEG) treatments but was almost not affected by cold stress. Drought and salt tolerances were significantly decreased in OsHsfB2b-overexpressing transgenic rice, but were enhanced in the OsHsfB2b-RNAi transgenic rice. Under drought stress, the OsHsfB2b-overexpressing transgenic rice exhibited increased relative electrical conductivity (REC) and content of malondialdehyde (MDA) and decreased proline content compared with the wild type, while the lower REC and MDA content and increased proline content were found in the OsHsfB2b-RNAi transgenic rice. These results suggest that OsHsfB2b functions as a negative regulator in response to drought and salt stresses in rice, with its existing B3 repression domain (BRD) that might be necessary for the repressive activity. The present study revealed the potential value of OsHsfB2b in genetic improvement of rice.


Effect of different LED light quality combination on the content of vitamin C, soluble sugar, organic acids, amino acids, antioxidant capacity and mineral elements in green onion (Allium fistulosum L.).
The effects of blue-white, green-white, yellow-white, and red-white light combinations on the nutrient composition and antioxidant capacity of pseudo-stems and leaves of 'Yuanzang' green onion were investigated using light-emitting diodes (LEDs) with precise modulation of light quality, using white light as the control. The results showed that the leaf pigment, vitamin C, soluble sugar, organic acids, free amino acids, mineral elements, and antioxidant levels were significantly higher in green onion under blue-white combined light treatment, followed by white and red-white combined light, while green-white and yellow-white combined light significantly reduced fruit quality and antioxidant capacity. In conclusion, supplementation with blue LED light was the most effective light condition to improve palatability, nutritional value, and storage resistance of green onion by enhancing various nutrients in the plants, increasing antioxidant levels, and delaying plant aging.


Electron microscopic examination of skin and conjunctival biopsy specimens in neuronal storage diseases.
Skin and conjunctival biopsy specimens from fourteen patients with neuronal storage diseases were investigated using an electron microscope. The diseases were Tay-Sachs disease, ceroid-lipofuscinosis (Jansky-Bielschowsky type), Niemann-Pick disease (type B), highly suspected adrenoleukodystrophy, I-cell disease, mucolipidosis of the beta-galactosidase deficient type, Hurler disease, Hunter disease and Morquio disease. This examination provided valuable diagnostic information on some neuronal storage diseases but not on Morquio disease or highly suspected adrenoleukodystrophy. False negative results may sometimes occur using this examination method. However, this examination suggests the usefulness of skin and conjunctival biopsy specimens as a diagnostic tool in some neuronal storage diseases.


Is the pure and impure distinction of orbital fractures clinically relevant with respect to ocular and periocular injuries? A retrospective study of 473 patients.
To determine the association of "pure" orbital fractures (POF) and "impure" orbital fractures (IOF) with ocular and periocular injuries. A retrospective study of patients with orbital fractures was designed. The predictor variable was the orbital's fracture configuration (pure versus impure). The primary outcome variables were ocular and periocular injuries classified as mild, moderate, and severe. The secondary outcome was the need for surgical repair. Standard statistics for patient characteristics, the Fisher exact test for categorical variables, and the Mann-Whitney U test for continuous variables were computed to compare fractures. The sample was composed of 473 patients (220 POF and 253 IOF). No significant association between the two groups with regard to ocular and periocular injuries was found. Combined medial wall and floor fractures and naso-orbito-ethmoidal (NOE) fractures had the highest incidence of severe injury (34.5%, p = 0.02). Le Fort fractures were associated with moderate ocular and periocular injuries (36.4%, p = 0.01). Impure orbital fractures were more frequently associated with the need for surgical treatment (p = 0.04) than were POF. The present study has demonstrated that the pure and impure distinction of orbital fractures was not clinically relevant with respect to ocular and periocular injuries. However, our findings seem to suggest that other parameters such as the direction of the impact and/or its magnitude, rather than merely the pure or impure configuration, could be involved in determining the risk of developing concomitant ocular and periocular injuries.


Analysis of the drivers of CO2 emissions and ecological footprint growth in Australia.
This paper investigates the determinants of environmental degradation in Australia from 1990 to 2017, using ecological footprint analysis and the well-established logarithmic mean Divisia index (LMDI) decomposition method. Additionally, decoupling factor analysis was performed to examine the link between environment related variables (CO2 emissions and ecological footprint) and their determinants such as real income and population. The decomposition analysis considered the impact of five different factors on CO2 emissions: income effect, population, energy intensity, energy structure, and carbon intensity. For decoupling factor analysis, the link between ecological footprint and its two determinants, real income and population, was examined. Furthermore, the possible decoupling between CO2 emissions and these determinants was also analyzed, because CO2 emissions are the main cause of the country's increasing ecological footprint. The present study has a more comprehensive approach because it analyzes the factors affecting environmental degradation in Australia by assigning two proxies (CO2 emissions and ecological footprint) as dependent variables. The results confirmed that Australia's ecological reserve substantially declined over the past three decades due to deforestation and energy industries. The LMDI results demonstrated that income effect, population, and carbon intensity were the main factors that raised Australia's CO2 emissions, whereas the energy intensity factor substantially curbed them. The reducing impact of energy structure on CO2 emissions was minimal; thus, Australia was not able to prevent an upward trend in CO2 emissions. Lastly, an analysis of Australia's CO2 emissions according to economic activities was conducted for the period between 1990 and 2017 in order to understand other factors that may have affected environmental sustainability.


Transplant Kidney Retrograde Ureteral Stent Placement and Exchange: Overcoming the Challenge.
To present a reliable technique for fluoroscopic controlled, large-bore, ureteral stent placement and exchange in transplant kidneys with persistent ureterovesical strictures. We reviewed the medical charts of all patients who underwent kidney transplant with persistent ureterovesical strictures who underwent ureteral stent placement or exchange at our institution between 2005 and 2015 using the new technique. Clinical characteristics and treatment outcomes of the study cohort were analyzed. Ureteral stent insertion or stent exchange, using this technique, was performed in 32 renal transplant units. Median operating time was 24 minutes (interquartile range, 21-36.75 minutes). The overall success rate of the technique at first attempt was 96.9%. In 1 patient, drainage of the transplanted kidney with a nephrostomy tube was indicated after procedure failure. No other local or systemic complications were encountered, and no stent encrustation was noted in this cohort of patients. Renal function remained stable in all patients during a median follow-up of 59 months (interquartile range, 28-61 months). Herein, we present in detail a step-by-step technique for the insertion and exchange of large-bore ureteral stents in transplanted kidneys. The technique was shown to be safe, effective, and highly successful.


Comparison of retinol-binding protein and beta 2-microglobulin determination in urine for the early detection of tubular proteinuria.
The specificity, sensitivity and stability of beta 2-microglobulin (beta 2-m) and retinol-binding protein (RBP) in urine as indices of tubular proteinuria were compared. In vitro experiments show that RBP in urine is stable down to pH 4.5, whereas beta 2-m degrades below pH 5.5. This was confirmed by the relationships between pH and the concentration of both proteins in the urines from 150 healthy subjects. Urinary RBP was independent of pH (r = 0.125) but in contrast at pH below 6, beta 2-m concentration was inversely correlated with pH (r = 0.54, p less than 0.05). The comparison of urinary excretion of RBP and beta 2-m in 68 patients with renal diseases shows that in absence of a pH effect, the sensitivity and specificity of both proteins as indices of tubular proteinuria are rather similar. Therefore, in view of its greater stability in urine, RBP appears to be a more practical and reliable index of proximal tubular function than beta 2-m.


The Effect of Curcumin on the Expression of INFγ, TNF-α, and iNOS Genes in PBMCs Infected with Leishmania major [MRHO/IR/75/ER].
Leishmaniasis, caused by the Leishmania parasite, is one of the most important tropical neglected diseases. The urgent search for effective, inexpensive, and preferably herbal anti-leishmanial agents, is needed. Curcumin is a natural polyphenolic compound derived from turmeric that is well known for its antioxidant, anti-inflammatory, anti-tumor, and anti-cancer activity. The present work evaluates the anti-leishmanial [Leishmania major] activity of curcumin. The infected PBMCs were treated with curcumin. The ROS level at 6, 12, 24 h and gene expression levels at 24, 48, and 72 h of PBMCs after treatment with curcumin were determined. Based on the results, the curcumin concentrations of 268 μM [24 h] and 181.2 μM [72 h] were defined as IC50 against L. major promastigotes. Treatment of L. major infected-peripheral blood mononuclear cells [PBMCs] with IC50 concentrations of curcumin, depending on exposure time, significantly induced the reactive oxygen species [ROS] generation and increased the expression levels of interferongamma [IFN-γ], tumor necrosis factor-alpha [TNF-α], and nitric oxide synthase [iNOS] genes. These findings suggest the potential of curcumin against Leishmaniasis.


The in vitro effect of prolactin on the growth, motility and expression of prolactin receptors in larvae of Toxocara canis.
The in vitro effect of prolactin (PRL) on the growth and motility of Toxocara canis larvae was assessed. Additionally, the expression and location of prolactin receptors (PRL-Rs) were determined in the larvae. Larvae of T. canis were incubated with different concentrations of PRL for different periods of time. The stimulated larvae accelerated their enlargement and increased their motility. The mean percentage of PRL-R+ cells in non-stimulated larvae, measured by flow cytometry was 7.3±0.3%. Compared with non-stimulated larvae, the mean fluorescence intensity (p<0.05) increased in larvae incubated with 40ng/mL of PRL for 10 days. A 465-bp length fragment was amplified from larvae gDNA by PCR. The sequence of this fragment showed 99% similarity with the gene fragment that codes for the PRL-R of the domestic dog. A high concentration of PRL-Rs was immune-located in the posterior region of the larval intestine; therefore, the intestinal cells in this region were most likely the targets for this hormone. Based on these results, PRL-Rs were identified in T. canis larvae, and the in vitro stimulation with PRL increased the number of these receptors, accelerated the growth and modified the activity of larvae. All of the above suggest that T. canis larvae are evolutionarily adapted to recognize the PRL of their definitive host and furthermore might explain the reactivation of tissue-arrested larvae during the gestation of bitches, which does not occur in gestating females of other species.


A controlled trial of colchicine in primary biliary cirrhosis. Trial design and preliminary report.
Colchicine (1 mg/day), or an identical placebo, was given to 64 patients with primary biliary cirrhosis in a double-blind controlled trial. Due to a novel, pair-matched trial design, the two groups were exceptionally well matched at entry. In comparison with placebo, colchicine produced a beneficial effect on serum albumin and bilirubin levels at 3 months in patients who had abnormal liver function (bilirubin greater than 20 mumol/l) at entry: (albumin, P = 0.047; bilirubin, P = 0.022). In patients with normal liver function at entry (bilirubin less than 20 mumol/l), beneficial effects were noted on total globulin levels at 3 months (P = 0.013) and on immunoglobulin G levels at 3 and 6 months (P = 0.044 and 0.001, respectively). At 18 months, survival estimate in the colchicine and placebo groups were 84% and 69%, respectively. The difference did not reach significance. Colchicine produced an early improvement in liver function and immunoglobulin levels. Few serious side effects were encountered, and colchicine clearly merits long-term study in the treatment of primary biliary cirrhosis.


Thioredoxin-1 contributes to protection against DON-induced oxidative damage in HepG2 cells.
Leucocytes are susceptible to the toxic effects of deoxynivalenol (DON), which is a trichothecene mycotoxin produced by a number of fungi including Fusarium species. One mechanism of action is mediated by reactive oxygen species (ROS). The liver is an important target for toxicity caused by foreign compounds including mycotoxins. On the other hand, little is known about the influence of the redox state on hepatocytes treated with DON. The present study investigated the effect of DON on the cytosolic redox state and antioxidative system in the human hepatoma cell line HepG2. The cell viability of human monocyte cell line THP-1 or leukemia cell line KU812 treated with 2.5 and 5 μmol/l DON were significantly reduced. However, HepG2 cells showed no toxic effects under the same conditions and did not exhibit an increased oxidative state. Further experiments showed that thioredoxin-1 (Trx-1) protein levels but not glutathione increased in the cells treated with 10 μmol/l DON. In addition, the enhancement of Trx-1 content was repressed by antioxidants. These results suggest that DON-induced accumulation of Trx-1 in HepG2 cells plays one of the key roles in protection against cytotoxicity caused by DON and that the mechanism may be mediated by the antioxidant properties of Trx-1.


The duodenal mucosa in patients with renal failure: response to 1,25(OH)2D3.
The structure of the duodenal mucosa was evaluated in duodenal biopsy samples obtained from patients with moderate renal failure (MRF) and in dialysis patients (HD) in an effort to examine the possibility that changes in duodenal mucosa may contribute to the impaired calcium absorption in renal failure (RF). The effect of therapy with 1,25(OH)2D3 on the duodenal mucosa in the HD patients was also studied. The results show that both MRF and HD patients have reduction in calcium reabsorption and in the length of their intestinal villi and crypts of Lieberkuhn. In the HD patients, these structural changes were more severe. Treatment with 1,25(OH)2D3 produced significant improvement in calcium reabsorption (P less than 0.01) as well as in length of villus and crypt (P less than 0.02) and increased mitotic activity in the crypts (P 0.02). Electron microscopy revealed the microvilli to be shorter, irregularly distributed, moth-eaten, and grainy, with these abnormalities disappearing after treatment. The data show that duodenal mucosa in RF exhibits structural abnormalities, which were normalized after 1,25(OH)2D3 therapy, and suggest that these derangements may play a role in the defective calcium reabsorption in RF.


Quantitative analysis of 18/FDG-PET in the presurgical evaluation of patients suffering from refractory partial epilepsy. Comparison with CT, MRI, and combined subdural and depth. EEG.
CT, MRI, 18/FDG-PET and Depth. EEG, performed with subdural and depth electrodes were part of the presurgical evaluation in 22 patients. Statistical analysis of 18/FDG-PET was performed to compare cerebral utilization of glucose to that of normal age matched controls. The findings of CT, MRI, and quantitative analysis of PET are compared with those of ictal Depth. EEG. A positive correlation between CT and Depth. EEG was obtained in 23% of the patients and between MRI and Depth. EEG. in 50%. For both imaging techniques a negative correlation was found in 5%. Regional abnormalities were found with quantified PET in 95% of the patients and were concordant with Depth. EEG. for side of onset in 77% of the patients and for lobe of onset in 59%. A possibly false localising PET result for lobe of onset was obtained in 8 patients (36%). Limitations of PET were most apparent in patients with regional mesiolimbic or bilateral seizure onset. A favourable outcome of surgery was associated usually with positive convergence of both methods. PET may be a valuable contribution to the research and management of partial complex epilepsy, but at present cannot be considered a reliable alternative to invasive EEG methods in patients without clear unilateral focus localization on surface EEG.


Impact of a One-Stop Hematuria Clinic on Overall Survival and Bladder Tumor Recurrence.
One-stop clinics have emerged as a tool to optimize the therapeutic management of cancer patients. The main purpose of this study was to assess the role of the one-stop hematuria clinic (OSHC), as compared to a conventional clinic (CC), on the overall and disease-free survival of patients with bladder cancer. A five-year follow-up retrospective and single-center study was conducted in patients with primary bladder tumor diagnosed between 2006 and 2015. The primary outcomes were five-year overall survival and one-year relapse rate. A total of 394 patients (160 in OSHC and 234 in CC) were included. No differences were observed in terms of age, sex, smoking habit or risk group between the OSHC and CC groups. The average times from first symptom to diagnosis (24.9 ± 29.1 vs. 100.7 ± 93.6 days) and from first symptom to treatment (70.2 ± 34.0 vs. 155.0 ± 102.9 days) were significantly lower in the OSHC group than in the CC group (p < 0.001 each). There was no significant difference in the five-year survival rate between OSHC and CC (103/160 vs. 150/234, respectively; p = 0.951), although the proportion of relapses during the first year was significantly lower in the OSHC group (35/139, 25.2%) than in the CC one (74/195, 38.0%; p = 0.02). OSHC significantly reduced the diagnosis and treatment times. The early-relapse rate was significantly lower in the OSHC group, although the five-year survival rate was similar.


Effects of d-amphetamine on schedule-induced escape.
Pigeons were trained to respond on a fixed-ratio schedule during which 90 responses produced 3 sec of grain reinforcement (FR 90). Concurrently, a separate key was available on which a response initiated a time-out from the FR schedule and turned off the discriminative stimuli associated with the FR. A second response on the same key terminated the time-out and reinstated the fixed ratio. The pigeons demonstrated a pattern of escape responding immediately following the grain reinforcement. d-Amphetamine (0.5, 1.0, 3.0 mg/kg) was administered 30 min before a probe session. During the probe sessions grain presentation was decreased to 2 sec to generate maximum escape responding. The FR response rate showed a dose related increase with doses of 0.5-1.0 mg/kg, while the same doses produced a dose related decrease in the rate of schedule-induced escape. The highest dose of 3.0 mg/kg of d-amphetamine eliminated FR and schedule-induced escape responding in all but one animal. The drug effects on a topographically similar response from the same animal during the same session suggests differential effects on schedule-controlled and schedule-induced behavior.


Evaluating specificity of sequential extraction for chemical forms of lead in artificially-contaminated and field-contaminated soils.
In the present study, we evaluated a commonly employed modified Bureau Communautaire de Référence (BCR test) 3-step sequential extraction procedure for its ability to distinguish forms of solid-phase Pb in soils with different sources and histories of contamination. When the modified BCR test was applied to mineral soils spiked with three forms of Pb (pyromorphite, hydrocerussite and nitrate salt), the added Pb was highly susceptible to dissolution in the operationally-defined "reducible" or "oxide" fraction regardless of form. When three different materials (mineral soil, organic soil and goethite) were spiked with soluble Pb nitrate, the BCR sequential extraction profiles revealed that soil organic matter was capable of retaining Pb in more stable and acid-resistant forms than silicate clay minerals or goethite. However, the BCR sequential extraction for field-collected soils with known and different sources of Pb contamination was not sufficiently discriminatory in the dissolution of soil Pb phases to allow soil Pb forms to be "fingerprinted" by this method. It is concluded that standard sequential extraction procedures are probably not very useful in predicting lability and bioavailability of Pb in contaminated soils.


Orally administration of Neolentinus lepideus extracts attenuated ethanol induced accumulation of hepatic lipid in mice.
In this study, we examined the effects of the water extract of Neolentinus lepideus (WENL), an edible mushroom, on ethanol-induced hepatic lipid accumulation. Ethanol-induced oil red O-positive spots on AML-12 hepatocytes were attenuated by WENL treatment. Furthermore, the oral administration of WENL in acute and chronic ethanol-fed mouse models resulted in the decrease in blood triglyceride and the accumulation of lipid droplets in the liver. Interestingly, the transcriptional expression related to lipid metabolisms, such as sterol regulatory element-binding protein 1, and cytochrome P450 2E1, was decreased by WENL treatment in both ethanol-induced AML-12 hepatocytes and our chronic ethanol-fed mouse models. In addition, WENL effectively attenuated the ethanol induced activation of MAP kinases and NF-κB in AML-12 hepatocytes. Taken together, our results suggested that WENL can be effective in alleviating alcohol-induced hepatic lipid accumulation and may be used as potential candidate for the prevention of alcoholic fatty liver disease.


Identification of noncovalent dimeric complexes of the recombinant murine S100 protein CP10 by electrospray ionization mass spectrometry and chemical cross-linking.
CP10 is a chemotactic S100 protein expressed by murine myeloid cells. A specific noncovalently linked dimeric complex of recombinant Ala43 CP10 was identified after electrospray ionization mass spectrometry using a nondenaturing solvent of 5-mM ammonium acetate (pH 6.5) and source temperature of 50 degrees C. With a low cone voltage (75 V), major ions were observed at approximately 2075, 2305, and 2613 Da, which were attributed to partially desolvated multiply charged noncovalently linked dimeric species (+10, +9, and +8 charge states, respectively). Deconvolution produced a broad peak centered around 20750 Da corresponding to the approximate mass of dimeric recombinant Ala43 CP10. Increasing the cone voltage, the collisionally activating the complex, gradually reduced the intensity of these dimeric ions, with a concomitant increase in higher and lower charge state monomeric ions. The intensities of these dimeric ions were greatly reduced in spectra recorded with a source temperature of 140 degrees C and cone voltage of 75 V, indicating a thermally unstable noncovalent complex. Similar spectra were obtained using recombinant CP10. Specific noncovalent S100 dimeric complexes were confirmed by chemically cross-linking recombinant Ala43 CP10 or CP10 with bis (sulfosuccinimidyl) suberate, followed by SDS/PAGE. The dominant silver-stained and CP10-immunoreactive component migrated at 20,000 suggested that the complex represents the major isoform in solution.


Fear of blood draw is associated with inflated expectations of faint and prefaint reactions to blood donation.
Although the risk of fainting and prefaint reactions (e.g., dizziness, lightheadedness) is low during blood donation, there is evidence that this risk remains a concern for many donors. This study sought to measure perceived risk for such reactions within the general population and to relate perceived risk to individual reports of fear of having blood drawn. A sample of 1019 men and women (52.2% male; mean ± SD age, 37.2 ± 12.3 years; range, 18-80 years) completed an anonymous online survey that included questions that asked about their 1) estimation of the frequency of faint and prefaint symptoms experienced by blood donors and 2) fear of having blood drawn. Survey respondents overestimated the risk of both faint and prefaint reactions to blood donation, with estimates of fainting risk being more than 20 times the actual risk. Further, the perceived risk of both faint reactions (F(4,1008) = 25.88, p < 0.001) and prefaint reactions (F(4,1008) = 17.37, p < 0.001) was higher among those who reported greater fear of having blood drawn. The general public has inflated expectations of the risk for faint and prefaint reactions to blood donation, suggesting that efforts to educate prospective donors with accurate information may help to reduce this relatively common concern.


Is there an age limit for thrombolytic therapy?
Thrombolytic therapy has revolutionized the treatment of acute myocardial infarction. The mortality of infarction increases very steeply with increasing age > 65 years. One-month mortality in such patients is in the range of 20-30%. The proportional benefit of lytic treatment is somewhat less in these older patients, but since mortality is high, the absolute benefit is as large or larger than that in younger patients. The risks of stroke due to thrombolysis are balanced between increased risk of cerebral hemorrhage but decreased risk for ischemic/embolic stroke. This trade-off results, overall, in a slightly increased stroke rate of about 1-2 per 1,000 nonfatal strokes, but with about 20 fewer deaths per 1,000 myocardial infarctions. In addition to these striking mortality benefits, there are also important reductions in infarct size, leading to decreased morbidity from heart failure or arrhythmias.


Influence of sex on reinstatement of cocaine-conditioned place preference.
To explore sex differences in reinstatement of conditioned place preference, we subjected intact male and female Long Evans rats to an extended conditioned place preference (CPP) paradigm, which included observations of acquisition, extinction, and reinstatement of a preference to cocaine-paired stimuli. In a series of experiments, separate groups of animals were given six 30-min pairings of one chamber with cocaine (3, 5, 10, 15, 20, 25mg/kg) and six of the other with saline on alternate days. Overall, there were no sex differences in acquisition of cocaine CPP at any of the six doses tested (p>0.05). All animals established cocaine CPP at each of the six doses tested during the acquisition test, with the exception of the group of females conditioned with 5mg/kg. Preferences for the cocaine-paired chamber were successfully extinguished for both males and females after an extinction-training period. CPP reinstatement was achieved by the groups of males and females given training and priming doses of 10, 15, 20, and 25mg/kg (p<0.05). Overall, our reinstatement data demonstrate that reinstatement of cocaine CPP is greater for female versus male animals. Females showed a greater magnitude of reinstatement of cocaine CPP when trained and primed with 15 and 25mg/kg as compared to males (p<0.05). Further, at the three highest doses tested (15, 20, and 25mg/kg), females showed a greater magnitude of CPP in the reinstatement phase of CPP compared to that of the initial acquisition phase (p<0.05). The reinstatement data for the males show that the 20mg/kg dose resulted in the highest levels of reinstatement preference for male rats. These results indicate that sex differences in reinstatement to conditioned behavior maybe due, in part, to females forming a stronger association for the salience of the drug and the environment in which it was administered.


Perception of childhood obesity in mothers of preschool children.
The purpose of this study was to identify the perception of childhood obesity in mothers of preschool children using Q methodology. A total of 38 Q statements about childhood obesity were obtained from 41 participants. The QUANL PC program was used to analyze the results. There were three types of perception toward obesity in mothers of preschool children: the "authoritative discipline type," the "generous home meal focused type," and the "home meal based on household financial situation type." The perception of mothers toward childhood obesity can affect the extent of maternal interaction with children or meal preparation for the family. Based on these results, it is necessary to plan specific programs according to the types of maternal perception toward childhood obesity.


Exercise for perinatal depressive symptoms: A systematic review and meta-analysis of randomized controlled trials in perinatal health services.
Exercise improves perinatal depressive (PD) symptoms, but reports call for more robust evidence. This systematic review and meta-analysis aimed at synthesizing evidence exclusively from randomized controlled trials (RCTs) examining the effects of exercise on PD symptoms in women recruited through perinatal health services. Nine e-databases and fifteen systematic reviews were searched for relevant RCTs. Exercise-specific tools extracted/coded data. A meta-analysis using a random effects model (Standardized Mean Difference [SMD]) investigated the effects of exercise on PD scores post-intervention. From 285 records, 14 RCTs (2.025 participants) were considered eligible including two RCTs with clinically diagnosed PD women. Exercise showed a statistically significant, small, overall antidepressant effect (SMD = -0.21, 95% CI = -0.31, -0.11, p = 0.0001) with low/non-significant heterogeneity (Q = 17.82, I 2 = 16%, p = 0.27). Only the fail-safe criterion recorded marginally significant publication bias, but trim-fill analysis added no study. Sensitivity analyses increased the overall effect in RCTs showing lower risk of bias or delivering ≥150 min/week moderate intensity aerobic exercise. Subgroup analyses revealed significant antidepressant effects for exercise across various settings, delivery formats, depressive symptoms severities and outcome measures used. Heterogeneity was low/non-significant in all analyses (I 2 ≤ 50%). Hedges' g corrections did not influence the results. Study limitations include the small number of available trials and clinically diagnosed PD samples and the variety of exercise modalities. Exercise improved PD symptoms, especially in RCTs with lower risk of bias or with ≥150 min/day moderate intensity aerobic exercise interventions. Findings are clinically useful but more RCTs for clinically diagnosed PD women are needed for firmer conclusions.


Vitamin D and Zinc Supplementation to Improve Treatment Outcomes among COVID-19 Patients in India: Results from a Double-Blind Randomized Placebo-Controlled Trial.
There remains a need to identify low-cost interventions to improve coronavirus disease 2019 (COVID-19) outcomes. Vitamin D and zinc play a role in respiratory infections and could hold value as part of therapeutic regimens. To determine the effect of vitamin D or zinc supplementation on recovery from COVID-19. We conducted a double-blind, randomly assigned 2 x 2 factorial placebo-controlled trial with 1:1:1:1 allocation ratio, enrolling nonpregnant adults with COVID-19 from hospitals in Mumbai and Pune, India (NCT04641195). Participants (N = 181) were randomly assigned to vitamin D3 (180,000 IU bolus, then 2000 IU daily), zinc (40 mg daily), vitamin D3 and zinc, or placebo, for 8 wk. Participants were followed until 8 wk. The primary outcome was time to resolution of fever, cough, and shortness of breath. Secondary outcomes were duration of individual symptoms; need for assisted ventilation; duration of hospital stay; all-cause mortality; and blood biomarkers, including nutritional, inflammatory, and immunological markers. We observed no effect of vitamin D or zinc supplementation on time to resolution of all 3 symptoms [vitamin D hazard ratio (HR): 0.92; 95% confidence interval (95% CI): 0.66, 1.30; P = 0.650; zinc HR: 0.94; 95% CI: 0.67, 1.33; P = 0.745)]. Neither vitamin D nor zinc supplementation was associated with secondary outcomes, except for increased endline serum vitamin D with vitamin D supplementation [median (interquartile range) difference between endline and baseline for vitamin D: 5.3 ng/mL (-2.3 to 13.7); for no vitamin D: -1.4 ng/mL (-5.6 to 3.9); P = 0.003]. We observed nonsignificant increases in serum zinc at endline following zinc supplementation. There was no evidence of interaction between vitamin D and zinc supplementation, no effect of either on hypercalcemia, and no adverse events. Results suggest that neither vitamin D nor zinc supplementation improves COVID-19 treatment outcomes in this population. However, much larger-scale evidence, particularly from populations with vitamin D or zinc deficiency and severe infection, is required to corroborate our findings. This trial was registered at ClinicalTrials.gov and the Clinical Trials Registry of India as NCT04641195 and CTRI/2021/04/032593 respectively.


Initial Experience with a COVID-19 Screening Chatbot Before Radiology Appointments.
Guidelines for COVID-19 issued by the Centers for Disease Control and Prevention prompted state and local governments to mandate safety measures for screening high-risk patient populations and for institutions to look for ways to limit human contact when possible. The aim of this study was to determine the feasibility of an automated communication system (chatbot) for COVID-19 screening before patients' radiology appointments and to describe patient experiences with the chatbot. We developed a chatbot for COVID-19 screening before outpatient radiology examination appointments and tested it in a pilot study from July 6 to August 31, 2020. The chatbot assessed the presence of any symptoms, exposure, and recent testing. User experience was assessed via a questionnaire based on a 5-point Likert scale. Multivariable logistic regression was performed to predict response rate. The chatbot COVID-19 screening SMS message was sent to 4687 patients. Of these patients, 2722 (58.1%) responded. Of the respondents, 46 (1.7%) reported COVID-19 symptoms; 34 (1.2%) had COVID-19 tests scheduled or pending. Of the 1965 nonresponders, authentication failed for 174 (8.8%), 1496 (76.1%) did not engage with the SMS message, and 251 (12.8%) timed out of the chatbot. The mean rating for the chatbot experience was 4.6. In a multivariable logistic regression model predicting response rate, English written-language preference independently predicted response (odds ratio, 2.71 [95% CI, 1.77-2.77]; P = .007). Age (P = 0.57) and sex (P = 0.51) did not predict response rate. SMS-based COVID-19 screening before scheduled radiology appointments was feasible. English written-language preference (not age or sex) was associated with higher response rate.


Deep body core temperatures in industrial workers under thermal stress.
To date, no field study has continuously monitored the deep body core temperatures of industrial workers. A program to continuously measure deep body core temperatures in 36 industrial workers working 10-, 12-, and 12.5-hour day and nightshifts in a hot, deep, underground mine in the Tropics was conducted. No heat illness occurred in these workers during the study. Miniaturized radio-transponders ("pills") taken orally were used to measure temperature during the transit time in the gastrointestinal tract. Commonly recommended limits for industrial hyperthermia are 38.0 degrees C, or an increase of +1 degree C. The results showed that miners regularly exceeded these limits in terms of maximum deep body core temperature (average, 38.3 degrees C; standard deviation, 0.4 degree C), maximum temperature rise (1.4 degrees C, 0.4 degree C), and maximum heat storage (431 kJ, 163 kJ) without reporting any symptoms of heat illness. A significant component of the observed elevated core temperatures was attributable to the normal circadian rhythm, which was measured at 0.9 degree C (standard deviation, 0.2 degree C). Evidence was found that workers "self-pace" when under thermal stress.


A parkinsonian kindred.
We report 8 cases of clinical idiopathic Parkinson disease in one kindred. None of the patients presented anomalous symptoms and all responded normally to routine L-Dopa therapy. On the basis of these findings we analyse the possible etiological role of heredity in Parkinson disease.


Perioperative bridging anticoagulation for atrial fibrillation-the first randomised controlled trial.
Patients who have atrial fibrillation (AF) have increased thromboembolic risk. This risk is mitigated through use of anticoagulants, traditionally with vitamin K antagonists such as warfarin, and more recently with drugs such as Xa and thrombin inhibitors. Since anticoagulants increase the risk of bleeding, uncertainty exists regarding their use in the perioperative period. The risk of thromboembolism for each patient must be balanced against risk of bleeding; anticoagulation medication may be continued, replaced with a short-acting alternative or withheld entirely. Until recently, evidence on best management relied on expert opinion and observational studies. The recent publication of a randomised, double-blind, placebo-controlled trial (BRIDGE) has added important information to the knowledge base. BRIDGE ClinicalTrials.gov, NCT00786474.


[Intradermal metal deposits in an industrial worker].
We describe a 75-year-old patient with asymptomatic grey pigmentation on the face and fingers. He had worked over two decades in cutting high-voltage cables. The cutting procedures were performed without a face shield or protection gloves. The patient presented with gray punctate lesions beside some homogeneously stained zones. Histologically, the deposits presented in the dermal tissue in a horse-shoe, oval, or splinter-like shape. The foreign body material was embedded by a few CD68-positive macrophages. Undyed histological sections were investigated via two-dimensional micro-synchrotron X-ray fluorescence analysis (SRXRF). The deposits were identified as zinc (Zn), copper (Cu), nickel (Ni), and strontium (Sr), which were strongly associated with maximal sulfur (S) concentrations. This association is presumably induced by complex binding between thiol groups and metal ions such as Zn, Ni etc. However, the iron (Fe) distribution patterns were quite different to those of Zn, Cu, or Ni. These heavy metals are major components of the metal wires that the patient worked with in his profession. To the best of our knowledge, this is the first case report in the dermatological literature of intradermal metal deposits identified via SRXRF analysis.


Ready, set, go! The role of organizational readiness to predict adoption of a family caregiver training program using the Rogers' diffusion of innovation theory.
Caregivers FIRST is an evidence-based program addressing gaps in caregivers' skills. In 2020, the Veterans Health Administration Caregiver Support Program (CSP) nationally endorsed Caregivers FIRST, offering credit in leadership performance plans to encourage all VA medical centers (VAMCs) to implement locally. This study examines the association of organizational readiness with VAMC adoption of Caregivers FIRST. In a cohort observational study, we surveyed CSP managers about their facilities' readiness to implement using the Organizational Readiness for Implementing Change (ORIC) instrument and compared change commitment and change efficacy domains among VAMCs "adopters" defined as delivering Caregivers FIRST within 1 year of the national announcement to those that did not ("non-adopters"). Within "adopters," we categorized time to adoption based on Rogers' diffusion of innovation theory including "innovators," "early adopters," "early majority," "late adopters," and "laggards." Organizational readiness and site characteristics (facility complexity, staffing levels, volume of applications for caregiver assistance services) were compared between "adopters," "non-adopters," and between time to adoption subcategories. Separate logistic regression models were used to assess whether ORIC and site characteristics were associated with early adoption among "adopters." Fifty-one of 63 (81%) VAMCs with CSP manager survey respondents adopted Caregivers FIRST during the first year. ORIC change commitment and efficacy were similar for "adopters" and "non-adopters." However, sites that adopted earlier (innovators and early adopters) had higher ORIC change commitment and efficacy scores than the rest of the "adopters." Logistic regression results indicated that higher ORIC change commitment (odds ratio [OR] = 2.57; 95% confidence interval [CI], 1.11-5.95) and ORIC change efficacy (OR = 2.60; 95% CI, 1.12-6.03) scores were associated with increased odds that a VAMC was an early adopter (categorized as an "innovator," "early adopter", or "early majority"). Site-level characteristics were not associated with Caregivers FIRST early adoption. To our knowledge, this study is the first to prospectively assess organizational readiness and the timing of subsequent program adoption. Early adoption was associated with higher ORIC change commitment and change efficacy and not site-level characteristics. These findings yield insights into the role of organizational readiness to accelerate program adoption. ClinicalTrials.gov, NCT03474380. Registered on March 22, 2018.


The nationwide Danish healthcare service for children and adolescents with gender dysphoria opened in 2016, based on clinical experience from other European countries and early follow-up studies, implying that early medical transition resulted in better physical and psychological outcomes. This review discusses how a rapid increase of referrals, especially among adolescent birth-assigned girls, and other factors such as high rates of psychiatric morbidity and varying developmental trajectories of gender identity have affected international and Danish healthcare in recent years.


Nerve growth factor increases substance P, cholecystokinin and vasoactive intestinal polypeptide immunoreactivities in primary sensory neurones of newborn rats.
Immunoreactive substance P, somatostatin, gastrin/cholecystokinin and vasoactive intestinal polypeptide were studied in lumbar dorsal root ganglia of 14-day-old rats treated from day 2 to 11 of life with nerve growth factor. Increased staining intensity of neuronal cell bodies and processes for substance P, gastrin/cholecystokinin and vasoactive intestinal polypeptide was observed by immunohistochemistry indicating increased neuronal peptide concentrations. These results were supported by radioimmunoassays showing increased ganglionic levels of substance P and vasoactive intestinal polypeptide. Both techniques, however, failed to show a significant increase of somatostatin levels.


Is uniform target dose possible in IMRT plans in the head and neck?
Various published reports involving intensity-modulated radiotherapy (IMRT) plans developed using automated optimization (inverse planning) have demonstrated highly conformal plans. These reported conformal IMRT plans involve significant target dose inhomogeneity, including both overdosage and underdosage within the target volume. In this study, we demonstrate the development of optimized beamlet IMRT plans that satisfy rigorous dose homogeneity requirements for all target volumes (e.g., +/-5%), while also sparing the parotids and other normal structures. The treatment plans of 15 patients with oropharyngeal cancer who were previously treated with forward-planned multisegmental IMRT were planned again using an automated optimization system developed in-house. The optimization system allows for variable sized beamlets computed using a three-dimensional convolution/superposition dose calculation and flexible cost functions derived from combinations of clinically relevant factors (costlets) that can include dose, dose-volume, and biologic model-based costlets. The current study compared optimized IMRT plans designed to treat the various planning target volumes to doses of 66, 60, and 54 Gy with varying target dose homogeneity while using a flexible optimization cost function to minimize the dose to the parotids, spinal cord, oral cavity, brainstem, submandibular nodes, and other structures. In all cases, target dose uniformity was achieved through steeply varying dose-based costs. Differences in clinical plan evaluation metrics were evaluated for individual cases (eight different target homogeneity costlets), and for the entire cohort of plans. Highly conformal plans were achieved, with significant sparing of both the contralateral and ipsilateral parotid glands. As the homogeneity of the target dose distributions was allowed to decrease, increased sparing of the parotids (and other normal tissues) may be achieved. However, it was shown that relatively few patients would benefit from the use of increased target inhomogeneity, because the range of improvement in the parotid dose is relatively limited. Hot spots in the target volumes are shown to be unnecessary and do not assist in normal tissue sparing. Sparing of both parotids in patients receiving bilateral neck radiation can be achieved without compromising strict target dose homogeneity criteria. The geometry of the normal tissue and target anatomy are shown to be the major factor necessary to predict the parotid sparing that will be possible for any particular case.


Total torsion of three-dimensional lines of curvature.
A curve γ in a Riemannian manifold M is three-dimensional if its torsion (signed second curvature function) is well-defined and all higher-order curvatures vanish identically. In particular, when γ lies on an oriented hypersurface S of M, we say that γ is well positioned if the curve's principal normal, its torsion vector, and the surface normal are everywhere coplanar. Suppose that γ is three-dimensional and closed. We show that if γ is a well-positioned line of curvature of S, then its total torsion is an integer multiple of 2π; and that, conversely, if the total torsion of γ is an integer multiple of 2π, then there exists an oriented hypersurface of M in which γ is a well-positioned line of curvature. Moreover, under the same assumptions, we prove that the total torsion of γ vanishes when S is convex. This extends the classical total torsion theorem for spherical curves.


Influence of Temperature on the Life-Cycle Dynamics of Aedes albopictus Population Established at Temperate Latitudes: A Laboratory Experiment.
The mosquito species Aedes albopictus has successfully colonized many areas at temperate latitudes, representing a major public health concern. As mosquito bionomics is critically affected by temperature, we experimentally investigated the influence of different constant rearing temperatures (10, 15, 25, and 30 °C) on the survival rates, fecundity, and developmental times of different life stages of Ae. albopictus using a laboratory colony established from specimens collected in northern Italy. We compared our results with previously published data obtained with subtropical populations. We found that temperate Ae. albopictus immature stages are better adapted to colder temperatures: temperate larvae were able to develop even at 10 °C and at 15 °C, larval survivorship was comparable to the one observed at warmer conditions. Nonetheless, at these lower temperatures, we did not observe any blood-feeding activity. Adult longevity and fecundity were substantially greater at 25 °C with respect to the other tested temperatures. Our findings highlight the ability of Ae. albopictus to quickly adapt to colder environments and provide new important insights on the bionomics of this species at temperate latitudes.


Invasion of infectious diseases in finite homogeneous populations.
We consider the initial invasion of an infectious disease in a finite, homogeneous population. Methodology for evaluating the basic reproduction number, R(0), and the probability mass function of secondary infections is presented. The impact of finite population size, and infectious period distribution (between exponential, two-phase gamma, and constant), is assessed. Implications for infectious disease invasion and estimation of infectious disease model and parameters from data of secondary infections by initially infected individuals in naive, finite, homogeneous populations are reported. As any individual interacts with a finite number of contacts during their infectious period, these results are important to the study of infectious disease dynamics.


A single-center experience with liver transplantation for Wilson's disease.
Wilson's disease is an inherited disorder of copper metabolism, presenting with prominent hepatic and neurologic manifestations. There is an established place for liver transplantation in the presence of liver disease, while the indication for neurologic manifestations is debated. Between 1993 and 2005, 11 patients were liver transplanted for Wilson's disease at our institution. We retrospectively reviewed the medical records of the patients. The pathology of the explanted livers was analyzed. The patients were divided into three groups based on the evolution of the disease. Postoperative data gathered included patient and graft outcome, complications, neurologic status, and copper metabolism. Six males and five females were transplanted at a mean age of 29.7 yr (range 15-48 yr). Three patients had a fulminant presentation, two patients had decompensation of established disease, and six patients had chronic disease. Neurologic features were prominent in five patients. The pathologic analysis of the explanted graft showed cirrhosis in all patients. The five patients with fulminant and acute on chronic presentations also showed necrosis in the explant. The mean postoperative follow-up was 56.8 months (range 10-129 months). Two patients were re-transplanted. One patient died because of severe sepsis. Two patients with severe neurologic dysfunction showed significant remission of symptoms. Liver transplantation is a safe and effective treatment for both acute and chronic presentations of Wilson's disease. Acute presentation correlates with the presence of necrosis in the explanted liver. In our series, there was a relevant improvement of the neurologic features after transplantation.


Directional X Chromosome Skewing of White Blood Cells from Subjects with Heterozygous Mosaicism for the Variant IRAK1 Haplotype.
Random X chromosome (ChrX) inactivation and consequent cellular mosaicism for the active ChrXs in white blood cells (WBCs) is unique to females and may contribute to sex-biased modulation of the innate immune response. Polymorphic differences between the two parental ChrXs may result in ChrX skewing of circulating WBCs (ChrX inactivation-ratio (XCI) > 3) driven by differences in stem cell selection and activity in the bone marrow or WBC trafficking at the periphery. Independent of the mechanism, ChrX skewing may result in genotype-phenotype discrepancies. This study aimed to develop an allele-specific assay and test its applicability in clinical samples to determine the "direction" of ChrX skewing in the variant IRAK1 haplotype, a common X-linked polymorphism with major clinical impacts. Because alternative splice variants of IRAK1 are also produced in the region surrounding the critical single-nucleotide polymorphism (SNP, rs1059703), we also tested the abundance of alternative splice variant IRAK1 transcripts. The expression of splice variants IRAK1-B and IRAK1-C was about 30 and 50% of the full-length (IRAK1-A) in WBCs from healthy subjects (n = 53). IRAK1-A, B, and C showed about 30% lower expression level in males (n = 25) than females (n = 28). By contrast, the expression levels of IRAK1-A, B, and C were not affected by the variant IRAK1 haplotype in either sex. Allele-specific primers generated WT and variant-IRAK1 amplicons with high selectivity, and on average produced about half the expression levels of each transcript in heterozygous IRAK1-mosaic females. Because injury was shown to induce de novo ChrX skewing of WBCs, we tested the directional XCI ratio changes in WBC in a sample of trauma patients heterozygous for the variant IRAK1 haplotype (n = 18). Using the allele-specific assay in combination with the DNA methylation status at the polymorphic HUMARA locus, we found that at admission, about 60% the patients presented XCI ratios skewed toward WBCs with active ChrXs carrying the variant-IRAK1 similar to healthy controls. De novo, trauma-induced XCI ratio changes showed increased extravasation of the more abundant mosaic WBC subset without reversal in the direction of ChrX skewing during the injury course.


An enzyme-linked direct antiglobulin test for assessing erythrocyte bound immunoglobulins.
An enzyme-linked direct antiglobulin test (DAGT) for assessing erythrocyte-bound IgG, IgM and IgA is described. The test is carried out in microtitre plates using heavy chain-specific, alkaline phosphatase-linked, goat anti-human globulin reagents with p-nitrophenyl phosphate as substrate. Results are expressed in optical density (OD) units per 3.6 X 10(7) red cells. The method is reproducible, with coefficients of variation of 0.056, 0.093 and 0.087 for IgG, IgM and IgA respectively. The linear relationship between the amount of red cell-bound antibody and the OD reading for each immunoglobulin class shows that the method is suitable for quantitative studies. Healthy individuals were found to have small amounts of immunoglobulin bound to their red cells with mean values of 0.251, 0.087 and 0.128 OD units per 3.6 X 10(7) red cells for IgG, IgM and IgA respectively; there was no difference between male and female subjects. In the clinical situation, the enzyme-linked DAGT was considered to show significantly increased amounts of cell-bound immunoglobulin when the results were more than three standard deviations above the mean and the quantitative results permitted an accurate assessment of the progress and response to treatment of patients with autoimmune haemolysis.


Differences for T-Cell Subtypes in Aspiration Biopsies of Patients With Kidney Transplant Under Polyclonal and Monoclonal Immunosuppressive Treatments.
Thymoglobulin, or antithymocyte globulin (ATG), and anti-interleukin 2α (IL-2α) chain receptor antibody (IL-2αRAb) achieve comparable good results in kidney transplantation notwithstanding different actions on immune cells. Previously, we reported the usefulness of flow cytometry (FC) analysis of lymphocyte subsets present in peripheral blood sample (PBL) and fine-needle aspiration biopsies (FNABs) for clinical surveillance, as, FC reaches very high predictive positive values for acute rejection diagnosis. Now we report an FC study on 2 kidney transplantation (KT) groups under ATG (n = 19) and IL-2αRAb (n = 24) treatment. Both groups were further treated with calcineurin inhibitors mycophenolate mofetil (MMF) and prednisone. PBL and FNAB samples were collected on day 7 post-KT, stained for several T- and B-lymphocyte subsets, and acquired using FACScan. Statistical analysis were done by Mann-Whitney U test. FNAB results showed a significant downregulation by ATG of CD3 (P < .001), CD4 (P = .009), CD4CD29 (P = .003), and CD2 (P ≤ .001) and significant upregulation of death receptor (DR) (P = .03), CD3CD69 (P < .001), and CD3CD25 (P < .0001) as compared to groups treated with IL-2αRAb. For PBL, the same trend was seen for CD3, CD4, CD2, CD3CD25, CD3CD69, CD4CD29, and DR plus a downregulation of CD45RO (P = .001) and an upregulation of CD4CD45RA (P < .0001) in IL-2αRAb. This study shows that among stable KTs, ATG as compared to IL-2αRAb induces a significant downregulation of a subset of T-memory (CD4CD29) cells but an upregulation of antigen-experienced cells (CD45RO). Further, ATG decreases CD2, CD3, CD4, and naïve (CD45RA) and stimulates T cells as translated by CD3CD69 and DR. As it should be expected from an IL-2αRAb agent, CD25 cells were virtually eliminated.


18F-FDG PET/CT in paediatric lymphoma: comparison with conventional imaging.
In children with Hodgkin's disease and non-Hodgkin's lymphoma, the ability of (18)F-fluoro-2-deoxy-D-glucose PET/CT and conventional imaging (CI) to detect malignant lesions and predict poor lesion response to therapy was assessed and compared. A retrospective review of findings reported on PET/CT and CI was performed using a lesion-based analysis of 16 lymph node and 8 extra-nodal regions. Lesions were defined by histopathological findings or follow-up > 6 months. The study included 209 PET/CT scans with a valid CI comparator. A total of 5,014 regions (3,342 lymph node, 1,672 extra-nodal) were analysed. PET/CT performed significantly better than CI in the detection of malignant lesions with sensitivity and specificity of 95.9 and 99.7% compared to 70.1 and 99.0%, respectively. For predicting poor lesion response to therapy, PET/CT had fewer false-positive lesions than CI. The specificity for predicting poor lesion response to treatment for PET/CT was 99.2% compared to 96.9% for CI. PET/CT was the correct modality in 86% of lesions with discordant findings. PET/CT is more accurate than CI in detecting malignant lesions in childhood lymphoma and in predicting poor lesion response to treatment. In lesions with discordant findings, PET/CT results are more likely to be correct.


Erythroid and myeloid maturation patterns related to progenitor assessment in the myelodysplastic syndromes.
Patterns of erythropoiesis and granulopoiesis were studied in 15 patients with myelodysplastic syndromes and in one with smouldering leukaemia by correlating CFU-C, BFU-E and CFU-E cloning efficiency with erythroid and myeloid maturation indices derived from quantitative 14C-autoradiography and with ferrokinetics. Maturation index of a cell lineage was defined as the ratio of cell production rate increase from the first to the last proliferative compartment over the corresponding normal value. The myeloid maturation index was reduced in all cases, but CFU-C progenitor frequency was increased by a factor of 3. Erythroid maturation index was also reduced in most cases, and BFU-E progenitor frequency was reduced by a factor of 2. Similarly, CFU-E cloning efficiency corrected for the erythroid maturation index was 2.5-10-fold lower than normal. Comparison of the erythroid maturation index with ferrokinetics revealed a constant ratio of ineffective erythropoiesis with a maturation disturbance in the proliferative pool twice that in the non-proliferative pool. These findings indicate basic qualitative and quantitative abnormalities and a difference in the patterns of production of erythroid and myeloid cells in the myelodysplastic syndromes: Myeloid progenitors are increased in number but their maturation is grossly abnormal. On the other hand, the apparent reduction in erythroid progenitors and the reduced erythroid maturation index are attributable to both premature cell death of the more mature erythroblasts and an increased proerythroblast proliferation, i.e. extra divisions in the proerythroblast compartment at the expense of maturation.


The relative contributions of disease label and disease prognosis to Alzheimer's stigma: A vignette-based experiment.
The classification of Alzheimer's disease is undergoing a significant transformation. Researchers have created the category of "preclinical Alzheimer's," characterized by biomarker pathology rather than observable symptoms. Diagnosis and treatment at this stage could allow preventing Alzheimer's cognitive decline. While many commentators have worried that persons given a preclinical Alzheimer's label will be subject to stigma, little research exists to inform whether the stigma attached to the label of clinical Alzheimer's will extend to a preclinical disorder that has the label of "Alzheimer's" but lacks the symptoms or expected prognosis of the clinical form. The present study sought to correct this gap by examining the foundations of stigma directed at Alzheimer's. It asked: do people form stigmatizing reactions to the label "Alzheimer's disease" itself or to the condition's observable impairments? How does the condition's prognosis modify these reactions? Data were collected through a web-based experiment with N = 789 adult members of the U.S. general population (median age = 49, interquartile range, 32-60, range = 18-90). Participants were randomized through a 3 × 3 design to read one of 9 vignettes depicting signs and symptoms of mild stage dementia that varied the disease label ("Alzheimer's" vs. "traumatic brain injury" vs. no label) and prognosis (improve vs. static vs. worsen symptoms). Four stigma outcomes were assessed: discrimination, negative cognitive attributions, negative emotions, and social distance. The study found that the Alzheimer's disease label was generally not associated with more stigmatizing reactions. In contrast, expecting the symptoms to get worse, regardless of which disease label those symptoms received, resulted in higher levels of perceived structural discrimination, higher pity, and greater social distance. These findings suggest that stigma surrounding pre-clinical Alzheimer's categories will depend highly on the expected prognosis attached to the label. They also highlight the need for models of Alzheimer's-directed stigma that incorporate attributions about the condition's mutability.


Cellular immunity, HLA-class I antigens, and family history of psychiatric disorder in endogenous psychoses.
We found an increased lymphocyte proliferation after stimulation with an antigen "cocktail" in 49 schizophrenic patients and 37 patients suffering from affective psychosis, compared with 45 healthy control subjects. On the basis of this and other findings such as increased numbers of CD3+ and CD4+ cells, an increased ratio of CD4+/CD8+ cells, and a reduced level of suppressor cell activity in schizophrenia and endogenous depression, we investigated the influence of the human leukocyte antigen-Class I (HLA-A, HLA-B, HLA-C) system on the altered immune function and evaluated the relationship to immune function of a family history of psychiatric disorders. A cluster analysis of cases with regard to the HLA-Class I antigens was first performed in a group of 133 healthy control subjects, and two immunogenetically different clusters were found; then 86 patients (49 schizophrenics, 37 affective psychoses) for whom immune functional data were available were assigned to the two HLA-I clusters that had been determined in the control subjects. Analyses of variance (ANOVAs) showed no differences in immune function between the two clusters. With respect to the cluster assignment and the family history of psychiatric diseases, a two-way ANOVA revealed significant differences in the lymphocyte response to the antigen cocktail, in the number of CD8+ cells, and in one suppressor cell assay. When patients were compared by ANOVA on the basis of family history of psychiatric disorder, patients with a positive family history showed a significantly higher number of CD4+ cells and a higher CD4+/CD8+ ratio. Moreover, certain HLA genes, especially HLA-A1, HLA-B8, HLA-B16, and HLA-C2 seemed to be related to the immune function and/or to the immune function and the family history.


Exploring the situational motivation of medical students through clinical medicine level test: a cross-sectional study.
China's Clinical Medicine Level Test (CMLT) was designed to evaluate the key factors that affect the learning outcome of medical students prior to entering clinical practice. In this study, we systemically analyzed the performance of a cohort of medical students at Jinan University School of Medicine participating in the recent CMLT. The analytical results of the medical students' written and objective structured clinical examination (OSCE) scores showed that their academic performance was predominantly associated with students' internship allocations, although other demographic characteristics such as sex, age, geographical origin of students, and grade point average (GPA) might be sporadically related to the students' OSCE performance at different OSCE stations. To explore the inherent reasons behind this, a survey was implemented among the medical students who participated in the examination to further interpret the factors influencing the students' learning outcome. The findings of this questionnaire manifested that intrinsic motivation and identified regulation acted as the major motivational profiles for the medical students from three different internship sites, whereas external regulation emerged as the crucial factor to make the students perform well academically in the CMLT. The result of this study suggested that strengthening the quality control of the clinical learning environment and improving medical administration may still be the most effective approaches to ensure the quality of clinical medical education.


Recent developments in the production and utilization of photosynthetic microorganisms for food applications.
The growing use of photosynthetic microorganisms for food and food-related applications is driving related biotechnology research forward. Increasing consumer acceptance, high sustainability, demand of eco-friendly sources for food, and considerable global economic concern are among the main factors to enhance the focus on the novel foods. In the cases of not toxic strains, photosynthetic microorganisms not only provide a source of sustainable nutrients but are also potentially healthy. Several published studies showed that microalgae are sources of accessible protein and fatty acids. More than 400 manuscripts were published per year in the last 4 years. Furthermore, industrial approaches utilizing these microorganisms are resulting in new jobs and services. This is in line with the global strategy for bioeconomy that aims to support sustainable development of bio-based sectors. Despite the recognized potential of the microalgal biomass value chain, significant knowledge gaps still exist especially regarding their optimized production and utilization. This review highlights the potential of microalgae and cyanobacteria for food and food-related applications as well as their market size. The chosen topics also include advanced production as mixed microbial communities, production of high-value biomolecules, photoproduction of terpenoid flavoring compounds, their utilization for sustainable agriculture, application as source of nutrients in space, and a comparison with heterotrophic microorganisms like yeast to better evaluate their advantages over existing nutrient sources. This comprehensive assessment should stimulate further interest in this highly relevant research topic.


Prevalence of Femoroacetabular Impingement Syndrome among Young and Middle-aged White Adults.
The purpose of the study was to determine the prevalence of femoroacetabular impingement syndrome (FAIS) in white adults 20 to 49 years of age. Participants were white men and women aged 20-49 years, recruited through random digit dialing from the population of Metro Vancouver, British Columbia, Canada. Participants filled out a self-administered questionnaire and underwent a physical examination and radiographs of both hips. FAIS was defined as a combination of hip symptoms, physical signs of impingement, and radiological findings of cam or pincer morphology as recommended by the Warwick Agreement. All analyses were weighted to reflect the population from which the sample was drawn. Data were obtained for 500 participants. In the study population, 48.9% were males and the age distribution was 32.2%, 31.4%, and 36.4% in the groups 20-29, 30-39, and 40-49 years, respectively. The physical signs of impingement correlated significantly with symptoms, but there was no significant association between either symptoms or physical examination with radiographic findings. FAIS on either side was found in 3.0% (95% CI 1.5-4.5) of the population. In this study, FAIS was present in 3% of whites aged 20-49 years. Further research is needed to develop consistent criteria for assessing hip symptoms, physical signs, and hip joint morphology, and to better understand the relationships between them.


Associations of BMI and Serum Urate with Developing Dementia: A Prospective Cohort Study.
Recent studies have suggested that a higher body mass index (BMI) and serum urate levels were associated with a lower risk of developing dementia. However, these reverse relationships remain controversial, and whether serum urate and BMI confound each other is not well established. To investigate the independent associations of BMI and urate, as well as their interaction with the risk of developing dementia. We analyzed a cohort of 502 528 individuals derived from the UK Biobank that included people aged 37-73 years for whom BMI and urate were recorded between 2006 and 2010. Dementia was ascertained at follow-up using electronic health records. During a median of 8.1 years of follow-up, a total of 2138 participants developed dementia. People who were underweight had an increased risk of dementia (hazard ratio [HR] = 1.91, 95% confidence interval [CI]: 1.24-2.97) compared with people of a healthy weight. However, the risk of dementia continued to fall as weight increased, as those who were overweight and obese were 19% (HR = 0.81, 95%: 0.73-0.90) and 22% (HR = 0.78, 95% CI: 0.68-0.88) were less likely to develop dementia than people of a healthy weight. People in the highest quintile of urate were also associated with a 25% (HR = 0.75, 95% CI: 0.64-0.87) reduction in the risk of developing dementia compared with those who were in the lowest quintile. There was a significant multiplicative interaction between BMI and urate in relation to dementia (P for interaction = 0.004), and obesity strengthens the protective effect of serum urate on the risk of dementia. Both BMI and urate are independent predictors of dementia, and there are inverse monotonic and dose-response associations of BMI and urate with dementia.


[Analysis on biomasses and contents of active components in roots of Salvia miltiorrhiza from different populations].
To provide some evidence for breeding excellent lines of Salvia miltiorrhiza. Contents of tanshinone II(A), cryptotanshinone, salvialic acid A and salvianolic acid B in root of S. miltiorrhiza from different populations were determined by HPLC. Total tanshinone and total salvianolic acids were determined by spectrophotometry. The biomass of individual plant from Zhongjiang of Sichuan province, content of tanshinone II(A), from Shanxi province, cryptotanshinone and total tanshinone from Zhongjiang of Sichuan province, salvialic acid A of High-Stem cultivation from Hebei province, salvianolic acid B and total salvianolic acids of tetroploid were higher than the other samples, respectively. With the value of biomass of individual plant multiplying contents of every active components as indicative constituents, the multiplying value from Zhongjiang of Sichuan province was higher than the other samples. With biomasses and effective components as indicative constituents, it suggested that S. miltiorrhiza from Zhongjiang of Sichuan province was a better derivative material.


Expression of SDF-1 alpha and nuclear CXCR4 predicts lymph node metastasis in colorectal cancer.
Although stromal cell-derived factor (SDF)-1 alpha and its receptor CXCR4 are experimentally suggested to be involved in tumorigenicity, the clinicopathological significance of their expression in human disease is not fully understood. We examined SDF-1 alpha and CXCR4 expression in colorectal cancers (CRCs) and their related lymph nodes (LNs), and investigated its relationship to clinicopathological features. Specimens of 60 primary CRCs and 27 related LNs were examined immunohistochemically for not only positivity but also immunostaining patterns for SDF-1 alpha and CXCR4. The relationships between clinicopathological features and SDF-1 alpha or CXCR4 expression were then analysed. Stromal cell-derived factor-1 alpha and CXCR4 expression were significantly associated with LN metastasis, tumour stage, and survival of CRC patients. Twenty-nine of 47 CXCR4-positive CRCs (61.7%) showed clear CXCR4 immunoreactivity in the nucleus and a weak signal in the cytoplasm (nuclear type), whereas others showed no nuclear immunoreactivity but a diffuse signal in the cytoplasm and at the plasma membrane (cytomembrane type). Colorectal cancer patients with nuclear CXCR4 expression showed significantly more frequent LN metastasis than did those with cytomembrane expression. Colorectal cancer patients with nuclear CXCR4 expression in the primary lesion frequently had cytomembrane CXCR4-positive tumours in their LNs. In conclusion, expression of SDF-1 alpha and nuclear CXCR4 predicts LN metastasis in CRCs.


Facilitating Transition from High School and Special Education to Adult Life: Focus on Youth with Learning Disorders, Attention-Deficit/Hyperactivity Disorder, and Speech/Language Impairments.
Youth with learning disorders, speech/language disorders, and/or attention-deficit/hyperactivity disorder may experience significant struggles during the transition from high school to postsecondary education and employment. These disorders often occur in combination or concurrently with behavioral and emotional difficulties. Incomplete evaluation may not fully identify the factors underlying academic and personal challenges. This article reviews these disorders, the role of special education law for transitional age youth in public schools, and the Americans with Disabilities Act in postsecondary educational and employment settings. The role of the child and adolescent psychiatrist and the importance of advocacy for these youth are presented.


ERR-activated GPR35 promotes immune infiltration level of macrophages in gastric cancer tissues.
Enhancer release and retargeting (ERR) events could activate disease-causing gene promoters for increasing the expression level of oncogenes. Meanwhile, class A orphan GPCRs (oGPCRs) are known as potential biomarkers or drug targets for various cancers, such as gastric cancer (GC). Hence, systemic investigation of ERR events for class A oGPCRs in GC could help to explore biomarkers for GC. In this study, ENCODE and GTEx eQTL data were utilized to define ERR events in GC. Only GPR35 was then detected that could be activated by ERR in GC based on these data and ChIP-seq. Then, activated GPR35 functional in GC cells were explored by flow cytometry, cell-based wound healing assay, Transwell migration assay, and M2 polarization of macrophages assay. Meanwhile, according to TCGA and GEO database, overall survival, immune-related gene expression, and immune cell infiltration level in different GPR35 expressions were calculated. Here, we found ERR event activate GPR35 results in GC cells proliferation and migration, and partly immune cells significance exhaustion (CD8 + T-cells and CD4 + memory T-cells) and/or infiltration (T-cells and macrophage). Meanwhile, high GRP35 level leads to a poor prognosis in GC patients, probably partly due to it promoting the immune infiltration level of macrophages and then inducing polarization of M2 macrophages. Notably, GPR35's high expression in CTSB+ and CD68 + macrophage could be a genetic indicator for early warning of primary GC. Hence, our findings provide a novel activation approach for oGPCRs, and GPR35 could be determined as a new drugable receptor and early genetic indicator for GC.


[Detoxifying function of the liver in patients with rubromycosis during treatment with antimycotics].
Oral therapy with nizoral and griseofulvin influences the system of cytochrome P = 450-dependent monoxygenases of the liver, this resulting in the depression of antipyrine microsomal oxidation. Recommendations are given on how to regard the data of antipyrine test over the course of therapy with oral antimycotic drugs.


Atmospheric antibiotic resistome driven by air pollutants.
The atmosphere is an important reservoir and habitat for antibiotic resistance genes (ARGs) and is a main pathway to cause potential health risks through inhalation and ingestion. However, the distribution characteristics of ARGs in the atmosphere and whether they were driven by atmospheric pollutants remain unclear. We annotated 392 public air metagenomic data worldwide and identified 1863 ARGs, mainly conferring to tetracycline, MLS, and multidrug resistance. We quantified these ARG's risk to human health and identified their principal pathogenic hosts, Burkholderia and Staphylococcus. Additionally, we found that bacteria in particulate contaminated air carry more ARGs than in chemically polluted air. This study revealed the influence of typical pollutants in the global atmosphere on the dissemination and risk of ARGs, providing a theoretical basis for the prevention and mitigation of the global risks associated with ARGs.


Molecular determinants of high affinity phenylalkylamine block of L-type calcium channels.
The high affinity phenylalkylamine (-)D888 blocks ion currents through L-type Ca2+ channels containing the alpha 1C subunit with an apparent Kd of 50 nM, but N-type Ca2+ channels in the pheochromocytoma cell line PC12 are blocked with a 100-fold higher Kd value of 5 microM. L-type Ca2+ channels containing alpha 1C subunits with the site-directed mutations Y1463A, A1467S, or I1470A in the putative transmembrane segment S6 in domain IV (IVS6) were 6-12 times less sensitive to block by (-)D888 than control alpha 1C. Ca2+ channels containing paired combinations of these mutations were even less sensitive to block by (-)D888 than the single mutants, and channels containing all three mutations were > 100 times less sensitive to (-)D888 block, similar to N-type Ca2+ channels. In addition, the Y1463A mutant and all combination mutants including the Y1463A mutation had altered ion selectivity, suggesting that Tyr-1463 faces the pore and is involved in ion permeation. Since these three critical amino acid residues are aligned on the same face of the putative IVS6 alpha-helix, we propose that they contribute to a receptor site in the pore that confers a high affinity block of L-type channels by (-)D888.


Effects of a mixture of low doses of atrazine and benzo[a]pyrene on the rat seminiferous epithelium either during or after the establishment of the blood-testis barrier in the rat seminiferous tubule culture model.
Atrazine (ATZ), a widely used agricultural pesticide and benzo[a]pyrene (BaP), a ubiquitous environmental human carcinogen can induce alterations of spermatogenesis. In the present study, we showed first that our seminiferous tubule culture model, in bicameral chambers, allowed the settlement of the blood-testis barrier (BTB) in 8-day-old male rat cultures and the differentiation of spermatogonia into round spermatids.The effect of a mixture of 1 μg/L of ATZ and 1 μg/L of BaP was then investigated either during or after the establishment of the BTB by using 8- or 20-22-day-old rats. Cultures were performed over a 3-week period. Our results show that claudin-11 and connexin 43 two proteins of the BTB, were impaired by the mixture which also reduced the number of round spermatids (the direct precursors of spermatozoa), by targeting the middle to late pachytene spermatocytes. These effects were observed in 8- and 20-22-day -old rat seminiferous tubule cultures. However, the decrease of the number of round spermatids was faster and more marked in the 8-day- than in the 20-22-day -old rat seminiferous tubule cultures. Our study emphasizes the possible influence of the age of an individual on the effect of (a) toxicant(s) on spermatogenesis.


Chronic thromboembolic pulmonary hypertension - assessment by magnetic resonance imaging.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe disease that has been ignored for a long time. However, with the development of improved therapeutic modalities, cardiologists and thoracic surgeons have shown increasing interest in the diagnostic work-up of this entity. The diagnosis and management of chronic thromboembolic pulmonary hypertension require a multidisciplinary approach involving the specialties of pulmonary medicine, cardiology, radiology, anesthesiology and thoracic surgery. With this approach, pulmonary endarterectomy (PEA) can be performed with an acceptable mortality rate. This review article describes the developments in magnetic resonance (MR) imaging techniques for the diagnosis of chronic thromboembolic pulmonary hypertension. Techniques include contrast-enhanced MR angiography (ce-MRA), MR perfusion imaging, phase-contrast imaging of the great vessels, cine imaging of the heart and combined perfusion-ventilation MR imaging with hyperpolarized noble gases. It is anticipated that MR imaging will play a central role in the initial diagnosis and follow-up of patients with CTEPH.


Seasonal variability of sialo-glycoconjugates in the brain of the Djungarian hamster (Phodopus sungorus).
The influence of season, photoperiod and ambient temperature on the content of proteins, sialo-glycoproteins and gangliosides and on the composition of gangliosides of three different brain regions (cortex, cerebellum and basalbrain) of the Djungarian dwarf hamster (Phodopus sungorus) had been investigated. Concomittantly changes in body wt and fur colouration were recorded. Dwarf hamsters living under natural photoperiod and ambient temperature conditions ("outside") showed a distinct annual cycle in body wt (summer: about 45 g; winter: about 25 g) and fur colouration (summer: dark grey; winter: whitish). Among the three brain regions the mean concentration of proteins ranged between 120 and 155 mg protein/g wet wt. The sialo-glycoprotein content varied between 260 and 410 micrograms NeuAc/g wet wt, and that of gangliosides between 800 and 1650 micrograms NeuAc/g wet wt. Seasonal fluctuations were not found. The composition of brain gangliosides remained uninfluenced throughout the year in the cerebellum, whereas seasonal variations were observed in cortex and basalbrain. Consequently the concentration ratio of the two major mammalian ganglioside fractions GD1a vs GT1b remained almost stable in cerebellum (0.3). In contrast to this the seasonal values of cortex and basalbrain changed from 0.6 and 0.8 in winter to 0.7 and 1.1 in summer. This indicated a higher polarity of the gangliosides in these brain regions during cold adaptation. The results are discussed with regard to modulatory functions of neuronal gangliosides for the process of synaptic transmission during seasonal adaptation.


Hot-pressed membrane assemblies enhancing the biofilm formation and nitrogen removal in a membrane-aerated biofilm reactor.
Membrane-aerated biofilm reactor (MABR) is gaining popularity in wastewater treatment as a result of the low-energy delivery of oxygen from the carrier side and reduced sludge waste production, although its wider application suffers from the difficulty in microbial colonization on the smooth, hydrophobic membrane surface. In this study, a newly designed membrane/non-woven fabric assembly, prepared via a facile hot-pressing method, is demonstrated to be efficient in promoting the biofilm formation and nitrogen removal in MABR. The assembly achieved rough surface structure to retain biomass whilst sustained the surface hydrophobicity for a high oxygen transfer ability, which is crucial to support a resilient biofilm. Compared with the slower biomass growth and severe detachment of biofilm in the control, a thicker biofilm was quickly developed on the hot-pressed membrane assembly. High loading rates of organic matter, ammonia nitrogen and total nitrogen (TN) in the MABR using the hot-pressed membrane were 154.9 ± 5.4 g COD/(m2·d), 25.5 ± 0.6 g N/(m2·d) and 22.6 ± 0.7 g N/(m2·d), respectively. Particularly, the removal efficiency of TN was up to 82.8%, which was 2.5 times higher than the control. Furthermore, the biofilm grown on the hot-pressed membrane assembly organized a stable microbial community structure with a steady evolution to achieve a synergistic denitrifying function. Among the bacterial phylotypes, OLB8 might be crucial in denitrification. This study highlighted the significance of this facile membrane modification method to improve the process performance of MABR in wastewater treatment.


Ethics and Privacy in Social Media Research for Mental Health.
This review provides an overview of recent research which uses social media data in the context of mental health. It also provides an overview of challenges in relation to consent, privacy, and usage of such data. A broad range of research has been conducted in recent years, using text-based and visual data from social media platforms, for purposes such as risk detection at the individual level, providing crisis outreach, and developing a better understanding of the lived experience of mental ill-health. Challenges remain in relation to obtaining truly informed consent for research using social media data-however platforms allowing data donation may address these concerns. There is an imperative need to ensure that privacy is preserved at all stages of the research process, from data collection, to analysis, and the responsible use of raw data in publications.