The changing dynamics of neutralizing antibody response within 10 months of SARS-CoV-2 infections.
There are limited data on how long neutralizing antibody (NAb) response elicited via primary SARS-CoV-2 infection will last. Eighty-four serum samples were obtained from a prospective cohort of 42 laboratory-confirmed COVID-19 inpatients at the time of discharge from the hospital and in the late convalescent phase. A virus neutralization assay was performed to determine the presence and titers of NAbs with authentic SARS-CoV-2. Long-term dynamics of NAbs and factors that may have an impact on humoral immunity were investigated. Mild and moderate/severe patients were compared. The mean sampling time was 11.12 ± 5.02 days (4-28) for the discharge test and 268.12 ± 11.65 days (247-296) for the follow-up test. NAb response was present in 83.3% of the patients about 10 months after infection. The detectable long-term NAb rate was significantly higher in mild patients when compared to moderate/severe patients (95.7% vs. 68.4%, p = 0.025). In the follow-up, NAb-positive and -negative patients were compared to determine the predictors of the presence of long-term humoral immunity. The only significant factor was disease severity. Patients with mild infections have more chance to have NAbs for a longer time. Age, gender, and comorbidity did not affect long-term NAb response. NAb titers decreased significantly over time, with an average rank of 24.0 versus 19.1 (p = 0.002). Multivariate generalized estimating equation analysis revealed that no parameter has an impact on the change of NAb titers over time. The majority of the late convalescent patients still had detectable low levels of neutralizing antibodies. The protective effect of these titers of NAbs from re-infections needs further studies.


Mitochondrial injury induced by nanosized titanium dioxide in A549 cells and rats.
The nanosized titanium dioxide (nano-TiO2) is an important nanoscale compound applied in many different fields because of its superior performance. Here, an anatase nano-TiO2 showed cytotoxicity in a dosage-dependent manner, which was in accordance with changes of A549 cell ultrastructure, A549 cell viability and intracellular ATP level. The lungs of rats treated with single intratracheal instillation of nano-TiO2 were injured, which was demonstrated by changes of alveolar epithelial cell ultrastructure, lung tissue pathology and lung tissue MDA level. The results of this study indicated that nano-TiO2 should be related to the generation of intracellular reactive oxygen species (ROS), which injured mitochondria and prevented the synthesis of ATP. The cells were approaching to apoptosis eventually. In macroscopic view, the lungs inevitably suffered.


In vivo optical coherence tomography feasibility for bladder disease.
Optical coherence tomography is a new imaging modality capable of imaging luminal surface of biological tissue in the near infrared range with a spatial resolution close to the cellular level. We identified characteristic optical coherence tomography patterns for nonproliferative and proliferative inflammation, and malignant alterations of the bladder. Optical coherence tomography was performed to image the bladder of 66 patients. The probe passed through the operating channel of a cystoscope and was pressed onto the mucosal site of interest. A mucosal biopsy of the image site was obtained. Optical coherence tomography was used to construct 680 images of the bladder and the images were compared with histology slides. Optical coherence tomography images of normal bladder showed 3 layers, namely the mucosa or transitional epithelium, submucosa and smooth muscle. In exudative processes there were poor light scattering areas in the connective tissue layer. Images of bladders with proliferative cystitis revealed nonuniform thickening of the epithelium or hyperplasia. Squamous metaplasia appeared as thicker and less transparent epithelium with a jagged boundary. Images of transitional cell carcinoma were characterized by the complete loss of a regular layered structure of the bladder wall and the penetration depth of optical imaging was slight. This study provides the characteristic optical coherence tomography pattern of nonproliferative and proliferative inflammation, and the characteristic appearance of severe dysplasia and transitional cell carcinoma. This technique may be useful as a guide for biopsy and for assisting in establishing resection margins.


Phase II study of use of a single cycle of induction chemotherapy and concurrent chemoradiotherapy containing capecitabine/cisplatin followed by surgery for patients with resectable esophageal squamous cell carcinoma: long-term follow-up data.
This phase II study evaluated the feasibility and efficacy of one cycle of induction chemotherapy, followed by concurrent chemoradiotherapy (CRT) featuring capecitabine/cisplatin, followed in turn by surgery, in the treatment of patients with resectable esophageal squamous cell carcinoma. Between March 2003 and April 2005, 54 patients with stage II or III esophageal cancer were treated with induction chemotherapy (cisplatin 60 mg/m(2) on day 1; capecitabine 1,000 mg/m(2) bid on days 1-14) followed by concurrent radiotherapy (46 Gy in 23 fractions) and chemotherapy (cisplatin 30 mg/m(2) on days 1, 8, 15, and 22; capecitabine 800 mg/m(2) bid 5 days/week). Surgery was performed within 8 weeks of the end of radiotherapy. Median age of the patients was 64.5 years (range, 45-74 years). After CRT, 52 patients (96%) showed a clinical response, including 26 (48%) who exhibited a complete response (CR). Surgery was performed on 41 patients (76%), with 20 (37%) achieving pathologic CR and 3 (6%) dying of postoperative pneumonia. At a median follow-up time of 74.2 months (range, 64.3-84.8 months), 16 patients (30%) had experienced tumor recurrence and 36 (67%) had died. Of the 41 patients who underwent esophagectomy, 5 (12%) had exclusively locoregional disease and 7 (17%) had distant metastasis, whereas no one had both. The 5-year progression-free and overall survival rates were 30.2% (95% confidence interval [CI], 18.0-42.4%) and 37.0% (95% CI, 24.1-50.0%), respectively. A trimodal approach, consisting of a single cycle of induction chemotherapy, CRT containing capecitabine and cisplatin, and surgery, was feasible and effective in patients with resectable esophageal squamous cell carcinoma.


The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer.
There is increasing and consistent evidence that cancer-associated inflammation is a key determinant of outcome in patients with cancer. Various markers of inflammation have been examined over the past decade in an attempt to refine stratification of patients to treatment and predict survival. One routinely available marker of the systemic inflammatory response is the neutrophil-lymphocyte ratio (NLR), which is derived from the absolute neutrophil and absolute lymphocyte counts of a full blood count. To date, over 60 studies (>37,000 patients) have examined the clinical utility of the NLR to predict patient outcomes in a variety of cancers. The present systematic review examines and comments on the clinical utility of the NLR. The NLR had independent prognostic value in (a) unselected cohorts (1 study of >12,000 patients), (b) operable disease (20 studies, >4000 patients), (c) patients receiving neoadjuvant treatment and resection (5 studies, >1000 patients), (d) patients receiving chemo/radiotherapy (12 studies, >2000 patients) and (e) patients with inoperable disease (6 studies, >1200 patients). These studies originated from ten different countries, in particular UK, Japan, and China. Further, correlative studies (15 studies, >8500 patients) have shown that NLR is elevated in patients with more advanced or aggressive disease evidenced by increased tumour stage, nodal stage, number of metastatic lesions and as such these patients may represent a particularly high-risk patient population. Further studies investigating the tumour and host-derived factors regulating the systemic inflammatory response, in particular the NLR, may identify novel treatment strategies for patients with cancer.


Mutagenicity of methyl isocyanate in the modified test conditions of Ames Salmonella/microsome liquid-preincubation procedure.
Methyl isocyanate (MIC) was tested for mutagenicity using the Ames Salmonella/microsome liquid-preincubation procedure with slight modification of test conditions. In the modification the preincubation mixture was incubated at 10 degrees C for 60 min. MIC was assayed both in the presence and absence of Aroclor-1254-induced S9, using 5 tester strains of Salmonella typhimurium, TA97a, TA98, TA100, TA102 and TA104. MIC induced mutagenic response in two base-pair substitution strains, TA100 and TA104, in the presence and absence of S9. However, mutagenic response in the presence of S9 was low as compared to that in the absence of S9. In the comparative mutagenic activity at 3 different preincubation test conditions (37 degrees C for 20 min, 20 degrees C for 40 min and 10 degrees C for 60 min), optimum mutagenic response was observed at 10 degrees C for the 60-min test condition. However, no mutagenic response was observed at 37 degrees C for the 20-min test condition.


Inhibition by anti-inflammatory agents of contraction induced by epidermal growth factor-urogastrone in isolated longitudinal smooth muscle strips from guinea-pig stomach.
1. Epidermal growth factor-urogastrone (EGF-URO) caused a concentration-dependent contractile response of longitudinal muscle strips from the gastric body of the guinea-pig stomach. The contractile response to EGF-URO was monophasic, with tension returning rapidly to baseline. Desensitization was evident in that further addition of EGF-URO to the organ bath did not cause a second contraction. 2. Preincubation with indomethacin, ibuprofen, naproxen and aspirin markedly inhibited the contractions induced by EGF-URO with an order of potency (indomethacin greater than naproxen greater than ibuprofen greater than aspirin) that reflected the ability of these agents to inhibit cyclo-oxygenase. 3. The data indicate that prostanoids mediate the action of EGF-URO in the longitudinal muscle preparation. 4. Auranofin (0.5 to 50 microM), a chrysotherapeutic agent with antiproliferative properties used for treating rheumatoid arthritis, also markedly inhibited the EGF-URO response; however, other gold-containing compounds (aurothioglucose or gold sodium thiomalate at 30 to 100 microM) failed to cause significant inhibition. 5. Preincubation of preparations for 2 h with 1 microM hydrocortisone, prednisolone or dexamethasone caused an inhibition of EGF-URO-induced contraction of approximately 50%. However, steroids lacking either a 17 alpha-hydroxyl (corticosterone) or an 11 beta-hydroxyl (cortisone, deoxycorticosterone, prednisone) substituent did not inhibit the contraction caused by EGF-URO. For hydrocortisone, the inhibitory effect was half-maximal at 0.2 microM and was maximal at 1 microM. Cycloheximide (10 microM) blocked the inhibitory action of hydrocortisone and potentiated the contractile action of EGF-URO. 6. The ability of a variety of steroidal and non-steroidal anti-inflammatory agents to interfere with the action of EGF-URO in a smooth muscle preparation suggests that these agents may also inhibit the action of EGF-URO mediated by prostanoids in other target tissues. 7. The data also point to a potential role for EGF-URO in regulating gastric motility.


The spectrum of renal involvement in male patients with infertility related to excretory-system abnormalities: phenotypes, genotypes, and genetic counseling.
While reproductive technologies are increasingly used worldwide, epidemiologic, clinical and genetic data regarding infertile men with combined genital tract and renal abnormalities remain scarce, preventing adequate genetic counseling. In a cohort-based study, we assessed the prevalence (1995-2014) and the clinical characteristics of renal disorders in infertile males with genital tract malformation. In a subset of 34 patients, we performed a detailed phenotype analysis of renal and genital tract disorders. Among the 180 patients with congenital uni- or bilateral absence of vas deferens (CU/BAVD), 45 (25 %) had a renal malformation. We also identified 14 infertile men with combined seminal vesicle (SV) and renal malformation but no CU/BAVD. Among the 34 patients with detailed clinical description, renal disease was unknown before the assessment of the infertility in 27 (79.4 %), and 7 (20.6 %) had chronic renal failure. Four main renal phenotypes were observed: solitary kidney (47 %); autosomal-dominant polycystic kidney disease (ADPKD, 0.6 %); uni- or bilateral hypoplastic kidneys (20.6 %); and a complex renal phenotype associated with a mutation of the HNF1B gene (5.8 %). Absence of SV and azoospermia were significantly associated with the presence of a solitary kidney, while dilatation of SV and necroasthenozoospermia were suggestive of ADPKD. A dominantly inherited renal disease (ADPKD or HNF1B-related nephropathy) is frequent in males with infertility and combined renal and genital tract abnormalities (26 %). A systematic renal screening should be proposed in infertile males with CU/BAVD or SV disorders.


Innate immunity and vaccine.
Immune adjuvant is an artificial pathogen-associated molecular patterns (PAMP) for potentiating various immune responses. Vaccine represents one event that is capable of inducing immune response caused by antigen and PAMP stimuli, which act on antigen-presenting dendritic cells (mDCs). Here, we introduce the pathways by which CTL and NK cells are driven through mDC maturation in response to adjuvants.


Down-regulation of protein kinase C and of an endogenous 80-kDa substrate in transformed fibroblasts.
Subconfluent cultures of NIH-3T3 fibroblasts transformed by the Ha-ras, Ki-v-ras, v-src, and v-fms oncogene proteins all possess elevated steady-state levels of diacylglycerol, the endogenous activator of protein kinase C, as compared to the nontransformed parental lines. These oncogene-transformed fibroblasts also exhibit a significantly decreased level of cellular protein kinase C activity as measured by four different criteria: phorbol ester-stimulated phosphorylation of an endogenous 80-kilodalton (80 kDa) substrate; phorbol ester-stimulated changes in 86Rb uptake; enzymatic assay; and [3H]phorbol ester binding. In all cases, the transformed cells demonstrated an attenuated response to phorbol ester addition and a lower phorbol ester binding capacity as compared to the parental lines. Western analysis of the endogenous 80-kDa substrate of protein kinase C revealed a significantly lower level of this protein in the transformed cells than in the untransformed controls, and this decrease could be mimicked in parental cells by long-term incubation with phorbol esters, suggesting that the level of the 80-kDa protein is regulated by the state of activation of protein kinase C. These effects do not appear to be nonspecific responses to autocrine secretions by the transformed cells. They may represent an unsuccessful attempt by the transformed cells to negatively modulate the constitutive proliferative signals generated by the oncogene products.


Interventions targeting absences increase adherence and reduce abandonment of childhood cancer treatment in El Salvador.
In El Salvador, about 200 new cases of pediatric cancer are diagnosed each year, and survival rates approach 70%. Although treatment is available at no cost, abandonment of therapy has remained at a steady yearly rate of 13% during the past decade. A time sensitive adherence tracking procedure (TS-ATP) was recently implemented to detect missed appointments, identify their causes, and intervene promptly. Procedure The study team was informed daily of patient/family failure to attend medical appointments in the pediatric oncology unit; the families were contacted and interviewed to ascertain and address the reasons. Patients who did not return after this initial contact were contacted again through local health clinics and municipalities. Law enforcement was a last resort for patients undergoing frontline treatment with a good prognosis., The system was adapted to clinical urgency: families of patients undergoing induction therapy were contacted within 24 hr, those in other therapy phases, within 48 hr, and those who had completed treatment, within one week. Reasons for absence were obtained by telephone or in person. The annual rate of abandonment was reduced from 13-3% during the 2 years period. There were 1,111 absences reported and 1,472 contacts with caregivers and institutions. The three main reasons for absences were financial needs (165, 23%), unforeseen barriers (116, 16%), and domestic needs (86, 12%). Use of the treatment adherence tracking system to locate and communicate with patients/families after missed appointments and the allocated aid stemming from these interviews substantially reduced abandonment and non-adherence.


A Novel Navigation for Laparoscopic Anatomic Liver Resection Using Indocyanine Green Fluorescence.
Among all laparoscopic liver resection techniques, anatomic liver resection is one of the most challenging procedures, with disorientation readily occurring during the laparoscopic approach compared with the open approach.1 Thus, navigation is warranted for laparoscopic anatomic liver resection. Recent research has remarkably established intraoperative fluorescence imaging techniques using indocyanine green fluorescence (ICG) in the field of liver surgery.2-4 This report describes real-time navigation for anatomic liver resection using the novel ICG system, PINPOINT (Stryker, Kalamazoo, MI). The target Glissonian pedicle was identified and temporally clamped after confirmation of blood supply to the preserved adjacent segment using ultrasonography. Next, 1.5 mg of ICG was intravenously administered using the negative counterstaining method. After 3 min of administration, the ICG-stained area could be readily recognized. Parenchymal transection was subsequently initiated along the interface between the ICG-positive and ICG-negative areas using the Pringle maneuver. Using PINPOINT, laparoscopic anatomic liver resection was performed for 16 patients. The extent of liver resection comprised two left hepatectomies, three right-anterior sectionectomies, three right-anterior sectionectomies, and eight segmentectomies. The identification rate of clear demarcations in the ICG images was 100%. The intraoperative blood loss was 226 mL, and the operative time was 305 min. Only one patient encountered the major postoperative complication of ascites, and all the patients attained R0 resection. Because the images provided by the ICG system are clearer than conventional ICG images, it could facilitate real-time navigation for laparoscopic anatomic liver resection.


Carbonic anhydrase 9 (CA9) expression in tumor cells enhances sensitivity to tirapazamine.
Carbonic anhydrase 9 (CA9) is over-expressed in many human solid tumors under conditions of low oxygen concentration and can be associated with a low probability of survival. In this study, stable CA9-expressing cell lines were established using the CA9 gene-defective human C33a cell line and the HeLa cell line to investigate the role of CA9 in response to ionizing radiation and hypoxia-selective cytotoxin, Tirapazamine (TPZ). Human CA9 cDNA or an empty vector was transfected into the C33a and HeLa cell lines and C33a-vector, C33a-CA9, HeLa-vector, and HeLa-CA9 cell lines were produced accordingly. Sensitivity of the C33a-vector/C33a-CA9 cells to ionizing radiation and TPZ was measured using clonogenic assays. The alkaline comet assay was used to measure single strand DNA breaks caused by TPZ in the C33a-vector, C33a-CA9, HeLa-vector, and HeLa-CA9 cell lines. Radiation sensitivity, as determined with clonogenic survival assays, of C33a-vector/C33a-CA9 cells did not differ under either normoxic or hypoxic conditions. However, increased clonogenic sensitivity to TPZ was observed in C33a-CA9 cells under the hypoxic condition by 26% (95% CI 14-39%, P = 0.02 in comparison to the C33a-vector cells). The comet assay showed significantly greater DNA damage in the C33a-CA9 cells compared with that of the C33a-vector cells with the same treatment under hypoxic conditions, supporting the results of the clonogenic survival data. Because this difference in the amount of DNA damage was not observed for the hypoxic HeLa-CA9/HeLa-vector cell lines, both of which have induced CA9 expression by hypoxia, the enhanced sensitivity of C33a-CA9 cells to TPZ is considered to be due to the specific condition of CA9 over-expression. Our results suggest the possibility that CA9 over-expression in tumors might be exploited to increase the treatment effects of TPZ.


Experimental and theoretical studies on the acetaldehyde reaction with (+)-catechin.
Acetaldehyde plays a key role in determining some wine properties. Interesting is the reaction of acetaldehyde with flavonoids, as the ensuing products can alter wine color, astringency, colloidal stability. Many studies reported on the formation of ethylidene-bridged flavan-3-ols as products of the reaction between acetaldehyde and either (+)-catechin or (-)-epicatechin. In white wines after one year of incubation with acetaldehyde only vinyl-(+)-catechin and vinyl-(-)-epicatechin were observed, while no ethylidene linked oligomers were detected. This observation prompted us to study the reaction of (+)-catechin with acetaldehyde in wine model solution through an experimental and theoretical approach, with the purpose of exploring the nature of the species involved along with the mechanisms leading to them. The products of the reaction were observed over 38 days. The results showed that ethylidene-bridged catechins are the first products to be formed but over time the dissociation of these dimers causes vinyl-catechins to accumulate.


Acute eosinophilic cholecystitis in association with hepatic echinococcosis.
A patient with acute eosinophilic cholecystitis is presented. This was in association with hepatic hydatid disease and was the presenting feature of that disease.


[Operations of vascular brain tumors using pharmacologico-physical metabolic depression and hypotension. Report of experiences in 50 operations].
On the basis of experience gained in operations for cerebral tumours rich in blood vessels in 50 patients the advantages of the combination of a pharmacological-physical reduction of the metabolism and hypotension is dealt with. Nitroprusside sodium hypotension is inferior to this procedure. The experience gained in the different groups is broken down in detail.


Significance of p53 overexpression in bone marrow biopsies from patients with bone marrow failure: aplastic anemia, hypocellular refractory anemia, and hypercellular refractory anemia.
Among patients with bone marrow failure, differentiating acquired aplastic anemia (AA) from hypocellular refractory anemia (hypo RA) can be a difficult and challenging task. Morphological, cytochemical, immunocytochemical, and cytogenetic studies may provide tools for discriminating between both entities. In addition, differences in the pattern of proliferation and apoptosis of bone marrow cells in AA and in the myelodysplastic syndrome have been reported. Because of the correlation between p53 and apoptosis, we examined the overexpression of p53 on bone marrow biopsies in RA and AA. Our study included 14 patients with hypo RA, 14 patients with hypercellular (hyper) RA, ten patients with classic acquired AA, and 37 hematologically normal individuals. p53 was overexpressed in eight (57%) hypo RA patients and 11 (79%) hyper RA patients. All normal individuals and patients with AA showed no overexpression of p53 in their marrow. These results were statistically significant:p < 0.01 (AA vs hypo RA), p<0.001 (AA vs hyper RA), while the difference between hypo RA and hyper RA was not statistically significant. We conclude that p53 overexpression in bone marrow biopsies is a valuable tool for studying bone marrow failure and may provide additional information to help differentiate hypo RA from acquired AA.


Baseline sebum IL-1α is higher than expected in afro-textured hair: a risk factor for hair loss?
To investigate changes in sebum cytokines in response to hair cosmetics. Design and setting A prospective study at a University hospital. We used a novel method for scalp surface sebum collection (Sebutape(®)) on three visits, sequentially a week apart, to investigate changes in six cytokines in 36 healthy women before and after shampoo and compared various chemical treatments (ammonium thioglycolate, "lye" sodium hydroxide and "no-lye" guanidine hydroxide relaxers) performed by a professional hairdresser. Significant levels detected were IL-1 alpha (IL-1α) and IL-1 receptor antagonist (IL-1ra), which were higher in untreated scalp vs. forehead: P < 0.001. Baseline levels of scalp sebum IL-1α were 18 times higher than IL-1ra. The levels of IL-1α decreased uniformly after shampoo (visit 1) and various chemical treatments (both crown and vertex all P < 0.001 - visit 2) but increased on follow-up at visit 3. Decreases in IL-1ra mimicked IL-1α at the vertex [after shampoo (P = 0.018) and visit 3 (P = 0.014)], but not on the crown, a finding which may suggest site-specific scalp predisposition to inflammation. The ratio of IL-1ra/IL-1α increased in all groups after all chemical treatments and on follow-up (all P < 0.001) but was surprisingly not significantly different from natural hair that underwent shampoo. A wider cytokine panel may reveal response differences in treatment groups. Baseline inflammatory scalp cytokines are higher than expected and reduce with shampooing. Scrutiny of the influence of hair moisturizer formulations and shampoo intervals and studies investigating pro-fibrotic cytokines are required. This may elucidate the predilection of afro-textured hair to scarring alopecia.


Selenomethionine mitigate PM2.5-induced cellular senescence in the lung via attenuating inflammatory response mediated by cGAS/STING/NF-κB pathway.
Particulate matter 2.5 (PM2.5) is a widely known atmospheric pollutant which can induce the aging-related pulmonary diseases such as acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary fibrosis (IPF). In recent years, with the increasing atmospheric pollution, airborne fine PM2.5, which is an integral part of air pollutants, has become a thorny problem. Hence, this study focused on the effect of PM2.5 on cellular senescence in the lung, identifying which inflammatory pathway mediated PM2.5-induced cellular senescence and how to play a protective role against this issue. Our data suggested that PM2.5 induced time- and concentration-dependent increasement in the senescence of A549 cells. Using an inhibitor of cGAS (PF-06928215) and an inhibitor of NF-κB (BAY 11-7082), it was revealed that PM2.5-induced senescence was regulated by inflammatory response, which was closely related to the cGAS/STING/NF-κB pathway activated by DNA damage. Moreover, our study also showed that the pretreatment with selenomethionine (Se-Met) could inhibit inflammatory response and prevent cellular senescence by hindering cGAS/STING/NF-κB pathway in A549 cells exposed to PM2.5. Furthermore, in vivo C57BL/6J mice model demonstrated that aging of mouse lung tissue caused by PM2.5 was attenuated by decreasing cGAS expression after Se-Met treatment. Our findings indicated that selenium made a defense capability for PM2.5-induced cellular senescence in the lung, which provided a novel insight for resisting the harm of PM2.5 to human health.


Intravitreal bevacizumab for macular oedema secondary to branch retinal vein occlusion.
To report short-term results of intravitreal bevacizumab (IVB) injection for macular oedema (ME) associated with branch retinal vein occlusion (BRVO). Retrospective interventional case series of 12 eyes of 12 consecutive patients. IVB injections (1.25 mg/0.05 ml) were given as needed based on the presence of ME on optical coherence tomography. Changes in Snellen visual acuity (VA) and central macular thickness (CMT) were analysed using the Student's paired t-test. At a mean follow-up of 9.8 months (range: 6-17 months), the mean number of IVB injections given was 4 (range: 1-6). No ocular or systemic side effects were noted. The differences in logMAR VA between baseline and 1 month, between baseline and 6 months, and between baseline and final follow-up were statistically significant (P<0.05). The differences in CMT between baseline and 1 month, baseline and 6 months, and between baseline and final follow-up were also statistically significant (P<0.05). Short-term results indicate that IVB is useful in decreasing ME and improving VA in eyes with BRVO.


Two-week stimulation or blockade of the sympathetic nervous system in man: influence on body weight, body composition, and twenty four-hour energy expenditure.
Seven lean healthy young men were studied for 6 weeks during exposure to pharmacologic inhibition or stimulation of the sympathetic nervous system. For a period of 2 weeks their beta-adrenergic receptors were either blocked with propranolol hydrochloride (160 mg/d) or stimulated with terbutaline sulphate (15 mg/d). After a further 2 weeks of placebo administration (500 mg lactose/d), the subjects crossed over to the drug they had not been taking at the beginning of the experiment for another 14 days. During the last five days of each 2-week period, the subjects consumed a weight-maintaining diet, composed of 12% protein, 48% carbohydrate, and 40% fat. They consumed exactly the same menus on the same days during the subsequent study periods. Body weight and physical activity were measured every day for 6 weeks. Daily heart rate and nitrogen excretion were measured continuously for days at the end of each 2-week period, the last two days of which were spent in a respiration chamber where energy expenditure and a variety of metabolic parameters were measured. In the respiration chamber on the propranolol, placebo, and terbutaline treatments, respectively, significant differences were observed in mean daily heart rate (65 +/- 3, 75 +/- 4, and 84 +/- 4 beats/min), mean sleeping heart rate (51 +/- 2, 56 +/- 3, and 62 +/- 3 beats/min), nitrogen excretion (13.6 +/- 0.7, 12.6 +/- 0.6, and 11.9 +/- 0.6 g/d), fat oxidation (+1,045 +/- 95, +1,243 +/- 148, and +1,278 +/- 84 kcal/d) and thyroid hormones (12.0 +/- 0.7, 15.7 +/- 0.9, and 17.2 +/- 1.0 T3/T4 ratio).(ABSTRACT TRUNCATED AT 250 WORDS)


Quantitative capillary gel electrophoresis assay of phosphorothioate oligonucleotides in pharmaceutical formulations.
Quantitative capillary gel electrophoresis (QCGE) has been developed for the accurate quantitation of a 21-mer phosphorothioate oligonucleotide, ISIS 2922, and its degradation products in an intravitreal formulation. The electrokinetic mode of injection employed by CGE necessitates formulation of the external reference standard in a sample matrix similar to that of the drug product and the use of an internal standard for improved accuracy and precision. The analytical method detailed in this paper has demonstrated the necessary accuracy, precision, linearity, range, selectivity and ruggedness for use in routine drug product analysis and stability monitoring of phosphorothioate oligonucleotides.


Retraction Note: Oncogenic transformation of human lung bronchial epithelial cells induced by arsenic involves ROS-dependent activation of STAT3-miR-21-PDCD4 mechanism.
This article has been retracted.


Cr(VI) removal using different reducing agents combined with fly ash leachate: A comparative study of their efficiency and potential mechanisms.
Remediation of high concentrations of Cr(VI) in wastewater involves its chemical reduction to Cr(III), a product with low toxicity that can be easily removed. To date, NaBH4 has rarely been used to reduce Cr(VI). This article reports a comparative study of Cr(VI) removal by NaBH4 and five sulfur-based reducing agents (FeSO4, Na2S2O5, NaHSO3, Na2S2O3, and Na2SO3). The potential mechanisms of Cr(VI) removal by these six reducing agents with and without fly ash leachate (FAL) are also discussed. The results revealed that the reduction and subsequent removal of Cr(VI) are influenced by the hydrolysis and ionization of the reducing agents in solution. Thus, the reduction reaction was significantly enhanced when Na2S2O5 and NaHSO3 were added in excess of 600 mg L-1. Combined with FAL, smaller amounts of NaBH4 were required to reduce Cr(VI) to Cr(III) at pH 3.0 compared to those with the other reducing agents. NaBH4 combined with FAL at a dose of 100 mg L-1 afforded a total Cr (CrT) removal of 96.32% within 20 min, a value much higher than that obtained with the other reducing agents. The catalytic mechanism of NaBH4 for such a FAL-catalyzed Cr(VI) reduction system is similar to that of acid catalysis via the hydrolysis of the Fe(III) and Al(III) species in FAL. Improvement of the CrT removal was also observed via Cr(VI) entrapment in the structure of Fe(III) and Al(III) metal hydroxides. These results indicate that relatively low loadings of NaBH4 combined with FAL show great promise for Cr(VI) pollution remediation.


A Lactococcus lactis-vectored oral vaccine induces protective immunity of mice against enterotoxigenic Escherichia coli lethal challenge.
Enterotoxigenic Escherichia coli (ETEC) is a global primary pathogenic bacterium causing diarrhoea in human and a wide variety of neonatal animals. Lactococcus lactis as non-pathogenic and food-grade lactic acid bacteria has already been explored as a vector for mucosal vaccine. Here, the current study was undertaken to evaluate the live recombinant L. lactis (rL. lactis) vaccine expressing the trivalent enterotoxin protein STa-LTB-STb and the F5 fimbrial antigen (SLS-F5) with OmpH of Yersinia enterocolitica in protection against ETEC. Western blot confirmed the expression of fusion protein SLS-F5-OmpH in nisin-controlled expression (NICE) system. Mice orally immunized with rL. lactis-SLS-F5-OmpH were observed to produce high levels of mucosal SIgA and serum IgG antibodies, while also inducing increases in the production of CD4+ and CD8+ T cells, lymphocyte proliferation, and secretion of cytokines. Moreover, orally immunized mice produced complete protection after ETEC challenge. The above results suggested that rL. lactis-SLS-F5-OmpH has the potential as a candidate for oral vaccine against ETEC.


Long-term preservation of fungal isolates in commercially prepared cryogenic microbank vials.
Since 1994, 6,198 yeasts and 391 molds belonging to 25 and 37 species, respectively, were stored in Microbank cryogenic vials at >/=-130 degrees C in liquid nitrogen and at -70 degrees C in a freezer. All of the isolates, with the exception of 45 yeasts and 15 dermatophytes, were recovered from both storage temperatures. Good reproducibility was demonstrated for amphotericin B, fluconazole, and voriconazole MICs determined for random isolates.


Approach to adult patients with primary hypothyroidism in some special situations: a position statement from the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM).
Primary hypothyroidism is a common disorder in clinical practice. The management of most cases of hypothyroidism is usually straightforward, but the best approach in some special situations may raise questions among physicians. This position statement was prepared by experts from the Brazilian Society of Endocrinology and Metabolism to guide the management of three special situations, namely, hypothyroidism in the elderly, subclinical hypothyroidism in patients with heart disease, and difficult-to-control hypothyroidism. The authors prepared the present statement after conducting a search on the databases MEDLINE/PubMed, LILACS, and SciELO and selecting articles with the best evidence quality addressing the selected situations. The statement presents information about the current approach to patients in these special situations.


Effect of insulin-like growth factor-I on cholesterol side-chain cleavage cytochrome P450 messenger ribonucleic acid expression in ovarian theca-interstitial cells stimulated to differentiate in vitro.
Currently available evidence supports the hypothesis that insulin-like growth factor-I (IGF-I) may play a role in stimulating ovarian theca-interstitial cell (TIC) differentiation in preantral follicles. The purpose of the present studies was to examine the potential role of IGF-I in TIC differentiation by determining the effects of IGF-I on cholesterol side-chain cleavage cytochrome P450 (P450SCC) mRNA expression in TIC stimulated to differentiate in vitro. TIC were isolated from the ovaries of hypophysectomized immature rats by Percoll gradient centrifugation and cultured in the presence and absence of LH and IGF-I up to 6 days. At various times cytoplasmic RNA was extracted from the TIC and P450SCC mRNA was measured by specific assay using reverse transcription followed by the polymerase chain reaction. Increasing concentrations of LH (0-1 microgram/ml) stimulated a dose-related increase in P450SCC mRNA (ED50 = 36.2 +/- 5.5 ng/ml) which reached maximal levels at 100 ng/ml of LH. Addition of IGF-I (30 ng/ml) caused a small increase in P450SCC mRNA over TIC treated with LH alone but did not alter the ED50 for LH stimulation. IGF-I alone also stimulated an increase in P450SCC mRNA which reached approximately 3-fold over unstimulated levels at 100 ng/ml. In the presence of LH, IGF-I stimulated a dose-related increase in P450SCC mRNA (ED50 = 1.2 +/- 0.05 ng/ml). Time-course studies revealed that expression of P450SCC mRNA was greatest at 2 days in TIC treated with IGF-I alone, LH alone or LH plus IGF-I and then declined at 4 and 6 days.(ABSTRACT TRUNCATED AT 250 WORDS)


[GEMICOMED/GEIRAS-SEIMC recommendations for the management of Candida auris infection and colonization].
Candida auris is a new species of Candida that causes nosocomial outbreaks in several countries around the world, including Spain. C.auris is resistant to fluconazole and multi- and pan-resistant strains have been described. It is highly transmissible and can survive long term in the hospital environment, causing long-lasting outbreaks that are difficult to detect in early stages, and making it difficult to control and eradicate. It is currently an emerging threat to global health. This document provides a set of guidelines, developed by a multidisciplinary team, to limit the impact and facilitate the control of C.auris infection based on the experiences gathered in the Spanish and English outbreaks. The implementation of early and strict surveillance and control measures is essential to prevent the spread of the outbreak, which can spread over time, posing a significant risk to complex, critical and immunocompromised surgical patients. Immediate notification of C.auris isolation to clinical and infection control teams, as well as to health authorities and institutions, is essential to implement infection control measures at all levels in a timely manner, to prevent internal and inter-centre transmission, and to ensure a proper surveillance and prevention to patients who are already colonized and can develop an infection.


Multicenter Study of Dynamic High-Density Functional Substrate Mapping Improves Identification of Substrate Targets for Ischemic Ventricular Tachycardia Ablation.
The goal of this study was to evaluate the role of dynamic substrate changes in facilitating conduction delay and re-entry in ventricular tachycardia (VT) circuits. The presence of dynamic substrate changes facilitate functional block and re-entry in VT but are rarely studied as part of clinical VT mapping. Thirty patients (age 67 ± 9 years; 27 male subjects) underwent ablation. Mapping was performed with the Advisor HD Grid multipolar catheter. A bipolar voltage map was obtained during sinus rhythm (SR) and right ventricular sense protocol (SP) single extra pacing. SR and SP maps of late potentials (LP) and local abnormal ventricular activity (LAVA) were made and compared with critical sites for ablation, defined as sites of best entrainment or pace mapping. Ablation was then performed to critical sites, and LP/LAVA identified by the SP. At a median follow-up of 12 months, 90% of patients were free from antitachycardia pacing (ATP) or implantable cardioverter-defibrillator shocks. SP pacing resulted in a larger area of LP identified for ablation (19.3 mm2 vs. 6.4 mm2) during SR mapping (p = 0.001), with a sensitivity of 87% and a specificity of 96%, compared with 78% and 65%, respectively, in SR. LP and LAVA observed during the SP were able to identify regions critical for ablation in VT with a greater accuracy than SR mapping. This may improve substrate characterization in VT ablation. The combination of ablation to critical sites and SP-derived LP/LAVA requires further assessment in a randomized comparator study.


Effect of spontaneous exercise on antioxidant capacity in rat muscles determined by electron spin resonance.
The effect of physical activity on antioxidant capacity in muscle remains unknown. This study investigated the effect of spontaneous exercise on antioxidant capacity in rat muscles determined by electron spin resonance (ESR), which is a technique for the direct detection of free radicals. Ten-week-old male Wistar rats were housed individually in cages with a running wheel. Rats were classified as high activity (HA), middle activity (MA) or low activity group (LA), based on an assessment of running distance covered over a 23-week period. After 23 weeks of housing, soleus (Sol), plantaris (Pl), gastrocnemius [deep/surface portions (GasD/GasS)] and heart (Hrt) muscles were isolated, and scavenging activity against superoxide anions (O(2)(*-)) and hydroxyl radicals (HO(*)) was determined by ESR using a spin-trap chemical. The citrate synthase (CS) activity was used as a marker of mitochondrial oxidative phosphorylation capacity. Among the parameters measured, only O(2)(*-) scavenging activity in GasD significantly correlated with the running distance. The highest scavenging activity was observed in Hrt of HA rats. The O(2)(*-) scavenging activity in Pl of MA rats was significantly higher than that of LA rats. The O(2)(*-) scavenging activity of Sol and GasS was not significantly different between the three groups. Furthermore, the HO(*) scavenging activity of any muscle specimens was similar among the three groups and did not correlate with running distance at all. CS activity did not significantly differ between the three groups. These data suggest that O(2)(*-) scavenging activity in specific types of muscle tissues would increase especially in spontaneously active animals. However, HO(*) scavenging activity would not.


Does the lack of regression-associated mRNA expression render a rat ventral prostate epithelial cell line androgen independent?
A series of rapidly dividing epithelial (RDE) cell lines have been isolated from primary cultures of rat ventral prostate (RVP) epithelial cells. Unlike androgen-dependent secretory epithelial cells, the RDE cells in culture do not express the androgen-dependent secretory proteins, nor do they express the androgen-repressed cell death sequences (TRPM-2) found in the epithelial cells during prostatic regression. Screening of a cDNA clone library established from RDE cell mRNA has yielded a number of RDE cell-specific sequences. One of these, RDE-.25 is a 250-base mRNA. The sequence of RDE-.25 shows considerable homology with the rat growth hormone gene and two murine oncogene sequences. We believe that the absence of androgen-repressed cell death sequence expression confers androgen independence for survival and growth, while the expression of RDE-.25 may represent an autocrine growth stimulus which greatly increases the rate of cell division in these cells.


Mucosal physical and chemical innate barriers: Lessons from microbial evasion strategies.
The innate immune system has evolved since millions of years under a selective pressure. Among the different host mechanisms selected and conserved as a first line of defense, the gastrointestinal mucus layer constitutes an efficient physical and chemical barrier against invading microbes. Mucin glycoproteins and antimicrobial peptides are the major components of the mucus barrier, and evidences prove that they form an effective protection against most microbes. However, successful pathogens have evolved evasion strategies to circumvent this defense barrier. Here, we discuss the interactions between pathogens, mucins, and antimicrobial peptides, and the mechanisms that pathogens have developed to evade the innate defense systems of the intestinal mucosal barrier.


Differential expression of glycans in the urothelial layers of horse urinary bladder.
Urothelium is a multilayer epithelium covering the inner surface of the urinary bladder that acts as a blood-urine barrier and is involved in maintaining the wellbeing of the whole organism. Glycans serve in the maturation and differentiation of cells and thus play a key role in the morphology and function of the multilayered epithelium. The aim of the present study was to examine the glycoprotein pattern of the horse urinary bladder urothelium by lectin histochemistry. The study involved urinary bladders from four horse stallions. Tissue sections were stained with a panel of eleven lectins, in combination with saponification and sialidase digestion (Ks). Basal cells displayed high-mannose N-glycans (Con A), α2,6-linked sialic acid (SNA), and O-linked sialoglycans with sialic acids linked to Galβl,3GalNAc (T antigen) (KsPNA) and terminal N-acetylgalactosamine (Tn antigen) (KsSBA). The young intermediate cells expressed terminal N-acetylglucosamine (GlcNAc) (GSA II), galactose (GSA I-B4), T- and Tn antigens (PNA, SBA). The mature intermediate cells showed additional high-mannose N-glycans, O-linked sialoglycans (sialyl-T antigen, sialyl-Tn antigen), α2,6- and α2,3-linked sialic acid (MAL II), α1,2-linked fucose (UEA I), and GlcNAc (KsWGA). The latter residue marked the boundary with the overlying surface layer. Few Con A positive intermediate cells were seen to cross the entire urothelium thickness. The surface cells showed additional glycans such as T antigen and sialic acids linked to GalNAc binding DBA (KsDBA). Few surface cells contained α1,3-linked fucose (LTA), whereas some other cells displayed intraluminal secretion of mucin-type glycans terminating with GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA). The luminal surface expressed the most complex glycan pattern in the urothelium because only α1,3-linked fucose lacked among the demonstrated glycans. This study showed that the glycan pattern becomes more complex from the basal to surface layer of the urothelium and that surface cells could modify the composition of urine via the secretion of glycoproteins.


Meta-analysis of QTLs and candidate genes associated with seed germination in rice (Oryza sativa L.).
Seed germination is one of the critical stages of plant life, and many quantitative trait loci (QTLs) control this complex trait. Meta-analysis of QTLs is a powerful computational technique for estimating the most stable QTLs regardless of the population's genetic background. Besides, this analysis effectively narrows down the confidence interval (CI) to identify candidate genes (CGs) and marker development. In the current study, a comprehensive genome-wide meta-analysis was performed on QTLs associated with germination in rice. This analysis was conducted based on the data reported over the last two decades. In this case, various analyses were performed, including seed germination rate, plumule length, radicle length, germination percentage, coleoptile length, coleorhiza length, radicle fresh weight, germination potential, and germination index. A total of 67 QTLs were projected onto a reference map for these traits and then integrated into 32 meta-QTLs (MQTLs) to provide a genetic framework for seed germination. The average CI of MQTLs was considerably reduced from 15.125 to 8.73 cM compared to the initial QTLs. This situation identified 728 well-known functionally characterized genes and novel putative CGs for investigated traits. The fold change calculation demonstrated that 155 CGs had significant changes in expression analysis. In this case, 112 and 43 CGs were up-regulated and down-regulated during germination, respectively. This study provides an overview and compares genetic loci controlling traits related to seed germination in rice. The findings can bridge the gap between QTLs and CGs for seed germination. The online version contains supplementary material available at 10.1007/s12298-022-01232-1.


Metabolomics and pharmacodynamic analysis reveal the therapeutic role of Prunella vulgaris oil on intrauterine adhesion rats.
Metabolomics is applied to explore the curative effect of complex systems, such as Chinese medicine. Intrauterine adhesion (IUA) harms the reproductive system and affects fertility, and hence is a significant public health concern. Prunella vulgaris oil (PVO) protects the reproductive system and exerts anti-inflammatory effects, but its effect on IUA and the underlying mechanism is unclear. In this study, we established a serum metabolomics method based on GC-TOF-MS to evaluate the mechanism of PVO in the IUA rat model established by mechanical injury and infection. Animal experiments showed that PVO improves the inflammatory response in the uterus of IUA model rats and reduces the content of inflammatory factors to improve the microenvironment of the reproductive system. It also regulates the expression of TGF-β1 and Smad-related mRNA and protein to inhibit fibrosis. Metabolomics indicated a significant abnormality in serum metabolism in IUA rats, and a total of 51 differential markers were screened and identified. After PVO treatment, these metabolic abnormalities improved significantly. The metabolic pathway analysis revealed that PVO affects glyoxylate and dicarboxylate metabolism, and β-alanine metabolism pathways. This study showed that PVO significantly improves inflammation and fibrosis in IUA rats combined with the pharmacological results. The primary mechanism is related to regulating the metabolism of amino acids and their derivatives to balance the associated disorders and control energy metabolism.


Imaging nascent RNA dynamics in Dictyostelium.
Dictyostelium cells have great utility for live imaging of single gene transcriptional dynamics. The cells allow efficient molecular genetics, for targeting of RNA reporters and fluorescent proteins to individual, defined loci. Dictyostelium cells share many signalling, chromatin and nuclear characteristics of larger eukaryotes, yet the cells have a relatively simple scattered differentiation programme, allowing imaging of transcriptional events in the context of stochastic developmental choices. This review will detail the methods and considerations for imaging nascent RNA dynamics at single genes in living Dictyostelium cells.


Mitochondrial functions in stem cells.
Mitochondria fulfill multiple cellular functions beyond ATP production, including several functions that are specialized for distinct tissue types (thermogenesis, steroidogenesis). Recent evidence indicates that mitochondrial activities are regulated within cell lineages, and through incompletely understood mechanisms, are important for specification of cell fate. Stem cells represent the apex of cell lineages, capable of self-renewal and multi-potential differentiation into cells with limited proliferative capacity, and are of intense interest in regenerative medicine. Examples of stem cells include embryonic stem cells and adult somatic stem cells. Tumor-initiating cells are also often described as cancer stem cells. For all of these cell types, the association of mitochondrial bioenergetic function or other mitochondrial phenotypes raises interesting questions about the regulation of 'stemness'.


Daytime sleepiness and associated factors in Japanese school children.
To examine daytime sleepiness and sleepiness interrelationship with sleep-wake patterns, eating habits, physical activity, and TV/video game time. A cross-sectional survey with 9,261 school children (mean age of 12.8 years) from 93 junior high schools in Toyama prefecture, Japan. The main outcome measures were daytime sleepiness during schooldays and sleepiness interrelationship with sleep-wake patterns, eating habits, physical activity, and visual media use. A total of 2,328 children (25.2%) reported sleepiness almost always and 4,401 (47.6%) sleepiness often. Regarding sex difference, a higher proportion of girls reported sleepiness in comparison to boys (79% vs 66%, P < .001). Higher body mass index values were associated with the presence of sleepiness. In girls with preferences for daily snack (versus those who reported no snack) sleepiness presented significantly (P < .001) higher values. Reduced sleep time was significantly associated with sleepiness. The prevalence of sleepiness did not significantly differ among groups who had 7.5 hours sleep or more. A dose-response relation was found between sleepiness and sleep disturbances, physical activity, and media use time. Sleep insufficiency represents a main cause for daytime sleepiness in Japanese junior high school children. Proper sleep habits, high physical activity level, and limited TV viewing time should be promoted among school children.


Percutaneous cardiopulmonary bypass for the treatment of hypothermic circulatory collapse.
Environmentally induced hypothermia has a very high mortality. Cardiopulmonary bypass affords the best chance of survival from hypothermia but can be time-consuming to institute. We have utilized percutaneous cardiopulmonary bypass with recently developed bypass catheters to resuscitate a patient with profound hypothermia complicated by circulatory collapse. Percutaneous cardiopulmonary bypass appears to be the treatment of choice for profound hypothermia.


Pericardial Fat Is Associated With Less Severe Multiorgan Failure Over Time in Patients With Coronavirus Disease-19: The Maastricht Intensive Care COVID Cohort.
Pericardial fat (PF) and epicardial adipose tissue (EAT) may enhance the proinflammatory response in corona virus-19 (COVID-19) patients. Higher PF and EAT volumes might result in multiorgan failure and explain unfavorable trajectories.The aim of this study was to examine the association between the volume of PF and EAT and multiorgan failure over time. All mechanically ventilated COVID-19 patients with an available chest computed tomography were prospectively included (March-June 2020). PF and EAT volumes were quantified using chest computed tomography scans. Patients were categorized into sex-specific PF and EAT tertiles. Variables to calculate Sequential Organ Failure Assessment (SOFA) scores were collected daily to indicate multiorgan failure. Linear mixed-effects regression was used to investigate the association between tertiles for PF and EAT volumes separately and serial SOFA scores over time. All models were adjusted. Sixty-three patients were divided into PF and EAT tertiles, with median PF volumes of 131.4 mL (IQR [interquartile range]: 115.7, 143.2 mL), 199.8 mL (IQR: 175.9, 221.6 mL), and 318.8 mL (IQR: 281.9, 376.8 mL) and median EAT volumes of 69.6 mL (IQR: 57.0, 79.4 mL), 107.9 mL (IQR: 104.6, 115.1 mL), and 163.8 mL (IQR: 146.5, 203.1 mL). Patients in the highest PF tertile had a statistically significantly lower SOFA score over time (1.3 [-2.5, -0.1], P =0.033) compared with the lowest PF tertile. EAT tertiles were not significantly associated with SOFA scores over time. A higher PF volume is associated with less multiorgan failure in mechanically ventilated COVID-19 patients. EAT volumes were not associated with multiorgan failure.


Principles of Targeted Therapy for Melanoma.
Targeted BRAF and MEK inhibition has become an appropriate first-line treatment of BRAF-mutant advanced cutaneous melanoma. The authors present an overview of the MAPK pathway as well as the other major pathways implicated in melanoma development. Melanoma brain metastases are a devastating complication of melanoma that can be traced to derangements in cell signaling pathways, and the current evidence for targeted therapy is reviewed. Finally, activating KIT mutations are rarely found to cause melanomas and may provide an actionable target for therapy. The authors review the current evidence for targeted KIT therapy and summarize the ongoing clinical trials.


Solvent-free automated thermal desorption-gas chromatography/mass spectrometry for direct screening of hazardous compounds in consumer textiles.
The global production of textiles utilizes numerous large-volume chemicals that may remain to some extent in the finished garments. Arylamines, quinolines, and halogenated nitrobenzene compounds are possible mutagens, carcinogens and/or skin sensitizers. For prevention, control of clothing and other textiles must be improved, especially those imported from countries without regulations of textile chemicals. An automated analytical methodology with on-line extraction, separation, and detection would largely simplify screening surveys of hazardous chemicals in textiles. Automated thermal desorption-gas chromatography/mass spectrometry (ATD-GC/MS) was developed and evaluated as a solvent-free, direct chemical analysis for screening of textiles. It requires a minimum of sample handling with a total run time of 38 min including sample desorption, chromatographic separation, and mass spectrometric detection. For most of the studied compounds, method quantification limit (MQL) was below 5 µg/g for 5 mg of textile sample, which is sufficiently low for screening and control of quinoline and arylamines regulated by EU. Several chemicals were detected and quantified when the ATD-GC/MS method was applied in a limited pilot screening of synthetic fiber garments. A number of arylamines were detected, where some of the halogenated dinitroanilines were found in concentrations up to 300 µg/g. This is ten times higher than the concentration limit for similar arylamines listed by the EU REACH regulation. Other chemicals detected in the investigated textiles were several quinolines, benzothiazole, naphthalene, and 3,5-dinitrobromobenzene. Based on the present results, we suggest ATD-GC/MS as a screening method for the control of harmful chemicals in clothing garments and other textiles.


Transhepatic insertion of vascular dialysis catheters in children: a safe, life-prolonging procedure.
Central venous catheters (CVC) have been inserted percutaneously since 1989. This technique has been adapted for transhepatic insertion of large-bore catheters in children with occluded central veins. Three children aged 5, 11, and 12 years required hemodialysis or plasmaphoresis for treatment of life-threatening conditions. All central veins were occluded, thus transhepatic insertion of a large-bore catheter was necessary. All children underwent successful placement using a combination of ultrasound guidance and fluoroscopy. No complications occurred. Transhepatic insertion of large-bore catheters can be performed safely in children. Catheter removal should be accompanied by track embolization to prevent exsanguinating hemorrhage. Transhepatic insertion of dialysis catheters is a safe alternative in children with occluded central veins.


Dimer conformation of soluble PECAM-1, an endothelial marker.
Platelet endothelial cell adhesion molecule 1 (PECAM-1) is a cell surface receptor widely distributed on endothelium and hematopoietic-derived cells, and maintain the integrity of the blood vessels. PECAM-1 is widely recognized as an endothelial cell marker. The homophilic interaction through its extracellular domain of PECAM-1 (soluble PECAM-1, or sPECAM-1) is important to its functions. However, structural details for such dimerization are not fully understood. Here we report the production of recombinant sPECAM-1 in large quantity by Drosophila expression system and the small-angle X-ray diffraction (SAXS) study. The recombinant sPECAM-1 was found to form one population of dimer, but not oligomer, and was able to bind to heparin immobilized on a chip in surface plasmon resonance imaging (SPRi) binding experiments. The results of SAXS demonstrated that sPECAM-1 formed a symmetric homodimer of Ω-shape in solution, and each protomer adopted an extended conformation. The dimer is mediated through the intermolecular interactions through the first N-terminal domain (D1) of sPECAM-1. This model provides new structural information for its homophilic interaction mechanism.


Developmental toxicity, immunotoxicity and cardiotoxicity induced by methidathion in early life stages of zebrafish.
Methidathion is a highly effective organophosphorus pesticide and is extensively utilized for the control of insects in agricultural production. However, there is little information on the adverse effects and underlying mechanisms of methidathion on aquatic organisms. In this work, embryonic zebrafish were exposed to methidathion at concentrations of 4, 10, and 25 mg/L for 96 h, and morphological changes and activities of antioxidant indicators alterations were detected. In addition, the locomotor behavioral abilities of zebrafish exposed to methidathion were also measured. To further explore the mechanism of the toxic effects of methidathion, gene expression levels associated with cardiac development, cell apoptosis, and the immune system were tested through qPCR assays. The findings revealed that methidathion exposure could induce a decrease in survival rate, hatchability, length of body, and increase in abnormality of zebrafish, as well as cardiac developmental toxicity. The LC50 value of methidathion in zebrafish embryos was determined to be about 30.72 mg/L at 96 hpf. Additionally, methidathion exposure triggered oxidative stress in zebrafish by increasing SOD activity, ROS, and MDA content. Acridine orange (AO) staining indicated that methidathion exposure led to apoptosis, which was mainly distributed in the pericardial region. Furthermore, significant impairments of locomotor activity in zebrafish larvae were induced by methidathion exposure. Lastly, the expression of pro-inflammatory factors including IFN-γ, IL-6, IL-8, CXCL-clc, TLR4, and MYD88 significantly up-regulated in exposed zebrafish. Taken together, the results in this work illustrated that methidathion caused developmental toxicity, cardiotoxicity, and immunotoxicity in embryogenetic zebrafish.


[Education for health and the drug problem. The design of a protocol].
The article is a report on a training exercise with a group of student health visitors to verify their health education ability. The choice of the subject-matter (drugs) as well as that of the group addressed (the elderly) is subordinate to the main aim of the exercise, which is to test to feasibility and the importance of giving oneself a method of work.


Tuberculosis infection-control practices in United States emergency departments.
To determine the frequency with which patients with suspected tuberculosis (TB) or TB risk factors present to US emergency departments and to describe current ED TB infection-control facilities and practices. Mailed survey of a sample of EDs in US acute care facilities. A random sample (n = 446) of subjects who responded to a 1992 survey of all US municipal, Veterans Affairs, and university-affiliated hospitals and a 20% random sample of all private hospitals with more than 100 beds conducted by the Centers for Disease Control and Prevention (CDC). We collected data on patient demographics and general ED characteristics, TB isolation facilities and policies, and employee tuberculin skin-testing policies and results. Of 446 facilities surveyed, 305 surveys (68.4%) were returned. The proportions of facilities reporting that patients suspected of having TB are seen daily, weekly, monthly, and less frequently were, respectively, 12.6%, 17.2%, 23.3%, and 46.9%. The proportion of EDs in which indigent patients are cared for on a daily basis was 89%; the homeless, 57.5%; the HIV-infected, 35.9%; i.v. drug users, 45.4%; and recent immigrants, 30%. Written criteria for isolation of patients with suspected TB at triage or in the ED were in place in 56% and 76% of facilities, respectively. TB isolation rooms fulfilling CDC guidelines were available in triage or waiting areas in 1.7% of facilities and in 19.6% of EDs. Air venting directly outside, high-efficiency particulate air filtration of recirculated air, and UV germicidal lights were used in 21%, 17%, and 8% of general patient care areas of EDs, respectively. At least one ED employee had shown tuberculin skin test conversion in 16.1% of EDs in 1991; this figure was 26.9% in 1992. Patients with TB or at risk for TB are often treated in US EDs, and the risk for transmission of TB in this setting appears to be increasing. Prolonged waiting times and lack of infection-control facilities in EDs may contribute to this problem. Consideration should be given to implementation of policies and facilities recommended by the CDC.


Bone-related behaviours of captive chimpanzees (Pan troglodytes) during two excavating experiments.
After stone tools, bone tools are the most abundant artefact type in the Early Pleistocene archaeological record. That said, they are still relatively scarce, which limits our understanding of the behaviours that led to their production and use. Observations of extant primates constitute a unique source of behavioural data with which to construct hypotheses about the technological forms and repertoires exhibited by our hominin ancestors. We conducted two different experiments to investigate the behavioural responses of two groups of captive chimpanzees (Pan troglodytes; n = 33 and n = 9) to disarticulated, defleshed, ungulate bones while participating in a foraging task aimed at eliciting excavating behaviour. Each chimpanzee group was provided with bone specimens with different characteristics, and the two groups differed in their respective experience levels with excavating plant tools. We found that several individuals from the inexperienced group used the provided bones as tools during the task. In contrast, none of the individuals from the experienced group used bones as excavating tools, but instead continued using plant tools. These chimpanzees also performed non-excavating bone behaviours such as percussion and tool-assisted extraction of organic material from the medullary cavity. Our findings serve as a proof-of-concept that chimpanzees can be used to investigate spontaneous bone tool behaviours such as bone-assisted excavation. Furthermore, our results raise interesting questions regarding the role that bone characteristics, as well as previous tool-assisted excavating experience with other raw materials, might have in the expression of bone tool-assisted excavation.


Human amniotic epithelial cells attenuate TGF-β1-induced human dermal fibroblast transformation to myofibroblasts via TGF-β1/Smad3 pathway.
Keloids are raised dermal scars that extend beyond the boundaries of the initial injury. To date, there is no treatment to erase scars completely in humans. Growing evidence has shown that the human amniotic epithelial cells have anti-fibrotic properties and can reduce the fibrosis of lung and liver. However, it is unknown whether and how they can influence human keloids. The aim of this study was to investigate whether factors secreted by human amniotic epithelial cells have anti-fibrotic effects on human keloids and to clarify the potential transduction mechanism. Human amniotic epithelial cells were isolated and identified both with flow cytometry and immunofluorescent. The α-smooth muscle actin, collagen-I and III gene and protein expression of transforming growth factor (TGF)-β1-treated human adult dermal fibroblasts were partly abolished by human amniotic epithelial cells conditioned medium through stimulating the expression of matrix metalloproteinase (MMP). Furthermore, human amniotic epithelial cells conditioned medium effectively attenuated nuclear import of the Smad2/3 complex. Soluble human leukocyte antigen G, a human amniotic epithelial cell-derived factor, significantly decreased collagen production in TGF-β1-induced human dermal fibroblasts, although the effect on collagen production was less than that of human amniotic epithelial cell-conditioned medium. This study demonstrates that human amniotic epithelial cells conditioned medium could down-regulate the expression of fibrosis-related molecules by regulating MMP and tissue inhibitor of metalloproteinase levels, and suppress TGF-β1-induced fibroblast transition, in which the TGF-β1/Smad3 pathway is likely involved. These findings suggest that human amniotic epithelial cells are a potential therapeutic compound for the treatment of keloids.


Evidence that SE is distal to LU on chromosome 19q.
Analysis of a family informative for chromosome 19 loci establishes that the Lutheran blood group locus (LU) lies between the third component of human complement (C3) and the secretor loci (SE). Previously published lod scores for C3:LU are increased from 2.94 to 3.80. The linkage relationships (zeta and theta) between C3, LU, and SE are examined, and the proposed order and approximate genetic distances are determined to be: pter--C3-10.6cM-cen-7.4cM-LU-9cM-SE--qter.


[Reproduction of the volume of biological objects by foreshortened roentgenograms].
The processing of a set of foreshortening roentgenograms by optico-holographic methods has been effected, its purpose being to obtain a three-dimensional image in a broad range of viewing angles. At the same time, the cross-sections of an object were synthetized by using an optical variant ofthe method providing for the synthesis of projecting functions and optical filtration of the synthetized image. The resolution power of the methods described is assessed.


Parasitoids of the goldenrod gall moth: effects of scale on spatial density dependence.
A parasitoid assemblage consisting of four hymenopteran species caused larval and pupal mortality of the host Gnorimoschema gallaeosolidaginis. In the absence of discrete host patches, the relationship between densities of hosts and parasitized hosts was examined on scales of 0.25, 1, 4, 16 and 25 m2 within a 400 m2 plot and between ten 16 m2 plots within a 1·3 km2 area. Within the 400 m2 plot, positive density dependence was observed on scales of 1, 4 and 16 m2. Rates of parasitism were found to be density independent across the ten 16 m2 plots. The nature of parasitoid and host spatial patterns were examined at the 400 m2 plot by using Goodall's (1974) paired-quadrat variance function, and by fitting the observed distribution of galls and parasitized galls to the Poisson and negative binomial on three scales. Postive density dependence at the 400 m2 plot occurred in the context of a host density gradient and may indicate aggregation of search time by parasitoids. However, significant responses on scales of 4 and 16 m2 may only reflect the sum of parasitoid responses on lower scales because of this gradient. Predominance of significant responses on a 1 m2 scale may be related to the high degree of variation in host density, and limits to active searching range of parasitoids.


Effects of fundic distention on pentagastrin-stimulated gastric acid secretion in man.
The acid secretory effect of combined stimulation with balloon distention of the fundus and body of the stomach and intravenous infusion of pentagastrin has been studied in patients with duodenal ulcer (DU) and in healthy subjects. In 8 nonoperated DU subjects and in 5 DU patients subjected to proximal gastric vagotomy, low grade fundic distention moderately enhanced the acid output evoked by a threshold dose of pentagastrin. Fundic distention with a baloon volume eliciting a maximal acid response to distention either left unchanged or suppressed the maximal acid secretory rate produced by pentagastrin in 7 nonoperated and 6 vagotomized DU patients and in 5 healthy subjects. The heterogeneous secretory effects of maximal stimulus combination suggest that fundic distention has a complex action on acid secretion eliciting a hitherto unknown inhibitory effect as well as a cholinergic activation of the parietal cell area. This complex action may explain the failure of fundic distention to augment markedly the action of pentagastrin in the present study.


Relationships between levels of membrane-bound glucuronidase and the associated protein egasyn in mouse tissues.
Mouse beta-glucuronidase has a dual intracellular localization, being present in both endoplasmic reticulum and lysosomes of several tissues. Previous studies demonstrated that the protein egasyn is complexed with microsomal but not lysosomal glucuronidase and that a mutant lacking egasyn is deficient in microsomal, but not lysosomal, glucuronidase. By means of a recently developed radioimmunoassay for egasyn, the relationship between microsomal glucuronidase levels and egasyn levels has been examined in various adult tissues, during postnatal development in liver, and after androgen induction of glucuronidase in kidney. The results indicate that the relative availability of egasyn determines the balance between glucuronidase incorporation into membranes and that into lysosomes.


Global analysis of phosphoproteome dynamics in embryonic development of zebrafish (Danio rerio).
The zebrafish (Danio rerio) is a popular animal model used for studies on vertebrate development and organogenesis. Recent research has shown a similarity of approximately 70% between the human and zebrafish genomes and about 84% of human disease-causing genes have common ancestry with that of the zebrafish genes. Zebrafish embryos have a number of desirable features, including transparency, a large size, and rapid embryogenesis. Protein phosphorylation is a well-known PTM, which can carry out various biological functions. Recent MS developments have enabled the study of global phosphorylation patterns by using MS-based proteomics coupled with titanium dioxide phosphopeptide enrichment. In the present study, we identified 3500 nonredundant phosphorylation sites on 2166 phosphoproteins and quantified 1564 phosphoproteins in developing embryos of zebrafish. The distribution of Ser/Thr/Tyr phosphorylation sites in zebrafish embryos was found to be 88.9, 10.2, and 0.9%, respectively. A potential kinase motif was predicted using Motif-X analysis, for 80% of the identified phosphorylation sites, with the proline-directed motif appearing most frequently, and 35 phosphorylation sites having the pSF motif. In addition, we created six phosphoprotein clusters based on their dynamic pattern during the development of zebrafish embryos. Here, we report the largest dataset of phosphoproteins in zebrafish embryos and our results can be used for further studies on phosphorylation sites or phosphoprotein dynamics in zebrafish embryos.


General practitioners' anticipated risk of cancer at referral and their attitude to risk taking and to their role as gatekeeper.
General practitioners have to deal with situations characterized by real but low likelihoods of serious illness. We aimed to investigate variations in general practitioners' anticipated risk of cancer when referring a patient and associations both with general practitioners' attitudes to risk taking and with their gatekeeper role. In January 2012, all 835 active general practitioners in the county of Aarhus, Denmark, received a questionnaire including the Physician Reaction to Uncertainty scale, The Tolerance for Ambiguity scale, the Physician Risk Attitude scale and a number of single items assessing anticipated risk of cancer when referring a hypothetical 50-year-old patient, use of intuition and perception of their role as a gatekeeper. A total of 568 (68.0%) practitioners completed and returned the questionnaire. The median anticipated risk of cancer was 30% (inter-quartile range: 15%-50%) and the 5%-95% centiles were 5% and 80%. Increasing tolerance for ambiguity was strongly related to a declining anticipated risk of cancer. None of the other risk attitudes were associated with the anticipated risk of cancer at referral. Increased general practitioners' age was related to increased anticipated risk of cancer when referring (25% for general practitioners under 45 years to 43% for those 60 years or over) but not statistically important. General practitioners either overestimate the risk of cancer when referring for suspected cancer or they appear to need to be very sure of the cancer diagnosis before referral. Further, focus on tolerance for ambiguity should be included in the education of general practitioners.


Diagnosis of discoid lateral meniscus of the knee on MR imaging.
To establish the quantitative MR diagnostic criteria for discoid lateral meniscus, MR imaging of 60 knees with arthroscopically confirmed discoid lateral menisci and 134 knees with semilunar lateral menisci were analyzed. Following four quantitative parameters were measured. (1) Meniscal width (MW): The minimum meniscal width on the coronal slice. (2) Ratio of the meniscus to the tibia (RMT): The ratio of minimum meniscal width to maximum tibial width on the coronal slice. (3) Percent coverage of the meniscus (PCM): The ratio of the sum of the width of the anterior and posterior horns to the meniscal diameter on the sagittal slice showing the maximum meniscal diameter. (4) Continuity of the anterior and posterior horns (CAPH): The number of consecutive sagittal slices showing continuity between the anterior and posterior horns of the meniscus on the sagittal slice. The cut-off values of each parameter to discriminate between the discoid and semilunar meniscus were calculated based on a univariate logistic regression analysis. The sensitivity and specificity were also calculated for each of 4 parameters and combinations of these parameters. The cut-off value was 15 mm for the MW, 20% for the RMT, 75% for the PCM, and 3 slices for the CAPH. The sensitivity and specificity of the four parameters ranged between 87% and 50% and between 99% and 92%, respectively. The most accurate diagnostic criterion was either the RMT > or = 20% or the PCM > or = 75%, and the sensitivity and specificity were 95% and 97%, respectively, even when torn menisci were included.


Recombinant AAV serotype 1 transduction efficiency and tropism in the murine brain.
Recombinant adeno-associated virus serotype 2 (rAAV2) vectors have shown promise as therapeutic agents for neurologic disorders. However, intracerebral administration of this vector leads to preferential transduction of neurons and a restricted region of transgene expression. The recently developed rAAV vectors based upon nonserotype 2 viruses have the potential to overcome these limitations. Therefore, we directly compared a rAAV type 1 to a type 2 vector in the murine brain. The vectors were engineered to carry identical genomes (AAV2 terminal repeat elements flanking an enhanced green fluorescent protein expression cassette) and were administered by stereotaxic-guided intracerebral injection. We found that the rAAV1 vector (rAAV1-GFP) had a 13- to 35-fold greater transduction efficiency than that of the rAAV2 vector (rAAV2-GFP). Also, rAAV1-transduced cells were observed at a greater distance from the injection site than rAAV2-transduced cells. Neurons were the predominant cell type transduced by both vector types. However, in contrast to rAAV2-GFP, rAAV1-GFP was capable of transducing glial and ependymal cells. Thus, rAAV1-based vectors have biologic properties within the brain distinct from that of rAAV2. These differences might be capitalized upon to develop novel gene transfer strategies for neurologic disorders.


Merging existing practices with new ones: the adjustment of organizational routines to using cancer patient pathways in primary healthcare.
The introduction of new tools can bring unintended consequences for organizational routines. Cancer Patient Pathways (CPP) were introduced into the Swedish healthcare system in 2015 to shorten time to diagnosis and treatment. Primary healthcare (PHC) plays a central role since cancer diagnosis often begins in PHC units. Our study aimed to understand how PHC units adjusted organizational routines to utilizing CPPs. Six PHC units of varied size from both urban and rural areas in northern Sweden were included. Grounded theory method was used to collect and analyse group interviews at each unit. Nine group interviews with nurses and physicians, for a total of 41 participants, were performed between March and November 2019. The interviews focused on CPPs as tools, the PHC units' routines and providers' experiences with using CPPs in their daily work. Our analysis captured how PHC units adjusted organizational routines to utilizing CPPs by fusing existing practices with new practices to offer better quality of care. Specifically, three overarching organizational routines within the PHC units were identified. First, Manoeuvring diverse patient needs with easier patient flow, the PHC units handled the diverse needs of the population while simultaneously drawing upon CPPs to ease the patient flow within the healthcare system. Second, (Dis) integrating internal know-how, the PHC units drew upon internal competence even when PHC know-how was not taken into account by those driving the CPP initiative. Third, Coping with unequal relationships toward secondary care, the PHC units dealt with being in an unequal position while adopting CPPs instead further decreased possibilities to influence decision-making between care-levels. Adopting CPPs as a tool within PHC units brought various unintended consequences in organizational routines. Our study from northern Sweden illustrates that the PHC know-how needs to be integrated into the healthcare system to improve the use of new tools as CPP. Further, the relationships between different levels of care should be taken in account when introducing new tools for healthcare. Also, when adopting innovations, unintended consequences need to be further explored empirically in diverse healthcare contexts internationally in order to generate deeper knowledge in the research area.


Net uptake of aspartate by a high-affinity rat cortical synaptosomal transport system.
Reuptake of neuroactive amino acids by high affinity transport systems (Km approximately 10 micrometer) is thought to terminate the action of these substances. Since homoexchange can complicate the interpretation of uptake experiments, it is necessary to demonstrate net inward transport of neuroactive amino acids before uptake can be considered as a likely mechanism for transmitter inactivation. When rat cortical synaptosomes are incubated with 10 micrometer [14C]L-aspartate, net (chemical) and apparent (radioactive) uptake into the synaptosomal fractions are equivalent. Although there is net aspartate uptake into the synaptosome fraction, aspartate exchange can be demonstrated in a variety of conditions. Net uptake exhibits the characteristics of high-affinity transport systems including Na+-and temperature-dependence. Furthermore, KCl (or RbCl)--1 micrometer--are required for net uptake but not radioactive or apparent uptake. LiCl, NH4Cl, CsCl, and choline chloride fail to support net uptake. Ouabain (0.1 micrometer) inhibits net uptake to a greater extent than apparent uptake. Although glutamate inhibits aspartate uptake (and vice versa), the net uptake of the combination is greater than that of each alone. The demonstration of net uptake of aspartate by a high-affinity system is consonant with the idea that this system may play a role in its inactivation in the synaptic region.


Predicting seat belt use in fatal motor vehicle crashes from observation surveys of belt use.
There is a large difference between the rates of observed seat belt use by the general public and belt use by motor vehicle occupants who are fatally injured in crashes. Seat belt use rates of fatally injured occupants, as reported in the Fatality Analysis Reporting System (FARS), are much lower than the use rates found in observation surveys conducted by the states. A series of mathematical models describing the empirical relationship between FARS and observed rates were explored. The initial model was a 'straw man' and used two simplifying assumptions: (a) belt users and nonusers are equally likely to be involved in 'potentially fatal collisions', and (b) belts are 45% effective in preventing deaths. The model was examined by comparing each state's FARS use rate with the predicted rate. The model did not fit the state data points even when possible biases in the data were controlled. We next examined the assumptions in the model. Changing the seat belt effectiveness parameter provided a reasonable fit, but required an assumption that seat belts are 67% effective in preventing fatalities. The inclusion of a risk coefficient for non-belted occupants also provided a reasonable fit between the model and data. A variable risk model produced the best fit with the data. The major finding was that a model consistent with the data can be obtained by incorporating the assumption that nonusers of seat belts have a higher risk of involvement in potentially fatal collisions than do seat belt users. It was concluded that unbelted occupants are over-represented in fatal collisions for two reasons: (a) because of a greater chance of involvement in potentially fatal collisions in the first place, and (b) because they are not afforded the protection of seat belts when a collision does occur.


Monoclonal antibodies against the bacterial-like organism associated with citrus greening disease.
Hybridoma clones secreting specific monoclonal antibodies (mAb) against the bacterium-like organism associated with citrus greening disease were produced from homogenates of infected phloem tissues used as immunogens in mice immunizations. Differential ELISA and immunofluorescence were used to screen for hybridomas secreting mAb against the greening organism (GO). Two such hybridoma clones were obtained. The mAb were specific for the GO. No cross-reactions were seen with any of the other phloem-limited prokaryotes tested nor with healthy plant material.


Role of progesterone on dexamethasone-induced alterations in placental vascularization and progesterone receptors in rats†.
Intrauterine growth restriction (IUGR) is manifested by lower maternal progesterone levels, smaller placental size, and decreased placental vascularity indicated by lower expression of vascular endothelial growth factor (VEGF). Studies showed that progesterone increases angiogenesis and induces VEGF expression in different tissues. Therefore, the aim of the present study is to evaluate the effect of progesterone on placental vascular bed and VEGF expression and the modulation of nuclear and membranous progesterone receptors (PR) in dexamethasone-induced rat IUGR model. Pregnant Sprague-Dawley rats were allocated into four groups and given intraperitoneal injections of either saline, dexamethasone, dexamethasone, and progesterone or progesterone. Injections started on gestation day (DG) 15 and lasted until the days of euthanization (19 and 21 DG). Enzyme-linked immunosorbent assay was used to evaluate plasma progesterone levels. Real-time PCR and western blotting were used to evaluate gene and protein expressions of VEGF, and PR in labyrinth and basal placental zones. Immunohistochemistry was used to locate VEGF and different PRs in placental cells. Immunofluorescence was used to monitor the expression of blood vessel marker (αSMA). Dexamethasone decreased the vascular bed fraction and the expression of VEGF in both placental zones. Progesterone co-treatment with dexamethasone prevented this reduction. Nuclear and membrane PRs showed tissue-specific expression in different placental zones and responded differently to both dexamethasone and progesterone. Progesterone treatment improves the outcomes in IUGR pregnancy. Progesterone alleviated DEX-induced IUGR probably by promoting placental VEGF and angiogenesis.


Non-similar solution development for entropy optimized flow of Jeffrey liquid.
Mixed convection in dissipative entropy optimized stagnation point flow of nanomaterial towards stretching Riga sheet is addressed. Brownian and thermophoresis diffusions for nanomaterial are accounted. Constitutive relations for Jeffrey material are utilized. Non-similar solutions for the governing differential systems are developed. OHAM is employed for the convergent series solutions development. Outcomes of pertinent variables on flow quantities of interest are graphically organized. Finally the concluding remarks are arranged.


Corticotomies and Orthodontic Tooth Movement: A Systematic Review.
A systematic review was conducted to examine the evidence for the effectiveness and safety of corticotomy-facilitated orthodontics. Electronic databases (Ovid Medline, EMBASE, Cochrane, SCOPUS, and Web of Science) were searched for articles that examined the rate of corticotomy-facilitated orthodontic tooth movement and its effects on the periodontium, root resorption, and tooth vitality. Unpublished literature was searched electronically through ClinicalTrials.gov (http://www.clinicaltrials.gov) and the ISRCTN registry (http://www.controlled-trials.com). Relevant orthodontic journals and reference lists also were checked for eligible studies. Randomized clinical trials (RCTs) and controlled clinical trials (CCTs) were considered. Two article reviewers independently assessed the search results, screened the relevant articles, performed data extraction, and evaluated the methodologic quality of the studies. Fourteen eligible articles (6 RCTs and 8 CCTs) were included in the review. There was a statistically meaningful increase in the rate of tooth movement compared with controls for all corticotomy techniques assessed. Some studies reported that acceleration in tooth movement was only temporary (lasting a few months). Corticotomy procedures did not seem to produce unwanted adverse effects on the periodontium, root resorption, and tooth vitality. The quality of the body of evidence was regarded as low owing to the presence of multiple methodologic issues, high risks of bias, and heterogeneity in the included articles. Corticotomy procedures can produce statistically and clinically meaningful temporary increases in the rate of orthodontic tooth movement with minimal side-effects. Additional high-quality randomized clinical trials are needed to allow more definitive conclusions.


MicroRNA-506 modulates insulin resistance in human adipocytes by targeting S6K1 and altering the IRS1/PI3K/AKT insulin signaling pathway.
The incidence of obesity has increased rapidly, becoming a worldwide public health issue that involves insulin resistance. A growing number of recent studies have demonstrated that microRNAs play a significant role in controlling the insulin signaling network. For example, miR-506-3p expression has been demonstrated to correlate with insulin sensitivity; however, the underlying mechanism remains unknown. In this study, we found that miR-506-3p enhanced glucose uptake by 2-deoxy-D-glucose uptake assays and regulated the protein expression of key genes involved in the PI3K/AKT insulin signaling pathway including IRS1, PI3K, AKT, and GlUT4. We next predicted ribosomal protein S6 kinase B1 (S6K1) to be a candidate target of miR-506-3p by bioinformatics analysis and confirmed using dual-luciferase assays that miR-506-3p regulated S6K1 expression by binding to its 3'-UTR. Moreover, modulating S6K1 expression counteracted the effects of miR-506-3p on glucose uptake and PI3K/AKT pathway activation. In conclusion, miR-506-3p altered IR in adipocytes by regulating S6K1-mediated PI3K/AKT pathway activation. Taken together, these findings provide novel insights and potential targets for IR therapy.


Myosin-Va proteolysis by Ca2+/calpain in depolarized nerve endings from rat brain.
Myosin-Va is a molecular motor that may participate in synaptic vesicle cycling. Calpain cleaves myosin-Va in vitro at methionine 1141 in the tail domain. We show that intracellular proteolysis of myosin-Va occurs in rat cortical synaptosomes depolarized in the presence of calcium, evidenced by the formation of an 80 k polypeptide that co-migrates in SDS-PAGE with the 80 k fragment produced by the in vitro proteolysis of myosin-Va by calpain. Anti-myosin-Va antibody recognized this polypeptide in Western blots and immunoprecipitated it from synaptosome extracts. Calpastatin, a calpain-specific inhibitor, or leupeptin, a general cysteine protease inhibitor, suppressed or blocked formation of the 80 k polypeptide depending on membrane permeability. We conclude that myosin-Va undergoes intracellular proteolysis by endogenous calpain, when synaptosomes are depolarized in the presence of calcium, at the same cleavage site previously identified in vitro, thus, making it a target for calcium signaling during synaptic activation.


A genotypic and spatial epidemiologic analysis of Massachusetts' Mycobacterium tuberculosis cases from 2012 to 2015.
Massachusetts had a rate of 2.8 cases of tuberculosis (TB) per 100,000 individuals in 2015. Although TB in Massachusetts is on the decline, the case rate remains far above the 2020 National TB Target of 1.4 per 100,000. To reduce the TB case rate in Massachusetts, it is necessary to understand the local epidemiology and transmission risks. We used an existing TB case database of Massachusetts TB cases in the time frame from 2012 to 2015, which links de-identified patient demographic information with TB genotypes obtained from the United States Centers for Disease Control and Prevention's (CDC) TB Genotyping Information Management System database. Two or more cases with identical genotypes, which were close in space (within 50 km), as determined in a geographic information system (GIS), and time (3 years), were considered TB clusters. We analyzed 543 genotyped cases. We identified a total of 85 cases that met the TB cluster criteria, and a total of 33 clusters. US-born individuals (p = 0.003), homeless individuals (p = 0.001) and those reporting illicit substance use (p = 0.001) and alcohol use (p = 0.001) were more likely to appear in a TB cluster. Through a combined genotypic and spatial epidemiological approach, we identified populations and individuals more likely to be in a TB cluster. Testing populations identified as at risk for being in a TB cluster, and providing appropriate treatment, may decrease the overall TB case rate and support efforts to achieve national 2020 TB targets.


Frequency distribution of antigens in the human platelet antigen-1 system in the western Indian population.
Neonatal alloimmune thrombocytopenic purpura (NAITP) occurring because of fetomaternal incompatibility in the human platelet antigen-1 (HPA-1) system is increasingly being detected worldwide. Several studies have reported the frequency and distribution of HPA-1 alleles in different countries and ethnic populations. A paucity of data regarding the frequency of the antigens in the HPA-1 system in the Indian population prompted an undertaking of this study. The molecular method of genotyping the platelet antigens is preferred to serology. It will enable future prenatal diagnosis in mothers suspected to have NAITP so that they can be managed better. Five hundred six unrelated subjects were screened for the alleles in the HPA-1 system, of which 185 were healthy males and 321 were females. DNA was extracted from the peripheral blood WBCs of these subjects, followed by PCR amplification and agarose gel electrophoresis of the PCR-amplified products. Four hundred two out of 506 subjects (79.44%) were found to be homozygous for HPA-1a. Ninety-nine subjects (19.57%) were heterozygous HPA-1a/HPA-1b, and five subjects out of 506 (0.99%) were homozygous for HPA-1b. Homozygosity for HPA-1b exists in the Indian population at a frequency of 0.99 percent, whereas homozygosity for HPA-1a is present in approximately 79 percent of the population. Hence, 0.98 x 0.79 of the females (0.77%) in the reproductive age group are likely to be pregnant with an HPA-1a-positive fetus, leading to a setting in which NAITP might develop. The development of NAITP also depends on the HLA type of the mother; nevertheless, the number of pregnancies in which the fetus is at risk for NAITP in India is quite significant.


The truths behind the statistics of surgical treatment for hypertensive brainstem hemorrhage in China: a review.
Hypertensive brainstem hemorrhage (HBSH) is of high morbidity and mortality rate. But many clinical studies were written in Chinese and had not been reviewed. A systemic review of Chinese clinical studies for HBSH was performed. A systemic literature search in PubMed, Web of Science, China National Knowledge Infrastructure, and Weipu database and Wanfang database up to March 2020 was performed. Clinical control studies including a surgical evacuation (SE) group and a conservative management (CM) group were included. The clinical outcome and mortality rate were compared. Ten cohort studies were included, involving 944 participants (304 in the SE group and 640 in the CM group). All included patients were comatose, with the average age ranged from 45 to 65 years old. Among five studies using mRS or GOS as outcome score, a total of 16.6% (89/535) of patients achieve self-maintenance with minor disabilities, including 26.8% (34/127) in the SE group and 13.5% (55/408) in the CM group. The overall mortality rate in the SE group was 27.6%, ranged from 9.3 to 60% among different studies. The overall mortality rate in the CM group was 60.6%, ranged from 18.5 to 100.0%. Elder and comatose HBSH patients are not contraindicated for surgery. The review showed that this group of patients obtained a better outcome and lower mortality rate after surgical treatment. The quality of included studies was relatively low, but a high-level clinical study on HBSH is of great difficulty, as both clinicians and patients faced various sociological issues rather than pure medical problems.


Life-threatening reaction to indigo carmine--a sulfa allergy?
Indigo carmine is commonly used during cystoscopy when evaluating for lower urinary tract safety after gynecologic surgery. We report a case of severe hypotension and bradycardia following intravenous indigo carmine injection in a patient with known sulfa allergy.