New method for arbuscular mycorrhizal fungus spore separation using a microfluidic device based on manual temporary flow diversion.
Arbuscular mycorrhizal fungi are beneficial components often included in biofertilizers. Studies of the biology and utilization of these fungi are key to their successful use in the biofertilizer industry. The acquisition of isolated spores is a required step in these studies; however, spore quality control and spore separation are bottlenecks. Filtered and centrifuged spores have to be hand-picked under a microscope. The conventional procedure is skill-demanding, labor-intensive, and time-consuming. Here, we developed a microfluidic device to aid manual separation of spores from a filtered and centrifuged suspension. The device is a single spore streamer equipped with a manual temporary flow diversion (MTFD) mechanism to select single spores. Users can press a switch to generate MTFD when the spore arrives at the selection site. The targeted spore flows in a stream to the collection chamber via temporary cross flow. Using the device, spore purity, the percentage of spore numbers against the total number of particles counted in the collecting chamber reached 96.62% (median, n = 10) which is greater than the spore purity obtained from the conventional method (88.89% (median, n = 10)).


Intra-articular anaesthesia mitigates established pain in experimental osteoarthritis: a preliminary study of gait impulse redistribution as a biomarker of analgesia pharmacodynamics.
Develop a sensitive, functional biomarker of persistent joint pain in a large animal model of experimental osteoarthritis. Evaluate Impulse Ratio as a measure of weight distribution among supporting limbs throughout the early natural history of osteoarthritis and with local anaesthesia and analgesia. The distribution of weight bearing in the trot of 11 skeletally-mature dogs was analyzed before and after unilateral surgical intervention (cranial cruciate transection or distal femoral focal impact). The short-term effects of two analgesic treatments (intra-articular lidocaine and intra-dermal meloxicam) were then evaluated as an index of pain relief based on the redistribution of weight-bearing impulse between normal and injured limbs. Impulse Ratio was able to resolve weight redistribution between limbs in both long-term (weekly for over 400 days) and short-term (15 min intervals) joint evaluations. Joint pain relief from lidocaine administration could be reliably tracked over its brief acting time course. Meloxicam administration resulted in ambiguous results, where average weight bearing in the injured limb did not increase, but the variability of limb use changed transiently and reversibly. Joint function and the role of persistent joint pain in the development of osteoarthritis can be investigated effectively and efficiently in a large animal model through the use of Impulse Ratio. Impulse Ratio can be a functionally relevant and sensitive biomarker of locomotion-related joint pain.


Correction to: Recalibration and validation of the Swiss lichen bioindication methods for air quality assessment.
The correct fig. 2 is presented in this paper.


Experimental studies of the etiology of genital exhibitionism.
Several studies are reported which examine the critical stimuli and responses as well as personality factors important in genital exhibitionism. Using penile volume measurement, sex history questionnaires, personality tests, and behavioral observations, it was found that (1) exhibitionists responded most to mature females and were comparable to normals in reactions to children and men; (2) while exhibitionists indicated narcissistic desires in exposing, in a laboratory study they did not differ from controls in reactions to exposing with various reactions of the female, from sexual arousal and admiration to fear and anger; (3) the only strong features distinguishing exhibitionists from controls and other sexually anomalous subjects were peeping associated with orgasm and outdoor solitary masturbation; (4) exhibitionists seemed to be less assertive and less feminine than controls, but results were weak and inconsistent; (5) exhibitionists and controls did not differ in separation and divorce or marital satisfaction; (6) blood testosterone and penile reactivity of exhibitionists were within normal limits. Overall, the results suggest that most major theories of genital exhibitionism are wanting. It is suggested that narcissism and pedophilia be examined further in connection with exhibitionism.


Potent and highly selective kappa opioid receptor agonists incorporating chroman- and 2,3-dihydrobenzofuran-based constraints.
Two novel chemical classes of kappa opioid receptor agonists, chroman-2-carboxamide derivatives and 2,3-dihydrobenzofuran-2-carboxamide derivatives, were synthesized. These agents exhibited high and selective affinity for the kappa opioid receptor.


Phenotypic and molecular characterization of extended-spectrum β-lactamase/AmpC- and carbapenemase-producing Klebsiella pneumoniae in Iran.
The objective of the current study is to evaluate the phenotypic and molecular characterization of ESBL/AmpC- and carbapenemase-producing K. pneumoniae isolates in Iran. From October 2018 until the end of April 2020, different clinical samples were collected and K. pneumoniae isolates were identified using conventional biochemical tests and PCR assay. Antibiotic susceptibility pattern was determined using the Kirby-Bauer disk diffusion method. Modified Hedge Test (MHT) was applied to the identification of carbapenemase-producing K. pneumoniae. ESBL and AmpC-producing K. pneumoniae were detected using Double Disc Test (DDT) and Disc Potentiation Test (DPT), respectively. The presence of carbapenemase, ESBL, and AmpC encoding genes was screened by Polymerase Chain Reaction (PCR) assay. A total of 100 K. pneumoniae isolates were collected. K. pneumoniae isolates had the highest resistance rate to cefazolin (66%) and cefotaxime (66%). Meropenem and amikacin with sensitivity rates of 76% and 69% were the most effective antimicrobial agents on K. pneumoniae isolates. It was found that 12 (12%), 27 (27%), and 9 (9%) K. pneumoniae isolates were positive in MHT, DDT, and DPT tests, respectively. Among the carbapenemase-encoding genes, blaOXA-48 (24%) and blaIMP (13%) genes had the highest frequency, while blaKPC and blaGIM genes were not detected among K. pneumoniae isolates. blaTEM (48%) and blaCMY (8%) genes had the highest frequency among ESBL and AmpC β-lactamase-encoding genes, respectively. It is vital to adopt effective control strategies for K. pneumoniae infections and ensure rapid identification of antibiotic resistance profile.


Isolation and molecular identification of keratinophilic fungi from public parks soil in Shiraz, Iran.
Keratinophilic fungi are an important group of fungi that live in soil. The aim of this study was to isolate and identify keratinophilic fungi from the soil of different parks in Shiraz. A total of 196 soil samples from 43 parks were collected. Isolation of the fungi was performed by hair bait technique. The isolated colonies were identified by morphologic feature of macro- and microconidia and molecular method, using DNA sequence analysis. ITS region of ribosomal DNA was amplified and the PCR products were sequenced. Results. 411 isolates from 22 genera were identified. Fusarium (23.8%), Chrysosporium (13.13%), Acremonium (12.65%), Penicillium (12.39%), Microsporum gypseum (1.94%), Bionectria ochroleuca (1.21%), Bipolaris spicifera (1.21%), Scedosporium apiospermum (0.82%), Phialophora reptans (0.82%), Cephalosporium curtipes (0.49%), Scedosporium dehoogii (0.24%), Ochroconis constricta (0.24%), Nectria mauritiicola (0.49%), Chaetomium (0.49%), Scopulariopsis (0.24%), Malbranchea (0.24%), and Tritirachium (0.24%) were the most important isolates. Most of the fungi were isolated from the soils with the PH range of 7 to 8. Our study results showed that many keratinophilic fungi isolated from the parks soil are important for public health and children are an important group at a high risk of being exposed to these fungi.


Acute but not chronic graft-versus-host disease is associated with a reduction of circulating CD4(+)CD25 (high)CD127 (low/-) regulatory T cells.
Defects in central and peripheral tolerance are thought to contribute to life-threatening graft-versus-host disease (GvHD), a severe complication following allogeneic stem cell transplantation (SCT). Recent investigations have demonstrated regulatory T cells (Tregs) to suppress allogeneic immune reactions. Therefore, SCT patients with no or critically low numbers of Tregs may have an increased risk of GvHD. To address this hypothesis, we analyzed the recovery of CD4(+)CD25(high)CD127(low/-) Tregs in the peripheral blood of patients who have never developed GvHD (n = 6), patients who developed acute/chronic GvHD (n = 18), and patients who developed chronic GvHD without an earlier acute manifestation (n = 5) every 30 days for the first 6 months after peripheral blood SCT (PBSCT). The number of Tregs continuously improved in acute/chronic GvHD patients, but always remained lower than Tregs quantified in patients who never developed a GvHD. In contrast, chronic GvHD patients who did not develop acute GvHD earlier displayed significantly increased Treg cell numbers at the timepoint of chronic inflammation. These results indicate that numerically deficient Tregs following PBSCT are associated with the development of acute but not chronic GvHD.


Predictive ability of anthropometric indices in identifying metabolic syndrome among US adolescents 10 to 19 years old: Analysis from the National Health and Nutrition Examination Survey 2011 to 2018 data set.
The aim of this study was to identify the best anthropometric indices for predicting metabolic syndrome in US adolescents. A cross-sectional study analyzed data of adolescents ages 10 to 19 y using the National Health and Nutrition Examination Survey 2011 to 2018 data. The receiver operating characteristic areas under the curve (AUCs) of waist circumference z score, body roundness index, body mass index, and A Body Shape Index in identifying predicting metabolic syndrome were assessed. Furthermore, sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios of all anthropometric indices were calculated. A total of 5496 adolescents were included in the analysis. Waist circumference z score had an AUC of 0.90 (95% CI, 0.89-0.91), sensitivity of 95.0% (95% CI, 89.4-98.1), and specificity of 74.8% (95% CI, 73.6, 76.0). Body roundness index had an AUC of 0.88 (95% CI, 0.87-0.89), sensitivity of 96.7% (95% CI, 91.7-99.1), and specificity of 75.2% (95% CI, 74.1-76.4). Body mass index z score had an AUC of 0.83 (95% CI, 0.81-0.85), sensitivity of 97.5% (95% CI, 92.9-99.5), and specificity of 68.2% (95% CI, 66.9-69.4). A Body Shape Index had an AUC of 0.59 (95% CI, 0.56-0.61), sensitivity of 75.0% (95% CI, 66.3-82.5), and specificity of 50.9% (95% CI, 49.5-52.2). Our study found waist circumference z score and body roundness index were the best predictors of predicting metabolic syndrome compared with body mass index z score and A Body Shape Index in both boys and girls. We recommend that future studies develop global cutoff points for these anthropometric indices and examine their performance in a multi-country setting.


Structures, biosynthesis, and bioactivities of prodiginine natural products.
Prodiginines are a large family of microbial secondary metabolites with a core structure of tripyrrole rings. They exhibit not only diverse chemical structures but also rich biological activities, such as anti-cancer, anti-microbial, anti-algae, anti-parasitic, pesticides, and UV radiation resistance. The preferred cytotoxicity to cancer cells rather than normal cells indicates a good biological selectivity and safety, which makes the prodiginines promising candidates for drug development and novel additives for food processing. Until now, 33 prodiginine natural products have been identified in various bacteria, including Serratia, Hahella, Pseudoalteromonas, Vibrio, Zooshikella, Streptomyces, and Actinomadura. However, most efforts are still focused on the star molecule prodigiosin, while little yet is known about other prodiginine members, which retards the research and application of prodiginine compounds. To gain insight into the prodiginine family, we reviewed the recent discoveries on their chemical structures, biosynthesis, biological activities, and mechanisms of action. We believe this article will provide a guideline for new research on prodiginines, such as the discovery of new congeners and drug development. KEY POINTS: • The prodiginines are a large family of natural products with a core structure of tripyrrole rings and exhibit various bioactivities. • The prodiginines have a widespread distribution among many environmental microbes and diverse biosynthetic pathways, indicating important ecological roles and a great potential for new congeners. • The potent biological activities and good selectivity of action make prodiginines good lead compounds for drug development.


Re-evaluation of glucagon1-6: the N-terminal hexapeptide of glucagon is not biologically active in the hepatic adenylate cyclase system.
The N-terminal hexapeptide of glucagon and the corresponding carboxamide analog, were prepared by solid-phase synthesis and tested for biological activity in the hepatic adenylate cyclase system. Both peptides were found to be inactive, even at concentrations of 10 mM. The differences observed in the activity of our compounds compared to previous reports, is ascribed to the presence of a contaminant found in earlier preparations which activates adenylate cyclase.


Anterior fresh frozen structural allografts in the thoracic and lumbar spine. Do they work if combined with posterior fusion and instrumentation in adult patients with kyphosis or anterior column defects?
This was a prospective study of 24 adult patients with kyphosis or anterior column spinal defects treated with anterior fresh frozen allograft for anterior column defects and posterior instrumentation and autogenous grafting. The objectives of the study were to assess the effectiveness of the anterior allograft in maintaining sagittal correction and to assess anterior incorporation. Twenty-four patients were followed for a minimum of 2 years (range, 2 + 0-5 + 4 years). Upright radiographs were analyzed before surgery, immediately after surgery, and at the final follow-up examination to assess success of anterior fusion and maintenance of correction. A strict four-point grading system was used. Two independent observers analyzed the radiographic results. Only two patients showed some collapse of their anterior allograft. The other 22 patients maintained correction, attaining a Grade I or Grade II fusion. Semiconstrained instrumentation ws used posteriorly in the two patients who had graft collapse. Anterior structural allograft worked effectively to maintain correction of kyphosis if combined with posterior instrumentation and autogenous grafting. Rigid forms of posterior instrumentation were preferred.


The effects of leisure time physical activity on depression among older women depend on intensity and frequency.
Leisure time physical activity (LTPA) is beneficial for late-life depression (LLD). The main purpose of this study was to estimate the associations between LTPA parameters (intensity, duration, frequency) and LLD. Through the 2018 Women Health Needs Survey, data on 1,892 women aged 55-70 in Hunan, China, were studied. Depression was measured by the 9-item Patient Health Questionnaire (PHQ-9). Self-reported LTPA parameters were collected. Binary logistic regression models were used to compute odds ratios (OR) for LTPA for predicting depression. Sensitivity analyses were conducted to examine the effect of missing values. Moderate LTPA volume (OR = 0.582, p = 0.027, 95% CI [0.360-0.941] for 150-299 min/week and OR = 0.392, p = 0.002, 95% CI [0.215-0.714] for ≥300 min/week) was associated with reduced depression, while vigorous LTPA could increase the risk (OR = 2.414, p = 0.029, 95% CI [1.095-5.325] for <75 min/week and OR = 3.824, p = 0.007, 95% CI [1.439-10.158] for ≥75 min/week). Frequent (6-7 days/week), moderate LTPA had a lower risk (OR = 0.570, p = 0.021, 95% CI [0.353-0.918]), while frequent (≥3 days/week), vigorous LTPA increased the risk (OR = 5.103, p = 0.001, 95% CI [1.977-13.172]). The adjusted relationship between the duration and depression was not observed. The results were supported by the sensitivity analysis based on missing value replacement. In this cross-sectional study, LTPA data were self-reported and no data on light LTPA were collected. Moderate LTPA, associated with mental health benefits, should be recommended for older women instead of vigorous LTPA.


Migraine stroke: a possible complication of both migraine with and without aura.
We describe four migraine patients who developed an ischemic stroke during their typical migraine attacks. Cerebral infarction as a possible complication of migraine without aura is discussed. We propose a review of the migraine stroke definition of the International Headache Society.


Is the intergenerational transmission of overweight 'gender assortative'?
Using almost two decades worth of data from the Health Survey for England, that contain representative records of clinically measured weight and height, this paper studies whether parents and children's overweight (including obesity) is 'gender assortative'. Our findings suggest that the intergenerational transmission of parent's overweight differs by children's sex and is statistically different for fathers and mothers. Gender assortative overweight is stronger among pre-school age and school-aged children. The parent-child associations are large and precisely estimated, heterogeneous by children's age and sex and stronger among white children and children of older parents. These results suggest there is a gender assortative intergenerational association of overweight.


Brainstem atrophy is linked to extrapyramidal symptoms in frontotemporal dementia.
Extrapyramidal (EP) symptoms are a known feature in a subpopulation of patients with behavioral variant frontotemporal dementia (bvFTD). Concomitant EP symptoms with FTD-like neuropsychiatric symptoms are also core features in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). This complicates the early diagnosis of these disorders. Our retrospective register study aimed to discover imaging (MRI and FDG-PET) biomarkers to differentiate PSP, CBD, and bvFTD patients with extrapyramidal symptoms (EP +) from bvFTD patients without EP symptoms (EP-). The records of 2751 patients were screened for the diagnoses and presence of EP symptoms. A total of 222 patients were submitted to imaging analysis and applicable imaging data were recovered from 139 patients. Neuroimaging data were analyzed using Freesurfer software. In the whole cohort, EP + patients showed lower volumes of gray matter compared to EP- patients in the putamen (p = 0.002), bilateral globus pallidum (p = 0.002, p = 0.042), ventral diencephalon (p = 0.002) and brain stem (p < 0.001). In the bvFTD subgroup, there was volumetric difference between EP + and EP- patients in the brain stem. FDG-PET scans in the bvFTD patient subgroup showed that EP + patients had comparative hypometabolism of the superior cerebellar peduncle (SCP) and the frontal lobes. We discovered that EP symptoms are linked to brainstem atrophy in bvFTD patients and the whole cohort. Also, evident hypometabolism in the SCP of bvFTD EP + patients was detected as compared to bvFTD EP- patients. This could indicate that the EP symptoms in these diseases have a more caudal origin in the brainstem than in Parkinson's disease.


Very-early-onset inflammatory bowel disease versus late-onset inflammatory bowel disease in relation to clinical phenotype: A cross-sectional study.
Inflammatory bowel disease (IBD) is a chronic condition and children are affected by the disease's burden and therapeutic interventions for much longer than adults. Children of various ages can be diagnosed with IBD. The research was carried out at the Pediatric Gastroenterology Clinic at Cairo University's Faculty of Medicine's Children's Hospital. From January 2013 to December 2017, this single-center observational cross-sectional study included 197 children aged 14 years and compared the clinical phenotypes of very-early-onset IBD (VEO-IBD) in patients aged six years and late-onset IBD (LO-IBD) in patients aged six to 14 years. Children with IBD at less than six years of age have a more colonic phenotype than children diagnosed later in life, who are more likely to have ileocolonic diseases (p = 0.002). In VEO-disease Crohn's (VEO-CD), growth failure/poor weight gain was 14%, while in LO-CD, it was 31%. Children with VEO-IBD do not always present with more severe disease than older children. Most clinical features in children with VEO-ulcerative colitis (VEO-UC) and LO-UC were similar at the first presentation, with the exception of abdominal pain, which was significantly less common in the VEO-UC group (p = 0.001) and hematochezia, which was significantly more common in the LO-UC group (p = 0.048). Children with VEO-disease Crohn's (VEO-CD) had a higher risk of bloody stools, diarrhea and fever (p = 0.013, p = 0.001 and p = 0.008, respectively), but a lower risk of abdominal pain (p = 0.000). Growth failure/poor weight gain occurred in 14% of VEO-CD patients and 31% of LO-CD patients. In LO-UC, abdominal pain and hematochezia were significantly more common. In LO-CD, hematochezia, diarrhea and fever were significantly more common. In LO-IBD-U, abdominal pain and diarrhea were significantly more common.


Functional Microneedle Patch for Wound Healing and Biological Diagnosis and Treatment.
Wound healing, especially chronic wounds, has been one of the major challenges in the field of biomedicine. Drug therapy alone is not effective, so a variety of functional wound healing dressings have been developed. Microneedles have attracted more and more attentions in the field of wound healing dressings due to their penetration and high drug delivery efficiency. In this review, all the studies on the application of microneedles in wound healing in recent years are summarized, classify different microneedles according to their functions in the process of wound healing, discuss the current challenges in the transformation of microneedle technology toward clinical applications, and finally look forward to the future design and development directions of microneedles in this field.


Insulin gene is a target in activin receptor-like kinase 7 signaling pathway in pancreatic beta-cells.
Activins regulate pancreatic development, differentiation and insulin secretion. Activin receptor-like kinase 7 (ALK7) has been identified as a receptor for Nodal and Activin AB and B, and is expressed in pancreatic islets and beta-cell lines. In this study, human insulin promoter was activated by Smad2, Smad3 and the pancreatic and duodenal homeobox factor-1 (PDX-1) in the ALK7 pathway. A conserved Smad binding element was related to the promoter activation. Phosphorylated Smad2/Smad3 and PDX-1 were bound to insulin gene with Nodal and Activin AB, and the phosphorylated Smad2/Smad3 interacted with PDX-1. These results indicate that one of the direct target genes of Nodal and Activin AB signals is the insulin gene in pancreatic beta-cells and that PDX-1 is directly involved in the ALK7-Smad pathway.


Effect of treatment with branched-chain amino acids during sorafenib therapy for unresectable hepatocellular carcinoma.
To examine the effect of branched-chain amino acid (BCAA) therapy for patients with unresectable hepatocellular carcinoma (HCC) treated with sorafenib. Seventy-eight subjects with unresectable HCC with a serum level of albumin of 3.5 g/dL or less treated with sorafenib were evaluated. They were classified into two groups: those receiving BCAA granules (n = 34; BCAA group) or a regular diet (n = 44; control group). We compared overall survival and administration period of sorafenib, and analyzed absolute changes in serum levels of albumin during sorafenib therapy in 41 patients who continued sorafenib therapy for 1 month or more with a follow up of more than 3 months. Median survival time (MST) in BCAA and control groups was 350 and 143 days (P = 0.007), respectively. Median administration period of sorafenib in the two groups was 59 and 41 days (P = 0.018). In the 41 patients described above, at 1 month, there was no significant change in the serum level of albumin between the two groups, but at 3 months, the difference in the absolute change in the serum level of albumin in the two groups reached significance (P = 0.023). In these subgroup analyses, the administration period of sorafenib as well as the MST in the BCAA group were significantly longer than those in the control group (P = 0.020 and = 0.004). BCAA treatment during sorafenib therapy in HCC patients is useful for maintaining hepatic functional reserve, which may help to avoid early discontinuance of sorafenib therapy and improve survival.


Leucine supplementation combined with resistance exercise improves the plasma lipid profile of dexamethasone-treated rats.
The impact of leucine supplementation and resistance exercise (RE) on plasma lipid profile was evaluated in adult rats treated with dexamethasone, an experimental model of dyslipidemia. Total cholesterol did not differ among groups. Furthermore, leucine supplementation did not promote improvement in the plasma total cholesterol and LDL-c of the animals. However, plasma TG and VLDL-c were significantly decreased and HDL-c increased after 7 days of leucine supplementation combined with RE. In conclusion, leucine supplementation combined with RE, but not isolated, improved the plasma lipid profile of dexamethasone-induced dyslipidemic rats.


Partitioning of CO(2) incorporation among planktonic microbial guilds and estimation of in situ specific growth rates.
Partitioning of CO(2) incorporation into oxygenic phototrophic, anoxygenic phototrophic, and chemolithoautotrophic guilds was determined in a freshwater lake (Lake Cisó, Banyoles, Spain). CO(2) incorporation into the different types of microorganisms was studied at different depths, during diel cycles, and throughout the year. During winter holomixis, the whole lake became anoxic and both the anoxygenic and chemolithoautotrophic guilds were more active at the surface of the lake, whereas the activity of the oxygenic guild was negligible. During stratification, the latter guild was more active in the upper metalimnion, whereas the anoxygenic guild was more active in the lower metalimnion. Specific growth rates and doubling times were estimated for the most conspicuous phototrophic microorganisms. Doubling times for Cryptomonas phaseolus ranged between 0.5 and 192 days, whereas purple sulfur bacteria (Chromatiaceae-like) ranged between 1.5 and 238 days. These growth rates were similar to those calculated with a different approach in previous papers and indicate slow-growing populations with very large biomass. Overall, the annual total CO(2) incorporation in Lake Cisó was 220 g C m(-2). Most of the CO(2) incorporation, however, was due to the chemolithoautotrophic guild (61% during holomixis and 56% during stratification), followed by the anoxygenic phototrophic guild (35 and 19%, respectively) and the oxygenic phototrophs (4 and 25%, respectively), making dark carbon fixation the key process in the autotrophic metabolism of the lake.


The continuing conundrum in oligometastatic breast carcinoma: A real-world data.
The optimal management in Oligometastatic (OM) breast carcinoma is not defined. To identify the prognostic factors influencing OM and the effect of Locoregional treatment (LRT) on survival in OM. Patients with ≤5 metastases and each with ≤ 5 cm size were defined as OM. Data of OM were extracted from the Institute Registry between 2012 and 2018. The impact of prognostic factors on survival was analysed by univariate and multivariate Cox regression. The Kaplan Meier survival curves were used to plot PFS and OS. There were 170 patients with OM. The median follow-up was 61 months. Median OS was 43.3 months. The median OS was 74 months in OMD vs 22.7 months in Oligorecurrent disease (ORD) with 5year OS rate of 55.3% vs 16.5% respectively. In the multivariate analyses of OMD both Ki67 ≤ 50% and hormone therapy (HT) showed significant favourable survival outcome. While premenopausal status and HT showed significant survival benefits in ORD. The worse survival outcome in ORD could be because of their aggressive biology and deficit in LRT compared to literature review. The prognostic factors were swayed by the uneven distribution of HR status, grade and Ki67. The survival of OM was influenced by OMD, Ki67 ≤ 50%, premenopausal status and HT. The lesser survival rates of OM in the long term suggest the need for curative LRT to metastatic sites and primary tumor. The potential role of HT and targeted therapy with or without LRT need to be assessed in future randomised trials.


Mid-Term Outcomes of Retroperitoneal and Transperitoneal Exposures in Open Aortic Aneurysm Repair.
There have been a number of studies comparing perioperative outcomes of the retroperitoneal (RP) and transperitoneal (TP) approaches to open aortic aneurysm repair (OAR), many of which have shown conflicting results. There remains a paucity of data comparing these 2 exposures beyond 30 days. The purpose of this study was to evaluate the mid-term outcomes between RP and TP exposures in OAR. This is a retrospective review of elective OAR from a single institution from 2010 to 2014 with at least one year of follow-up. Patients with any prior aortic repair, prior midline TP or RP exposures, prior small bowel obstruction (SBO), or prior abdominal wall hernia repair were excluded. Patients' demographics, comorbidities, intraoperative details, and postoperative variables up to 5 years were compared. Primary outcomes were all-cause mortality, aortic or arterial reinterventions, incisional reinterventions, SBO or reintervention for SBO, and composite reintervention. Of the 273 OARs identified, 136 OARs (86 TP and 50 RP exposures) met criteria for the study. The average follow-up was 43.4 months. Of the preoperative and intraoperative characteristics, patients with RP exposures were significantly more likely to be female (30% vs. 12.8%; P = .014) and to have larger aneurysm (6.1 ± 1.02 cm vs. 5.4 ± 1.01 cm; P < .001), tube graft (48% vs 19.8%; P < .001), and renal bypass (30% vs. 2.3%; P < .001). Patients with TP exposures were significantly more likely to have inferior mesenteric artery reimplantation (15.1% vs. 4%; P = .046), infrarenal clamping (65.9% vs. 22%; P < .001), and iliac aneurysm (36% vs. 4%; P < .001). During mid-term follow-up, there was not a difference in all-cause survival at 3 years (95.8% vs. 95.8%; P = .52). Although there were more incisional hernias in the TP group (48% vs. 8%; P < .001), there was no difference in incisional reinterventions (14% vs. 6%; P = .36). There were no differences in aortic or arterial reinterventions (5% vs. 4%; P = .86), SBO (7% vs. 0%; P = .99), intervention for SBO (3% vs. 0%; P = .99), or composite reinterventions (16% vs. 10%; P = .6) between the TP and RP exposures. In mid-term follow-up, OAR through TP exposure had more incisional hernias compared with RP exposure. However, there is no difference in mortality or composite reinterventions between approaches.


Higher Risk, Higher Reward? Self-Reported Effects of Real-World Cannabis Use in Parkinson's Disease.
Despite limited evidence, people with Parkinson's disease (PD) use cannabis for therapeutic purposes. Given barriers to performing randomized trials, exploring real-world experiences with cannabis in PD is valuable. Investigate the frequency and magnitude of symptomatic effects reported with cannabis use in PD. An anonymous, 15-question, web-based survey was deployed on Fox Insight. Cannabis product types were defined (by relative tetrahydrocannabinol [THC] and cannabidiol [CBD] content) and respondents were asked to reference product labels. Questions focused on use patterns and subjective effects on 36 predefined symptoms (rated -2-markedly worse to +2-markedly better). 1,881 people with PD responded (58.5% men; mean age 66.5; 50.5% <3 years of PD). 73.0% of respondents reported medicinal use, though 30.8% did not inform their doctor. 86.7% knew their type of cannabis product: 54.6% took higher CBD, 30.2% higher THC, and 15.2% took similar amounts of THC and CBD products. Most common use was oral administration, once daily, for less than six months. Frequent improvements were reported for pain, anxiety, agitation, and sleep (>50% of respondents, mean magnitude 1.28-1.51). Dry mouth, dizziness, and cognitive changes were common adverse effects (20.9%-30.8%, mean -1.13 to -1.21). Higher THC users reported more frequent improvements in depression, anxiety, and tremor, and more frequent worsening in dry mouth and bradykinesia than other product types. Respondents with PD reported using more CBD products, via oral administration, with mild subjective benefits primarily for sleep, pain, and mood. Higher THC products may be higher risk/higher reward for PD-related symptoms.


Cost-effectiveness of KRAS testing in metastatic colorectal cancer patients in the United States and Germany.
The objective of this study was to determine the cost-effectiveness of testing for KRAS mutations before administering EGFR inhibitors such as cetuximab and panitumumab for patients with advanced metastatic colorectal cancer (mCRC) in the United States and Germany. We developed a lifetime Markov model of costs and survival associated with treating mCRC patients to assess the impact of KRAS testing before administering EGFR inhibitor-containing chemotherapy regimens. Overall, combination therapies involving cetuximab plus irinotecan/FOLFIRI had a better life expectancy (25.83 weeks) than cetuximab or panitumumab alone. Use of KRAS testing (assuming KRAS mutant patients receive only irinotecan) was equally effective and saved $12,428 per patient in the United States. When KRAS mutant patients received best supportive care, the life expectancy decreased slightly (24.26 weeks vs. 25.83 weeks) and the costs decreased by $13,501 in the United States and €9,560 in Germany. For patients treated with cetuximab alone, use of KRAS testing to identify mutations lowered costs by $8,040 per patient in the U.S. analysis and €3,856 per patient in the German analysis. For patients treated with panitumumab alone, use of KRAS testing to identify mutations lowered costs by $7,546 per patient in the U.S. analysis and €4,612 per patient in the German analysis. Model results were sensitive to the cost of chemotherapy regimens and the prevalence of KRAS mutations in the population. Under most scenarios, using KRAS testing to select patients for EGFR inhibitor therapy saved $7,500-$12,400 per patient in the United States and €3,900-€9,600 per patient in Germany with equivalent clinical outcomes.


P92 steel and inconel 617 alloy welds joint produced using ERNiCr-3 filler with GTAW process: Solidification mechanism, microstructure, mechanical properties and residual stresses.
The objective of the current study was to analyse the microstructure, mechanical characteristics, and residual stresses of a dissimilar welded joint (DWJ) made of P92 steel and the Inconel alloy 617 (IN617) using the gas tungsten arc welding (GTAW) method. The ERNiCr-3 filler was selected to produce the conventional V groove (VG) and narrow V groove (NVG) butt joint. The filler deficient zones in the weldments, such as the filler deficient beach, i.e. unmixed zone (UZ), peninsula, and island, as well as the distinct heat-affected zone (HAZ), were visible near the interface of ERNiCr-3 filler weld and P92 steel due to the distinct differences in the chemical composition, microstructure, and mechanical properties between the filler and P92 base metal (BM). A very narrow partial melted zone (PMZ) and almost negligible UZ and HAZ were noticed at the interface of IN617 and ERNiCr-3 weld metal and it occurred mainly due to the similarity in microstructure and melting point. The austenitic microstructure of ERNiCr-3 filler weld was accompanied by precipitates enriched with Ti and Nb along with the inter-dendritic space. At room temperature, the mechanical properties of both the groove joints were evaluated, and the test results indicated that the welded joint satisfied the standard requirements for AUSC power plants' boiler applications. The tensile test results showed the failure from ERNiCr-3 filler weld with a tensile strength of 627 ± 2 MPa and 636 ± 3 MPa for VG and NVG welded joints, respectively. A poor weld metal impact toughness in comparison to the BMs was attributed to the presence of the brittle Ti(C, N) and Nb(C) particles in the interdendritic space. The impact toughness for the NVG weld joint was measured higher than for the VG weld joint. A significant hardness deviation was measured along the weldments that might be due to heterogeneous microstructure, i.e. UZ, HAZ, delta ferrite, and weld metal. To impart the ductility and temper the martensite in P92 HAZ, post-weld heat treatment (PWHT) was also performed, and a studied their effect on microstructure evolution across the weldments and mechanical properties. Groove design also showed a significant effect on residual stress variation. The work highlights the groove geometry, welding procedure, evolution of the microstructure along the weldments, mechanical characteristics, and residual stress variation of DWJ of P92 steel and IN617 alloy. In comparison to conventional VG joints, the NVG joints exhibited superior mechanical properties and lower residual stress values.


Rapid Deployment Valves Are Advantageous in the Redo Setting: A Single-Centre Retrospective Study.
The spectrum on how to manage aortic valve disease continues to widen. The purpose of this study is to add further clarification to the role of rapid deployment valves (RDVs) by comparing their outcomes with traditional sutured valves (TSVs) in the reoperative aortic valve replacement (AVR) setting. This study was a retrospective review of all patients undergoing a second surgical reoperation for aortic valve disease. Patients were categorized into 2 groups: RDV and TSV. Cox proportional hazards regression models were used to determine the association between exposures of interest and the primary and secondary outcomes, after adjusting for all the baseline characteristics. The primary outcome was major adverse cardiovascular events (MACE) within 3 years, which was the composite of all-cause death, readmission for myocardial infarct, readmission for stroke, and readmission for heart failure. A total of 307 patients made up the study population from 2010 to 2019. Of those, 254 patients received TSV, and 53 patients received RDV. RDV patients were significantly older than TSV patients by 10 years, on average. Shorter cardiopulmonary bypass (CPB) times were found with the RDV group. There was no significant difference in the primary outcome of MACE within 3 years. This single-centre large cohort study of patients with reoperative AVR found that RDVs facilitate smoother operations by saving 1 hour of cross-clamp time and CPB time. Furthermore, RDVs have comparable outcomes with TSVs, despite the significantly older patient population.


Mycotic aneurysm of the descending thoracic aorta in a 2-kg neonate.
Umbilical artery catheterization is often performed in critically ill neonates. Infection and thromboembolic events are relatively frequent complications, but aneurysm formation is rare. We describe the case of a premature baby who developed a rapidly expanding aneurysm of the descending thoracic aorta, secondary to a highly placed infected umbilical catheter. The rapid progression under medical therapy prompted us to replace the thoracic aorta with an 8-mm polytetrafluoroethylene graft, using extracorporeal circulation and core cooling. The baby had an excellent recovery and was discharged home after a prolonged antibiotic course. He is being followed with repeated imaging studies for a small abdominal aneurysm. We describe a novel approach to this rare and complicated problem and provide a review of the literature on the subject.


Elevated titer of antibodies to Simian sarcoma virus envelope antigen (gp70) and normal response to influenza virus in untreated Danish Hodgkin's patients.
Untreated Danish Hodgkin's disease (HD) patients and paired age- and sex-matched controls were tested for serum antibodies to Epstein-Barr virus (EBV), six strains of influenza virus and Simian sarcoma virus/Simian sarcoma-associated virus [SSV(SSAV)] antigens. HD sera showed significantly elevated titers against EBV and both increased incidence and mean titer of antibodies to the envelope glycoprotein of SSV(SSAV), whereas testing against the influenza viruses revealed no differences between HD and controls. A focus reduction assay demonstrated a low incidence in HD and controls of sera with neutralizing effects against SSV(SSAV) and the "baboon" C-type virus component of the human HL-23 virus complex, which seemed coupled to HL-A type W19.


Hepatocyte-like cells derived from human induced pluripotent stem cells using small molecules: implications of a transcriptomic study.
Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs) hold great promise in toxicological applications as well as in regenerative medicine. Previous efforts on hepatocyte differentiation have mostly relied on the use of growth factors (GFs) to recapitulate developmental signals under in vitro conditions. Recently, the use of small molecules (SMs) has emerged as an attractive tool to induce cell fate transition due to its superiority in terms of both quality and cost. However, HLCs derived using SMs have not been well characterized, especially on the transcriptome level. HLCs were differentiated from human iPSCs using a protocol that only involves SMs and characterized by transcriptomic analysis using whole genome microarrays. HLCs derived using the SM protocol (HLC_SM) displayed specific hepatic marker expression and demonstrated key hepatic functions. Transcriptomic analysis of the SM-driven differentiation defined a hepatocyte differentiation track and characterized the expression of some key marker genes in major stages of hepatocyte differentiation. In addition, HLC_SM were scored with CellNet, a bioinformatics tool quantifying how closely engineered cell populations resemble their target cell type, and compared to primary human hepatocytes (PHHs), adult liver tissue, fetal liver tissue, HLCs differentiated using GFs (HLC_GF), and commercially available HLCs. Similar to HLC_GF, HLC_SM displayed a mixed phenotype of fetal and adult hepatocytes and had relatively low expression of metabolic enzymes, transporters, and nuclear receptors compared to PHHs. Finally, the differentially expressed genes in HLC_SM compared to HLC_GF and to PHHs were analyzed to identify pathways and upstream transcription regulators which could potentially be manipulated to improve the differentiation of HLCs. Overall, the present study demonstrated the usefulness of the SM-based hepatocyte differentiation method, offered new insights into the molecular basis of hepatogenesis and associated gene regulation, and suggested ways for further improvements in hepatocyte differentiation in order to obtain more mature HLCs that could be used in toxicological studies.


[1-(4-chloro-3-nitrobenzenesulfonyl)-1H-indol-3-yl]-methanol, an indole-3-carbinol derivative, inhibits glutamate release in rat cerebrocortical nerve terminals by suppressing the P/Q-type Ca2+ channels and Ca2+/calmodulin/protein kinase A pathway.
Indole-3-carbinol (I3C), found in cruciferous vegetables, has been proposed to exhibit neuroprotective effects. This study aimed to investigate the effect of the I3C derivative [1(4-chloro-3-nitrobenzenesulfonyl)-1H-indol-3-yl]-methanol (CIM), which has superior pharmacokinetic properties to I3C, on glutamate release in rat cerebrocortical nerve terminals (synaptosomes). We observed that CIM dose-dependently inhibited glutamate release evoked by the potassium channel blocker 4-aminopyridine (4-AP). CIM-mediated inhibition of glutamate release was attributed to reduced exocytosis, as it correlated with the removal of extracellular calcium and blocking of the vesicular glutamate transporter but not the glutamate transporter. In addition, CIM decreased 4-AP-evoked intrasynaptosomal Ca2+ elevation; however, it did not alter the synaptosomal membrane potential. The inhibition of P/Q-typeCa2+ channels abolished the effect of CIM on 4-AP-evoked glutamate release, and the effect was not prevented by intracellular Ca2+ release inhibitors. Moreover, the molecular docking study showed that CIM exhibited the highest binding affinity with the P/Q-type Ca2+channels. Finally, the CIM-mediated inhibition of glutamate release was sensitive to calmodulin, adenylate cyclase (AC), and protein kinase A (PKA) inhibitors. Based on these results, we propose that CIM, through the direct suppression of P/Q-type Ca2+ channels, decreases Ca2+ influx and the activation of Ca2+/calmodulin/AC/PKA signaling, thereby inhibiting glutamate release. This finding is crucial for understanding the role of CIM in the central nervous system and for exploiting its potential in therapeutic interventions.


A new species of Allosathes Gaud, Atyeo & Berla (Astigmata: Crypturoptidae) on feathers of the Chilean tinamou, Nothoprocta perdicaria (Tinamiformes: Tinamidae) in Chile.
Allosathes anitae n. sp. Casanueva & González-Acuña (Astigmata: Crypturoptidae), collected on the Chilean tinamou Nothoprocta perdicaria (Tinamiformes: Tinamidae) from different localities of the Ñuble Province, Chile, is described. Comments on its affinities and differences with Allosathes anepiandrius Gaud, Atyeo & Berla are also included.


Profiling of behavioral effects evoked by ketamine and the role of 5HT2 and D2 receptors in ketamine-induced locomotor sensitization in mice.
Ketamine has addictive potential, a troublesome fact due to its promising use as a therapeutic drug. An important phenomenon associated with drug addiction is behavioral sensitization, usually characterized as augmented locomotion. However, other behaviors may also be susceptible to sensitization, and/or interfere with locomotor activity. Thus, this study drew a comprehensive behavioral 'profiling' in an animal model of repeated administration of ketamine. Adult Swiss mice received single daily ketamine injections (30 or 50 mg/Kg, i.p.), which were followed by open field testing for 7 days (acquisition period, ACQ). A ketamine challenge (sensitization test, ST) was carried out after a 5-day withdrawal. Locomotion, rearing, grooming, rotation and falling were assessed during ACQ and ST. All behaviors were affected from the first ACQ day onwards, with no indication of competition between locomotion and the other behaviors. Only locomotion in response to 30 mg/Kg of ketamine both escalated during ACQ and expressed increased levels at ST, evidencing development and expression of locomotor sensitization. Considering the involvement of serotonin 5HT(2) and dopamine D(2) receptors on addiction mechanisms, we further tested the involvement of these receptors in ketamine-induced sensitization. Ketanserin (5HT2 antagonist, 3 mg/Kg, s.c.) prevented ketamine-evoked development of locomotor sensitization. However, ketanserin pretreatment during ACQ failed to inhibit its expression during ST. Raclopride (D2 antagonist, 0.5 mg/Kg, s.c.) evoked less robust reductions in locomotion but prevented the development of ketamine-evoked sensitization. Pretreatment during ACQ further inhibited the expression of sensitization during ST. These results indicate that a partial overlap in serotonergic and dopaminergic mechanisms underlies ketamine-induced locomotor sensitization.


High-efficiency adenovirus-mediated in vivo gene transfer into neonatal and adult rodent skeletal muscle.
Several methodological limitations have emerged in the use of viral gene transfer into skeletal muscle. First, because the nuclei of mature muscle fibers do not undergo division, the use of strategies involving replicative integration of exogenous DNA is greatly limited. Another important limitation concerns the maturation-dependent loss in muscle fiber infectivity with adenoviral vectors. In this study, we investigated the possibility that high-titer infections with recombinant adenovirus, expressing a foreign marker gene under the control of a strong viral promoter, can significantly improve the efficiency of gene transfer in vivo into neonatal and adult rat skeletal muscle. High-titer (2 x 10(10) plaque forming units) intramuscular injection of replication-defective adenovirus vector, expressing green fluorescent protein (GFP) under the control of cytomegalovirus promoter, resulted in GFP expression in 99 +/- 0.34% of fibers in the adult soleus muscle and in approximately 85 +/- 1.44% of fibers in the adult tibialis anterior muscle. Interestingly, reduction in injected adenoviral dose significantly reduced the number of GFP-positive fibers in the adult tibialis anterior muscle, but not in the soleus muscle. However, in neonates, adenoviral infection resulted in GFP expression in 96-99% of the fibers in the tibialis anterior and the gastrocnemius muscles regardless of administered adenoviral dose.


Analysis of a rare melanoma patient with a spontaneous CTL response to a MAGE-A3 peptide presented by HLA-A1.
We describe an HLA-A1 melanoma patient who has mounted a spontaneous cytolytic T cell (CTL) response against an antigenic peptide encoded by gene MAGE-A3 and presented by HLA-A1. The frequency of anti-MAGE-3.A1 CTLp was 5 x 10(-7) of the blood CD8 cells, with a dominant clonotype which was present in six out of seven independent anti-MAGE-3.A1 CTL clones. After vaccination with a recombinant poxvirus coding for the MAGE-3.A1 antigen, the blood frequency of anti-MAGE-3.A1 CTLp increased tenfold. Twenty-two independent CTL clones were derived. Surprisingly, only one of them corresponded to the dominant clonotype present before vaccination. Two new clonotypes were repeated 12 and 7 times, respectively. Our interpretation of these results is that the spontaneous anti-MAGE-3.A1 CTL response pre-existing to vaccination was polyclonal, and that the vaccine restimulated only some of these clones. To estimate the incidence of spontaneous anti-MAGE-3.A1 CTL responses in melanoma patients with a tumor expressing gene MAGE-A3, we measured the blood frequency of anti-MAGE-3.A1 T cells in 45 patients, and found only two clear responses.


Superior Capsule Reconstruction With Fascia Lata Allograft Has Initial Stiffness and Ultimate Load Comparable to the Native Shoulder Superior Capsule: A Cadaveric Biomechanical Study.
The purpose of this study was to compare the biomechanical characteristics of a fascia lata superior capsule reconstruction (FL-SCR) to the native superior capsule. The native superior capsule of 8 cadaveric shoulders was tested with cyclic loading from 10 to 50 N for 30 cycles in 20° of glenohumeral abduction followed by load to failure at 60 mm/min. Following native superior capsule testing, FL-SCR was performed, which was tested as described for the native capsule. Paired t test was used for statistical analyses with P < .05 for significance. The stiffness for cycle 1 to 50 N was significantly higher for the native superior capsule compared to the FL-SCR (P = .001). By cycle 30, the stiffness between the two was not statistically different (P = .734). During load to failure, the initial stiffness to 2 mm for the FL-SCR and the native superior capsule was not statistically different (P = .262). The linear stiffness and yield load of the native superior capsule were significantly greater than that of the FL-SCR (94.5 vs 28.0 N/mm, P = .013; 386.9 vs 123.8 N, P = .029). There was no significant difference in ultimate load between the native superior capsule and the FL-SCR (444.9 vs 369.0 N, P = .413). FL-SCR has initial stiffness and ultimate load similar to the native superior capsule. The biomechanical properties of FL allograft make it an appealing option as a graft choice for superior capsule reconstruction.


Astasia-abasia and psychogenic tremor post-temporal lobectomy.
Temporal lobectomy can be complicated by somatoform disorders, psychiatric illnesses and non-epileptic psychogenic seizures. We report a woman who developed astasia-abasia and psychogenic tremor following temporal lobectomy for refractory epilepsy. To our knowledge, this type of conversion reaction following temporal lobectomy has not been previously reported.


The optimal locomotion on gradients: walking, running or cycling?
On level ground, cycling is more economical than running, which in turn is more economical than walking in the high speed range. This paper investigates whether this ranking still holds when moving on a gradient, where the three modes are expected to be mainly facing the same burden, i.e. to counter gravity. By using data from the literature we have built a theoretical framework to predict the optimal mode as a function of the gradient. Cycling was found to be the mode of choice only below 10-15% gradient, while above it walking was the least expensive locomotion type. Seven amateur bikers were then asked to walk, run and ride on a treadmill at different gradients. The speed was set so as to maintain almost constant the metabolic demand across the different gradients. The results indicate that the "critical slope", i.e. the one above which walking is less expensive than cycling (and running), is about 13-15%. One subject was loaded during bipedal gaits with a bicycle-equivalent mass, to simulate to cross-country cycling situation. The critical slope was close to 20%, due to the higher metabolic cost of loaded walking and running. Part of the findings can be explained by the mechanically different paradigms of the three locomotion types.


Assessing the toxicity after moderately hypofractionated prostate and whole pelvis radiotherapy compared to conventional fractionation.
To evaluate acute and late gastrointestinal (GI) and genitourinary (GU) toxicities after moderately hypofractionated (HF) or conventionally fractionated (CF) primary whole-pelvis radiotherapy (WPRT). Primary prostate-cancer patients treated between 2009 and 2021 with either 60 Gy at 3 Gy/fraction to the prostate and 46 Gy at 2.3 Gy/fraction to the whole pelvis (HF), or 78 Gy at 2 Gy/fraction to the prostate and 50/50.4 Gy at 1.8-2 Gy/fraction to the whole pelvis (CF). Acute and late GI and GU toxicities were retrospectively assessed. 106 patients received HF and 157 received CF, with a median follow-up of 12 and 57 months. Acute GI toxicity rates in the HF and CF groups were, respectively, grade 2: 46.7% vs. 37.6%, and grade 3: 0% vs. 1.3%, with no significant difference (p = 0.71). Acute GU toxicity rates were, respectively, grade 2: 20.0% vs. 31.8%, and grade 3: 2.9% vs. 0%, (p = 0.04). We compared prevalence of late GI and GU toxicities between groups after 3, 12, and 24 months and did not find any significant differences (respectively, p = 0.59, 0.22, and 0.71 for GI toxicity; p = 0.39, 0.58, and 0.90 for GU toxicity). Moderate HF WPRT was well tolerated during the first 2 years. Randomized trials are needed to confirm these findings.


Aligning AI Optimization to Community Well-Being.
This paper investigates incorporating community well-being metrics into the objectives of optimization algorithms and the teams that build them. It documents two cases where a large platform appears to have modified their system to this end. Facebook incorporated "well-being" metrics in 2017, while YouTube began integrating "user satisfaction" metrics around 2015. Metrics tied to community well-being outcomes could also be used in many other systems, such as a news recommendation system that tries to increase exposure to diverse views, or a product recommendation system that opstimizes for the carbon footprint of purchased products. Generalizing from these examples and incorporating insights from participatory design and AI governance leads to a proposed process for integrating community well-being into commercial AI systems: identify and involve the affected community, choose a useful metric, use this metric as a managerial performance measure and/or an algorithmic objective, and evaluate and adapt to outcomes. Important open questions include the best approach to community participation and the uncertain business effects of this process.


[Delayed delivery in multiple pregnancy: about a case and literature review].
Delayed delivery is designed to allow the remaining fetus(es) to develop after premature expulsion of the first twin in the second trimester of pregnancy. This decision is aimed to allow the remaining fetus(es) to reach full fetal growth. We here report a clinical case of delayed delivery in a patient with triple pregnancy in whom the time between the expulsion of the first twin and the birth of the third twin was 10 weeks. The purpose of this study was to highlight the benefit and indications for delayed delivery.


Cutaneous reactions to non-steroidal anti-inflammatory drugs.
We retrospectively reviewed the records of 195 patients with suspected cutaneous reactions from NSAIDs. Two hundred and six different non-steroidal anti-inflammatory drugs (NSAIDs) were suspected of causing cutaneous reactions, and the most frequent suspected causative NSAID was ibuprofen (25.7%). Angioedema and/or urticaria were the most frequent cutaneous reactions (54.4%), and the foremost suspected causative drug for these reactions was ibuprofen. The second most frequently found cutaneous reaction was maculopapular eruption (26.2%), and celecoxib was the most commonly suspected causative NSAID for it. The primary suspected NSAIDs causing fixed drug eruption were in enolic acid group. Furthermore, drug hypersensitivity syndrome was diagnosed in five patients, and Stevens-Johnson syndrome and toxic epidermal necrolysis were detected in five patients.


Functional integrity of the retrosplenial cortex is essential for rapid consolidation and recall of fear memory.
Memory storage is a temporally graded process involving different phases and different structures in the mammalian brain. Cortical plasticity is essential to store stable memories, but little is known regarding its involvement in memory processing. Here we show that fear memory consolidation requires early post-training macromolecular synthesis in the anterior part of the retrosplenial cortex (aRSC), and that reversible pharmacological inactivation of this cortical region impairs recall of recent as well as of remote memories. These results challenge the generally accepted idea that neocortical areas are slow encoding systems that participate in the retrieval of remote memories only.


Epidemiological big data and analytical tools applied in the control programmes on parasitic diseases in China: NIPD's sustained contributions in 70 years.
The analysis of epidemiological data has played an important role for the academic research carried out by the National Institute of Parasitic Diseases, China CDC, since its foundation in 1950s. Those researches, e.g., the temporal-spatial patterns of disease transmission and the identification of risk factors, have contributed significantly to the national parasitic disease control and elimination programmes in China. With the development and application of epidemiological data analysis in the last decade, all research results improve our understanding of parasitic diseases epidemiology and related health issues through the application platform of epidemiological big data and analytical tools. In particular, implementation research on analytical predictions on disease outbreak or epidemic risks have provided references to the scientific guidance on effective preventions and interventions in the parasitic disease elimination in China, such as fliariasis, malaria and schistosomiasis. This review has reflected the function of data accumulation and application of temporospatial tools in parasitic diseases control, and the ways of the NIPD's sustained contributions to the disease control programmes in China.


Can inhaled prostacyclin stimulate surfactant in ELBW infants?
Respiratory distress syndrome (RDS) causes significant hypoxia in extremely low birth weight (ELBW) infants. We report an ELBW infant with RDS and pulmonary hypertension whose hypoxia did not respond to inhaled nitric oxide but improved with inhaled prostacyclin. We propose that inhaled prostacyclin alleviated the hypoxia by stimulating surfactant secretion.


Distal anterior cerebral artery aneurysms: bifrontal basal anterior interhemispheric approach.
Distal anterior cerebral artery (DACA) aneurysms are uncommon. Most authors have reported technical difficulties during surgery for these aneurysms, and a variety of surgical approaches have been advocated. Over a period of 5 years (1999-2003), 67 patients with DACA aneurysms were operated. Twenty-eight of these were operated on through the bifrontal basal anterior interhemispheric approach. Of the 28 patients, 68% were in poor clinical grade (Hunt and Hess grade III-V) and 89.3% had a Fisher grade III and IV on computed tomography scan. A surgical trajectory about 2 to 3 cm superior to the anterior cranial fossa floor led directly to the aneurysm. Proximal control was achieved before aneurysm dissection and parallel clipping. Good outcome (Glasgow Outcome Scale V and IV) was seen in 57.19 of the patients, 14.3% had a poor outcome, and 28.6% died. The cause of death in most patients was found to be a poor clinical grade, postoperative infarct, or presence of multiple aneurysms. The advantages of the bifrontal basal anterior interhemispheric approach were the following: (a) It provided the shortest and a direct trajectory to the aneurysm. (b) Proximal control of the parent A(2) vessels could be easily achieved. (c) Release of cerebrospinal fluid from basal cisterns could be done, if necessary. (d) There was a minimal distortion of or traction over the aneurysm.


Comparative proteomic analysis reveals intracellular targets for bacillomycin L to induce Rhizoctonia solani Kühn hyphal cell death.
Bacillomycin L, a natural iturinic lipopeptide produced by Bacillus amyloliquefaciens, is characterized by strong antifungal activity against a variety of agronomically important filamentous fungi including Rhizoctonia solani Kühn. To further understand its antifungal actions, proteomes were comparatively studied within R. solani hyphal cells treated with or without bacillomycin L. The results show that 39 proteins were alternatively expressed within cells in response to this lipopeptide, which are involved in stress response, carbohydrate, amino acid and nucleotide metabolism, cellular component organization, calcium homeostasis, protein degradation, RNA processing, gene transcription, and others, suggesting that, in addition to inducing cell membrane permeabilization, iturin exhibits antibiotic activities by targeting intracellular molecules. Based on these results, a model of action of bacillomycin L against R. solani hyphal cells was proposed. Our study provides new insight into the antibiotic mechanisms of iturins.


Death associated with bronchography. Question role of heating the contrast agent.
A young woman died following bronchography. The bilateral bronchogram done under general anesthesia without fluoroscopic control was associated with extensive small airway filling or "alveolarization" of the contrast medium. The oily Dionosil used had been heated in an autoclave. Experiments showed that the viscosity of oily Dionosil decreases with heating. The lowered viscosity could have contributed to the increased "alveolarization" of the contrast agent and death of the patient.


Real-world clinical outcome and toxicity data and economic aspects in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy: the experience of the Hellenic Cooperative Oncology Group.
We evaluated real-world clinical outcomes and toxicity data and assessed treatment-related costs in patients with advanced breast cancer who received treatment with cyclin-dependent kinase inhibitors (CDKi). We conducted a prospective-retrospective analysis of patients with advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who received a CDKi, in combination with endocrine therapy, at any line of treatment. The primary endpoint was progression-free survival (PFS). Cost analysis was conducted from a public third-payer (National Organization for Healthcare Services Provision (EOPYY)) perspective, assessing only costs related to direct medical care, including drug therapy costs and adverse drug reaction (ADR)-related costs. From July 2015 to October 2019, 365 women received endocrine therapy combined with CDKi; median age was 61 years, postmenopausal 290 (80.6%) patients. CDKi were administered as first-line treatment in 149 (40.9%) patients, second-line treatment in 96 (26.4%) and third-line treatment and beyond in 119 (32.7%) patients. The most common adverse events were neutropenia, anaemia, thrombocytopenia and fatigue. Grade 3-4 adverse events occurred in 86 (23.6%) patients, whereas 8 (2.2%) patients permanently discontinued treatment due to toxicity. The median PFS for patients who received CDKi as first-line, second-line and third-line treatment and beyond was 18.7, 12 and 7.4 months, respectively. The median overall survival since the initiation of CDKi treatment was 29.9 months (95% CI: 23.0-not yet reached (NR)). The mean pharmaceutical therapy cost estimated per cycle was 2 724.12 € for each patient, whereas the main driver of the ADR-related costs was haematological adverse events. Treatment with CDKi was well tolerated, with a low drug discontinuation rate. Patients who received CDKi as first-line treatment had improved PFS and OS compared with second-line treatment and beyond. The main component of direct medical costs assessed in the cost analysis comprises CDKi pharmaceutical therapy costs. NCT04133207.


Human brain in tissue culture. II. Studies of long-term cultures.
This paper describes the techniques used to maintain and reconstitute from storage adult human brain cells in culture. Growth characteristics, cell morphology, lifespan, and karyotypic analysis of cell lines derived from patients with multiple sclerosis (MS), non-MS neurologic diseases, and normal brains are compared.


Spin blockade and exchange in Coulomb-confined silicon double quantum dots.
Electron spins confined to phosphorus donors in silicon are promising candidates as qubits because of their long coherence times, exceeding seconds in isotopically purified bulk silicon. With the recent demonstrations of initialization, readout and coherent manipulation of individual donor electron spins, the next challenge towards the realization of a Si:P donor-based quantum computer is the demonstration of exchange coupling in two tunnel-coupled phosphorus donors. Spin-to-charge conversion via Pauli spin blockade, an essential ingredient for reading out individual spin states, is challenging in donor-based systems due to the inherently large donor charging energies (∼45 meV), requiring large electric fields (>1 MV m(-1)) to transfer both electron spins onto the same donor. Here, in a carefully characterized double donor-dot device, we directly observe spin blockade of the first few electrons and measure the effective exchange interaction between electron spins in coupled Coulomb-confined systems.


Unknown: Multiple asymptomatic skin colored to yellowish papules over vulva.
Multiple syringomas of the vulva are an unusal finding. We report a 42-year-old woman with a 2 year history of asymptomatic yellow papules on the vulva that were proven to be syringomas by histopathologic examination.


Poynting theorem constraints on the signs of the imaginary parts of the electromagnetic constitutive parameters: comment.
Contrary to an unphysical conclusion obtained by Alavikia et al. [J. Opt. Soc. Am. A32, 522 (2015)JOAOD60740-323210.1364/JOSAA.32.000522], the imaginary parts of both the permittivity and the permeability of any linear, homogeneous, passive, spatially local, dielectric-magnetic material are always positive, independent of the signs of their real parts.


Enhancement of rat peripheral nerve regeneration through artery-including silicone tubing.
Regeneration of rat sciatic nerve across a 5-mm excised gap was investigated after the proximal and distal stump were inserted into a silicone tubing including a native artery. Usual tubulation (silicone tube only) was used as the control. After 4, 8, and 15 weeks, the extent of nerve regeneration was evaluated electrophysiologically and histologically. The nerve regeneration and intraneural vascular reconstruction that occurred within silicone tubing with an arterial blood supply were more successful than those that occurred in the control. In the 4 weeks following implantation, the enhancement of maturation in the regenerating axons was especially noticeable. The advantages of the present procedure are (i) the provision of continuous guidance for neural outgrowth; (ii) an increased supply of nutrients for regenerating nerve fibers and Schwann cells; (iii) an increased supply of oxygen by arterial highly oxygenated blood; and (iv) the stimulation of an exchange effect within the tube due to the pumping action of artery.


New Stereoselective Biocatalysts for Carboligation and Retro-Aldol Cleavage Reactions Derived from d-Fructose 6-Phosphate Aldolase.
d-Fructose 6-phosphate aldolase (FSA) catalyzes the asymmetric cross-aldol addition of phenylacetaldehyde and hydroxyacetone. We conducted structure-guided saturation mutagenesis of noncatalytic active-site residues to produce new FSA variants, with the goal of widening the substrate scope of the wild-type enzyme toward a range of para- and meta-substituted arylated aldehydes. After a single generation of mutagenesis and selection, enzymes with diverse substrate selectivity scopes were identified. The kinetic parameters and stereoselectivities for a subset of enzyme/substrate combinations were determined for the reactions in both the aldol addition and cleavage reaction directions. The achieved collection of new aldolase enzymes provides new tools for controlled asymmetric synthesis of substituted aldols.


Evaluation of damage induced by Kwkt and Pikt zymocins against Brettanomyces/Dekkera spoilage yeast, as compared to sulphur dioxide.
Over the last few decades, the use of zymocins as biological tools to counteract contamination by spoilage yeast in beverages and food has been widely studied. This study examined the damage induced by the Kwkt and Pikt, two zymocins produced by Kluyeromyces wickerhamii and Wickerhanomyces anomalus, respectively, with antimicrobial activity against Brettanomyces/Dekkera wine-spoilage yeast. The physiological and biochemical characterization of both of these proteins revealed that only Pikt showed a strict relationship between β-glucosidase activity and killer activity. The minimum inhibitory concentrations and minimum fungicidal concentrations of Kwkt and Pikt showed inhibitory activities against Brettanomyces/Dekkera yeast. Cytofluorimetric evaluation of cell death was based on both cell membrane permeability and cell metabolism, using fluorescence techniques under increasing zymocin levels over different incubation times. The antimicrobial actions of Kwkt and Pikt were also compared with the mode of action of sulphur dioxide. In this last case, the induction of the viable but noncultivable (VBNC) state was confirmed, with the consequent recovery of Brettanomyces yeast after medium replacement. In contrast, Kwkt and Pikt caused irreversible death of these yeast, without recovery of sensitive cells. Kwkt and Pikt could be proposed as fungistatic or fungicide biocontrol agents in winemaking to control the colonization and development of Brettanomyces/Dekkera yeasts. These data support the potential use of zymocins to reduce wine contamination as an alternative to sulphur dioxide that act on sensitive cells. Differently from sulphur dioxide, that could induce a reversible VBNC state, Kwkt and Pikt determine the irreversible damage on sensitive yeasts, ensuring the complete control of spoilage Brettanomyces yeast.


Acquired paralytic strabismus in Southern Taiwan.
Third, fourth, and sixth cranial nerve (CN3, CN4, and CN6) palsies are not uncommon in neuro-ophthalmology. The time and quality of recovery depend on the causes of the cranial nerve palsy. The purpose of our study was to evaluate the causes and outcome of acquired paralytic strabismus (PS) in a southern Taiwan population. This study involved a retrospective chart review of patients at Kaohsiung Veterans General Hospital from January 2006 through July 2009. A total of 196 patients were enrolled. Outcomes and recovery times were recorded for the patients who exhibited C3, C4, and C6 palsies. The patients were categorized into four etiologic groups: vascular, idiopathic, traumatic, and neoplastic. The onset of PS, its continuing medical management, recovery, and other outcomes were followed up in these patients over a period of up to 10 years. The mean age of the 196 patients enrolled was 58.35 ± 17.60 years (range 11-90 years), and the mean follow-up time was 13.6 months. Seventy-seven patients (39.29%) had CN3 palsy, 38 patients (19.39%) had CN4 palsy, and 81 patients (41.33%) had CN6 palsy. The most common causes were vascular diseases (35.20%), followed by trauma (33.67%), and idiopathic causes (21.94%). About 50% of the patients recovered within 6 months. Among the four etiologic groups of patients, the vascular group showed the best recovery: about half of the patients recovered within 3 months. Longer recovery periods were necessary for patients in the neoplastic group than for those in the traumatic, vascular, and idiopathic groups (p = 0.01; p < 0.001; p < 0.001, respectively). The prognosis for patients with PS depended mostly on the cause of their disease. Patients with PS attributable to a vascular cause had a better prognosis than the other patients, and those in the neoplastic group required the longest time to recover.


Use of enriched stable isotopes to determine bioavailability of trace elements in humans.
Use of stable isotopes with analysis by thermal ionization mass spectrometry can determine trace element availability from dietary sources safely and with a high degree of accuracy. Stable isotopes of zinc (70Zn), copper (65Cu) and iron (58Fe) were fed with semipurified diets to humans. Excretion of isotopes was determined by isotope dilution in fecal composites collected for 15 days following the feedings. A thermal ionization, magnetic sector mass spectrometer was used to measure isotopic ratios. Total mineral content of fecal composites was determined by atomic absorption spectrophotometry. Mean absorption of zinc, iron and copper in six elderly men was 17.3, 8.7 and 26.0% respectively. Results agreed closely with absorption determined simultaneously in the same subjects using radioisotopes.


Photodynamic therapy--an alternative pathway in the treatment of recurrent breast cancer.
Validity of photodynamic therapy for treatment of recurrent breast cancer. Patients were intravenously administered with a metal-free haematoporphyrine derivative for tumor sensibilization. For irradiation both monochromatic and white light was used. Monochromatic light at a wavelength of 632 nm was supplied by an Argon-Dye laser, whereas a halogen lamp provided white light. Narrowband red light came into use in case of one patient. Therapy included recurrent diseases of breast carcinoma, especially disseminary skin metastases, local recurrences, and lymphangiosis. Classical pretreatment was ineffective for the therapeuted patient group. The healing potency of photodynamic therapy for our patient group is enumerated in detail. No differences in the therapeutic effect were seen using either Argon Dye laser or noncoherent light sources. Photodynamic therapy appears to be a valuable treatment to classical therapeutic intervention providing a selective destruction of tumor cells without further affecting life quality.


Mortality Rates From COVID-19 Are Lower In Unionized Nursing Homes.
More than 40 percent of all reported coronavirus disease 2019 (COVID-19) deaths in the United States have occurred in nursing homes. As a result, health care workers' access to personal protective equipment (PPE) and infection control policies in nursing homes have received increased attention. However, it is not known whether the presence of health care worker unions in nursing homes is associated with COVID-19 mortality rates. Therefore, we used cross-sectional regression analysis to examine the association between the presence of health care worker unions and COVID-19 mortality rates in 355 nursing homes in New York State. Health care worker unions were associated with a 1.29-percentage-point reduction in mortality, which represents a 30 percent relative decrease in the COVID-19 mortality rate compared with facilities without these unions. Unions were also associated with greater access to PPE, one mechanism that may link unions to lower COVID-19 mortality rates.


Evidence for a new, high-molecular weight isoform of protein kinase C in rat hippocampus.
We describe a new form of protein kinase C (PKC) with a molecular weight of 97 kDa, higher than the known forms of vertebrate PKC. This putative new high-molecular weight isoform, which we are calling PKC (HMW), is increased in the membrane fraction either upon application of phorbol esters or with afferent synaptic stimulation of Schaffer collaterals in hippocampal slices. The protein cross-reacts on immunoblot with affinity-purified polyclonal antiserum raised against a peptide derived from the carboxy-terminus of PKC eta; it does not cross-react, however, with antiserum against the amino-terminal region of PKC eta. In the tissues examined, PKC(HMW) is localized primarily in brain, in contrast to PKC eta, which is found predominantly in lung and skin.


Context-specific activations are a hallmark of the neural basis of individual differences in general executive function.
Common executive functioning (cEF) is a domain-general factor that captures shared variance in performance across diverse executive function tasks. To investigate the neural mechanisms of individual differences in cEF (e.g., goal maintenance, biasing), we conducted the largest fMRI study of multiple executive tasks to date (N = 546). Group average activation during response inhibition (antisaccade task), working memory updating (keep track task), and mental set shifting (number-letter switch task) overlapped in classic cognitive control regions. However, there were no areas across tasks that were consistently correlated with individual differences in cEF ability. Although similar brain areas are recruited when completing different executive function tasks, activation levels of those areas are not consistently associated with better performance. This pattern is inconsistent with a simple model in which higher cEF is associated with greater or less activation of a set of control regions across different task contexts; however, it is potentially consistent with a model in which individual differences in cEF primarily depend on activation of domain-specific targets of executive function. Brain features that explain commonalities in executive function performance across tasks remain to be discovered.


Bioengineered immunomodulatory organelle targeted nanozymes for photodynamic immunometabolic therapy.
Intelligent nanomedicines integrated with stimuli-responsive components enable on-demand customizable treatment options which would improve therapeutic outcome and reduce systemic toxicity. In this work, we explore the synergistic therapeutic potential of photodynamic therapy and immunometabolic modulation to achieve tumour regression and to trigger an adaptive immunity to prevent tumour recurrence. The therapeutic potential of the fabricated Bioengineered Immunomodulatory Organelle targeted Nanozymes (BIONs) was tested on 3D printed mini-brains which could effectively recapitulate the biologically relevant interactions between glioblastoma cells and macrophages. In the presence of glioblastoma organotypic brain slices, activated BIONs upregulated the cell surface expression of CD86, a costimulatory molecule and CD83, maturation marker, on monocyte derived dendritic cells, suggesting its ability to elicit a strong immune response. Furthermore, the antigen pulsed dendritic cells by chemotaxis and transendothelial migration readily relocate into the draining lymph node where they present the antigenic cargo to enable the proliferation of T lymphocytes. The stealth and tunable catalytic activity of BIONs prevent ROS mediated diseases such as acute kidney injury by providing environment dependent protection without compromising on its promising anti-cancer activity.


Correlation of antidepressive agents and the mortality of end-stage renal disease.
Depression is one of the most common psychological disorders in end-stage renal disease (ESRD) patients and is associated with impaired quality of life and increased mortality and rate of hospitalization. We aimed to examine the contributions of depression and the use of antidepressive agents in the mortality of ESRD patients. A retrospective observatory study was conducted using the National Health Insurance Research Database in Taiwan. Patients with newly diagnosed as ESRD during the year 2001 to 2007 were collected. A total of 2312 ESRD patients were identified in the database. Statistical analyses were conducted to examine the contributions of depression and exposure of antidepressive agents in mortality rates of ESRD patients. Diagnosis of depression did not influence mortality rate (mortality rate in patients with depression: 26.5%; mortality rate in patients without depression: 26.2%; P= 1.000). Those who had antidepressive agents exposure had significantly higher mortality rate (mortality rate: 32.3%) than those who did not (mortality rate: 24.5%) (P < 0.001). Our findings suggest that (i) the mortality rate of ESRD patients was not affected by the diagnosis of depression, and (ii) exposure of antidepressive agents in ESRD patients was associated with a higher mortality rate. The high mortality rate in ESRD patients exposed to antidepressive agents can be a bias by indication. Equally, a true contribution of the antidepressive agents cannot be ruled out and this needs clarification.


Gene structure and expression profile of Manduca sexta prophenoloxidase-activating proteinase-3 (PAP-3), an immune protein containing two clip domains.
Prophenoloxidase-activating proteinase-3 (PAP-3) is a component of the defence system in Manduca sexta. We have isolated genomic clones and elucidated the organization of this gene. The 3' end of exon 2, the entire exon 3 and the 5' end of exon 4 encode the two amino-terminal clip domains. Southern blot analysis suggested a single copy of the PAP-3 gene in the genome. We identified several putative immune-responsive elements in the upstream region. The PAP-3 gene is not highly expressed in the fat body during larval development until the wandering stage begins. The mRNA level is high in the epithelium, fat body and haemocytes. Tissue-specific alternative splicing occurs in the fat body and trachea. A bacterial injection markedly induced the gene expression in the fat body and haemocytes.


Outcomes associated with anaesthetic techniques for caesarean section in low- and middle-income countries: a secondary analysis of WHO surveys.
Associations between anaesthetic techniques and pregnancy outcomes were assessed among 129,742 pregnancies delivered by caesarean section (CS) in low- and middle-income countries (LMICs) using two WHO databases. Anaesthesia was categorized as general anaesthesia (GA) and neuraxial anaesthesia (NA). Outcomes included maternal death (MD), maternal near miss (MNM), severe maternal outcome (SMO), intensive care unit (ICU) admission, early neonatal death (END), neonatal near miss (NNM), severe neonatal outcome (SNO), Apgar score <7 at 5 minutes, and neonatal ICU (NICU) admission. A two-stage approach of individual participant data meta-analysis was used to combine the results. Adjusted odds ratio (OR) with 95% confidence intervals (CIs) were presented. Compared to GA, NA were associated with decreased odds of MD (pooled OR 0.28; 95% CI 0.10, 0.78), MNM (pooled OR 0.25; 95% CI 0.21, 0.31), SMO (pooled OR 0.24; 95% CI 0.20,0.28), ICU admission (pooled OR 0.17; 95% CI 0.13, 0.22), NNM (pooled OR 0.63; 95% CI 0.55, 0.73), SNO (pooled OR 0.55; 95% CI 0.48, 0.63), Apgar score <7 at 5 minutes (pooled OR 0.35; 95% CI 0.29, 0.43), and NICU admission (pooled OR 0.53; 95% CI 0.45, 0.62). NA therefore was associated with decreased odds of adverse pregnancy outcomes in LMICs.


Persistent ST-segment elevation following pericardiocentesis: caution with thrombolytic therapy.
We report a case of persistent electrocardiographic ST-elevation following pericardiocentesis despite lack of evidence for transmural infarction or vasospasm. The electrocardiographic pattern was felt to reflect subepicardial injury due to a small myocardial laceration. The implications of this finding are discussed.


Cefoxitin in the prevention and treatment of infections.
A review of the literature indicates that cefoxitin is an effective single-agent therapy for community-acquired intra-abdominal infections, pelvic infections, and surgical prophylaxis. Hospital-acquired intra-abdominal infections may require the addition of an aminoglycoside.


Effects of different gelatinization degrees of starch in potato flour on the quality of steamed bread.
The effect of four kinds of potato flour with different gelatinization degrees on the quality of steam bread was investigated in the present study. Results showed that medium-well flour (MWF) and potato flakes (PF) steamed bread, particularly MWF steamed bread, possessed the desired product properties liked by consumers. The MWF steamed bread had the highest appearance score (42.78) and total sensory evaluation score (81.60), and the PF steamed bread exhibited the highest specific volume (1.84 mL/g) and taste score (43.05). An increase in the degree of potato flour gelatinization led to an increase in dough gas retention coefficient from 80.20 mL/100 mL to 85.17 mL/100 mL and a more uniform and dense dough microstructure. During dough preparation, the increased gelatinization degree of potato flours enhanced the hydroscopicity competition between potato starch and gluten, resulting in a flocculent gluten network and increased potato starch volume during steaming. During steaming, steamed bread with higher gelatinization degree of potato flour formed a homogenous and dense starch gel-gluten double network, making them softer with more uniform gas cells and larger specific volume. Thus, this study provides a perspective of the effect of starch gelatinization on steamed bread quality.


Role of Transbronchial Needle Core Biopsy in the Diagnosis of Mediastinal Diseases: Experience With an Innovative Endoscopic Technique Using a Rigid Tru-Cut Needle.
Enlarged lymph nodes or mediastinal masses diagnosed by computed tomographic scan before the advent of bronchoscopic procedures (TBNA or EBUS) were usually investigated using a thoracic surgical approach. In this paper, we report the experience with the use of a modified rigid tru-cut needle in the bioptical approach to mediastinal masses; to determine whether it could be considered a valid alternative to surgery, we investigated the diagnostic accuracy of this new endoscopic technique. A total of 156 selected patients with radiographic evidence of lymphadenopathy or mediastinal masses (subcarinal and paratracheal with a short-axis diameter >3 cm) were studied in our center by rigid bronchoscopy using a 18-G tru-cut needle to obtain a core biopsy of the lesion. In 140 of 156 cases (89.7%), a histologically correct diagnosis was reached without perioperative or postoperative complications. A total of 114 (81.4%) malignant and 26 (18.6%) benign lesions were diagnosed avoiding further invasive surgical approach. Our results confirm that, in selected cases, transbronchial rigid core biopsy could be considered a safe and valid alternative technique to more invasive surgical approach in the diagnosis of mediastinal diseases.


Clinical learning evaluation questionnaire: a reliable and valid tool for the evaluation of clinical education by educators and students.
The clinical learning evaluation questionnaire can be used in the clinical trial period of medical students to measure the effectiveness of the clinical learning environment. The purpose of this study was to collect validity evidence of an adapted questionnaire to measure the transcultural adaptation of a Persian version of CLEQ. A total of 200 questionnaires were completed by students who were at the end of their clinical rotation. The study instrument was the latest version of the CLEQ consists of 18 Items in four dimensions. The CLEQ was translated into Persian language through a four-step process of forward and backward translation. Data analysis was performed on two softwares, SPSS, version 22 and Lisrel, version 8.8. The results showed that the 18-question CLEQ could be applied to the Persian translation of the tool. The response process evidence of the Persian questionnaire was established through feedback from 15 students in the sample group. The content validity index (CVI) for the items were between 0.8 and 0.9, and the content validity ratio (CVR) for the entire questionnaire was 0.9. The 4-factor feature of CLEQ was good model fit. The internal consistency analysis indicated that the Cronbach's alpha values for all items of the 18-item questionnaire were equal to 0.87 and for the subscales were 0.68 to 0.79. The Persian translation of the 4-factor CLEQ has sufficient validity evidence to measure the transcultural adaptability of clinical education activities by instructors and students. The validity evidence are content, response process and internal structure. We recommend that the English 6-factor and 6-factor versions of CLEQ be tested on medical students at multiple foreign academic institutions to assess their efficiency.


Morphometrical analysis of preantral follicular survival of VEGF-treated bovine ovarian cortex tissue following xenotransplantation in an immune deficient mouse model.
The increasing number of cancer survivors the past decades, has sparked the need for fertility preservation strategies. Due to predominantly ethical constraints, human research material is scarce. A bovine in vitro model is a valuable alternative. Therefore, the following objectives were defined: 1) to xeno-graft bovine ovarian cortex tissue in immune deficient mice as a study-model for female fertility preservation strategies; 2) to stereologically quantify vascularization in Vascular Endothelial Growth Factor (VEGF)-treated and non-treated tissue; 3) to study preantral follicular survival in situ, after xenotransplantation. Bovine ovarian tissue strips were incubated with or without VEGF prior to grafting into female, neutered BALB/c-nu mice (n=16). Non-transplanted cortical tissue was used as a control. At time zero (control), two (2 weeks) and four (4 weeks) weeks after transplantation, grafts were retrieved and assessed by von Willebrand Factor and caspase-3 immunostaining. Data were analyzed using a linear mixed model. In the VEGF+ grafts, 31% of the follicles were considered 'alive' 2 weeks after transplantation, compared to only 17% in the VEGF- grafts (P<0.05). However, no difference could be detected 4 weeks after transplantation (P=0.76) with less follicles being considered 'alive' after transplantation (22%), compared to the control (47.5%) (P<0.05). Finally, the vascular surface density was significantly less in the grafts, irrespective of the transplantation period or the use of VEGF. Although the transplantation process overall negatively influenced the number of viable follicles and vascular density, VEGF exposure prior to transplantation can favor follicle survival during a 2 weeks transplantation period.


Baseline serum low-density lipoprotein cholesterol levels predict response to hepatitis C virus therapy in HIV/hepatitis C virus coinfected patients.
High levels of serum low-density lipoprotein cholesterol are associated with better response to pegylated interferon and ribavirin in hepatitis C virus monoinfected patients. There are no data concerning this topic in HIV/hepatitis C virus coinfected patients in whom lipid disorders are particularly common. To assess the association between baseline lipid levels and sustained virologic response to pegylated interferon and ribavirin in coinfected patients. A total of 260 HIV/hepatitis C virus coinfected patients under treatment with pegylated interferon and ribavirin and who had a baseline serum lipid profile were included in this retrospective study. Thirty-eight (24%) patients with genotypes 1-4 and 64 (63%) with genotypes 2-3 achieved sustained virologic response. Forty-nine (44%) patients with serum low-density lipoprotein cholesterol levels 100 mg/dl or more showed sustained virologic response compared with 53 (36%) with lower values [adjusted odds ratio: 2.51; 95% confidence interval: 1.40-4.87; P = 0.003]. This association was independent of the remaining predictors of sustained virologic response which were genotypes 2-3, plasma hepatitis C virus RNA 600,000 IU/ml or less, exposure to at least 80% of the planned therapy and lack of concomitant antiretroviral therapy. The rate of sustained virologic response in patients with genotype 1 and low-density lipoprotein cholesterol at least 100 mg/ml was 31% compared with 17% in those with lower values (adjusted odds ratio: 2.19; 95% confidence interval: 1.04-4.66; P = 0.040). The corresponding figures in subjects with genotypes 2-3 were 73 and 58% [2.71 (0.99-7.46); P = 0.054]. No other lipid was associated with response. Higher low-density lipoprotein cholesterol levels predict sustained virologic response to pegylated interferon and ribavirin in HIV/hepatitis C virus coinfected patients. This might be used to improve the rate of sustained virologic response in this setting.


Cloning of a second nm23-M1 cDNA: expression in the central nervous system of adult mouse and comparison with nm23-M2 mRNA distribution.
Nm23 has been identified as a gene family encoding different isoforms of the nucleoside diphosphate kinase. This protein is a key enzyme in the control of cellular concentrations of nucleoside triphosphates. Moreover, it has been shown to play important roles in various cellular functions such as differentiation and metastasis. In the present study, a second cDNA for nucleoside diphosphate kinase A (Nm23-M1) was isolated from a cDNA library of mouse embryonic stem cells. This clone encodes the same putative 152 aminoacids long protein as an already published cDNA but is longer in both its 5' and 3' untranslated regions. Tissue and cellular distribution of nm23-M1 mRNA was investigated by using Northern blot analysis and in situ hybridization. Nm23-M1 transcripts were found to be widely distributed throughout the mouse central nervous system with prominent expression in several restricted areas. No differences were noticed between the distribution of long and short transcripts. Furthermore, a similar pattern of expression was described in the central nervous system for nm23-M2 mRNA, encoding a second isoform of the nucleoside diphosphate kinase. However, the transcript of this isoform displayed a wider distribution and was expressed in all organs analysed by northern blotting. The possible involvement of nm23-M1 in differentiation of mouse nervous system is further discussed.


A biocompatible theranostic nanoplatform based on magnetic gadolinium-chelated polycyclodextrin: in vitro and in vivo studies.
A novel theranostic nanoplatform was prepared based on Fe3O4 nanoparticles (NPs) coated with gadolinium ions decorated-polycyclodextrin (PCD) layer (Fe3O4@PCD-Gd) and employed for Curcumin (CUR) loading. The dissolution profile of CUR indicated a pH sensitive release manner. Fe3O4@PCD-Gd NPs exhibited no significant toxicity against both normal and cancerous cell lines (MCF 10A and 4T1, respectively); while the CUR-free NPs showed more toxicity against 4T1 than MCF 10A cells. In vivo anticancer study revealed appropriate capability of the system in tumor shrinking with no tissue toxicity and adverse effect on body weight. In vivo MR imaging of BALB/c mouse showed both T1 and T2 contrast enhancement on the tumor cells. Fe3O4@PCD-Gd/CUR NPs showed significant features as a promising multifunctional system having appropriate T1-T2 dual contrast enhancement and therapeutic efficacy in cancer theranostics.


Human Papillomavirus and Potentially Relevant Biomarkers in Tonsillar and Base of Tongue Squamous Cell Carcinoma.
Human papillomavirus (HPV)-positive tonsillar- and base of tongue cancer is increasing epidemically and has much better outcome than corresponding HPV-negative cancer and most other head and neck cancers with around 80% 3-year disease free survival with conventional radiotherapy and surgery. Consequently, most HPV-positive cancer patients may not require the intensified chemoradiotherapy given to many head and neck cancer patients and would, with tapered treatment, avoid several severe side-effects. Moreover, intensified therapy has not improved survival and treatment alternatives are needed. To identify patients eligible for tapered or targeted therapy, additional biomarkers are required. Several studies have, therefore, focused on finding predictive markers, some of which are also potentially targetable. To conclude, better-tailored therapy, either as tapered or targeted, is important for increasing numbers of patients with HPV-positive tonsillar- and base of tongue cancer. This review deals with some of these issues and presents some promising markers.


Ethyl 10-cyano-7-hy-droxy-6-oxo-3-phenyl-8,9,10,10a-tetra-hydro-6H-benzo[c]chromene-10-carboxyl-ate.
In the title compound, C23H19NO5, the cyano group adopts an axial orientation and the ester group an equatorial orientation. The dihedral angle between the pendant phenyl group and the benzene ring of the fused-ring system is 25.97 (8)°. Intra-molecular O-H⋯O and C-H⋯O hydrogen bonds are observed and the packing is consolidated by C-H⋯O and C-H⋯π inter-actions.