Hoganbooth6387

Orthorexia nervosa has been receiving considerable attention and several tools have been developed to assess it, for instance, the "Düsseldorf Orthorexie Scale" (DOS). Such scale is a validated test to measure orthorexic eating behavior and it has shown good psychometric properties. Therefore, this study aimed to transculturally adapt and validate the Brazilian version of the DOS (DOS-BR).

DOS-BR was obtained using the back-translation process after two reviews done by a focus group and after running a pilot-test (n = 64). A self-report questionnaire was administered to a sample of Brazilian dietitians and Nutrition college students (n = 486). To examine the factor structure of the DOS-BR, exploratory factor analysis and confirmatory factor analysis were conducted. The ordinal alpha was examined. Test-retest reliability was evaluated in a sub-sample (n = 159). Convergent validity was assessed by conducting correlation analyses between the DOS-BR and other theoretically related tools (EAT-26 and OCI-R) within the sub-sample.

A three-factor structure was revealed for the DOS-BR properly fitted (KMO = 0.787). The test showed good internal consistency with an ordinal alpha of 0.795, and it also had excellent test-retest reliability of 0.776. DOS-BR median score was 17 (14-22) in Measurement 1 and 19 (17-22) in Measurement 2. The total score had a positive and moderate correlation with eating disorders symptoms (0.488) and a positive and weak correlation with obsessive-compulsive symptoms (0.224).

The DOS-BR was culturally and psychometrically adequate for the samples of Brazilian Nutrition-related subjects. The tool is indicated as a reliable alternative to evaluate orthorexia nervosa in Brazilian scenery.

Descriptive (cross-sectional) study, Level V.

Descriptive (cross-sectional) study, Level V.Most surgeons have traditionally been reluctant toward minimally-invasive surgery for bile duct tumors. This study aimed to perform a systematic literature review on perioperative and oncologic results of pure laparoscopic and robotic curative-intent surgery for hilar cholangiocarcinoma. According to the PRISMA statement, a systematic review was conducted into Pubmed, EMBASE and Cochrane. A critical appraisal of study was performed according to the Joanna Briggs Institute tools. Nineteen studies (12 on pure laparoscopy and 7 on robotics) were included 7 case reports, 9 case series, 3 case-control (193 patients). The pooled conversion, morbidity, biliary leak and mortality rates were 5.5%, 43%, 16.4% and 4%. The weighted mean of operative time, blood loss and postoperative stay were 388 min, 446 mL and 14 days. For pure laparoscopy, the pooled R0 rate was 86%; overall survival and disease-free survival rates ranged from 85 to 100% and from 80 to 100% (median observation time 6-18 months). For robotic surgeries, the pooled R0 rate was 69% and overall survival rates ranged from 90 to 100% (median observation time 5-15 months). Case reports were overall of high quality, case series of moderate / high-quality, case-control studies ranged from low to high quality. In selected patients, minimally-invasive surgery for Klatskin tumors appears feasible, safe, satisfactory for perioperative outcomes and adequate for oncologic results. However, the results are based on few studies, limited in patient numbers and with allocation criteria more restrictive than open, reporting short follow-up and mainly with non-comparative design evidence of higher quality is recommended.Stem cells play a pivotal role in the developmental stages of an organism and in adulthood as well. Therefore, it is not surprising that stem cells constitute a focus of extensive research. Indeed, several decades of stem cell research have tremendously increased our knowledge on the mechanistic understandings of stem cell biology. Interestingly, revealing the fundamental principles of stem cell biology has also fostered its application for therapeutic purposes. Many of the attributes that the stem cells possess, some of which are unique, allow multifaceted exploitation of stem cells in the treatment of various diseases. Cancer, the leading cause of mortality worldwide, is one of the disease groups that has been benefited by the potentials of therapeutic applications of the stem cells. While the modi operandi of how stem cells contribute to cancer treatment are many-sided, two major principles can be conceived. One mode involves harnessing the regenerative power of the stem cells to promote the generation of blood-forming cells in cancer patients after cytotoxic regimens. A totally different kind of utility of stem cells has been exercised in another mode where the stem cells can potentially deliver a plethora of anti-cancer therapeutics in a tumor-specific manner. While both these approaches can improve the treatment of cancer patients, there exist several issues that warrant further research. This review summarizes the basic principles of the utility of the stem cells in cancer treatment along with the current trends and pinpoints the major obstacles to focus on in the future for further improvement.

The socket seal surgery (SSS) technique is a common alternative for the management of the post-extraction sockets that requires a primary closure of the wound to promote proper regeneration and ridge preservation.

To learn about the effect of different SSS techniques on alveolar ridge preservation MATERIAL AND METHODS Two independent and calibrated reviewers conducted an electronic search in PubMed, Cochrane, and Web of Science for randomized clinical trials (RCT) published up to June 2020. The evaluation of the risk of bias in the included studies was carried out following the Cochrane manual for interventions of systematic reviews, version 5.1.0. A meta-analysis of ridge width changes at - 1, - 3, and - 5 mm cutoff points from bone crest was conducted using a random-effects model. The risk of types I and II errors against accrued data was appraised obtaining the required information size using a trial sequential analysis package (TSA).

A total of 135 sockets located in the esthetic zone were evaluated techniques to improve clinical results in ridge preservation. More clinical studies in the form of clinical trials are required to demonstrate the superiority of one technique over another.

There are several predictable SSS techniques to improve clinical results in ridge preservation. More clinical studies in the form of clinical trials are required to demonstrate the superiority of one technique over another.

This review summarizes the evidence on rehabilitation for people with Parkinson's disease, including when to refer, what rehabilitation professionals should address, and how to deliver rehabilitation care.

Clinical practice guidelines support physical therapy, occupational therapy, and speech-language pathology for Parkinson's disease. However, integrating guidelines into practice may be difficult. Implementation studies take into account patient and clinician perspectives. Synthesizing guidelines with implementation research can improve local delivery. There is moderate to strong evidence supporting physical therapy, occupational therapy, and speech-language pathology soon after diagnosis and in response to functional deficits. We propose a framework of three pathways for rehabilitation care (1) consultative proactive rehabilitation soon after diagnosis for assessment, treatment of early deficits, and promotion meaningful activities; (2) restorative rehabilitation to promote functional improvements; and bilitation for long-term monitoring of exercise, meaningful activities, safety, contractures, skin integrity, positioning, swallowing, and communication.

This study aimed to develop and evaluate a population pharmacokinetic model and limited sampling strategy for isoniazid to be used in model-based therapeutic drug monitoring.

A population pharmacokinetic model was developed based on isoniazid and acetyl-isoniazid pharmacokinetic data from seven studies with in total 466 patients from three continents. Three limited sampling strategies were tested based on the available sampling times in the dataset and practical considerations. The tested limited sampling strategies sampled at 2, 4, and 6h, 2 and 4h, and 2h after dosing. The model-predicted area under the concentration-time curve from 0 to 24h (AUC

) and the peak concentration from the limited sampling strategies were compared to predictions using the full pharmacokinetic curve. Bias and precision were assessed using the mean error (ME) and the root mean square error (RMSE), both expressed as a percentage of the mean model-predicted AUC

or peak concentration on the full pharmacokinetic curve.

Performd therapeutic drug monitoring strategy for personalized dosing of isoniazid using sampling at 2 and 4 h after dosing was successfully developed. Prospective evaluation of this strategy will show how it performs in a clinical therapeutic drug monitoring setting.The influence of test anxiety on academic difficulties has been investigated in typically developing students, but the mechanism underlying the influence remains unclear, especially for those with specific learning disabilities (SpLDs). This study examined the role of metacognition in the relationship between test anxiety and literacy difficulties among Chinese typically developing adolescents as well as those who have been identified as having an SpLD and significant literacy difficulties (i.e., typically functioning SpLD) and without significant literacy difficulties (i.e., high-functioning SpLD) in Taiwan. A total of 238 first-year undergraduate students were recruited from eleven universities in South Taiwan. Among 238 students, 105 were identified to have SpLDs, and 133 were typically developing students. These students were asked to complete questionnaires on demographics, test anxiety, metacognition, and literacy difficulties (i.e., reading and writing). Structural equation modeling analyses showed that test anxiety among Chinese adolescents was linked to literacy difficulties but that only high-functioning and typically functioning students with SpLDs experienced a direct effect (without mediation by other factors). For those without SpLDs, the influence of test anxiety on literacy difficulties was not direct but significantly mediated by metacognition. Various components of these students' metacognition had mediating effects on different literacy difficulties. Test anxiety might influence the reading and writing difficulties of typically developing adolescents and those with typically functioning and high-functioning SpLDs through different mechanisms. Moreover, teachers at the university level are encouraged to consider students' test anxiety and metacognition when preparing their teaching materials.

In India, more than two-thirds of the total health expenditure is incurred through out-of-pocket expenditure (OOPE) by households. Morbidity events thus impose excessive financial risk on households. The Sustainable Development Goals Target 3.8 specifies financial risk protection for achieving universal health coverage (UHC) in developing countries. This study aimed to estimate the impact of OOPE on catastrophic health expenditure (CHE) and impoverishment effects by types of morbidity in India.

Data came from the 75th round of the National Sample Survey (NSS) on the theme 'Social consumption in India Health', which was conducted during the period from July 2017 to June 2018. For the present study, 56,722 households for hospitalisation, 29,580 households for outpatient department (OPD) care and 6285 households for both (OPD care and hospitalisation) were analysed. Indices, namely health care burden, CHE, poverty head count ratio and poverty gap ratio using standard definitions were analysed.

Households whealth system financing policies and strict implementation that will provide financial risk protection to households in India.

Dietary intake is a primary source of cadmium (Cd) exposure in the non-smoking population. Plant foods containing metal-binding plant compounds such as polyphenols, phytates, and phytochelatins may reduce Cd bioavailability and result in lower Cd body burden. In this study, we investigated the association between plant food intake and urinary creatinine-adjusted Cd (uCd), a well-established marker of Cd body burden.

Participants were from a cross-sectional sample of 1901 adults in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Dietary intake was assessed with a food frequency questionnaire. We created a 12-point plant food score (PFS) based on reported intake across seven categories (fruits, vegetables, legumes, nuts/seeds, whole grains, tea, and wine). Higher scores indicated higher consumption and diversity of plant food intake. Multivariable linear regression models were used to estimate the association between PFS and uCd. Due to the influence of age and smoking on Cd status, stratified analyses were conducted.

Mean PFS was 5.4 (SD 2.2) and mean uCd was 0.53µg/g creatinine (SD 0.39). In adjusted models, PFS was not associated with uCd (p > 0.05). In stratified analyses, PFS was inversely associated with uCd (p = 0.047) with a 1-point higher PFS associated with 0.018µg/g lower uCd among middle-aged (45-59) adults. No significant association was observed between PFS and uCd in older (≥ 60) adults. The association of PFS and uCd did not differ by smoking status.

Our findings suggest higher plant food intake is associated with lower Cd body burden in middle-aged but not older adults.

Our findings suggest higher plant food intake is associated with lower Cd body burden in middle-aged but not older adults.

To assess the long-term clinical outcomes following lateral alveolar ridge augmentation using a collagenated xenogeneic bone block (CXBB) and staged implant placement.

A total of n = 9 patients (9 implants) were available for the analysis. Each subject had received lateral ridge augmentation using a size-adapted rigidly fixed CXBB and contour augmentation at single-tooth gaps. Implant placement was performed after 24 weeks of submerged healing. Clinical parameters (e.g., bleeding on probing (BOP), probing pocket depth (PD), mucosal recession (MR)) were recorded at 16 to 20 weeks after the cementation of the crown (baseline) and scheduled for 0.5 (visit 1 (V1)), 1.5 (V2), 2.5 (V3), 3.5 (V4), and 4.5 (V5) years after implant loading.

Changes in clinical parameters commonly remained low throughout the entire observation period. Significant changes to baseline were merely noted for mean BOP scores at V4 (19.14 ± 17.75%; n = 7; P = 0.029) and mean PD scores at V2 (0.78 ± 0.98 mm; n = 9; P = 0.044) and V3 (1.33 ± 1.05 mm; n = 9; P = 0.009), respectively.

CXBB was associated with high clinical implant success and survival rates on the long-term.

CXBB was associated with high clinical implant success and survival rates on the long-term.Moxidectin (MOX) is a macrocyclic lactone approved worldwide for the treatment of both endo- and ecto-parasites in many mammalian species. The aim of this study was to assess the efficacy of MOX as a treatment against parasites in a range of mammalian species. An electronic literature search was performed for publications to the 1st September 2020. A total of 205 papers were retrieved and screened against all required criteria; hence, 35 were papers were reviewed in this study. The level of evidence and methodological quality was analysed, where a total of 13 publications were categorised as a 'randomised control trial', seven were categorised as a 'non-randomised control trial' and 15 as an 'experimental control trial'. The overall methodological quality of the publications was considered low, low to moderate, moderate, moderate to high and high in ten, four, twelve, five and a further four, respectively. We assessed the treatment and possible toxicity of MOX in 13 mammalian species, six investigations reported adverse effects to MOX in a small percentage of individuals. The authors reported observed reactions that were typically mild symptoms that did not require additional therapies, and/or resolved themselves. Further studies are needed to assess the efficacy of MOX treatment in a larger number of species, particularly in wildlife.A novel myxozoan parasite is identified and described from mudskipper, Boleophthalmus dussumieri, collected from a brackishwater ecosystem in Maharashtra, India. Ellipsomyxa boleophthalmi sp. nov. was found in the gallbladder of 58 of 60 fish examined (96.7%). The parasite formed disporous plasmodia that varied in size and shape, and the thin-walled, ellipsoidal and elongated myxospores measured 9.0-10.7 × 6.0-7.8 μm. The two, spherical polar capsules measured 2.7 μm in diameter and enclosed 3-4 coils of polar tubules. Histological observations of infected gallbladder revealed the attachment of disporous plasmodial stages of the parasite to the gallbladder wall with fine pseudopodia. Under the scanning electron microscope (SEM), the myxospores showed a distinct central sutural line and two distinct depressions on the opposite sides at the openings of polar capsules. SEM also revealed the engulfment of microvilli of gallbladder wall by pseudopodia of the plasmodial stages. Analysis of the partial fragment of the SSU rDNA region (1386 bp) showed less than 98% sequence similarity with the other reported Ellipsomyxa spp. In the phylogenetic tree, the present species formed as a distinct subclade within the major clade of Ellipsomyxa spp. The unique morphological and morphometric features of the myxospore, together with the molecular analysis, allowed us to conclude that the present myxozoan is a new species and is named Ellipsomyxa boleophthalmi sp. nov., after the generic name of the host. This is the first report on the occurrence of the genus Ellipsomyxa in B. dussumieri.The increase in some wildlife species is of global concern. The utilization of wildlife meat as food and feed represents a potential source of food-borne pathogens; this is particularly a potential concern for the use of wild board as a food source in Japan. Regarding food safety and an animal infectious disease control, however, little is known about the infection level of zoonotic pathogens including Toxoplasma gondii (T. gondii) in wild boar populations in their natural habitats in Japan. A total of 1279 blood samples from 41 prefectures were collected from apparently healthy wild boars during the three hunting periods (September to February) of 2014-2015, 2015-2016, and 2017-2018. Out of these sera, 461 samples tested positive by a commercial indirect ELISA for T. gondii, and the total apparent and adjusted true seroprevalence were estimated to 36.0% (95% confidence interval [CI], 33.4-38.7) and 31.3% (95% CI, 33.1-38.9), respectively. The seroprevalence was significantly higher in yearlings and adults than in piglets (P less then 0.05); however, no significant difference according to gender was noted. These results indicate the importance of adequate heating of wild boar meat before consumption to prevent transmission of T. gondii to humans. Furthermore, freezing meat for several days before cooking is recommended to reduce the risk of infection. In addition, although the incidence of toxoplasmosis in pig farms is relatively low in Japan, biosecurity measures against the felids and the varied intermediate hosts should be strengthened, especially, at the farms located in the wild boar habitats to prevent livestock infection.Cryptosporidium is a genus of single-celled protozoa, infecting a wide range of animals and humans. Although Cryptosporidium infections of cattle have been reported in some provinces in China, there is no available information on the prevalence and predominant species of Cryptosporidium in cattle in Jiangxi province. To investigate the prevalence of Cryptosporidium in cattle in Jiangxi province of China, 556 fecal samples were collected from eight farms in four cities and the SSU rRNA locus of Cryptosporidium was amplified from the DNA of each fecal sample by PCR. The overall prevalence of Cryptosporidium was 12.8% (71/556) in cattle in Jiangxi province, with 24.3% (54/222) in Nanchang city, 7.8% (13/166) in Gao'an city, 3.7% (4/108) in Xinyu city, and 0.0% (0/60) in Ji'an city. The differences of the prevalence rates by region, breed, and age groups were statistically significant. All positive PCR products of Cryptosporidium were successfully sequenced and identified as three Cryptosporidium species, namely Cryptosporidium bovis (1/556, 0.18%), Cryptosporidium ryanae (7/556, 1.3%), and Cryptosporidium andersoni (63/556, 11.3%). Furthermore, 36 C. andersoni isolates were successfully classified into three MLST (multilocus sequence typing) subtypes based on four genetic loci (MS1, MS2, MS3, and MS16). The predominant MLST subtype was A4, A4, A4, A1 (n = 30). These findings not only revealed the prevalence and predominant species of Cryptosporidium in cattle in Jiangxi province, but also provided a baseline for studying the genetic structure of C. andersoni, offering a novel resource for better understanding of the epidemiology of Cryptosporidium infection in cattle in Jiangxi province, southeastern China.The chromosome compaction of chromatin fibers results in the formation of the nucleosome, which consists of a DNA unit coiled around a core of histone molecules associated with linker histone. The compaction of chromatin fibers has been a topic of controversy since the discovery of chromosomes in the 19th century. Although chromatin fibers were first identified using electron microscopy, the chromatin fibers on the surface of chromosome structures in plants remain unclear due to shrinking and breaking caused by prior chromosome isolation or preparation with alcohol and acid fixation, and critical point drying occurred into dehydration and denatured chromosomal proteins. This study aimed to develop a high-quality procedure for the isolation and preparation of plant chromosomes, maintaining the native chromosome structure, to elucidate the organization of chromatin fibers on the surface of plant chromosomes by electron microscopy. A simple technique to isolate intact barley (Hordeum vulgare) chromosomes with a high yield was developed, allowing chromosomes to be observed with a high-resolution scanning ion microscopy and helium ion microscopy (HIM) imaging technology, based on a scanning helium ion beam. HIM images from the surface chromatin fibers were analyzed to determine the size and alignment of the chromatin fibers. The unit size of the chromatin fibers was 11.6 ± 3.5 nm and was closely aligned to the chromatin network model. Our findings indicate that compacting the surface structure of barley via a chromatin network and observation via HIM are powerful tools for investigating the structure of chromatin.

A reprogramming of secondary metabolism to acclimate to nitrogen deficiency was seen in grapevine eliciting an accumulation of strigolactones and jasmonate. This response links with photosynthetic compensation and enhanced ripening. In addition to the metabolism directly related to nitrogen assimilation, long-term nitrogen depletion may affect plant secondary metabolism, in turn affecting grapevine performance. In this work, the effect of nitrogen deficit was investigated in V. vinifera cv. Barbera potted vines following three years of deprivation, using a combination of morpho-physiological assessments and mass spectrometry-based untargeted metabolomics. Plants grown under nitrogen limitation showed reduced growth and even more curtailed yields, lowered SPAD values, and a quite preserved leaf gas exchange, compared to plants grown under non-limiting nitrogen availability. Ripening was decidedly accelerated, and berry composition improved in terms of higher sugar and phenolic contents under nitrogen-limitines profile, reflected in the modulation of photosynthetic performance, canopy growth, and possibly fruit quality.

Compare side-to-side differences for knee kinematics between anatomic single-bundle (SB) and anatomic double-bundle (DB) ACLR during downhill running at 6 and 24months post ACLR using high-accuracy dynamic stereo X-ray imaging. It was hypothesized that anatomic DB ACLR would better restore tibio-femoral kinematics compared to SB ACLR, based on comparison to the contralateral, uninjured knee.

Active individuals between 14 and 50years of age that presented within 12months of injury were eligible to participate. Individuals with prior injury or surgery of either knee, greater than a grade 1 concomitant knee ligament injury, or ACL insertion sites less than 14mm or greater than 18mm were excluded. Subjects were randomized to undergo SB or DB ACLR with a 10mm-wide quadriceps tendon autograft harvested with a patellar bone block and were followed for 24months. Dynamic knee function was assessed during treadmill downhill running using a dynamic stereo X-ray tracking system at 6 and 24months after surgery. Three-dimensional tibio-femoral kinematics were calculated and compared between limbs (ACLR and uninjured contralateral) at each time point.

Fifty-seven subjects were randomized (29DB) and 2-year follow-up was attained from 51 (89.5%). No significant differences were found between SB and DB anatomic ACLR for any of the primary kinematic variables.

Contrary to the study hypothesis, double-bundle reconstruction did not show superior kinematic outcomes compared to the single-bundle ACLR. While neither procedure fully restored normal knee kinematics, both anatomic reconstructions were similarly effective for restoring near-normal dynamic knee function. The findings of this study indicate both SB and DB techniques can be used for patients with average size ACL insertion sites.

Level I.

Level I.

The primary purpose of this study was to determine the union rate and time for surgical- and non-surgical treatment of stress fractures of the proximal fifth metatarsal (MT5). The secondary purpose was to assess the rate of adverse bone healing events (delayed union, non-union, and refractures) as well as the return to sports time and rate.

A literature search of the EMBASE (Ovid), MEDLINE (PubMed), CINAHL, Web of Science and Google Scholar databases until March 2020 was conducted. Methodological quality was assessed by two independent reviewers using the methodological index for non-randomized studies (MINORS) criteria. The primary outcomes were the union time and rate. Secondary outcomes included the delayed union rate, non-union rate, refracture rate, and return to sport time and rate. A simplified pooling technique was used to analyse the different outcomes (i.e. union rate, time to union, adverse bone healing rates, return to sport rate, and return to sport time) per treatment modality. Additionally,ies. Return to pre-injury level of sport time was 14.5weeks (117 fractures) for surgical treatment and 9.9weeks (6 fractures) for non-surgical treatment.

Surgical treatment of stress fractures of the proximal fifth metatarsal results in a higher bone union rate and a shorter union time than non-surgical treatment. Additionally, surgical and non-surgical treatment both showed a high return to sport rate (at any level), albeit with limited clinical evidence for non-surgical treatment due to the underreporting of data.

Level IV, systematic review.

Level IV, systematic review.

Biologicals, in combination with chemotherapy, are recommended as first-line treatment of metastatic colorectal cancer (mCRC); however, evidence guiding the appropriate management of older patients with mCRC is limited.

This study was undertaken to compare the efficacy and safety outcomes in older versus younger patients with mCRC who received first-line biological therapy.

This retrospective analysis used pooled data from five trials undertaken by the Spanish Cooperative Group for the Treatment of Digestive Tumours. All were studies of adults with advanced CRC who received first-line treatment with chemotherapy plus bevacizumab, cetuximab or panitumumab, stratified by age (≥ 65 vs. < 65 years). Endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and safety.

In total, 999 patients from five studies were included in the analysis 480 (48%) were aged ≥ 65 years, and 519 (52%) were aged < 65 years. Median PFS did not differ significantly between patients aged ≥ 65 and < 65 years (9.9 vs. 9.4 months; hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.88-1.17). Median OS was significantly shorter in older than in younger patients (21.3 vs. 25.0 months; HR 1.21; 95% CI 1.04-1.41). There was no significant difference between older and younger patients in ORR (59 vs. 62%). Patients aged ≥ 65 years experienced significantly more treatment-related grade 3 or higher adverse events (61.67%) than did patients aged < 65 years (45.86%).

Biologicals plus chemotherapy is an effective first-line treatment option for selected patients aged ≥ 65 years with mCRC and has a manageable safety profile and efficacy comparable to that observed in younger patients.

Biologicals plus chemotherapy is an effective first-line treatment option for selected patients aged ≥ 65 years with mCRC and has a manageable safety profile and efficacy comparable to that observed in younger patients.Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania and transmitted by the bite of a sand fly. To date, most available drugs for treatment are toxic and beyond the economic means of those affected by the disease. Protein disulfide isomerase (PDI) is a chaperone protein that plays a major role in the folding of newly synthesized proteins, specifically assisting in disulfide bond formation, breakage, or rearrangement in all non-native proteins. In previous work, we demonstrated that Leishmania major PDI (LmPDI) has an essential role in pathogen virulence. Furthermore, inhibition of LmPDI further blocked parasite infection in macrophages. In this study, we utilized a computer-aided approach to design a series of LmPDI inhibitors. Fragment-based virtual screening allowed for the understanding of the inhibitors' modes of action on LmPDI active sites. The generated compounds obtained after multiple rounds of virtual screening were synthesized and significantly inhibited target LmPDI reductase activity and were shown to decrease in vitro parasite growth in human monocyte-derived macrophages. This novel cheminformatics and synthetic approach led to the identification of a new series of compounds that might be optimized into novel drugs, likely more specific and less toxic for the treatment of leishmaniasis.

Despite expert consensus guidelines, data is scarce on how to switch patients with type2 diabetes when treatment with glucagon-like peptide1 (GLP-1) receptor agonists is not effective and whether a switch to semaglutide brings any benefit on glucose and weight control for patients with type2 diabetes.

Retrospective cohort analysis of patients with type2 diabetes who were switched from any GLP-1 agonist in a stable dose to subcutaneously administered semaglutide. Primary endpoint was change of glycated haemoglobin (HbA1c) at 6months. Secondary endpoints were weight, body mass index (BMI), heart rate, blood pressure and adverse events.

In total, 77 patients (median age 65years) with long-standing type2 diabetes (median 15years, median HbA1c 8.4%/68mmol/l, median BMI 33kg/m

) were included. HbA1c was significantly lower 6months after switching to semaglutide (7.3%; 56mmol/l). Median body weight was significantly lower at 3months (94kg) and 6months (93kg) compared to baseline (98kg). An equipotential dose switch of semaglutide was used in 61 patients (79%) and a stepwise initiation approach was used in 16 patients (21%). Both treatment regimens improved glucose control and weight. Side effects occurred in 28 patients (36%).

Switching to semaglutide from established GLP-1 analogue therapy improved HbA1c and body weight. Both equipotential and stepwise dosing initiation appear to be effective and well tolerated.

Switching to semaglutide from established GLP-1 analogue therapy improved HbA1c and body weight. Both equipotential and stepwise dosing initiation appear to be effective and well tolerated.

The test with the highest diagnostic accuracy for diabetes insipidus is copeptin measurement after hypertonic saline infusion. However, the procedure is cumbersome and unpleasant due to rapid sodium increase. An oral stimulation test would be highly desirable. Macimorelin, an oral ghrelin agonist, is a newly approved diagnostic test for growth hormone (GH) deficiency, but its effects on copeptin/vasopressin are unknown and the effects on other pituitary hormones only scarcely investigated.

In this prospective, interventional, proof-of-concept study Copeptin and anterior pituitary hormones were measured in 28 healthy volunteers on two test days at baseline, 30, 45, 60, 90 and 120min after a single dose of macimorelin (first visit 0.5mg/kg, second visit 0.75mg/kg).

Baseline copeptin levels were 5.26pmol/L [1.57, 6.81] and did not change after macimorelin intake (0.5mg/kg maximal median change 0.40 [- 0.49, 0.65] pmol/L, p = 0.442; 0.75mg/kg - 0.13 [- 0.45, 0.17] pmol/L, p = 0.442. Median GH levels increased from 3.67mU/L with a maximal median change of 94.66 [IQR 56.5; 110.96] mU/L, p < 0.001. No effect was seen on cortisol, ACTH, LH and FSH levels. Prolactin (max. median change 100 [2.5; 146.5] mU/L, p = 0.004) and free thyroxine (fT4) (0.5 [0.2; 0.8] pmol/L, p < 0.001) increased, whereas TSH decreased (- 0.18 [- 0.22, - 0.09] mU/L, p < 0.001).

We confirm an increase of GH upon macimorelin in healthy volunteers. However, macimorelin did not stimulate copeptin and therefore does not provide an oral test alternative for the diagnosis of diabetes insipidus. Additionally, a stimulatory effect was seen for prolactin and fT4, but not for ACTH and gonadotropic hormones.

The trial was registered on ClinicalTrials.gov (NCT03844217) on February 18, 2019.

The trial was registered on ClinicalTrials.gov (NCT03844217) on February 18, 2019.The study aimed to evaluate the efficacy of group cognitive behavioural therapy (CBT) in medicated adults with attention-deficit/hyperactivity disorder (ADHD) with a multidimensional evaluation and follow-up to week 36. Ninety-eight adult ADHD were randomly allocated to the CBT combined with medication (CBT + M) group or the medication (M) only group. The primary endpoint was the ADHD-Rating Scale (ADHD-RS). Secondary endpoints included emotional symptoms, self-esteem, automatic thoughts, quality of life (QoL), and executive function (EF). The outcome measures were obtained at baseline (T1), after the 12-week CBT treatment (T2), and at two follow-up time points (week 24, T3, and week 36, T4). Compared to the M-only group, the patients in the CBT + M group showed an overall significantly greater reduction from baseline in ADHD core symptoms (ADHD-RS total score at T3, and inattention subscale at T2 and T3), depression and anxiety symptoms (T2-T4), state anxiety (T2 and T3) and trait anxiety (T2), automatic thoughts questionnaire at T3, and QoL (physical domain, psychological domain, and social domain, most significant at T3 and weakened at T4). These findings further confirmed the efficacy of CBT on multiple dimensions and verified improvements in automatic thinking in adult ADHD. The superiority of the combination treatment mainly manifested in reduced inattention, emotional symptoms, and maladaptive thoughts and improved QoL. Trial registration number ChiCTR1900021705 (March-05-2019).

To investigate the sensitivity of visual read (VR) to detect early amyloid pathology and the overall utility of regional VR.

[

F]Flutemetamol PET images of 497 subjects (ALFA+ N= 352; ADC N= 145) were included. Scans were visually assessed according to product guidelines, recording the number of positive regions (0-5) and a final negative/positive classification. Scans were quantified using the standard and regional Centiloid (CL) method. The agreement between VR-based classification and published CL-based cut-offs for early (CL = 12) and established (CL = 30) pathology was determined. An optimal CL cut-off maximizing Youden's index was derived. Global and regional CL quantification was compared to VR. Finally, 28 post-mortem cases from the [

F]flutemetamol phase III trial were included to assess the percentage agreement between VR and neuropathological classification of neuritic plaque density.

VR showed excellent agreement against CL = 12 (κ= .89, 95.2%) and CL = 30 (κ= .88, 95.4%) cut-offs. ROC analysis resulted in an optimal CL = 17 cut-off against VR (sensitivity = 97.9%, specificity = 97.8%). Each additional positive VR region corresponded to a clear increase in global CL. Regional VR was also associated with regional CL quantification. Compared to mCERAD

-based classification (i.e., any region mCERAD

> 1.5), VR was in agreement in 89.3% of cases, with 13 true negatives, 12 true positives, and 3 false positives (FP). Regional sparse-to-moderate neuritic and substantial diffuse Aβ plaque was observed in all FP cases. Regional VR was also associated with regional plaque density.

VR is an appropriate method for assessing early amyloid pathology and that grading the extent of visual amyloid positivity could present clinical value.

VR is an appropriate method for assessing early amyloid pathology and that grading the extent of visual amyloid positivity could present clinical value.Several species of fungus from the genus Aspergillus are implicated in pulmonary infections in immunocompromised patients. Broad screening methods for fungal infections are desirable, as cultures require a considerable amount of time to provide results. Herein, we developed degradation and detection methods to produce and detect D-glucosamine (GlcN) from Aspergillus niger, a species of filamentous fungus. Ultimately, these techniques hold the potential to contribute to the diagnosis of pulmonary fungal infections in immunocompromised patients. In the following studies, we produced GlcN from fungal-derived chitin to serve as a marker for Aspergillus niger. To accomplish this, A. niger cells were lysed and subjected to a hydrochloric acid degradation protocol. Products were isolated, reconstituted in aqueous solutions, and analyzed using hydrophilic interaction liquid chromatography (HILIC) in tandem with electrospray ionization time-of-flight mass spectrometry. Our results indicated that GlcN was produced from A. niger. To validate these results, products obtained via fungal degradation were compared to products obtained from the degradation of two chitin polymers. The observed retention times and mass spectral extractions provided a two-step validation confirming that GlcN was produced from fungal-derived chitin. Our studies qualitatively illustrate that GlcN can be produced from A. niger; applying these methods to a more diverse range of fungi offers the potential to render a broad screening method for fungal detection pertinent to diagnosis of fungal infections.The objective of this study was to investigate the feasibility of using glycine nano-selenium (NS-Gly) as a feed supplement and to evaluate its influence on production performance, egg quality, serum biochemistry, oxidative status, and the intestinal morphology and absorption of laying hens. A total of 864 hens at 40 weeks were randomly assigned into six groups including the basal diet (control, 0.13 mg Se/kg); basal diet + 0.30 mg Se/kg (Na2SeO3) diet; and basal diet + 0.15, 0.30, 0.45, and 0.60 mg Se/kg (NS-Gly) diet. After 8 weeks of Se supplementation, no difference was observed among the treatments on production performance and egg quality (P > 0.05). The levels of albumin (ALB) and alanine aminotransferase (GPT) were significantly influenced by dietary Se supplementation (P  less then  0.05). In the serum, the level of glutathione peroxide (GSH-Px) was significantly increased in the groups with the dietary NS-Gly supplementation (P  less then  0.05). The superoxide dismutase (SOD) and total antioxidant NS-Gly groups (P  less then  0.05). In the jejunum, the expression of B0AT1 was similar to that in the duodenum, and the expression of rBAT increased significantly in the 0.30 and 0.45 mg/kg NS-Gly groups (P  less then  0.05). The mRNA level of PepT1 increased significantly in the 0.30 mg/kg SS group. Conclusively, dietary NS-Gly supplementation could improve the antioxidant capacity, as well as the structure of small intestine in laying hens, although have no significant effects on the production performance and egg quality.For birds, the uterus is an important part for eggshell mineralization, and the establishment of the endometrial epithelial cell (EEC) model was beneficial to the study of uterine function. This study was conducted to establish a culture model of primary EECs of laying hens and explore the effects of zinc on primary EEC proliferation, zinc transport, and calcium deposition in vitro. The EECs were isolated and cultured via type I collagenase digestion, and in the logarithmic phase during 2-5 days, and then reached the plateau phase on the 7th day of inoculation. Results showed that the proliferation of EECs treated by 50 μM ZnSO4 or zinc-methionine (Zn-Met) were markedly promoted at 24-h or 48-h treating time (P  less then  0.05). In later experiments, the EECs were divided into three groups, involving a control group (no zinc treated), ZnSO4 group (50 μM zinc treated) and a Zn-Met group (50 μM zinc treated). Results showed the relative fluorescence intensity of Ca2+ in the Zn-Met group was significantly higher than that in the control group (P  less then  0.05). As for zinc transporters, it was only observed that mRNA levels of metallothionein (MT) in EECs showed a significant difference (P  less then  0.05) between the Zn-Met group and the control. In conclusion, the EECs of laying hens isolated by scraping and digested collagenase I were with better adherent growth. Moreover, Zn-Met can increase intracellular Ca2+ concentration and upregulate expressions of MT mRNA in the EECs of laying hens.

To evaluate and report the complications, and to analyse antimicrobial stewardship aspects following prostate biopsies (P-Bx) based on the data from a 9-year global study.

The primary outcome was to compare complications after P-Bx between patients of two cohorts 2010-2014 and 2016-2019. Primary outcomes included symptoms of lower and severe/systemic urinary tract infection (LUTIS and SUTIS, respectively), and positive urine culture. Readmission to hospital after P-Bx, need for additional antimicrobial therapy, consumption of different antimicrobial agents for prophylaxis and therapy were evaluated. Students t test and chi-square test were used for comparative analyses.

Outcome data were available for 1615 men. Fluoroquinolones-based prophylaxis rate increased from 72.0% in 2010-2014 to 78.6% in 2015-2019. Overall rates of complications increased from 6 to 11.7% including an increase in symptomatic complications from 4.7 to 10.2%, mainly due to an increase in LUTIS. Rates of patients seeking additional neal biopsy route.

Scleral buckling (SB) is usually considered an extraocular operation premeditated to have a low risk of sympathetic ophthalmia (SO). Here we report a rare case of presumed SO in a young female patient following SB.

A nineteen-year-old female patient was referred for visual loss in her left eye due to macula off inferior long-standing rhegmatogenous retinal detachment (RRD). The best corrected visual acuity (BCVA) was 20/400 in the left eye. SB with 360 degrees encircling band, an inferior segmental tire with one spot cryoretinopexy at the break site, and subretinal fluid drainage was performed. BCVA was improved to 20/80 and the retina was totally attached 1 week after the operation. The patient referred to the hospital 6 weeks later with severe visual loss in both eyes as counting finger 1 m. Patient examination indicated bilateral multifocal serous retinal detachment (SRD) and vitreous cells. The patient, diagnosed with SO, received intravenous corticosteroid pulse therapy and mycophenolate mofetil for treatment. The inflammation was controlled and SRD resolved after a 5-day intravenous treatment without being relapsed after 6 months. Consequently, BCVA became 20/20 and 20/50 in the right and left eye, respectively, after 6 months. The findings of systemic workup were negative for any extraocular disease or systemic involvement.

Since SB is a procedure without manipulating intraocular tissues, it is considered to impose a low risk for SO. This report presented SO occurrence after successful SB. Some factors may induce SO, including inciting the choroid and retinal pigment epithelium with cryoretinopexy or perforating for drainage.

Since SB is a procedure without manipulating intraocular tissues, it is considered to impose a low risk for SO. This report presented SO occurrence after successful SB. Some factors may induce SO, including inciting the choroid and retinal pigment epithelium with cryoretinopexy or perforating for drainage.In 2014, over 60% of medical schools were incorporating point of care ultrasound (POCUS) into their curriculum. Today, over 6 years later, many more schools are teaching POCUS or are in the planning stages of implementing a POCUS curriculum. In 2019, the AAMC reported that 53 schools or over one-third of US medical schools have multi-site campuses for undergraduate medical education. Implementation of a POCUS educational initiative at a multi-site campus presents unique challenges for teaching a uniform curriculum statewide. This article will discuss the POCUS curriculum and implementation process at a large multi-site institution.Biosurfactants are environment compatible surface-active biomolecules with multifunctional properties which can be utilized in various industries. In this study a biosurfactant producing novel plant growth promoting isolate Pseudomonas guariconensis LE3 from the rhizosphere of Lycopersicon esculentum is presented as biostimulant and biocontrol agent. Biosurfactant extracted from culture was characterized to be mixture of various mono- and di-rhamnolipids with antagonistic activity against Macrophomina phaseolina, causal agent of charcoal rot in diverse crops. Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H NMR) analysis confirmed the rhamnolipid nature of biosurfactant. PCR analysis established the presence of genes involved in synthesis of antibiotics diacetylphloroglucinol, phenazine 1-carboxylic acid and pyocyanin, and lytic enzymes chitinase and endoglucanase suggesting biocontrol potential of the isolate. Plant growth promoting activities shown by LE3 were phosphate solubilization and production of siderophores, indole acetic acid (IAA), ammonia and 1-aminocyclopropane-1-carboxylate deaminase (ACCD). To assemble all the characteristics of LE3 various bioformuations were developed. Amendment of biosurfactant in bioformulation of LE3 cells improved the shelf life. Biosurfactant amended formulation of LE3 cells was most effective in biocontrol of charcoal rot disease of sunflower and growth promotion in field conditions. The root adhered soil mass of plantlets inoculated with LE3 plus biosurfactant was significantly higher over control. Biosurfactant amended formulation of LE3 cells caused maximum yield enhancement (80.80%) and biocontrol activity (75.45%), indicating that addition of biosurfactant improves the plant-bacterial interaction and soil properties leading to better control of disease and overall improvement of plant health and yield.

Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia (TEA) was previously shown to reduce right and left ventricular systolic function and effective pulmonary arterial elastance. At conditions of constant paced heart rate, cardiac output and systemic hemodynamics were unchanged. In this study, we further investigated the effect of cardiac sympathicolysis during physical stress and increased oxygen demand.

In a cross-over design, 12 patients scheduled to undergo thoracic surgery performed dynamic ergometric exercise tests with and without TEA. Hemodynamics were monitored and biventricular function was measured by transthoracic two-dimensional and M-mode echocardiography, pulsed wave Doppler and tissue Doppler imaging.

TEA attenuated systolic RV function (TV S' - 21%, P < 0.001) and LV function (MV S' - 14%, P = 0.025), but biventricular diastolic function was not affected. HR (- 11%, P < 0.001), SVI (- 15%, P = 0.006), CI (- 21%, P < 0.001) and MAP (- 12%, P < 0.001) were deduced increases in LV and RV function. These data indicate that additional mechanisms besides those controlled by the cardiac sympathetic nervous system are involved in the regulation of cardiac function during dynamic exercise. Trial registration Clinical trial registration Nederlands Trial Register, NTR 4880 http//www.trialregister.nl/trialreg/admin/rctview.asp?TC=4880 .Thresholds for Helicoverpa zea (Boddie) in cotton Gossypium hirsutum L. have been understudied since the widespread adoption of Bt cotton in the United States. Our study was possible due to the widespread presence of H. zea populations with Cry-toxin resistance. We initiated progressive spray timing experiments using three Bt cotton brands (Deltapine, Stoneville, and Phytogen) widely planted across the U.S. Cotton Belt expressing pyramided toxins in the Cry1A, Cry2, and Vip3Aa19 families. We timed foliar insecticide treatments based on week of bloom to manipulate H. zea populations in tandem with crop development during 2017 and 2018. We hypothesized that non-Bt cotton, cotton expressing Cry toxins alone, and cotton expressing Cry and Vip3Aa19 toxins would respond differently to H. zea feeding. We calculated economic injury levels to support the development of economic thresholds from significant responses. Pressure from H. zea was high during both years. Squares and bolls damaged by H. zea had the strongest negative yield associations, followed by larval number on squares. There were fewer yield associations with larval number on bolls and with number of H. zea eggs on the plant. Larval population levels were very low on varieties expressing Vip3Aa19. Yield response varied across experiments and varieties, suggesting that it is difficult to pinpoint precise economic injury levels. Nonetheless, our results generally suggest that current economic thresholds for H. zea in cotton are too high. Economic injury levels from comparisons between non-Bt varieties and those expressing only Cry toxins could inform future thresholds once H. zea evolves resistance to Vip3Aa19.