Mcknightbauer4964

High levels of timeout responding were noted in a subset of rats that acquired MDPV self-administration ("high-responders", n = 5), and the FR5 dose-response curve for MDPV was shifted upward for these rats relative to their "low-responder" (n = 6) counterparts. "High-responders" also self-administered more infusions of oxycodone under an FR5 schedule of reinforcement than "low-responders"; however, this was not coupled with increased levels of timeout responding.

The present data suggest thata subset of individuals with a history of using synthetic cathinones may be particularly vulnerable to the abuse of oxycodone.

The present data suggest that a subset of individuals with a history of using synthetic cathinones may be particularly vulnerable to the abuse of oxycodone.Intravenous (IV) ketamine has been shown to have rapid and robust antidepressant effects in adults with treatment-resistant depression (TRD). Urological toxicity has been observed in chronic ketamine abusers as evidenced by dysuria, urgency, and hematuria. The foregoing observation provides the basis for evaluating whether ketamine-induced urological toxicity (KIUT) is associated with sub-anesthetic doses of ketamine (0.5-1.0 mg/kg) in adults with mood disorders. The overarching objective of this article is to identify potential mechanisms of KIUT which appears to be dose and frequency dependent. Available research indicates that high-frequency ketamine is associated with disruption of the urothelial barrier as well as direct ketamine toxicity (i.e., decreased expression of junction proteins) in KIUT of the bladder. Chronic and high-frequency ketamine use is also associated with bladder inflammation mediated via neurogenic and IgE inflammation. Other non-mutually exclusive causes are nerve hyperplasia, hypersensitivity, cell apoptosis, microvascular damage, and overexpression of carcinogenic genes. Notwithstanding the evidence of KIUT in ketamine abusers, there is no evidence that ketamine and/or esketamine treatment in adults with mood disorders is associated with KIUT. However, all patients receiving ketamine/esketamine for mood disorder treatment should be queried about genitourinary symptoms during acute and, where applicable, maintenance dosing.

The aim of this study was to investigate the associations between quality of life and both perceived and objective availability of local green and blue spaces in people with dementia, including potential variation across rural/urban settings and those with/without opportunities to go outdoors.

This study was based on 1540 community-dwelling people with dementia in the Improving the experience of Dementia and Enhancing Active Life (IDEAL) programme. Quality of life was measured by the Quality of Life in Alzheimer's Disease (QoL-AD) scale. A list of 12 types of green and blue spaces was used to measure perceived availability while objective availability was estimated using geographic information system data. Regression modelling was employed to investigate the associations of quality of life with perceived and objective availability of green and blue spaces, adjusting for individual factors and deprivation level. Interaction terms with rural/urban areas or opportunities to go outdoors were fitted to test whether the associations differed across these subgroups.

Higher QoL-AD scores were associated with higher perceived availability of local green and blue spaces (0.82; 95% CI 0.06, 1.58) but not objective availability. The positive association between perceived availability and quality of life was stronger for urban (1.50; 95% CI 0.52, 2.48) than rural residents but did not differ between participants with and without opportunities to go outdoors.

Only perceived availability was related to quality of life in people with dementia. Future research may investigate how people with dementia utilise green and blue spaces and improve dementia-friendliness of these spaces.

Only perceived availability was related to quality of life in people with dementia. Future research may investigate how people with dementia utilise green and blue spaces and improve dementia-friendliness of these spaces.

Keratoconus is a potentially blinding condition that slowly deforms the cornea in young people. Despite the increasing prevalence of keratoconus, the exact aetiology of the condition is unknown. This first systematic review examines the evidence of eye rubbing and its association with keratoconus and presents the findings of the meta-analysis.

Two independent reviewers searched the electronic databases for all potential articles published from 1st of January 1900 to 31st of July 2020 on eye rubbing and keratoconus. The researchers assessed the methodological quality of the studies using the Newcastle-Ottawa scale for observational studies. The assessment for statistical heterogeneity was estimated using chi-square and I-square (I

) tests. A p value of < 0.05 was considered as statistically significant and I

 < 30% as homogenous. Begg funnel plot was used to interpret the asymmetry or small study effects.

Eight case-control studies were included in this systematic review. Two studies assessed eyeal methodological quality. Additionally, the cause-effect temporal relationship cannot be determined. Further studies are needed to address this intricate relationship of eye rubbing and its induction, ongoing progression, and severity of keratoconus.One of the major hurdles for the advancement of cancer immunotherapy is lack of robust, accessible experimental models. We aimed to produce an ex-vivo organ culture (EVOC) model of immunotherapy for non-small cell lung cancer (NSCLC). Freshly resected early stage tumors were collected from the operating room, fragmented to clusters  less then  450 µm and cultured with fetal calf serum and human autologous serum. The resulting EVOC includes cancer epithelial cells within tumor tissue clusters and immune cells. Original tissue features are reflected in the EVOCs. The response to immune checkpoint inhibitors (ICI) was assessed by IFNγ gene induction. Interestingly, IFNγ EVOC induction was numerically higher when anti-CTLA4 was added to anti-PD-L1 treatment, supporting the notion that anti-CTLA4 impacts cancer partly through tumor-resident immune cells. In parallel, immunohistochemistry (IHC) for key immune-related proteins was performed on the formalin-fixed paraffin embedded (FFPE) corresponding tumors. EVOC IFNγ induction by ICI correlated with basal non-induced IFNγ, CD8, CD4 and FOXP3 mRNA levels within EVOCs and with tumor-FFPE-IHC for CD8 and granzyme B. A weaker correlation was seen with tumor-FFPE-IHC for CD3, CD4, CD68, FOXP3 and tumor-PD-L1. Tertiary lymphoid structure density was also correlated with the ICI response. Our study provides novel data about biomarkers that correlate with ICI-induced response of early stage NSCLC. Retention of the microenvironment and minimal addition of exogenous factors suggest this model to reliably represent the original tumor. The cluster-based EVOC model we describe can provide a valuable, yet simple and widely applicable tool for the study of immunotherapy in NSCLC.

Necrotizing fasciitis (NF) is a rapidly progressive inflammatory infection of the fascia, with secondary necrosis of the subcutaneous tissues. The severity of the disease depends on the virulence of the organism and host immunity. There is a paucity of reports on the prevalence of NF causing pathogens and management.

Retrospective data of patients treated for NF were collected from two tertiary care hospitals in Central Malaysia between January 2014 and December 2018.

A total of 469 NF patients were identified. More than half of the NF patients were males (n = 278; 59.28%). The highest number of cases was found among age groups between 30 and 79, with mean age of 56.17. The majority of the NF cases (n = 402; 85.72%) were monomicrobial. Streptococcus spp. (n = 89; 18.98%), Pseudomonas aeruginosa (n = 63; 13.44%) and Staphylococcus spp. (n = 61; 13.01%) were identified as the top three microorganisms isolated. Among the 469 NF cases, 173 (36.8%) were amputated or dead while 296 (63.1%) recovered. Proteus spp. (n = 19; 12.93%), Klebsiella pneumoniae (n = 18; 12.24%) and Escherichia coli (n = 14; 9.52%) were associated with all types of amputations. The most common antibiotic prescribed was unasyn (n = 284; 60.56%), followed by clindamycin (n = 56; 11.94%) and ceftazidime (n = 41; 8.74%). A total of 239 (61.8%) recovered while 148 (38.2%) were either amputated or dead when managed with the unasyn, clindamycin or ceftazidime.

This study represents the largest NF cases series in Malaysia highlighting the causative agents and management.

This study represents the largest NF cases series in Malaysia highlighting the causative agents and management.Endothelin-1 contributes to the constrictor response of the coronary arteries in patients with ischemia with normal coronary arteries. There is thus increasing evidence that endothelin-1 plays a role in coronary microvascular dysfunction (CMD). We investigated whether elevated endothelin-1 is associated with CMD in patients with coronary artery disease (CAD). We prospectively studied 49 consecutive CAD patients with 1- or 2-vessel disease (age 71 ± 10 years, 43 males). Myocardial blood flow (MBF) was measured by 15O-water PET/CT at rest and during stress, and the coronary flow reserve (CFR) was calculated by dividing the stress MBF by the rest MBF. A CFR of less than 2.0 in non-obstructive regions was defined as a marker of CMD. Eighteen out of 49 (37%) CAD patients had CMD. Endothelin-1 in patients with CMD was significantly higher than in those without CMD (2.27 ± 0.81 vs. 1.64 ± 0.48 pg/mL, P = 0.001). Accordingly, univariate ROC analysis showed that the continuous endothelin-1 levels significantly discriminated between the presence and absence of CMD (area under the curve = 0.746 [95%CI 0.592-0.899]). The dichotomous treatment of elevated endothelin-1 as 1.961 pg/mL or more yielded the optimal discriminatory capacity, with a sensitivity of 72.2% and a specificity of 71.0%. High endothelin-1 was still a significant predictor of CMD after adjusting for diabetes mellitus (odds ratio = 6.64 [1.75-25.22], P = 0.005). Endothelin-1 is associated with CMD in non-obstructive territories in patients with CAD, suggesting that endothelin-1 is a potential target for treating CMD in CAD patients.Preoperative frailty diminishes the potential for functional recovery after transcatheter aortic valve implantation (TAVI). However, perioperative changes in physical status and their impact on prognosis after TAVI have not previously been reported. Therefore, this study aimed to investigate whether perioperative changes in physical function affect prognosis in patients undergoing TAVI. We retrospectively reviewed 257 patients who underwent TAVI. The Short Physical Performance Battery (SPPB), an objective physical status assessment tool, was evaluated pre- and post-TAVI. Patients were divided into two groups (i) patients whose SPPB score declined in the perioperative period (the decline group) and (ii) patients whose SPPB score did not decline in the perioperative period (the non-decline group). The primary endpoint was unplanned hospitalization owing to heart failure or cardiovascular death following TAVI. The mean follow-up period was 385 ± 151 days, mean age was 83.2 ± 5.8 years, and 67% of the patients were women. Sixteen patients required readmission owing to heart failure, and seven experienced cardiovascular-related death. Kaplan-Meier analysis revealed that the event-free rate was significantly lower in the decline group (log-rank, p = 0.006). A stepwise multivariate logistic regression analysis showed that a perioperative change in SPPB was significantly associated with primary endpoints (odds ratio, 1.51; 95% confidence interval, 1.12-2.04). Perioperative change in physical function was an independent risk factor for heart failure, hospitalization, or cardiovascular death following TAVI.Anaerobic threshold (AT) from cardiopulmonary exercise tests (CPX) is the standard for measuring exercise intensity among patients with cardiovascular disease in Japan. However, it remains controversial whether AT represents the safety limit for exercise intensity in patients with cardiovascular disease. The purpose of this study was to investigate cardiac rehabilitation (CR) efficacy and safety with exercise intensities above the AT and at a traditional AT in a randomized trial. The participants included 57 patients who were admitted to the outpatient CR unit with a diagnosis of acute myocardial infarction. The participants were randomly divided as follows 25 patients in the AT group, who performed aerobic exercises with an intensity at the AT; and 32 patients in the "Over AT" group, who performed exercises at an intensity higher than the AT. The following components were measured maximum oxygen uptake (peak VO2), oxygen uptake at the AT (AT VO2), increase in oxygen uptake during exercise (ΔVO2/ΔWR) during tnt rate was associated with changes in isometric knee extension strength.Myocardial perfusion and perfusion reserve are diminished in patients with atrial fibrillation (AF). Phase-contrast (PC) cine magnetic resonance imaging (MRI) of the coronary sinus serves as a non-invasive means of quantifying coronary flow reserve (CFR) without any radioactive tracer. The present study aimed to evaluate the utility of PC cine MRI of the coronary sinus for assessing decreased CFR in patients with AF. We studied 362 patients with known or suspected coronary artery disease (CAD) [age 72 ± 9 years; 267 (74%) male; 90 (25%) had AF] and 20 age- and gender-matched control subjects [age 72 ± 9 years, 14 (70%) male]. Using a 1.5-T MR scanner and cardiac coils, blood flow of the coronary sinus (CBF) was quantified by PC cine MRI. CFR was calculated as CBF during adenosine triphosphate infusion divided by CBF at rest. CFR was significantly lower in patients with AF than in those without AF among all patients (n = 362) (2.45 ± 0.42 vs. 2.71 ± 0.58, p  less then  0.001), in patients with known CAD (n = 155) (2.40 ± 0.46 vs. 2.72 ± 0.58, p = 0.002), and in those with suspected CAD (n = 207) (2.49 ± 0.40 vs. 2.72 ± 0.59, p = 0.007). Significant differences in CFR were found between controls and patients without AF (3.12 ± 0.52 vs. 2.71 ± 0.58, p  less then  0.001). AF was independently associated with CFR in both known CAD patients [β = - 0.248, 95% confidence interval (CI) - 0.561 to - 0.119, p = 0.003) and suspected CAD patients (β =  - 0.154, 95% CI - 0.353 to - 0.034, p = 0.018). The presence of AF was related to impaired CFR in both known and suspected CAD patients. PC cine MRI of the coronary sinus can be useful for detecting impaired CFR in patients with AF.The aim of this study was to determine factors associated with physical fitness (PF) in children who underwent surgery for congenital heart disease (CHD). Sixty-six children (7-14 years) who underwent surgery for ventricular septal defect (n = 19), transposition of great arteries (n = 22), coarctation of aorta (n = 10), and tetralogy of Fallot (n = 15) were included. All children performed PF tests cardiorespiratory fitness, upper- and lower-limb muscle strength, speed, balance, and flexibility. Cardiac evaluation was done via echocardiography and cardiopulmonary exercise test. Factors related to child's characteristics, child's lifestyle, physical activity motivators/barriers, and parental factors were assessed. Linear regression analyses were conducted. The results showed no significant differences in physical activity (PA) level by CHD type. Boys had better cardiorespiratory fitness (difference = 1.86 ml/kg/min [0.51;3.22]) and were more physically active (difference = 19.40 min/day [8.14;30.66]), while girls had better flexibility (difference = - 3.60 cm [- 7.07;- 0.14]). Physical activity motivators showed an association with four out of six PF components cardiorespiratory fitness, coefficient = 0.063 [0.01;0.11]; upper-limb muscle strength, coefficient = 0.076 [0.01;0.14]; lower-limb muscle strength, coefficient = 0.598 [0.07;1.13]; and speed, coefficient = 0.03 [0.01;0.05]. Age, sex, and motivators together reached a maximum adjusted R2 = 0.707 for upper-limb strength. Adding other possible determinants did not significantly increase the explained variance. Apart from age and sex as non-modifiable determinants, the main target which might improve fitness would be the introduction of an intervention which increases the motivation to be active.

The objective was to identify the best parameter (pubis-cervix measurement, pubis-uterine fundus measurement or pubis-pouch of Douglas measurement) on transperineal ultrasound, based on the difference between measurements taken at rest and with the Valsalva maneuver, for presurgical differential diagnosis between uterine prolapse (UP) and cervical elongation (CE) without UP.

A prospective observational study of 60 consecutively recruited patients who underwent corrective surgery of the middle compartment (UP or CE without UP). A transperineal ultrasound was performed, and the descent of the pelvic organ was measured in relation to the posteroinferior margin of the pubis in the midsagittal plane, referencing the uterine fundus, pouch of Douglas and the cervix at rest and with the Valsalva test.

Receiver operating characteristic (ROC) curves were constructed for the three evaluated measures, based on the difference between rest and Valsalva, for the diagnosis of UP. For the pubis-cervix distance, an area under the curve (AUC) of 0.59 was obtained; for the pubis-uterine fundus distance, the AUC was 0.81; and for the pubis-pouch of Douglas distance, the AUC was 0.69. Based on the best AUC (the difference in the pubis-uterine fundus distance at rest and with the Valsalva maneuver), a cut-off point of 15mm was established for the diagnosis of UP (sensitivity 75%; specificity 95%; positive predictive value 86%; and negative predictive value 89%).

A difference of ≥15mm in the pubis-uterine fundus distance at rest and with the Valsalva maneuver is useful for differentiating UP from CE without UP by ultrasound.

A difference of ≥15 mm in the pubis-uterine fundus distance at rest and with the Valsalva maneuver is useful for differentiating UP from CE without UP by ultrasound.

We aimed to summarize the knowledge on the pathogenesis of pelvic organ prolapse (POP) generated in animal models.

We searched MEDLINE, Embase, Cochrane and the Web of Science to establish what animal models are used in the study of suggested risk factors for the development of POP, including pregnancy, labor, delivery, parity, aging and menopause. Lack of methodologic uniformity precluded meta-analysis; hence, results are presented as a narrative review.

A total of 7426 studies were identified, of which 51 were included in the analysis. Pregnancy has a measurable and consistent effect across species. In rats, simulated vaginal delivery induces structural changes in the pelvic floor, without complete recovery of the vaginal muscular layer and its microvasculature, though it does not induce POP. In sheep, first vaginal delivery has a measurable effect on vaginal compliance; measured effects of additional deliveries are inconsistent. Squirrel monkeys can develop POP. Denervation of their levator ani muscle facilitates this process in animals that delivered vaginally. The models used do not develop spontaneous menopause, so it is induced by ovariectomy. Effects of menopause depend on the age at ovariectomy and the interval to measurement. In several species menopause is associated with an increase in collagen content in the longer term. In rodents there were no measurable effects of age apart of elastin changes. We found no usable data for other species.

In several species there are measurable effects of pregnancy, delivery and iatrogenic menopause. Squirrel monkeys can develop spontaneous prolapse.

In several species there are measurable effects of pregnancy, delivery and iatrogenic menopause. Squirrel monkeys can develop spontaneous prolapse.

Post-partum, women often experience urinary incontinence (UI). However, the association between experienced UI bother and UI beliefs and help-seeking behavior is less known. Therefore, we aim to investigate the prevalence of self-reported UI, the level of experienced bother and beliefs, to explain help-seeking behavior for UI in women in the Netherlands from 6weeks to one year post-partum.

A digital survey among post-partum women, shared on social media, was used for recruitment. The survey consists of 1. demographic variables, 2. International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF), 3. ICIQ Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol), and 4. questions on beliefs and help-seeking behavior. For analysis, descriptive statistics and the independent samples t-test were used to determine differences between help- and non-help-seekers.

415 women filled in the survey. The mean age was 30.6years (SD 4.0, range 21-40) of which 48.2% was primiparous. The overall prevalence of UI was 57.1% (95% confidence interval (CI) (52.3-61.8)). Primiparous women reported a statistically significantly lower overall prevalence than multiparous women, 52.0% and 61.9% respectively (p= .043). UI was reported as bothersome in 38% of women, 25% of all women sought help. Help-seeking women showed significantly higher scores for bother, measured by the ICIQ-UI SF, than non-help seekers (p= .001).

More than half of all post-partum women in the Netherlands from 6weeks to one year post childbirth experience UI (57.1%), 38% classified their UI as bothersome. In total 25% of UI women sought professional help.

More than half of all post-partum women in the Netherlands from 6 weeks to one year post childbirth experience UI (57.1%), 38% classified their UI as bothersome. In total 25% of UI women sought professional help.

To summarize the clinical and radiological features of hepatic trichinellosis.

Patients diagnosed with trichinellosis and liver involvement in our institution since 2011 were included retrospectively. Then, qualified patients were divided into a seropositive group and a clinically diagnosed group. Preoperative liver CT and/or MRI images were evaluated independently by two radiologists. The correlations between the radiological and pathological features were evaluated by a radiologist and a pathologist. Independent t-tests were carried out to assess clinical data between groups and those reported in the previous literature. Values of P less than 0.05 were considered statistically significant.

Eventually, ten patients were enrolled, five in each group. All patients recovered successfully after surgical (n = 8) or conservative treatment (n = 2). The clinical, radiological, and pathological features were highly consistent between the two groups. All patients were under 60years of age (48.0 ± 7.9years in the seropositive group, 48.6 ± 10.1years in the clinically diagnosed group), and they were older than those previously reported in the literature (30.5 ± 17years, n  =  31; P = 0.032 and 0.028). Eosinophilia was found in four patients, and all were mildly increased (˂ 1.5 × 10

/L). Lesions in all patients were in the right lobe of the liver, and nine of them showed a characteristic 'curved tunnel' sign on DCE-MRI images. None of the patients had signs or evidence of extrahepatic infection.

The 'curved tunnel' sign on MRI is a typical radiological feature in hepatic trichinellosis.

The 'curved tunnel' sign on MRI is a typical radiological feature in hepatic trichinellosis.

To assess the feasibility of ablation planning based on fusion imaging of three-dimensional ultrasound/contrast-enhanced ultrasound (3D US/CEUS) with real-time US/CEUS for liver tumor thermal ablation.

Between January 2017 and December 2018, 85 hepatic tumors from 82 patients who underwent percutaneous ablation were included. First, intraprocedural 3D US/CEUS imaging was performed for ablation planning. Then, fusion imaging of 3D US/CEUS with real-time US/CEUS was used to guide the implementation of the plan, immediately evaluate the technical success and indicate the need for supplemental ablation. In addition, contrast-enhanced CT/MR imaging was performed 1month after the procedure to evaluate the presence of residual tumors, and follow-up scans were repeated every 3months.

The average liver tumor diameter was 28 ± 9mm (range, 10-55mm). 3D US/CEUS-based planning was successfully conducted in all 85 tumors with a 100% technical success rate of planning. The immediate evaluation by 3D CEUS/US-CEUS fusion imaging showed a 100% technical success rate of ablation. The 1-month CT/MR scans found a residual tumor in one intrahepatic cholangiocarcinoma patient; the technique efficacy rate was 98.8%. The median follow-up period was 21.5months (IQR 4-36months). During the follow-up period, the local tumor progression rate was 5.9% (5/84), and no major procedure-related complications occurred.

Ablation planning based on 3D US/CEUS-US/CEUS fusion imaging is feasible for liver tumors.

Ablation planning based on 3D US/CEUS-US/CEUS fusion imaging is feasible for liver tumors.The purpose of this review is to describe the potential sources of variability or discrepancy in interpretation of cystic renal masses under the Bosniak v2019 classification system. Strategies to avoid these pitfalls and clinical examples of diagnostic approaches are also presented. Potential pitfalls in the application of Bosniak v2019 are divided into three categories interpretative, technical, and mass related. An organized, comprehensive review of possible discrepancies in interpreting Bosniak v2019 cystic masses is presented with pictorial examples of difficult clinical cases and proposed solutions. The scheme provided can guide readers to consistent, precise application of the classification system. Radiologists should be aware of the possible sources of misinterpretation of cystic renal masses when applying Bosniak v2019. Knowing which features and types of cystic masses are prone to interpretive errors, in addition to the inherent trade-offs between the CT and MR techniques used to characterize them, can help radiologists avoid these pitfalls.Kaposi's sarcoma-associated herpesvirus (KSHV) is a human tumorigenic virus and the etiological agent of an endothelial tumor (Kaposi's sarcoma) and two B cell proliferative diseases (primary effusion lymphoma and multicentric Castleman's disease). While in patients with late stage of Kaposi's sarcoma the majority of spindle cells are KSHV-infected, viral copies are rapidly lost in vitro, both upon culture of tumor-derived cells or from newly infected endothelial cells. We addressed this discrepancy by investigating a KSHV-infected endothelial cell line in various culture conditions and in tumors of xenografted mice. We show that, in contrast to two-dimensional endothelial cell cultures, KSHV genomes are maintained under 3D cell culture conditions and in vivo. Additionally, an increased rate of newly infected cells was detected in 3D cell culture. Furthermore, we show that the PI3K/Akt/mTOR and ATM/γH2AX pathways are modulated and support an improved KSHV persistence in 3D cell culture. These mechanisms may contribute to the persistence of KSHV in tumor tissue in vivo and provide a novel target for KS specific therapeutic interventions. KEY MESSAGES In vivo maintenance of episomal KSHV can be mimicked in 3D spheroid cultures 3D maintenance of KSHV is associated with an increased de novo infection frequency PI3K/Akt/mTOR and ATM/ γH2AX pathways contribute to viral maintenance.

We studied EGFR mutations in circulating tumor DNA (ctDNA) and explored their role in predicting the progression-free survival (PFS) of non-small cell lung cancer (NSCLC) patients treated with erlotinib or gefitinib.

The L858R, T790M mutations and exon 19 deletions were quantified in plasma using digital droplet polymerase chain reaction (ddPCR). The dynamics of ctDNA mutations over time and relationships with PFS were explored.

In total, 249 plasma samples (1-13 per patient) were available from 68 NSCLC patients. The T790M and L858R or exon 19 deletion were found in the ctDNA of 49 and 56% patients, respectively. The median (range) concentration in these samples were 7.3 (5.1-3688.7), 11.7 (5.1-12,393.3) and 27.9 (5.9-2896.7) copies/mL, respectively. Using local polynomial regression, the number of copies of EGFR mutations per mL increased several months prior to progression on standard response evaluation.

This change was more pronounced for the driver mutations than for the resistance mutations. In conclusion, quantification of EGFR mutations in plasma ctDNA was predictive of treatment outcomes in NSCLC patients. In particular, an increase in driver mutation copy number could predict disease progression.

This change was more pronounced for the driver mutations than for the resistance mutations. In conclusion, quantification of EGFR mutations in plasma ctDNA was predictive of treatment outcomes in NSCLC patients. In particular, an increase in driver mutation copy number could predict disease progression.Changing to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved phosphorus homeostasis, rickets, lower-extremity deformities, mobility, and growth versus continuing oral phosphate and active vitamin D (conventional therapy) in a randomized, open-label, phase 3 trial involving children aged 1-12 years with X-linked hypophosphatemia. Patients were randomized (11) to subcutaneous burosumab or to continue conventional therapy. We present patient-reported outcomes (PROs) from this trial for children aged ≥ 5 years at screening (n = 35), using a Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-10 Health Survey for Children. PROMIS pain interference, physical function mobility, and fatigue scores improved from baseline with burosumab at weeks 40 and 64, but changed little with continued conventional therapy. Pain interference scores differed significantly between groups at week 40 (- 5.02, 95% CI - 9.29 to - 0.75; p = 0.0212) but not at week 64. Between-group differences were not significant at either week for physical function mobility or fatigue. Reductions in PROMIS pain interference and fatigue scores from baseline were clinically meaningful with burosumab at weeks 40 and 64 but not with conventional therapy. SF-10 physical health scores (PHS-10) improved significantly with burosumab at week 40 (least-squares mean [standard error] + 5.98 [1.79]; p = 0.0008) and week 64 (+ 5.93 [1.88]; p = 0.0016) but not with conventional therapy (between-treatment differences were nonsignificant). In conclusion, changing to burosumab improved PRO measures, with statistically significant differences in PROMIS pain interference at week 40 versus continuing with conventional therapy and in PHS-10 at weeks 40 and 64 versus baseline.Trial registration ClinicalTrials.gov NCT02915705.

First time analysis of the epidemiology, management and outcomes of patients with splenic injuries in Switzerland. This study aims to assess the effect of hospital treatment volume on successful non-operative management (NOM) in splenic injuries.

A multicentric registry-based study including all patients with splenic injuries entered into the Swiss Trauma Registry from 2015 to 2018 was conducted. Patients were stratified according to the hospitals treatment volume of splenic injuries. Primary outcome was the rate of successful NOM.

During the 4-year study period, 652 patients with splenic injury were included in the study. Median age of the study population was 42 (IQR 27-59) years, and median ISS was 26 (20-34). The overall rate of successful NOM was 86.5%. Median HLOS was 13 (8-21) days. In-hospital mortality was 7.2% (n = 47). The mean number of patients with splenic injuries per center and year was 14. Five out of 12 Level I trauma centers treating more patients than the mean (≥ 15/year) were defined as high-volume centers. Multivariable analysis adjusting for differences in baseline and injury characteristics revealed treatment in a high-volume center as an independent predictor for successful NOM (OR 2.15, 95% CI 1.28-3.60, p = 0.004) and shorter HLOS (RC - 2.39, 95% CI - 4.91/- 0.48, p = 0.017), however, not for reduced in-hospital mortality (OR 0.92, 95% CI 0.39-2.18, p = 0.845).

Higher hospital treatment volume was associated with a higher rate of NOM and shorter HLOS, but not lower mortality. These results constitute the basis for further quality improvement in the care of splenic injury patients within the trauma system in Switzerland.

Higher hospital treatment volume was associated with a higher rate of NOM and shorter HLOS, but not lower mortality. These results constitute the basis for further quality improvement in the care of splenic injury patients within the trauma system in Switzerland.

There are few studies on incidence rates, treatment and outcomes for peri-implant femoral fractures (PIFF) in the proximity of osteosynthesis. The purpose of this study was to investigate the incidence of PIFF following osteosynthesis of proximal femoral fractures.

This retrospective cohort study comprised a consecutive series of hip fracture patients aged 50years or older and operated with osteosynthesis between 2003 and 2015. Patients were followed-up until 2018, removal of implants or death, for a mean of 4years (range 0-15). Data on age, sex, housing, hip complications, and reoperations were recorded. The risk of PIFFs was assessed using Cox proportional hazards regression analysis. In patients with two fractures during the study period, only the first fracture was included.

A total of 1965 osteosynthesis procedures were performed, of which 382 were cephalomedullary nails (CMN), 933 sliding hip devices (SHD) and 650 pins. Mean age was 80years (range 50-104), 65% of patients were women. A total of 41sty for femoral neck fracture.

To evaluate the effectiveness of routine repeat computed tomography (CT) for nonoperative management (NOM) of adults with blunt liver and/or spleen injury.

We conducted a systematic review of randomized and non-randomized controlled trials (RCTs), quasi-experimental and observational studies of repeat CT in adult patients with blunt abdominal injury. We searched Medline, Embase, Web of Science, and Cochrane Central from their inception to October 2020 using Cochrane guidelines. Primary outcomes were change in clinical management (e.g., emergency surgery, embolization, blood transfusion, clinical surveillance), mortality, and complications. Secondary outcomes were hospital readmission and length of stay.

Search results yielded 1611 studies of which 28 studies including 2646 patients met our inclusion criteria. The majority reported on liver (n = 9) or spleen injury (n = 16) or both (n = 3). No RCTs were identified. Meta-analyses were not possible because no study performed direct comparisons of study outcomes across intervention groups. Only seven of the twenty-eight studies reported whether repeat CT was routine or prompted by clinical indication. In these 7 studies, among the 254 repeat CT performed, 188 (74%) were routine and 8 (4%) of these led to a change in clinical management. Of the 66 (26%)repeated CT prompted by clinical indication, 31 (47%) led to a change in management. We found no data allowing comparison of any other outcomes across intervention groups.

Routine repeat CT without clinical indication is not usefulin the management of patients with liver and/or spleen injury. However, effect estimates were imprecise and included studies were of low methodological quality. Given the risks of unnecessary radiation and costs associated with repeat CT, future research should aim to estimate the frequency of such practices and assess practice variation.

Systematic reviews and meta-analyses, Level II.

Systematic reviews and meta-analyses, Level II.

To identify the risk factors of calcineurin inhibitor (CNI)-associated new-onset diabetes mellitus (NODM) in chronic kidney disease (CKD) treatment.

We retrospectively screened patients treated with CNIs in our hospital from January 2015 to December 2018. The inclusion criteria were as follows a clear diagnosis of CKD and patients receiving CNI treatment. We compared patients with and without CNI-associated NODM.

Ninety-eight of the 336 assessed patients met the inclusion criteria, 15 (15.3% [15/98]) of whom developed CNI-associated NODM. Multiple logistic regression analysis revealed that baseline glycosylated hemoglobin (OR=4.141; 1.024-16.743; p=0.046) and CNI trough concentration (1 year) (OR=1.028; 1.009-1.047, p=0.004) were independent risk factors for NODM. In contrast, glucocorticoid type (prednisone) (OR=0.075; 0.011-0.526, p=0.009) was identified as an independent protective factor for NODM. Using a receiver operating characteristic curve, a cutoff cyclosporin A trough concentration of 102.1 ng/mL was identified as a predictive factor of NODM. Univariate logistic regression showed that the incidence of diabetes was significantly higher in patients with baseline glycosylated hemoglobin in non-diabetic range but higher than 5.65% (10.2% vs. 29.2%, p=0.038). One NODM patient (6.7% [1/15]) recovered at 12.7 months after the onset of diabetes mellitus.

We recommend that more attention be paid to patients with baseline glycosylated hemoglobin in non-diabetic range but higher than 5.65% during CKD treatment with CNIs. High trough concentrations of cyclosporin A, particularly those >102.1 ng/mL, contribute to NODM. CNI-associated NODM may be reversible in the treatment of CKD.

102.1 ng/mL, contribute to NODM. CNI-associated NODM may be reversible in the treatment of CKD.An actinomycete strain, designated YIM 98757T, was isolated from the hypersaline sediment of Aiding Lake in Xinjiang province, north-west China. The strain grew well on most media tested and no diffusible pigment was produced. The substrate mycelium was well developed and fragmented. No spores were formed. The whole-cell hydrolysates contained meso-diaminopimelic acid as the cell-wall diamino acid. Xylose, galactose, ribose were the major whole-cell sugars. The phospholipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides and an unknown phospholipid. The predominant menaquinone was MK-8(H4). The major fatty acid was iso-C160. The DNA G + C content was 69.1 mol%. Phylogenetic analysis indicated that the isolate belongs to the genus Haloechinothrix. However, it differed from its closest relative, H. alba YIM 98757 T in many phenotypic and chemotaxonomic characteristics. Moreover, the DNA-DNA and ANI relatedness values between the novel isolate and H. alba YIM 93221 T were 53.3% and 92.5%, respectively. Based on comparative analysis of polyphasic taxonomic data, strain YIM 98757 T represents a novel species of the genus Haloechinothrix, for which the name Haloechinothrix aidingensis sp. nov. is proposed. The type strain is YIM 98757T (= CGMCC 4.7627T = CCTCC AA 2020012).

To identify magnetic resonance imaging (MRI) features which aid differentiation of low-grade chondral tumours (LGCT-enchondroma and grade 1 chondrosarcoma) from high-grade chondral tumours (HGCT) in patients with enchondromatosis.

Approval from our local Research and Innovation Centre of The Institute of Orthopaedics was gained. Patients with enchondromatosis who had biopsy and/or resection of chondral lesions over a 13-year period were identified. The pre-biopsy MRI study was assessed by two experienced musculoskeletal radiologists for tumour origin (intramedullary or surface), cortical expansion, cortical destruction, bone marrow oedema, periosteal reaction, soft tissue mass and soft tissue oedema. MRI features were compared with the final histopathological diagnosis.

The study group comprised 25 males and 16 females, with a mean age of 34.9 years (range 6-81 years). Fifty-nine lesions were assessed (12 patients had > 1 tumour treated), including 43 LGCT and 16 HGCT. Significant MRI features suggesting malignant transformation to HGCT for both observers included bone oedema (p = < 0.001 and 0.002), periosteal reaction (p = 0.01) and soft tissue oedema (p = 0.001 and 0.05). Cortical destruction and soft tissue mass were predictors of HGCT in major long bones, but no significant differentiating features were identified in the hands and feet.

The presence of bone oedema, periosteal reaction and soft tissue oedema on MRI may indicate a high-grade malignant transformation of chondral tumours in patients with enchondromatosis.

The presence of bone oedema, periosteal reaction and soft tissue oedema on MRI may indicate a high-grade malignant transformation of chondral tumours in patients with enchondromatosis.The flavoenzyme D-amino acid oxidase (DAAO) is deputed to the degradation of D-enantiomers of amino acids. DAAO plays various relevant physiological roles in different organisms and tissues. Thus, it has been recently suggested that the goblet cells of the mucosal epithelia secrete into the lumen of intestine, a processed and active form of DAAO that uses the intestinal D-amino acids to generate hydrogen peroxide (H2O2), an immune messenger that helps fighting gut pathogens, and by doing so controls the homeostasis of gut microbiota. Here, we show that the DAAO form lacking the 1-16 amino acid residues (the putative secretion signal) is unstable and inactive, and that DAAO is present in the epithelial layer and the mucosa of mouse gut, where it is largely proteolyzed. In silico predicted DAAO-derived antimicrobial peptides show activity against various Gram-positive and Gram-negative bacteria but not on Lactobacilli species, which represent the commensal microbiota. Peptidomic analysis reveals the presence of such peptides in the mucosal fraction. Collectively, we identify a novel mechanism for gut microbiota selection implying DAAO-derived antimicrobial peptides which are generated by intestinal proteases and that are secreted in the gut lumen. In conclusion, we herein report an additional, ancillary role for mammalian DAAO, unrelated to its enzymatic activity.

Stigma decreases healthcare seeking and treatment adherence and increases the duration of untreated psychosis among people with first-episode psychosis (FEP). This study evaluated the efficacy of a brief video-based intervention in reducing stigma among youth toward individuals with FEP and schizophrenia. We hypothesized that the social-contact-based video intervention group would reduce stigma more than written vignette and control groups, and the vignette more than the control group.

Using Amazon Mechanical Turk, we recruited and assigned 1203 individuals aged 18-30 to either (a) video intervention, (b) written description of the same content ("vignette"), or (c) nonintervention control arm. In the 90-second video intervention, an empowered young woman with schizophrenia described her FEP and the aspects of successful coping with her everyday life difficulties, exposing the viewer to schizophrenia in the context of her personal narrative. Web-based self-report questionnaires assessed stigma domains, including social distance, stereotyping, separateness, social restriction, and perceived recovery.

A MANOVA showed a significant between-group effects for all 5 stigma-related subscales (P < .001). Post hoc pairwise tests showed significant differences between video and vignette vs control for all 5 stigma domains. Video and vignette groups differed significantly on social distance, stereotyping, and social restriction. Secondary analyses revealed gender differences across stigma domains in the video group only, with women reporting lower stigma.

A very brief social contact-based video intervention efficaciously reduced stigma toward individuals with FEP. This is the first study to demonstrate such an effect. Further research should examine its long-term sustainability.

A very brief social contact-based video intervention efficaciously reduced stigma toward individuals with FEP. This is the first study to demonstrate such an effect. Further research should examine its long-term sustainability.Recent therapeutic approaches to auditory verbal hallucinations (AVH) exploit the person-like qualities of voices. Little is known, however, about how, why, and when AVH become personified. We aimed to investigate personification in individuals' early voice-hearing experiences. We invited Early Intervention in Psychosis (EIP) service users aged 16-65 to participate in a semistructured interview on AVH phenomenology. Forty voice-hearers (M = 114.13 days in EIP) were recruited through 2 National Health Service trusts in northern England. We used content and thematic analysis to code the interviews and then statistically examined key associations with personification. Some participants had heard voices intermittently for multiple years prior to clinical involvement (M = 74.38 months), although distressing voice onset was typically more recent (median = 12 months). Participants reported a range of negative emotions (predominantly fear, 60%, 24/40, and anxiety, 62.5%, 26/40), visual hallucinations (75%, 30/40), bodily states (65%, 25/40), and "felt presences" (52.5%, 21/40) in relation to voices. Complex personification, reported by a sizeable minority (16/40, 40%), was associated with experiencing voices as conversational (odds ratio [OR] = 2.56) and companionable (OR = 3.19) but not as commanding or trauma-related. Neither age of AVH onset nor time since onset related to personification. Our findings highlight significant personification of AVH even at first clinical presentation. Personified voices appear to be distinguished less by their intrinsic properties, commanding qualities, or connection with trauma than by their affordances for conversation and companionship.The relationship between infrastructure, technology, model of care, and human resources influences patient outcomes and safety, staff productivity and satisfaction, retention of personnel, and treatment and social costs. This concept underpins the need for evidence-based design and has been widely adopted to inform hospital infrastructure planning. The aim of this review is to establish evidence-based, universally applicable key features of a burn unit that support function in a comprehensive patient-centered model of care. A literature search in medical, architectural, and engineering databases was conducted. Burn associations' guidelines and relevant articles published in English, between 1990 and 2020, were included, and the available evidence is summarized in the review. Few studies have been published on burn unit design in the past 30 years. Most of them focus on the role of design in infection control and prevention and consist primarily of descriptive or observational reports, opportunistic historical cohort studies, and reviews. The evidence available in the literature is not sufficient to create a definitive infrastructure guideline to inform burn unit design, and there are considerable difficulties in creating evidence that will be widely applicable. In the absence of a strong evidence base, consensus guidelines on burn unit infrastructure should be developed, to help healthcare providers, architects, and engineers make informed decisions, when designing new or renovated facilities.Optical films that alter light transmittance may reduce energy consumption in high-tech greenhouses, but their impact on crop physiology remains unclear. We compared the stomatal responses of Capsicum plants grown hydroponically under control glass (70% diffuse light) or the smart glass (SG) film ULR-80, which blocked >50% of short-wave radiation and ~9% of photosynthetically active radiation (PAR). SG had no significant effects on steady-state (gs) or maximal (gmax) stomatal conductance. In contrast, SG reduced stomatal pore size and sensitivity to exogenous abscisic acid (ABA), thereby increasing rates of leaf water loss, guard cell K+ and Cl- efflux, and Ca2+ influx. SG induced faster stomatal closing and opening rates on transition between low (100 µmol m-2 s-1) and high PAR (1500 µmol m-2 s-1), which compromised water use efficiency relative to control plants. The fraction of blue light (0% or 10%) did not affect gs in either treatment. Increased expression of stomatal closure and photoreceptor genes in epidermal peels of SG plants is consistent with fast stomatal responses to light changes. In conclusion, stomatal responses of Capsicum to SG were more affected by changes in light intensity than spectral quality, and re-engineering of the SG should maximize PAR transmission, and hence CO2 assimilation.Legionnaires' disease has been recognized since 1976 and Legionella pneumophila, still accounts for more than 95% of cases. Approaches in countries, including France, suggest that focusing risk reduction specifically on L. pneumophila is an effective strategy, as detecting L. pneumophila has advantages over targeting multiple species of Legionella. In terms of assays, the historically accepted plate culture method takes 10 days for confirmed Legionella spp. results, has variabilities which affect trending and comparisons, requires highly trained personnel to identify colonies on a plate in specialist laboratories and does not recover viable-but-non-culturable (VBNC) bacteria. Polymerase chain reaction is sensitive, specific and provides results in less than 24 h and determines the presence/absence of Legionella spp. and/or L. pneumophila DNA. Whilst specialist personnel and laboratories are generally required, there are now on-site PCR options but there is no agreement on comparing genomic units to colony forming units and action limits. Immunomagnetic separation assays are culture-independent, detect multiple Legionella species and results are available in 24 h, with automated processing options. Field-use lateral flow devices provide presence/absence determination of L. pneumophila serogroup 1 where sufficient cells are present, but testing potable waters is problematic. Liquid culture most probable number (MPN) assays provide confirmed L. pneumophila results in 7 days that are equivalent to or exceed plate culture, are robust and reproducible and can be performed in a variety of laboratory settings. MPN isolates can be obtained for epidemiological investigations. This accessible, non-technical review will be of particular interest to building owners, operators, risk managers and water safety groups to make informed decisions to reduce the risk of L. pneumophila.