There are no liquid oral glucocorticoids labelled for management of pruritus and clinical lesions of feline hypersensitivity dermatitis (feline HD).

First, to demonstrate that dexamethasone sodium phosphate (DexSP, DexajectSP, Henry Schein; Dublin, OH, USA; 4mg/mL), an intravenous glucocorticoid, can be absorbed by healthy cats when administered orally. Second, to demonstrate the efficacy of orally administered DexSP for reducing pruritus and clinical lesions in patients with feline HD.

Seven healthy and 12 client-owned cats with HD.

Healthy cats were administered a single dose of 0.2mg/kg DexSP p.o. and serum concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Feline HD patients were assessed with SCORing Feline Allergic Dermatitis (SCORFAD) and pruritus Visual Analog Scale (pVAS) at Visit 1 (V1) and after 20-31 days of receiving 0.2mg/kg/day DexSP p.o. (V2). Complete blood cell counts, serum chemistry profile, and urinalysis were performed in 50% of feline HD patients at both visits.

Healthy cats had detectable serum concentrations of DexSP following oral administration; concentrations ranged from 0.7 to 92.3ng/mL. Feline HD patients showed significant decreases in SCORFAD and pVAS scores from V1 to V2.

DexSP was absorbed when administered orally to healthy cats and 0.2mg/kg/day DexSP is an efficacious dose to rapidly improve the pruritus and clinical lesions associated with feline HD.

DexSP was absorbed when administered orally to healthy cats and 0.2 mg/kg/day DexSP is an efficacious dose to rapidly improve the pruritus and clinical lesions associated with feline HD.Although the long-term use of topical glucocorticoids (TGC) may induce skin atrophy including striae distensae (SD), patients with atopic dermatitis (AD) appear to have lesser degree of skin atrophy than those with psoriasis (PSO). Periostin, encoded by POSTN, is involved in tissue remodelling processes of chronic AD lesions. This study was designed to investigate the difference in the occurrence of skin atrophy in patients with AD or PSO when treated with TGC and to elucidate the association between skin atrophy and periostin. Big data analysis using Korean Health Claims Database was performed to determine the prevalence of SD in AD and PSO patients. Blood and skin eosinophils count and dermal fibrosis between AD and PSO patients were compared, and immunohistochemistry for periostin and mRNA sequencing in the dermis were performed. Animal experiments using AD and PSO murine model were conducted. Big data analysis revealed that patients with AD have significantly lesser degree of SD than patients with PSO. The ratio of the dermal fibrous tissues and eosinophil counts were significantly higher in AD patients. In AD skin, periostin was more widely distributed in the entire dermis and POSTN mRNAs were significantly upregulated. Dermal thickness and fibrosis were significantly higher in AD mice even after TGC treatment. A significant positive correlation was observed between dermal fibrosis and tissue eosinophil counts. Lesser skin atrophy in AD patients even after long-term TGC application could be resulted from skin fibrosis caused by increased tissue eosinophils and periostin deposition.There are four major classes of antifungals with the predominant mechanism of action being targeting of cell wall or cell membrane. As in other drugs, low solubility of these compounds has led to low bioavailability in target tissues. Enhanced drug dosages have effects such as toxicity, drug-drug interactions, and increased drug resistance by fungi. This article reviews the current state-of-the-art of antifungals, structure, mechanism of action, other usages, and toxic side effects. The emergence of nanoformulations to transport and uniformly release cargo at the target site is a boon in antifungal treatment. The article details research that lead to the development of nanoformulations of antifungals and potential advantages and avoidance of the lacunae characterizing conventional drugs. A range of nanoformulations based on liposomes, polymers are in various stages of research and their potential advantages have been brought out. It could be observed that under similar dosages, test models, and duration, nanoformulations provided enhanced activity, reduced toxicity, higher uptake and higher immunostimulatory effects. In most instances, the mechanism of antifungal activity of nanoformulations was similar to that of regular antifungal. There are possibilities of coupling multiple antifungals on the same nano-platform. Increased activity coupled with multiple mechanisms of action presents for nanoformulations a tremendous opportunity to overcome antifungal resistance. In the years to come, robust methods for the preparation of nanoformulations taking into account the repeatability and reproducibility in action, furthering the studies on nanoformulation toxicity and studies of human models are required before extensive use of nanoformulations as a prescribed drug.COVID-19 and climate change are both threats of immense proportions, however, the differing perception of climate change as far-off, projected and unpredictable, persists as a marked barrier to global action. COVID-19 is increasing awareness of the connection between human actions and environmental consequences. The current slowdown of fossil fuel use has given a glimpse of the quitter, cleaner and more caring world that effective climate change could also achieve. Decisions made in coming months can either „lock in” economic development patterns that will do permanent and escalating damage to the ecological systems, or, if wisely taken, can promote a healthier and greener world.

Workplace violence (WPV) includes verbal abuse, physical violence, bullying or mobbing, assault and sexual harassment. The area has been well researched in the developed and high-income countries among nurses and healthcare professionals, but in the case of the low and upper-middle-income countries, there remains a paucity of comprehensive data on the prevalence of WPV and its contributing factors.

To estimate the prevalence and determinants of WPV among nurses working in the South-East Asian Region and Western Pacific Regions.

Systematic review and Meta-analysis.

A comprehensive search was done to retrieve articles based on a PRISMA compliant protocol registered in PROSPERO CRD 42020223605. Study selection, quality assessment and data abstraction were independently done by the team members and discrepancies addressed through mutual consensus. Random-effect meta-analysis, I2statistics and subgroup analysis were done.

The review included 41studies conducted among 42,222 nurses from 13 countries. The mitment are vital for ensuring effective policies to combat WPV.

Our review highlights the emerging need to focus on the prevention of WPV among nurses working in lower, middle and upper-middle-income countries. Legislation changes and organisational commitment are vital for ensuring effective policies to combat WPV.

To describe essential aspects of care continuity from the perspectives of persons with complex care needs and their family carers.

Continuity of care is an important aspect of quality, safety and efficiency. For people with multiple chronic diseases and complex care needs, care must be experienced as connected and coherent, and consistent with medical and individual needs. The more complex the need for care, the greater the need for continuity across different competencies, services and roles.

A constructivist grounded theory approach was applied.

Sixteen patients with one or more chronic diseases needing both health care and social care, living in their private homes, and twelve family carers, were recruited. Semi-structured interviews were conducted and analysed with constructivist grounded theory. The COREQ checklist was followed.

A conceptual model of care continuity was constructed, consisting of five categories that were interconnected through the core category time and space. Patients’ and family carers’ experiences of care continuity and may guide the delivery of care to people with complex care needs.

A benefit of automatically transmitting or „wireless” CIEDs (W-CIED) is the prompt detection of device malfunction and arrhythmias. We hypothesized that the use of W-CIEDs would improve the efficiency of remote monitoring by decreasing unnecessary CIED remote transmissions because of the automatic detection of abnormalities.

To compare the frequency of patient-initiated transmissions in patients with W-CIEDs versus non-wireless CIEDs (NW-CIED) at a single pediatric and congenital heart center.

Retrospective cohort study of patients with W-CIEDs followed over a 2-year period compared to a similar cohort of patients with NW-CIED. All CIED remote transmissions during were reviewed for indication and outcome.

The W-CIED cohort had 87 patients; mean age 20 ± 13 years; NW-CIED cohort had 220 patients; mean age 22 ± (13) years. The mean number of symptomatic patient-initiated transmissions per patient was 0.93 ± 2.65 in the W-CIED cohort versus 0.39 ± 0.64 in the NW-CIED cohort (p≤.001). The mean number of asymptomatic patient-initiated transmission sent per patient in the W-CIED cohort was 1.86 ± 2.59versus 0.81 ± 1.41 in the NW-CIED cohort (p≤.0001). Type of device, age, and presence of congenital heart disease were not significantly associated with the incidence of patient-initiated remote monitoring transmissions.

The frequency of patient-initiated transmission was higher in the W-CIED cohort, contradictory to the study hypothesis. This may reflect a lack of patient understanding of the benefit or functionality of W-CIEDs and may be mitigated by education to both providers and patients.

The frequency of patient-initiated transmission was higher in the W-CIED cohort, contradictory to the study hypothesis. This may reflect a lack of patient understanding of the benefit or functionality of W-CIEDs and may be mitigated by education to both providers and patients.

Because of the heterogeneity of metastatic colorectal cancer (mCRC), a genome-wide analysis was performed to characterize the tumor immune microenvironment (TIME).

RNA-seq analysis of 62 primary CRCs without and 63 with systemic metastasis (SM- and SM+ groups) was conducted, and the data were used in a training set after adjustment by propensity score matching. Samples were further subdivided into those with hepatic metastasis (CHM subgroup), pulmonary metastasis (CPM subgroup), or concurrent CHM and CPM (concurrent group). Validation was done by quantitative reverse-transcription polymerase chain reaction using another 40 primary CRC samples.

Compared with the CHM or CPM subgroups, the concurrent group showed upregulated in inflammatory or immune processes, cytokine secretion, and myeloid leukocyte migration. Nine candidate genes were selected SM-specific IDO1, JAM3, and PDE2A; CHM- or CPM-specific BIRC7; CPM-specific HISI1H2BK, and both SM-specific and CHM- or CPM-specific EPHB6, LPL, THBD, and PPBP. In a validation set of primary CRCs, JAM3 and IDO1 (p = 0.044 and p = 0.036, respectively) were confirmed to show significant upregulation and downregulation, respectively, in the SM+ group, whereas HIST1H2BK (p = 0.017) was significantly upregulated in the CPM subgroup.

Our findings indicate that a host-suppressive TIME is established in the primary tumor of mCRC and identify immune-related site-specific markers of mCRC.

Our findings indicate that a host-suppressive TIME is established in the primary tumor of mCRC and identify immune-related site-specific markers of mCRC.Transmission electron microscopy (TEM) has greatly advanced our knowledge of hair growth and follicle morphogenesis, but complex preparations such as fixation, dehydration and embedding compromise ultrastructure. While recent developments with cryofixation have been shown to preserve the ultrastructure of biological materials close to native state, they do have limitations. This review will focus on each stage of the TEM sample preparation process and their effects on the structural integrity of follicles.TP53 mutations in acute myeloid leukemia (AML) are associated with resistance to standard treatments and dismal outcomes. The incidence and prognostic impact of the emergence of newly detectable TP53 mutations over the course of AML therapy has not been well described. We retrospectively analyzed 200 patients with newly diagnosed TP53 wild type AML who relapsed after or were refractory to frontline therapy. Twenty-nine patients (15%) developed a newly detectable TP53 mutation in the context of relapsed/refractory disease. The median variant allelic frequency (VAF) was 15% (range, 1.1%-95.6%). TP53 mutations were more common after intensive therapy versus lower-intensity therapy (23% vs. 10%, respectively; p = 0.02) and in patients who had undergone hematopoietic stem cell transplant versus those who had not (36% vs. 12%, respectively; p = 0.005). Lower TP53 VAF was associated with an increased likelihood of complete remission (CR) or CR with incomplete hematologic recovery (CRi) compared to higher TP53 VAF (CR/CRi rate of 41% for VAF less then 20% vs. 13% for VAF ≥ 20%, respectively). The median overall survival (OS) after acquisition of TP53 mutation was 4.6 months, with a 1-year OS rate of 19%. TP53 VAF at relapse was significantly associated with OS; the median OS of patients with TP53 VAF ≥ 20% was 3.5 months versus 6.1 months for those with TP53 VAF less then 20% (p less then  0.05). In summary, new TP53 mutations may be acquired throughout the course of AML therapy. Sequential monitoring for TP53 mutations is likely to be increasingly relevant in the era of emerging TP53-targeting therapies for AML.

Patients with germline/somatic BRCA1/BRCA2 mutations (g/sBRCA1/2) comprise a distinct biologic subgroup of pancreas ductal adenocarcinoma (PDAC).

Institutional databases were queried to identify patients who had PDAC with g/sBRCA1/2. Demographics, clinicopathologic details, genomic data (annotation sBRCA1/2 according to a precision oncology knowledge base for somatic mutations), zygosity, and outcomes were abstracted. Overall survival (OS) was estimated using the Kaplan-Meier method.

In total, 136 patients with g/sBRCA1/2 were identified between January 2011 and June 2020. Germline BRCA1/2 (gBRCA1/2) mutation was identified in 116 patients (85%). Oncogenic somatic BRCA1/2 (sBRCA1/2) mutation was present in 20 patients (15%). Seventy-seven patients had biallelic BRCA1/2 mutations (83%), and 16 (17%) had heterozygous mutations. Sixty-five patients with stage IV disease received frontline platinum therapy, and 52 (80%) had a partial response. The median OS for entire cohort was 27.6 months (95% CI, 24.9-34rapeutic benefit, and very durable outcomes are observed in a subset of patients who have g/sBRCA1/2 mutations with biallelic status.

g/sBRCA1/2 mutations did not appear to have different actionable utility. Platinum and PARPi therapies offer therapeutic benefit, and very durable outcomes are observed in a subset of patients who have g/sBRCA1/2 mutations with biallelic status.Central to protective humoral immunity is the activation of B cells and their terminal differentiation into antibody-secreting plasma cells. Long-lived plasma cells (LLPC) may survive for years to decades. Such long-lived plasma cells are also responsible for producing pathogenic antibodies that cause a variety of challenges such as autoimmunity, allograft rejection, and drug neutralization. Up to now, various therapeutic strategies aimed at durably eliminating pathogenic antibodies have failed, in large part due to their inability to efficiently target LLPCs. Several antibody-based therapies have recently gained regulatory approval or are in clinical phases of development for the treatment of multiple myeloma, a malignancy of plasma cells. We discuss the exciting potential of using these emerging cancer immunotherapies to solve the antibody problem.We studied the effect of peer- and self-observational feedback versus coaching feedback during technique training on performance in competitive adolescent cross-country skiers. Fifty-four skiers (14.3 ± 0.6 years) were divided into a control group and three intervention groups (dyad practice, video, or coaching feedback), which practiced in the asymmetrical uphill sub-technique G2 on one side (non-dominant side), but not the other (dominant side) for 6 × 30 min over a 5 weeks period, on roller skis outdoors. High-speed performance and skiing economy were assessed on a roller ski treadmill before and after the intervention, and a questionnaire was answered post-intervention. The video feedback (p = .025, d = .65) and coaching feedback (p = .007, d = .89) groups improved high-speed performance during the intervention and an ANCOVA showed a tendency for different change scores between interventions (F3,49 = 2.5, p = .068, η p 2 = .134), with a difference between the coaching feedback and dyad practice (p = .05). No change was seen in skiing economy in any group. Coaching feedback ranked higher on enjoyment compared with dyad practice (p less then .001) and led to higher self-perception of improved technique compared with the control group (p = .038). Overall, feedback from a competent coach seems better than observation for improving performance in young athletes, although self-observation through video with attentional cues seems a promising tool for increasing individual feedback when coaching large groups.

The aim of this retrospective study was to compare the efficacy and safety of different phototherapeutic modalities in the treatment of cutaneous lichen planus (LP).

We retrospectively analyzed the chart data of 53 patients with generalized LP who had been subjected to narrowband UVB (NB-UVB) or photochemotherapy (PUVA) between January 1997 and April 2020. Of these, 30 patients had received NB-UVB, 18 patients oral PUVA and 5 patients bath PUVA.

Fifty patients completed a full treatment course. The percentage of patients with a complete (>90% clearing) or good (51%-90% clearing) response was similar for NB-UVB versus PUVA (86.2% vs. 90.5%; P=1.00). The number of exposures required for obtaining a complete or good response was also comparable for both treatment groups (NB-UVB 28.9±12.3 vs. PUVA 25.4±10.1; P=.209). Adverse events, in particular gastrointestinal upsets, were recorded in 26.1% of patients treated with oral PUVA while none were observed with NB-UVB.

The therapeutic outcome and the number of treatments required for achieving a complete or good response were comparable for NB-UVB and PUVA; however, PUVA therapy was associated with a substantially higher rate of moderate adverse events.

The therapeutic outcome and the number of treatments required for achieving a complete or good response were comparable for NB-UVB and PUVA; however, PUVA therapy was associated with a substantially higher rate of moderate adverse events.We aimed to investigate the interventions of remdesivir in both diabetic and nondiabetic individuals who were suffering from a severe infection of novel coronavirus disease (COVID-19). In this study, we aimed to explore the relationship between therapeutic effectiveness of remdesivir and complications of diabetes mellitus by observing the recovery period among diabetic and nondiabetic patients associated with COVID-19 infection. A total of 850 COVID-19 patients were recruited for this study, out of which 48% were diabetic and 52% were nondiabetics. The results of this study indicated that nondiabetic individuals administered with remdesivir recovered from COVID-19 within 10 days showing a 95% confidence interval (p  less then  0.01), while the diabetic individuals recovered in 15 days. Nondiabetic patients administered with remdesivir exhibited higher chances of clinical improvement at 15th day than those who were associated with diabetes. Remdesivir administration improved the levels of various biochemical parameters, such as C-reactive protein, lactate dehydrogenase, d-Dimer, and ferritin both in diabetic and nondiabetic patients. However, a significant improvement (p  less then  0.01) was seen in the level of biochemical parameters among nondiabetic patients as compared to that of diabetic patients administered with remdesivir treatment. In the end, it was concluded that remdesivir could be considered as a possible therapeutic agent in the treatment of COVID-19 both in diabetic and nondiabetic situations. However, diabetic patients showed a delayed recovery as compared with that of nondiabetic patients, in which the recovery rate was high.

Atypical intraepidermal melanocytic proliferations (AIMP) is a descriptive term sometimes applied to biopsies that do not fulfill diagnostic criteria of melanoma. They are common on sun-damaged skin, but their definition and management are controversial.

To describe dermoscopic (DS), reflectance confocal microscopic (RCM) and histopathological features of AIMP and identify features associated with subsequent melanoma insitu (MIS).

A retrospective analysis of AIMP lesions correlated with patient outcome at two melanoma tertiary centers between 2005 and 2015.

Thirty-four patients were included. Nine (26%) patients had MIS in subsequent biopsies. Predictors of later MIS were target-like pattern (OR12.0 [CI 1.23, 117.41]; P=0.032) and high-density vascular network (OR12 [CI 1.23-117.41], P 0.032) on DS, and presence of dendritic cells touching each other (OR9.1 [CI 1.54, 54.59], P=0.014) on RCM. Clinical predictors of worse outcome included a previous history of MIS at the same site. Radiotherapy for AIMP had a high failure rate (all patients presented with recurrent disease, three as AIMP and two as MIS).

Considering that most cases in this series received non-surgical treatment at baseline, we recommend close monitoring for lesions with target-like pattern and density vascular network on DS and treatment for lesions with progression of atypia and/or with „confluent” dendritic cells on RCM. Although the number of patients in this series is very low, early surgery is recommended for MIS cases that recur as AIMP.

Considering that most cases in this series received non-surgical treatment at baseline, we recommend close monitoring for lesions with target-like pattern and density vascular network on DS and treatment for lesions with progression of atypia and/or with „confluent” dendritic cells on RCM. Although the number of patients in this series is very low, early surgery is recommended for MIS cases that recur as AIMP.

Young adult (YA) cancer survivors are at risk for financial toxicity during and after cancer treatment. Financial toxicity has been associated with medical-related cost-coping behaviors such as skipping or delaying treatment. The coronavirus disease 2019 (COVID-19) pandemic has resulted in dire economic consequences that may worsen financial hardship among young survivors.

This was a cross-sectional survey; data collection occurred online. A convenience sample was recruited through YA cancer advocacy groups and social media. Negative economic events associated with the COVID-19 pandemic (eg, income loss, increased debt, and decreased job security) and medical-related cost-coping were documented. A validated measure assessed cancer-related financial toxicity.

Participants (N = 212) had a mean age of 35.3 years at survey completion and a mean age of 27.4 years at diagnosis. Financial toxicity (mean, 14.0; SD, 9.33) was high. Two-thirds of the sample experienced at least 1 negative economic event during COeeds of YA survivors after the global pandemic.Coral bleaching has impacted reefs worldwide and the predictions of near-annual bleaching from over two decades ago have now been realized. While technology currently provides the means to predict large-scale bleaching, predicting reef-scale and within-reef patterns in real-time for all reef users is limited. In 2020, heat stress across the Great Barrier Reef underpinned the region’s third bleaching event in 5 years. Here we review the heterogeneous emergence of bleaching across Heron Island reef habitats and discuss the oceanographic drivers that underpinned variable bleaching emergence. We do so as a case study to highlight how reef end-user groups who engage with coral reefs in different ways require targeted guidance for how, and when, to alter their use of coral reefs in response to bleaching events. Our case study of coral bleaching emergence demonstrates how within-reef scale nowcasting of coral bleaching could aid the development of accessible and equitable bleaching response strategies on coral reefs. Also see the video abstract here https//youtu.be/N9Tgb8N-vN0.Proper regulation of B-cell function is essential for effective humoral immunity and maintenance of immune tolerance. Here, we found that FBW7 (F-box/WD40 repeat-containing protein 7) is highly expressed in germinal centre B and B1 cells, and confirmed that it has an intrinsic role in maintaining homeostasis of mature B cells and B-1 cells. FBW7 deletion led to an impairment of antibody response, and although germinal centre formation was not affected, antibody class-switch recombination and affinity maturation processes were defective. Likewise, memory immune response was severely impaired. Moreover, FBW7 ablation ameliorated the pathogenesis of an autoimmune disease model, collagen-induced arthritis, by reducing the production of anti-collagen II autoantibodies. Taken together, these data suggest that FBW7 may be an attractive target for developing new therapeutics for the treatment of autoimmune diseases.The continuous improvement of life expectancy of patients with chronic lymphocytic leukemia (CLL) has resulted in increased risk of second primary malignancy that potentially may affect survival and quality of life of CLL patients. We performed a systematic review to assess the risk and the clinical-pathological features and prognosis of cutaneous squamous cell carcinoma (cSCC) in patients with CLL. We searched PubMed, Embase, and Cochrane Central Register of Control Trials databases for articles published from database inception to December 31, 2019. English-language studies reporting original data on patients with a specific diagnosis of CLL and cSCC were included. Data were extracted using a standardized extraction form, and any discordance was resolved by consensus. Descriptive data were generated by pooling patients from eligible studies. Of the 4588 non-duplicate records identified, 55 articles met our inclusion criteria. These studies reported that CLL patients have a 3.2% prevalence of cSCC, with an 11.5% cSCC-related lethality and an overall risk of metastasis of 5.7% (7.3% for regional lymph node involvement and 3.8% for distant metastasis). The quality of evidence was limited by the high heterogeneity in the design, populations, and objectives of the included studies. This systematic review suggests that cSCC in CLL patients tends to behave less aggressively compared with the solid organ transplant recipients but has a higher morbidity and mortality than in the general population. Future prospective studies are needed to increase the quality of evidence and to determine the best treatment modalities and screening intervals for these patients.

We evaluated the changes in natural killer cell activity (NKA) during the entire treatment period of patients with resectable biliopancreatic cancers and investigated the predictors of the failure of recovery of NKA after surgery.

A total of 202 patients who underwent curative resection for biliopancreatic cancer were enrolled in the study. NKA levels were measured six times during the treatment period. We investigated whether there was any difference in postoperative NKA recovery according to the period-by-time NKA value.

NKA decreased after surgery (mean, 40 pg/ml) compared to the NKA value at admission (200.2 pg/ml), then began to increase from 3 weeks after surgery (139.7 pg/ml) and rose to normal NKA levels at 5 weeks (217.1 pg/ml). The pattern of NKA changes was distinct according to the NKA values at admission. In multivariate analysis, NKA values of less than 250 pg/ml at admission (odds ratio = 5.898, p = 0.044) were a predictor of NKA recovery failure 5 weeks after surgery.

NKA rapidly decreased after curative surgery for biliopancreatic cancer and recovered to normal levels about 5 weeks later. Clinicians should be aware and cautious that patients with low NKA at admission may fail to recover NKA postoperatively.

NKA rapidly decreased after curative surgery for biliopancreatic cancer and recovered to normal levels about 5 weeks later. Clinicians should be aware and cautious that patients with low NKA at admission may fail to recover NKA postoperatively.

Neoplasms originating from the „small bones of the lower limb and the overlapping joints” are rare but portend a serious prognosis. Current study utilizes a population-based registry in the United States to characterize the malignancies of the foot.

National Cancer Institute’s Surveillance, Epidemiology and End Result database from 1975 to 2017 was queried to report incidence and survival data in 514 patients in the Uited States. Kaplan-Meier and Cox Regression were used to determine the prognostic factors affecting survival. Chi square test was used to assess the correlation.

Hematological malignancies constituted 14.8% of the entire cohort. Incidence of the foot neoplasms was 0.024 per 100 000 persons in 2017 and has not significantly changed since 1975 (p > 0.05). Disease-specific-5-year survival for the entire cohort was 73%. On multivariate analysis younger age groups, „localized” stage and extent of surgical resection were predictors of improved outcomes. A significant correlation was found between amputation with male sex and Hispanic ethnicity.

The current study analyzes data from population-based registry reporting incidence and survival data for patients with neoplasms of the foot. Independent prognostic factors include age, stage and extent of surgical resection. Amputation was found to be associated with male sex and Hispanic ethnicity.

The current study analyzes data from population-based registry reporting incidence and survival data for patients with neoplasms of the foot. Independent prognostic factors include age, stage and extent of surgical resection. Amputation was found to be associated with male sex and Hispanic ethnicity.

To evaluate the impact of the presence and treatment of periodontal disease (PD) and apical periodontitis (AP) on the aorta and liver of obese and non-obese rats.

One hundred and forty Wistar rats were divided into two groups, according to the diet administered normal diet (-n), without obesity; and cafeteria diet (-c), with induced obesity. These groups were divided into seven subgroups according to the specific experimental protocols naïve control (NC); AP; AP with treatment (APt); PD; PE with treatment (PDt); AP and PD (APPD); and AP and PD with treatment (APPDt). AP and PD lesions were induced for four weeks. Four weeks after treatments, the animals were euthanatized, and the aorta and liver were dissected for histological evaluation. For the comparison of the thickness of the aorta between groups, the Kruskal-Wallis test was used, followed by the Mann-Whitney test. For the analysis of other variables related to the aorta and liver outcomes, logistic regression was carried out.

Both PD and AP were aic arch of obese and non-obese rats were observed in the presence of periodontal disease and apical periodontitis. The combination of PD and AP increased the aorta thickness in obese rats. A reduction of vascular endothelial lesions was observed with the treatments of PD and AP.This case study about an infant with epidermolysis bullosa and his fourteen-year-old mother involves pediatric genomic testing and concerns about the adolescent parent’s decision-making capacity. Four commentaries explore ethics issues in the case, including the following challenges The current ethics guidelines regarding informed decision-making for genomic testing and return of results have been relatively silent on how to involve parents who are minors in decision-making on behalf of their children. This lack of guidance can be particularly difficult for physicians when genetic test results revealing consanguinity raise concerns about sexual abuse of a minor, provoking questions about mandatory reporting requirements. Finally, medical teams may find themselves having to evaluate an adolescent parent’s capacity in making medical decisions for her child while questioning the role and relationship of her support person.The regulatory network of R2R3 MYB transcription factors in anthocyanin biosynthesis is not fully understood in blue-coloured berries containing delphinidin compounds. We used blue berries of bilberry (Vaccinium myrtillus) to comprehensively characterise flavonoid-regulating R2R3 MYBs, which revealed a new type of co-regulation in anthocyanin biosynthesis between members of MYBA-, MYBPA1- and MYBPA2-subgroups. VmMYBA1, VmMYBPA1.1 and VmMYBPA2.2 expression was elevated at berry ripening and by abscisic acid treatment. Additionally, VmMYBA1 and VmMYBPA1.1 expression was strongly downregulated in a white berry mutant. Complementation and transient overexpression assays confirmed VmMYBA1 and VmMYBA2 to induce anthocyanin accumulation. Promoter activation assays showed that VmMYBA1, VmMYBPA1.1 and VmMYBPA2.2 had similar activity towards dihydroflavonol 4-reductase (DFR) and anthocyanidin synthase (ANS), but differential regulation activity for UDP-glucose flavonoid 3-O-glucosyltransferase (UFGT) and flavonoid 3’5′-hydroxylase (F3’5’H) promoters. Silencing of VmMYBPA1.1 in berries led to the downregulation of key anthocyanin and delphinidin biosynthesis genes. Functional analyses of other MYBPA regulators, and a member of novel MYBPA3 subgroup, associated them with proanthocyanidin biosynthesis and F3’5’H expression. The existence of 18 flavonoid-regulating MYBs indicated gene duplication, which may have enabled functional diversification among MYBA, MYBPA1 and MYBPA2 subgroups. Our results provide new insights into the intricate regulation of the complex anthocyanin profile found in blue-coloured berries involving regulation of both cyanidin and delphinidin branches.

The results of total neoadjuvant therapy (TNT) for locally advanced rectal cancers (LARC) cannot be extrapolated to signet-ring cell cancers (SRCC) that have an extremely aggressive biology.

A retrospective study comparing long course chemoradiation (CTRT) against short course radiation (SCRT) and 12 weeks of chemotherapy for high-risk LARC. Primary endpoints were treatment failure and disease-free survival (DFS) RESULTS CTRT was given to 74 (59.7%) and SCRT/Chemotherapy to 50 patients (40.3%). Additional chemotherapy was required in 54.1% and 28%, respectively. Except for nodal staging, no other MRI parameter down-staged. Treatment failures were seen in 33.9% and 25.8% had progression. The peritoneum was the commonest site of progression (59.4%). Of the patients that were surgically explored, 63.7% had R0 resections and pathological complete response was seen in 9.7%. At a median follow-up of 35 months, 56.5% had DFS events with a 3-year DFS of 39.5%. Recurrences were noted in 45.1% after curative resections and the 3-year OS/DFS of these patients were 67.2%/56.4%. On multivariate regression, the type of preoperative therapy did not influence treatment failures or DFS.

SRCC is a very aggressive disease and none of the treatment strategies could show superiority over the other with very high peritoneal progression rates and relapses.

SRCC is a very aggressive disease and none of the treatment strategies could show superiority over the other with very high peritoneal progression rates and relapses.As the cosmeceutical market for nail products is growing, there is an emerging need for dermatologists to provide patients with evidence-based information regarding over-the-counter products and supplements for nail growth. By law, there is no required efficacy and safety assessment by the Food and Drug Administration prior to these products being made available to consumers. This carries financial and health consequences for patients seeking affordable and effective over-the-counter products to improve their nail conditions. In this comprehensive review, we discuss available oral nail growth products, their mechanisms of action, and side effects.

Oncology patients and physicians value empathy because of its association with improved health outcomes. Common measures of empathy lack consistency and were developed without direct input from patients. Because of their intense engagement with health care systems, oncology patients may have unique perspectives on what behaviors signal empathy in a clinical setting.

As part of a cross-sectional study of patient perspectives on clinician empathy at an academic cancer center in the northeastern United States, the authors solicited up to 10 free-text responses to an open-ended question about what clinician behaviors define empathy.

The authors categorized open-ended responses from 89 oncology patients into 5 categories representing 14 themes. These categories were relationship sensitivity, focus on the whole person, communication, clinician attributes, and institutional resources and care processes. Frequently represented themes, including listening, understanding, and attention to emotions and what matterhaviors cited by patients as empathic. These results can inform efforts to refine quality measures of empathy-associated behaviors in clinical practice. Cancer centers can use skills training to improve elements of communication.

Adolescent and young adult (AYA) patients with cancer have not seen the same improvements in survival as younger (pediatric) patients and older patients (adults 40 years old or older). This may be related to their lower participation in clinical trials.

This study examined AYA patient accrual to SWOG Cancer Research Network phase 1 to 3 clinical treatment trials for 29 cancers over 25 years (January 1996 to December 2020). Trial enrollments for AYA patients (15-39 years old) were compared with trial enrollments for older patients (40 years old or older) in SWOG and with US AYA cancer population rates derived from US Census and National Cancer Institute/Surveillance, Epidemiology, and End Results data.

In total, 84,219 patients were enrolled in SWOG treatment trials, including 7109 AYA patients (8.4%); in contrast, AYAs constituted 3.8% of the US cancer population. By histology, the highest proportions of AYA patients were in trials for Hodgkin disease (825 of 1220; 67.6%) and acute lymphocytic leukemia AYAs; this was twice the corresponding rate of 3.8% in the US cancer population. AYA patients were also more racially/ethnically diverse than older trial patients, although they were less racially/ethnically diverse than the US AYA cancer population.

Parental severe mental illness (SMI) increases the lifetime risk of mental and pediatric disorders in the offspring but little is known about specific disorders during early childhood. The primary aim was to investigate the incidence of mental and pediatric disorders among children 0-6years old exposed to parental SMI, and secondarily to investigate the distribution of disorders on specific child age.

A nationwide, register-based cohort study of 1,477,185 children born in Denmark between 1994.01.01 and 2016.12.31. Incidence rate ratios were calculated using Poisson regression analysis for any and specific mental and pediatric disorders.

IRR for any psychiatric disorder was elevated by a factor 2-5 among SMI offspring. Maternal schizophrenia resulted in the highest IRR = 5.23 (4.80-5.69) of any child psychiatric disorder. The risk of anxiety/OCD and attachment disorder among offspring exposed to parental, and in particular maternal, SMI was markedly raised with IRRs for anxiety/OCD between 7.59 and 17.02vention to promote mental and pediatric health among SMI offspring.A 47-year-old man with chronic plaque psoriasis and type II diabetes mellitus on ustekinumab 45mg 12 weekly injections, his first biologic therapy, was switched to adalimumab 40mg alternate weeks (10/02/2020) when his Psoriasis Area and Severity Index (PASI) was 11.4 due to loss of effectiveness. Due to the COVID-19 outbreak, the U.K Prime Minister advised clinically vulnerable people, including people on immunosuppressive medication with comorbidities including diabetes, to stay home avoiding face-to-face contact (23/03/2020). We performed a Critically Appraised Topic review to understand whether it was possible to remotely assess his response to adalimumab with AI assistance.This study aims to calculate the dose delivered to the upstream surface of a biocompatible flexible absorber covering lead for electron beam treatment of skin and subcutaneous tumour lesions for head and neck. Silicone (Ecoflex™ 00-30, Smooth-On, Easton, PA, USA) was used to cover the lead to absorb backscattered electrons from lead. A 3D printer (Zortrax M300, Zortrax, Olsztyn, Poland) was used to fabricate the lead shield. Analytic calculation, simplified Monte Carlo (MC) simulation, and detailed MC simulation which includes a modeling of metal-oxide-semiconductor field-effect transistor (MOSFET) detector were performed to determine the electron backscatter factor (EBF) for 6 MeV and 9 MeV electron beams of a Varian iX Silhouette. MCNP6.2 was used to calculate the EBF and corresponding measurements were carried out by using MOSFET detectors. The EBF was experimentally measured by the ratio of dose at the upstream surface of the silicone to the same point without the presence of the lead shield. The results derived by all four methods agreed within 2.8% for 6 MeV and 3.4% for 9 MeV beams. In detailed MC simulations, for 6 MeV, dose to the surface of 7-mm-thick absorber was 103.7 [Formula see text] 1.9% compared to dose maximum (Dmax) without lead. For 9 MeV, the dose to the surface of the 10-mm-thick absorber was 104.1 [Formula see text] 2.1% compared to Dmax without lead. The simplified MC simulation was recommended for practical treatment planning due to its acceptable calculation accuracy and efficiency. The simplified MC simulation was completed within 20 min using parallel processing with 80 CPUs, while the detailed MC simulation required 40 h to be done. In this study, we outline the procedures to use the lead shield covered by silicone in clinical practice from fabrication to dose calculation.

To assess and compare teaching of paediatric dentistry in the undergraduate curriculum among dental schools in the Arabian region.

A 28-item online cross-sectional questionnaire survey was conducted of undergraduate dental programme directors in the Arab region. The survey included questions related to the programme’s content, method of instruction on specific paediatric dentistry topics as well as the director’s opinion on the level of training obtained by the undergraduate students at the end of the programme.

The final sample included 31 dental schools representing undergraduate programmes in ten Arabian countries (60.8% response rate). All programmes provided theoretical and practical education on communicative behaviour management techniques and caries prevention. Pulpectomy and formocresol pulpotomy were taught in the form of theoretical and practical education in 87.1% and 80.6% of the programmes, respectively. The method of education on common orthodontic topics was mainly theoretical with the ea framework for future paediatric dentistry curriculum development and/or improvement in the Arabian region.

A multi-level county-wide campaign to reduce sugary drink consumption was associated with significant decreases in retail sales of soda and fruit drinks. The aim of the current study was to examine changes inadolescent beverage consumption during the campaign by race/ethnicity and neighborhood food environment.

Beverage consumption among adolescents was evaluated at four time points in a repeated cross-sectional survey of a racially and ethnically diverse sample of sixth graders (N = 13,129) from public middle schools in the county. Each school’s surrounding attendance zone (i.e., neighborhoods where students live) was characterized as providing high or low exposure to unhealthy food retail (e.g., convenience stores, fast-food restaurants). Logistic and multiple linear regression models were used to evaluate changes in beverage consumption over time by student race/ethnicity and high versus low unhealthy food exposure.

Over the 5 years, there were significant declines in the overall share of students who reported daily sugary drink consumption (49.4 to 36.9%) and their reported daily calories from these products (220 to 158 calories). However, disparities were observed, with higher levels of consumption among Black and Hispanic youth and among youth living in neighborhoods with more unhealthy food retail. Notably, Black students living in healthier neighborhood food environments reported significant decreases in daily consumption and calories after 5 years, while Black students living in neighborhoods with more convenience stores and fast-food outlets did not.

These findings suggest that both race/ethnicity and neighborhood food environments are important considerations when designing interventions to reduce sugary drink consumption among adolescents.

These findings suggest that both race/ethnicity and neighborhood food environments are important considerations when designing interventions to reduce sugary drink consumption among adolescents.

Nationwide, as of 20 June 2021, COVID-19 has claimed more than 599,000 lives and infected nearly 33 million people. Studies have shown that COVID-19 disproportionately affects some racial and ethnic minority groups. This study examined whether certain racial and ethnic groups were overrepresented in occupations with potentially high COVID-19 exposure risks, relative to their share in the total workforce. The study incorporates white collar workers, who to date have not gotten as much attention in terms of workers safety.

Using the March and April 2020 Current Population Survey and O*Net data, this study examined whether certain racial and ethnic groups were overrepresented in occupations with potentially high risk of exposure to COVID-19 (exposure to disease and infection at work, inability to maintain physical distancing at work, and inability to work from home) relative to their share in the total workforce.

The results showed that Black workers were overrepresented in occupations with high potential o reduce not only the spread of COVID-19 and infectious diseases but also their disproportionately high impact in certain minority racial and ethnic groups.

That thyroid hormones exert pleiotropic effects and have a contributory role in triggering seizures in patients with traumatic brain injury (TBI) can be hypothesized. We aimed at investigating thyroid function tests as prognostic factors of the development of seizures and of functional outcome in TBI.

This retrospective study enrolled 243 adult patients with a diagnosis of mild-to-severe TBI, consecutively admitted to our rehabilitation unit for a 6-month neurorehabilitation program. Data on occurrence of seizures, brain imaging, injury characteristics, associated neurosurgical procedures, neurologic and functional assessments, and death during hospitalization were collected at baseline, during the workup and on discharge. Thyroid function tests (serum TSH, fT4, and fT3 levels) were performed upon admission to neurorehabilitation.

Serum fT3 levels were positively associated with an increased risk of late post-traumatic seizures(LPTS) in post-TBI patients independent of age, sex and TBI severity (OR = 1.85, CI 95% 1.22-2.61, p < 0.01). Measured at admission, fT3 values higher than 2.76pg/mL discriminated patients with late post-traumatic seizures from those without, with a sensitivity of 74.2% and a specificity of 60.9%. Independently from the presence of post-traumatic epilepsy and TBI severity, increasing TSH levels and decreasing fT3 levels were associated with worse neurological and functional outcome, as well as with higher risk of mortality within 6months from the TBI event.

Serum fT3 levels assessed in the subacute phase post-TBI are associated with neurological and functional outcome as well as with the risk of seizure occurrence. Further studies are needed to investigate the mechanisms underlying these associations.

Serum fT3 levels assessed in the subacute phase post-TBI are associated with neurological and functional outcome as well as with the risk of seizure occurrence. Further studies are needed to investigate the mechanisms underlying these associations.

Infliximab, an anti-tumour necrosis factor (TNF)-α monoclonal antibody, has been approved in chronic inflammatory disease, including rheumatoid arthritis, Crohn’s disease and ankylosing spondylitis. This study aimed to investigate and characterise target-mediated drug disposition of infliximab and antigen mass turnover during infliximab treatment.

In this retrospective cohort of 186 patients treated with infliximab for rheumatoid arthritis, Crohn’s disease or ankylosing spondylitis, trough infliximab concentrations were determined from samples collected between weeks 0 and 22 after treatment initiation. Target-mediated pharmacokinetics of infliximab was described using target-mediated drug disposition modelling. Target-mediated elimination parameters were determined for rheumatoid arthritis and Crohn’s disease, assuming ankylosing spondylitis with no target-mediated elimination.

The quasi-equilibrium approximation of a target-mediated drug disposition model allowed a satisfactory description of inflixim study is the first to quantify the influence of target antigen dynamics on infliximab pharmacokinetics. Target-mediated elimination of infliximab may be complex, involving a multi-scale turnover of TNF-α, especially in patients with Crohn’s disease. Additional clinical studies are warranted to further evaluate and fine-tune dosing approaches to ensure sustained TNF-α inhibition.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide. Despite recent advances, more effective therapeutic options for patients with advanced HCC are still required. The aim of this Phase 2, multicenter, multinational, randomized, double-blind, placebo-controlled study (NCT02528643) was to investigate the potential benefit of enzalutamide in the treatment of patients with advanced HCC.

Patients aged ≥ 18 years diagnosed with advanced HCC (Barcelona Clinic Liver Cancer stage B or C and Child-Pugh class A at screening who had progressed on, or were intolerant to, sorafenib or other anti-vascular endothelial growth factor therapies) were randomized 21 to receive either enzalutamide 160mg daily or placebo. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and safety.

In total, 165 patients were randomized to enzalutamide (n = 110) or placebo (n = 55). The hazard ratio (HR) (95% confidence interval [CI]) for OS was 1.