Search

Background: The aim of this study is to evaluate the extent and associations with patient-reported disruptions to cancer treatment and cancer-related care during the COVID-19 pandemic utilizing nationally representative data. Methods: This analysis uses data from the 2020 National Health Interview Survey (NHIS), an annual, cross-sectional survey of US adults. Adults (age >18) who reported requiring current cancer treatment or other cancer-related medical care in the second half of 2020 were included. Estimated proportions of patients with self-reported changes, delays, or cancelations to cancer treatment or other cancer care due to the COVID-19 pandemic were calculated using sampling weights and associations with sociodemographic and other health-related variables were analyzed. Results: In total, 574 (sample-weighted estimate of 2,867,326) adults reported requiring cancer treatment and/or other cancer care since the start of the COVID-19 pandemic. An estimated 32.1% reported any change, delay, or cancelation. On sample-weighted univariable analysis, patients who were younger, female, had one or fewer comorbidities, and uninsured were significantly more likely to report disruptions. On sample-weighted, multivariable analysis, patients who were younger and female remained significant predictors. Nearly 90% of patients included in the study reported virtual appointment use. Patients reporting disruptions were also significantly more likely to report feelings of anxiety. Conclusions: An estimated 1/3 of patients experienced disruptions to cancer care due to the COVID-19 pandemic. Patients experiencing disruptions in care were more likely to be female or younger which may reflect risk stratification strategies in the early stages of the pandemic, and also had higher rates of anxiety. The longitudinal impact of these disruptions on outcomes merits further study.

Extended first-line therapy (1LT) has improved clinical outcomes in newly diagnosed multiple myeloma (NDMM). This retrospective study of NDMM patients evaluated the relationship between dose-attenuation of 1LT and duration of therapy (DOT) and DOT on outcomes.Adults with NDMM not undergoing stem cell transplant (SCT) from January 1, 2012 toMarch 31, 2018 from the Integrated Oncology Network were included; 300 were randomly selected for chart review. 1LT DOT, time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis. Marginal structural models evaluated relationships between DOT and TTNT, PFS, and OS at 2 years accounting for confounders and survival bias from the time-dependent nature of DOT.Of 300 chart-reviewed patients, 93 were excluded for incomplete data or meeting exclusion criteria. Among 207 NDMM patients, median age was 74 years; 146 (70.5%) did not receive dose-attenuation during 1LT. Patients with short DOT were older, frailer, with a higher comorbidity burden, and a significantly lower proportion had an Eastern Cooperative Oncology Group PS = 0. As DOT increased, more patients underwent dose-attenuation (p 0.0001). The median 1LT DOT was 20.9 (95% confidence interval [CI]: 13.9, 26.4) versus 4.2 months (95% CI: 3.2, 4.9) for patients receiving versus not receiving dose-attenuation, respectively (p 0.0001). After accounting for survival bias, confounder-adjusted TTNT was prolonged with each additional month of 1LT (odds ratio [OR]: 0.76 [95% CI: 0.75, 0.78]); likelihoods of risks of disease progression (OR: 0.87 [95% CI: 0.86, 0.88]) and death at 2 years (OR: 0.72 [95% CI: 0.70, 0.74]) were reduced with each month of 1LT (p 0.0001 for all outcomes).Dose-attenuated 1LT was associated with longer DOT among patients with non-SCT NDMM. Each additional month of 1LT was associated with a reduced adjusted likelihood of disease progression and death at 2 years. Dose-attenuation of 1LT can extend DOT; longer DOT may improve clinical outcomes.

Unlike mammals, zebrafish possess a remarkable ability to regenerate damaged retina after an acute injury. Retina regeneration in zebrafish involves the induction of Müller glia-derived progenitor cells (MGPCs) exhibiting stem cell-like characteristics, which are capable of restoring all retinal cell-types. The induction of MGPC through Müller glia-reprograming involves several cellular, genetic and biochemical events soon after a retinal injury. Despite the knowledge on the importance of Phosphatase and tensin homolog (Pten), which is a dual-specificity phosphatase and tumor suppressor in the maintaining of cellular homeostasis, its importance during retina regeneration remains unknown. Here, we explored the importance of Pten during zebrafish retina regeneration. The Pten gets downregulated upon retinal injury and is absent from the MGPCs, which is essential to trigger Akt-mediated cellular proliferation essential for retina regeneration. We found that the downregulation of Pten in the post-injury retina accelerates MGPCs formation, while its overexpression restricts the regenerative response. We observed that Pten regulates the proliferation of MGPCs not only through Akt pathway but also by Mmp9/Notch signaling. Mmp9-activity is essential to induce the proliferation of MGPCs in the absence of Pten. Lastly, we show that expression of Pten is fine-tuned through Mycb/histone deacetylase1 and Tgf-β signaling. The present study emphasizes on the stringent regulation of Pten and its crucial involvement during the zebrafish retina regeneration.

Therapeutic plasma exchange (TPE) is a well-established treatment modality in acute liver failure patients, but its efficacy in treating acute on chronic liver failure (ACLF) patients is yet to be established.To assess the efficacy and safety of TPE in patients with alcohol-associated ACLF who were nonresponders to standard medical treatment (SMT) and without immediate prospects for liver transplantation.Twenty-eight alcohol-related ACLF (grade II) patients (14 cases and 14 controls) were enrolled in the study. Cases underwent standard volume TPE along with SMT while the controls were on SMT alone. The change (baseline to day 10) in laboratory parameters, cytokine concentrations, clinical severity scores along with 30 and 90 day mortality rates were noted and compared between the two groups. The adverse events (AEs) were noted in the groups and analyzed.A total of 51 TPE procedures were performed in 14 patients (average of 3.62 procedures/patient). TPE was effective in reduction of serum bilirubin, ammonia, activated partial thromboplastin time, prothrombin time, international normalized ratio, and severity scores (ACLF Research Consortium, Maddrey's discriminant function, and model for end-stage liver disease) (P .05). There was no significant difference in the reduction of serum interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α concentrations among cases. Among the cases who received the complete TPE interventions, 30- and 90-day mortality rates were lower in the cases as compared to controls albeit only the 90-day mortality was significantly different. Procedure-related AEs was observed in 2% of procedures.TPE is an effective and well-tolerated bridge therapy in patients with alcohol-associated ACLF of moderate severity not improving on SMT and without immediate prospects for liver transplantation.

High levels of loneliness are prominent in teenagers ranging from ages 14-19. The 4-week Self-Care program, offered by the Heartfulness Institute, is designed to develop social-emotional skills and self-observation. This study examined the impact of the Self-Care program on loneliness in high school students in the United States in a randomized, wait-list control trial with baseline and postintervention assessments. High school participants, aged 14-19, were randomized into a control-wait-listed group (n = 54) and a Heartfulness group (n = 54). Both the groups completed the intervention and the presurveys and postsurveys online, assessing their loneliness with the UCLA Loneliness Scale. The initial analysis noted the baseline equivalence of the data. A repeated measures ANOVA found a significant time * group interaction, with a significant decrease in loneliness reported in the Heartfulness Intervention group but no significant pre-post difference in the control group. In summary, the short online intervention program consisting of self-care tools decreased loneliness scores in the participants. This study opens up a new valley of possibilities, apart from existing research, and demonstrates that the online intervention used might be helpful to decrease loneliness levels in teens.

Defined with a dual-mode of action, the hybrid molecule synthesis is an attractive strategy to endure the scientific challenges in drug discovery. Besides worthy development in cancer therapy, it is still a leading cause of death across the globe. Failure in terms of efficacy, selectivity and toxicity, the statistics of a potential drug to concrete the cancer is rather in bleak. In the present study, synthesized hybrid molecules were well characterized by spectroscopy techniques. The single-crystal X-ray crystallography study revealed the monoclinic crystal system of Dimethyl 1,4-dihydro-2,6-dimethyl-4-(3-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-1H-pyr azol-4-yl)pyridine-3,5-dicarboxylate (5 b) with spacegroupC2/c. MTT assay provided the anticancer property of the compounds Diethyl1,4-dihydro-3,5-dimethyl-4-(3-(5-methyl-1-phenyl-1H-pyrazol-4-yl) -1H-pyrazol-4-yl)pyridine-2,6-dicarboxylate (5 a) and 5-methyl-1-phenyl-4-(4-(4,5-diphenyl-1H-imidazol-2-yl)-1H-pyrazol-3-yl)- 1H-pyrazole (6 a) against A549 cell lines with the IC(50)values of 42.79 mu M and 55.13 mu M respectively. The AO-EB staining assay for cell death analysis confirmed the selective action of both5 aand6 a. Further, molecular docking confirmed the effective binding with cyclin-dependent kinase (CDK2) protein, suggesting that the target compounds are remarkable inhibitors in dysregulating the CDK2 protein in cancer cells.

Many enteric pathogens employ a type III secretion system (T3SS) to translocate effector proteins directly into the host cell cytoplasm, where they subvert signalling pathways of the intestinal epithelium. Here, we report that the anti-apoptotic regulator HS1-associated protein X1 (HAX-1) is an interaction partner of the T3SS effectors EspO of enterohaemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium, OspE of Shigella flexneri and Osp1STYM of Salmonella enterica serovar Typhimurium. EspO, OspE and Osp1STYM have previously been reported to interact with the focal adhesions protein integrin linked kinase (ILK). We found that EspO localizes both to the focal adhesions (ILK localisation) and mitochondria (HAX-1 localisation), and that increased expression of HAX-1 leads to enhanced mitochondrial localisation of EspO. Ectopic expression of EspO, OspE and Osp1STYM protects cells from apoptosis induced by staurosporine and tunicamycin. Depleting cells of HAX-1 indicates that the anti-apoptotic activity of EspO is HAX-1 dependent. Both HAX-1 and ILK were further confirmed as EspO1-interacting proteins during infection using T3SS-delivered EspO1. Using cell detachment as a proxy for cell death we confirmed that T3SS-delivered EspO1 could inhibit cell death induced during EPEC infection, to a similar extent as the anti-apoptotic effector NleH, or treatment with the pan caspase inhibitor z-VAD. In contrast, in cells lacking HAX-1, EspO1 was no longer able to protect against cell detachment, while NleH1 and z-VAD maintained their protective activity. Therefore, during both infection and ectopic expression EspO protects cells from cell death by interacting with HAX-1. These results suggest that despite the differences between EHEC, C. rodentium, Shigella and S. typhimurium infections, hijacking HAX-1 anti-apoptotic signalling is a common strategy to maintain the viability of infected cells.

We show that both supplemental and ambient magnetic fields modulate myogenesis. A lone 10 min exposure of myoblasts to 1.5 mT amplitude supplemental pulsed magnetic fields (PEMFs) accentuated in vi...

Objectives: To develop an evidence-based guideline for the non-pharmacological management of persistent headaches associated with neck pain (i.e., tension-type or cervicogenic). Methods: This guideline is based on systematic reviews of high-quality studies. A multidisciplinary expert panel considered the evidence of clinical benefits, cost-effectiveness, societal and ethical values, and patient experiences when formulating recommendations. Target audience includes clinicians; target population is adults with persistent headaches associated with neck pain. Results: When managing patients with headaches associated with neck pain, clinicians should (a) rule out major structural or other pathologies, or migraine as the cause of headaches; (b) classify headaches associated with neck pain as tension-type headache or cervicogenic headache once other sources of headache pathology has been ruled out; (c) provide care in partnership with the patient and involve the patient in care planning and decision making; (d) provide care in addition to structured patient education; (e) consider low-load endurance craniocervical and cervicoscapular exercises for tension-type headaches (episodic or chronic) or cervicogenic headaches >3 months duration; (f) consider general exercise, multimodal care (spinal mobilization, craniocervical exercise and postural correction) or clinical massage for chronic tension-type headaches; (g) do not offer manipulation of the cervical spine as the sole form of treatment for episodic or chronic tension-type headaches; (h) consider manual therapy (manipulation with or without mobilization) to the cervical and thoracic spine for cervicogenic headaches >3 months duration. However, there is no added benefit in combining spinal manipulation, spinal mobilization and exercises; and (i) reassess the patient at every visit to assess outcomes and determine whether a referral is indicated. Conclusions: Our evidence-based guideline provides recommendations for the conservative management of persistent headaches associated with neck pain. The impact of the guideline in clinical practice requires validation. Significance: Neck pain and headaches are very common comorbidities in the population. Tension-type and cervicogenic headaches can be treated effectively with specific exercises. Manual therapy can be considered as an adjunct therapy to exercise to treat patients with cervicogenic headaches. The management of tension-type and cervicogenic headaches should be patient-centred.

INTRODUCTION Curative radiotherapy is guideline treatment for inoperable patients of good performance status with Stage I & II Non-Small Cell Lung Cancer (NSCLC). The aim of this study was to evaluate radiotherapy patterns of care in these patients, the reasons for palliative treatment and the proportion of patients suitable for curative stereotactic ablative body radiotherapy (SABR). METHODS Electronic oncology databases at three institutions were queried to retrieve data on patients with inoperable Stage I & II NSCLC seen in radiation oncology clinics between 1/1/2008 and 31/12/2014. Suitability for SABR was defined as peripheral tumours less than 5 cm in size. Factors associated with curative treatment were determined using univariate and multivariate analyses. RESULTS Three-hundred-and-twelve patients were identified of whom 178 (57%) received curative radiotherapy, 58 (19%) palliative radiotherapy and 76 (24%) no radiotherapy. The main reason for receiving palliative rather than curative treatment was COPD or poor pulmonary function (26%). Method of diagnosis (P = 0.031), Simplified Comorbidity Score (P = 0.003), ECOG performance status (P = 0.016), FEV1% (P = 0.040), treating institution (P

Streptococcus pneumoniae, one of the major human respiratory pathogens, uses its repertoire of surface proteins to adhere to the epithelium of the nasopharynx and lungs leading to colonization. PfbA is a conserved surface protein of S. pneumoniae and helps the bacterium to colonize the host by recognizing the extracellular matrix (ECM) molecule fibronectin, as well as blood proteins like plasminogen and human serum albumin. The crystal structure of rPfbA150-607 revealed it to possess a beta-helical region similar to those of carbohydrate-active enzymes as well as a C-terminal segment that resembles the fibronectin-binding regions of fibronectin-binding proteins. To get more insight into the putative carbohydrate-binding property of PfbA and its binding to various host molecules, we generated three different constructs of PfbA and characterized them by ELISA, isothermal titration calorimetry and bio-layer interferometry experiments. Importantly, the isothermal titration calorimetry experiments revealed that PfbA binds to different saccharides. Further, ELISA and bio-layer interferometry experiments identified that (a) apart from fibronectin and plasminogen, the beta helix of PfbA also binds to other ECM molecules (b) lysines are not responsible for PfbA's binding to plasminogen, (c) in comparison with native fibrinogen, deglycosylated-fibrinogen exhibits reduced binding affinity towards PfbA implying the importance of sugar molecule-PfbA interaction and (d) the C-terminal region of PfbA binds exclusively to the N-terminal F1 modules of fibronectin. Thus, the results of this study show PfbA to be a versatile multidomain and multiligand-binding protein employing different binding mechanisms. These results could be useful for structure-based designing of inhibitors against PfbA.

Methamphetamine (METH) is a highly abused psychostimulant that is associated with an increased risk for developing Parkinson’s disease (PD). This enhanced vulnerability likely relates to the toxic effects of METH that overlap with PD pathology, for example, aberrant functioning of α-synuclein and parkin. In PD, peripheral factors are thought to contribute to central nervous system (CNS) degeneration. For example, α-synuclein levels in the enteric nervous system (ENS) are elevated, and this precedes the onset of motor symptoms. It remains unclear whether neurons of the ENS, particularly catecholaminergic neurons, exhibit signs of METH-induced toxicity as seen in the CNS. The aim of this study was to determine whether self-administered METH altered the levels of α-synuclein, parkin, tyrosine hydroxylase (TH), and dopamine-β-hydroxylase (DβH) in the myenteric plexus of the distal colon ENS. Young adult male Sprague-Dawley rats self-administered METH for 3 h per day for 14 days and controls were saline-yoked. Distal colon tissue was collected at 1, 14, or 56 days after the last operant session. Levels of α-synuclein were increased, while levels of parkin, TH, and DβH were decreased in the myenteric plexus in the METH-exposed rats at 1 day following the last operant session and returned to the control levels after 14 or 56 days of forced abstinence. The changes were not confined to neurofilament-positive neurons. These results suggest that colon biomarkers may provide early indications of METH-induced neurotoxicity, particularly in young chronic METH users who may be more susceptible to progression to PD later in life.