Although they are usually not considered to be diabetes complications, musculoskeletal disorders (MSKDs) are common in individuals with type 1 or type 2 diabetes and can strongly interfere with daily diabetes care, especially in people using diabetes technologies. The authors of this retrospective study in a population of 140 patients with type 1 diabetes report the distribution of subtypes of MSKDs and speculate about the mechanisms involved. The authors emphasize the need for multidisciplinary care involving not only the diabetes care team but also orthopedic surgeons. This report should lead to large, prospective studies to increase knowledge about these under-studied complications.

This study was an analysis of a national sample of U.S. medical office visits from 2014 to 2016, a period when evidence of effectiveness was emerging for a variety of beneficial type 2 diabetes agents with regard to potential reduction in diabetes comorbidities. Ideal therapy was defined as an American Diabetes Association–identified beneficial agent plus metformin. The associations between atherosclerotic cardiovascular disease or obesity and use of these agents were explored.

Structured diabetes education (SDE) is an evidence-based intervention that supports self-management in people with type 2 diabetes. In the United Kingdom, health care providers working in primary care settings are responsible for referring people with type 2 diabetes to SDE programs. However, national audits record a high percentage of nonattenders. We explored the personal experience of living with type 2 diabetes that led to individuals declining invitations to attend SDE programs. The themes suggested that emotional, cognitive, and social issues related to diagnosis and living with diabetes may be responsible for declining to attend SDE and that these factors may be masked by explanations of practical barriers. A person-centered approach to understanding the personal meaning of being diagnosed and living with type 2 diabetes may help to identify individuals’ psychosocial barriers to attending SDE.

People with type 1 diabetes may receive a significant portion of their care from primary care providers (PCPs). To understand the involvement of PCPs in delivering type 1 diabetes care, we performed surveys in California and Florida, two of the most populous and diverse states in the United States. PCPs fill insulin prescriptions but report low confidence in providing type 1 diabetes care and difficulty accessing specialty referrals to endocrinologists.

Adolescents with type 1 diabetes face self-management challenges that make it difficult for them to achieve good glycemic control. In our population of adolescents with poorly controlled type 1 diabetes, the use of continuous glucose monitoring (CGM) improved patients’ glycemic time in range (TIR) and identified hypoglycemia more frequently than with intermittent self-monitoring of blood glucose throughout a 4-week interval. However, the adolescents were unable to synthesize this information to problem-solve or reduce the frequency of hypoglycemic events. Setting SMART (specific, measurable, achievable, relevant, and time-bound) diabetes management goals and providing intensive diabetes education and support could increase adolescents’ TIR and prevent hypoglycemia.

Researchers investigated pain perception in patients with diabetic foot ulcers (DFUs) by analyzing pre- and postoperative physical function (PF), pain interference (PI), and depression domains of the Patient-Reported Outcome Measurement Information System (PROMIS). They hypothesized that 1) because of painful diabetic peripheral neuropathy (DPN), a majority of patients with DFUs would have high PROMIS PI scores unchanged by operative intervention, and 2) the initially assessed PI, PF, and depression levels would be correlated with final outcomes. Seventy-five percent of patients with DFUs reported pain, most likely because of painful DPN. Those who reported high PI and low PF were likely to report depression. PF, PI, and depression levels were unchanged after operative intervention or healing of DFUs.

Background:

Sex steroid hormones and sex hormone–binding globulin (SHBG) have been implicated in the etiology of invasive breast cancer, but their associations with risk of the precursor lesion, ductal carcinoma in situ (DCIS) of the breast, remain unclear.

Background:

Limited treatment options are available for oral mucositis, a common, debilitating complication of cancer therapy. We examined the association between daily delivery time of radiotherapy and the severity of oral mucositis in patients with head and neck cancer.

Background:

The recent expansion of treatment options in acute myeloid leukemia (AML) has necessitated a greater understanding of patient preferences for treatment benefits, about which little is known.

Background:

New technologies are being developed for early detection of multiple types of cancer simultaneously. To quantify the potential benefit, we estimated reductions in absolute cancer–related deaths that could occur if cancers diagnosed after metastasis (stage IV) were instead diagnosed at earlier stages.

Skeletal muscle wasting is a devastating consequence of cancer that contributes to increased complications and poor survival, but is not well understood at the molecular level. Herein, we investigated the role of Myocilin (Myoc), a skeletal muscle hypertrophy-promoting protein that we showed is downregulated in multiple mouse models of cancer cachexia. Loss of Myoc alone was sufficient to induce phenotypes identified in mouse models of cancer cachexia, including muscle fiber atrophy, sarcolemmal fragility, and impaired muscle regeneration. By 18 months of age, mice deficient in Myoc showed significant skeletal muscle remodeling, characterized by increased fat and collagen deposition compared with wild-type mice, thus also supporting Myoc as a regulator of muscle quality. In cancer cachexia models, maintaining skeletal muscle expression of Myoc significantly attenuated muscle loss, while mice lacking Myoc showed enhanced muscle wasting. Furthermore, we identified the myocyte enhancer factor 2 C (MEF2C) transcription factor as a key upstream activator of Myoc whose gain of function significantly deterred cancer-induced muscle wasting and dysfunction in a preclinical model of pancreatic ductal adenocarcinoma (PDAC). Finally, compared with noncancer control patients, MYOC was significantly reduced in skeletal muscle of patients with PDAC defined as cachectic and correlated with MEF2c. These data therefore identify disruptions in MEF2c-dependent transcription of Myoc as a novel mechanism of cancer-associated muscle wasting that is similarly disrupted in muscle of patients with cachectic cancer.Significance:This work identifies a novel transcriptional mechanism that mediates skeletal muscle wasting in murine models of cancer cachexia that is disrupted in skeletal muscle of patients with cancer exhibiting cachexia.

Determining mechanisms of resistance to αPD-1/PD-L1 immune-checkpoint immunotherapy is key to developing new treatment strategies. Cancer-associated fibroblasts (CAF) have many tumor-promoting functions and promote immune evasion through multiple mechanisms, but as yet, no CAF-specific inhibitors are clinically available. Here we generated CAF-rich murine tumor models (TC1, MC38, and 4T1) to investigate how CAFs influence the immune microenvironment and affect response to different immunotherapy modalities [anticancer vaccination, TC1 (HPV E7 DNA vaccine), αPD-1, and MC38] and found that CAFs broadly suppressed response by specifically excluding CD8+ T cells from tumors (not CD4+ T cells or macrophages); CD8+ T-cell exclusion was similarly present in CAF-rich human tumors. RNA sequencing of CD8+ T cells from CAF-rich murine tumors and immunochemistry analysis of human tumors identified significant upregulation of CTLA-4 in the absence of other exhaustion markers; inhibiting CTLA-4 with a nondepleting antibody overcame the CD8+ T-cell exclusion effect without affecting Tregs. We then examined the potential for CAF targeting, focusing on the ROS-producing enzyme NOX4, which is upregulated by CAF in many human cancers, and compared this with TGFβ1 inhibition, a key regulator of the CAF phenotype. siRNA knockdown or pharmacologic inhibition [GKT137831 (Setanaxib)] of NOX4 “normalized” CAF to a quiescent phenotype and promoted intratumoral CD8+ T-cell infiltration, overcoming the exclusion effect; TGFβ1 inhibition could prevent, but not reverse, CAF differentiation. Finally, NOX4 inhibition restored immunotherapy response in CAF-rich tumors. These findings demonstrate that CAF-mediated immunotherapy resistance can be effectively overcome through NOX4 inhibition and could improve outcome in a broad range of cancers.Significance:NOX4 is critical for maintaining the immune-suppressive CAF phenotype in tumors. Pharmacologic inhibition of NOX4 potentiates immunotherapy by overcoming CAF-mediated CD8+ T-cell exclusion.Graphical Abstract:http://cancerres.aacrjournals.org/content/canres/80/9/1846/F1.large.jpg.See related commentary by Hayward, p. 1799

Although genome-wide association studies (GWAS) have identified more than 100 colorectal cancer risk loci, most of the biological mechanisms associated with these loci remain unclear. Here we first performed a comprehensive expression quantitative trait loci analysis in colorectal cancer tissues adjusted for multiple confounders to test the determinants of germline variants in established GWAS susceptibility loci on mRNA and long noncoding RNA (lncRNA) expression. Combining integrative functional genomic/epigenomic analyses and a large-scale population study consisting of 6,024 cases and 10,022 controls, we then prioritized rs174575 with a C>G change as a potential causal candidate for colorectal cancer at 11q12.2, as its G allele was associated with an increased risk of colorectal cancer (OR = 1.26; 95% confidence interval = 1.17–1.36; P = 2.57 × 10–9). rs174575 acted as an allele-specific enhancer to distally facilitate expression of both FADS2 and lncRNA AP002754.2 via long-range enhancer–promoter interaction loops, which were mediated by E2F1. AP002754.2 further activated a transcriptional activator that upregulated FADS2 expression. FADS2, in turn, was overexpressed in colorectal cancer tumor tissues and functioned as a potential oncogene that facilitated colorectal cancer cell proliferation and xenograft growth in vitro and in vivo by increasing the metabolism of PGE2, an oncogenic molecule involved in colorectal cancer tumorigenesis. Our findings represent a novel mechanism by which a noncoding variant can facilitate long-range genome interactions to modulate the expression of multiple genes including not only mRNA, but also lncRNA, which provides new insights into the understanding of colorectal cancer etiology.Significance:This study provides an oncogenic regulatory circuit among several oncogenes including E2F1, FADS2, and AP002754.2 underlying the association of rs174575 with colorectal cancer risk, which is driven by long-range enhancer–promoter interaction loops.Graphical Abstract:http://cancerres.aacrjournals.org/content/canres/80/9/1804/F1.large.jpg.

Germline alterations of the tumor suppressor PTEN have been extensively characterized in patients with PTEN hamartoma tumor syndromes, encompassing subsets of Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome, Proteus and Proteus-like syndromes, as well as autism spectrum disorder. Studies have shown an increase in the risk of developing specific cancer types in the presence of a germline PTEN mutation. Furthermore, outside of the familial setting, somatic variants of PTEN occur in numerous malignancies. Here we introduce and discuss the prospect of moving toward a systems pathology approach for PTEN diagnostics, incorporating clinical and molecular pathology data with the goal of improving the clinical management of patients with a PTEN mutation. Detection of a germline PTEN mutation can inform cancer surveillance and in the case of somatic mutation, have value in predicting disease course. Given that PTEN functions in the PI3K/AKT/mTOR pathway, identification of a PTEN mutation may highlight new therapeutic opportunities and/or inform therapeutic choices.

BACKGROUND AND PURPOSE:

The massa intermedia is a normal midline transventricular thalamic connection. Massa intermedia aberrations are common in schizophrenia, Chiari II malformation, X-linked hydrocephalus, Cornelia de Lange syndrome, and diencephalic-mesencephalic junction dysplasia, among others. We have noticed that massa intermedia abnormalities often accompany other midline malformations. The massa intermedia has never been formally evaluated in a group of exclusively pediatric patients, to our knowledge. We sought to compare and contrast the prevalence, size, and location of the massa intermedia in pediatric patients with and without congenital midline brain abnormalities.

BACKGROUND AND PURPOSE:

In the medicolegal literature, notching of the corpus callosum has been reported to be associated with fetal alcohol spectrum disorders. Our purpose was to analyze the prevalence of notching of the corpus callosum in a fetal alcohol spectrum disorders group and a healthy population to determine whether notching occurs with increased frequency in the fetal alcohol spectrum disorders population.

BACKGROUND AND PURPOSE:

Diffuse intrinsic pontine glioma is a lethal childhood brain cancer with dismal prognosis and MR imaging is the primary methodology used for diagnosis and monitoring. Our aim was to determine whether advanced diffusion, perfusion, and permeability MR imaging metrics predict survival and pseudoprogression in children with newly diagnosed diffuse intrinsic pontine glioma.

BACKGROUND AND PURPOSE:

It is currently not completely clear how well radiologists perform in evaluating large-vessel occlusion on CTA in acute ischemic stroke. The purpose of this study was to investigate potential factors associated with diagnostic error.

वैश्विक महामारी कोरोना वायरस से निपटने के लिए लगाया गया लॉकडाउन जारी है। आज लॉकडाउन 3.0 का छठा दिन है। वहीं, देशभर में संक्रमित मरीजों की संख्या में लगातार बढ़ोतरी हो रही है

An analysis of the media consumption habits of people in the US shows that fake news makes up a tiny fraction of what they watch or read every day

Pepe helps keep Indian children healthy by reminding them to wash up

बीते बुधवार को सरकार ने फीचर फोन और लैंडलाइन यूजर्स के लिए आईवीआरएस सेवा लॉन्च की थी। वहीं, अब सरकार जियोफोन यूजर्स के लिए अलग से आरोग्य सेतु मोबाइल एप को पेश करने की तैयारी कर रही है।

शॉर्ट वीडियो एप लाईकी ज्वाइन करने का मतबल लाईकी के लाखों यूजर्स को रियल टाइम में कोरोना के संक्रमण के बारे में जानकारी देना और रोकधाम के उपाय को बताना है।

Safety fears derail plan to import reactors.

Drill detected no glitches, but improvements could still be made.

Global data on Fukushima challenge Japanese estimates.

Blizzard has some announcements. Square Enix has money! Jon doesn’t have a 3DS…still. And you have a new podcast.

As we gear up for E3, we get hyped about the latest games. That’s right, we’ve got some hot impressions on Harvester and Diablo II....

This research shows how different populations of people share most of the genetic susceptibilities to developing type 2 diabetes but do have some different genetic variations that can make them more or less susceptible to developing the condition.

The Oscar-winning sword-and-sandals Russell Crowe vehicle refreshed old cliches, before ushering in a spate of copycats

“Joey, do you like movies about gladiators?” the creepy pilot asks the small boy in Airplane!. To younger audiences, the joke no longer makes any sense. In Airplane!’s day, sword-and-sandals movies had become an outdated, unwittingly homoerotic joke. But then came Gladiator, and the joke was on us. Released 20 years ago this month, Ridley Scott’s Roman epic gave the old cliches a new lease of life. It was all here: Colosseum action! Rippling man-flesh! Tigers! But Gladiator had its cheesecake and ate it. It served up crowd-pleasing spectacle and airline-ad visuals but also solemn, Oscar-worthy drama (and, in retrospect, a fair degree of camp).

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U.S. Vice President Mike Pence's press secretary, the wife of one of President Donald Trump's senior advisers, has tested positive for the coronavirus, raising alarm about the virus' potential spread within the White House's inner most circle.

New Dlehi, May 09: Several Indians, who are stranded in at least seven countries due to coronavirus outbreak, is all set to fly back to their home country on Saturday in special flights under Vande Bharat Mission. According to officials,

The report by Crisil also added that the losses will climb if travel restrictions last longer in hubs such as Mumbai, Delhi, Chennai and Kolkata.

Noida Police Commissioner has written to national carrier Air India, requesting the airline to ensure that pilots and crew involved in repatriation flights should stay back in Delhi.

The stranded people hail from Tamil Nadu and they were working in the United Arab Emirates.

Rahul Gandhi seems to have descended into a spiral of far Left, subversive standpoint since Narendra Modi swept to power at the Centre and the Congress started losing state after state.