Notes

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pia, deserves further research. Some drugs, such as antihyperglycemic or bronchodilators, may directly alter refractive error. Intraocular pressure appears causative for myopia.
Besides regulating paracellular diffusion, claudin-19 modulates the expression of proteins essential for the retinal pigment epithelium (RPE). This study asks how RPE responds when the expression of claudin-19 is reduced.

In stem cell-derived RPE, claudin-19 and sequestosome-1/p62 (SQSTM1) were knocked down with siRNAs. Expression was monitored by quantitative RT-PCR and western blotting. Morphology and function were monitored by immunocytochemistry and transepithelial electrical resistance (TER). Phagocytosis of photoreceptor outer segments (POSs) was followed by fluorescence-activated cell sorting and western blotting. Pharmacology was used to assess the effects of AMP-activated protein kinase (AMPK) and SQSTM1 on phagocytosis. Enzymatic activity was measured using commercial assay kits.

Knockdown of claudin-19 reduced the TER without affecting the integrity of the apical junctional complex, as assessed by the distribution of zonula occludens-1 and filamentous actin. AMPK was activated without apparen RPE functions.
Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide with more than 1.85 million cases and 850 000 deaths annually. Of new colorectal cancer diagnoses, 20% of patients have metastatic disease at presentation and another 25% who present with localized disease will later develop metastases.

Colorectal cancer is the third most common cause of cancer mortality for men and women in the United States, with 53 200 deaths projected in 2020. Among people diagnosed with metastatic colorectal cancer, approximately 70% to 75% of patients survive beyond 1 year, 30% to 35% beyond 3 years, and fewer than 20% beyond 5 years from diagnosis. The primary treatment for unresectable metastatic CRC is systemic therapy (cytotoxic chemotherapy, biologic therapy such as antibodies to cellular growth factors, immunotherapy, and their combinations.) Clinical trials completed in the past 5 years have demonstrated that tailoring treatment to the molecular and pathologic features of the tumor improves omproved treatment outcomes with a median overall survival of 31.4 months in previously treated patients.

Advances in molecular profiling of metastatic CRC facilitate the ability to direct treatments to the biologic features of the tumor for specific patient subsets. Although cures remain uncommon, more patients can anticipate extended survival. Genomic profiling allows treatment selection so that more patients derive benefit and fewer are exposed to toxicity from ineffective therapies.
Advances in molecular profiling of metastatic CRC facilitate the ability to direct treatments to the biologic features of the tumor for specific patient subsets. Although cures remain uncommon, more patients can anticipate extended survival. Genomic profiling allows treatment selection so that more patients derive benefit and fewer are exposed to toxicity from ineffective therapies.
Thigh muscle weakness is associated with knee discomfort and osteoarthritis disease progression. Little is known about the efficacy of high-intensity strength training in patients with knee osteoarthritis or whether it may worsen knee symptoms.

To determine whether high-intensity strength training reduces knee pain and knee joint compressive forces more than low-intensity strength training and more than attention control in patients with knee osteoarthritis.

Assessor-blinded randomized clinical trial conducted at a university research center in North Carolina that included 377 community-dwelling adults (≥50 years) with body mass index (BMI) ranging from 20 to 45 and with knee pain and radiographic knee osteoarthritis. Enrollment occurred between July 2012 and February 2016, and follow-up was completed September 2017.

Participants were randomized to high-intensity strength training (n = 127), low-intensity strength training (n = 126), or attention control (n = 124).

Primary outcomes at the 18-month f5 N; P = .61), or between the high-intensity and low-intensity groups (2453 N vs 2475 N; adjusted difference, -21; 95% CI, -235 to 193 N; P = .85). check details There were 87 nonserious adverse events (high-intensity, 53; low-intensity, 30; control, 4) and 13 serious adverse events unrelated to the study (high-intensity, 5; low-intensity, 3; control, 5).

Among patients with knee osteoarthritis, high-intensity strength training compared with low-intensity strength training or an attention control did not significantly reduce knee pain or knee joint compressive forces at 18 months. The findings do not support the use of high-intensity strength training over low-intensity strength training or an attention control in adults with knee osteoarthritis.

ClinicalTrials.gov Identifier NCT01489462.
ClinicalTrials.gov Identifier NCT01489462.
Pregnancy may be a key window to optimize cardiovascular health (CVH) for the mother and influence lifelong CVH for her child.

To examine associations between maternal gestational CVH and offspring CVH.

This cohort study used data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study (examinations July 2000-April 2006) and HAPO Follow-Up Study (examinations February 2013-December 2016). The analyses included 2302 mother-child dyads, comprising 48% of HAPO Follow-Up Study participants, in an ancillary CVH study. Participants were from 9 field centers across the United States, Barbados, United Kingdom, China, Thailand, and Canada.

Maternal gestational CVH at a target of 28 weeks' gestation, based on 5 metrics body mass index, blood pressure, total cholesterol level, glucose level, and smoking. Each metric was categorized as ideal, intermediate, or poor using pregnancy guidelines. Total CVH was categorized as follows all ideal metrics, 1 or more intermediate (but 0 poor) metrics, 1 poor metri-12.82]).

In this multinational cohort, better maternal CVH at 28 weeks' gestation was significantly associated with better offspring CVH at ages 10 to 14 years.
In this multinational cohort, better maternal CVH at 28 weeks' gestation was significantly associated with better offspring CVH at ages 10 to 14 years.
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