Agricultural Injuries among Farmers and Ranchers in the Central United States during 2011-2015.

The high risk of occupational fatalities in agriculture is well documented, but information on non-fatal injuries is lacking due to challenges in injury surveillance. This surveillance study explored the frequency, characteristics, and risk factors for non-fatal injuries among farmers and ranchers in the central United States. The Central States Center for Agricultural Safety and Health (CS-CASH), in collaboration with the USDA National Agricultural Statistics Service (NASS), conducted annual surveys (n = 34,777 sent) during 2011-2015 covering a seven-state region (Iowa, Kansas, Minnesota, Missouri, North Dakota, Nebraska, and South Dakota). The average response rate was 32% in the five consecutive annual surveys. The average injury incidence rate was 7.0 injuries/100 operators per year. Most injuries (89%) occurred during agricultural work. The most frequent sources of injury were livestock (22%), machinery (13%), and hand tools (12%). Risk factors for injury included: male gender, younger age (vs. 65+ years), farming as the primary occupation, greater work time, greater land area, ranch (vs. farm), organic farming, internet access, and production of several types of crops and animals. Most injuries (56%) required a doctor visit, and 12% required hospitalization. The average medical costs were $1,936 out of pocket and $8,043 paid by insurance. The combined average costs for most serious injuries were $7,858. Most injuries (66%) resulted in some lost time from agricultural work, and 13% were serious, resulting in more than 30 days of lost work time. The non-fatal injury rate for self-employed farmers and ranchers was higher than that of hired agricultural workers reported by the Bureau of Labor Statistics. This result reaffirms farming/ranching as a dangerous occupation and emphasizes the need for efforts to prevent agricultural injuries, especially those associated with identified injury sources and risk factors.

Abnormal joint powers before and after the onset of claudication symptoms.

OBJECTIVE: Claudication is the most common manifestation of peripheral arterial disease, producing significant ambulatory compromise. Our study evaluated patients with bilateral lower limb claudication and characterized their gait abnormality based on advanced biomechanical analysis using joint torques and powers. METHODS: Twenty patients with bilateral claudication (10 with isolated aortoiliac disease and 10 with combined aortoiliac and femoropopliteal disease) and 16 matched controls ambulated on a walkway while 3-dimensional biomechanical data were collected. Patients walked before and after onset of claudication pain. Joint torques and powers at early, mid, and late stance for the hip, knee, and ankle joints were calculated for claudicating patients before and after the onset of claudication pain and were compared to controls. RESULTS: Claudicating patients exhibited significantly reduced hip and knee power at early stance (weight-acceptance phase) due to decreased torques produced by the hip and knee extensors. In mid stance (single-limb support phase), patients had significantly reduced knee and hip power due to the decreased torques produced by the knee extensors and the hip flexors. In late stance (propulsion phase), reduced propulsion was noted with significant reduction in ankle plantar flexor torques and power. These differences were present before and after the onset of pain, with certain parameters worsening in association with pain. CONCLUSIONS: The gait of claudication is characterized by failure of specific and identifiable muscle groups needed to perform normal walking (weight acceptance, single-limb support, and propulsion). Parameters of gait are abnormal with the first steps taken, in the absence of pain, and certain of these parameters worsen after the onset of claudication pain.

Abnormal Microvascular Architecture, Fibrosis, and Pericyte Characteristics in the Calf Muscle of Peripheral Artery Disease Patients with Claudication and Critical Limb Ischemia.

Work from our laboratory documents pathological events, including myofiber oxidative damage and degeneration, myofibrosis, micro-vessel (diameter = 50-150 µm) remodeling, and collagenous investment of terminal micro-vessels (diameter ≤ 15 µm) in the calf muscle of patients with Peripheral Artery Disease (PAD). In this study, we evaluate the hypothesis that the vascular pathology associated with the legs of PAD patients encompasses pathologic changes to the smallest micro-vessels in calf muscle. Biopsies were collected from the calf muscle of control subjects and patients with Fontaine Stage II and Stage IV PAD. Slide specimens were evaluated by Quantitative Multi-Spectral and Fluorescence Microscopy. Inter-myofiber collagen, stained with Masson Trichrome (MT), was increased in Stage II patients, and more substantially in Stage IV patients in association with collagenous thickening of terminal micro-vessel walls. Evaluation of the Basement Membrane (BM) of these vessels reveals increased thickness in Stage II patients, and increased thickness, diameter, and Collagen I deposition in Stage IV patients. Coverage of these micro-vessels with pericytes, key contributors to fibrosis and BM remodeling, was increased in Stage II patients, and was greatest in Stage IV patients. Vascular pathology of the legs of PAD patients extends beyond atherosclerotic main inflow arteries and affects the entire vascular tree-including the smallest micro-vessels.

Altered Metabolomic Profile in Patients with Peripheral Artery Disease.

Peripheral artery disease (PAD) is a common atherosclerotic disease characterized by narrowed or blocked arteries in the lower extremities. Circulating serum biomarkers can provide significant insight regarding the disease progression. Here, we explore the metabolomics signatures associated with different stages of PAD and investigate potential mechanisms of the disease. We compared the serum metabolites of a cohort of 26 PAD patients presenting with claudication and 26 PAD patients presenting with critical limb ischemia (CLI) to those of 26 non-PAD controls. A difference between the metabolite profiles of PAD patients from non-PAD controls was observed for several amino acids, acylcarnitines, ceramides, and cholesteryl esters. Furthermore, our data demonstrate that patients with CLI possess an altered metabolomic signature different from that of both claudicants and non-PAD controls. These findings provide new insight into the pathophysiology of PAD and may help develop future diagnostic procedures and therapies for PAD patients.

Postmyotomy dysphagia after laparoscopic surgery for achalasia.

AIM: To determine predictive factors for postoperative dysphagia after laparoscopic myotomy for achalasia. METHODS: Logistic regression was used to investigate the possible association between the response (postoperative dysphagia, with two levels: none/mild and moderate/severe) and several plausible predictive factors. RESULTS: Eight patients experienced severe or moderate postoperative dysphagia. The logistic regression revealed that only the severity of preoperative dysphagia (with four levels: mild, moderate, severe, and liquid) was a marginally significant (P=0.0575) predictive factor for postoperative dysphagia. CONCLUSION: The severity of postoperative dysphagia is strongly associated with preoperative dysphagia. Preoperative symptomatology can significantly impact patient outcome.

Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice.

The thiazolidinediones, such as rosiglitazone, increase peripheral insulin sensitivity and their use is proposed for the treatment of Alzheimer's disease. However, the mechanisms underlying the potential beneficial effects of rosiglitazone in Alzheimer's disease remain unclear. In previous studies, we observed that Tg2576 Alzheimer mice develop peripheral insulin resistance with age and have much higher serum corticosterone levels than wild-type mice when fasted overnight. We further showed that both of these defects can be ameliorated by rosiglitazone administration. Here, we report that during behavioral testing which involves repetitive overnight fasting, Tg2576 mice administered rosiglitazone exhibited better spatial learning and memory abilities and had lower serum corticosterone levels than untreated Tg2576 mice. When untreated Tg2576 mice were administered metyrapone, a drug that blocks glucocorticoid production, their spatial learning and memory abilities and serum corticosterone levels were similar to those of rosiglitazone-treated mice. We further report here that rosiglitazone attenuated reductions in insulin-degrading enzyme (IDE) mRNA and activity, and reduced amyloid beta-peptide (Abeta)42 levels without affecting amyloid deposition, in the brains of Tg2576 mice. These results demonstrate that rosiglitazone attenuates learning and memory deficits in Tg2576 mice and suggest that the effects of the drug on learning and memory, brain IDE levels, and brain Abeta42 levels in the mice may be due to its glucocorticoid-lowering actions.

American founder mutation for Lynch syndrome. Prevalence estimates and implications.

BACKGROUND: Recently, a new founder mutation, an exon 1-6 deletion in a mismatch repair gene (MMR), MSH2, in nine kindreds with Lynch syndrome was reported. In 3 of the kindreds this mutation was traced by genealogy through 11-12 generations to a common founder, and thus termed the American Founder Mutation (AFM). Since then, 13 additional 'unrelated' kindreds with AFM were detected by a recently designed single polymerase chain reaction. This test might serve as first-line screening for Lynch syndrome mutations, provided AFM was prevalent, which is assessed in the current study. METHODS: The number of current AFM carriers and the incidence of Lynch syndrome caused by AFM were estimated based on population growth of mutation carriers derived from genealogy data. For cross-checking, its annual incidence was also estimated based on published epidemiology data. RESULTS: There are 18,981 (5th and 95th percentiles, 6038 and 34,466, respectively) expected current AFM carriers, or 160 (range 51-290) Lynch syndrome cases diagnosed per year due to AFM estimated based on genealogy data. The incidence estimate closely overlaps with that based on published epidemiology data, which is 114-400 cases per year. CONCLUSIONS: A large number of AFM carriers are likely to exist in the U.S., which harbors significant implications for cancer control. Given the ease of detection, testing for AFM not only among members of the existing AFM families, but also among all patients with Lynch syndrome in the U.S. is proposed.

Genetic dissection of myocilin glaucoma.

Primary open-angle glaucoma (POAG) is a complex disease with unknown causes. However, in the past decade, POAG has been linked to six chromosomal regions, of which the gene MYOC encoding myocilin and the gene OPTN encoding optineurin have been identified to harbor causal mutations (disease-causing variants, DCV). POAG caused by DCV at MYOC has been termed "myocilin glaucoma". Clinically, DCV at MYOC may manifest as a typical POAG, normal tension glaucoma, or ocular hypertension without glaucoma. Individuals with the Arg46Stop mutation that almost knocks out the entire coding sequence may have severe glaucoma or no glaucoma. Genetically, myocilin glaucoma follows autosomal dominant, recessive or no pattern of inheritance. DCV at MYOC cause POAG in interaction with environmental factors and DCV at other loci. Most DCV at MYOC are relatively young, and the Gln368Stop mutation is exclusively European in origin. The overall frequency of DCV at MYOC is similar among African, Caucasian and Asian probands with POAG. Because of this fact and the higher prevalence of POAG in African descendants compared with Caucasians or Asians, the overall frequency of DCV at MYOC is several-fold higher in the general population of African descendants, which is in part responsible for their higher prevalence of POAG. Although the Arg46Stop mutation was often observed in normal controls, Arg46Stop carriers tend to have higher risk of developing POAG. Polymorphisms at several loci including MYOC are associated with POAG, and play an important role in the pathogenesis of POAG.

Response to preoperative chemoradiation in stage II and III rectal cancer.

PURPOSE: The purpose of this study was to determine whether a complete pathologic response after neoadjuvant therapy in rectal cancer patients improves disease control and survival. METHODS: The study reviewed Stage II and III rectal cancer patients treated with preoperative chemoradiation and resected for cure. Complete pathologic response was defined as no cancer in the resected specimen. The main outcome measures were cancer-specific and disease-free survival in patients achieving a complete pathologic response and a noncomplete pathologic response. Kaplan-Meier curves were evaluated using log-rank analysis. RESULTS: Eighty-nine rectal cancer patients received neoadjuvant chemoradiation followed by radical resection for cure. Twenty-one patients (24 percent) achieved a complete pathologic response. Median follow-up for the complete pathologic response group was 23.5 months and 31 months for the noncomplete pathologic response group. There were more Stage III patients in the noncomplete pathologic response group than the complete pathologic response group (P = 0.005). Complete pathologic response patients were less likely to receive postoperative adjuvant chemotherapy than noncomplete pathologic response patients (P = 0.004). Cancer-specific and disease-free survival were not statistically different between the two groups. However, a trend was noted toward improved survival and decreased recurrence in association with a complete pathologic response. CONCLUSION: Stage III patients were less likely to be in the complete pathologic response group than Stage II patients. Complete pathologic response patients were less likely to receive postoperative adjuvant chemotherapy than noncomplete pathologic response patients. Complete pathologic response after neoadjuvant chemoradiation for rectal cancer patients demonstrated a trend toward improved survival and decreased recurrence compared with noncomplete pathologic response patients.