Rationale, study design and methodology of the LANDMARC trial: a 3-year, pan-India, prospective, longitudinal study to assess management and real-world outcomes of diabetes mellitus.

AIM: India contributes towards a large part of the worldwide epidemic of diabetes and its associated complications. However, there are limited longitudinal studies available in India to understand the occurrence of diabetes complications over time. This pan-India longitudinal study was initiated to assess the real-world outcomes of diabetes across the country. METHODS: The LANDMARC study is the first prospective, multicentre, longitudinal, observational study investigating a large cohort of people with type 2 diabetes mellitus across India over a period of 3 years. The primary objective of this ongoing study is to determine the proportion of people developing macrovascular diabetes complications over the duration of the study (36 months ± 45 days) distributed over seven visits; the secondary objective is to evaluate microvascular diabetes complications, glycaemic control and time-to-treatment adaptation or intensification. Overall, 6300 participants (aged 25-60 years) diagnosed with type 2 diabetes for at least 2 years will be included from 450 centres across India. Data will be recorded for baseline demographics, comorbidities, glycaemic measurements, use of anti-hyperglycaemic medications and any cardiovascular or other diabetes-related events occurring during the observational study period. CONCLUSIONS: The LANDMARC study is expected to reveal the trends in complications associated with diabetes, treatment strategies used by physicians, and correlation among treatment, control and complications of diabetes within the Indian context. The findings of this study will help to identify the disease burden, emergence of early-onset complications and dose titration patterns, and eventually develop person-centred care and facilitate public health agencies to invest appropriate resources in the management of diabetes. (Trial Registration No: CTRI/2017/05/008452).

A low-power, high-speed, 9-channel germanium-silicon electro-absorption modulator array integrated with digital CMOS driver and wavelength multiplexer.

We demonstrate the first germanium-silicon C-band electro-absorption based waveguide modulator array and echelle-grating-based silicon wavelength multiplexer integrated with a digital CMOS driver circuit. A 9-channel, 10Gbps SiGe electro-absorption wavelength-multiplexed modulator array consumed a power of 5.8mW per channel while being modulated at 10.25Gbps by 40nm CMOS drivers delivering peak-to-peak voltage swings of 2V, achieving a modulation energy-efficiency of ~570fJ/bit including drivers. Performance up to 25Gbps on a single-channel SiGe modulator and CMOS driver is also reported.

Left pulmonary artery hypoplasia presenting with unilateral hyperluscent lung.

Agenesis or hypoplasia of the right or left pulmonary arteries are among the rarest pulmonary artery anomalies with left sided anomalies being reported even less frequently. Pulmonary artery agenesis should be suspected in asymptomatic patients if a plain chest X-ray shows asymmetric lung fields, lung hypoplasia, or hyperinflation of the contralateral lung. It must be considered as a rare cause of recurrent lower respiratory tract infections in childhood and in subjects with a low threshold for or recurrent "High Altitude Pulmonary Edema".

Isolation and genetic analysis of bovine viral diarrhea virus from infected cattle in indiana.

Species and biotype distribution was determined in 44 bovine viral diarrhea virus- (BVDV-) positive samples submitted to the Animal Disease Diagnostic Laboratory (ADDL) in Indiana during 2006-2008. BVDV RNA was detected in the 5'-untranslated region and N(pro) region using reverse transcriptase PCR followed by sequencing analysis of the PCR product. Additionally, cases were classified into one of six categories according to history and/or lesions: acute symptomatic, hemorrhagic, respiratory distress, reproductive, persistent infection (PI), and mucosal disease (MD). Of 44 BVDV-positive samples, 33 were noncytopathic (ncp), 10 were cytopathic (cp), and one presented both ncp and cp biotypes. Sequencing analysis demonstrated that all samples belonged to BVDV-1a, BVDV-1b, or BVDV-2. The most common isolate was ncp BVDV-1b, (44%) followed by ncp BVDV-2a (24%). Among the six categories, respiratory clinical signs were the most common (36%) followed by PI (25%) and MD (16%).

Cutaneous and systemic poxviral disease in red (Tamiasciurus hudsonicus) and gray (Sciurus carolinensis) squirrels.

From September 2005 through October 2006, fibromatosis was diagnosed in 2 red squirrels (Tamiasciurus hudsonicus) and 1 gray squirrel (Sciurus carolinensis). All 3 squirrels had multifocal to coalescing, tan, firm alopecic cutaneous nodules. Two squirrels also had pulmonary nodules. Histologically, the cutaneous nodules had marked epidermal hyperplasia, with ballooning degeneration of keratinocytes, spongiosis, and eosinophilic cytoplasmic inclusions. The dermis was expanded by proliferation of atypical mesenchymal cells with cytoplasmic inclusions. Additional findings included pulmonary adenomatous hyperplasia with cytoplasmic inclusions, renal tubular epithelial hyperplasia with cytoplasmic inclusions, atypical mesenchymal proliferation in the liver, and atypical mesenchymal proliferation with cytoplasmic inclusions in the seminal vesicles. Ultrastructurally, poxviral particles were observed in skin scrapings and sections of cutaneous and pulmonary nodules. Polymerase chain reaction targeting the highly conserved Leporipoxvirus DNA polymerase gene was positive using DNA extracted from the cutaneous lesions of all 3 squirrels. Nucleotide sequence of the 390 base PCR amplicons was closely related to that of other members of the genus Leporipoxvirus. To the authors' knowledge, this is the first report of cutaneous and systemic poxviral disease in American red squirrels with molecular characterization of the squirrel fibroma virus.

Prevalence and characterization of bovine viral diarrhea virus in the white-tailed deer population in Indiana.

Bovine viral diarrhea (BVD) is one of the economically important diseases of cattle. For many years, different types of vaccines have been commercially available, yet this disease is hard to control in high-density population areas. Detection and isolation of bovine viral diarrhea virus (BVDV) from any potential reservoir is vital, especially when considering virus eradication from a herd or locale. One potential source is wild ruminants. Ear notches and lymph nodes were collected from the wild population of white-tailed deer (Odocoileus virginianus) during deer hunting season in Indiana and tested for BVDV with a commercial BVD antigen capture enzyme-linked immunosorbent assay. Two samples out of 745 collected samples were positive, and subsequently cp and ncp BVDV was isolated from 1 ear notch and 1 lymph node. These isolates were genotyped as type 1a and 1b based on sequence analysis of the 5' untranslated region (UTR). The results of the present study indicate that the prevalence of BVDV in the white-tailed deer population of Indiana is about 0.3%. Wild ruminants infected with BVDV should be taken into consideration during an eradication program of BVDV from the livestock population.

Mesial temporal lobe epilepsy: pathogenesis, induced rodent models and lesions.

Mesial temporal lobe epilepsy (MTLE), the most common epilepsy in adults, is generally intractable and is suspected to be the result of recurrent excitation or inhibition circuitry. Recurrent excitation and the development of seizures have been associated with aberrant mossy fiber sprouting in the hippocampus. Of the animal models developed to investigate the pathogenesis of MTLE, post-status epilepticus models have received the greatest acceptance because they are characterized by a latency period, the development of spontaneous motor seizures, and a spectrum of lesions like those of MTLE. Among post-status epilepticus models, induction of systemic kainic acid or pilocarpine-induced epilepsy is less labor-intensive than electrical-stimulation models and these models mirror the clinicopathologic features of MTLE more closely than do kindling, tetanus toxin, hyperthermia, post-traumatic, and perinatal hypoxia/ischemia models. Unfortunately, spontaneous motor seizures do not develop in kindling or adult hyperthermia models and are not a consistent finding in tetanus toxin-induced or perinatal hypoxia/ischemia models. This review presents the mechanistic hypotheses for seizure induction, means of model induction, and associated pathology, especially as compared to MTLE patients. Animal models are valuable tools not only to study the pathogenesis of MTLE, but also to evaluate potential antiepileptogenic drugs.

Toxoplasmosis in a woodchuck (Marmota monax) and two American red squirrels (Tamiasciurus hudsonicus).

Toxoplasmosis was diagnosed in a woodchuck (Marmota monax) and 2 American red squirrels (Tamiasciurus hudsonicus). The woodchuck was euthanized by a wildlife rescue organization in New York after progressive clinical signs of head tilt, circling, and rapid weight loss. Necropsy examination revealed acute subdural hemorrhage over the right cerebral hemisphere. Histologic lesions included meningoencephalitis, myocarditis, and hepatitis. Protozoal cysts were present in affected and unaffected neuroparenchyma. The squirrels were found dead, emaciated, and moderately infested with fleas near a park in northern Indiana. In both squirrels, the lungs were consolidated with numerous nodules up to 2 mm in diameter. Histologically, pneumonia and encephalitis were associated with intracellular and free protozoa. Additional histologic lesions included multifocal lymphoplasmacytic encephalitis with intralesional protozoa in both squirrels. The protozoa were positive with Toxoplasma gondii-specific immunohistochemistry and had ultrastructural features consistent with T. gondii in both squirrels. A real-time polymerase chain reaction test using T. gondii-specific probes demonstrated protozoal DNA in the lung, brain, and kidney of the squirrels and in the brain and heart of the woodchuck. To the authors' knowledge, this is the first report of toxoplasmosis in woodchucks or American red squirrels. Because rodents are common near urban settlements, this finding underscores their role as important intermediate hosts for T. gondii.

Extensive lesions of monkeypox in a prairie dog (Cynomys sp).

Monkeypox with extensive lesions was diagnosed in a prairie dog that was involved in a recent human outbreak of monkeypox in the Midwestern United States. Gross lesions included oral ulcers, pulmonary consolidation, enlarged cervical and thoracic lymph nodes, and multifocal, small, white umbilicated plaques in the gastrointestinal wall. Microscopic lesions were extensive in the lungs and consisted of fibrinonecrotic bronchopneumonia with vasculitis and poorly defined eosinophilic intracytoplasmic inclusion bodies in cells thought to be alveolar epithelial cells, histiocytes, and fibroblasts. Multifocal necrotizing lesions, often accompanied by myxedema, were also present in most of the other examined organs. Aggregates of pox viral particles were observed within lesions by transmission electron microscopy. Monkeypox virus infection was confirmed by real-time polymerase chain reaction and virus culture at the Centers for Disease Control and Prevention. This report highlights the difficulties of rapid diagnosis of exotic or emerging diseases and further substantiates the prairie dog as an animal model of monkeypox.

Investigation of an outbreak of encephalomyelitis caused by West Nile virus in 136 horses.

OBJECTIVE: To describe an outbreak of encephalomyelitis caused by West Nile virus (WNV) in horses in northern Indiana. DESIGN: Case series. ANIMALS: 170 horses. PROCEDURES: Horses with clinical signs suggestive of encephalomyelitis caused by WNV were examined. Date, age, sex, breed, and survival status were recorded. Serum samples were tested for anti-WNV antibodies, and virus isolation was attempted from samples of brain tissue. Climate data from local weather recording stations were collected. An epidemic curve was constructed, and case fatality rate was calculated. RESULTS: The most common clinical signs were ataxia, hind limb paresis, and muscle tremors and fasciculations. Eight horses had been vaccinated against WNV from 2 to 21 days prior to the appearance of clinical signs. West Nile virus was isolated from brain tissue of 2 nonvaccinated horses, and anti-WNV IgM antibodies were detected in 132 nonvaccinated horses; in 2 other nonvaccinated horses, anti-WNV antibodies were detected and WNV was also isolated from brain tissue. Thirty-one (22.8%) horses died or were euthanatized. The peak of the outbreak occurred on September 6, 2002. Ambient temperatures were significantly lower after the peak of the outbreak, compared with prior to the peak. CONCLUSIONS AND CLINICAL RELEVANCE: The peak risk period for encephalomyelitis caused by WNV in northern Indiana was mid-August to mid-September. Reduction in cases coincided with decreasing ambient temperatures. Because of a substantial case fatality rate, owners of horses in northern Indiana should have their horses fully protected by vaccination against WNV before June. In other regions of the United States with a defined mosquito breeding season, vaccination of previously nonvaccinated horses should commence at least 4 months before the anticipated peak in seasonal mosquito numbers, and for previously vaccinated horses, vaccine should be administered no later than 2 months before this time.

Epidemiologic study of relationships between consumption of commercial canned food and risk of hyperthyroidism in cats.

OBJECTIVE: To determine whether the increasing prevalence of feline hyperthyroidism is the result of aging of the cat population and whether consumption of canned foods at various times throughout life is associated with increased risk of hyperthyroidism. DESIGN: Retrospective and case-control studies. STUDY POPULATION: Medical records of 169,576 cats, including 3,570 cats with hyperthyroidism, evaluated at 9 veterinary school hospitals during a 20-year period, and 109 cats with hyperthyroidism (cases) and 173 cats without hyperthyroidism (controls). PROCEDURE: Age-adjusted hospital prevalence of hyperthyroidism was calculated by use of Veterinary Medical Database records. On the basis of owners' questionnaire responses, logistic regression was used to evaluate associations between consumption of canned food and development of hyperthyroidism. RESULTS: Age-specific hospital prevalence of feline hyperthyroidism increased significantly from 1978 to 1997. Overall, consumption of pop-top canned (vs dry) food at various times throughout life and each additional year of age were associated with greater risk of developing hyperthyroidism. In female cats, increased risk was associated with consumption of food packaged in pop-top cans or in combinations of pop-top and non-pop-top cans. In male cats, increased risk was associated with consumption of food packaged in pop-top cans and age. CONCLUSIONS AND CLINICAL RELEVANCE: These findings suggest that the increasing prevalence of feline hyperthyroidism is not solely the result of aging of the cat population and that canned foods may play a role.

Purification of turkey coronavirus by Sephacryl size-exclusion chromatography.

Sephacryl S-1000 size-exclusion chromatography was used to purify turkey coronavirus (TCoV) from infected turkey embryo. TCoV was propagated in the 22-day-old turkey embryos. Intestines and intestinal contents of infected embryos were harvested and homogenized. After low speed centrifugation, the supernatant was concentrated by ultracentrifugation through a cushion of 30 or 60% sucrose solution, or by ammonium sulfate precipitation. The purification methods included sucrose gradient and Sephacryl S-1000 size-exclusion chromatography. Ultracentrifugation through a cushion of 60% sucrose solution was better than the other two methods for concentration of TCoV from intestinal homogenate. The most effective method for purifying TCoV and removing extraneous materials was size-exclusion chromatography as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. More spike-rich particles were observed in the sample purified by chromatography than those purified by sucrose gradient as examined by electron microscopy. Differentiation of turkey anti-TCoV antiserum from normal turkey serum was better achieved by ELISA plates coated with TCoV preparation purified by size-exclusion chromatography than that purified by sucrose density gradient. The results indicated that Sephacryl S-1000 chromatography was useful for purification of TCoV.

Characterization of turkey coronavirus from turkey poults with acute enteritis.

The present study was to characterize turkey coronavirus associated with turkey poult enteritis and mortality. Intestinal contents or intestines from affected turkey poults and inoculated turkey embryos contained coronaviruses as revealed by electron microscopy or were positive for turkey coronavirus by immunofluorescent antibody assay. Sucrose density gradient ultracentrifugation of the virus-containing intestinal homogenate yielded two opalescent bands corresponding to the buoyant densities of 1.14-1.15 and 1.18-1.20 g/ml, respectively. Coronaviral particles from intestinal contents or the sucrose density gradient preparation were mainly spherical in shape and had envelope and central depression. They were surrounded by a fringe of regularly spaced petal-shaped projections attached to the particles by a short stalk. Purified viruses hemagglutinated rabbit erythrocytes with a titer of 16. Major protein bands of purified viruses analyzed by SDS-PAGE were located at 200, 100-110, 50-60, and 30-35 kDa. The patterns of protein bands were consistent with those of Minnesota or Quebec turkey coronavirus isolates. A 568 bp nucleotide fragment of turkey coronavirus spike protein gene was amplified from RNA of inoculated turkey embryo intestine or purified virus. Sequence analysis of the 568 bp PCR product revealed high degree of identity with the corresponding spike protein gene sequence of human and bovine coronaviruses. The results indicated that turkey coronavirus was associated with turkey poults with acute enteritis.

Prevention for the older woman. A practical guide to hormone replacement therapy and urogynecologic health.

Decisions to begin or continue hormone replacement therapy (HRT) are individualized, depending on a woman's anticipated benefits and risks from HRT. Estrogen, especially when begun early in menopause, has been shown to be beneficial in the prevention and treatment of osteoporosis. Potential risks of HRT include gallbladder disease, thromboembolism, and breast cancer. Systemic or topical estrogen can improve postmenopausal vaginal atrophy, vasomotor symptoms, and cervical cytologic changes. Treatment of other urogynecologic changes, such as vulval dystrophy and urinary incontinence, can relieve symptoms and improve the older woman's quality of life.

Humoral and cellular immune responses in turkey poults infected with turkey coronavirus.

The objective of the present study was to elucidate the kinetics of humoral and cellular immune responses of turkey poults infected with turkey coronavirus (TCV). Turkey poults were orally inoculated with TCV at 10 d of age, and the immune responses were analyzed at 1, 3, 7, 14, 21, 28, 42, and 63 d postinfection (PI) in three different experiments. Total Ig to TCV was initially detected at 7 and 14 d PI in Experiments 1 and 3. In addition, Ig gradually increased from 7 to 21 d PI and remained at 80 immunofluroescent antibody assay (IFA) titers or more thereafter. Lymphocyte proliferation responses of spleen cells to concanavalin A were higher in TCV-infected turkeys than in noninfected control turkeys with significant differences (P < 0.05) being noted at 14 and 63 d PI in Experiment 2 and at 3 and 28 d PI in Experiment 3. Strong IFA staining response to TCV antigen was observed in intestines of turkeys at 1, 3, and 7 d PI, and the response declined from 14 to 28 d PI in Experiment 3. In Experiment 3, the IgG isotype antibody response to TCV was markedly increased after 21 d PI and remained high until 63 d PI. The IgM isotype antibody response to TCV was 1.40 and 0.91 at 7 and 14 d PI, respectively. The IgA isotype antibody response to TCV was very low as detected at 7 (0.13), 14 (0.20), and 21 (0.17) d PI. Turkeys infected with TCV had significantly higher (P < 0.05) antibody response to sheep erythrocytes than noninfected controls at 7 d PI. Virus-specific lymphocyte proliferation response of spleen cells was significantly stimulated (P < 0.05) at 63 d PI in Experiment 3. The proportion of the CD4+ subpopulation of T lymphocytes was significantly increased (P < 0.05) at 1, 7, and 21 d PI in Experiment 3. The results indicate that humoral and cellular immunities to TCV are elicited in turkeys following infection with TCV.

Prevention for the older woman. A practical guide to assessing physical and cognitive function.

Life expectancy of women is greater than that of men at every age. Thus, an older woman is more likely than a man to be living without a spouse and living alone. It is important in caring for an older woman to establish how well she is functioning physically and cognitively and in what activities she may need assistance. Given the high prevalence of dementia with advanced age, screening for dementia should be considered in women over age 75. Although their risk of suicide is lower, older women are more likely to be depressed than older men, regardless of race, ethnic background, or economic status. Late-life depression is treatable, and screening should be considered in the presence of a major life change, recent stroke, or MI.

Coronary artery disease in women: different, often undertreated.

Cardiovascular disease is responsible for more deaths in women each year than all other causes combined. Women have different cardiac presentations than men and are more likely to be underdiagnosed and undertreated for coronary artery disease. This article addresses gender-specific issues in prevention, diagnosis, and treatment of coronary artery disease.

Differences in breast cancer screening rates: an issue of ethnicity or socioeconomics?

Previous reports suggest that use of preventive measures, such as screening mammography (SM), differs by ethnicity. It is unclear, however, if this is determined directly by ethnicity or indirectly by related socioeconomic factors. We studied self-reported data from 18,245 women aged 40-49 who participated in the Behavioral Risk Factor Surveillance System telephone survey in 1992 and 1993. Of these, 11,509 (63%) reported having obtained mammography within the preceding 2 years for screening purposes only. Using reports of other preventive healthcare behaviors, education level, socioeconomic status, and healthcare access problems as independent variables, bivariate associations were assessed, and a logistic regression model was developed. Models for each ethnic group were developed, with consistent results. Women who engaged in other preventive health measures, such as Pap smear (odds ratio [OR] 8.99, 95% confidence interval [CI] = 7.6-10.7), cholesterol measurement (OR 2.64, 95% CI = 2.3-3.0), and seatbelt use, were more likely to obtain SM. Women with healthcare access or insurance problems (OR 0. 59, 95% CI = 0.5-0.7) and current smokers (OR 0.71, CI = 0.6-0.8) had a lower likelihood of obtaining SM. Ethnicity, alcohol use, marital status, and education level were not significantly associated with women's reports of SM. Although ethnicity apparently does not influence a woman's likelihood of obtaining SM, access to healthcare and insurance and engaging in other healthy behaviors do. Health policy planners should consider the importance of these related factors when developing preventive health programs for women.