Protein kinetic signatures of the remodeling heart following isoproterenol stimulation

Protein temporal dynamics play a critical role in time-dimensional pathophysiological processes, including the gradual cardiac remodeling that occurs in early-stage heart failure. Methods for quantitative assessments of protein kinetics are lacking, and despite knowledge gained from single-protein studies, integrative views of the coordinated behavior of multiple proteins in cardiac remodeling are scarce. Here, we developed a workflow that integrates deuterium oxide (²H₂O) labeling, high-resolution mass spectrometry (MS), and custom computational methods to systematically interrogate in vivo protein turnover. Using this workflow, we characterized the in vivo turnover kinetics of 2,964 proteins in a mouse model of β-adrenergic–induced cardiac remodeling. The data provided a quantitative and longitudinal view of cardiac remodeling at the molecular level, revealing widespread kinetic regulations in calcium signaling, metabolism, proteostasis, and mitochondrial dynamics. We translated the workflow to human studies, creating a reference dataset of 496 plasma protein turnover rates from 4 healthy adults. The approach is applicable to short, minimal label enrichment and can be performed on as little as a single biopsy, thereby overcoming critical obstacles to clinical investigations. The protein turnover quantitation experiments and computational workflow described here should be widely applicable to large-scale biomolecular investigations of human disease mechanisms with a temporal perspective.     

Efficacy of a single dose of cefazolin as a prophylactic antibiotic in primary arthroplasty

We analyzed the wound infection rate of 1,367 primary total hip and knee arthroplasties performed between 1991 and 1999. Two hundred and fifteen arthroplasties were performed with 3 doses (3 x 750 mg) of cefuroxime, and 1,152 arthroplasties were performed with a single preoperative dose (1 x 1 g) of cefazolin as antimicrobial prophylaxis. All wound infections that occurred within 2 years of the index surgery were analyzed. The deep wound infection rate of total hip arthroplasty was 1.1% (95% confidence interval [CI], 0%-3.3%) in the cefuroxime group and 1.1% (95% CI, 0%-2.2%) in the cefazolin group (Fisher's exact test, P = 1.0). The deep wound infection rate of total knee arthroplasty in the cefuroxime group (1.6%; 95% CI, 0%-3.8%) was not significantly different from the cefazolin group (1.0%; 95% CI, 0.3%-1.7%) (Fisher's exact test, P =.63). We concluded that a single dose (1 g) of cefazolin given at anesthetic induction offered similar protection to 3 doses (3 x 750 mg) of cefuroxime in preventing infection in primary total joint arthroplasty.     

Tobacco,alcohol intake,and diet in relation to adenocarcinoma of the esophagus and gastric cardia

Little is known about the etiology of adenocarcinoma of the distal esophagus/cardia, a cancer which has increased in incidence in the United States over the last two decades. We analyzed data on smoking, alcohol use, dietary intake, and other factors obtained from 173 hospitalized males with adenocarcinoma of the distal esophagus/cardia (cases) and 4,544 hospitalized males with diseases not related to smoking and of other organ systems than the gastrointestinal tract (controls). Cases of squamous cell carcinoma of the esophagus (n=136) and adenocarcinoma of the distal stomach (n=122) were included as separate case groups. All subjects were interviewed in 28 hospitals in eight cities in the US between 1981 and 1990. After adjustment for covariates, the odds ratio (OR) for adenocarcinoma of the distal esophagus/cardia for current smokers was 2.3 (95 percent confidence interval [CI]=1.4–3.9) and that for ex-smokers was 1.9 (CI=1.2–3.0) relative to never-smokers. The OR for drinkers of four or more ounces of whiskey-equivalents of alcohol per day (relative to those consuming less than one drink per week) was 2.3 (CI=1.3–4.3). Intakes of total fat and vitamin A from animal sources were significant risk factors and fiber intake was associated inversely with adenocarcinoma of the distal esophagus/cardia. Although the number of female cases of adenocarcinoma of the distal esophagus/cardia was small (n=21), significant associations were observed for smoking and alcohol.Dr Kabat is in the Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, NY, USA. At the time of this work be was with the Division of Epidemiology, American Health Foundation, New York, NY. Drs Ng and Wynder are with the Division of Epidemiology, American Health Foundation. Address correspondence to Dr Kabat, Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Belfer Bldg, Rm 1302, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Supported by National Cancer Institute Program Project grant CA32617 and Center grant CA17613.     

Prospective study of community-acquired rotavirus infection.

We determined titers of group A rotavirus common antibodies and neutralizing antibodies against serotypes 1 to 4 of prototype human rotavirus (HRV) in cord blood and serum specimens obtained from 38 infants at 4-month intervals from birth until 2 years of age. Nineteen of the infants developed one episode of HRV diarrhea each, and they were matched by age and birth weight with the other 19 infants, who did not develop HRV diarrhea during the follow-up period. We estimated the incidence rate of HRV infection for the two groups of infants combined to be a minimum of 1.34 episodes per infant per year, which is 22 times more common than the occurrence of overt disease caused by the virus in this community. The infection occurred constantly throughout the first 2 years of infancy, whereas all but one of the 19 episodes of overt disease occurred before 12 months of age. Seven of these overt episodes were preceded by at least one episode of subclinical infection earlier, and the other seven were probably due to primary HRV infection. The remaining five episodes occurred before 4 months of age, so that we could not ascertain whether they were due to primary infections because of the presence of maternal antibodies. We showed that levels of HRV antibodies in serum specimens obtained before clinical onset of diarrhea varied widely, and, for most infants in the diarrheal group, levels of these antibodies were similar to those in the serum specimens obtained at the same times from the corresponding age- and birth weight-matched control infants. Nevertheless, the age at which overt disease caused by HRV was most prevalent coincided with the time when the maternal antibodies had declined to low levels but the infants had not yet acquired high titers of these antibodies in their sera.     

One stage placement of permanent implant compared to two stage tissue expander reconstruction

With the advent of the skin sparing mastectomy, immediate breast reconstruction with placement of the definitive prosthesis at the time of mastectomy is possible. The question remains: does single-stage prosthetic reconstruction result in greater numbers of complications or rates of re-operation, compared to two-stage tissue expander reconstruction? A retrospective cohort study of a single centre?s experience with these techniques was carried out. From 2004 to 2012, 54 cases of immediate breast reconstruction with implant were identified, and 108 cases of immediate breast reconstruction using a tissue expander were identified. Gathered preoperative data included tumour, prior exposure to radiation, preoperative chemotherapy, smoking, and comorbidities. Complication rates, as well as the rate of secondary operations, were examined. There were no significant increased risks in the rate of post-operative complications (p?=?.910, odds ratio?=?0.9) nor in the rate of re-operation (p?=?0.421, odds ratio?=?1.4) associated with the insertion of a definitive prosthesis at the time of skin sparing mastectomy. However, previously radiated breasts experienced a 100% rate of wound complications in our subset of 9 breasts that underwent one stage breast reconstruction with immediate final prosthesis placement. Our study suggests that patients with early stage disease can undergo single stage breast reconstruction without increased risk of complications nor need for secondary operations. While the mean time to completion of the reconstructive process is shortened by 5 months with the single stage technique, implant based breast reconstruction requires careful counseling and patient selection in radiated patients.     

Long-term disease-free survival in three ovarian cancer patients with a single relapse

Recurrent ovarian cancer with long-term survival is uncommon and often associated with poor prognosis. We report three cases of patients with advanced ovarian cancer who have achieved long-term disease-free survival following a single prior relapse. Case 1 relapsed with a localized bulky tumor and received a complete surgical resection and chemotherapy. Case 2 had a persistent central pelvic tumor after debulking surgery and second-line chemotherapy, and yet achieved excellent control with concurrent chemoradiation to the true pelvis. Case 3 relapsed with paraaortic lymph node metastasis and probable lung metastasis (subsequently negated by positron emission tomography) and received chemotherapy alone. These three patients have since remained disease-free for 13, 12, and seven years, respectively, since their first relapse. We conclude that select patients can obtain long-term disease-free survival after the first relapse by accurate restaging and aggressive multimodality treatment.     

Investigation of SLC2A1 26177A/G gene polymorphism via high resolution melting curve analysis in Malaysian patients with diabetic retinopathy

PurposeIn this study, we aimed to investigate the possible association between SLC2A1 26177A/G polymorphism and diabetic retinopathy (DR) in Malaysian patients with type 2 diabetes.MethodsGenomic DNA was extracted from 211 Malaysian type 2 diabetic patients (100 without retinopathy [DNR], 111 with retinopathy) and 165 healthy controls. A high resolution melting assay developed in this study was used to detect SLC2A1 26177A/G polymorphism followed by statistical analysis.ResultsA statistically significant difference in 26177 G minor allele frequency between healthy controls (19.7 %) and total patient group (26.1 %) (p < 0.05, Odd ratio = 1.437, 95% Confidence interval = 1.015–2.035) as well as between healthy controls (19.7 %) and DNR patients (27.5%) (p < 0.05, Odd ratio = 1.546, 95% Confidence interval = 1.024–2.336) was shown in this study. However, when compared between DR and DNR patients, there was no significant difference (p > 0.05).ConclusionsThis is the first study which shows that SLC2A1 26177G allele is associated with type 2 diabetes in Malaysian population but not with DR.     

Transmission modes of severe acute respiratory syndrome coronavirus 2 and implications for infection control: a review

The complete picture regarding transmission modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. This review summarises the available evidence on its transmission modes, our preliminary research findings and implications for infection control policy, and outlines future research directions. Environmental contamination has been reported in hospital settings occupied by infected patients, and is higher in the first week of illness. Transmission via environmental surfaces or fomites is likely, but decontamination protocols are effective in minimising this risk. The extent of airborne transmission is also unclear. While several studies have detected SARS-CoV-2 ribonucleic acid in air samples, none has isolated viable virus in culture. Transmission likely lies on a spectrum between droplet and airborne transmission, depending on the patient, disease and environmental factors. Singapore’s current personal protective equipment and isolation protocols are sufficient to manage this risk.     

A comparative study of epithelial cell proliferation between the odontogenic keratocyst, orthokeratinized odontogenic cyst, dentigerous cyst, and ameloblastoma

OBJECTIVES: The aim of the present study was to compare the proliferation index of the epithelial cells between odontogenic keratocysts (OKC), orthokeratinized odontogenic cysts (OOC), dentigerous cysts (DC), and ameloblastomas. MATERIALS AND METHODS: The proliferation index, employing a novel cell proliferation marker IPO-38, was studied by the immunohistochemical technique in 10 OKC, seven OOC, eight DC and 10 ameloblastomas. RESULTS: The ameloblastoma had no higher labeling index (LI) of IPO-38 than the OKC (P = 0.910) but had higher LI than the OOC (P = 0.001) and DC (P = 0.000); the OKC had higher LI than the OOC (P = 0.002) and DC (P = 0.000); and the OOC had higher LI than the DC (P = 0.011). IPO-38-positive cells in the OKC and OOC were located principally in the suprabasal cell layers while the ameloblastoma were found in the peripheral portion in particularly, the follicular and plexiform types. CONCLUSION: These findings support previous studies that the proliferation indices are useful in predicting the different biological behavior of the odontogenic lesions and the OKC should be regarded as a benign tumor rather than simply an odontogenic cyst.