Suppression of serum lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism by intensive insulin therapy in the first year of type 1 diabetes mellitus: Prospective InLipoDiab1 study

Background and aimsCholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are crucial proteins in reverse cholesterol transport. There are insufficient data on regulating these proteins by insulin therapy in type 1 diabetes mellitus (T1DM). We aimed to assess prospectively the impact of insulin therapy initiation on transfer proteins serum levels in adults with newly diagnosed T1DM.Methods and results57 adults with newly diagnosed T1DM were enrolled in the InLipoDiab1 Study. All participants were treated with subcutaneous insulin in the model of intensive insulin therapy since the diagnosis of diabetes. Serum PLTP and CETP concentrations were measured at diagnosis, after three weeks, six months, and after one year of insulin treatment, using the immunoenzymatic method ELISA.A significant decrease in PLTP and CETP concentrations were demonstrated during twelve months of insulin therapy in newly diagnosed T1DM. The dynamics of changes in the level of these proteins varied depending on the occurrence of remission after a year of the disease. In the group without remission, a significant decrease in PLTP and CETP levels appeared after six months of follow-up. The remission group was characterized by a decrease in proteins concentration only after one year of treatment. In the non-remission group, significant negative correlations were found between the daily dose of insulin and levels of PLTP and CETP.ConclusionExogenous insulin is an inhibitor of lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism in the first year of treatment.     

Multivariate analysis of risk factors for development of duodenal ulcer in Helicobacter pylori-infected patients

BACKGROUND: Although Helicobacter pylori is a significant etiologic factor of peptic ulcer disease, it remains unknown why ulcers develop only in the minority of infected individuals. AIM: The aim of this cross-sectional study was to evaluate the association between the presence of duodenal ulcer in H. pylori-infected patients and different risk factors. METHODS: A total of 122 H. pylori-infected patients were enrolled; 79 had duodenal ulcer and 43 gastritis. Univariate analysis was conducted using either Fisher's exact test or exact Cochrane-Armitage trend test. In multivariate analysis the logistic model was used. RESULTS: Univariate analysis indicated six factors (male sex, smoking, antral H. pylori density, CAGA presence in antrum, and VACA s1a presence in antrum and corpus). Four factors (sex, smoking-alcohol index, H. pylori density index, and CAGA index) were found to be significant in multivariate analysis. The best model predicting duodenal ulcer included male sex, smoking, presence of H. PYLORI on histopathology in antrum and CAGA presence in corpus. CONCLUSION: Although several risk factors were significantly associated with duodenal ulcer, we failed in the identification of either a single risk factor or a set of factors that can unequivocally differentiate patients with ulcer from those with gastritis.     

Gentamicin affects melanogenesis in normal human melanocytes

Background: Aminoglycoside antibiotics, including gentamicin, despite their ability to induce adverse effects on pigmented tissues, remain valuable and sometimes indispensable for the treatment of various infections. It is known that gentamicin binds to melanin biopolymers, but the relation between this drug affinity to melanin and its toxicity is not well documented. The aim of this work was to examine the impact of gentamicin on viability and melanogenesis in HEMa-LP (light pigmented) and HEMn-DP (dark pigmented) normal human melanocytes.

Methodology/principal findings: The effect of gentamicin on cell viability was determined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay; melanin content and tyrosinase activity were measured spectrophotometrically. It has been demonstrated that gentamicin induces concentration-dependent loss in melanocytes viability. The application of antibiotic in concentration of 10?mM causes higher reduction in viability of the light pigmented melanocytes (by about 74%) when compared with the dark pigmented ones (by about 62%). The value of the concentration of a drug that produces loss in cell viability by 50% (EC₅₀) for both cell lines was found to be ～7.5?mM. It has been shown that gentamicin causes inhibition of tyrosinase activity and reduces melanin content in light pigmented melanocytes significantly more than in the dark pigmented cells.

Conclusion/significance: We have found that gentamicin modulates melanization process in melanocytes in vitro, what may explain the potential role of melanin biopolymer in the mechanisms of undesirable toxic effects of this drug in vivo, as a result of its accumulation in pigmented tissues. We have also stated that the melanogenesis process in light pigmented melanocytes is more sensitive to the inhibitory effect of gentamicin than in the dark pigmented cells.     

A Model of Shared Mycobacteriology Testing Services: Lessons Learned

Objective

The need for public health laboratories (PHLs) to prioritize resources has led to increased interest in sharing diagnostic services. To address this concept for tuberculosis (TB) testing, the New York State Department of Health Wadsworth Center and the Rhode Island State Health Laboratories assessed the feasibility of shared services for the detection and characterization of Mycobacterium tuberculosis complex (MTBC).

Methods

We assessed multiple aspects of shared services including shipping, testing, reporting, and cost. Rhode Island State Health Laboratories shipped MTBC-positive specimens and isolates to Wadsworth Center. Average turnaround times were calculated and cost analysis was performed.

Results

Testing turnaround times were similar at both PHLs; however, the availability of conventional drug susceptibility testing (DST) results for Rhode Island primary specimens and isolates were extended by approximately four days of shipping time. An extended molecular testing panel was performed on every specimen submitted from Rhode Island State Health Laboratories to Wadsworth Center, and the total cost per specimen at Wadsworth Center was $177.12 less than at Rhode Island State Health Laboratories, plus shipping. Following a mid-study review, Wadsworth Center provided testing turnaround times for detection (same day), species determination of MTBC (same day), and molecular DST (2.5 days).

Conclusion

The collaboration between Wadsworth Center and Rhode Island State Health Laboratories to assess shared services of TB testing highlighted a successful model that may serve as a guideline for other PHLs. The provision of additional rapid testing at a lower cost demonstrated in this study could potentially improve patient management and result in significant cost and resource savings if used in similar models across the country.Public health laboratories (PHLs) are essential for disease prevention and control. They serve as a first line of defense by rapidly recognizing and averting the spread of communicable diseases. In addition, they play a critical role in providing specialized tests for low-incidence, high-risk diseases, such as tuberculosis (TB), rabies, and botulism.¹ Due to recent economic constraints, many PHLs have suffered financial pressures, including budget and staffing cuts. In some cases, PHLs have reduced or eliminated certain tests, creating a potential risk to the public''s health. As an alternative to the discontinuation of services, one suggested approach was the investigation of shared services with other PHLs in different jurisdictions through testing directories and pilot projects with assistance and support from the Centers for Disease Control and Prevention (CDC) and the Association of Public Health Laboratories (APHL).^2,3TB, which is caused by the bacteria Mycobacterium tuberculosis, is a disease for which PHLs play an important role by providing diagnostics that contribute to prevention. Despite an overall decline in cases, TB continues to be a significant burden on social, public health, and economic systems in the United States.⁴ Maintaining a comprehensive and efficient laboratory system is critical to the continued decline of TB rates and overall prevention and control of TB in the United States. However, providing comprehensive TB testing services is becoming increasingly expensive per case identified. Additionally, retaining technical proficiency remains a challenge, especially as many experienced personnel are lost to retirement and are difficult to replace.⁵In 2013, a total of 9,582 new TB cases were reported in the United States, with an incidence rate of 3.0 cases per 100,000 population. Only four states reported more than 500 cases of TB: California, Texas, New York, and Florida, accounting for half of all TB cases in the United States. The TB incidence rate in New York State (NYS) is 4.4 per 100,000 population.⁴ The overall number of TB cases in NYS has decreased slightly over time, while the number of drug-resistant TB (DR TB) cases has remained steady during the past five years. Additionally, the percentage of multidrug-resistant TB (MDR TB) cases in NYS has increased from 1.3% to 3.6% during the past five years.⁶ In contrast, the TB incidence rate in Rhode Island is 2.6 per 100,000 population, and the overall number of TB cases has remained constant; DR TB and MDR TB cases in Rhode Island are rare.^4,7 Given the low number of TB-positive specimens received each year in Rhode Island State Health Laboratories, developing an extensive, increasingly molecular-based, testing program for TB may not be cost effective. In contrast, a high proportion of specimens received each year by the NYS Department of Health Wadsworth Center are Mycobacterium tuberculosis complex (MTBC) positive, including DR TB and MDR TB cases, and an extensive testing program has been implemented.We assessed the feasibility of shared services for the detection and characterization of MTBC between Wadsworth Center and Rhode Island State Health Laboratories during a 10-month time period. Multiple aspects critical to the implementation of shared services were examined, including shipping, testing, reporting, and cost. During this project, Wadsworth Center provided services to Rhode Island State Health Laboratories for rapid detection of MTBC, MTBC species identification, rapid detection of mutations associated with rifampin and isoniazid resistance, and conventional drug susceptibility testing (DST). Importantly, this partnership allowed Wadsworth Center to assess its ability to share its extended testing capabilities with another PHL, determine if the additional services provided were beneficial to patient treatment and outcomes, and identify any potential issues with this testing approach.     

The self-reported use of research in clinical practice: A survey of occupational therapists in Sweden

Background: Today, healthcare providers and occupational therapists are increasingly required to rely on evidence-based practices. In both outpatient and inpatient settings, the use of research-based practices can be identified using the Research Utilization Measure questionnaire. Aim: This study explores how occupational therapists in Sweden perceive research utilization. Method: The Research Utilization Measure was sent to 807 randomly selected occupational therapists in Sweden, and the response rate was 59% (n = 472). Results: The majority of respondents (56%, n = 256) reported use of research-based knowledge in their practice “very or rather often”, although 49% (n = 225) of the therapists noted that they “very seldom or never” discussed research findings with their managers. Differences in answers for most items were related to degree of education and length of experience. Occupational therapists with higher education levels more often reported use of research in their clinical practice and therapists with greater experience less often reported use of research in their clinical practice. Conclusion: Education seems to influence the degree to which occupational therapists rely on research to inform their practices. A future challenge for managers and occupational therapists is to create strategic discussions on how to implement treatment that is based on current research.