The risk factors and laboratory diagnostics for post renal transplant tuberculosis: a case-control, country-wide study on definitive cases

Background. Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipients and, because of its infrequency and the lack of medical awareness, it is usually misdiagnosed. This study was carried out to determine frequency and weight of multiple risk factors for post kidney transplantation TB.
Methods. A total of 44 cases (0.3%), out of 12,820 patients from 12 major kidney transplantation centers in Iran from 1984 to 2003, were compared with 184 healthy transplant subjects who were transplanted by the same surgical team.
Results. The mean age of cases and controls was 37.7 (13–63) and 35.6 (8–67) years ( P =0.3), respectively. The mean duration of pre-transplantation hemodialysis was 30.3 (3–168) months in cases and 18.2 (1–180) months in controls ( P =0.03). A positive past history of TB was detected in 2 cases and 1 control ( P =0.3). The mean doses of initial and maintenance immunosuppressive drugs in cases and controls were not significantly different. A total of 25 cases (56.8%) and 60 controls (32.6%) had rejection before diagnosis of TB ( P =0.004; OR=2.7, CI_95%: 1.3–5.6).
Conclusions. To our knowledge, this is the first study that demonstrated an increase in the risk of post-transplant TB by increasing the duration of pre-transplant hemodialysis and the number of post-transplant rejection episodes as 2 immunocompromised states. Further study is needed to clarify our new findings, specifically in relation to different immunosuppressive regimens.     

mtDNA mutations increase tumorigenicity in prostate cancer

Mutations in the mtDNA have been found to fulfill all of the criteria expected for pathogenic mutations causing prostate cancer. Focusing on the cytochrome oxidase subunit I (COI) gene, we found that 11-12% of all prostate cancer patients harbored COI mutations that altered conserved amino acids (mean conservation index=83%), whereas <2% of no-cancer controls and 7.8% of the general population had COI mutations, the latter altering less conserved amino acids (conservation index=71%). Four conserved prostate cancer COI mutations were found in multiple independent patients on different mtDNA backgrounds. Three other tumors contained heteroplasmic COI mutations, one of which created a stop codon. This latter tumor also contained a germ-line ATP6 mutation. Thus, both germ-line and somatic mtDNA mutations contribute to prostate cancer. Many tumors have been found to produce increased reactive oxygen species (ROS), and mtDNA mutations that inhibit oxidative phosphorylation can increase ROS production and thus contribute to tumorigenicity. To determine whether mutant tumors had increased ROS and tumor growth rates, we introduced the pathogenic mtDNA ATP6 T8993G mutation into the PC3 prostate cancer cell line through cybrid transfer and tested for tumor growth in nude mice. The resulting mutant (T8993G) cybrids were found to generate tumors that were 7 times larger than the wild-type (T8993T) cybrids, whereas the wild-type cybrids barely grew in the mice. The mutant tumors also generated significantly more ROS. Therefore, mtDNA mutations do play an important role in the etiology of prostate cancer.     

rTMS for the Treatment of Depression: a Comprehensive Review of Effective Protocols on Right DLPFC

Major depressive disorders (MDDs) are the most common and debilitating diseases worldwide. Repetitive transcranial magnetic stimulation (rTMS) has been widely used as an alternative or adjunctive treatment for different types of depression disorders, including drug-resistant major depressions. Despite controversial findings on the therapeutic outcomes of this technique, the general consent is developing this technique as an alternative treatment for depression disorders. Notwithstanding one protocol of rTMS has been approved by FDA for the acute treatment of major depression, studies are ongoing for finding more efficient protocols. This study aimed to comprehensively overview the effective rTMS protocols applied on left dorsolateral prefrontal cortex DLPFC for MDDs. The databases of PubMed (1985–2015), Web of Sciences (1985–2015), and Google Scholar (1980–2015) were searched using the set terms. The obtained results were screened for the relevant contents by two authors, and the appropriate studies were selected for further review. The most widely used protocols for depression are 1Hz for right and 10Hz for left DLPFC. In addition, the main parameters of these protocols and the main neurophysiological mechanisms of two common frequencies of 1 and 10 Hz are summarized. Different protocols of rTMS, particularly low versus high frequencies, result in significantly different electrophysiological and neurocognitive changes in the subject. Low frequency rTMS modulates frontal alpha power asymmetry and high frequency protocols influence more broader regions and wider electrophysiological characteristics of the brain.     

Increased the circulating levels of malondialdehyde in patients with obstructive sleep apnea: a systematic review and meta-analysis

Sleep and Breathing - Obstructive sleep apnea (OSA) is a prevalent sleep disorder associated with increased risk of cardiovascular disease. Several studies have&nbsp;demonstrated elevated...     

Implication of invalidation concept in fibromyalgia diagnosis

Clinical Rheumatology - The invalidation or social pain is an important but neglected issue in polysymptomatology of fibromyalgia (FM). This study sought whether tracing-perceived invalidation...     

Measuring tuberculosis burden, trends, and the impact of control programmes

The targets for tuberculosis control, framed within the United Nations' Millennium Development Goals, are to ensure that the incidence per head of tuberculosis is falling by 2015, and that the 1990 prevalence and mortality per head are halved by 2015. In monitoring progress in tuberculosis control, the ultimate aim for all countries is to count tuberculosis cases (incidence) accurately through routine surveillance. Disease prevalence surveys are costly and laborious, but give unbiased measures of tuberculosis burden and trends, and are justified in high-burden countries where many cases and deaths are missed by surveillance systems. Most countries in which tuberculosis is highly endemic do not yet have reliable death registration systems. Verbal autopsy, used in cause-of-death surveys, is an alternative, interim method of assessing tuberculosis mortality, but needs further validation. Although several new assays for Mycobacterium tuberculosis infection have recently been devised, the tuberculin skin test remains the only practical method of measuring infection in populations. However, this test typically has low specificity and is therefore best used comparatively to assess geographical and temporal variation in risk of infection. By 2015, every country should be able to assess progress in tuberculosis control by estimating the time trend in incidence, and the magnitude of reductions in either prevalence or deaths.     

Articular cartilage of the knee 3 years after ACL reconstruction: A quantitative T2 relaxometry analysis of 10 knees

Background and purpose

T1ρ or T2 relaxation imaging has been increasingly used to evaluate the cartilage of the knee. We investigated the cartilage of ACL-reconstructed knees 3 years after surgery using T2 relaxation times.

Patients and methods

10 patients with a clinically successful unilateral ACL reconstruction were examined 3 years after surgery. Multiple-TE fast-spin echo sagittal images of both knees were acquired using a 3T MRI scanner for T2 mapping of the tibiofemoral cartilage. T2 values of the superficial and deep zones of the tibiofemoral cartilage were analyzed in sub-compartmental areas and compared between the ACL-reconstructed and uninjured contralateral knees.

Results

Higher T2 values were observed in 1 or more sub-compartmental areas of each ACL-reconstructed knee compared to the uninjured contralateral side. Most of the T2 increases were observed at the superficial zones of the cartilage, especially at the medial compartment. At the medial compartment of the ACL-reconstructed knee, the T2 values of the femoral and tibial cartilage were increased by 3–81% compared to the uninjured contralateral side, at the superficial zones of the weight-bearing areas. T2 values in the superficial zone of the central medial femoral condyle differed between the 2 groups (p = 0.002).

Interpretation

The articular cartilage of ACL-reconstructed knees, although clinically satisfactory, had higher T2 values in the superficial zone of the central medial femoral condyle than in the uninjured contralateral side 3 years after surgery. Further studies are warranted to determine whether these patients would undergo cartilage degeneration over time.ACL reconstruction is widely used to restore stability of the knee after ACL injury. However, after 10–15 years of follow-up, osteoarthritis (OA) has been reported in 15–85% of patients (Ajuied et al. 2013, Chalmers et al. 2014). Radiographic features of OA appear only after substantial deterioration has occurred, and several years—or even decades—probably separate the first molecular changes from overt radiographic changes. Considerable progress has been made in explaining these early molecular changes by detecting alterations in the biochemical composition of the cartilage using MRI biomarkers such as T1ρ, T2, dGEMRIC, and sodium MRI (Choi and Gold 2011). These studies indicated that MR measurements of biomarkers might be an efficient tool for detection of changes in the biochemical composition of articular cartilage.Recently, some studies have used biochemical MRI methods to investigate the matrix changes in articular cartilage following ACL reconstruction, and early changes in the biochemical composition of articular cartilage in ACL-reconstructed knees have been investigated in relation to healthy populations or uninjured contralateral knees (Li et al. 2011, Haughom et al. 2012, Hirose et al. 2013, Su et al. 2013, Van Ginckel et al. 2013, Theologis et al. 2014). As progression of cartilage degeneration can be a long-term process, data on changes in the biochemical properties of cartilage at different postoperative times and in different patient populations are necessary for quantitative evaluation of cartilage degeneration after the surgery. We therefore conducted this study to evaluate the biochemical status of articular cartilage in ACL-reconstructed knees using T2 relaxation times (T2 values) at 3-year follow-up. The uninjured, healthy contralateral knees were used as a control, to eliminate inter-subject variation. The working hypothesis was that the cartilage in ACL-reconstructed knees would have higher T2 values than cartilage in uninjured contralateral knees 3 years after surgery.