Lack of association of KIR2DL1-R245 and KIR2DL1-C245 with HIV-1 control in black South Africans with HLA-C2

Activating/inhibitory Killer-cell Immunoglobulin-like Receptors (KIRs) partly regulate Natural Killer (NK) cells. KIR2DL1 allotypes with cysteine at position-245 (KIR2DL1-C²⁴⁵) express at lower levels and demonstrate weaker inhibitory signaling compared to allotypes with arginine at position-245 (KIR2DL1-R²⁴⁵). The functional consequence of either allotype in infectious diseases is unknown. Since NK cells mediate antiviral immunity, we investigated KIR2DL1-R²⁴⁵ and KIR2DL1-C²⁴⁵ in association with HIV-1 virological control in untreated immunocompetent black South Africans. Allotype carriage, determined by KIR2DL1 sequencing, was similar between uninfected South Africans (n = 104) and other black African populations, but differed significantly from Europeans, while no significant differences were noted between uninfected and HIV-1-infected individuals (n = 52). KIR2DL1 expression, measured by flow cytometry, in uninfected individuals showed higher KIR2DL1-R²⁴⁵ expression compared to KIR2DL1-C²⁴⁵ in white donors (n = 27), while black donors (n = 21) generally expressed lower levels of both allotypes. KIR2DL1 expression was reduced in HLA-C2 carriers, most evident in black HLA-C2/C2 donors. KIR2DL1-R²⁴⁵ and KIR2DL1-C²⁴⁵ did not associate with viral load when HLA-C2 ligands were present, however in HLA-C1 homozygotes, individuals with only KIR2DL1-R²⁴⁵, showed lower viral loads compared to carriers of both allotypes. The lack of association of KIR2DL1-R²⁴⁵ or KIR2DL1-C²⁴⁵ with HIV-1 control in HLA-C2 carriers may relate to lower KIR2DL1 expression levels in a population with high HLA-C2 prevalence.     

Increased response variability as a marker of executive dysfunction in veterans with post-traumatic stress disorder

The stability of cognitive control processes over time can be indexed by trial-to-trial variability in reaction time (RT). Greater RT variability has been interpreted as an indicator of executive dysfunction, inhibitory inefficiency, and excessive mental noise. Previous studies have demonstrated that combat veterans with post-traumatic stress disorder (PTSD) show substantial impairments in inhibitory control, but no studies have examined response variability in this population. In the current experiment, RT variability in the Go/NoGo response inhibition task was assessed for 45 veterans with PTSD and 34 control veterans using the intra-individual coefficient of variation (ICV) and ex-Gaussian analysis of RT distributions. Despite having mean RTs that were indistinguishable from controls, the PTSD patients had significantly greater RT variability as measured by ICV. More variable RTs were in turn associated with a greater number of false alarm errors in the patients, suggesting that less consistent performers were less successful at inhibiting inappropriate responses. RT variability was also highly correlated with self-reported symptoms of PTSD, depression, and attentional impulsiveness. Furthermore, response variability predicted diagnosis even when controlling for PTSD symptom severity. In turn, PTSD severity was correlated with self-rated attentional impulsiveness. Deficits in the top-down cognitive control processes that cause greater response variability might contribute to the maintenance of PTSD symptomology. Thus, the distractibility issues that cause more variable reaction times might also result in greater distress related to the trauma.     

Subtyping of Salmonella enterica Serovar Newport Outbreak Isolates by CRISPR-MVLST and Determination of the Relationship between CRISPR-MVLST and PFGE Results

Salmonella enterica subsp. enterica serovar Newport (S. Newport) is the third most prevalent cause of food-borne salmonellosis. Rapid, efficient, and accurate methods for identification are required to track specific strains of S. Newport during outbreaks. By exploiting the hypervariable nature of virulence genes and clustered regularly interspaced short palindromic repeats (CRISPRs), we previously developed a sequence-based subtyping approach, designated CRISPR–multi-virulence-locus sequence typing (CRISPR-MVLST). To demonstrate the applicability of this approach, we analyzed a broad set of S. Newport isolates collected over a 5-year period by using CRISPR-MVLST and pulsed-field gel electrophoresis (PFGE). Among 84 isolates, we defined 38 S. Newport sequence types (NSTs), all of which were novel compared to our previous analyses, and 62 different PFGE patterns. Our data suggest that both subtyping approaches have high discriminatory abilities (>0.95) with a potential for clustering cases with common exposures. Importantly, we found that isolates from closely related NSTs were often similar by PFGE profile as well, further corroborating the applicability of CRISPR-MVLST. In the first full application of CRISPR-MVLST, we analyzed isolates from a recent S. Newport outbreak. In this blinded study, we confirmed the utility of CRISPR-MVLST and were able to distinguish the 10 outbreak isolates, as defined by PFGE and epidemiological data, from a collection of 20 S. Newport isolates. Together, our data show that CRISPR-MVLST could be a complementary approach to PFGE subtyping for S. Newport.     

Relationship of akathisia to aggressive and self-injurious behaviour: A prevalence study in a UK tertiary referral centre

INTRODUCTION: Akathisia is a common and distressing side-effect associated with antipsychotic drug administration. The relationship between akathisia and five forms of expressed aggression is investigated. METHOD: Sixty-four mentally disordered patients were assessed for the point prevalence of akathisia, using Barnes' rating scale for drug-induced akathisia. 1 The five types of aggression studied were: verbal abuse/ aggression, threatening behaviour/violence, physical aggression, destruction of property and deliberate self-harm, all of which are routinely recorded for patients. RESULTS: Fourteen subjects (21.9%) experienced akathisia, which was approximately four times more likely to occur in women than in men: four (6.3%) had pseudoakathisia. Akathisia was statistically significantly associated with threatening behaviour (P<0.05) and physical aggression (P<0.05). CONCLUSION: The data provide evidence for a relationship between the experience of akathisia and the expression of two forms of aberrant behaviour.     

Ultra-low microcurrent in the management of diabetes mellitus,hypertension and chronic wounds: Report of twelve cases and discussion of mechanism of action

Oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus and cardiovascular diseases including hypertension. The low levels of antioxidants accompanied by raised levels of markers of free radical damage play a major role in delaying wound healing. Ultra-low microcurrent presumably has an antioxidant effect, and it was shown to accelerate wound healing. The purpose of the study is to investigate the efficacy of ultra-low microcurrent delivered by the Electro Pressure Regeneration Therapy (EPRT) device (EPRT Technologies-USA, Simi Valley, CA) in the management of diabetes, hypertension and chronic wounds. The EPRT device is an electrical device that sends a pulsating stream of electrons in a relatively low concentration throughout the body. The device is noninvasive and delivers electrical currents that mimic the endogenous electric energy of the human body. It is a rechargeable battery-operated device that delivers a direct current (maximum of 3 milliAmperes) of one polarity for 11.5 minutes, which then switched to the opposite polarity for another 11.5 minutes. The resulting cycle time is approximately 23min or 0.000732 Hz and delivers a square wave bipolar current with a voltage ranging from 5V up to a maximum of 40 V. The device produces a current range of 3 mA down to 100 nA. Twelve patients with long standing diabetes, hypertension and unhealed wounds were treated with EPRT. The patients were treated approximately for 3.5 h/day/5 days a week. Assessment of ulcer was based on scale used by National Pressure Ulcer Advisory Panel Consensus Development Conference. Patients were followed-up with daily measurement of blood pressure and blood glucose level, and their requirement for medications was recorded. Treatment continued from 2-4 months according to their response. Results showed that diabetes mellitus and hypertension were well controlled after using this device, and their wounds were markedly healed (30-100%). The patients either reduced their medication or completely stopped after the course of treatment. No side effects were reported. The mechanism of action was discussed.     

Receipt of cancer treatment summaries and follow-up instructions among adult cancer survivors: results from a national survey

Purpose

The purpose of this study is to examine reporting of treatment summaries and follow-up instructions among cancer survivors.

Methods

Using the 2010 National Health Interview Survey, we created logistic regression models among cancer survivors not in treatment (n?=?1,345) to determine characteristics associated with reporting treatment summaries and written follow-up instructions, adjusting for sociodemographic, access, and cancer-related factors. Findings are presented for all survivors and those recently diagnosed (≤4 years). We also examined unadjusted associations between written instructions and subsequent surveillance and screening.

Results

Among those recently diagnosed, 38 % reported receiving treatment summaries and 58 % reported written instructions. Among all survivors, approximately one third reported summaries and 44 % reported written instructions. After adjustment, lower reporting of summaries was associated with cancer site, race, and number of treatment modalities among those recently diagnosed, and white vs. black or Hispanic race/ethnicity, breast vs. colorectal cancer, >10 vs. ≤5 years since diagnosis, no clinical trials participation, and better than fair health among all survivors. For instructions, lower reporting was associated with no trials participation and lower income among those recently diagnosed, and increasing age, white vs. black race, lower income, >10 vs. ≤5 years since diagnosis, 1 vs. ≥2 treatment modalities, no trials participation, and at least good vs. fair/poor health among all survivors. Written instructions were associated with reporting provider recommendations for breast and cervical cancer surveillance, and recent screening mammograms.

Conclusion

Many recently diagnosed cancer survivors did not report receiving treatment summaries and written follow-up instructions. Opportunities exist to examine associations between use of these documents and recommended care and outcomes, and to facilitate their adoption.

Implications for cancer survivors

Cancer survivors who have completed therapy should ask their providers for treatment summaries and written follow-up instructions, and discuss with them how their cancer and therapy impact their future health care.