Influence of attention-deficit/hyperactivity disorder symptoms on methadone treatment outcome

A review of 687 consecutive admissions to a Midwestern methadone maintenance program was undertaken to establish the prevalence of ADHD symptoms and their association with treatment outcome. Of the 687 admissions, 396 (58%) patients self-reported experiencing one or more ADHD symptoms during the two weeks prior to admission, and 131 (19%) patients reported ADHD symptoms that significantly interfered with functioning in daily activities. At nine months post-admission, the patients who reported significant symptoms of ADHD were able to reduce their drug use but were less likely to have achieved abstinence than those who did not report significant symptoms (p < or = 0.001). The authors discuss the importance of screening for ADHD symptoms in methadone treatment programs and propose interventions believed helpful in improving management of ADHD symptoms and improving outcome.     

Antinociceptive effect of sucrose ingestion in the human

Sucrose ingestion has been shown to alleviate pain and distress in rats, human infants as well as adults. Sucrose induced analgesia is related to the reward value associated with its sweet taste. The sweet taste of sucrose is a stimulus for the activation of endogenous opioid pool. The opioids in turn modulate pain perception. It has been demonstrated in a number of animal and human studies that sucrose ingestion increases the hypothalamic/CSF opioid levels. This gains support from the results obtained from naloxone challenge test, a neuro-endocrine method for assessment of endogenous opioid tone. Moreover, the analgesic effects of sucrose can be reversed by administration of opioid antagonists such as naloxone. On the other hand, long-term sucrose ingestion leads to hyperalgesia in rats and it has been hypothesized to result from a complex interaction of sucrose with the endogenous opioid system leading to a deficiency of opioids. In the present article mechanisms underlying sucrose induced analgesia including the interaction of the palatability and reward value of food with the neural substrates and its neuro-chemical basis have been reviewed in the light of both animal and human studies. In addition, clinical application of the knowledge about sucrose and its modulatory effect on the endogenous opioid system has been suggested.     

HIV and carotid atherosclerosis: a mediational model

ABSTRACT

Cardiovascular disease (CVD) is the leading cause of death in the US and is a significant contributor to morbidity and mortality for people living with HIV (PLWH). This study examined the association between HIV infection, cocaine usage, and inflammatory markers, and their combined association with carotid atherosclerosis among young and middle-aged adults with HIV. Participants (N?=?494) were enrolled based on HIV status and cocaine use. Blood pressure, body mass index (BMI), and cocaine use were assessed. Cytokines and growth factors, IL-1a, IL-6, TNFα and VEGF, and immune activation markers, sCD14 and sCD163 were measured. Participant age was 36.2 years (SD?=?9.5); 50% were male, 49% female and 1% transgender; 39% were HIV-positive, 50% were current or past smokers, and 39% endorsed cocaine use. A path analysis showed an indirect effect of HIV serostatus on the presence of carotid atherosclerotic plaques (Indirect Effect?=?0.048, SE?=?0.024, p?=?.043), when controlling age, BMI, smoking, and cocaine use. This effect was mediated by inflammatory markers and changes in blood pressure. Findings point to putative underlying mechanisms leading to atherosclerosis among PLWH.     

Septic Cardiomyopathy: From Basics to Management Choices

Septic cardiomyopathy (SCM) is increasingly recognized as a potential complication of septic shock; it is understood to be a reversible left ventricular systolic dysfunction. The presence of SCM in septic shock, in previous studies, infer a poorer prognosis as it significantly increases the mortality rate of patients to 70%-90% and its incidence varies from 18% to 40% of septic shock patients. The pathogenesis is unclear, but believed to be a combination of bacterial toxins, cytokines, nitric oxide, and cardiac mitochondrial dysfunction, that depresses intrinsic cardiac contractility. The presence of SCM can be diagnosed in patients using a bedside transthoracic echocardiogram which typically shows left ventricular ejection fraction <45% and right ventricular dilatation. For management, levosimendan provides a good hemodynamic response without increasing cardiac oxygen demand when compared to dobutamine, while more invasive techniques such as extracorporeal membrane oxygenation, and intra-aortic balloon pulsation are being explored as well as potential rescue strategies for patients with severe SCM.     

Autologous Fascial Slings for Surgical Management of Stress Urinary Incontinence: A Come Back

Stress urinary incontinence (SUI) is a common type of urinary incontinence adversely affecting the quality of life of women. For mild SUI, life style changes, pelvic floor exercises and medical treatment with duloxetine may help. Most patients of moderate to severe SUI usually require surgical treatment. Various surgical treatment options include Kelly’s plication, Burch colposuspension, bulking agents and sling surgeries. Although, suburethral fascial slings including the autologous rectus fascia slings were in vogue before 1990, they were overtaken by minimally invasive, faster and easier artificial midurethral slings (tension free vaginal tape and transobturator tape). However, observation of serious long-term and life changing complications of synthetic midurethral slings like mesh erosion, chronic pelvic pain and dyspareunia led to their adverse publicity and medico legal implications for the operating surgeons. This led US FDA (Food and Drug Administration) to issue a warning against their use. Currently, their use has significantly decreased in many countries, and they are no longer available in some countries. This has led to renaissance of use of natural autologous fascial sling, especially rectus fascia for surgical management of SUI. Although performing rectus fascia sling surgery is technically more challenging, takes longer, has more short-term morbidity like voiding dysfunction, their long-term success is high with very little risk of serious complications like mesh erosion, chronic pelvic pain and dyspareunia. However, multicentric trials and longer follow ups are needed before it’s routine recommendation This review discusses the role of autologous fascial sling (especially rectus fascia) for the surgical management of SUI in the current time and the need of ongoing training of this procedure to gynecology residents and urogynecology fellows.     

Deficiency of the splicing factor RBM10 limits EGFR inhibitor response in EGFR-mutant lung cancer

Molecularly targeted cancer therapy has improved outcomes for patients with cancer with targetable oncoproteins, such as mutant EGFR in lung cancer. Yet, the long-term survival of these patients remains limited, because treatment responses are typically incomplete. One potential explanation for the lack of complete and durable responses is that oncogene-driven cancers with activating mutations of EGFR often harbor additional co-occurring genetic alterations. This hypothesis remains untested for most genetic alterations that co-occur with mutant EGFR. Here, we report the functional impact of inactivating genetic alterations of the mRNA splicing factor RNA-binding motif 10 (RBM10) that co-occur with mutant EGFR. RBM10 deficiency decreased EGFR inhibitor efficacy in patient-derived EGFR-mutant tumor models. RBM10 modulated mRNA alternative splicing of the mitochondrial apoptotic regulator Bcl-x to regulate tumor cell apoptosis during treatment. Genetic inactivation of RBM10 diminished EGFR inhibitor–mediated apoptosis by decreasing the ratio of (proapoptotic) Bcl-xS to (antiapoptotic) Bcl-xL isoforms of Bcl-x. RBM10 deficiency was a biomarker of poor response to EGFR inhibitor treatment in clinical samples. Coinhibition of Bcl-xL and mutant EGFR overcame the resistance induced by RBM10 deficiency. This study sheds light on the role of co-occurring genetic alterations and on the effect of splicing factor deficiency on the modulation of sensitivity to targeted kinase inhibitor cancer therapy.