Patterns of ambulatory activity in subjects with and without intermittent claudication

PURPOSE: This study compared the patterns of ambulatory activity in subjects with and without intermittent claudication. METHODS: The study participants were 98 subjects limited by intermittent claudication and 129 controls who were matched for age, gender, and race. Subjects were assessed on their ambulatory activity patterns for 1 week with a small, lightweight step activity monitor attached to the ankle using elastic Velcro (Velcro Industries BV, Manchester, NH) straps above the lateral malleolus of the right leg. The step activity monitor recorded the number of strides taken on a minute-to-minute basis, the time spent ambulating, and the time and number of strides measured at low (<15 strides/min), medium (15 to 30 strides/min), and high (>30 strides/min) cadences. RESULTS: Subjects with intermittent claudication took fewer total strides each day than the controls (3149 +/- 1557 strides/d vs 4230 +/- 1708 strides/d; P < .001) and fewer strides at medium (1228 +/- 660 strides/day vs 1638 +/- 724 strides/day; P = .001) and high (766 +/- 753 strides/day vs 1285 +/- 1029 strides/day; P < .001) cadences. Subjects with intermittent claudication also had a lower daily average cadence than the controls (11.8 +/- 2.9 strides/min vs 13.5 +/- 3.1 strides/min; P < .001) and spent less total time ambulating each day (264 +/- 109 min/day vs 312 +/- 96 min/day; P = .034), primarily at medium (58 +/- 30 min/day vs 75 +/- 32 min/day; P < .001) and at high (19 +/- 17 min/day vs 30 +/- 22 min/day; P = .001) cadences. CONCLUSION: Intermittent claudication is associated with lower total daily ambulatory activity owing both to less time ambulating and to fewer strides taken while ambulating, particularly at moderate and high cadences.     

Multidisciplinary management of ductal carcinoma in situ: a 10-year experience

BACKGROUND: Two ductal carcinoma in situ (DCIS) treatment controversies are (1) what is the preferred margin for patients undergoing lumpectomy plus radiation, and (2) is there a subgroup that can be safely treated with lumpectomy alone? A multidisciplinary team was established to evaluate these issues. METHODS: Patients with DCIS who were candidates for breast-conservation were divided into 2 groups. Group 1 had a minimum 5-mm margin and received radiation, and group 2 had a minimum 10-mm margin and received no radiation. RESULTS: One hundred fifty-two patients (153 cancers) met the inclusion criteria. The median follow-up was 8.2 years. Overall, there were 6 recurrences (3.92%); 1 of 71 recurred in group 1 (1.40%), and 5 of 82 recurred in group 2 (6.01%). CONCLUSION: Five-millimeter margins plus radiation results in low rates of recurrence. A subgroup of DCIS patients can be identified in which radiation can be safely avoided. The multidisciplinary team approach to managing DCIS enhances the potential for improved outcomes.     

Increased GABA<Subscript>B</Subscript> Receptor Subtype Expression in the Nucleus of the Solitary Tract of the Spontaneously Hypertensive Rat

Expression of GABA(B) receptor messenger RNA (mRNA) in the central nervous system was compared between the spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rat. Polymerase chain reaction (PCR) revealed all the isoforms except B1e in cortex, hypothalamus, and medulla oblongata. In the nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM), the B1a-c and 1 g isoforms were present as well as B2. Real-time PCR detected significantly higher levels of B1a (p < 0.01) and B2 (p < 0.05) mRNA in the NTS of SHR compared to WKY. A significant increase in B1a expression (p < 0.05) was detected in VLM. Immunolabeling suggested presynaptic and postsynaptic expression of B1a, B1b, and B2 subtypes throughout the NTS, with significant differences in distribution patterns and labeling between subtypes and between SHR and WKY. These findings suggest that GABA(B) receptors expressed by neurones in NTS may be involved in cardiovascular regulation and that changes in GABA(B) mRNA expression levels may contribute to the hypertensive state in SHR.     

Sanguinarine-dependent induction of apoptosis in primary effusion lymphoma cells

Primary effusion lymphoma (PEL) is an incurable, aggressive B-cell malignancy that develops rapid resistance to conventional chemotherapy. In efforts to identify novel approaches to block proliferation of PEL cells, we found that sanguinarine, a natural compound isolated from the root plant Sanguinaria canadendid, inhibits cell proliferation and induces apoptosis in a dose-dependent manner in several PEL cell lines. Our data show that sanguinarine treatment of PEL cells results in up-regulation of death receptor 5 (DR5) expression via generation of reactive oxygen species (ROS) and causes activation of caspase-8 and truncation of Bid (tBid). Subsequently, tBid translocates to the mitochondria causing conformational changes in Bax, leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosol. Sanguinarine-induced release of cytochrome c results in activation of caspase-9 and caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage, leading to induction of caspase-dependent apoptosis. In addition, we show that pretreatment of PEL cells with carbobenzoxy-Val-Ala-Asp-fluoromethylketone, a universal inhibitor of caspases, abrogates caspase and PARP activation and prevents cell death induced by sanguinarine. Moreover, treatment of PEL cells with sanguinarine down-regulates expression of inhibitor of apoptosis proteins (IAP). Finally, N-acetylcysteine, an inhibitor of ROS, inhibits sanguinarine-induced generation of ROS, up-regulation of DR5, Bax conformational changes, activation of caspase-3, and down-regulation of IAPs. Taken together, our findings suggest that sanguinarine is a potent inducer of apoptosis of PEL cells via up-regulation of DR5 and raise the possibility that this agent may be of value in the development of novel therapeutic approaches for the treatment of PEL.     

A potential association between obesity and reduced effectiveness of COVID-19 vaccine-induced neutralizing humoral immunity

Due to the adverse effects of obesity on host immunity, this study investigated the effectiveness of COVID-19 vaccines (BNT162b2, ChAdOx-nCov-2019, and mRNA-1273) in inducing anti-SARS-CoV-2 Spike (S) neutralizing antibodies among individuals with various obesity classes (class I, II, III, and super obesity). Sera from vaccinated obese individuals (n = 73) and normal BMI controls (n = 46) were subjected to S-based enzyme-linked immunosorbent assay (ELISA) and serum-neutralization test (SNT) to determine the prevalence and titer of anti-SARS-CoV-2 neutralizing antibodies. Nucleocapsid-ELISA was also utilized to distinguish between immunity acquired via vaccination only versus vaccination plus recovery from infection. Data were linked to participant demographics including age, gender, past COVID-19 diagnosis, and COVID-19 vaccination profile. S-based ELISA demonstrated high seroprevalence rates (>97%) in the study and control groups whether samples with evidence of past infection were included or excluded. Interestingly, however, SNT demonstrated a slightly significant reduction in both the rate and titer of anti-SARS-CoV-2 neutralizing antibodies among vaccinated obese individuals (60/73; 82.19%) compared to controls (45/46; 97.83%). The observed reduction in COVID-19 vaccine-induced neutralizing humoral immunity among obese individuals occurs independently of gender, recovery from past infection, and period from last vaccination. Our data suggest that COVID-19 vaccines are highly effective in inducing protective humoral immunity. This effectiveness, however, is potentially reduced among obese individuals which highlight the importance of booster doses to improve their neutralizing immunity. Further investigations on larger sample size remain necessary to comprehensively conclude about the effect of obesity on COVID-19 vaccine effectiveness on humoral immunity induction.     

Advancements in left ventricular assist devices to prevent pump thrombosis and blood coagulopathy

Mechanical circulatory support (MCS) devices, such as left ventricular assist devices (LVADs) are very useful in improving outcomes in patients with advanced-stage heart failure. Despite recent advances in LVAD development, pump thrombosis is one of the most severe adverse events caused by LVADs. The contact of blood with artificial materials of LVAD pumps and cannulas triggers the coagulation cascade. Heat spots, for example, produced by mechanical bearings are often subjected to thrombus build-up when low-flow situations impair washout and thus the necessary cooling does not happen. The formation of thrombus in an LVAD may compromise its function, causing a drop in flow and pumping power leading to failure of the LVAD, if left unattended. If a clot becomes dislodged and circulates in the bloodstream, it may disturb the flow or occlude the blood vessels in vital organs and cause internal damage that could be fatal, for example, ischemic stroke. That is why patients with LVADs are on anti-coagulant medication. However, the anti-coagulants can cause a set of issues for the patient—an example of gastrointestinal (GI) bleeding is given in illustration. On account of this, these devices are only used as a last resort in clinical practice. It is, therefore, necessary to develop devices with better mechanics of blood flow, performance and hemocompatibility. This paper discusses the development of LVADs through landmark clinical trials in detail and describes the evolution of device design to reduce the risk of pump thrombosis and achieve better hemocompatibility. Whilst driveline infection, right heart failure and arrhythmias have been recognised as LVAD-related complications, this paper focuses on complications related to pump thrombosis, especially blood coagulopathy in detail and potential strategies to mitigate this complication. Furthermore, it also discusses the LVAD implantation techniques and their anatomical challenges.     

Acute bilateral loss of vision as organic manifestation of repressed psychological stress: A case report

Comprehensive clinical assessment with integrated team approach is crucial in managing cases of non‐organic visual loss. Apart from pharmacotherapy, psychosocial rehabilitation should also be adequately addressed.