Xenophagy in Helicobacter pylori‐ and Epstein–Barr virus‐induced gastric cancer

Helicobacter pylori and Epstein–Barr virus (EBV) account for roughly 80% and 10%, respectively, of gastric carcinomas worldwide. Autophagy is an evolutionarily conserved and intricately regulated cellular process that involves the sequestration of cytoplasmic proteins and organelles into double‐membrane autophagosomes that eventually fuse with lysosomes for degradation of the engulfed content. Emerging evidence indicates that xenophagy, a form of selective autophagy, plays a crucial role in the pathogenesis of H. pylori‐ and EBV‐induced gastric cancer. Xenophagy specifically recognizes intracellular H. pylori and EBV and physically targets these pathogens to the autophagosomal–lysosomal pathway for degradation. In this connection, H. pylori or EBV‐induced dysregulation of autophagy may be causally linked to gastric tumourigenesis and therefore can be exploited as therapeutic targets. This review will discuss how H. pylori and EBV infection activate autophagy and how these pathogens evade recognition and degradation by the autophagic pathway. Elucidating the molecular aspects of H. pylori‐ and EBV‐induced autophagy will help us better understand the pathogenesis of gastric cancer and promote the development of autophagy modulators as antimicrobial agents. Published by John Wiley & Sons, Ltd     

Importance of Airflow for Physiologic and Ergogenic Effects of Precooling

Context:

Cooling the body before exercise (precooling) has been studied as an ergogenic aid for many thermal conditions; however, airflow accompanying exercise is seldom reported.

Objective:

To determine whether the physiologic and ergogenic benefits of precooling before endurance exercise may be negated with semirealistic airflow in hot conditions.

Design:

Crossover study.

Setting:

Climate-controlled chamber in a research laboratory.

Patients or Other Participants:

Ten fit, healthy cyclists.

Intervention(s):

After a familiarization trial, participants completed 4 randomized, counterbalanced sessions consisting of no precooling versus precooling and no fan airflow versus airflow (~4.8 m/s) during exercise. Precooling was via chest-deep immersion (~24°C) for 1 hour or until core temperature dropped 0.5°C. Participants then cycled at 95% ventilatory threshold in a hot environment (temperature = 30°C, relative humidity = 50%) until volitional exhaustion, core temperature reached >39.5°C, or heart rate reached >95% of maximum.

Main Outcome Measure(s):

Thermal strain was assessed via core temperature (esophageal and rectal thermistors) and mean skin temperature (thermistors at 10 sites) and cardiovascular strain via heart rate and ratings of perceived exertion.

Results:

Endurance time (28 ± 12 minutes without precooling or airflow) increased by 30 ± 23 minutes with airflow (~109%; 95% confidence interval = 12, 45 minutes; P < .001) and by 16 ± 15 minutes with precooling (~61%; 95% confidence interval = 4, 25 minutes; P = .013), but it was not further extended when the strategies were combined (29 ± 21 minutes longer than control). During cycling without precooling or airflow, mean core and skin temperatures were higher than in all other trials. Precooling reduced heart rate by 7–11 beats/min during the first 5 minutes of exercise, but this attenuation ended by 15 minutes.

Conclusions:

Most laboratory-based precooling studies have (inadvertently) overestimated the extent of the physiologic and ergogenic benefits for typical athlete-endurance situations. Precooling increases work capacity effectively when airflow is restricted but may have little or no benefit when airflow is present.Key Words: exercise, thermoregulation, endurance, cardiovascular strain, convection, cooling

Key Points

• To attain realistic physiologic- and performance-specific results when testing athletes in a laboratory environment, airflow must be provided, at least for athletes who compete in sports in which there is natural airflow during competition (eg, running, cycling, and rowing).
• Precooling is especially effective in reducing the initial cardiovascular and thermal strain of exercise exertion for activities lasting <15 minutes.
• Combining precooling and airflow did not enhance performance results and did not decrease the thermal or cardiovascular strain of exercise any more than providing airflow alone in laboratory situations. Therefore, in sports that do not require protective gear, the benefits of precooling may be overestimated in the current literature.

Heat production during exercise causes body temperature to rise, challenging thermoregulatory homeostasis. High rates of body heat storage are associated with reduced exercise capacity in humans^1–3 and other animals.⁴ Moderate heat strain combined with exercise has been shown to lower cardiac output, stroke volume, and central blood volume and to compromise cutaneous and even muscle perfusion.⁵ Although it has been shown that exercise in the heat can be limited by a critically high internal core temperature (T_C),^1,4 others have found that central fatigue occurs gradually as T_C increases,⁶ potentially altering exercise pacing.⁷ Thus, the roles of high T_C and cardiovascular strain as limiting factors in heat tolerance are not disputed, and interventions that delay or lessen the total volume of thermal strain experienced may improve work capacity.Cooling the body before exercise (precooling) has been studied as an ergogenic aid for a range of exercise and environmental circumstances. Precooling is considered to benefit performance by widening the available margin for heat storage,³ thus allowing more work to be completed before the individual''s core body temperature reaches the point at which impairments may arise. For example, fluid balance and cardiovascular strain may theoretically benefit from precooling via delayed or reduced requirements for sweating, cutaneous vasodilation, and redirected blood flow.^1,8 Precooling can elicit varying physiologic and psychophysical effects. Some have reported that marked decreases in core and skin temperature at the onset of exercise as well as decreases in heart rate (HR) and cutaneous blood flow increase the volume of work completed,^3,8 whereas others have shown less effective performance benefits⁹ or even adverse effects,¹⁰ although the disparities in the literature among various precooling, exercise, and thermometry protocols are substantial.^11–13A notable limitation within the precooling literature and, therefore, its interpretation, is that the natural airflow accompanying laboratory-based exercise is either seldom reported or is artificially low. Restricting airflow in warm environments reduces convective and evaporative heat loss,¹⁴ increases cardiovascular drift,¹⁵ and impairs exercise tolerance.^16,17 This has been demonstrated when comparing stationary cycling in a laboratory with minimal airflow versus the same exercise with simulated outdoor wind and solar radiant heat load or with actual outdoor cycling.¹⁸ Namely, sweating rates were higher without fans compared with fanned or outdoor cycling (although the increase in rectal temperature was attenuated only in outdoor cycling in that study, unlike in other studies).^14,17 Overall, the potential for an artificially low heat transfer exists within much of the precooling literature, which may lead to an overestimation of its physiologic and performance effects. Analogous to this potential overestimation, Saunders et al¹⁷ proposed that adequate laboratory airflow could negate any beneficial physiologic or performance effects from rehydration during cycling in the heat.The purpose of our study, therefore, was to determine the separate and combined effects of precooling and exercise-realistic airflow on thermal, cardiovascular, and exercise tolerance responses during exercise in a warm, laboratory-based environment. We hypothesized that both precooling-only and airflow-only trials would decrease thermal, cardiovascular, and psychophysical strain and increase endurance capacity, whereas these benefits of precooling would be lessened in the presence of airflow.     

Virtual chromoendoscopy in small bowel capsule endoscopy: New light or a cast of shadow?

AIM: To evaluate whether virtual chromoendoscopy can improve the delineation of small bowel lesions previously detected by conventional white light small bowel capsule endoscopy(SBCE). METHODS: Retrospective single center study. One hundred lesions selected from forty-nine consecutive conventional white light SBCE(SBCE-WL) examinations were included. Lesions were reviewed at three Flexible Spectral Imaging Color Enhancement(FICE) settings and Blue Filter(BF) by two gastroenterologists with ex-perience in SBCE, blinded to each other's findings, whoranked the quality of delineation as better, equivalent or worse than conventional SBCE-WL. Inter-observer percentage of agreement was determined and analyzed with Fleiss Kappa(k) coefficient. Lesions selected for the study included angioectasias(n = 39), ulcers/ero-sions(n = 49) and villous edema/atrophy(n = 12). RESULTS: Overall, the delineation of lesions was im-proved in 77% of cases with FICE 1, 74% with FICE 2, 41% with FICE 3 and 39% with the BF, with a percent-age of agreement between investigators of 89%(k = 0.833), 85%(k = 0.764), 66%(k = 0.486) and 79%(k = 0.593), respectively. FICE 1 improved the delineation of 97.4% of angioectasias, 63.3% of ulcers/erosions and 66.7% of villous edema/atrophy with a percentage of agreement of 97.4%(k = 0.910), 81.6%(k = 0.714) and 91.7%(k = 0.815), respectively. FICE 2 improved the delineation of 97.4% of angioectasias, 57.1% of ulcers/erosions and 66.7% of villous edema/atrophy, with a percentage of agreement of 89.7%(k = 0.802), 79,6%(k = 0.703) and 91.7%(k = 0.815), respectively. FICE 3 improved the delineation of 46.2% of angioecta-sias, 24.5% of ulcers/erosions and none of the cases of villous edema/atrophy, with a percentage of agreement of 53.8% [k = not available(NA)], 75.5%(k = NA) and 66.7%(k = 0.304), respectively. The BF improved the delineation of 15.4% of angioectasias, 61.2% of ulcers/erosions and 25% of villous edema/atrophy, with a per-centage of agreement of 76.9%(k = 0.558), 81.6%(k = 0.570) and 25.0%(k = NA), respectively.CONCLUSION: Virtual chromoendoscopy can improve the delineation of angioectasias, ulcers/erosions and villous edema/atrophy detected by SBCE, with almost perfect interobserver agreement for FICE 1.     

Ecological Correlates of Depression and Self-Esteem in Rural Youth

The current study examines individual-, social-, and school-level characteristics influencing symptoms of depression and self-esteem among a large sample (N = 4,321) of U.S. youth living in two rural counties in the South. Survey data for this sample of middle-school students (Grade 6 to Grade 8) were part of the Rural Adaptation Project. Data were analyzed using ordered logistic regression. Results show that being female, having a low income, and having negative relationships with parents and peers are risk factors that increase the probability of reporting high levels of depressive symptoms and low levels of self-esteem. In contrast, supportive relationships with parents and peers, high religious orientation, ethnic identity, and school satisfaction increased the probability of reporting low levels of depressive symptoms and high levels of self-esteem. There were few school-level characteristics associated with levels of depressive symptoms and self-esteem. Implications are discussed.     

Inflammatory activation: cardiac, renal, and cardio-renal interactions in patients with the cardiorenal syndrome

Although inflammation is a physiologic response designed to protect us from infection, when unchecked and ongoing it may cause substantial harm. Both chronic heart failure (CHF) and chronic kidney disease (CKD) are known to cause elaboration of several pro-inflammatory mediators that can be detected at high concentrations in the tissues and blood stream. The biologic sources driving this chronic inflammatory state in CHF and CKD are not fully established. Traditional sources of inflammation include the heart and the kidneys which produce a wide range of pro-inflammatory cytokines in response to neurohormones and sympathetic activation. However, growing evidence suggests that non-traditional biomechanical mechanisms such as venous and tissue congestion due to volume overload are also important as they stimulate endotoxin absorption from the bowel and peripheral synthesis and release of pro-inflammatory mediators. Both during the chronic phase and, more rapidly, during acute exacerbations of CHF and CKD, inflammation and congestion appear to amplify each other resulting in a downward spiral of worsening cardiac, vascular, and renal functions that may negatively impact patients’ outcome. Anti-inflammatory treatment strategies aimed at attenuating end organ damage and improving clinical prognosis in the cardiorenal syndrome have been disappointing to date. A new therapeutic paradigm may be needed, which involves different anti-inflammatory strategies for individual etiologies and stages of CHF and CKD. It may also include specific (short-term) anti-inflammatory treatments that counteract inflammation during the unsettled phases of clinical decompensation. Finally, it will require greater focus on volume overload as an increasingly significant source of systemic inflammation in the cardiorenal syndrome.     

Concomitant dysregulation of androgen secretion and dysfunction of adipose tissue induced insulin resistance

Hyperandrogenism and hyperinsulinemia have resulted from dysfunction of the theca cell of the ovary and adipose tissue and each one potentiates the other in patients with androgen excess disorders e.g., polycystic ovary disease and idiopathic hirsutism. Possible external and/or internal triggers can produce such cellular dysfunction. There is evidence that sodium valproate acts as a trigger of cellular dysfunction and produces both hyperinsulinemia and hyperandrogenism. Therefore, the elimination of these triggers can help the patients to recover from hyperinsulinemia, insulin resistance and hyperandrogenism.