Plasma Total Glutathione in Humans and its Association with Demographic and Health-Related Factors

The tripeptide glutathione is proposed to be protective against a number of chronic diseases including cardiovascular disease and cancer. However, there have been few studies of plasma glutathione levels in humans and in those studies the numbers of participants have been very small. In an exploratory analysis the determinants of plasma total glutathione (GSHt) were investigated in a group of 100 volunteers aged 18–61 years in Atlanta, Georgia, USA during June and July 1989. Data on demographic and health-related factors were collected by interview and plasma GSHt was measured using a recently modified laboratory method. The mean concentration of plasma GSHt for all 100 participants was 761 pg/1, with a standard deviation of 451 pg/1, a range of 86–2889 pg/1 and a median of 649 pg/1. Men had significantly higher levels of plasma GSHt than women (924 v. 692 pg/1; P = 0.006). Seventh-day Adventists participating in the present study had higher plasma GSHt levels than other subgroups defined by race and/or religion. Among Seventh-day Adventists consumption of a vegetarian diet was associated with increased plasma GSHt concentration (P = 0.002). Plasma GSHt levels also appeared to vary by race, but relationships with race could not be clearly disassociated from relationships with religion. Among white participants plasma GSHt concentration decreased with age in women but increased with age in men (P = 0.05). Few other factors were associated with plasma GSHt concentration, although use of oral contraceptives (P=0.10) was somewhat associated with decreased plasma GSHt levels. These findings suggest that plasma GSHt levels may vary with several demographic and health-related attributes and support the need for further research on this potentially important disease-preventive compound. © 1993, The Nutrition Society. All rights reserved

Biogeochemical and ecological impacts of boundary currents in the Indian Ocean

Monsoon forcing and the unique geomorphology of the Indian Ocean basin result in complex boundary currents, which are unique in many respects. In the northern Indian Ocean, several boundary current systems reverse seasonally. For example, upwelling coincident with northward-flowing currents along the coast of Oman during the Southwest Monsoon gives rise to high productivity which also alters nutrient stoichiometry and therefore, the species composition of the resulting phytoplankton blooms. During the Northeast Monsoon most of the northern Indian Ocean boundary currents reverse and favor downwelling. Higher trophic level species have evolved behavioral responses to these seasonally changing conditions. Examples from the western Arabian Sea include vertical feeding migrations of a copepod (Calanoides carinatus) and the reproductive cycle of a large pelagic fish (Scomberomorus commerson). The impacts of these seasonal current reversals and changes in upwelling and downwelling circulations are also manifested in West Indian coastal waters, where they influence dissolved oxygen concentrations and have been implicated in massive fish kills. The winds and boundary currents reverse seasonally in the Bay of Bengal, though the associated changes in upwelling and productivity are less pronounced. Nonetheless, their effects are observed on the East Indian shelf as, for example, seasonal changes in copepod abundance and zooplankton community structure. In contrast, south of Sri Lanka seasonal reversals in the boundary currents are associated with dramatic changes in the intensity of coastal upwelling, chlorophyll concentration, and catch per unit effort of fishes. Off the coast of Java, monsoon-driven changes in the currents and upwelling strongly impact chlorophyll concentrations, seasonal vertical migrations of zooplankton, and sardine catch in Bali Strait. In the southern hemisphere the Leeuwin is a downwelling-favorable current that flows southward along western Australia, though local wind forcing can lead to transient near shore current reversals and localized coastal upwelling. The poleward direction of this eastern boundary current is unique. Due to its high kinetic energy the Leeuwin Current sheds anomalous, relatively high chlorophyll, warm-core, downwelling eddies that transport coastal diatom communities westward into open ocean waters. Variations in the Leeuwin transport and eddy generation impact many higher trophic level species including the recruitment and fate of rock lobster (Panulirus cygnus) larvae. In contrast, the transport of the Agulhas Current is very large, with sources derived from the Mozambique Channel, the East Madagascar Current and the southwest Indian Ocean sub-gyre. Dynamically, the Agulhas Current is upwelling favorable; however, the spatial distribution of prominent surface manifestations of upwelling is controlled by local wind and topographic forcing. Meanders and eddies in the Agulhas Current propagate alongshore and interact with seasonal changes in the winds and topographic features. These give rise to seasonally variable localized upwelling and downwelling circulations with commensurate changes in primary production and higher trophic level responses. Due to the strong influence of the Agulhas Current, many neritic fish species in southeast Africa coastal waters have evolved highly selective behaviors and reproductive patterns for successful retention of planktonic eggs and larvae. For example, part of the Southern African sardine (Sardinops sagax) stock undergoes a remarkable northward migration enhanced by transient cyclonic eddies in the shoreward boundary of the Agulhas Current. There is evidence from the paleoceanographic record that these currents and their biogeochemical and ecological impacts have changed significantly over glacial to interglacial timescales. These changes are explored as a means of providing insight into the potential impacts of climate change in the Indian Ocean

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012

OBJECTIVE: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. DESIGN: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. RESULTS: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). CONCLUSIONS: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients

“Well, It Should Be Changed for One, Because It’s Our Bodies”: Sex Workers’ Views on Canada’s Punitive Approach towards Sex Work

Background: The regulation of sex work is contentious in all countries, including for governments, the public, and sex workers themselves. Research shows sex workers’ perspectives are ignored during policy formation in most cases. This is despite the fact they have unique insider knowledge and are directly affected by the policies that are enacted. Methods: We analyzed the accounts of a heterogeneous sample of adult sex workers (N = 218) residing in different urban cities in Canada to find out their views on current laws and their recommendations for reform. The interviews were conducted in 2012–2013 prior to the implementation of the 2014 Protection of Communities and Exploited Persons Act. The paper thus provides an opportunity to compare the changes desired by Canadian sex workers with changes put into law by the Act. Results: Although the interview questions did not directly ask about the current legal system, 121 expressed an opinion. Three main themes emerged from the qualitative analysis: (1) the challenges that criminalization posed to sex workers; (2) the workers’ suggestions for legal reform; and (3) potential issues with legal reform. Conclusions: We discuss the contributions our qualitative findings make to the scholarship on sex work regulation and call for further research that includes sex workers’ voices in decision-making regarding changes to policies affecting their lives

Glutathione in Foods Listed in the National Cancer Institute\u27s Health Habits and History Food Frequency Questionnaire

Glutathione (GSH) is an antioxidant and anticarcinogen that is present in plant and animal tissues that form the bulk of the human diet. Recent studies show that GSH is absorbed intact in rat small intestine and that oral GSH increases plasma GSH concentration in humans. To provide a database for epidemiological studies of dietary intake of GSH and risk of diseases in humans; we have measured the content of GSH in the foods listed in the National Cancer Institute\u27s Health Habits and History Questionnaire. Foods were purchased in the Atlanta area and prepared as most commonly consumed in the United States. GSH analyses were performed using a high-performance liquid chromatography technique with a method of additions to correct for losses during sample preparation. A separate set of samples was run after treatment with dithiothreitol to measure the total of GSH and its disulfide forms (GSHJ. The results show that dairy products, cereals, and breads are generally low in GSH; fruits and vegetables have moderate to high amounts of GSH; and freshly prepared meats are relatively high in GSH Frozen foods generally had GSH contents similar to fresh foods, whereas other forms of processing and preservation generally resulted in extensive loss of GSH Thus this database will allow researchers to examine the relationship between dietary GSH and risk of cancers and other diseases. © 1992, Taylor & Francis Group, LLC. All right reserved

Additional file 2: of Sex workers as peer health advocates: community empowerment and transformative learning through a Canadian pilot program

Peer Health Educators Training Program Session Evaluation Form. (DOCX 12 kb