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Clinical and preclinical research have identified sex differences in substance use and addiction-related behaviors. Historically, substance use disorders are more prevalent in men than women, though this gap is closing. Despite this difference, women appear to be more susceptible to the effects of many drugs and progress to substance abuse treatment more quickly than men. While the glutamate system is a key regulator of addiction-related behaviors, much of the work implicating glutamate signaling and glutamatergic circuits has been conducted in men and male rodents. An increasing number of studies have identified sex differences in drug-induced glutamate alterations as well as sex and estrous cycle differences in drug seeking behaviors. This review will describe sex differences in the glutamate system with an emphasis on implications for substance use disorders, highlighting the gaps in our current understanding of how innate and drug-induced alterations in the glutamate system may contribute to sex differences in addiction-related behaviors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Estradiol has been shown to have neuroprotective effects, and acute estradiol treatment enhances hippocampal neurogenesis in the female brain. However, little is known about the effects of repeated administration of estradiol on the female brain, or about the effects of estradiol on the male brain. Gonadectomized male and female adult rats were injected with 5-bromo-2-deoxyuridine (BrdU) (200 mg/kg), and then 24 h later were given subcutaneous injections of either estradiol benzoate (33 mug/kg) or vehicle daily for 15 days. On day 16, animals were perfused and the brains processed to examine cells expressing Ki-67 (cell proliferation), BrdU (cell survival), doublecortin (young neuron production), pyknotic morphology (cell death), activated caspase-3 (apoptosis), and Fluoro-Jade B (degenerating neurons) in the dentate gyrus. In female rats, repeated administration of estradiol decreased the survival of new neurons (independent of any effects on initial cell proliferation), slightly increased cell proliferation, and decreased overall cell death in the dentate gyrus. In male rats, repeated administration of estradiol had no significant effect on neurogenesis or cell death. We therefore demonstrate a clear sex difference in the response to estradiol of hippocampal neurogenesis and apoptosis in adult rats, with adult females being more responsive to the effects of estradiol than males.

The emergence of evidence-based health care at an operational level is well underway in the National Health Service, driven on by clinical effectiveness initiatives. Unless evidence-based care is supported by evidence-based policymaking, the environment will not be conducive to effective professional practice. The article describes a methodology that has been developed to meet the needs of the Project for the Enhancement of the Welsh-Protocols for Investment in Health Gain. A detailed description of the background, aims, methods, planning, and supporting documentation of the project is given. The methodological principles are transferable to other policymaking scenarios.

Purpose: To assess possible triggers and cofactors for chronic fatigue syndrome (CFS) and to compare levels of selected cytokines between cases and an appropriately matched control group., Patients and Methods: We conducted a case-control study of 47 cases of CFS obtained through a regional CFS research program maintained at a tertiary care medical center. One age-, gender-, and neighborhood-matched control was identified for each case through systematic community telephone sampling. Standardized questionnaires were administered to cases and controls. Sera were assayed for transforming growth factor-beta (TGF-beta), interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and antibody to Borrelia burgdorferi and Babesia microti., Results: Cases were more likely to have exercised regularly before illness onset than controls (67% versus 40%; matched odds ratio (MOR) = 3.4; 95% CI = 1.2 to 11.8; P = 0.02). Female cases were more likely to be nulliparous prior to onset of CFS than controls (51% versus 31%; MOR = 8.0; 95% CI = 1.03 to 170; P = 0.05). History of other major factors, including silicone-gel breast implants (one female case and one female control), pre-morbid history of depression (15% of cases, 11% of controls) and history of allergies (66% of cases, 51% of controls) were similar for cases and controls. However, cases were more likely to have a diagnosis of depression subsequent to their diagnosis of CFS compared to a similar time frame for controls (MOR = undefined; 95% CI lower bound = 2.5; P < 0.001). Positive antibody titers to B burgdorferi (one case and one control) and B microti (zero cases and two controls) were also similar., Conclusions: Further investigation into the role of prior routine exercise as a cofactor for CFS is warranted. This study supports the concurrence of CFS and depression, although pre-morbid history of depression was similar for both groups.

Background: Most airline and military transport planes are flown by crews that have been teamed together for a short amount of time before disbanding and becoming part of a different crew (formed crew concept). Some military operations use a fixed crew concept, pairing crewmembers together for an indefinite period. This research investigated the effect of crew formation policy on aircrew performance during missions in U.S. Air Force KC-135 (tanker) simulators., Method: The performance of fixed aircrews is compared to formed aircrews flying the same simulator mission scenario, which included an in-flight emergency. Cockpit resource management (CRM) behavioral data and error data were collected by trained observers for 17 crews (9 fixed and 8 formed)., Results: The results show that fixed crews committed more minor errors (4.4 per mission) than formed crews (2.6 per mission), t(14) = 2.32, p = 0.036. No differences were found concerning major errors or CRM behavioral indicators., Conclusions: The results suggest the possibility of a "familiarity decline," where aircrew performance declines when crewmembers become too familiar with each other and may affect flight safety.

Historically, transport crews are formed to fly a brief series of sorties together. But what would be the effect of keeping crews together longer? This research investigates the effect of crewing policies on accident rates. We compare the crew coordination performance of fixed teams that work together indefinitely with that of formed teams that work together for shorter periods. We researched 74 accident investigation records of two jet transport aircraft of the U.S. Air Force over 20-year periods. These aircraft used both fixed and formed crews. The "ineffective crew coordination" accident rates for formed crews were significantly safer (z = 12.5 for one aircraft and 2.1 for another p < 0.05). This may imply that airlines and military commands could enhance flight safety by following a formed crew policy. However, further study is needed to identify more completely the effects of crew policies on sortie effectiveness.

This study examines the links between random breath testing (RBT), driver perception of the likelihood of apprehension if illegally drink-driving, and drink-driving behaviour in Adelaide, South Australia. It is based on information gained from surveys of night-time drivers in metropolitan Adelaide, during 1987, 1989 and 1991. Overall, about 25% of the sample in each year thought that illegal drink-driving was likely to result in apprehension. This perception was consistently lower for males and for those aged less than 30 years than for their counterparts, however, there was evidence that it increased with exposure to RBT, notably when that exposure was recent. Also, compared with other drivers, fewer drivers who thought that apprehension was likely had an illegal blood alcohol concentration (BAC) when surveyed, or reported that they would be likely to drive if they thought that they had an illegal BAC. However, the majority of drivers who thought that detection was unlikely also reported that they would be unlikely to drink-drive. These results suggest the need for some re-direction of current RBT activities.

An in-depth study of 79 vehicle crashes on rural roads in an area of about 100 km radius around Adelaide examined sociodemographic and psychophysiological characteristics of the drivers and riders involved. In many respects this sample of crashes was similar to a much larger number of police-reported crashes in the same area but included: relatively more crashes with severe or fatal injuries; more crashes on divided roads, on sealed roads and on curves; and more crashes involving trucks. Alcohol and lack of seat belt use were shown to be major problems in these rural crashes. The drivers and riders most strongly associated with these particular problems were males, in blue collar occupations and with limited education; they tended to be aged 30 years or more in the case of alcohol abuse, and were likely to be under 30 years in the case of restraint misuse. The attitudes of these drivers and riders, and other characteristics likely to have contributed to their involvement in a crash, are discussed. There is a need to develop specific and effective countermeasures to reduce drink-driving and increase seat belt wearing in rural areas.

The paucity of virus-laden CD4+ cells in individuals infected with human immunodeficiency virus type-1 (HIV-1) contrasts with the greatly reduced numbers and function of these lymphocytes. A pathway is described whereby dendritic cells carry HIV-1 to uninfected T cells, amplifying the cytopathic effects of small amounts of virus. After exposure to HIV-1, dendritic cells continue to present superantigens and antigens, forming clusters with T cells that are driven to replicate. Infection of the dendritic cells cannot be detected, but the clustered T cells form syncytia, release virions, and die. Carriage of HIV-1 by dendritic cells may facilitate the lysis and loss of antigen specific CD4+ T cells in acquired immunodeficiency syndrome.

An alloagglutinin was identified in the serum of an M-negative diabetic patient. The agglutinin reacted with all commercial M-positive red cell samples. Routine crossmatches showed no incompatibility. This anti-M would only agglutinate M-positive red cell samples that had been incubated in 2% glucose for a minimum of 2 h at 37 degrees C, 2 days at 22 degrees C, or 1 week at 4 degrees C. Reactive red cell samples, when washed and incubated in saline, gradually became non-reactive. This antibody reacted optimally in low ionic strength solution at 16 degrees C for 20 min where MM red cells were agglutinated to a titer of 256, score 85; and MN red cells were agglutinated to a titer of 128, score 66. The antibody was denatured by 2-mercaptoethanol and was inhibited by a crude M tryptic isolate and by 2% glucose, but not by other sugars prepared at a 2% concentration.

The serologic reactivity of a monoclonal anti-C3d and commercial "monospecific" anti-C3 and polyspecific antiglobulin reagents was compared. The testing consisted of a direct antiglobulin test performed on donor and patient cells and on in vivo and in vitro complement-coated cells; an indirect antiglobulin test was performed with low-ionic-strength solution crossmatches. The monoclonal anti-C3d demonstrated reactivity very similar to that of the commercial heterogeneous rabbit anti-C3d; it gave relatively few weak "false positive" reactions with normal donor and patient red blood cells, and comparably strong reactions with in vitro and in vivo C3d-coated red blood cells. The results suggest a promising future for monoclonal antiglobulin reagents.

Avocado sunblotch viroid (ASBV) has been detected down to a level of about 20 pg per gram fresh weight of leaves by the use of a dot-blot hybridization procedure and partially purified nucleic acid extracts. Three [32P]DNA probes were compared, two prepared from full-length ASBV clones in the single-strand M13mp93 vector and the other by primer extension on purified ASBV. All three probes gave the same sensitivity of detection of ASBV. The methods developed have also been used successfully for the routine detection of potato spindle tuber viroid, citrus exocortis viroid, and coconut cadang cadang viroid.

The serum from a 47-year-old man who had not been transfused previously was tested with reagent red cells selected from different commercial manufacturers to confirm the presence of an alloanti -N. Agglutination of homozygous N-positive red cells at 22 degrees C ranged from score 3 to 12. This variable reactivity was found to be due to pH, and the optimal reactivity was in test media below pH 7.

Since his report on last year's meeting of the American College of Cardiology in Dallas was so well received, we asked Dr James M. Barker to attend this year's meeting, held in Anaheim, California, and again give us a primary care physician's perspective.-R.B.H.