Essential role for cyclic AMP and its receptor protein in Yersinia enterocolitica virulence

Insertion mutations were isolated in cya and crp of Yersinia enterocolitica, which encode adenylate cyclase and the cyclic AMP (cAMP) receptor protein (CRP). The cya and crp mutants were affected for the production of proteins exported by the Ysc, Ysa, and flagellar type III secretion systems (TTSS). Protein production by each TTSS was restored when the respective mutation was complemented by a plasmid-encoded copy of the wild-type gene. Both cya and crp mutants exhibited reduced virulence for orally infected BALB/c mice in a 50% lethal dose analysis. Examination of bacterial survival in host tissues showed that cya and crp mutants colonized Peyer's patches and, to a lesser extent, mesenteric lymph nodes. However, the mutants did not appear to disseminate to the liver and spleen of infected mice. An initial examination of the effectiveness of Y. enterocolitica cya and crp mutants to stimulate protective immunity against subsequent challenge with virulent bacteria in mice was promising. The results indicate that the cAMP-CRP regulatory system is required for Y. enterocolitica virulence.     

Routine HLA-B27 typing by flow cytometry: differentiation of the products of HLA-B*2702, B*2705 and B*2708

Patient HLA-B27 typing is widely performed as an aid to the diagnosis of several diseases, particularly ankylosing spondylitis. Typing by flow cytometry, using monoclonal antibodies, has been shown to be a potentially useful alternative to classical serology on account of its speed, simplicity and economy. However, we required a flow cytometry typing procedure that would accurately differentiate HLA-B27 (Bw4) from B2708 (Bw6) and not be confounded by other HLA-B7/B27 cross-reactive group antigens. Accordingly, we evaluated the simultaneous use of two monoclonal antibody preparations, ABC-m3-FITC (anti-B27 + weak B7)/BB7.1-PE (anti-B7) and FD705-FITC (anti-B27), by testing a highly selected panel of 62 reference lymphocytes containing examples of all HLA-B7/B27 cross-reactive group antigens, including: HLA-B42, B47, B48, B73, B703, B2702, B2705 and B2708. In addition, 268 whole blood samples from routine patient requests for B27-associated disease typing were tested in parallel with HLA-B typing using the standard complement-dependent microlymphocytoxicity test. The detailed specificity of the three monoclonal antibodies was established and the products of HLA-B*2702, B*2705 and B*2708 were found to be readily differentiated from each other and all other HLA-B7/B27 cross-reactive HLA-B antigens.     

Effect of lithium carbonate therapy on thyroid immune status in manic depressive patients: a prospective study

Serum thyroid autoantibodies to thyroglobulin (TG) and thyroid microsomes (M) were measured by ELISA prospectively in 37 manic depressive patients prior to receiving lithium carbonate and during therapy with this drug for a mean of 16.2 months. They were also measured once in 27 normal subjects and several times in five psychiatric patients not receiving lithium. Sixteen patients (43%) had either thyroglobulin, microsomal antibodies or both before receiving lithium therapy. During therapy significant fluctuations in antibody titre, both upwards and downwards were observed in ten out of 12 patients with M antibodies and in nine out of 11 with TG antibodies. The fluctuations in antibody titre are consistent with an immunomodulatory effect of lithium as has been shown in animal studies. It is suggested that psychiatric patients should have thyroid antibodies measured routinely before and during lithium therapy.     

Immunogenetics of two new HLA alleles: A*0108 and B*4031

Two new alleles, HLA-A*0108 and B*4031, were identified in north-western European Caucasoid subjects. A*0108 differed from A*010101 by a single substitution (C to T) at position 216 in exon 3, resulting in an amino acid difference of Arg to Trp at position 163. It was present on a haplotype with B*1501/60/70/71; Cw*0303; DRB1*1301; DRB3*0202; DQA1*0103; DQB1*0603 and its product reacted as a normal HLA-A1 specificity. B*4031 differed from B*4001 by two nucleotides in exon 3 (positions 20 (G to C) and 69 (A to G)) resulting in two amino acid differences (Arg to Ser at position 97 and Asn to Asp at position 114). It was found on a haplotype with HLA-A*03; Cw*0304; DRB1*0404/32; DRB4*0101/3/5; DQA1*03; DQB1*0302 and has the HLA-B60 specificity. Both alleles have frequencies of < 0.0002 in the largely north-western European Caucasoid blood donor population resident in Wales.     

Identification of HLA-A*0224: implications for PCR-SSP HLA typing

We describe a novel HLA-A*02 allele, A*0224, that was identified after a comparison of DNA and serological typing revealed a discrepancy in the HLA-A types: HLA-A2 was defined by serology but was not detected by the polymerase chain reaction using sequence-specific primers (PCR-SSP). DNA sequencing indicated the presence of a variant HLA-A*02 allele that differed from A*0201 by a single base (C/A) at position 453. This base substitution corresponded to the annealing site of a primer common to the two A*02-amplifying PCR-SSP mixtures used in the method. This provides an explanation for the results and highlights a limitation of PCR-SSP methods even where two PCR mixtures are used to detect alleles. Serological titration studies suggested that A*0201, A*0205 and A*0224 are unlikely to be differentiated during routine serological typing.     

Retroesophageal right subclavian artery with persistent ductus arteriosus

We report an adult male cadaver with persistence of the ductus arteriosus and a right retroesophageal artery. The retroesophageal artery was first appreciated as a retropharyngeal mass during the dissection of this area. Both the left and right vertebral arteries originated in normal fashion. The thoracic duct of our specimen drained into the junction of the left internal jugular and left subclavian veins. We believe this to be the first report of simultaneous right retroesophageal subclavian artery and patent ductus arteriosus. The anatomy and embryology of these two anomalies in the same specimen are discussed.     

Trends of Prosthetic Joint Infection Organisms and Recurrence for a Single High-Volume Arthroplasty Surgeon Over 20 Years

BackgroundProsthetic joint infection (PJI) is a morbid complication following total joint arthroplasty (TJA). PJI diagnosis and treatment has changed over time, and patient co-management with a high-volume musculoskeletal infectious disease (MSK ID) specialist has been implemented at our institution in the last decade.MethodsWe retrospectively evaluated all consecutive TJA patients treated for PJI between 1995 and 2018 by a single high-volume revision TJA surgeon. Microbial identities, antibiotic resistance, prior PJI, and MSK ID consultation were investigated.ResultsIn total, 261 PJI patients (median age 66 years, interquartile range 57-75) were treated. One-year and 5-year reinfection rates were 15.8% (95% confidence interval [CI] 11.6-20.7) and 22.1% (95% CI 17.0-27.7), respectively. Microbial identities and antibiotic resistances did not change significantly over time. Despite seeing more prior PJI patients (53.3% vs 37.6%, P = .012), MSK ID-managed patients had similar infection rates as non-MSK ID-managed patients (hazard ratio [HR] 1.02, 95% CI 0.6-1.75, P = .93). Prior PJI was associated with higher reinfection risk (HR 2.39, 95% CI 1.39-4.12, P = .002) overall and in patients without MSK ID consultation, specifically (HR 2.78, 95% CI 1.37-5.65, P = .005). This risk was somewhat lower and did not reach significance in prior PJI patients with MSK ID consultation (HR 1.97, 95% CI 0.87-4.48, P = .106).ConclusionWe noted minimal differences in microbial/antibiotic resistances for PJI over 20 years in a single institution, suggesting current standards of PJI treatment remain encouragingly valid in most cases. MSK ID involvement was not associated with lower reinfection risk overall; however, in patients with prior PJI, the risk of reinfection appeared to be somewhat lower with MSK ID involvement.Level of EvidenceLevel IV–Case Series.     

ACFAS Clinical Consensus Statement: Acute Achilles Tendon Pathology

Injuries to the Achilles tendon are a challenge to the foot and ankle surgeon. In recent years, research has led to a relative change in the way that many surgeons view acute Achilles tendon rupture. In an effort to fully evaluate these trends, as well as to evaluate all aspects of care for acute Achilles tendon rupture, the American College of Foot and Ankle Surgeons convened a panel of experts to create a clinical consensus statement to address selected aspects of care of the acute Achilles tendon injury.     

How does yoga reduce stress? A clinical trial testing psychological mechanisms

Yoga interventions can reduce stress, but the mechanisms underlying that stress reduction remain largely unidentified. Understanding how yoga works is essential to optimizing interventions. The present study tested five potential psychosocial mechanisms (increased mindfulness, interoceptive awareness, spiritual well-being, self-compassion and self-control) that have been proposed to explain yoga's impact on stress. Forty-two participants (62% female; 64% White) in a yoga program for stress reduction completed surveys at baseline (T1), mid-intervention (T2) and post-intervention (12 weeks; T3). We measured two aspects of stress, perceived stress and stress reactivity. Changes were assessed with paired t-tests; associations between changes in mechanisms were tested in residual change models. Only stress reactivity decreased, on average, from T1 to T3. Except for self-compassion, all psychosocial mechanisms increased from T1 to T3, with minimal changes from T2 to T3. Except for self-control, increases in each mechanism were strongly associated with decreases in both measures of stress between T1 and T2 and decreases in perceived stress from T1 to T3 (all p's < 0.05). Increased psychosocial resources are associated with stress reduction. Yoga interventions targeting these resources may show stronger stress reduction effects. Future research should test these linkages more rigorously using active comparison groups and larger samples.     

Porndemic? A Longitudinal Study of Pornography Use Before and During the COVID-19 Pandemic in a Nationally Representative Sample of Americans

Of the many changes in daily life brought about by the COVID-19 pandemic, social distancing efforts and governmentally mandated lockdowns were among the most drastic. Coinciding with these changes, popular pornography websites made some previously premium content available for free, spurring dramatic increases in traffic to these websites. This increase in time spent at home and reported increases in traffic to specific pornographic websites led to some speculation that pornography use might generally increase over the course of the pandemic and that problematic use might also increase. To test these speculations and quantify the effects of the pandemic and its associated restrictions on social behaviors on pornography use, we analyzed data from a longitudinal sample of American adults. Baseline, nationally representative data were collected in August 2019 via YouGov (N?=?2518). Subsequent data were collected in February 2020 (n?=?1677), May 2020 (n?=?1533), August 2020 (n?=?1470), and October 2020 (n?=?1269). Results indicated that, in May 2020, immediately following the height of the first wave of pandemic-related lockdowns, more people reported past-month pornography use than at other follow-up time points, but less did so than at baseline. Among those who reported use in May 2020, only 14% reported increases in use since the start of the pandemic, and their use returned to levels similar to all other users by August 2020. In general, pornography use trended downward over the pandemic, for both men and women. Problematic pornography use trended downward for men and remained low and unchanged in women. Collectively, these results suggest that many fears about pornography use during pandemic-related lockdowns were largely not supported by available data.