A novel microelectromechanical systems (MEMS) actuation technique is developed for retinal scanning display and imaging applications allowing effective drive of a two-axes scanning mirror to wide ...angles at high frequency. Modeling of the device in mechanical and electrical domains, as well as the experimental characterization is described. Full optical scan angles of 65deg and 53deg are achieved for slow (60 Hz sawtooth) and fast (21.3 kHz sinusoid) scan directions, respectively. In combination with a mirror size of 1.5 mm, a resulting thetas opt D product of 79.5 degmiddotmm for fast axis is obtained. This two-dimensional (2-D) magnetic actuation technique delivers sufficient torque to allow non-resonant operation as low as dc in the slow-scan axis while at the same time allowing one-atmosphere operation even at fast-scan axis frequencies large enough to support SXGA (1280 times 1024) resolution scanned beam displays
IgA plays an important early neutralizing role after SARS-CoV-2 infection. Systemically administered vaccines typically produce an IgM/IgG predominant response. We evaluated the serum anti-spike ...(anti-S) IgG, anti-nucleocapsid (anti-N) IgG and anti-S IgA response following vaccination against SARS-CoV-2 in a cohort of first-responders. Among the 378 completely vaccinated participants, 98% were positive for anti-S IgG and 96% were positive for anti-S IgA. Nine percent were positive for anti-N IgG suggesting prior exposure to SARS-CoV-2. No statistically significant difference was seen in IgA response based on prior evidence infection (p = 0.18). Ninety-eight of those receiving the Moderna vaccine (98%) were positive for anti-S IgA as compared to 91% of those who received the Pfizer vaccine (p = 0.0009). The high proportion of participants observed to have a positive anti-S IgA response after vaccination suggests that the vaccines elicit a systemic response characterized by elevated levels of both IgG and IgA.
Depletional induction therapies are routinely used to prevent acute rejection and improve transplant outcome. The effects of depleting agents on T‐cell subsets and subsequent T‐cell reconstitution ...are incompletely defined. We used flow cytometry to examine the effects of rabbit antithymocyte globulin (rATG) on the peripheral T‐cell repertoire of pediatric and adult renal transplant recipients. We found that while rATG effectively depleted CD45RA+CD27+ naïve and CD45RO+CD27+ central memory CD4+ T cells, it had little effect on CD45RO+CD27− CD4+ effector memory or CD45RA+CD31−, CD45RO+CD27+ and CD45RO+CD27− CD8+ T cell subsets. When we performed a kinetic analysis of CD31+ recent thymic emigrants and CD45RA+/RO+ T cells, we found evidence for both thymopoiesis and homeostatic proliferation contributing to immune reconstitution. We additionally examined the impact of rATG on peripheral CD4+Foxp3+ T cells. We found that in adults, administration of rATG‐induced peripheral expansion and new thymic emigration of T cells with a Treg phenotype, while CD4+Foxp3+ T cells of thymic origin predominated in children, providing the first evidence that rATG induces Treg in vivo. Collectively our data indicate that rATG alters the balance of regulatory to memory effector T cells posttransplant, providing an explanation for how it positively impacts transplant outcome.
This prospective study examines the contribution of thymopoiesis versus homeostatic proliferation to immune reconstitution following rATG and the influence of rATG on the emergence of Treg in renal transplant recipients.
Although an individual's total fat mass predicts morbidities such as coronary artery disease and diabetes, the anatomical distribution of adipose tissue is a strong and independent predictor of such ...adverse health outcomes. Thus, obese individuals with most of their fat stored in visceral adipose depots generally suffer greater adverse metabolic consequences than similarly overweight subjects with fat stored predominantly in subcutaneous sites. A fuller understanding of the biology of central obesity will require information regarding the genetic and environmental determinants of human fat topography and of the molecular mechanisms linking visceral adiposity to degenerative metabolic and vascular disease. Here we attempt to summarize the growing body of data relevant to these key areas and, in particular, to illustrate how recent advances in adipocyte biology are providing the basis for new pathophysiological insights.
Mycobacterium abscessus infections have been reported as adverse events related to medical tourism. We report M. abscessus meningitis in a patient who traveled from Colorado, USA, to Mexico to ...receive intrathecal stem cell injections as treatment for multiple sclerosis. We also review the management of this challenging central nervous system infection.
Experimentally elevated potassium causes a clear pattern of electrocardiographic changes, but, clinically, the reliability of this pattern is unclear. Case reports suggest patients with renal ...insufficiency may have no electrocardiographic changes despite markedly elevated serum potassium. In a prospective series, 46% of patients with hyperkalemia were noted to have electrocardiographic changes, but no clear criteria were presented.
Charts were reviewed for patients who were admitted to a community-based hospital with a diagnosis of hyperkalemia. Inclusion criteria were potassium >/=6 with a concurrent electrocardiogram. Data were abstracted regarding comorbid diagnoses, medications, and treatment. Potassium concentrations were documented along with other electrolytes, pH, creatinine, and biomarkers of cardiac injury. Coincident, baseline, and follow-up electrocardiograms were examined for quantitative and qualitative changes in the QRS and T waves as well as the official cardiology readings.
Ninety patients met criteria; two thirds were older than 65, and 48% presented with renal failure. Common medications included beta blockers, insulin, and aspirin; 80% had potassium <7.2. The electrocardiogram was insensitive for diagnosing hyperkalemia. Quantitative assessments of T-wave amplitude corroborated subjective assessments of T-wave peaking; however, no diagnostic threshold could be established. The probability of electrocardiographic changes increased with increasing potassium. The correlation between readers was moderate.
Given the poor sensitivity and specificity of electrocardiogram changes, there is no support for their use in guiding treatment of stable patients. Without identifiable electrocardiographic markers of the risk for complications, management of hyperkalemia should be guided by the clinical scenario and serial potassium measurements.
Transplant centers have varying policies for marijuana (MJ) use in donors, transplant candidates, and recipients. Rationales for these differences range from concerns for fungal complications, ...impaired adherence, and drug interactions. This paper reviews the current status of MJ policies and practices in transplant centers and results of a survey sent to the American Society of Transplantation (AST) membership by the Executive Committee of the AST Infectious Diseases Community of Practice.The purpose of the survey was to compare policies and concerns of MJ use to actual observed complications. Of the 3321 surveys sent, 225 members (8%) responded. Transplant centers varied in their approval processes, differing even in organ types within the same institutions. Furthermore, there was discordance among transplant centers in their perceived risks of marijuana use as opposed to complications actually observed. An increasing number of states continue to legalize medical and recreational MJ resulting in widespread availability. Further research is needed to assess the validity of concerns for complications of MJ use in potential donors and recipients. Ultimately, standardized guidelines should be established based on studies and evidence‐based criteria to assist transplant programs in their policies around the use of cannabis in their donors and recipients.
Human obesity has an inherited component, but in contrast to rodent obesity, precise genetic defects have yet to be defined. A mutation of carboxypeptidase E (CPE), an enzyme active in the processing ...and sorting of prohormones, causes obesity in the fat/fat mouse. We have previously described a women with extreme childhood obesity (Fig. 1), abnormal glucose homeostasis, hypogonadotrophic hypogonadism, hypocortisolism and elevated plasma proinsulin and pro-opiomelanocortin (POMC) concentrations but a very low insulin level, suggestive of a defective prohormone processing by the endopeptidase, prohormone convertase 1 (PC1; ref. 4). We now report this proband to be a compound heterozygote for mutations in PC1. Gly-->Arg483 prevents processing of proPC1 and leads to its retention in the endoplasmic reticulum (ER). A-->C+4 of the intro-5 donor splice site causes skipping of exon 5 leading to loss of 26 residues, a frameshift and creation of a premature stop codon within the catalytic domain. PC1 acts proximally to CPE in the pathway of post-translational processing of prohormones and neuropeptides. In view of the similarity between the proband and the fat/fat mouse phenotype, we infer that molecular defects in prohormone conversion may represent a generic mechanism for obesity, common to humans and rodents.
Incarcerated people remain a priority group in efforts to control and reverse the HIV epidemic. Following release, social instability and reengagement in key transmission risk behaviors increase the ...risk of secondary transmission of HIV. Targeted programs have been developed to facilitate reengagement in care on reentry. Evaluation of the impact of these initiatives requires a systematic, confidential, framework for assessment of linkage to care for persons released from corrections. By linking HIV viral load surveillance data to corrections release data, the time to the first laboratory monitoring service in the community as well as the virologic status can be assessed. Using this method, we linked release data for sentenced individuals released from Massachusetts state correctional facilities in 2012 to HIV surveillance data from the Massachusetts HIV/AIDS Surveillance Program (MHASP) for the years 2012-2013. We identified 41 individuals with HIV released in 2012. Ninety-one percent had identified virologic assessments post release, 41% within 30 days. Thirty-three percent did not have a viral load assessed for more than 90 days and 31% had detectable virus at the time of their initial assessment. Persons with longer incarcerations (> 180 days) were more likely to have suppressed viral load at the time of follow-up (p = 0.05). This work demonstrates the important value of HIV laboratory surveillance data and correctional release data as a tool to assess linkage to care following release from corrections. We encourage jurisdictions to explore utilizing similar methodology to evaluate the effectiveness of the linkage to HIV care after release from incarceration.
The use of dual antiretroviral therapy (ART) regimens for treatment of HIV is increasing. The contemporary combination of boosted darunavir with dolutegravir has not been widely studied.
This was a ...retrospective cohort study that evaluated treatment-experienced individuals within three large urban clinics prescribed boosted darunavir with dolutegravir (study regimen) dual therapy. Follow-up was defined as the number of days from regimen initiation until the last HIV RNA determination on the study regimen. Virological outcomes, HIV RNA ≤50 copies/ml (undetectable), were assessed overall and by baseline HIV RNA status.
Of 65 individuals included, 83% were at least 3-class antiretroviral-experienced and median time since starting ART was 19 years (IQR 13-22). Median follow-up was 419 days (IQR 286-744). An undetectable HIV RNA was achieved by 62/65 (95%) individuals at any time point on the study regimen. At the end of follow-up 61/65 (94%) individuals remained undetectable, including 48/49 (98%) with an undetectable HIV RNA at baseline (those changing for optimization) and 13/16 (81%) with viraemia at baseline (those changing therapy during virological failure). At the end of follow-up, 55 (85%) individuals were still taking the study regimen. No individuals stopped therapy due to virological failure or intolerance.
In a highly treatment-experienced cohort, boosted darunavir with dolutegravir dual therapy demonstrated high rates of virological success, even in those with detectable HIV RNA prior to initiating the study regimen. Further study of this potent, simple, high-barrier dual-class regimen is warranted.
PDF
