Expression of Fc gamma receptors on splenic T cells of mice infected with Plasmodium chabaudi adami

In previous studies, it was shown that mice infected with Plasmodium chabaudi adami have a deficiency in their production of IgG1 immunoglobulin, suggesting isotype-specific immunoregulation. In order to examine this phenomenon in further detail the expression of Fc gamma receptors (Fc gamma R) on T cells obtained from mice infected with P. chabaudi was studied by flow cytometry. There was an increase in the number of splenic T cells which expressed Fc gamma R during infection. At the peak of the acute stage of infection (10-15 days) up to 40% of T cells were positive for Fc gamma R expression. These Fc gamma R were present on about 40% of both Lyt-2+ and L3T4+T cells. The isotype preference of these receptors on control Thy-1+ T cells is IgG1 greater than IgG2b greater than IgG2a as determined by an inhibition assay and fluorescence-activated cell sorter (FACS) analysis. However, 2 to 3 weeks after infection this pattern was altered such that IgG2b and IgG2a represented the major isotypes binding to the Fc gamma R of the L3T4+ T cell. At this stage of infection Fc gamma R on L3T4+ cells fail to bind IgG1. In the Lyt-2% T cells IgG1 and IgG2b remained the best inhibitors. These data suggest that there may be changes in Fc gamma R expression on T cells during infection reflected particularly in a decreased ability of IgG1 to bind to the Fc gamma R of L3T4+ cells.     

The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe

The chemokine receptor CCR5 is encoded by the CMKBR5 gene located on the p21.3 region of human chromosome 3, and constitutes the major co- receptor for the macrophage-tropic strains of HIV-1. A mutant allele of the CCR5 gene, Delta ccr5 , was shown to provide to homozygotes with a strong resistance against infection by HIV. The frequency of the Delta ccr5 allele was investigated in 18 European populations. A North to South gradient was found, with the highest allele frequencies in Finnish and Mordvinian populations (16%), and the lowest in Sardinia (4%). Highly polymorphic microsatellites (IRI3.1, D3S4579 and IRI3.2, D3S4580 ) located respectively 11 kb upstream and 68 kb downstream of the CCR5 gene deletion were used to determine the haplotype of the chromosomes carrying the Delta ccr5 variant. A strong linkage disequilibrium was found between Delta ccr5 and specific alleles of the IRI3.1 and IRI3.2 microsatellites: >95% of the Delta ccr5 chromosomes carried the IRI3.1-0 allele, while 88% carried the IRI3.2-0 allele. These alleles were found respectively in only 2 or 1.5% of the chromosomes carrying a wild-type CCR5 gene. From these data, it was inferred that most, if not all Delta ccr5 alleles originate from a single mutation event, and that this mutation event probably took place a few thousand years ago in Northeastern Europe. The high frequency of the Delta ccr5 allele in Caucasian populations cannot be explained easily by random genetic drift, suggesting that a selection advantage is or has been associated with homo- or heterozygous carriers of the Delta ccr5 allele.      

Severe stenoses and persistent occlusions of the middle cerebral artery: hemodynamic and metabolic consequences studied by positron tomography

Using positron emission tomography and the 15O continuous inhalation technique, we have measured the regional cerebral blood flow (rCBF) oxygen extraction fraction (rOEF) and oxygen consumption (rCMRO2) of non-infarcted tissue in six patients with either tight stenosis (N = 3) or occlusion (N = 3) of the trunk of the middle cerebral artery (MCA); these arterial lesions were shown to be persistent on late and/or repeated angiograms. The patients were studied 1 to 6 months after their last cerebral ischemic event. The data were analyzed in 4 cm2 regions of interest (fig. 1) and were compared to age-matched control values. Regional right/left ratios were tested for significance individually by comparison to 95 p. 100 confidence limits found in control subjects. We found a significant reduction in mean rCBF in the affected MCA territory; concomitantly, there was a lesser decrease in rCMRO2 significant only in the peri-sylvian area; this was associated with a moderate but significant increase in rOEF in the same areas (Table II, fig. 2 and 3). Individually, the reduction in rCBF and the increased rOEF were significant in 5/6 and 2/6 patients, respectively (Table III). These data indicate that rCBF is decreased distal to persistent hemodynamic MCA obstruction in most patients. This hypoperfusion appears due in part to a mild degree of cerebral ischemia (as demonstrated by the occurrence of "misery perfusion"), indicating inadequate perfusion pressure distal to the MCA obstruction. This was associated with a metabolic depression of the cortex possibly resulting from either neuronal loss, or deactivation (diaschisis), or long-standing hemodynamic local failure or any combination of the three.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of extra-intracranial arterial bypass on cerebral blood flow and oxygen metabolism in humans

Twelve patients, eleven with a carotid obstruction and one with an occlusion of the middle cerebral artery, were studied before and after a successful unilateral extra-intracranial arterial by-pass, (EIAB) using PET and the 15-0 steady-state technique to measure regional cerebral blood flow (CBF), oxygen extraction fraction and oxygen metabolic rate (CMRO2). In the whole group of patients, both CBF and CMRO2 increased significantly on both cerebral hemispheres after EIAB, returning toward control levels defined in age-matched subjects. Mean oxygen extraction fraction, on the other hand, was not affected. Individually, three different effects of EIAB emerged: 1) Alleviation of a state of long standing unilateral "misery-perfusion", as reported earlier; 2) parallel increase of CBF and CMRO2 bilaterally, which appeared due to improvement of a hemodynamic depression of metabolism, the precise mechanism of which remains obscure; 3) Complex, unexpected changes in the CBF-CMRO2 couple again resulting in increases in CMRO2. This metabolic improvement afforded by EIAB in our patients has not been reported before; it suggests that long-standing hemodynamic failure may induce a metabolic depression that is still potentially reversible by surgical revascularization.     

Hybrid Approach to Estimation of Underreporting of Tuberculosis Case Notification in High-Burden Settings With Weak Surveillance Infrastructure: Design and Implementation of an Inventory Study

BackgroundThe greatest risk of infectious disease undernotification occurs in settings with limited capacity to detect it reliably. World Health Organization guidance on the measurement of misreporting is paradoxical, requiring robust, independent systems to assess surveillance rigor. Methods are needed to estimate undernotification in settings with incomplete, flawed, or weak surveillance systems. This study attempted to design a tuberculosis (TB) inventory study that balanced rigor with feasibility for high-need settings.ObjectiveThis study aims to design a hybrid TB inventory study for contexts without World Health Organization preconditions. We estimated the proportion of TB cases that were not reported to the Ministry of Health in 2015. The study sought to describe TB surveillance coverage and quality at different levels of TB care provision. Finally, we aimed to identify structural-, facility-, and provider-level barriers to notification and reasons for underreporting, nonreporting, and overreporting.MethodsRetrospective partial digitalization of paper-based surveillance and facility records preceded deterministic and probabilistic record linkage; a hybrid of health facilities and laboratory census with a stratified sampling of HFs with no capacity to notify leveraged a priori knowledge. Distinct extrapolation methods were applied to the sampled health facilities to estimate bacteriologically confirmed versus clinical TB. In-depth interviews and focus groups were used to identify causal factors responsible for undernotification and test the acceptability of remedies.ResultsThe hybrid approach proved viable and instructive. High-specificity verification of paper-based records in the field was efficient and had minimal errors. Limiting extrapolation to clinical cases improved precision. Probabilistic record linkage is computationally intensive, and the choice of software influences estimates. Record absence, decay, and overestimation of the private sector TB treatment behavior threaten validity, meriting mitigation. Data management demands were underestimated. Treatment success was modest in all sectors (R=37.9%–72.0%) and did not align with treatment success reported by the state (6665/8770, 75.99%). One-fifth of TB providers (36/178, 20%) were doubtful that the low volume of patients with TB treated in their facility merited mastery of the extensive TB notification forms and procedures.ConclusionsSubnational inventory studies can be rigorous, relevant, and efficient in countries that need them even in the absence of World Health Organization preconditions, if precautions are taken. The use of triangulation techniques, with minimal recourse to sampling and extrapolation, and the privileging of practical information needs of local decision makers yield reasonable misreporting estimates and viable policy recommendations.     

Effects of Coronavirus Disease Pandemic on Tuberculosis Notifications,Malawi

The coronavirus disease (COVID-19) pandemic might affect tuberculosis (TB) diagnosis and patient care. We analyzed a citywide electronic TB register in Blantyre, Malawi and interviewed TB officers. Malawi did not have an official COVID-19 lockdown but closed schools and borders on March 23, 2020. In an interrupted time series analysis, we noted an immediate 35.9% reduction in TB notifications in April 2020; notifications recovered to near prepandemic numbers by December 2020. However, 333 fewer cumulative TB notifications were received than anticipated. Women and girls were affected more (30.7% fewer cases) than men and boys (20.9% fewer cases). Fear of COVID-19 infection, temporary facility closures, inadequate personal protective equipment, and COVID-19 stigma because of similar symptoms to TB were mentioned as reasons for fewer people being diagnosed with TB. Public health measures could benefit control of both TB and COVID-19, but only if TB diagnostic services remain accessible and are considered safe to attend.     

Projected Economic Burden of Periprosthetic Joint Infection of the Hip and Knee in the United States

BackgroundIn addition to the significant morbidity and mortality associated with periprosthetic joint infection (PJI), the cost of treating PJI is substantial. Prior high-quality national estimates of the economic burden of PJI utilize data up to 2009 to project PJI growth in the United States through 2020. Now in the year 2020, it is appropriate to evaluate these past projections and incorporate the latest available data to better understand the current scale and burden of PJI in the United States.MethodsThe Nationwide Inpatient Sample (2002-2017) was used to identify rates and associated inpatient costs for primary total knee arthroplasty (TKA) and total hip arthroplasty (THA) and PJI-related revision TKA and THA. Poisson regression was utilized to model past growth and project future rates and cost of PJI of the hip and knee.ResultsUsing the most recent data, the combined annual hospital costs related to PJI of the hip and knee were estimated to be $1.85 billion by 2030. This includes $753.4 million for THA PJI and $1.1 billion for TKA PJI, in that year. Increases in PJI costs are mainly attributable to increases in volume. Although the growth in incidence of primary THA and TKA has slowed in recent years, the incidence of PJI and the cost per case of PJI remained relatively constant from 2002 to 2017.DiscussionUnderstanding the current and potential future financial burden of PJI for surgeons, patients, and healthcare systems is essential. There is an urgent need for efficacious preventive strategies in reducing rates of PJI after THA and TKA.     

Identifying the minimal important difference in patient-reported outcome measures in the field of people with severe mental illness: a pre–post-analysis of the Illness Management and Recovery Programme

Quality of Life Research - Complementary interventions for persons with severe mental illness (SMI) focus on both personal recovery and illness self-management. This paper aimed to identify the...     

NCL-5D3: a new monoclonal antibody recognizing low molecular weight cytokeratins effective for immunohistochemistry using fixed paraffin-embedded tissue

Production of a new monoclonal antibody designated NCL-5D3 is described. The antibody recognizes several low molecular weight cytokeratins, in particular cytokeratin Moll number 8 as determined by immunoblotting studies, and is highly effective for immunocytochemistry using routinely processed paraffin-embedded material. Staining is enhanced by prior treatment of the sections with trypsin. Assessment using a wide variety of normal and neoplastic tissue indicates reactivity with all tissues of simple or glandular epithelial origin, and in addition with many squamous carcinomas. Thus the antibody should prove of value in diagnostic histopathology.     

FINAL REPORT ABOUT STAGE Ⅱ COLLABORATION PROJECT ON LEPROSY REHABILITATION

Objective. To undertake the pilot experiments of prevention of disability (POD) in 14 different geographical areas to serve as examples for future development of rehabilitation work in China and in Asia. Mahods. According to the principles mid national criterion, 27 000 people affected by leprosy were selected and assessed using disability record forms at beginning and followed up regularly for observing changes of different indica-tors. Results. A total of 197 neuritis cases were detected and treated with prednisolone out of 1 407 new or active cas-es. Serf-care training of eyes, hands and feet were conducted for 10 500 disabled people affected by leprosy. Compre-hensive therapy was given to 1 804 cases having comphcated ulcers of which 1 055 cases have got their ulcers healed. Out of 706 prostheses, 613 were given to patients with satisfactory results. Surgical treatment was given to 269 cases and 251 have shown good progress. Conclusion. Most of patients have got benefit from the project in function or appearance which is very helpful for their going back to the society and agreed by foreign experts during the final evaluation. The experiences from the pro-ject can be implemented in the whole country.