In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP).

Plasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)n repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)n epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)n. In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions.

Deployment of the 1st Area Medical Laboratory to South Korea in Response to the COVID-19 Pandemic.

In December 2019, an outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome (SARS)-CoV-2, occurred in Wuhan city, Hubei province, China.1 South Korea saw its first confirmed Coronavirus Disease 2019 (COVID-19) case on January 20, 2020, when an infected woman from Wuhan, China arrived in S. Korea via Incheon International Airport.1 By mid-February, SARS-CoV-2 was rapidly spreading in the southern city of Daegu, S. Korea in proximity to three US Forces Korea (USFK) military installations. COVID-19 cases continued to increase during the following weeks, reaching a peak of nearly 1,000 confirmed cases per day by the end of February. As cases surged dramatically, over 28,000 USFK service members, family members, and Department of Defense (DoD) employees were at a risk of exposure to COVID-19. On February 24, clinicians diagnosed the first confirmed case in the USFK population, a 61 year-old widow of a retired service member. This individual, who experienced a mild illness, was the spouse of a retired US military veteran living in S. Korea. The retiree and his spouse both had access to military posts in S. Korea, and the spouse tested positive after she had been on one of the military bases in Area IV (Figure 1). The following day, USFK reported its first confirmed case in a service member, which was the triggering event for the 1st Area Medical Laboratory (AML) to deploy to S. Korea.

Trends in total knee replacement surgeries and implications for public health, 1990-2000.

OBJECTIVES: Total joint replacements are important surgical interventions for treating severe arthritis of weight-bearing joints. The most common indication for total knee replacement (TKR) is osteoarthritis of the knee joint. The goals of this study were to assess the trend in rate of TKR in Wisconsin and to describe the economic impact of these surgical procedures on the health care system. METHOD: A population-based cross-sectional study of TKR surgeries was conducted among Wisconsin residents aged > or = 45 years. The Wisconsin inpatient hospital discharge data from 1990 through 2000 were used. Rates were age-adjusted to the 2000 U.S. population, and charges for TKR were adjusted for inflation. RESULTS: From 1990 through 2000, the age-adjusted rate for TKR increased by 81.5% (from 162 to 294 per 100,000; p<0.001). The rate increased the most among the youngest age group (45-49 years), rate ratio 5.1 for men, 4.2 for women. The total charges for TKR increased from 69.4 million dollars to 148 million dollars (109.2% inflation-adjusted increase). Medicare received the highest proportion of charges for TKR procedures, but throughout the study period, the proportion of charges covered by private insurance increased by 39%. CONCLUSIONS: The rate and costs of TKR procedures among Wisconsin residents increased substantially from 1990 through 2000, especially among younger age groups. Changes in medical practices probably accounted for some of this increase, but these trends also may reflect an increased prevalence of osteoarthritis, which in turn may be related to dramatic increases in the number of individuals who are overweight.

Effect of subtle positioning flaws on measured bone mineral density of the hip.

Careful hip positioning is necessary for accurate and precise measurement of bone mineral density (BMD) by dualenergy X-ray absorptiometry (DXA). Large, intentional rotational deviations from best hip position reportedly increase measured BMD at the femoral neck. The aim of this study is to determine the effect of unintentional, subtle deviations from best hip position ("flaws") on expected and measured BMD of the hip and its subregions. Two hundred DXA scans (GE/Lunar Prodigy) performed in the dual-femur mode were randomly selected and scrutinized for hip-positioning flaws. Hips were sorted by side (right/left), positioning quality (flawless/flawed), and specific positioning flaw (under/over-rotation and adduction/abduction). Individual hip pairs in which at least one hip was flawlessly positioned were further sorted as flawless/flawless, flawless/vertically flawed, flawless/rotationally flaw, and flawless/dually flawed. Differences and direction of difference in BMD between sorted groups and within individual hip pairs were analyzed by univariate analysis (t-test for equal samples). Two hundred hip pairs (400 individual hip scans) were analyzed. Overall, there was no significant difference in BMD between all right and all left hips or between all flawlessly positioned and all flawed hips. In hip pairs in which one hip was flawlessly positioned and the contralateral hip position was flawed (vertically, rotationally, or both), the measured BMD of the latter hip was not predictably greater than the former. Average absolute intrapair BMD difference between hip subregions was 0.038+/-0.001 g/cm2 and was unaffected by the presence or type of positioning flaw. Net intrapair difference between sorted hip groups and within hip pairs was negligible, indicating that the direction of the variance was equally positive and negative. In the practice of clinical densitometry, subtle positioning flaws do not generate predictable changes in measured BMD at any hip region of interest. The current teaching that rotational deviations from best hip position results in a greater measured BMD needs to be reconsidered when comparing a rotationally flawed hip with a contralateral flawlessly positioned hip.

Collaborative/Participatory research.

Collaborative (or, participatory) research involves a working relationship between at least one academic institution's research unit and one community-based organization. The community-based organizations of interest are those from and representing underserved communities. Barriers to collaboration, approaches to overcoming such barriers, and principles for the maintenance of good collaborative research relations are given. Representatives of the underserved and academic research units tend to interact in a collaborative/participatory relationship by means of formal committees. How the degrees of power of the underserved on such committees might be understood is discussed in terms of a model from Arnstein's 1971 article and the value of participation for the underserved is discussed.

Gluteus minimus necrotic muscle debridement diminishes heterotopic ossification after acetabular fracture fixation.

OBJECTIVE: The aetiology and pathogenesis of heterotopic ossification (HO) are still obscure. We evaluated the impact of necrotic gluteus minimus muscle (GMM) debridement on the formation of HO after operative treatment of posterior wall (PW) and associated transverse-posterior wall acetabular fracture (Tr/PW) fixations utilizing a Kocher-Langenbeck surgical exposure. METHODS: Thirty-one consecutive patients with displaced PW or associated Tr/PW acetabular fracture-dislocations were operatively treated by a single surgeon using a Kocher-Langenbeck surgical exposure. Strict soft tissue technique was observed and self-retaining retractors were not used. Necrotic GMM was debrided in an attempt to diminish ectopic bone formation. RESULTS: Twenty-nine patients were available for post-operative clinical and radiographic evaluations. HO occurred in 12 patients. Significant HO (Brooker class III or IV) was noted in only three patients (10%). There were no complications associated with debridement of necrotic GMM. CONCLUSIONS: Necrotic GMM resection diminishes HO formation comparably to other reported series in which non-steroidal anti-inflammatory medications were used. Resection of the necrotic GMM from the zone of injury has proved to be an efficient and safe method of preventing significant HO in patients after operative fixation of PW and associated Tr/PW acetabular fractures treated through a Kocher-Langenbeck approach.

Artritis reumatoidea precoz / Early rheumatoid arthritis

El diagnostico de artritis reumatoidea precoz se basa generalmente en la anamnesis y el examen fisico y suele establecerse por exclusion. El diagnostico diferencial puede plantear dificultades debido a las grandes variaciones en cuanto edad, sexo, sintomas sistemicos, hallazgos del examen fisico y distribucion de la artropatia. La terapia intensiva inicial debe incluir educacion del paciente, reposo, ejercicios graduados, consejeria y tratamiento farmacologico apropiado. La ausencia de nodulos subcutaneos y de erosion articular puede significar un mejor pronostico en la artritis reumatoidea. La presencia de factor reumatoide, eosinofilia, trombocitosis o vasculitis indica una evolucion menos favorable