Performance of a histidine-rich protein 2 rapid diagnostic test, Paracheck Pf®, for detection of malaria infections in Ugandan pregnant women

Improved laboratory diagnosis is critical to reduce the burden of malaria in pregnancy. Peripheral blood smears appear less sensitive than Plasmodium falciparum histidine-rich protein 2-based rapid diagnostic tests (RDTs) for placental malaria infections in studies conducted at delivery. In this study, 81 women in Uganda in the second or third trimester of pregnancy were followed-up until delivery. At each visit, peripheral blood was tested by blood smear, RDT, and nested species-specific polymerase chain reaction (PCR). Sensitivity and specificity of the tests was calculated with PCR, which detected 22 infections of P. falciparum, as the gold standard. The sensitivity and specificity of blood smears were 36.4% (95% confidence interval [CI] = 18.0-59.2%) and 99.6% (95% CI = 97.7-100%), respectively. The corresponding values for RDT were 31.8% (95% CI = 14.7-54.9%) and 100% (95% CI = 98.3-100%). The RDTs could replace blood smears for diagnosis of malaria in pregnancy by virtue of their relative ease of use. Field-based sensitive tests for malaria in pregnancy are urgently needed.     

Impact of COVID-19 on cancer management in military hospitals of Saudi Arabia

Objectives:To evaluate the impact of COVID-19 on cancer management in Saudi Arabia’s military hospitals.Methods:This multi-centric, retrospective study compared cancer patients diagnosed from February-July 2019 and 2020, focusing on the time duration for acceptance and time for oncologic treatment initiation. Eligibility and referral status were recorded. Clinical data of COVID-19-positive cancer patients were collected and evaluated their outcomes and survival.Results:Data of 1574 cancer patients (mean age, 57.1 years) were collected. Mean time for acceptance was 7.3 days in 2019 and 8 days in 2020, with no statistically significant difference. Mean time for oncology treatment initiation was 38.4 days in 2019 and 44.3 days in 2020, with no statistically significant difference. The number of new cancer patients decreased in 2020 but increased in peripheral hospitals. It decreased in Riyadh and Jeddah hospitals. Concerning referral status, a statistically significant modification was recorded only in Riyadh and Tabuk hospitals. No significant changes observed in time duration for acceptance of new patients and oncology treatment initiation from 2019-2020. A total of 76 COVID-19-positive cancer patients recorded; 72% were symptomatic, 73.6% recovered, 22.3% died due to COVID-19 complications, and 8% died due to cancer; cancer progressed in 7 patients.Conclusion:COVID-19 did not affect oncology service in Saudi Arabia’s military hospitals. New cancer cases reduced during the pandemic. Cancer patients are at increased risk for COVID-19 complications, including death.     

Ability of laypersons to use the cincinnati prehospital stroke scale

Objective

Early stroke recognition optimizes patients' opportunities to benefit from therapeutic options. Prehospital stroke recognition is suboptimal. If 9-1-1 dispatchers used stroke-identification tools, prehospital stroke recognition might occur more rapidly and accurately. The Cincinnati Prehospital Stroke Scale (CPSS) is a brief, effective tool used by emergency medical services and hospital personnel to identify stroke. The study's goal was to determine whether laypersons could be instructed to use the CPSS over the telephone.

Methods

Adult visitors (laypersons) to a tertiary care emergency department were enrolled. Using a mock patient, laypersons were instructed to use the CPSS via telephone by an investigator simulating a 9-1-1 dispatcher. The patient randomly portrayed clinically normal and abnormal patient types. The layperson's ability to convey CPSS instructions to the patient and relay findings to the investigator was scored.

Results

Seventy laypersons were enrolled (35 each for normal and abnormal patient types). Average age was 48 years, 63% were female, and 40% never attended college. Facial droop and speech instructions were administered with 100% accuracy. Arm drift instructions were administered with 99% accuracy. Layperson accuracies for interpreting findings were 93% for facial droop, 93% for arm drift, and 97% for speech. Overall, stroke symptoms were detected with 94% sensitivity (95% CI 87, 100) and 83% specificity (95% CI 70, 95).

Conclusion

Laypersons correctly administered and interpreted the CPSS when directed to do so over the telephone by a trained investigator. These findings suggest that the CPSS may be a useful tool in early prehospital detection of stroke by dispatchers.     

LC3-associated phagocytosis in bone marrow macrophages suppresses acute myeloid leukemia progression through STING activation

The bone marrow (BM) microenvironment regulates acute myeloid leukemia (AML) initiation, proliferation, and chemotherapy resistance. Following cancer cell death, a growing body of evidence suggests an important role for remaining apoptotic debris in regulating the immunologic response to and growth of solid tumors. Here, we investigated the role of macrophage LC3–associated phagocytosis (LAP) within the BM microenvironment of AML. Depletion of BM macrophages (BMMs) increased AML growth in vivo. We show that LAP is the predominate method of BMM phagocytosis of dead and dying cells in the AML microenvironment. Targeted inhibition of LAP led to the accumulation of apoptotic cells (ACs) and apoptotic bodies (ABs), resulting in accelerated leukemia growth. Mechanistically, LAP of AML-derived ABs by BMMs resulted in stimulator of IFN genes (STING) pathway activation. We found that AML-derived mitochondrial damage–associated molecular patterns were processed by BMMs via LAP. Moreover, depletion of mitochondrial DNA (mtDNA) in AML-derived ABs showed that it was this mtDNA that was responsible for the induction of STING signaling in BMMs. Phenotypically, we found that STING activation suppressed AML growth through a mechanism related to increased phagocytosis. In summary, we report that macrophage LAP of apoptotic debris in the AML BM microenvironment suppressed tumor growth.     

Secondary biogenic amine deficiencies: genetic etiology,therapeutic interventions,and clinical effects

neurogenetics - Monoamine neurotransmitter disorders present predominantly with neurologic features, including dystonic or dyskinetic cerebral palsy and movement disorders. Genetic conditions that...     

Novel sigma (sigma) receptor agonists produce antidepressant-like effects in mice.

Many antidepressant drugs interact with sigma receptors and accumulating evidence suggests that these proteins mediate antidepressant-like effects in animals and humans. sigma Receptors are localized in brain regions affected in depression, further strengthening the hypothesis that they represent logical drug development targets. In this study, two novel sigma receptor agonists (UMB23, UMB82) were evaluated for antidepressant-like activity in mice. First, radioligand binding studies confirmed that the novel compounds had preferential affinity for sigma receptors. Second, the forced swim test, a well established animal model for screening potential antidepressant drugs, showed that both compounds dose-dependently reduced immobility time. The sigma receptor antagonist BD1047 attenuated the antidepressant-like effects of UMB23 and UMB82. Third, locomotor activity suggested that the effects of UMB23 and UMB82 in the forced swim test were not due to non-specific motor activating effects. Together, the data provide further evidence that sigma receptor agonists represent a possible new class of antidepressant medication.     

Feeding Practices and Growth in Yemeni Children

A nutritional survey in the Tihama region of Yemen allowed an analysis of the relationship between infant feeding practices and the growth of children 3-23 months of age. The survey was conducted in 1979 on a representative sample of 364 preschool children 3-23 months of age. After adjustment for demographic and socioeconomic factors, breast feeding was found to be associated with higher weight-for-length and weight-for-age. The strongest beneficial effect of breast feeding on weight-for-length was seen at 3-6 months, a weaker effect at 7-12 months, and essentially no effect over 12 months of age. A higher weight-for-age was seen in breast-fed infants 3-6 months of age only. Introducing other foods was associated with higher weight-for-length only in children 13-23 months of age. Neither breast feeding nor introducing other foods was associated with length-for-age. Infant feeding practices appear to be associated with weight gain, but not linear growth in Yemeni infants.