An acquired G-CSF receptor mutation results in increased proliferation of CMML cells from a patient with severe congenital neutropenia.

Severe congenital neutropenia (CN) is characterized by a maturation arrest of myelopoiesis at the promyelocyte stage. Treatment with pharmacological doses of recombinant human granulocyte colony-stimulating factor (rh-G-CSF) stimulates neutrophil production and decreases the risk of major infectious complications. However, approximately 15% of CN patients develop myeloid malignancies that have been associated with somatic mutations in the G-CSF receptor (G-CSFR) and RAS genes as well as with acquired monosomy 7. We report a CN patient with chronic myelomonocytic leukemia (CMML) who never received rh-G-CSF. Molecular analysis demonstrated a somatic G-CSFR mutation (C2390T), which led to expression of a truncated G-CSFR protein in the CMML. Normal G-CSFR expression was unexpectedly absent in primary and cultured CMML. In addition, CMML cells showed monosomy 7 and an oncogenic NRAS mutation. In vitro culture revealed a G-CSF-dependent proliferation of CMML cells, which subsequently differentiated along the monocytic/macrophage lineage. Our results provide direct evidence for the in vivo expression of a truncated G-CSFR in leukemic cells, which emerged in the absence of rh-G-CSF treatment and transduces proliferative signals.     

The Second Wave of COVID-19: Clinical Pharmacy Services During a Field Hospital Operation

The second wave of COVID-19 emerged in the late fall months in the state of Massachusetts and inadvertently caused a rise in the number of cases requiring hospitalization. With a field hospital previously opened in central Massachusetts during the Spring of 2020, the governor decided to reimplement the field hospital. Although operations were effectively accomplished during the first wave, the reimplementation of the field hospital came with its new set of challenges for operating a satellite pharmacy. Experiences gathered include new pharmacy operation workflows, the clinical role of pharmacy services, introduction of remdesivir treatment, and pharmacy involvement in newly diagnosed diabetes patients requiring insulin teaching. Pharmacy services were successful in adapting to the rapidly growing number in patients with a total of over 600 patients served in a course of 2 months.     

Screening for depression in pregnant women with HIV infection

OBJECTIVE: To determine the utility of screening for depression in pregnant women with human immunodeficiency virus (HIV) infection. STUDY DESIGN: Women with HIV infection who received prenatal care at an inner-city institution between March 2004 and March 2006 were offered the Beck Depression Inventory (BDI), a screening tool to detect depressive symptomatology. Scores >9 were considered positive. RESULTS: Of 51 subjects who participated, 53% had positive screening scores for depression. Of those whose scores were positive, 33% had no prior history of psychiatric illness. Those in whom HIV was diagnosed during pregnancy had higher mean and median BDI scores than those with HIV diagnosed before pregnancy (21.2 vs. 13.3 and 21 vs. 9.5, respectively; p = 0.049). Two factors were associated with positive screenings: history of psychiatric disease (p = 0.001) and history of substance abuse (p = 0.042). Patients with positive screenings first presented for prenatal care at a later gestational age and had fewer prenatal visits than those without evidence of depression (14.9 vs. 12.0, p = 0.035 and 9.2 vs. 11.3, p = 0.045). More than half (56%) who screened positive received psychological care during the prenatal period. CONCLUSION: Women with HIV infection should routinely be screened for depression during pregnancy. Those with positive screens should be offered formal psychological evaluation.     

Optimal reproductive competence of oocytes retrieved through follicular flushing in minimal stimulation IVF

The objective of this study was to assess the reproductive competence of oocytes obtained by follicular flushing in poor responder patients. This prospective comparative study, at the University of Paris XI, Assistance Publique des Hopitaux de Paris, INSERM Unit 782, was performed on 165 infertile IVF embryo transfer candidates. A total of 271 consecutive minimal stimulation IVF cycles were studied. Oocyte retrieval was performed 34 h after human chorionic gonadotrophin administration and oocytes were allocated into two groups according to their retrieval method: oocytes obtained in the first follicular aspiration (FA, n = 127); and oocytes retrieved in the subsequent follicular flushing (FF, n = 102). The principal outcome was to evaluate clinical pregnancy and embryo implantation rates. Thus, patient characteristics, fertilization rate and clinical pregnancy rate per oocyte were comparable in both of groups. In contrast, embryo morphology (41 versus 59%, P < 0.01) and implantation rates (20.4 versus 34.8%, P < 0.04) were better in the FF group. In conclusion, an optimal reproductive competence was observed in oocytes retrieved by follicular flushing in minimal stimulation IVF in poor responder patients.     

Induced hyper and hypo amino acidemia in the ovine fetus near term: effects on electrocortical activity

Amino acid infusate (Primene) and insulin euglycemic (insulin + 10% dextrose) clamp techniques were used in the ovine fetus near term and the impact on the incidence of low-voltage and high-voltage electrocortical (ECOG) activities was determined. Fetal sheep were studied over a 2-hour control period and a subsequent 6-hour experimental period.With the Primene infusion, the basic and neutral amino acids were increased by 43% and 25%, respectively, whereas the acidic amino acids showed little change. With the insulin/dextrose infusion, the basic and neutral amino acids decreased by 48% and 30%, respectively, whereas the acidic amino acids were again little changed. A small fall in arterial oxygen saturation and an increase in fetal heart rate for both groups can be attributed to an insulin-mediated increase in fetal metabolic rate. Despite the moderate increases and decreases in circulating amino acid levels, there was no significant change in the mean percent time or duration of fetal ECOG activities for either study group.     

Immunomodulatory and anti-SARS activities of Houttuynia cordata

BACKGROUND: Severe acute respiratory syndrome (SARS) is a life-threatening form of pneumonia caused by SARS coronavirus (SARS-CoV). From late 2002 to mid 2003, it infected more than 8000 people worldwide, of which a majority of cases were found in China. Owing to the absence of definitive therapeutic Western medicines, Houttuynia cordata Thunb. (Saururaceae)(HC) was shortlisted by Chinese scientists to tackle SARS problem as it is conventionally used to treat pneumonia. AIM OF THE STUDY: The present study aimed to explore the SARS-preventing mechanisms of HC in the immunological and anti-viral aspects. RESULTS: Results showed that HC water extract could stimulate the proliferation of mouse splenic lymphocytes significantly and dose-dependently. By flow cytometry, it was revealed that HC increased the proportion of CD4(+) and CD8(+) T cells. Moreover, it caused a significant increase in the secretion of IL-2 and IL-10 by mouse splenic lymphocytes. In the anti-viral aspect, HC exhibited significant inhibitory effects on SARS-CoV 3C-like protease (3CL(pro)) and RNA-dependent RNA polymerase (RdRp). On the other hand, oral acute toxicity test demonstrated that HC was non-toxic to laboratory animals following oral administration at 16 g/kg. CONCLUSION: The results of this study provided scientific data to support the efficient and safe use of HC to combat SARS.