Association among income loss, financial strain and depressive symptoms during COVID-19: evidence from two longitudinal studies.

BACKGROUND: The COVID-19 pandemic has major ramifications for global health and the economy, with growing concerns about economic recession and implications for mental health. Here we investigated the associations between COVID-19 pandemic-related income loss with financial strain and mental health trajectories over a 1-month course. METHODS: Two independent studies were conducted in the U.S and in Israel at the beginning of the outbreak (March-April 2020, T1; N = 4 171) and at a 1-month follow-up (T2; N = 1 559). Mixed-effects models were applied to assess associations among COVID-19-related income loss, financial strain, and pandemic-related worries about health, with anxiety and depression, controlling for multiple covariates including pre-COVID-19 income. FINDINGS: In both studies, income loss and financial strain were associated with greater depressive symptoms at T1, above and beyond T1 anxiety, worries about health, and pre-COVID-19 income. Worsening of income loss was associated with exacerbation of depression at T2 in both studies. Worsening of subjective financial strain was associated with exacerbation of depression at T2 in one study (US). INTERPRETATION: Income loss and financial strain were uniquely associated with depressive symptoms and the exacerbation of symptoms over time, above and beyond pandemic-related anxiety. Considering the painful dilemma of lockdown versus reopening, with the tradeoff between public health and economic wellbeing, our findings provide evidence that the economic impact of COVID-19 has negative implications for mental health. FUNDING: This study was supported by grants from the National Institute of Mental Health, the US-Israel Binational Science Foundation, Foundation Dora and Kirsh Foundation.

Low-dose alemtuzumab for GvHD prevention followed by prophylactic donor lymphocyte infusions in high-risk leukemia.

We analyzed the use of low-dose alemtuzumab in a cohort of 158 consecutive patients who underwent allogeneic PBSC transplantation. Patients with high-risk acute leukemia were prospectively screened for prophylactic donor lymphocyte infusion (pDLI). Lymphocytes were administered repeatedly at low and non-escalating doses (0.5-1 × 106/kg). Low-dose alemtuzumab was effective in prevention of acute GvHD after sibling or well-matched unrelated transplantation, whereas a more intensified approach was needed after mismatched transplantation. The cumulative incidence of chronic moderate/severe chronic-GvHD (cGvHD) was 15.6%. In total, 63 high-risk leukemia patients were eligible for pDLI. Only 1 out of the 39 pDLI recipients relapsed as compared with 7 out of the 24 recipients, who did not receive pDLI due to logistical hurdles. In multivariate analysis, the use of adjuvant lymphocyte therapy was significantly associated with reduced incidence of relapse and improved disease-free survival. In summary, low-dose alemtuzumab confers to a low cGvHD incidence and the administration of pDLIs in this context is very likely to reduce relapse risk in high risk leukemia patients. This is translated in an estimated 5-year probability of GvHD-free and relapse-free survival of 43.3% for the 136 leukemia patients.

G-CSF-primed BM for allogeneic SCT: revisited.

G-SCF-mobilized PBSC (GPB) grafts have a higher cell dose and somewhat more committed progenitor cells than steady-state BM (SBM), resulting in faster engraftment and faster immunological reconstitution. On the other hand, transplant related mortality (TRM), disease-free survival (DFS) and overall survival (OS) are similar both for PB and for BM. In contrast to SBM, G-CSF-primed BM (GBM) grafts stimulate HSC proliferation, increasing cell dose and thus resulting in faster engraftment because of higher cell dose infused, or because of treatment with G-CSF. Furthermore, GBM may induce tolerance and functional modulations in donor hematopoiesis and immunity, further reducing GVHD incidence, which is already lower with SBM compared with GPB grafts. Overall, a growing body of clinical evidence suggests that GBM transplants may share the advantages of GPB transplantations, without the associated increased risk of GVHD, and might be an attractive graft source for allogeneic SCTs.

Suprasellar and intrasellar paragangliomas.

Neoplasms of the sellar region are entities with a large differential diagnosis. Although paraganglionic cells have not been demonstrated in the pituitary or adjacent structures, the existence of sellar region paragangliomas is well-documented. To elucidate, in this area the nature of these unusual tumors is relatively difficult. Clinical history, physical examination, radiographic investigation as well as intraoperative gross observation are the same as those of sellar meningioma or pituitary adenoma. Immunohistochemistry, using neuroendocrine markers and electron microscopy are the two definitive diagnostic methods to differentiate among these entities. The clinical management, the possible pathogenesis of the tumor, the importance of immunohistochemistry in making the diagnosis and the clinical outcome of these patients are discussed.

Cytosolic phospholipase A2 is responsible for prostaglandin E2 and leukotriene B4 formation in phagocyte-like PLB-985 cells: studies of differentiated cPLA2-deficient PLB-985 cells.

Our previously established model of cytosolic phospholipase A(2) (cPLA(2))-deficient, differentiated PLB-985 cells (PLB-D cells) was used to determine the physiological role of cPLA(2) in eicosanoid production. Parent PLB-985 (PLB) cells and PLB-D cells were differentiated toward the monocyte or granulocyte lineages using 5 x 10(-)(8) M 1,25 dihydroxyvitamin D(3) or 1.25% dimethyl sulfoxide, respectively. Parent monocyte- or granulocyte-like PLB cells released prostaglandin E(2) (PGE(2)) when stimulated by ionomycin, A23187, opsonized zymosan, phorbol 12-myristate 13-acetate, or formyl-Met-Leu-Phe (fMLP), and monocyte- or granulocyte-like PLB-D cells did not release PGE(2) with any of the agonists. The kinetics of cPLA(2) translocation to nuclear fractions in monocyte-like PLB cells stimulated with fMLP or ionomycin was in correlation with the kinetics of PGE(2) production. Granulocyte-like PLB cells, but not granulocyte-like PLB-D cells, secreted leukotriene B(4) (LTB(4)) after stimulation with ionomycin or A23187. Preincubation of monocyte-like parent PLB cells with 100 ng/ml lipopolysaccharide (LPS) for 16 h enhanced stimulated PGE(2) production, which is in correlation with the increased levels of cPLA(2) detected in these cells. LPS preincubation was less potent in increasing PGE(2) and LTB(4) secretion and did not affect cPLA(2) expression in granulocyte-like PLB cells, which may be a result of their lower levels of surface LPS receptor expression. LPS had no effect on monocyte- or granulocyte-like PLB-D cells. The lack of eicosanoid formation in stimulated, differentiated cPLA(2)-deficient PLB cells indicates that cPLA(2) contributes to stimulated eicosanoid formation in monocyte- and granulocyte-like PLB cells.

Essential requirement of cytosolic phospholipase A(2) for stimulation of NADPH oxidase-associated diaphorase activity in granulocyte-like cells.

We have previously established a model of cytosolic phospholipase A(2) (cPLA(2))-deficient differentiated PLB-985 cells (PLB-D cells) and demonstrated that cPLA(2)-generated arachidonic acid (AA) is essential for NADPH oxidase activation. In this study we used this model to investigate the physiological role of cPLA(2) in regulation of NADPH oxidase-associated diaphorase activity. A novel diaphorase activity assay, using 4-iodonitrotetrazolium violet as an electron acceptor, was used in permeabilized neutrophils and PLB-985 cells differentiated toward the granulocytic or monocytic phenotypes. Phorbol 12-myristate 13-acetate, guanosine 5'-3-O- (thio)triphosphate (GTP gamma S), or FMLP stimulated a similar diphenylene iodonium-sensitive diaphorase activity pattern in neutrophils and in differentiated parent PLB-985 cells. This diaphorase activity was not detected in undifferentiated cells, but developed during differentiation. Furthermore, diaphorase activity could not be stimulated in permeabilized neutrophils from X-linked CGD patients and in differentiated gp91(phox)-targeted PLB-985 cells that lacked normal expression of gp91(phox), but was restored to these cells following transduction with retrovirus encoding gp91(phox). The differentiated PLB-D cells showed no diaphorase activity when stimulated by either GTP gamma S or FMLP, and only partial activation when stimulated with phorbol 12-myristate 13-acetate. Diaphorase activity in response to either agonists was fully restored by the addition of 10 microm free AA. The permeabilized cell 4-iodonitrotetrazolium violet reduction assay offers a unique tool for the evaluation of NADPH oxidase-associated diaphorase activity in stimulated whole cells. These results establish an essential and specific physiological requirement of cPLA(2)-generated AA in activation of electron transfer through the FAD reduction center of NADPH oxidase.

The NADPH oxidase diaphorase activity in permeabilized human neutrophils and granulocytic like PLB-985 cells.

The phagocyte NADPH oxidase is a multicomponent transport chain that generates superoxide, a precursor of microbicidal oxidants, important for host defense. This transport chain is contained mainly in the large membrane subunit of the oxidase (gp91phox), and transfers electrons from cytosolic NADPH, through FAD binding and heme centers, to molecular oxygen (Babior, 1999; Fujii and Kakinuma, 1991; Rotrosen et al., 1992; Segal and Abo, 1993). Cross et al. have recently described a novel NADPH oxidase diaphorase activity present in the membrane fraction of activated neutrophils, using a cell free model (Cross et al., 1994). This diaphorase activity is measured by the artificial electron acceptor 4-iodonitrotetrazolium violet (INT) and is attributed to the reduction of the flavin center of the flavocytochrome (Cross et al., 1994; Li and Guillory, 1997). In the present study we establish a system for detecting diaphorase activity in intact cells. Neutrophils and PLB-985 cells, that were differentiated using 1.25% dimethyl sulfoxide (DMSO) to granulocyte phenotype, were permeabilized by electroporation, and diaphorase activity was determined using INT. Neutrophils and differentiated PLB-985 cells stimulated by PMA or GTP gamma S showed a diaphorase activity that was not present in unstimulated differentiated cells. The diaphorase activity could not be detected in undifferentiated cells and was developed during differentiation. The pattern of diaphorase activity in stimulated parent differentiated PLB cells was similar to that observed in stimulated human neutrophils. The permeabilized-INT cell system offers a unique tool for the evaluation of NADPH oxidase diaphorase activity, in whole cells.