The Stress of Parenting in the Postpartum Period During the COVID-19 Pandemic.

Background: The COVID-19 pandemic produced a major shift in parental roles, which disproportionally exacerbated existing challenges for low-income new parents. Our objective was to identify pandemic-related parenting challenges experienced by low-income postpartum individuals in the context of the early months of the COVID-19 pandemic. Methods: Semistructured interviews with 40 low-income postpartum individuals were conducted within 10 weeks after giving birth in April 2020-June 2020. Interviews addressed maternal health and well-being, parental stress, including COVID-related barriers to providing for children, and access to essential services. Interview themes were developed using the constant comparative method. Results: Half (n = 20) the participants identified as non-Hispanic Black and 38% (n = 15) as Hispanic; 75% (n = 30) were parents of multiple children. Parenting-related themes included challenges of parenting multiple children, barriers to maintaining self-care, and novel barriers to providing for children. Participants discussed handling new roles as educators, struggles with entertaining, allocating time among children, and effects of the pandemic on older children. Participants frequently described their lack of alone time, changes in self-care and coping strategies due to continuous parenting, and effects on maternal mental health like increased anxiety. Many participants reported lack of communal support, financial stress, and difficulty accessing services. Conclusions: New burdens introduced by the pandemic challenged low-income individuals' health and well-being. Understanding these psychosocial stressors and developing interventions to ameliorate these burdens may be key to promoting family health during difficult times; one potential solution for preventing postpartum depression is offering continual social services. Clinical Trial No.: NCT03922334.

Megalin/lipoprotein receptor-related protein 2 autoimmunity and kidney disease.

In this issue of Clinical Kidney Journal, Gamayo et al. describe two cases of anti-low-density lipoprotein receptor-related protein 2 (LRP2) nephropathy. This is a recently described entity that has features of both tubulointerstitial disease and segmental membranous nephropathy. The originality of the present report consists of the association of a disease thought to be rare (only 13 in prior described patients, 11 in the past year) with B-cell lymphoproliferative disease. Together with the finding of a third case among 224 elderly patients studied, this raises the issue of the underdiagnoses of LRP2 nephropathy, on top of the potential association to B-cell malignancy. We now put these findings in context within the wider frame of autoimmunity against megalin/LRP2 and related antigens such as Fx1A and CD69.

Mitochondrial division inhibitor 1 disrupts oligodendrocyte Ca2+ homeostasis and mitochondrial function.

Mitochondrial fission mediated by cytosolic dynamin related protein 1 (Drp1) is essential for mitochondrial quality control but may contribute to apoptosis as well. Blockade of Drp1 with mitochondrial division inhibitor 1 (mdivi-1) provides neuroprotection in several models of neurodegeneration and cerebral ischemia and has emerged as a promising therapeutic drug. In oligodendrocytes, overactivation of AMPA-type ionotropic glutamate receptors (AMPARs) induces intracellular Ca2+ overload and excitotoxic death that contributes to demyelinating diseases. Mitochondria are key to Ca2+ homeostasis, however it is unclear how it is disrupted during oligodendroglial excitotoxicity. In the current study, we have analyzed mitochondrial dynamics during AMPAR activation and the effects of mdivi-1 on excitotoxicity in optic nerve-derived oligodendrocytes. Sublethal AMPAR activation triggered Drp1-dependent mitochondrial fission, whereas toxic AMPAR activation produced Drp1-independent mitochondrial swelling. Accordingly, mdivi-1 efficiently inhibited Drp1-mediated mitochondrial fission and did not prevent oligodendrocyte excitotoxicity. Unexpectedly, mdivi-1 also induced mitochondrial depolarization, ER Ca2+ depletion and modulation of AMPA-induced Ca2+ signaling. These off-target effects of mdivi-1 sensitized oligodendrocytes to excitotoxicity and ER stress and eventually produced oxidative stress and apoptosis. Interestingly, in cultured astrocytes mdivi-1 induced nondetrimental mitochondrial depolarization and oxidative stress that did not cause toxicity or sensitization to apoptotic stimuli. In summary, our results provide evidence of Drp1-mediated mitochondrial fission during activation of ionotropic glutamate receptors in oligodendrocytes, and uncover a deleterious and Drp1-independent effect of mdivi-1 on mitochondrial and ER function in these cells. These off-target effects of mdivi-1 limit its therapeutic potential and should be taken into account in clinical studies.

CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype.

PURPOSE: CLAPO syndrome is a rare vascular disorder characterized by capillary malformation of the lower lip, lymphatic malformation predominant on the face and neck, asymmetry, and partial/generalized overgrowth. Here we tested the hypothesis that, although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism. METHODS: We clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from 9 patients using high-throughput, deep sequencing. RESULTS: We identified five activating mutations in the PIK3CA gene in affected tissues from 6 of the 9 patients studied; one of the variants (NM_006218.2:c.248T>C; p.Phe83Ser) has not been previously described in developmental disorders. CONCLUSION: We describe for the first time the presence of somatic activating PIK3CA mutations in patients with CLAPO. We also report an update of the phenotype and natural history of the syndrome.

The Choice of Hemodialysis Membrane Affects Bisphenol A Levels in Blood.

Bisphenol A (BPA), a component of some dialysis membranes, accumulates in CKD. Observational studies have linked BPA exposure to kidney and cardiovascular injury in humans, and animal studies have described a causative link. Normal kidneys rapidly excrete BPA, but insufficient excretion may sensitize patients with CKD to adverse the effects of BPA. Using a crossover design, we studied the effect of dialysis with BPA-containing polysulfone or BPA-free polynephron dialyzers on BPA levels in 69 prevalent patients on hemodialysis: 28 patients started on polysulfone dialyzers and were switched to polynephron dialyzers; 41 patients started on polynephron dialyzers and were switched to polysulfone dialyzers. Results were grouped for analysis. Mean BPA levels increased after one hemodialysis session with polysulfone dialyzers but not with polynephron dialyzers. Chronic (3-month) use of polysulfone dialyzers did not significantly increase predialysis serum BPA levels, although a trend toward increase was detected (from 48.8±6.8 to 69.1±10.1 ng/ml). Chronic use of polynephron dialyzers reduced predialysis serum BPA (from 70.6±8.4 to 47.1±7.5 ng/ml, P<0.05). Intracellular BPA in PBMCs increased after chronic hemodialysis with polysulfone dialyzers (from 0.039±0.002 to 0.043±0.001 ng/10(6) cells, P<0.01), but decreased with polynephron dialyzers (from 0.045±0.001 to 0.036±0.001 ng/10(6) cells, P<0.01). Furthermore, chronic hemodialysis with polysulfone dialyzers increased oxidative stress in PBMCs and inflammatory marker concentrations in circulation. In vitro, polysulfone membranes released significantly more BPA into the culture medium and induced more cytokine production in cultured PBMCs than did polynephron membranes. In conclusion, dialyzer BPA content may contribute to BPA burden in patients on hemodialysis.

Klotho, phosphate and inflammation/ageing in chronic kidney disease.

Evidence is emerging for the inflammatory nature of many ageing-associated diseases, including atherosclerosis, vascular calcification, diabetes and chronic kidney disease (CKD), among others. Ageing itself results in chronic low-grade inflammation that promotes end-organ damage. Inflammatory organ damage, in turn, may contribute to inflammation. Recent research has identified the kidney-secreted hormone Klotho as a central player at the ageing-inflammation interface. Thus, systemic or local renal inflammation decreases kidney Klotho expression. Klotho down-regulation may be induced by specific cytokines such as tumour necrosis factor-α or TWEAK through the canonical activation of the inflammatory transcription factor nuclear factor kappa B (NFκB) and, specifically RelA. In addition, inflammatory cytokines lead to the epigenetic inactivation of Klotho transcription. Klotho itself has antioxidant and anti-inflammatory properties and the canonical NFκB component RelA is one of its targets. Klotho is a key regulator of phosphate balance and a role of phosphate in ageing has been shown. However, the potential relationship between phosphate and inflammation requires further clarification. A correct understanding of these interactions may lead to the design of novel therapeutic approaches to CKD and CKD-related inflammatory and ageing features as well as to inflammation/ageing in general.

Neisseria gonorrhoeae productora de betalactamasa

De un total de 674 pacientes, 308 hombres y 366 mujeres, se aisló Neisseria gonorrhoeae por cultivo en 27.3 po ciento y 14.2 po ciento para cada sexo respectivamente. A 126 de los aislamientos se les determinó la capacidad de producir betalactamasa, utilizando los métodos iodométrico, acidométrico y de la cefalosporina cromagénica. En 1987, 26 por ciento de los pacientes tenía N. gonorrhoeae productora de betalactamasa, en 1988 fueron 26.3 y en 1989 llegaron a 63.2. Este resultado no es aplicable a la infección gonocóccica en la población general, por ser un grupo altamente seleccionado con problemas de resistencia al tratamiento.

Uretritis masculina: importancia de la chlamydia trachomatis y de otros agentes

Se estudiaron 100 hombres para definir la etiología de su uretritis mediante exámenes directos y cultivos para Neisseria gonorrhoeae e inmunofluorescencia directa para Chlamydia trachomatis. Se halló infección por Chlamydia en 31 pacientes y por Neisseria en 16; había infección mixta en siete individuos y TRICHOMONAS VAGINALIS en uno; no se demostró ninguno de estos agentes en 45 casos. La evolución fue significativamente más larga en los pacientes con chlamydiasis y en los de uretritis de etiología desconocida. En la uretritis por Chlamydia la secreción uretral fue escasa y de características acuosa, mucoide o mixta; asimismo fue frecuente la ausencia de secrecion en los pacientes con uretritis no goncóccica. Se llama la atención hacia la necesidad de estudiar la importancia de la infección por Chlamydia trachomatis