SARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery.

Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic resulting from zoonotic transmission of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Severe symptoms include viral pneumonia secondary to infection and inflammation of the lower respiratory tract, in some cases causing death. We developed primary human lung epithelial infection models to understand responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface cultures of proximal airway epithelium and 3D organoid cultures of alveolar epithelium were readily infected by SARS-CoV-2 leading to an epithelial cell-autonomous proinflammatory response. We validated the efficacy of selected candidate COVID-19 drugs confirming that Remdesivir strongly suppressed viral infection/replication. We provide a relevant platform for studying COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and future emergent respiratory pathogens. ONE SENTENCE SUMMARY: A novel infection model of the adult human lung epithelium serves as a platform for COVID-19 studies and drug discovery.

[Universal cytomegalovirus infection screening in premature newborns less than 1500 g]. / Cribado universal de infección por citomegalovirus en prematuros de menos de 1.500 g.

INTRODUCTION: Cytomegalovirus (CMV) infection is endemic, and children who attend day care are the most important source of infection. OBJECTIVE: To establish recommendations based on the medical evidence on the vertical transmission of cytomegalovirus in preterm infants weighing less than 1500g at birth. BACKGROUND: Infection in pregnant women may be primary or secondary. Although there is fetal infection, 85% of newborn infants are asymptomatic. Symptoms of infection include low birth weight, hepatosplenomegaly, thrombocytopenia, microcephaly and neurological disorders. The prognosis of symptomatic children is very poor, with high mortality and neurological disorders. The virus can be reactivated during breast feeding, and early infection is possible through breast milk, probably with little impact in term infants, although the long-term neurological outcome worsens in preterm infants. The diagnostic method of choice is the identification of CMV in urine; the determination in the first two weeks of life suggests congenital infection; later it can be acquired at birth or through breast milk or contaminated blood transfusion. CONCLUSION AND RECOMMENDATION: Determine viral DNA at 4-6 weeks of life by protease chain reaction. If it is positive, monitoring of samples from the first days of life and breast milk are mandatory. This should allow the newborn to be classified into three states: "Without CMV infection", "Congenital CMV infection", "Acquired CMV infection".

Renin is an angiotensin-independent profibrotic mediator: role in pulmonary fibrosis.

The pathogenesis of idiopathic pulmonary fibrosis (IPF) is probably the result of interplay between cytokines/chemokines and growth factors. The renin-angiotensin (Ang) system is involved, although its profibrotic effect is attributed to Ang II. However, recent studies suggest that renin, through a specific receptor, is implicated in fibrogenesis. In this study, the expression of renin and renin receptor was examined in normal and IPF lungs and fibroblasts. Normal human lung fibroblasts were stimulated with renin or transfected with renin small interfering RNA (siRNA), and the expression of transforming growth factor (TGF)-ß1 and α-1-type I collagen was analysed. Normal lungs and lung fibroblasts expressed renin, which was strongly upregulated in IPF lungs and fibroblasts (∼10-fold increase; p<0.05). Immunocytochemistry showed intense renin staining in IPF fibroblasts. Renin-stimulated lung fibroblasts displayed an increase in the expression of TGF-ß1 (mean ± sd 1.8 × 10(3) ± 0.2 × 10(3) versus 1.2 × 10(3)± 0.3 × 10(3) mRNA copies per 18S ribosomal RNA; p<0.01) and collagen (5.93 × 10(2)± 0.66 × 10(2) versus 3.28 × 10(2) ± 0.5 × 10(2); p<0.01), while knocking down renin expression using siRNA provoked a strong decrease of both molecules. These effects were independent of Ang II, since neither losartan nor captopril decreased these effects. Renin also decreased matrix metalloprotease-1 expression and induced TGF-ß1 activation (163 ± 34 versus 110 ± 15 pg active TGF-ß1 per mg total protein). These findings highlight the possible role of renin as an Ang II-independent profibrotic factor in lung fibrosis.

Computed tomography for femoral and tibial torsion in children with clubfoot.

Forty-seven children with 70 clubfeet had computed tomography studies performed to determine the degree of femoral, tibial, and total limb torsion in both lower limbs. The total limb torsion angle (angle between the axis of the femoral neck and the axis of the ankle), which describes the relationship between femoral and tibial torsion, was used to evaluate the whole rotational deformity of the lower limb. The children were between the ages of 2 and 10 years (mean, 5 years) at the time of the computed tomography study. The mean femoral torsion was 25 degrees in the limbs with a clubfoot and 23 degrees in the contralateral limbs of patients with a unilateral clubfoot. The mean tibial torsion was 25 degrees in the limbs with a clubfoot and 24 degrees in the contralateral limb of patients with a unilateral clubfoot. The authors observed decreases of anterior femoral torsion corresponding to increases in age, consistent with the observations made by other authors of studies of children without clubfoot. External tibial torsion increased with age, with similar values in limbs with and without clubfoot. Ten limbs (nine with clubfoot, one without clubfoot) had femoral torsion greater than the means plus one standard deviation and 12 limbs (eight with clubfoot, four without clubfoot) had tibial torsion less than the means minus one standard deviation. The authors found four limbs (all with clubfoot) in three patients with lower than the mean minus one standard deviation of the total limb torsion angle (intoeing). Overall, there was no appreciable difference in the amount of femoral or tibial torsion in limbs with and without a clubfoot.

Pentoxifylline modulates meningeal inflammation in experimental bacterial meningitis.

Pentoxifylline has been shown to decrease endotoxin-induced tumor necrosis factor alpha production and reverse the inflammatory actions of interleukin-1 (IL-1) and tumor necrosis factor on leukocyte function. Because of the potential role of this cytokine-leukocyte interaction in the pathogenesis of bacterial meningitis, we investigated the ability of pentoxifylline to modulate meningeal inflammation in the rabbit meningitis model. Pentoxifylline treatment (initially an intravenous injection of 20 mg/kg followed by 6 mg/kg per h) started 20 min before intracisternal injection of 20 ng of Haemophilus influenzae type b lipooligosaccharide (endotoxin) reduced significantly concentrations in cerebrospinal fluid of leukocytes (P less than 0.0001), protein (P less than 0.001), and lactate (P less than 0.001) during the 9-h infusion compared with values in intravenous-saline-treated rabbits. When pentoxifylline was given 1 h after H. influenzae type b endotoxin, the mean peak lactate and leukocyte concentrations in cerebrospinal fluid were significantly lower than those in control animals. Pentoxifylline also significantly decreased lactate and protein concentrations (P less than 0.05) and tended to diminish leukocyte counts (P = 0.08) compared with results in control animals after antibiotic-induced release of endotoxin in animals with H. influenzae meningitis. In this regard, dexamethasone was superior to pentoxifylline and no synergism was observed when the drugs were combined. Additionally, pentoxifylline attenuated meningeal inflammatory changes induced by intracisternal inoculation of 10 ng of rabbit recombinant IL-1 beta compared with results in either dexamethasone- or saline-treated animals. We conclude that pentoxifylline is effective in this animal model in modulating the meningeal inflammatory response following intracisternal inoculation of H. influenzae type b endotoxin or organisms or rabbit recombinant IL-1beta.

Algunos aspectos de la presion arterial en el area rural de Jalisco, parte II. / Some aspects of blood pressure in the rural area of Jalisco part II

El presente estudio da a conocer prevalencia y algunas caracteristicas epidemiologicas de una poblacion de 1.564 personas con cifras de presion altas, utilizando tres tipos de criterio. Se observo una prevalencia declarada de 7,7% en hombres y de 10,8% en mujeres y una prevalencia real que varia segun el criterio utilizado y el sexo. Las mayores frecuencias estuvieron en las cifras altas de presion distolica segun el criterio de la OMS. Se discute la influencia del factor sobrepeso y bajo peso asociado a cifras altas de presion arterial