Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency.

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs)1,2, conferring a predisposition to life-threatening COVID-19 pneumonia3. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52LOF/IκBδGOF). By contrast, neutralizing autoantibodies against type I IFNs are not found in individuals who are heterozygous for NFKB2 variants causing haploinsufficiency of p100 and p52 (hereafter, p52LOF/IκBδLOF) or gain-of-function of p52 (hereafter, p52GOF/IκBδLOF). In contrast to patients with APS-1, patients with disorders of NIK, RELB or NF-κB2 have very few tissue-specific autoantibodies. However, their thymuses have an abnormal structure, with few AIRE-expressing medullary thymic epithelial cells. Human inborn errors of the alternative NF-κB pathway impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases.

Ozone Prevents Cochlear Damage From Ischemia-Reperfusion Injury in Guinea Pigs.

The cochlea is an end organ, which is metabolically dependent on a nutrient and oxygen supply to maintain its normal physiological function. Cochlear ischemia and reperfusion (IR) injury is considered one of the most important causes of human idiopathic sudden sensorineural hearing loss. The aim of the present study was to study the efficacy of ozone therapy against cochlear damage caused by IR injury and to investigate the potential clinical use of this treatment for sudden deafness. Twenty-eight guinea pigs were randomized into four groups. The sham group (S) (n = 7) was administered physiological saline intraperitoneally (i.p.) for 7 days. The ozone group (O) (n = 7) was administered 1 mg/kg of ozone i.p. for 7 days. In the IR + O group (n = 7), 1 mg/kg of ozone was administered i.p. for 7 days before IR injury. On the eighth day, the IR + O group was subjected to cochlear ischemia for 15 min by occluding the bilateral vertebral artery and vein with a nontraumatic clamp and then reperfusion for 2 h. The IR group was subjected to cochlear IR injury. After the IR procedure, the guinea pigs were sacrificed on the same day. In a general histological evaluation, cochlear and spiral ganglionic tissues were examined with a light microscope, and apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The apoptotic index (AI) was then calculated. Blood samples were sent for analyses of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase, malondialdehyde (MDA), the total oxidant score (TOS), and total antioxidant capacity (TAC). Data were evaluated statistically using the Kruskal-Wallis test. The AI was highest in the IR group. The AI of the IR + O group was lower than that of the IR group. The biochemical antioxidant parameters SOD and GSH-Px and the TAC values were highest in the O group and lowest in the IR group. The MDA level and TOS were highest in the IR group and lowest in the O group. Controlled ozone administration stimulated endogenous antioxidant defense systems, thereby helping the body to combat IR injury. Although this study revealed a statistically significant decrease in cochlear IR damage following ozone therapy, further studies will be necessary to explain the protective mechanisms of ozone therapy in cochlear IR injury.

A Novel and Modified Technique in the Prone Position for Radiotherapy Processes in Children.

The i-gel has a thick airway tube and occasionally, achieving the airway can be difficult because of obstruction in the prone position. The authors aimed at solving this problem and used a modified i-gel airway in the prone position for radiotherapy processes in children.

Effects of gamma-hydroxybutyrate on cerebrospinal fluid lactate and glucose levels after spinal cord trauma.

This study aims to evaluate the effects of gamma-hydroxybutyrate (GHB) after spinal cord trauma (SCT). Twenty rabbits were divided equally into four groups: group I was the sham-operated group, group II suffered from SCT but received no treatment, group III was given a dose of 400 mg/kg of GHB intravenously before SCT and group IV received the same dose after SCT. Cerebrospinal fluid (CSF) samples were obtained 30 min before SCT (T(0)), at 60 (T(1)) and 120 min (T(2)) after SCT. There was a threefold increase in lactate levels from baseline value at T(2) in group II, while statistically significant elevation of the lactate levels were not observed in groups III and IV. Glucose levels at T(1) and T(2) were significantly lower in groups III and IV compared with the control group. The findings of this study demonstrate that GHB can control the increase of CSF lactate and glucose levels following SCT and that this metabolic effect may be associated with neuroprotective physiological changes.