Modulation of host epigenome by coronavirus infections and developing treatment modalities for COVID-19 beyond genetics.

The recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) outbreak has resulted in coronavirus disease 2019 (COVID-19) pandemic worldwide, affecting millions of lives. Although vaccines are presently made available, and vaccination drive is in progress to immunize a larger population; still the risk of SARS-CoV-2 infection and related mortality is persistent amid threats of the third wave of the ongoing pandemic. In the scenario of unavailability of robust and efficient treatment modalities, it becomes essential to understand the mechanism of action of the virus and deeply study the molecular mechanisms (both at the virus level and the host level) underlying the infection processes. Recent studies have shown that coronaviruses (CoVs) cause-specific epigenetic changes in the host cells to create a conducive microenvironment for replicating, assembling, and spreading. Epigenetic mechanisms can contribute to various aspects of the SARS-CoV-2 multiplication cycle, like expressing cytokine genes, viral receptor ACE2, and implicating different histone modifications. For SARS-CoV-2 infection, viral proteins are physically associated with various host proteins resulting in numerous interactions between epigenetic enzymes (i.e., histone deacetylases, bromodomain-containing proteins). The involvement of epigenetic mechanisms in the virus life cycle and the host immune responses to control infection result in epigenetic factors recognized as emerging prognostic COVID-19 biomarkers and epigenetic modulators as robust therapeutic targets to curb COVID-19. Therefore, this narrative review aimed to summarize and discuss the various epigenetic mechanisms that control gene expression and how these mechanisms are altered in the host cells during coronavirus infection. We also discuss the opportunities to exploit these epigenetic changes as therapeutic targets for SARS-CoV-2 infection. Epigenetic alterations and regulation play a pivotal role at various levels of coronavirus infection: entry, replication/transcription, and the process of maturation of viral proteins. Coronaviruses modulate the host epigenome to escape the host immune mechanisms. Therefore, host epigenetic alterations induced by CoVs can be considered to develop targeted therapies for COVID-19.

Restoration of Thoracolumbar Spine Stability and Alignment in Elderly Patients Using Minimally Invasive Spine Surgery (MISS). A Safe and Feasible Option in Degenerative and Traumatic Spine Diseases.

Minimally invasive spine surgery (MISS), including percutaneous pedicle-screw fixation (PPSF), mini-open transforaminal lumbar interbody fusion (m-open TLIF), vertebroplasty, and stentoplasty, allows the preservation of neurological function and the restoration of spine stability, while reducing associated risks and complications. This study aimed to analyze the safety and efficacy of MISS in elderly patients suffering from degenerative or traumatic thoracolumbar diseases. Forty-five patients (28 females), with a mean age of 73 years (range 65-89), suffering from osteoporotic vertebral fractures (24), degenerative spondylolisthesis (15), and lumbar canal stenosis with instability and/or de novo scoliosis (6) were included.Twenty-one patients underwent PPSF and m-open TLIF. The remaining patients received PPSF without interbody fusion, and in six of these fenestrated screws were used for vertebral body cement augmentation.Functional evaluation was obtained with a visual analog scale (VAS) and the Oswestry Disability Index (ODI) pre- and postoperatively. Preoperative imaging included X-rays, computed tomography (CT), and magnetic resonance imaging (MRI). Patients were followed-up with X-rays, and a CT scan was also obtained at the last follow-up. Follow-up ranged from 6 to 59 months (mean 28 months). Follow-up CT scan documented intersomatic fusion in only 14 % of patients treated with m-open TLIF. Despite the high incidence of non-union, mean VAS and ODI scores showed a significant improvement, with a reduction of mean VAS from 9 to 4 and a reduction of mean ODI from 76.33 to 38.15 %. Only three patients developed postoperative complications. No patients showed neurological deficits.Minimally invasive spine surgery for degenerative and traumatic spinal diseases is a safe and effective treatment also in elderly patients.

Epidemiology of nutritional rickets in children.

In most developing countries, nutritional rickets is a major health problem. The aim of this study was to explore the magnitude of nutritional rickets among Saudi infants, and the various clinical presentations, as well as to address the possible operating risk factors behind the disease. We carried out a retrospective study at King Abdulaziz Medical City-King Fahad National Guard Hospital in Riyadh, Saudi Arabia. The records of Saudi infants under the age of 14 months over a 10-year period (between January 1990 and January 2000) were reviewed. Infor-mation collected included age, sex, clinical presentations, biochemical, radiological findings, infant nutrition, presence of other nutritional deficiencies and exposure to sunlight. There were 283 infants diagnosed with nutritional rickets due to Vitamin D deficiency (67% males) who were between 6 and 14 months of age. Among the total, 70% were exclusively breast-fed, and 23% were breast-fed until the age of 1 year. The most frequent clinical presentation was hypo-calcemic convulsions (34%) followed by chest infections (33%) and gastroenteritis (25%). In conclusion, nutritional rickets is still prevalent in Saudi Arabia with the primary etiology being vitamin D deficiency. Therefore we recommend that every infant, who is exclusively on breast-feeding, has routine supplement of vitamin D in the range of 200 IU/day (alone or as apart of multivitamin), started soon after birth until the time of weaning.

Efficacy of recombinant human growth hormone in children with juvenile rheumatoid arthritis and growth failure.

Ten patients with juvenile rheumatoid arthritis (JRA) and growth failure were treated with recombinant human growth hormone (GH) for 1 to 3 years at a dosage of 0.57 IU/kg/wk. All the patients had been on prednisone at a mean dosage of 4.12 mg p.o. daily. GH was low in one patient, two patients had a borderline level and seven patients had adequate response to provocative tests or post-sleep measurement. Serum IGF-I was found to be low in five of six patients. Mean growth velocity increased from 2.45 cm/yr to 4.79 cm/yr after 1 year's treatment with GH (P<0.004). Six patients continued on GH treatment for a second year and continued to have a better growth velocity, with a mean of 5.43 cm/yr (P<0.014). Two patients entered puberty during the second year of GH treatment. This study demonstrates the potential beneficial effect of GH treatment in patients with JRA with growth failure of systemic onset or polyarticular onset who are on prednisone. Further study is needed to determine the long-term effect of GH treatment on ultimate height.

Group A beta-haemolytic streptococcal infection and Henoch-Schonlein purpura with cardiac, renal and neurological complications.

A 6-year-old girl had a group A beta-haemolytic streptococcal (GABS) throat infection and Henoch-Schonlein purpura (HSP). The clinical course was complicated by nephrotic syndrome due to crescentic glomerulonephritis, transient neurological symptoms due to focal ischaemia of the brain, and congestive cardiac failure due to myocarditis. The clinical presentation highlights the diversity of systemic involvement in HSP, the transient nature of apparently serious central nervous system involvement, and a possible role of GABS in its aetiology.