Usher syndrome:Genetic diagnosis and current therapeutic approaches

Usher Syndrome(USH)is the most common deaf-blind syndrome,affecting approximately 1 in 6000 people in the deaf population.This genetic condition is characterized by a combination of hearing loss(HL),retinitis pigmentosa,and,in some cases,vestibular areflexia.Among the subtypes of USH,USH type 1 is considered the most severe form,presenting profound bilateral congenital deafness,vestibular areflexia,and early onset RP.USH type 2 is the most common form,exhibiting congenital moderate to severe HL for low frequencies and severe to profound HL for high frequencies.Conversely,type 3 is the rarest,initially manifesting mild symptoms during childhood that become more prominent in the first decades of life.The dual impact of USH on both visual and auditory senses significantly impairs patients'quality of life,restricting their daily activities and interactions with society.To date,9 genes have been confirmed so far for USH:MYO7A,USH1C,CDH23,PCDH15,USH1G,USH2A,ADGRV1,WHRN and CLRN1.These genes are inherited in an autosomal recessive manner and encode proteins expressed in the inner ear and retina,leading to functional loss.Although non-genetic methods can assist in patient triage and disease extension evaluation,genetic and molecular tests play a pivotal role in providing genetic counseling,enabling appropriate gene therapy,and facilitating timely cochlear implantation(CI).The CRISPR/Cas9 system and viral-based gene replacement therapy have recently emerged as highly promising techniques for treating USH.Regarding drug therapy,PTC-124 and Nb54 have been identified as promising drug interventions for genetic HL in USH.Simultaneously,CI has proven to be critical in the restoration of hearing.This review aims to summarize the genetic and molecular diagnosis of USH and highlight the importance of early diagnosis in Cuzzuol BR et al.Diagnosis and current treatments of USH WJO https://www.wjgnet.com 2 January 19,2024 Volume 11 Issue 1 guiding appropriate treatment strategies and improving patient prognosis.

Helicobacter pylori infection in pregnant women:Gastrointestinal symptoms and pregnancy-related disorders

Helicobacter pylori(H.Pylori)is a gram-negative,flagellated and spiral-shaped bacterial pathogen that impacts approximately 46%among pregnant women globally and has been associated with various maternal-fetal complications.Iron deficiency anemia,fetal growth restriction,cardiovascular diseases,and insufficient nutrient absorption can be observed in pregnant women,as well as miscarriages and pregnancy-specific hypertensive disease,such as pre-eclampsia.Thus,the evidence supports the influence of H.pylori infection on fetal implantation/placentation failure,and positive strains of the cytotoxin-associated gene A of H.Pylori were reported as the most prevalent in these conditions.However,current knowledge indicates a relationship between this infection and the occurrence of hyperemesis gravidarum,characterized by frequent nausea and vomiting.Regarding the diagnosis of this bacterial infection,non-invasive approaches such as stool antigen test,urea breath test,and serological tests are more accepted during pregnancy,as they are easy to carry out and cost-effective.Finally,the bacteria eradication therapy should consider the risks and benefits for the pregnant woman and her child,with pharmacological intervention depending on the clinical presentation.

Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs:A literature review

Chronic myeloid leukemia(CML)is a myeloproliferative neoplasm and was the first neoplastic disease associated with a well-defined genotypic anomaly―the presence of the Philadelphia chromosome.The advances in cytogenetic and molecular assays are of great importance to the diagnosis,prognosis,treatment,and monitoring of CML.The discovery of the breakpoint cluster region(BCR)-Abelson murine leukemia(ABL)1 fusion oncogene has revolutionized the treatment of CML patients by allowing the development of targeted drugs that inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein.Tyrosine kinase inhibitors(known as TKIs)are the standard therapy for CML and greatly increase the survival rates,despite adverse effects and the odds of residual disease after discontinuation of treatment.As therapeutic alternatives,the subsequent TKIs lead to faster and deeper molecular remissions;however,with the emergence of resistance to these drugs,immunotherapy appears as an alternative,which may have a cure potential in these patients.Against this background,this article aims at providing an overview on CML clinical management and a summary on the main targeted drugs available in that context.

COVID-19 neuropsychiatric repercussions:Current evidence on the subject

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has affected the entire world,causing the coronavirus disease 2019(COVID-19)pandemic since it was first discovered in Wuhan,China in December 2019.Among the clinical presentation of the disease,in addition to fever,fatigue,cough,dyspnea,diarrhea,nausea,vomiting,and abdominal pain,infected patients may also experience neurological and psychiatric repercussions during the course of the disease and as a post-COVID-19 sequelae.Thus,headache,dizziness,olfactory and gustatory dysfunction,cerebrovascular disorders,neuromuscular abnormalities,anxiety,depression,and post-traumatic stress disorder can occur both from the infection itself and from social distancing and quarantine.According to current evidence about this infection,the virus has the ability to infect the central nervous system(CNS)via angiotensin-converting enzyme 2(ACE2)receptors on host cells.Several studies have shown the presence of ACE2 in nerve cells and nasal mucosa,as well as transmembrane serine protease 2,key points for interaction with the viral Spike glycoprotein and entry into the CNS,being olfactory tract and blood-brain barrier,through hematogenous dissemination,potential pathways.Thus,the presence of SARS-CoV-2 in the CNS supports the development of neuropsychiatric symptoms.The management of these manifestations seems more complex,given that the dense parenchyma and impermeability of brain tissue,despite protecting the brain from the infectious process,may hinder virus elimination.Still,some alternatives used in non-COVID-19 situations may lead to worse prognosis of acute respiratory syndrome,requiring caution.Therefore,the aim of this review is to bring more current points related to this infection in the CNS,as well as the repercussions of the isolation involved by the pandemic and to present perspectives on interventions in this scenario.

Effects of nutrients on immunomodulation in patients with severe COVID-19:Current knowledge

Recent research has demonstrated that critically ill patients with coronavirus disease 2019(COVID-19)show significant immune system dysregulation.Due to that,some nutrients that influence immunomodulation have been suggested as a form of treatment against the infection.This review collected the information on the impact of vitamins on the prognosis of COVID-19,with the intention of facilitating treatment and prevention of the disease risk status in patients.The collected information was obtained using the PubMed electronic database by searching for articles that relate COVID-19 and the mechanisms/effects of the nutrients:Proteins,glucose,lipids,vitamin B12,vitamin D,calcium,iron,copper,zinc,and magnesium,including prospective,retrospective,and support articles.The findings reveal an optimal response related mainly to omega-3,eicosapentaenoic acid,docosahexaenoic acid,calcium,and iron that might represent benefits in the treatment of critically ill patients.However,nutrient supplementation should be done with caution due to the limited availability of randomized controlled studies.

Syndemic aspects between COVID-19 pandemic and social inequalities

Although the coronavirus disease 2019(COVID-19)pandemic has reached all over the world population,it has demonstrated a heterogeneous impact on different populations.The most vulnerable communities which coexist daily with the social inequalities like low access to hygiene and personal protection products,crowded residences,and higher levels of chronic diseases have a higher risk of contact and the spread of infection,beyond unfavorable clinical outcomes.The elevation of the risk of infection exposure can be related to gender due to the presence of a larger contingent of women in essential services,as well as frontline and cleaning professionals who regardless of gender have the greatest exposure to the virus.Such exposures can contribute to the development of fear of contaminating themselves or their family members associated also with the work stress,both of which are related to the emergence of mental disturbances in these populations.Furthermore,conditions of unsanitary living and low socioeconomic status,populations at war,pre-existing social barriers,and ethnicity have contributed to more impact of the pandemic both in the exposure to the virus and access to health services,COVID-19 management,and management of other pathologies.At the same time,factors such as the closing of non-essential services,the loss of jobs,and the increase in household spending aggravated the social vulnerabilities and impacted the family economy.Lastly,the COVID-19 pandemic contributed still more to the impact on women's health since it propitiated a favorable environment for increasing domestic violence rates,through the segregation of women from social life,and increasing the time of the victims with their aggressors.