Ethanol changes Nestin-promoter induced neural stem cells to disturb newborn dendritic spine remodeling in the hippocampus of mice

Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus.We found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive days.EtOH markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood.EtOH(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in vitro.Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 pathway.In vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.

Universal newborn hearing screening program in Saudi Arabia: Current insight

Newborn hearing screening(NHS) programs are essential to identify hearing loss early in life and to improve outcomes in children. In Saudi Arabia, the national NHS program has been operational since 2016;however, few studies have evaluated its status, and none have covered all provinces across the country. This cross-sectional retrospective study provides an overview of the program's status across all provinces, focusing on screening coverage rates, referral/fail rates, and follow-up procedures. In 2021, 199,034 newborns were screened, with a coverage rate of 92.6% and an overall referral/fail rate of 1.87%. These performance measures provide a foundation for future progress and improvements. This study highlights the importance of ongoing efforts to enhance the program's effectiveness and sustainability.

A core scientific problem in the treatment of central nervous system diseases:newborn neurons

It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.

Balloon dilation of congenital perforated duodenal web in newborns: Evaluation of short and long-term results

BACKGROUND Incomplete congenital duodenal obstruction(ICDO)is caused by a congenitally perforated duodenal web(CPDW).Currently,only six cases of balloon dilatation of the PDW in newborns have been described.AIM To present our experience of balloon dilatation of a perforated duodenal memb-rane in newborns with ICDO.METHODS Five newborns who underwent balloon dilatation of the CPDW along a prein-stalled guidewire between 2021 and 2023 were included.Nineteen newborns diagnosed with ICDO who underwent laparotomy were included in the control group.RESULTS In all cases,good anatomical and clinical results were obtained.In three cases,a follow-up study was conducted after 1 year.The average time to start enteral feeding per os was significantly earlier in the study group(4.4 d)than in the laparotomic group(21.2 days;P<0.0001).The time spent by patients in the intensive care unit and hospital after balloon dilatation was also significantly shorter.We determined the selection criteria for possible and effective CPDW balloon dilatation in newborns as follows:(1)Presence of dynamic radiographic signs of the passage of a radiopaque substance beyond the zone of narrowing or radiographic signs of pneumatisation of the duodenum and small bowel distal to the web;(2)presence of endoscopic signs of CPDW;(3)successful cannulation with a guidewire performed parallel to the endoscope,with holes in the congenital duodenal web;and(4)successful positioning of the balloon performed along a freestanding guidewire on the web.CONCLUSION Strictly following selection criteria for newborns with ICDO caused by CPDW ensures that endoscopic balloon dilatation using a pre-installed guidewire is safe and effective and shows good 1-year follow-up results.

A Comparison between Late Preterm and Term Infants with Respiratory Distress Syndrome, Early-Onset Sepsis, and Neonatal Jaundice in Ecuadorian Newborns

Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: Epidemiological, observational, and cross-sectional, with two cohorts of patients. Settings: IESS Quito Sur Hospital at Quito, Ecuador, from February to April of 2020. Participants: This study included 204 newborns, 102 preterm infants, 102 term infants. Results: There are significant differences between late preterm infants and term infants, with a p-value of 0.000 in the prevalence of early sepsis, 70.59% vs. 35.29%. In respiratory distress syndrome between late and term premature infants, significant differences were observed with a p-value of 0.000, the proportion being 55.58% vs. 24.51% respectively. The prevalence of jaundice is higher in term infants with a p value of 0.002, 72.55%, versus 51.96% in late preterm infants, and the mean value of bilirubins in mg/dL was higher in term infants 14.32 versus 12.33 in late preterm infants;this difference is statistically significant with a p value of 0.004. Admission to the NICU is more frequent in late preterm infants with a p-value of 0.000, being 42.16% for late preterm infants vs. 7.84% in term infants;the mean of the hospital days with p-value 0.005, was higher in late preterm infants 4.97 days vs. 3.55 days for term newborns. Conclusion: Due to the conditions of their immaturity, late preterm infants are 2.86 times more likely to present early sepsis than full-term newborns. It is shown that late preterm infants are 2.69 times more likely to have respiratory distress syndrome compared to term infants, therefore, late preterm infants have a longer hospital stay of 4.97 days versus 3.55 days in term infants. Jaundice and mean bilirubin levels are higher in term infants due to blood group incompatibility and insufficient breastfeeding.

Draft of an Anthropometric Reference System for Full-Term Cameroonian Newborns: Prospective Study with Analytical Aim in the Maternity Wards of Douala

Introduction: Anthropometry applied to newborns is a reliable indicator of the quality of fetal growth. The latter is influenced by genetic, racial and nutritional factors varying from one population to another, explaining why a standard cannot be applied to all populations. Research question: should the Caucasian frame of reference be dogmatically applied in our African context? Multicenter studies are therefore necessary;hence the interest of this work, the main objective of which was to describe the anthropometric profile of full-term newborns in the city of Douala. Methodology: We carried out a cross-sectional study with an analytical aim and prospective data collection in the maternity wards of the Douala General Hospital, Laquintinie Hospital, District hospitals of Deido, Nylon and Bonassama over a period of 4 months (January to April 2020). We were interested in any newborn, born alive, vaginally or by cesarean section, seen in the first 24 hours from a full-term single-fetal pregnancy whose mother had given consent. We excluded newborns whose term was unclear and those with congenital malformations or signs of embryo-foetopathy. Data collection was done using structured and pre-tested survey sheets. The study variables were obstetric and anthropometric. Statistical analyzes were carried out with CS Pro 7.3 and SPSS version 25.0 software. The Student, Chi-square and Fischer tests were used to compare the means of the variables, the percentages with a significance threshold P value Results: During the study period, 305 full-term newborns were included, divided into 172 boys and 133 girls. The average anthropometric parameters of the full-term newborn in the city of Douala were: average weight: 3305 grams, average height: 49.8 centimeters, average head circumference: 34.6 centimeters, average upper arm circumference: 11.3 centimeters, circumference average thoracic: 32.8 centimeters. The percentile distribution showed a 10th percentile at 2656 grams and a 90th percentile at 3966 grams for weight defining the limits for small-for-gestational-age neonates and macrosomes. Conclusion: The anthropometric data of the full-term newborn in the city of Douala were: an average weight of 3305.4 grams, an average height of 49.8 centimeters, an average head circumference of 34.2 centimeters, an average upper arm circumference of 11.3 centimeters, and an average thoracic circumference of 32.8 centimeters with higher valuesin male newborns.

Etiology analysis for term newborns with severe hyperbilirubinemia in eastern Guangdong of China

BACKGROUND Neonatal hyperbilirubinemia is one of the common diseases of newborns that typically presents with yellow staining of skin,resulting in sequelaes such as hearing loss,motor and intellectual development disorders,and even death.The pathogenic factors of neonatal hyperbilirubinemia are complex.Different cases of hyperbilirubinemia may have a single or mixed etiology.AIM To explore the etiological characteristics of severe hyperbilirubinemia in term newborns of eastern Guangdong of China.METHODS Term newborns with severe hyperbilirubinemia in one hospital from January 2012 to December 2021 were retrospectively analyzed.The etiology was determined according to the laboratory results and clinical manifestations.RESULTS Among 1602 term newborns with hyperbilirubinemia in eastern Guangdong of China,32.20%(580/1602)was severe hyperbilirubinemia.Among the causes of severe hyperbilirubinemia,neonatal hemolysis accounted for 15.17%,breast milk jaundice accounted for 12.09%,infection accounted for 10.17%,glucose-6-phosphate dehydrogenase(G6PD)deficiency accounted for 9.14%,and the coexistence of multiple etiologies accounted for 6.55%,unknown etiology accounted for 41.72%.ABO hemolysis and G6PD deficiency were the most common causes in the 20 cases with bilirubin encephalopathy.94 severe hyperbilirubinemia newborns were tested for uridine diphosphate glucuronosyl transferase 1A1(UGT1A1)*6 variant(rs4148323,c.211G>A,p.Arg71Gly),9 cases were 211 G to A homozygous variant,37 cases were 211 G to A heterozygous variant,and 48 cases were wild genotypes.CONCLUSION The main cause for severe hyperbilirubinemia and bilirubin encephalopathy in eastern Guangdong of China were the hemolytic disease of the newborns,G6PD deficiency and infection.UGT1A1 gene variant was also a high-risk factor for neonatal hyperbilirubinemia.Targeted prevention and treatment according to the etiology may reduce the occurrence of bilirubin encephalopathy and kernicterus.

Various aspects of hearing loss in newborns:A narrative review

Hearing loss is considered the most common birth defect.The estimated prevalence of moderate and severe hearing loss in a normal newborn is 0.1%-0.3%,while the prevalence is 2%-4%in newborns admitted to the newborn intensive care unit.Neonatal hearing loss can be congenital(syndromic or nonsyndromic)or acquired such as ototoxicity.In addition,the types of hearing loss can be conductive,sensorineural,or mixed.Hearing is vital for the acquisition of language and learning.Therefore,early detection and prompt treatment are of utmost importance in preventing the unwanted sequel of hearing loss.The hearing screening program is mandatory in many nations,especially for high-risk newborns.An automated auditory brainstem response test is used as a screening tool in newborns admitted to the newborn intensive care unit.Moreover,genetic testing and screening for cytomegalovirus in newborns are essential in identifying the cause of hearing loss,particularly,mild and delayed onset types of hearing loss.We aimed to update the knowledge on the various aspects of hearing loss in newborns with regard to the epidemiology,risk factors,causes,screening program,investigations,and different modalities of treatment.

Effect of caffeine in the intraventricular hemorrhage of the preterm newborn

There are around 15 million preterm newborns(PT) eve ry year(Atienza-Navarro et al., 2020).With these figures in mind,prematurity represents a major health problem worldwide and it is a leading cause of infant mortality,accounting for up to 35%of all deaths among newborns(Atienza-Navarro et al.,2020) and up to 18% of the deaths among children under 5 years of age.

Isolation of Leclercia adecarboxylata Producing Carbapenemases in A Newborn Female

Leclercia adecarboxylata is a Gram-negative bacterium belonging to the Enterobacteriaceae family.To our knowledge,this is the first report of a carbapenem-resistant L.adecarboxylata strain isolated from a healthy newborn.The L.adecarboxylata strain isolated in this study carried four plasmids that may serve as reservoirs for antibiotic resistance genes.Plasmids 2 and 4 did not harbor any antimicrobial resistance genes.Plasmid 3 is a novel plasmid containing three resistance genes.The bla IMP gene harbored in the strain was most similar to bla IMP-79 at the nucleotide level,with a similarity of 99.4%(737/741).This case highlights the importance of considering L.adecarboxylata as a potential cause of infections in children.

Host Genetic Background Impacts Microbiome Composition in Newborn Alligator

Genetic factors play a key role in determination of the structure of the cloacal flora for newborn Chinese Alligators.We collected the cloacal microbiomes for 24 newborn Chinese Alligators from three different genetic backgrounds for 16S gene amplicon sequencing.The number of cloacal flora for the Chinese Alligators from different groups was comparable but differed structurally.There were variations in proportions of floral compositions at the phylum and family levels;however,the main difference was at the genus level.There were two significant differences in richness and evenness among the three groups.Non-metric multidimensional scaling NMDS analysis revealed that the 24 samples could be clearly divided into three categories based on their genetic backgrounds(stress=0.0244).Thus,we postulated that newborn Chinese Alligators with different genetic backgrounds have different immune strengths,which affects individual responses to environmental microorganisms.In summary,newborn Chinese Alligators from different genetic backgrounds exhibit variations in cloacal microbiome.

Distortion product otoacoustic emissions in newborn babies with and without late-term maternal iron deficiency anaemia

Background:Studies on animals have demonstrated that maternal iron deficiency anaemia(IDA)could result in decreased cochlear sensory hair cells and reduced amplitudes of distortion-product otoacoustic emissions(DPOAEs)of young guinea pigs.Thus,it is essential to study the functioning of cochlear hair cells using DPOAEs in human newborn babies with maternal IDA.The current study explores maternal IDA’s effect on DPOAEs in newborn babies.Method:A total of 110 newborn babies with gestational age≥34 weeks were considered and a‘betweensubjects’design was used.The participants were divided into 3 groups-“Normal”(61 babies without maternal IDA),“Mild”(28 babies with mild maternal IDA)and“Moderate”(21 babies with moderate maternal IDA).The cord blood was collected and the DPOAEs were recorded for each baby for a range of frequencies(1 k 8 kHz)and a range of intensities(7040 dB SPL in 10 dB steps).Results:The analysis of both DP-gram and DP input-output(I/O)function showed that there was no significant difference(p>0.05)across the normal,mild,and moderate groups in the overall presence of DPOAEs as well as the amplitude across frequencies or intensities(7040 dB SPL).Also,the overall correlation of RBC indices with DPOAE amplitude across frequencies as well as the slope of the I/O function showed no relationship.Conclusion:The current study concludes that there is no effect of late-term maternal IDA on the DPOAEs of newborn babies.

Hospital Outcome of Newborns with a Health Cheque System in Comparison to Those Without

Introduction: The health cheque system is a prepayment mechanism aimed at reducing neonatal and maternal mortality through improving the management of pregnant women. The pregnant woman with the health cheque system that she pays at six thousand francs XAF (African financial community) is covered free of charge for all the care provided by the cheque system in the health facilities accredited to the health cheque project. We did a study, with objective to determine the hospital outcome of newborns with a health cheque system (HCS) compared to those without health cheque system. Method: A descriptive cross-sectional study with retrospective data collection was carried out at the Ngaoundere Regional Hospital from January 2018 to September 2021. Results: During our study period, 2985 newborns were received. We saw an increase in admissions over the years, particularly in the group of newborns with the health cheque system. Comparatively, the percentage of newborns cured in the health cheque system group was 76.73% (n = 1643) versus 77.72% (n = 656) those in the non-health cheque system group. Those who died were 8.96% (n = 192) in the health cheque system group compared to 6.27% (n = 53) in the non-health cheque system group. Conclusions and Recommendations: Most patients admitted to our service have the health cheque system. We notice an increase in hospital attendance with the health cheque project. The outcome of the newborn under the health cheque system is not different from that without health cheque system. The health cheque system was successful in getting the larger number of newborns into care. The next step is to put strategies in place to keep these patients in care for the duration of hospitalization.

Uterovaginal Prolapse in the Newborn: A Case Report from the University Hospital of Conakry

Uterovaginal prolapse is an exceptional pathology in the newborn. It is defined by the descent and protrusion of the uterus and vaginal walls to the outside via the vaginal orifice. It particularly affects newborns with neural tube defects. The diagnosis is usually made at birth. Different types of conservative or surgical treatment have been suggested for genital prolapse in neonates. We report the case of a newborn of 6 hours of life who was received for congenital utero-vaginal without neural tube closure anomaly. He was successfully treated with digital reduction of the mass associated with a cerclage of the vaginal orifice. Conclusion: Digital reduction of the prolapse associated with a cerclage of the vaginal orifice is simple, effective and avoids any recurrence.

Insulin Sensitivity of Term Newborns Exposed in Utero to HIV and Antiretrovirals in Yaoundé

Introduction: Antiretrovirals (ARVs) and the human immunodeficiency virus (HIV) are implicated in the onset of insulin resistance. They cross the placental barrier thereby inducing early modifications of the fetal environment. The aim of our study was to assess insulin sensitivity in full-term newborns exposed in utero to HIV and ARVs in Yaoundé. Materials and Methods: We conducted an analytical cross-sectional study in 2 maternities in the city of Yaoundé from November 2021 to June 2022. We generated two groups of newborns (NBs): one group born to HIV positive mothers on ARVs and the other control group born to HIV negative mothers. Clinical data from mothers and NBs were collected. A homeostatic model assessment of insulin resistance (HOMA-IR) like index with C peptide served to assess insulin sensitivity. We used the Spearman correlation to measure the strength of association between insulin sensitivity and the different variables. A p-value Results: Of 70 neonates included, 35 were born to HIV positive mothers on ARVs and 35 to HIV negative mothers. The median age of HIV positive and negative mothers was 30 (27 - 32) and 34 (24 - 47) years, respectively (p = 0.791). The body mass index before pregnancy as well as the average newborn weights were comparable in both groups. The ARV protocol associating Tenofovir, Lamivudine, Efavirenz was used by 97.1% of HIV positive mothers. In the exposed NBs group, C peptide was significantly lower (p < 0.001) and blood glucose significantly higher (p < 0.001). The median values of HOMA-IR were 1.4 (0.8 - 1.9) and 2 (1.4 - 2.6) (p = 0.001) for exposed and unexposed NBs, respectively. Conclusion: Newborns exposed to HIV and ARVs had lower C peptide levels and were more sensitive to insulin. Close metabolic monitoring of these newborns would allow early diagnosis and management of any glucose regulation disorder.

Practices of Maternity’s Care Providers in the Municipality of Kozah 1 Regarding the Administration of Vitamin K1, Eye Care, and Umbilical Cord Care in Immediate Postpartum Newborns

Background: Neonatal mortality is a real public health problem in the world and particularly in countries with limited resources. Essential care remains an effective means of reducing this mortality. Objective: To evaluate the practice of administering of vitamin K1, ocular and cord care in maternity wards in the Kozah 1 municipality. Method: This is a cross-sectional study conducted from March 1st to June 30th, 2022 in all maternity wards in the Kozah 1 municipality. Socioprofessional aspects of providers and those related to the administration of vitamin K1, ocular and cord care were studied. Results: Eighty-five (85) maternity providers were included in this study. The average age of the providers was 36.2 years with extremes of 21 and 55 years. Providers were midwives (51.8%), childbirth attendants (35.3%), and matrons (12.9%). The average length of practice was 9.5 years with extremes of 1 and 28 years. For three out of four providers (75.3%), the postpartum period was defined as a period of 02 hours following delivery. The importance of cord, ocular care, and administration of vitamin K1 in postpartum was known respectively by 84.7%, 98.8%, and 92.9% of the providers. Chlorhexidine gel was used by 81.2% of providers for umbilical cord care. For ocular disinfection, more than half of the providers (52.9%) reported using half-diluted povidone iodine. No center had displayed care protocol. Conclusion: This study highlighted the level of knowledge and practice of three essential postpartum care practices. The products used for the different care practices are consistent with recommendations but vary according to the care providers.

Neurodevelopmental Outcome of Newborns Aged More than 34 Weeks Gestational Age Managed for Birth Asphyxia in Douala (Cameroon): A Single Hospital-Based Study

Background: Perinatal asphyxia is a common cause of mortality and of morbidity including motor and neurodevelopmental abnormalities. The aim of this study was to evaluate the post-hospital outcome of neonates treated for perinatal asphyxia at the Douala Gynaeco-Obstetric and Pediatric Hospital (DGOPH) in Cameroon. Patients and Methods: We conducted a hospital-based cross-sectional study with both a retrospective and prospective data collection, conducted over a period of 3 months and involving neonates above 34 weeks of gestational age who were managed for perinatal asphyxia at DGOPH from August 2015 to February 2020. Socio-demographic, perinatal, motor, nutritional and neuro-developmental out-of-hospital data were recorded. The assessment of the child’s psychomotor development was evaluated through gross motor skills, fine motor skills, language and social contact. We calculated the development quotient (DQ) by dividing the developmental age (DA) by the actual age (RA) of the patient. The data were entered and analyzed using excel and Stata version 15 software. Results: Among the 58 newborns included in our study, males were the most represented (59%). The mean age was 36.5 ± 14.16 months (Extremes: 12 months and 66 months). The majority of patients were born at term (79%), had a birth weight between 2500 and 4000 grams (69%), were resuscitated (95%), and had an Apgar score < 7 at the 5th minute of life (67%). SARNAT stages II and III counted for 48%. Neurodevelopmental abnormalities were found in 25.5% of patients with gross motor delay (mainly tetraparesis) representing 23.5%, fine motor delay 27.5%, impairment in social contact 31% language speech delay. The majority of the children had a normal development quotient (78.4%). Conclusion: The short-term and long-term outcome of newborns who experienced perinatal asphyxia in our setting is marked by numerous impairments in developmental milestones leading to disability.

Newborn with Giant Non-Involuting Congenital Hemangioma: Mechanisms of Allodynia, Hyperalgesia and Treatment

In a newborn affected by a non involuting congenital hemangioma we measured allodynia through the application of a standard tactile stimulus and hyperalgesia through the regular administration of the Comfort scale which rates pain intensity. The baby presented signs of these pathological events over long periods of the disease. They may be attributed to the high amount of the nociceptive ligands in the hemangioma microenviroment and to the elevated concentration of TNF-alpha and IL-6 in the blood. For a long time, the pain was relieved by a combination of opioids, adjuvants and paracetamol, but also by thalidomide and unexpectedly by interferon alpha. A mechanism-based pain treatment needs to take into account the processes underlying pain and also the ongoing pathology.

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Mucopolysaccharidosis typeⅢB:a current review and exploration of the AAV therapy landscape

Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase.This results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological dysfunction.Current treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢB.Adeno-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential cures.Our group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy mice.Here,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.