The Small Non-coding Vault RNA1-1 Acts as a Riboregulator of Autophagy.

Vault RNAs (vtRNA) are small non-coding RNAs transcribed by RNA polymerase III found in many eukaryotes. Although they have been linked to drug resistance, apoptosis, and viral replication, their molecular functions remain unclear. Here, we show that vault RNAs directly bind the autophagy receptor sequestosome-1/p62 in human and murine cells. Overexpression of human vtRNA1-1 inhibits, while its antisense LNA-mediated knockdown enhances p62-dependent autophagy. Starvation of cells reduces the steady-state and p62-bound levels of vault RNA1-1 and induces autophagy. Mechanistically, p62 mutants that fail to bind vtRNAs display increased p62 homo-oligomerization and augmented interaction with autophagic effectors. Thus, vtRNA1-1 directly regulates selective autophagy by binding p62 and interference with oligomerization, a critical step of p62 function. Our data uncover a striking example of the potential of RNA to control protein functions directly, as previously recognized for protein-protein interactions and post-translational modifications.

Small noncoding vault RNA2-1 disrupts gut epithelial barrier function via interaction with HuR.

Vault RNAs (vtRNAs) are small noncoding RNAs and highly expressed in many eukaryotes. Here, we identified vtRNA2-1 as a novel regulator of the intestinal barrier via interaction with RNA-binding protein HuR. Intestinal mucosal tissues from patients with inflammatory bowel diseases and from mice with colitis or sepsis express increased levels of vtRNAs relative to controls. Ectopically expressed vtRNA2-1 decreases the levels of intercellular junction (IJ) proteins claudin 1, occludin, and E-cadherin and causes intestinal epithelial barrier dysfunction in vitro, whereas vtRNA2-1 silencing promotes barrier function. Increased vtRNA2-1 also decreases IJs in intestinal organoid, inhibits epithelial renewal, and causes Paneth cell defects ex vivo. Elevating the levels of tissue vtRNA2-1 in the intestinal mucosa increases the vulnerability of the gut barrier to septic stress in mice. vtRNA2-1 interacts with HuR and prevents HuR binding to claudin 1 and occludin mRNAs, thus decreasing their translation. These results indicate that vtRNA2-1 impairs intestinal barrier function by repressing HuR-facilitated translation of claudin 1 and occludin.

Structure, Dynamics and Functional Implications of the Eukaryotic Vault Complex.

Vault ribonucleoprotein particles are naturally designed nanocages, widely found in the eukaryotic kingdom. Vaults consist of 78 copies of the major vault protein (MVP) that are organized in 2 symmetrical cup-shaped halves, of an approximate size of 70x40x40 nm, leaving a huge internal cavity which accommodates the vault poly(ADP-ribose) polymerase (vPARP), the telomerase-associated protein-1 (TEP1) and some small untranslated RNAs. Diverse hypotheses have been developed on possible functions of vaults, based on their unique capsular structure, their rapid movements and the distinct subcellular localization of the particles, implicating transport of cargo, but they are all pending confirmation. Vault particles also possess many attributes that can be exploited in nanobiotechnology, particularly in the creation of vehicles for the delivery of multiple molecular cargoes. Here we review what is known about the structure and dynamics of the vault complex and discuss a possible mechanism for the vault opening process. The recent findings in the characterization of the vaults in cells and in its natural microenvironment will be also discussed.

Emerging functional principles of tRNA-derived small RNAs and other regulatory small RNAs.

Recent advancements in small RNA sequencing have unveiled a previously hidden world of regulatory small noncoding RNAs (sncRNAs) that extend beyond the well-studied small interfering RNAs, microRNAs, and piwi-interacting RNAs. This exploration, starting with tRNA-derived small RNAs, has led to the discovery of a diverse universe of sncRNAs derived from various longer structured RNAs such as rRNAs, small nucleolar RNAs, small nuclear RNAs, Y RNAs, and vault RNAs, with exciting uncharted functional possibilities. In this perspective, we discuss the emerging functional principles of sncRNAs beyond the well-known RNAi-like mechanisms, focusing on those that operate independent of linear sequence complementarity but rather function in an aptamer-like fashion. Aptamers use 3D structure for specific interactions with ligands and are modulated by RNA modifications and subcellular environments. Given that aptamer-like sncRNA functions are widespread and present in species lacking RNAi, they may represent an ancient functional principle that predates RNAi. We propose a rethinking of the origin of RNAi and its relationship with these aptamer-like functions in sncRNAs and how these complementary mechanisms shape biological processes. Lastly, the aptamer-like function of sncRNAs highlights the need for caution in using small RNA mimics in research and therapeutics, as their specificity is not restricted solely to linear sequence.

Fundamental Neurochemistry Review: At the intersection between the brain and the immune system: Non-coding RNAs spanning learning, memory and adaptive immunity.

Non-coding RNAs (ncRNAs) are highly plastic RNA molecules that can sequester cellular proteins and other RNAs, serve as transporters of cellular cargo and provide spatiotemporal feedback to the genome. Mounting evidence indicates that ncRNAs are central to biology, and are critical for neuronal development, metabolism and intra- and intercellular communication in the brain. Their plasticity arises from state-dependent dynamic structure states that can be influenced by cell type and subcellular environment, which can subsequently enable the same ncRNA with discrete functions in different contexts. Here, we highlight different classes of brain-enriched ncRNAs, including microRNA, long non-coding RNA and other enigmatic ncRNAs, that are functionally important for both learning and memory and adaptive immunity, and describe how they may promote cross-talk between these two evolutionarily ancient biological systems.

Vault RNA1-1 riboregulates the autophagic function of p62 by binding to lysine 7 and arginine 21, both of which are critical for p62 oligomerization.

Cellular processes can be regulated at multiple levels, including transcriptional, post-transcriptional, and post-translational mechanisms. We have recently shown that the small, noncoding vault RNA1-1 negatively riboregulates p62 oligomerization in selective autophagy through direct interaction with the autophagic receptor. This function is highly specific for this Pol III transcript, but the determinants of this specificity and a mechanistic explanation of how vault RNA1-1 inhibits p62 oligomerization are lacking. Here, we combine biochemical and functional experiments to answer these questions. We show that the PB1 domain and adjacent linker region of p62 (aa 1-122) are necessary and sufficient for specific vault RNA1-1 binding, and we identify lysine 7 and arginine 21 as key hinges for p62 riboregulation. Chemical structure probing of vault RNA1-1 further reveals a central flexible loop within vault RNA1-1 that is required for the specific interaction with p62. Overall, our data provide molecular insight into how a small RNA riboregulates protein-protein interactions critical to the activation of specific autophagy.

Computed tomography study of cranial vault thickness in Malaysian subadult population.

Cranial vault thickness (CVT) and its variations provide valuable insights into an individual's biological attributes such as age and sex. This paper aimed to assess the correlations of CVT with age and sex and develop a regression model for age estimation in Malaysian subadults using computed tomography (CT) images. A total of 521 CT images (male/female: 279/242; age range: 0-20 years; Malay/Chinese/Indian: 221/145/155) were included in the study. Correlations of CVT measurements with age and sex, including frontal bone thickness (FBT), occipital bone thickness (OBT), left parietal bone thickness (LPBT), and right parietal bone thickness (RPBT) were assessed and regression formulae were developed for age estimation in subadults. A significant correlation between CVT measurements and age was demonstrated (p < 0.001). Age estimation was most accurate in the younger age group (< 2 years) at frontal and occipital, and accuracy decreases in the older age groups. Additionally, sexual dimorphism was evident in the frontal and parietal bone thickness within the age range of 3-6 years and 16-20 years, respectively. In conclusion, the findings suggested CVT measurements could be used to corroborate other age estimation methods for subadults.

Crosstalk between vault RNAs and innate immunity.

PURPOSE: Vault (vt) RNAs are noncoding (nc) RNAs transcribed by RNA polymerase III (RNA Pol III) with 5'-triphosphate (5'-PPP) termini that play significant roles and are recognized by innate immune sensors, including retinoic acid-inducible protein 1 (RIG-I). In addition, vtRNAs adopt secondary structures that can be targets of interferon-inducible protein kinase R (PKR) and the oligoadenylate synthetase (OAS)/RNase L system, both of which are important for activating antiviral defenses. However, changes in the expression of vtRNAs have been associated with pathological processes that activate proinflammatory pathways, which influence cellular events such as differentiation, aging, autophagy, apoptosis, and drug resistance in cancer cells. RESULTS: In this review, we summarized the biology of vtRNAs and focused on their interactions with the innate immune system. These findings provide insights into the diverse roles of vtRNAs and their correlation with various cellular processes to improve our understanding of their biological functions.

Maintaining the apex: a novel technique for vault suspension during vaginal hysterectomy.

INTRODUCTION AND HYPOTHESIS: Post-hysterectomy vault prolapse poses significant challenges to patients and surgeons alike. Despite numerous surgical interventions during initial vaginal hysterectomy to counteract this, a comparative analysis of their efficacy is limited. This study introduces a pioneering technique intended to avert vault prolapse during vaginal hysterectomy by harmoniously merging level 1 and level 2 support. METHODS: After obtaining informed consent, we recorded a variation of the McCall technique performed during vaginal hysterectomy and anterior repair. Patient follow-ups were conducted up to 6 months post-operation to evaluate anatomical outcomes and quality of life. RESULTS: A total of 46 women underwent the surgery. Anatomical evaluations at the 6-month mark were commendable, with no recurrence instances. Quality-of-life assessments, using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12), showcased substantial improvement. CONCLUSION: Our novel approach to vault suspension provides an uncomplicated, easily impartible, surgical procedure utilizing standard sutures. We believe that this approach is both enduring and safe.

Effect of ciliary sulcus angle on the prediction of the vault for phakic implantable collamer lens in the KS formula.

PURPOSE: We aimed to explore the effects of the ciliary sulcus angle (CSA) on accurate prediction of the vault after phakic implantable collamer lens (EVO ICL Model V4c) using the KS formula. METHODS: Patients were classified according to the size of CSA: group A, narrow angle (CSA < 30°); group B, normal angle (CSA = 30-90°); and group C, wide angle (CSA > 90°). Further, differences between the actual vault dimensions at 3 months postoperatively and the preoperatively predicted vault dimensions in the three groups were analyzed. RESULTS: This study included 223 eyes of 223 individuals. In groups A-C, the difference in the preoperative vault dimensions of the three groups predicted with the KS formula was not statistically significant (P = 0.056). The actual vault dimensions at 3 months postoperatively were significantly different between the three groups (P < 0.001). Moreover, the difference between the actual and predicted vaults by the KS formula was statistically significant (P < 0.001). In the 3 months, after surgery, the percentages of patients with a low vault (< 250 µm) were 0%, 3%, and 29% in groups A, B, and C, respectively. Further, the percentages of patients with an ideal vault (250-750 µm) in the postoperative period were 66%, 84%, and 71% in groups A, B, and C, respectively. Finally, the percentages of patients with a high vault (> 750 µm) in the postoperative period were 34%, 13%, and 0% in groups A, B, and C, respectively. Notably, the distribution of the vault among the three groups was statistically significant (P < 0.001). CONCLUSION: The size of CSA significantly affects the predictiveness of the vault by the KS formula, with the most pronounced effect on the angles < 30° and > 90°. Therefore, CSA should be considered when selecting the lens size using the KS formula preoperatively. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200065501.

Predictability comparison of sizing parameters for postoperative vault after implantable Collamer lens implantation.

PURPOSE: This study aims to assess the accuracy of three parameters (white-to-white distance [WTW], angle-to-angle [ATA], and sulcus-to-sulcus [STS]) in predicting postoperative vault and to formulate an optimized predictive model. METHODS: In this retrospective study, a cohort of 465 patients (comprising 769 eyes) who underwent the implantation of the V4c implantable Collamer lens with a central port (ICL) for myopia correction was examined. Least absolute shrinkage and selection operator (LASSO) regression and classification models were used to predict postoperative vault. The influences of WTW, ATA, and STS on predicting the postoperative vault and ICL size were analyzed and compared. RESULTS: The dataset was randomly divided into training (80%) and test (20%) sets, with no significant differences observed between them. The screened variables included only seven variables which conferred the largest signal in the model, namely, lens thickness (LT, estimated coefficients for logistic least absolute shrinkage of -0.20), STS (-0.04), size (0.08), flat K (-0.006), anterior chamber depth (0.15), spherical error (-0.006), and cylindrical error (-0.0008). The optimal prediction model depended on STS (R2=0.419, RMSE=0.139), whereas the least effective prediction model relied on WTW (R2=0.395, RMSE=0.142). In the classified prediction models of the vault, classification prediction of the vault based on STS exhibited superior accuracy compared to ATA or WTW. CONCLUSIONS: This study compared the capabilities of WTW, ATA, and STS in predicting postoperative vault, demonstrating that STS exhibits a stronger correlation than the other two parameters.

Prevalence and associated factors of depression among women with advanced pelvic organ prolapse in Northwest Ethiopia: cross-sectional study.

BACKGROUND: Depression is a symptom characterized by sadness, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, feelings of tiredness and poor concentration. One of the most common mental illnesses in the world and a major contributor to morbidity and mortality is depression. The purpose of this study was to ascertain the prevalence of depression and the risk factors associated with it in women who had advanced pelvic organ prolapse. METHODS: A facility-based cross-sectional study was conducted to determine depression among advanced pelvic organ prolapse women at Gondar University Comprehensive Specialized Hospital. All women who have advanced pelvic organ prolapse were consecutively included till it reached a total of 367 participants over four months. A structured questionnaire was used to obtain the sociodemographic characteristics, clinical characteristics and depression status of the participants. Depression measures were obtained by using the Patient Health Questionnaire tool, which is validated in the Ethiopian local language for chronic illnesses including pelvic organ prolapse using a cut point of five and above, which is considered to indicate depression. Women who screened positive were linked to a psychiatric clinic for further evaluation and treatment. Data was entered into a computer using Epi Info version 3.5.3 and then exported to STATA version 14 for analysis. Multivariable logistic regressions were fitted and odds ratios with 95% confidence intervals with a P value less than 0.05 were used to identify statistically significant factors. RESULTS: The prevalence of depression was found to be 47.1% (95% CI: 43-52%). Being rural (AOR = 4.8; CI: 1.11-16.32), having a history of divorce because of pelvic organ prolapse (AOR = 5.5; CI: 1.85-16.32) and having a history of urinary symptoms (AOR = 3.1; CI: 1.12-8.59) were found to be independently associated with depression. CONCLUSIONS: The prevalence of depression among women with advanced pelvic organ prolapse in this study is high as compared to other studies. Depression screening strategies should be designed for the early identification and treatment of depression among women with advanced pelvic organ prolapse.

Postoperative complications and unanticipated healthcare encounters following mini-laparotomy vs. laparoscopic/robotic-assisted sacrocolpopexy: a comparative retrospective study.

BACKGROUND: Pelvic organ prolapse is a debilitating condition impacting lives of millions of women worldwide. Sacrocolpopexy (SCP) is considered an effective and durable surgical technique for treatment of apical prolapse. The aim of this study was to compare short-term outcomes including postoperative complications and unanticipated healthcare encounters between patients who underwent SCP with a mini-laparotomy approach compared to patients treated with laparoscopic and robotic-assisted laparoscopic SCP. METHODS: This was a retrospective cohort study including patients treated for apical prolapse at a university affiliated urogynecology practice. Patients over the age of 18 who underwent abdominal SCP between 2019 and 2023 were included. The cohort was formed into two groups: (1) Patients who underwent SCP through a mini-laparotomy incision (Mini-lap group); (2) Patients who underwent laparoscopic or robotic-assisted laparoscopic SCP (Lap/Robot group). RESULTS: A total of 116 patients were included in the final analysis. Ninety patients underwent either laparoscopic or robotic-assisted SCP, whereas 26 patients underwent SCP with a mini-laparotomy approach. Study participants exhibited a mean age of 63.1 ± 10.3 years, mean body mass index (BMI) of 25.8 ± 4.9 Kg/m2, and 77.6% of them identified as Caucasian. Upon comparison of demographic and past medical history between groups there were no statistically significant differences in age, BMI, menopausal status, race, parity or comorbid conditions. Patients in the Mini-lap group were less likely to have undergone previous abdominal surgery (11.5% vs. 50.6%, p < 0.001) and had more severe apical prolapse (stage 4 prolapse, 40% vs. 21.2%, p < 0.001) than their counterparts in the Lap/robot group. Regarding intraoperative parameters, length of surgery was significantly shorter in the Mini-lap group compared to the Lap/robot group (97.3 ± 35.0 min vs. 242.0 ± 52.6 min, p < 0.001). When focusing on the primary outcome, postoperative complications within the first 30 days after surgery, there were no differences noted between groups. Additionally, the number of unanticipated healthcare encounters, such as phone calls, clinic visits, emergency department visits, urgent care visits, readmissions and reoperations were similar between groups. CONCLUSIONS: Mini-laparotomy approach for SCP is safe with comparable intra- and postoperative complications, and unanticipated healthcare encounters compared to conventional minimally invasive methods.

Influencing factors comparing different vault groups after phakic implantable collamer lens implantation: review and meta-analysis.

BACKGROUND: Studies on the factors affecting vault after posterior chamber phakic Implantable Collamer Lens (ICL) have been carried out, but most of them are single-centered and subjective selections of parameters. The present study aimed to systematically analyze the factors for vault. METHODS: A systematic review of case series, case-control, and cohort studies derived from the articles published in PubMed, the Cochrane Library, Embase, Web of Science, CNKI, CBM, Wanfang and VIP, as well as ClinicalTrials, which were conducted to search for studies on factors of vault using four core terms: phakic intraocular lenses, vault, risk factor and observational study, from January 01, 1997, to February 20, 2023. The included studies were meta-analyzed quantitatively and described qualitatively. Subsequently, meta-regression and subgroup analysis were used. RESULTS: We identified 13 studies (1,607 subjects), and 14 factors were considered. Meta-analysis showed that anterior chamber depth (ACD), horizontal corneal white-to-white (hWTW), ICL-size, and age are dual effects of the abnormal vaults; anterior chamber volume (ACV) and lens thickness (LT) are a one-way effect; while axial length (AL), ICL- spherical equivalent (ICL-SE) and Km are insignificant. In addition, descriptive analysis of anterior chamber angle (ACA), horizontal sulcus to sulcus (hSTS), ciliary processes height (T value), crystalline lens rise (CLR), and gender showed that all factors except gender tend to have significant effects on vault. Sensitivity analysis showed stable combined results. Country and design respectively affect the heterogeneity in ACD and ICL-size at low vault, while design affects the heterogeneity in ACD at high vault. No publication bias exists. CONCLUSIONS: Vault after ICL is related to multiple factors, especially anterior segmental biologic parameters, and they are weighted differently. We hope to provide a reference for the selection and adjustment of ICL.

A case of pediatric primary osteolytic extradural and complicated hydatid cyst revealed by a skull vault swelling.

Hydatidosis is a parasitic infestation whose etiological agent is the larva of the cestode Echinococcus granulosus. It is a zoonosis, and the human being behaves as an accidental intermediate host in the parasitic cycle with pediatric predominance. The most frequent clinical presentation is hepatic, followed by pulmonary, with cerebral hydatidosis being extremely rare. Imaging is characteristic, generally dealing with single cystic lesion, usually unilocular and less frequently multilocular, located mainly intraaxially. Extradural hydatid cyst, whether primary or secondary, remains very rare or even exceptional. The primary disease remains extremely rare, and its clinical picture is related to the number, size, and location of the lesions. Infection within these cerebral hydatid cysts remains an extremely rare occurrence, and only few cases were reported previously in the literature. The authors report the nosological review of the clinical, imaging, surgical, and histopathological records of a pediatric primary osteolytic extradural and complicated hydatid cyst in a 5-year-old North African male patient coming from a rural area who presented for progressive onset of a painless left parieto-occipital soft swelling without any neurological disorder with good outcomes after surgery. The authors report this case due the fact that it had not been documented before in the pediatric population and to the success of the specialized treatment.

Posterior cranial vault distraction in children with syndromic craniosynostosis: the era of biodegradable materials-a comprehensive review of the literature and proposed novel global application.

Distraction osteogenesis is utilized to increase intracranial volume in the treatment of restrictive pathologies, most commonly syndromic synostosis. Children too young for open calvarial vault expansion or other systemic or local contraindications to a direct reconstructive approach benefit greatly from distraction osteogenesis, typically addressing posterior vault expansion. Wound infection, cerebrospinal fluid (CSF) leak, device failure, need for a second surgery for removal, and cost, are issues that can limit the use of this approach. These challenges are more pronounced in low- and middle-income countries (LMICs) due to lack of access to the device, the financial burden of the need for a second surgery, and the severity of the implications of infection and CSF leak. Over the last five decades, there has been an increased acceptance of bioresorbable instrumentation in craniofacial surgery. Poly L-lactic acid, polyglycolic acid, and polydioxanone are the most commonly used polymers. New resorbable fixation tools such as ultrasound-activated pins and heat-activated pins are superior to conventional bioresorbable screws in allowing attachment to thinner bone plates. In this paper, we present a review of the literature on cranial vault distraction and the use of bioresorbable materials and propose a novel design of a fully absorbable cranial distractor system using external magnetic distraction control, eliminating the need for external activation ports and a second surgery to remove the hardware. The application of this technology in LMIC settings could advance access to care and treatment options for patients with syndromic synostosis.

A diffusion tensor imaging comparison of white matter development in nonsyndromic craniosynostosis to neurotypical infants.

PURPOSE: Nonsyndromic craniosynostosis (NSC) is associated with neurocognitive deficits, and intervention at infancy is standard of care to limit the negative effects of NSC on brain development. In this study, diffusion tensor imaging (DTI) was implemented to investigate white matter microstructure in infants with NSC undergoing cranial vault remodeling, and a comparison was made with white matter development in neurotypical controls. METHODS: Infants presenting with NSC (n = 12) underwent DTI scans before and after cranial vault remodeling. Neurotypical infants (n = 5), age matched to NSC patients at preoperative scans, were compared to preoperative DTI scans. Pre- and postoperative NSC scans were compared in aggregate, and the sagittal synostosis (n = 8) patients were evaluated separately. Finally, neurotypical infants from the University of North Carolina/University of New Mexico Baby Connectome Project (BCP), who underwent DTI scans at timepoints matching the NSC pre- and postoperative DTI scans, were analyzed (n = 9). Trends over the same time period were compared between NSC and BCP scans. RESULTS: No significant differences were found between preoperative NSC scans and controls. White matter development was more limited in NSC patients than in BCP patients, with microstructural parameters of the corpus body and genu and inferior and superior longitudinal fasciculi consistently lagging behind developmental changes observed in healthy patients. CONCLUSION: Infant white matter development appears more limited in NSC patients undergoing cranial vault remodeling relative to that in neurotypical controls. Further investigation is needed to explore these differences and the specific effects of early surgical intervention.

Undiagnosed sagittal synostosis as cause of "idiopathic" intracranial hypertension.

PURPOSE: Idiopathic intracranial hypertension (IIH) is a rare condition in children, but if diagnosed needs to be promptly treated to avoid clinical sequalae. The main purpose of this paper was to test our clinical experience with a cohort of normocephalic children with craniosynostosis who do not present in the routine way to craniofacial services, due to the normal head shape and age, diagnosed with IIH. METHODS: We retrospectively reviewed all children who were referred to neurosurgery from 2012 to 2022 for management of IIH on our prospectively kept database. We determined what treatments were offered and if there was an associated craniosynostosis. RESULTS: In total, 19 children were identified with an average age at referral of 11.5 years (st dev 4.0 years) with 11 male and 8 female. The most common presenting symptoms and signs were papilloedema (18/19), headaches (15/19), visual deterioration (9/19), nausea and vomiting (7/19) and diplopia (4/19). Five out of 19 children (26.3%) had a sagittal suture fused that was not identified at the time of treatment and all children were normocephalic. CONCLUSION: There is a cohort of children with IIH who will have concomitant craniosynostosis and ideally would benefit from cranial vault expansion as primary surgery rather than cerebrospinal fluid (CSF) diversion. We suggest all children with IIH requiring neurosurgical intervention have cross-sectional imaging to look for occult craniosynostosis prior to intervention.

Primary acalvaria with open-lip schizencephaly in indigenous South Papuan surviving newborn: a rare case report.

BACKGROUND: Acalvaria, or acrania, is a rare congenital cranial vault defect with neurocranium absences, including complete or part of calvaria flat bones, dura mater, and associated muscles, but with a still present in the central nervous system, skull base, facial bones, and skin-covered the defect. It is a sporadic incidence without apparent genetic factors confirmed. Acalvaria is often misdiagnosed as anencephaly; the distinguishable difference is that anencephaly has an absence (partial or complete) of the brain tissue, including the skull and scalp. Acalvaria is considered a fatal anomaly with a low survival rate, and only a few cases of extended survival have been reported until now. To the best of the author's knowledge, no acalvaria case has been published in Papua, and only one reported case of the coexistence of acalvaria with schizencephaly in Brazil (2018). CASE REPORT: Herein, we present a case of an indigenous South Papuan living newborn with primary acalvaria and open-lip schizencephaly in a frontoparietal region. A male newborn baby was born from a 39-year-old female Marind-Anim tribe patient with a 38th week of gestation, with no previous history of miscarriage, is not a consanguineous marriage, and had an unremarkable medical history during this pregnancy. Post-natal physical examinations showed an irregularly shaped head with 11.5 cm diameter concave of the right side, with a soft brain-like consistency palpable and the absence of half right frontoparietal calvarium covered with a presence of scalp and hair. Cranial 2-dimension ultrasonography shows an absence of half right frontoparietal calvaria bone with a complete presence of scalp and periosteum covering the defect with a fluid accumulation (anechoic) below the periosteum. A transverse axis view shows a complete structure but hypoplasia of brain cortex with visible slightly dysgenesis of gyrus and sulcus in both hemispheres convincing the acalvaria condition not anencephaly. A fluid accumulation above brain parenchyma of the frontoparietal region happened to be a cerebrospinal fluid coming from a wide-open cleft extending from the left lateral and fourth ventricles to the cerebral cortex, suggesting a typical condition of open-lip schizencephaly. Further health follow-ups until 6 months old showed still normal physical and behavioral development with no sign of complications. CONCLUSIONS: No standard acalvaria treatment is being established; conservative and supportive therapy is mostly taken considering their low survival rate. With the advancement of medical technology nowadays, surgical approaches, including scalp defect closure, bone graft, and 3D-printed defect filling, are being performed and have succeeded in a few cases. Long-term follow-up is required to monitor their neuro-psychological development and complication incidences that need further intervention.

Early posterior vault distraction osteogenesis changes the syndromic craniosynostosis treatment paradigm: long-term outcomes of a 23-year cohort study.

BACKGROUND: Early surgical management of syndromic craniosynostosis varies widely between centers, with patients typically undergoing multiple intracranial procedures through childhood. This study evaluates the long-term impact of early posterior vault distraction osteogenesis (PVDO) versus conventional treatment paradigms on the number and timing of subsequent craniofacial procedures. METHODS: We retrospectively analyzed the longitudinal operative patterns of patients with syndromic craniosynostosis treated from 2000 to 2023 with greater than five years of follow-up. Outcomes of patients who underwent early PVDO and conventional vault reconstruction were compared. RESULTS: Fifty-five patients met the inclusion criteria (30 PVDO and 25 conventional). Age at initial vault surgery was similar between the PVDO and conventional cohorts (7.6 vs. 8.8 months), as were baseline craniometrics (p > 0.05). Multiple fronto-orbital advancement (FOA) procedures were performed in only 1/30 (3%) PVDO-treated patient versus 12/25 (48%) conventionally-treated patients (p < 0.001). Twelve (40%) PVDO-treated patients did not undergo FOA at all. Among patients with Apert and Crouzon syndromes, fewer PVDO-treated patients required FOA prior to midface surgery (33% vs. 92%, p = 0.004) or repeat FOA (6% vs. 50%, p = 0.005) compared to conventionally-treated patients. Among patients with Muenke and Saethre-Chotzen syndromes, a similar proportion of patients required FOA in the PVDO and conventional cohorts (91% vs. 100%, p = 0.353), though no PVDO-treated patients required repeat FOA (0% vs. 44%, p = 0.018). CONCLUSIONS: Early PVDO is associated with a reduction in the high burden of both FOA and, critically, revisionary frontal procedures which are commonly seen in conventionally-treated patients with syndromic craniosynostosis.