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A novel approach for the synthesis of 1,3,4-oxa(thia)diazole aryl thioethers through a biocatalytic strategy has been introduced. By leveraging Myceliophthora thermophila laccase (Novozym 51003) as a catalyst, catechol undergoes oxidation to ortho-quinone, facilitating subsequent 1,4-thia-Michael addition reactions. The method offers efficiency and mild reaction conditions, demonstrating promise for sustainable synthesis pathways in organic chemistry. Using this approach, 13 new derivatives of 2,5-disubstituted-1,3,4-oxa(thia)diazole aryl thioethers, with a yield of 46-94%, were synthesized.
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The synthesis of all-carbon quaternary stereocenters containing nitriles is a very important and challenging subject in organic chemistry. We used a biocatalytic approach under mild conditions to obtain new derivatives of these scaffolds by oxidation of catechols by Myceliophthora thermophila laccase (Novozym 51003) to afford o-quinones and 1,4-addition of a series of carbon nucleophiles containing tertiary alkyle nitriles to these intermediates. Using this approach, α-cyano carbonyls bearing a quaternary stereocenter were also prepared. Finally, the yields for the prepared compounds were 72-94%.
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BACKGROUND: Dermal sinuses and encephaloceles are uncommon central nervous system malformations. The occurrence of these malformations in different members of a family is very rare. OBSERVATIONS: This report documents the unique case of a 10-month-old boy with a frontonasal encephalocele, born to a mother with a nasal dermal sinus. These two specific neural tube defects have not been previously reported as occurring between parent and child. LESSONS: This case demonstrates potential heritable links in central nervous system malformations through the occurrence of a frontonasal encephalocele in a child born to a mother with a dermal sinus. The connection between these two malformations in a heritable manner suggests a potential need for further research into the genetic pathogenesis of such defects to predict them more accurately within families. https://thejns.org/doi/10.3171/CASE23727.
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Deformational plagiocephaly, deformational brachycephaly, and deformational scaphocephaly are the most common types of skull deformities during the first year of life. Using a cranial remolding orthosis (CRO) can have an important role in achieving a satisfactory level of improvement in symmetry and proportion of the deformed skulls. However, there is no consensus on the most important parameters for the success or length of treatment with a CRO. In this study, we did a systematic literature review in PubMed, Scopus, Web of Science, and EMBASE on January 2023. Titles/abstracts of the found studies were screened by two independent reviewers. The Newcastle-Ottawa Scale was used to evaluate the quality of the included articles. The best evidence synthesis was considered to determine the strength of the reported factors. A total of 25 articles with an accumulated sample of 7594 participants were included. Nine predictive factors, including age at initiation of CRO treatment, CRO compliance, deformity severity, deformity type, torticollis, gestational age, gestational type, delivery method, and developmental delay, were considered for CRO treatment length or success. Moderate evidence suggests that CRO treatment length is linked to a patient's age at the start of treatment and the deformity severity. Moreover, treatment success is correlated with a patient's age at the start of treatment, CRO compliance, and deformity severity. Moderate evidence indicates that there is no relationship between the presence of torticollis and gestational age with CRO treatment success.
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A regioselective enzyme-catalyzed system is selected for the synthesis of 1,3,5-trisubstituted pyrazole derivatives by adding phenyl hydrazines, nitroolefins, and benzaldehydes. The reaction is performed in a one-pot vessel with a yield ranging from 49 to 90%. TLL@MMI, immobilized Thermomyces lanuginosus lipase (TLL) on a multivariate of MOF-5/IRMOF-3 (MMI), showed good performance for the catalysis of this reaction. The prepared biocatalyst was characterized by FTIR, XRD, SEM, and EDX. The thermal and solvent stability of TLL@MMI was investigated in MeOH and EtOH after 24 h incubation. In the presence of 100% concentrations of EtOH, TLL@MMI has 80% activity.
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OBJECTIVE: Preventative protocols have efficaciously reduced shunt infection in developed countries. However, the generalizability of these protocols in low-to-middle-income countries (LMICs) remains unclear. Previously, shunt insertion in the authors' center was routinely performed under institutional preventative precautions, which was updated via merging with the Hydrocephalus Clinical Research Network (HCRN) protocol. This study aimed to investigate the ventriculoperitoneal shunt (VPS) infection rates in pediatric patients following the implementation of the adapted protocol. METHODS: The adapted protocol was implemented in all first-time VPS implantations between 2011 and 2021. The primary outcome was a 6-month shunt infection. The Pearson chi-square test was used for categorical variables and the Mann-Whitney U-test for numeric variables to evaluate the correlation with shunt infection. RESULTS: A total of 352 first-time VPS procedures were performed adhering to the adapted protocol. The median age was 5 months, and 189 (53.7%) were male. Overall, 37 patients (10.5%) experienced shunt infection, with 30 (8.5%) occurring within the first 6 months, which was lower than 13.3% infection rate of the previous series of the same center. The infection rate was slightly higher than the 5.7% and 6.0% rates reported by HCRN studies. Patients with shunt infection were significantly younger (7.5 versus 17.5 months, P < 0.001). CONCLUSIONS: This study validates the efficacy of an adapted perioperative protocol in mitigating shunt infection in a high-volume center in a LMIC. Adhering to a step-by-step protocol, modified to suit the healthcare resources and financial constraints of LMICs, could maintain low shunt infection rates that are roughly comparable to those of centers in high-income countries.
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Países en Desarrollo , Hidrocefalia , Centros de Atención Terciaria , Derivación Ventriculoperitoneal , Humanos , Derivación Ventriculoperitoneal/métodos , Masculino , Femenino , Lactante , Hidrocefalia/cirugía , Preescolar , Protocolos Clínicos , Niño , Estudios Retrospectivos , Atención Perioperativa/métodosRESUMEN
Background: Spinal aneurysmal bone cysts (ABCs) are rare, histologically benign tumors with aggressive behavior, which may cause bone and soft-tissue destruction, particularly affecting neural elements. Management of these tumors, including treatment modalities and follow-up protocols, remains challenging. Case Description: A 7-year-old boy presented with chest wall pain persisting for two months before admission, accompanied by progressive mono paresis lasting ten days before admission. Myelopathy signs were evident during the examination. Imaging confirmed a multicystic lesion at the T6 level involving the posterior elements of the vertebra, with significant cord compression. Due to deteriorating neurological function, he underwent urgent laminectomy and neural decompression, followed by subtotal tumor resection. Postoperative histopathological examination confirmed the diagnosis of an ABC, and the patient experienced significant neurological recovery. However, after 21 days, the patient was readmitted to the emergency department with severe paraparesis. Magnetic resonance imaging revealed rapid growth of the residual tumor, leading to cord compression. He underwent aggressive total tumor resection, T6 vertebral body corpectomy, and fixation with pedicle screws and cage insertion. Following the second surgery, prompt neurological recovery occurred. Conclusion: This rare case report emphasizes the importance of a close follow-up protocol for spinal ABCs in the pediatric population. It highlights the challenges in managing these tumors and the need for vigilant monitoring to detect and address rapid recurrences.
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Various nanoflowers are synthesized for enzyme immobilization. In order to increase the activity of nanoflowers, in this study, 3D flower-like structured organic-inorganic hybrid nanoflowers (hNFs) with various lipases Rhizomucor miehei lipase (RML), Candida antarctica lipase B (CALB), Humicola insolens lipase (HIL), Thermomyces lanuginosus lipase (TLL), Eversa® Transform 2.0 (ET) a genetically modified enzyme derived of TLL and graphene quantum dots (GQDs) were prepared and characterized.Lipase hNFs [lipase-(Cu/Co)3(PO4)2] and lipase@GQDs hNFs [lipase@GQDs-(Cu/Co)3(PO4)2] were straightforwardly prepared through mixing with metal ion (Cu2+or Co2+) aqueous solutions with or without GQDs. The ET@GQDs-(Cu)3(PO4)2 hNFs demonstrated 687 % higher activity than ET-(Cu)3(PO4)2 hNFs and 650 % higher activity than the free ET. Similar results were also observed with other lipase hybrid nanoflowers. For example, TLL@GQDs-(Cu)3(PO4)2 hNFs exhibited a 557 % higher activity than TLL-(Cu)3(PO4)2 hNFs and a 463 % higher activity than free TLL. Additionally, TLL@GQDs-(Co)3(PO4)2 hNFs showed a 141 % higher activity than TLL-(Co)3(PO4)2 hNFs and a 304 % higher activity than free TLL. Upon examining pH and thermal stability, it was revealed that lipase@GQDs hNFs exhibited higher activity compared to free lipase and other hNFs without GQDs. The effect of metal ions, enzyme concentrations and amount of GQDs on the morphology and enzyme activity of the lipase-hNFs was examined.
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Grafito , Puntos Cuánticos , Lipasa/química , Enzimas Inmovilizadas/química , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
OBJECTIVE: Cervical saccular limited dorsal myeloschisis (LDM), previously so-called "cervical myelomeningocele," is a rare spinal dysraphism. Although the pathogenesis of true myelomeningocele is primary neurulation failure, LDM results from a delayed abnormality during the final stages of neurulation. The aim of the study was to evaluate the outcome of these patients and to assess the correlation of outcomes with the level and type of lesion. Also, pooled data from the literature on similar lesions were systematically reviewed. METHODS: A retrospective study was conducted at Children's Medical Center (CMC), Tehran, Iran. Information of patients who underwent surgery between 2004 and 2020 (i.e., the recent series) was extracted and combined with data from a previously published series from the same center that were obtained between 2000 and 2003 (CMC series). The literature was reviewed for all published cases, to be combined with the CMC series for further analyses. RESULTS: Twenty-two patients were included in the recent series. Combined with 16 previously published cases, 38 patients with a mean ± SD age at surgery of 11.75 ± 28.64 months were included in the CMC series. The rates of neurological deficit, hydrocephalus, and Chiari malformation type II in the CMC series were 26.32%, 39.47%, and 28.95%, respectively. The lesions were at the upper levels in 17 (44.7%) and lower cervical levels in 21 (55.3%) patients, with 31 cases (81.58%) diagnosed with stalk-type lesions and 7 cases (18.42%) with myelocystocele-type lesions. At final follow-up, 31 patients (81.57%) achieved sphincter continence, and all 36 accessible patients were ambulated, consisting of 28 (73.68%) independent and 8 (21.05%) dependent ambulation patients. The rates of Chiari malformation type II and hydrocephalus were insignificantly higher in patients with upper-level lesions, but those of neurological deficit, ambulation, and sphincter continence were not associated with level. The rates of hydrocephalus (p < 0.01), Chiari type II malformation (p < 0.01), and neurological deficit (p = 0.04) were significantly higher in the myelocystocele group. In the systematic review, 24.77% of patients had neurological deficit. Binary logistic regression showed that older age at surgery (p = 0.03) and associated spinal anomalies (p = 0.04) were significant predictors of deficits. Chiari type II malformation was significantly (p < 0.001) and hydrocephalus was marginally (p = 0.06) more common in patients with myelocystocele-type lesions. The rate of Chiari malformation type II was higher in patients with upper-level lesions (p = 0.02). CONCLUSIONS: Patients with cervical saccular LDM had better outcome compared with those patients with true myelomeningocele in more distal areas. According to the current series, most patients obtained ambulation and voiding continence, regardless of the level or type of lesion. Hydrocephalus, Chiari type II malformation, and neurological deficit were more common in patients with myelocystocele-type lesions.
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Malformación de Arnold-Chiari , Hidrocefalia , Meningomielocele , Disrafia Espinal , Niño , Humanos , Lactante , Preescolar , Meningomielocele/complicaciones , Malformación de Arnold-Chiari/cirugía , Estudios de Seguimiento , Estudios Retrospectivos , Irán , Disrafia Espinal/cirugía , Hidrocefalia/cirugía , Hidrocefalia/complicacionesRESUMEN
INTRODUCTION: The aim of the study was to investigate and identify the predictors associated with the incidence of seizures in patients with encephalocele (EC). METHODS: A retrospective analysis was undertaken of patients treated for EC at a tertiary medical center in Tehran between 2010 and 2021. Data including age at presentation, gender, location, size, and content of EC, ventriculomegaly, hydrocephalus, associated anomalies, and neurodevelopmental delay (NDD) were evaluated for their prognostic value. In addition, univariate and multivariate analyses were performed to identify the correlation between independent predictors and seizure incidence. RESULTS: One hundred and two cases of EC were identified. Seventy-one ECs (69.6%) were posterior ECs, while 31 (30.4%) were anterior. Neural tissue was found in 43 (42.2%) of the ECs. Thirty-three patients (32.4%) had ventriculomegaly, of which 90.9% underwent shunt placement for progressive or symptomatic hydrocephalus. Seizure was found in 26 (25.5%) patients. On univariate analysis, presence of other anomalies, postoperative infections, and NDD were associated with seizures (p < 0.05). When the anomalies were categorized into intracranial and extracranial groups in univariate analysis, none was associated with statistically significant increase in seizure (p values of 0.09 and 0.61, respectively). Although according to multivariate analysis, only the association between other associated anomalies and seizure was near significant (OR: 2.0, 95% CI: 0.95-4.2, p = 0.049). Children with NDD and postoperative infection were, respectively, 3.04 and 1.3 times more at risk to experience seizures compared to other patients. CONCLUSION: We found a rate of 25.5% risk of seizure in patients with EC. This study could not find any significant predictors of seizure in children with EC. However, pediatric patients with postoperative infections including sepsis, wound infection, and NDD require more consideration to reduce the risk of seizure.
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Encefalocele , Hidrocefalia , Humanos , Niño , Encefalocele/epidemiología , Encefalocele/cirugía , Encefalocele/complicaciones , Estudios Retrospectivos , Centros de Atención Terciaria , Resultado del Tratamiento , Irán/epidemiología , Convulsiones/etiología , Convulsiones/complicaciones , Hidrocefalia/epidemiología , Hidrocefalia/cirugía , Hidrocefalia/complicaciones , Complicaciones Posoperatorias/epidemiologíaRESUMEN
Increasing attention to peptides as prospective therapeutics has created a renaissance in searching for new alternatives to the current peptide synthetic approaches as well as their modification. In this context, it is necessary to develop different approaches for peptide ligation. Using enzymes as a novel strategy and powerful tool for the peptide and protein ligation has recently received a lot of attention. We here designed a fully convergent chemo-enzymatic peptide synthesis (CEPS) process for the synthesis of aviptadil a 28-mer therapeutic peptide with potential therapeutic effects in various medical contexts specially in the treatment of acute respiratory distress syndrome (ARDS) by coupling two peptide segments with four different peptiligase variants in aqueous environments. Our study reveals that peptiligase variants are capable of ligation reaction in 15 min. The overall time of ligation is shorter than those peptides with similar lengths and hinderance to aviptadil which reported for conventional synthesis by full solid-phase peptide synthesis. Yields ranged from 54 % to 76 %.
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Proteínas , Péptido Intestinal Vasoactivo , Fentolamina , Combinación de MedicamentosRESUMEN
Spinal intramedullary capillary hemangioma is a rare condition. Although most spinal/spinal cord hemangiomas are inborn in origin, perinatal presentation is uncommon. We present a neonate with an intramedullary hemangioma, born with communicating hydrocephalus and complete paraplegia. Spinal imagining showed an intradural mass with hemorrhagic foci, a low-lying conus medullaris, and scalloping of dorsal elements. Ventriculoperitoneal shunting was performed in an emergent setting, with cerebrospinal fluid showing a brownish appearance with high viscosity which implied a possible old hemorrhage. Tissue sample was taken from the spinal lesion in an elective setting. Histopathological examination revealed capillary lobules and extralobular large vessels resembling abnormal veins. The mentioned clues suggested that this congenital hemangioma had become symptomatic from the prenatal period. Though it is a are event, it should be kept in mind while evaluating a neonate with communicating hydrocephalus and weakness of extremities with or without cutaneous hemangiomatous stigmata.
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Hemangioma Capilar , Hemangioma , Hidrocefalia , Humanos , Recién Nacido , Femenino , Embarazo , Hemangioma Capilar/complicaciones , Hemangioma Capilar/diagnóstico por imagen , Hemangioma Capilar/cirugía , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/etiología , Hidrocefalia/cirugía , Paraplejía/etiología , Paraplejía/cirugía , ExtremidadesRESUMEN
Despite multi-modal therapies for patients with malignant brain tumors, their median survival is < 2 years. Recently, NK cells have provided cancer immune surveillance through their direct natural cytotoxicity and by modulating dendritic cells to enhance the presentation of tumor antigens and regulate T-cell-mediated antitumor responses. However, the success of this treatment modality in brain tumors is unclear. The main reasons are; the brain tumor microenvironment, the NK cell preparations and administration, and the donor selection. Our previous study showed that intracranial injection of activated haploidentical NK cells resulted in the eradication of glioblastoma tumor mass in the animal model without any evidence of tumor recurrence. Therefore, in the present study, we evaluated the safety of intra-surgical cavity or intra cerebrospinal fluid (CSF) Injectionofex vivoactivated haploidentical NK cells in six patients with recurrent glioblastoma multiform (GBM) and malignant brain tumors resistance to chemo/radiotherapy. Our results indicated that activated haploidentical NK cells express activator and inhibitor markers and can kill the tumor cells. However, their cytotoxic potential on patient-derived GBM (PD-GBM) was more than that of its cell line. Also, their infusion increased the overall disease control rate by about 33.3%, with a mean survival of 400 days. Moreover, we showed that local administration of the activated haploidentical NK cells in malignant brain tumors is safe, feasible, tolerated at higher doses, and cost-effective.
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Neoplasias Encefálicas , Glioblastoma , Animales , Recurrencia Local de Neoplasia/terapia , Recurrencia Local de Neoplasia/patología , Células Asesinas Naturales , Encéfalo/patología , Microambiente TumoralRESUMEN
This is a letter to share the clinical experience we had with neonates born with a specific feature of spina bifida. The lesion is like a meningocele containing skim amount of fluid, with a tiny dimple around the center of the cutaneous lesion which causes inward retraction of the dysplastic coverage. This feature is in favor of accompanied split cord malformation (SCM) type I, and the central nidus is in continuous with the dural sleeve around the bony septum of SCM. By recognition of this clinical clue, surgical repair can be planned to perform with appropriate provision, particularly foreseeing the amount of intraoperative bleeding and duration of anesthesia in the newborn patients.
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Meningocele , Defectos del Tubo Neural , Disrafia Espinal , Recién Nacido , Humanos , Meningocele/diagnóstico por imagen , Meningocele/cirugía , Meningocele/complicaciones , Imagen por Resonancia Magnética , Defectos del Tubo Neural/diagnóstico por imagen , Defectos del Tubo Neural/cirugía , Defectos del Tubo Neural/complicaciones , Disrafia Espinal/cirugía , Médula Espinal/cirugíaRESUMEN
A multicomponent enzyme-catalyzed process is suggested for the synthesis of a novel series of 1,3,4-oxadiazole thioether derivatives with yields ranging from 65 to 94%. Novozym 435, the immobilized form of Candida antarctica lipase B (CALB), was found to efficiently catalyze the reaction. The products were evaluated for antitumor activities against two cancer cell lines, HT-29 (human colorectal cancer cell) and HepG2 (human liver cancer cell), by MTT assays. Among them, two compounds exhibited higher antitumor activities, for both cell lines, compared to doxorubicin. In silico molecular docking and computational ADME analysis were performed to propose a mode of action for the anti-cancer activities and to predict drug-likeness, respectively.
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Antineoplásicos , Oxadiazoles , Humanos , Simulación del Acoplamiento Molecular , Oxadiazoles/farmacología , Biocatálisis , Catálisis , Esterificación , Ensayos de Selección de Medicamentos Antitumorales , Antineoplásicos/farmacología , Relación Estructura-ActividadRESUMEN
OBJECTIVE: Children with previous ventriculoperitoneal shunt (VPS) insertion due to hydrocephalus may refer to the hospital with various clinical complaints. Shunt malfunction is frequently diagnosed in these children necessitating shunt revision. Although increased head circumference, setting sun eye in younger children, and headache, nausea/vomiting, loss of consciousness, visual disturbance, and other signs of intracranial hypertension are common clinical manifestations of shunt malfunction, some patients may present with odd or unusual symptoms. Here, we present a series of patients with shunted hydrocephalus who presented with odd and unexpected clinical manifestations of shunt malfunction. METHODS: Eight children with shunt malfunction were enrolled in this series. The age, sex, age of shunting, etiology of hydrocephalus and management, post-shunt insertion symptoms/sign, revision surgery, outcome, and follow-up were evaluated. RESULTS: Patients were aged from 1 to 13 years (mean, 6.38 years). There were 5 males and 3 females. The odd presentation associated with shunt malfunction included facial palsy in three children, ptosis in 3 children, and torticollis and dystonia each in one child. All patients underwent shunt revision except for one patient in whom a new shunt was inserted. Follow-up showed improvement of the symptoms in all patients. CONCLUSION: In this series, we reported eight patients with unusual signs and symptoms following shunt malfunction that were successfully diagnosed and managed.
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Hidrocefalia , Derivación Ventriculoperitoneal , Niño , Masculino , Femenino , Humanos , Derivación Ventriculoperitoneal/efectos adversos , Hidrocefalia/etiología , Hidrocefalia/cirugía , Cefalea/etiología , Vómitos/etiología , Reoperación , Estudios RetrospectivosRESUMEN
OBJECTIVE: In recent decades, a significant body of research has focused on targeted therapies for the treatment of central nervous system (CNS) tumors to enhance the effectiveness of management strategies. However, most of these efforts have been centered in high-income countries, which renders the generalizability of their results to low- and middle-income countries questionable. Therefore, in this review, we systematically investigated the status of research conducted on targeted therapy for CNS tumors in low- and lower-middle-income countries to elucidate the contribution of these countries in advancing neuro-oncology. METHODS: A systematic search of 3 databases was performed using a predefined search strategy. After screening the articles based on our inclusion/exclusion criteria, the data were extracted to a predesigned Excel worksheet. RESULTS: A review of 44 included studies showed that India, Iran, and Lebanon were the only countries with a contribution to this field. All included studies were laboratory or animal experiments, and there were no clinical studies in this field. The most investigated CNS tumor was malignant glioma, and gene-targeted therapy was the most investigated category of targeted therapies in these countries. CONCLUSIONS: Low- and lower-middle-income countries comprise more than half of the world population, but they are deprived of targeted therapies against CNS tumors. Although there are basic experiments performed on this subject, they originate in a limited number of these countries. Therefore, targeted therapy is in its preliminary stage in these countries.
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Neoplasias del Sistema Nervioso Central , Glioma , Humanos , Países en Desarrollo , Renta , Neoplasias del Sistema Nervioso Central/terapia , IndiaRESUMEN
Highly functionalized pyrrolidine-2,3-diones can be synthesized efficiently and stereoselectively under mild conditions using a biocatalytic approach. The reaction led to the formation of new all-carbon quaternary stereocenters from Myceliophthora thermophila laccase (Novozym 51003) catalyzed oxidation of catechols to ortho-quinones and subsequent 1,4-addition with 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones. The reaction was conducted with various substituents on both reactants, resulting in 13 products in moderate to good yields (42-91%). The same 15 reactions were also tested with K3Fe(CN)6 as a catalyst, but here only one reaction resulted in a product (60% yield).
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Strategies for the covalent immobilization of enzymes depend on the type of functional group selected to perform the coupling reaction, and on the relative importance of selectivity, loading capacity, immobilization time and activity/stability of the resulting immobilized preparation. However, no single strategy is applicable for all covalent immobilization methods or can meet all these criteria, exemplifying the challenge of introducing a versatile process broadly compatible with the residues on the surface of proteins and the functional groups of common linkers. Here, we describe the use of isocyanide-based multi-component reactions for the carrier-bound and carrier-free covalent immobilization of enzymes. Isocyanide-based multi-component reactions can accept a wide variety of functional groups such as epoxy, acid, amine and aldehyde, as well as many commercially available bi-functional linkers, and are therefore suitable for either covalent coupling of enzymes on a solid support or intermolecular cross-linking of enzymes. In this strategy, an isocyanide is directly added to the reaction medium, the enzyme supplies either the exposed amine or carboxylic acid groups, and the support (in carrier-bound immobilization) or the bi-functional cross-linking agent (in carrier-free immobilization) provides another reactive functional group. The protocol offers operational simplicity, high efficiency and a notable reduction in time over alternative strategies, and can be performed by users with expertise in chemistry or biology. The immobilization reactions typically require 1-24 h.