Pharmacological Treatment of Degenerative Cervical Myelopathy: A Critical Review of Current Evidence.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

Repeated L5 Nerve Root Compromise Detected with Motor Evoked Potentials (MEP), but Not Electromyography (EMG): A Case Report.

We report a case where neuromonitoring, using motor evoked potentials (MEP), detected an intraoperative L5 nerve root deficit during a lumbosacral decompression and instrumented fusion procedure. Critically, the MEP changes were not preceded nor accompanied by any significant spontaneous electromyography (sEMG) activity. Presumptive L5 innervated muscles, including tibialis anterior (TA), extensor hallucis longus (EHL) and gluteus maximus, were targets for nerve root surveillance using combined MEP and sEMG techniques. During a high-grade spondylolisthesis correction procedure, attempts to align a left-sided rod resulted in repeated loss and recovery cycles of MEP from the TA and EHL. No accompanying EMG alerts were associated with any of the MEP changes nor were MEP variations seen from muscles innervated above and below L5. After several attempts, the rod alignment was achieved, but significant MEP signal decrement (72% decrease) remained from the EHL. Postoperatively, the patient experienced significant foot drop on the left side that recovered over a period of 3 months. This case contributes to a growing body of evidence that exclusive reliance on sEMG for spinal nerve root scrutiny can be unreliable and MEP may provide more dependable data on nerve root patency.

Estudio retrospectivo de 544 timpanoplastias con cartílago y pericondrio: resultados anatómicos y funcionales / A retrospective study of 544 tympanoplasty with cartilage and perichondrium: anatomical and functional results

Introducción: el cierre de las perforaciones timpánicas se realiza con diferentes materiales, entre ellos el cartílago y el pericondrio. En este estudio se compararon los resultados anatómicos y funcionales obtenidos con ambos materiales, y se evaluaron posibles factores asociados con los buenos resultados. Material y métodos: estudio retrospectivo en pacientes intervenidos de timpanoplastia sin mastoidectomía entre el 1 de enero de 2001 y el 31 de diciembre de 2018. Resultados: se incluyeron 544 timpanoplastias. En la mayoría se utilizó cartílago (78,5 %) y en el resto pericondrio. El cartílago se utilizó con mayor frecuencia en los menores de 18 años (p=0,001), perforaciones totales y subtotales (p=0,000) y timpanoplastias secundarias y terciarias (p=0,008). No hubo diferencias en el tiempo de seguimiento (15,68 ± 22,18 meses frente al 12,86 ± 14,9 meses, p=0,169). La tasa de éxito anatómico fue mayor en el grupo de cartílago, sin diferencias en los resultados auditivos (82 % con cartílago y 78,3 % con pericondrio). El éxito anatómico se relacionó con la técnica utilizada para la reconstrucción con cartílago, mientras que los resultados auditivos se asociaron significativamente con el estado de la mucosa del oído medio y la cadena de huesecillos en el momento de la cirugía y el éxito anatómico posquirúrgico. Conclusiones: con el cartílago se consiguieron mejores resultados anatómicos que con el pericondrio, sin diferencias a nivel funcional. Sin embargo, los resultados funcionales empeoraron si había patología a nivel del oído medio y en ausencia de restauración anatómica.

Introduction: Different materials are used to close tympanic perforations. This stu-dy aimed to compare anatomical results obtained with cartilage and perichondrium and evaluate factors associated with successful results. Material and method: Re-trospective study of patients who underwent tympanoplasty without mastoidectomy between January 1, 2001, and December 31, 2018. Demographic data, ear pathology, surgical intervention, and anatomical and functional results were collected. Results:544 tympanoplasty were included. Cartilage was the most used (78.5%). Cartilage was used more frequently in children under 18 years (p = 0.001), to reconstruct total and subtotal perforations (p = 0.000) and in secondary and tertiary tympanoplasty (p = 0.008). Follow-up time did not differ between the two groups (15.68 ± 22.18 months vs. 12.86 ± 14.9 months, p = 0.169). The anatomical success rate was higher in the cartilage group, with no significant differences in hearing outcomes (82% with cartilage and 78.3% with perichondrium). Anatomical success was related to the technique used for cartilage reconstruction (monoblock or palisade). Hearing re-sults were significantly associated with the state of middle ear mucosa at the time of surgery, the state and mobility of the ossicle chain, and post-surgical anatomical suc-cess. Conclusions: Cartilage achieved better anatomical results than perichondrium. Both materials were comparable on a functional level. However, the functional re-sults worsen if there is pathology of the middle ear (mucosa or chain of ossicles) and anatomical restoration is not achieved.

A Novel Lipase from Streptomyces exfoliatus DSMZ 41693 for Biotechnological Applications.

Genome mining of Streptomyces exfoliatus DSMZ 41693 has allowed us to identify four different lipase-encoding sequences, and one of them (SeLipC) has been successfully cloned and extracellularly expressed using Rhodococcus sp. T104 as a host. SeLipC was purified by one-step hydrophobic interaction chromatography. The enzyme is a monomeric protein of 27.6 kDa, which belongs to subfamily I.7 of lipolytic enzymes according to its phylogenetic analysis and biochemical characterization. The purified enzyme shows the highest activity at 60 °C and an optimum pH of 8.5, whereas thermal stability is significantly improved when protein concentration is increased, as confirmed by thermal deactivation kinetics, circular dichroism, and differential scanning calorimetry. Enzyme hydrolytic activity using p-nitrophenyl palmitate (pNPP) as substrate can be modulated by different water-miscible organic cosolvents, detergents, and metal ions. Likewise, kinetic parameters for pNPP are: KM = 49.6 µM, kcat = 57 s-1, and kcat/KM = 1.15 × 106 s-1·M-1. SeLipC is also able to hydrolyze olive oil and degrade several polyester-type polymers such as poly(butylene succinate) (PBS), poly(butylene succinate)-co-(butylene adipate) (PBSA), and poly(ε-caprolactone) (PCL). Moreover, SeLipC can catalyze the synthesis of different sugar fatty acid esters by transesterification using vinyl laurate as an acyl donor, demonstrating its interest in different biotechnological applications.

Basic quality indicators for clinical care of patients with major depression, schizophrenia, and bipolar disorder.

OBJECTIVE: To identify a set of indicators to monitor the quality of care for patients with major depression, schizophrenia, or bipolar disorder. METHODS: A group of 10 experts selected the most automatically applicable indicators from a total of 98 identified in a previous study. Five online sessions and 5 discussion meetings were performed to select the indicators that met theoretical feasibility criteria automatically. Subsequently, feasibility was tested in a pilot study conducted in two hospitals of the Spanish Health Service. RESULTS: After evaluating its measurement possibilities in the Spanish Health Service, and the fulfillment of all the quality premises defined, 16 indicators were selected. Three were indicators of major depression, 5 of schizophrenia, 3 of bipolar disorder, and 5 indicators common to all three pathologies. They included measures related to patient safety, maintenance and follow-up of treatment, therapeutic adherence, and adequacy of hospital admissions. After the pilot study, 5 indicators demonstrated potential in the automatic generation of results, with 3 of them related to treatments (clozapine in schizophrenia, lithium for bipolar disorder, and valproate in women of childbearing age). CONCLUSIONS: Indicators support the monitoring of the quality of treatment of patients with major depression, schizophrenia, or bipolar disorder. Based on this proposal, each care setting can draw up a balanced scorecard adjusted to its priorities and care objectives, which will allow for comparison between centers.

Molecular nanoribbon gels.

Herein, we show that twisted molecular nanoribbons with as many as 322 atoms in the aromatic core are efficient gelators capable of self-assembling into ordered π-gels with morphologies and sol-gel transitions that vary with the length of the nanoribbon. In addition, the nanoribbon gels show a red fluorescence and also pseudoconductivity values in the same range as current state-of-the-art π-gels.

Identification of novel extracellular putative chitinase and hydrolase from Geomyces sp. B10I with the biodegradation activity towards polyesters.

Cold-adapted filamentous fungal strain Geomyces sp. B10I has been reported to decompose polyesters such as poly(e-caprolactone) (PCL), poly(butylene succinate) (PBS) and poly(butylene succinate-co-butylene adipate) (PBSA). Here, we identified the enzymes of Geomyces sp. B10I, which appear to be responsible for its biodegradation activity. We compared their amino acid sequences with sequences of well-studied fungal enzymes. Partial purification of an extracellular mixture of the two enzymes, named hydrGB10I and chitGB10I, using ammonium sulfate precipitation and ionic exchange chromatography gave 14.16-fold purity. The amino acid sequence of the proteins obtained from the MALDI-TOF analysis determined the molecular mass of 77.2 kDa and 46.5 kDa, respectively. Conserved domain homology analysis revealed that both proteins belong to the class of hydrolases; hydrGB10I belongs to the glycosyl hydrolase 81 superfamily, while chitGB10I contains the domain of the glycosyl hydrolase 18 superfamily. Phylogenetic analysis suggests a distinct nature of the hydrGB10I and chitGB10I of Geomyces sp. B10I when compared with other fungal polyester-degrading enzymes described to date.

Biochemical and structural studies of two tetrameric nucleoside 2'-deoxyribosyltransferases from psychrophilic and mesophilic bacteria: Insights into cold-adaptation.

Nucleoside 2'-deoxyribosyltransferases (NDTs) catalyze the cleavage of glycosidic bonds of 2'-deoxynucleosides and the following transfer of the 2'-deoxyribose moiety to acceptor nucleobases. Here, we report the crystal structures and biochemical properties of the first tetrameric NDTs: the type I NDT from the mesophilic bacterium Enterococcus faecalis V583 (EfPDT) and the type II NDT from the bacterium Desulfotalea psychrophila (DpNDT), the first psychrophilic NDT. This novel structural and biochemical data permitted an exhaustive comparative analysis aimed to shed light into the basis of the high global stability of the psychrophilic DpNDT, which has a higher melting temperature than EfPDT (58.5 °C versus 54.4 °C) or other mesophilic NDTs. DpNDT possesses a combination of unusual structural motifs not present neither in EfPDT nor any other NDT that most probably contribute to its global stability, in particular, a large aliphatic isoleucine-leucine-valine (ILV) bundle accompanied by a vicinal disulfide bridge and also an intersubunit disulfide bridge, the first described for an NDT. The functional and structural features of DpNDT do not fit the standard features of psychrophilic enzymes, which lead us to consider the implication of (sub)cellular levels together with the protein level in the adaptation of enzymatic activity to low temperatures.

Mandibular osteoma as a cause of ankylosis and progressive trismus.

Osteomas are benign tumours of bone tissue restricted to the craniofacial skeleton. The aim of this article is to present and discuss the demographic and clinical aspects and the management of craniomaxillofacial osteomas. When the patient was submitted from primary care to our hospital, he was 68 years old, and he had ankylosis of the temporomandibular joint for the previos 4 years. A CT scan was performed, finding a giant mandibular osteoma. Conservative treatment and radiological follow-up were carried out with clinical stability. Osteomas more often are seen in the paranasal sinuses and in young adults, with no differences in gender. Most are asymptomatic, but they can cause local problems. For its diagnosis, CT is usually performed. Treatment options are conservative management and follow-up or surgery. Although rarely, they can recur. Mandibular peripheral osteoma is a rare entity. Depending on the symptoms, a conservative or surgical treatment can be chosen. A clinical and radiological follow-up is necessary to detect possible recurrences or enlargement.

Novel Bifunctional Acylase from Actinoplanes utahensis: A Versatile Enzyme to Synthesize Antimicrobial Compounds and Use in Quorum Quenching Processes.

Many intercellular communication processes, known as quorum sensing (QS), are regulated by the autoinducers N-acyl-l-homoserine lactones (AHLs) in Gram-negative bacteria. The inactivation of these QS processes using different quorum quenching (QQ) strategies, such as enzymatic degradation of the autoinducers or the receptor blocking with non-active analogs, could be the basis for the development of new antimicrobials. This study details the heterologous expression, purification, and characterization of a novel N-acylhomoserine lactone acylase from Actinoplanes utahensis NRRL 12052 (AuAHLA), which can hydrolyze different natural penicillins and N-acyl-homoserine lactones (with or without 3-oxo substitution), as well as synthesize them. Kinetic parameters for the hydrolysis of a broad range of substrates have shown that AuAHLA prefers penicillin V, followed by C12-HSL. In addition, AuAHLA inhibits the production of violacein by Chromobacterium violaceum CV026, confirming its potential use as a QQ agent. Noteworthy, AuAHLA is also able to efficiently synthesize penicillin V, besides natural AHLs and phenoxyacetyl-homoserine lactone (POHL), a non-natural analog of AHLs that could be used to block QS receptors and inhibit signal of autoinducers, being the first reported AHL acylase capable of synthesizing AHLs.

Crystalline supramolecular organic frameworks via hydrogen-bonding between nucleobases.

We report a crystalline supramolecular framework assembled by H-bonding interactions between covalently fused monomers equipped with two guanine-cytosine nucleobase pairs.

Elucidating Noncovalent Reaction Mechanisms: G-Quartet as an Intermediate in G-Quadruplex Assembly.

In analogy to covalent reactions, the understanding of noncovalent association pathways is fundamental to influence and control any supramolecular process. Following an approach that is reminiscent of covalent methodologies, we study here, for the first time, the mechanism of G-quadruplex formation in organic solvents. Our results support a reaction pathway in which the cation shifts the equilibrium towards a G-quartet transient intermediate, which then acts as a template in the formation of the G-quadruplex product.

Biochemical properties and biotechnological applications of microbial enzymes involved in the degradation of polyester-type plastics.

Application of polyester-degrading enzymes should be considered as an eco-friendly alternative to chemical recycling due to the huge plastic waste disposal nowadays. Many hydrolases from several fungi and bacteria have been discovered and successfully evaluated for their activity towards different aliphatic polyesters (PHA, PBS, PBSA, PCL, PLA), aromatic polyesters (PET, PBT, PMT) as well as their co-polyesters (PBST, PBAT, PBSTIL). This revision gives an up-to-date overview on the main biochemical features and biotechnological applications of those reported enzymes which are able to degrade polyester-based plastics, including different microbial polyester depolymerases, esterases, cutinase-like enzymes and lipases. Summarized information includes available protein sequences with the corresponding accession numbers deposited in NCBI server, 3D resolved structures, and data about optimal conditions for enzymatic activity and stability of many of these microbial enzymes that would be helpful for researchers in this topic. Although screening and identification of new native polyester hydrolases from microbial sources is undeniable according to literature, we briefly highlight the importance of the design of improved enzymes towards recalcitrant aromatic polyesters through different approaches that include site-directed mutagenesis and surface protein engineering.

Réplica: Síndrome de Guillain-Barré en tiempos de arbovirosis / Reply: Guillain-Barré syndrome in times of arbovirosis

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Gigantism in a McCune-Albright's syndrome with calcified GH-releasing pituitary adenoma: Case report and literature review.

BACKGROUND: McCune-Albright's syndrome (MAS) is a rare disorder that is characterized by café-au-lait macules, fibrous dysplasia of the skull and endocrinopathies like excessive secretion of growth hormone by a hyper-functional pituitary adenoma (PA). CASE: We describe the case of a 43-year-old male with history of Gigantism in 1990 secondary to a GH-secreting pituitary macroadenoma that was treated via microscopic transsphenoidal surgery at that time. He was reported as asymptomatic for 26 years until he developed headache and right temporal hemianopia with left amaurosis. Also ptosis and proptosis was found caused by a re-growth of the tumor on the follow up MRI. A second surgical procedure was performed via a dorsolateral craniotomy. Gross total resection was also achieved with a Neuropathology report of a pituitary adenoma tissue accompanied by extended dystrophic calcification and bone formation. CONCLUSION: This is a rare case of MAS. Gigantism within the context of a pituitary calcification raises special diagnostic and therapeutic challenges. The cause of the excessive secretion of GH in MAS is not well understood concluding that it seems to be a different etiology of patients with Acromegaly and Gigantism in non-MAS patients.

Agentes causales más frecuentes del síndrome de Guillain-Barré en un hospital de Veracruz, México / The most frequent causative agents of Guillain-Barré syndrome in a Mexican general hospital

Introducción. Con posterioridad a la oleada del virus del Zika y el incremento en la incidencia de síndrome de Guillain-Barré (SGB), se ha estudiado la relación causal, pero no se ha encontrado una plena correlación etiológica. Pacientes y métodos. Del 1 de enero al 31 de diciembre de 2017, se incluyeron pacientes con SGB. Además de las serologías básicas, se solicitaron determinaciones de enterovirus, virus del herpes, Campylobacter, hepatitis B y C, TORCH, virus de la inmunodeficiencia humana, Brucella y Salmonella. Resultados. Cohorte de siete pacientes de sexo masculino. A cinco pacientes se les analizó el líquido cefalorraquídeo, que era normal. A todos se les realizó una tomografía encefálica, también normal, y se realizó neuroconducción, que mostró polineuropatía inflamatoria desmielinizante aguda en cuatro casos y neuropatía motora axonal aguda en uno. Todos recibieron inmunoglobulinas intravenosas; tuvieron buen pronóstico cinco casos y hubo dos defunciones. No se informó de casos positivos al virus del Zika. Hubo un caso positivo al dengue, uno al chikungunya, cinco a Campylobacter y uno a enterovirus. Se informó de coinfecciones de dengue + Campylobacter en un caso y de chikungunya + Campylobacter en otro. Conclusiones. La presente cohorte demuestra que no fue posible establecer una relación causal entre el SGB y el virus del Zika, pero se identificaron otros agentes causales víricos y bacterianos, como dengue, chikungunya y enterovirus, y fue aún más destacable la identificación de los casos de Campylobacter

Introduction. After Zika virus outbreak and the increase in the incidence of Guillain-Barré syndrome (GBS), the causal relationship has been studied, however a full etiological correlation has not been found. Patients and methods. From January 1 to December 31, 2017, patients with GBS were included. In addition to the basic serologies, enterovirus, herpes, Campylobacter, hepatitis B and C, TORCH, HIV, Brucella and Salmonella were requested Results. Cohort of seven male patients. Five patients analyzed cerebrospinal fluid reporting normal; all of them underwent brain scan, reporting normal. Neuroconduction was performed, resulting in acute inflammatory demyelinating polyneuropathy in four cases and acute motor axonal neuropathy in one case. All received intravenous immunoglobulins, five cases had a good prognosis and two deaths. No positive cases were reported to Zika virus. A positive case was reported to dengue and another to chikungunya. Five positive cases were reported to Campylobacter. One case positive to enterovirus. Dengue + Campylobacter coinfections were reported in one case and chikungunya + Campylobacter in another case. Conclusions. The present cohort shows that it was not possible to establish a causal relationship between GBS and Zika virus, but other viral and bacterial causal agents were identified, such as dengue, chikungunya and enterovirus, with the identification of Campylobacter cases even more remarkable

Uracil grafted imine-based covalent organic framework for nucleobase recognition.

An imine-based covalent organic framework (COF) decorated in its cavities with uracil groups has shown selective recognition towards adenine in water. These results show how the confinement of the base-pair inside the COF's pores allows a remarkable selective recognition in aqueous media.

Quorum Sensing versus Quenching Bacterial Isolates Obtained from MBR Plants Treating Leachates from Municipal Solid Waste.

Quorum sensing (QS) is a mechanism dependent on bacterial density. This coordinated process is mediated by the synthesis and the secretion of signal molecules, called autoinducers (AIs). N-acyl-homoserine lactones (AHLs) are the most common AIs that are used by Gram-negative bacteria and are involved in biofilm formation. Quorum Quenching (QQ) is the interference of QS by producing hydrolyzing enzymes, among other strategies. The main objective of the present study was to identify QS and QQ strains from MBR wastewater treatment plants. A total of 99 strains were isolated from two Spanish plants that were intended to treat leachate from municipal solid waste. Five AHL producers were detected using AHL biosensor strains (Chromobacterium violaceum CV026 and Agrobacterium tumefaciens NT1). Fifteen strains of seventy-one Gram-positive were capable of eliminating or reducing at least one AHL activity. The analysis of 16S rRNA gene sequence showed the importance of the Pseudomonas genus in the production of biofilms and the relevance of the genus Bacillus in the disruption of the QS mechanism, in which the potential activity of lactonase or acylase enzymes was investigated with the aim to contribute to solve biofouling problems and to increase the useful lifespan of membranes.