Expression of Surfactant Protein D Distinguishes Severe Pandemic Influenza A(H1N1) from Coronavirus Disease 2019.

The differentiation between influenza and coronavirus disease 2019 (COVID-19) could constitute a diagnostic challenge during the ongoing winter owing to their clinical similitude. Thus, novel biomarkers are required to enable making this distinction. Here, we evaluated whether the surfactant protein D (SP-D), a collectin produced at the alveolar epithelium with known immune properties, was useful to differentiate pandemic influenza A(H1N1) from COVID-19 in critically ill patients. Our results revealed high serum SP-D levels in patients with severe pandemic influenza but not those with COVID-19. This finding was validated in a separate cohort of mechanically ventilated patients with COVID-19 who also showed low plasma SP-D levels. However, plasma SP-D levels did not distinguish seasonal influenza from COVID-19 in mild-to-moderate disease. Finally, we found that high serum SP-D levels were associated with death and renal failure among severe pandemic influenza cases. Thus, our studies have identified SP-D as a unique biomarker expressed during severe pandemic influenza but not COVID-19.

A retrospective study of the clinical phenotype and predictors of survival in non-Caucasian Hispanic patients with amyotrophic lateral sclerosis.

BACKGROUND: Little is known about the clinical phenotype of amyotrophic lateral sclerosis (ALS) in non-Caucasian populations. Here, we aimed to describe the clinical characteristics, prognostic factors and survival of Mexican patients with ALS. METHODS: We conducted a retrospective study by reviewing the medical records of patients with ALS that attended and were regularly followed at a third level hospital in Mexico City from 2000 to 2015. We calculated absolute and relative frequencies of the clinical characteristics from all the participants. We also estimated correlation coefficients between clinical features and overall survival. Additionally, survival rates were compared for all participants grouped according to different clinical features using the Kaplan-Meier method and the log-rank test. RESULTS: We enrolled 45 ALS patients, 53.33% had spinal-onset ALS and 46.66% presented bulbar ALS. The male/female ratio was 0.8. The mean age at onset of symptoms was 58.11 years. Mean survival time from onset was 64.73 ± 34.83 months. Cumulative survival rate after 5 years of disease onset was 44.44%. Age at onset and age at diagnosis inversely correlated with overall survival time. Also, we found that bulbar-onset, short diagnostic delay, percutaneous endoscopic gastrostomy, mechanical ventilation, and lower total cholesterol serum levels were associated with short survival. CONCLUSIONS: The clinical characteristics of Mexican ALS patients differ from the disease phenotype observed in Caucasians. Nonetheless, the predictive value of certain well-recognized prognostic factors remains consistent in our population. The current study provides relevant information for a better understanding of prognostic factors in ALS patients from Mexico and other Latin American countries.

Comparison of perioperative outcomes in obese and non-obese patients subjected to open lumbar spine surgery.

OBJECTIVE: Obesity is a global epidemic affecting developing countries. The relationship between obesity and perioperative outcomes during elective lumbar spine surgery remains controversial, especially in those without morbid disease. MATERIALS AND METHODS: We retrospectively revised the medical records of patients with lumbar spine degeneration subjected to elective surgery. The data retrieved included demographic and clinical characteristics, body mass index (BMI), obesity status (BMI ≥ 30), surgical interventions, estimated blood loss (EBL), operative time, length of stay (LOS), and post-operative complications. Perioperative outcomes were compared between Grade I-II obese and non-obese individuals. RESULTS: We enrolled 53 patients, 18 with Grade I-II obesity. Their median age was 51, with no differences in gender, comorbidities, laboratory parameters, and surgical procedures received between groups. No clinically relevant differences were found between grade I-II obese and non-obese participants in EBL (300 mL vs. 250 mL, p = 0.069), operative time (3.2 h vs. 3.0 h, p = 0.037), and LOS (6 days vs. 5 days, p = 0.3). Furthermore, BMI was not associated with the incidence of significant bleeding and long stay but showed a modest correlation with operative time. CONCLUSION: Grade I-II obesity does not increase surgical complexity nor perioperative complications during open lumbar spine surgery.

OBJETIVO: La obesidad es una epidemia mundial que afecta a países subdesarrollados. Su relación con los resultados de la cirugía de columna lumbar electiva sigue siendo controvertida, especialmente en obesos sin enfermedad mórbida. MÉTODOS: Se revisaron los expedientes de pacientes con degeneración de la columna lumbar sometidos a cirugía. Los datos recuperados incluyeron características demográficas y clínicas, índice de masa corporal (IMC), estado de obesidad (IMC > 30), intervenciones quirúrgicas, sangrado estimado, tiempo operatorio, tiempo de estancia y complicaciones. Los resultados se compararon entre individuos obesos grado I-II y controles. RESULTADOS: Se incluyeron 53 pacientes, 18 con obesidad de grado I-II. La edad media fue de 51 años, sin diferencias en el sexo, las comorbilidades, los parámetros de laboratorio y los procedimientos quirúrgicos recibidos entre grupos. No se encontraron diferencias relevantes entre los participantes obesos y los no obesos en sangrado (300 vs. 250 mL, p = 0.069), tiempo operatorio (3.2 vs. 3.0 horas, p = 0.037) y estancia (6 vs. 5 días, p = 0.3). El IMC no se asoció con hemorragia y larga estancia, pero mostró una correlación modesta con el tiempo operatorio. CONCLUSIONES: La obesidad grado I-II no predispone a complicaciones durante la cirugía de columna lumbar.

The rs11684747 and rs55790676 SNPs of ADAM17 influence tuberculosis susceptibility and plasma levels of TNF, TNFR1, and TNFR2.

Introduction: The proteolytic activity of A Disintegrin and Metalloproteinase 17 (ADAM17) regulates the release of tumor necrosis factor (TNF) and TNF receptors (TNFRs) from cell surfaces. These molecules play important roles in tuberculosis (TB) shaping innate immune reactions and granuloma formation. Methods: Here, we investigated whether single nucleotide polymorphisms (SNPs) of ADAM17 influence TNF and TNFRs levels in 224 patients with active TB (ATB) and 118 healthy close contacts. Also, we looked for significant associations between SNPs of ADAM17 and ATB status. TNF, TNFR1, and TNFR2 levels were measured in plasma samples by ELISA. Four SNPs of ADAM17 (rs12692386, rs1524668, rs11684747, and rs55790676) were analyzed in DNA isolated from peripheral blood leucocytes. The association between ATB status, genotype, and cytokines was analyzed by multiple regression models. Results: Our results showed a higher frequency of rs11684747 and rs55790676 in close contacts than ATB patients. Coincidentally, heterozygous to these SNPs of ADAM17 showed higher plasma levels of TNF compared to homozygous to their respective ancestral alleles. Strikingly, the levels of TNF and TNFRs distinguished participant groups, with ATB patients displaying lower TNF and higher TNFR1/TNFR2 levels compared to their close contacts. Conclusion: These findings suggest a role for SNPs of ADAM17 in genetic susceptibility to ATB.

Demographic and Clinical Characteristics of Patients With Cervical Spine Degeneration Reveal Frequent Cervicolumbar Tandem Spinal Stenosis in Mexico.

BACKGROUND: Limited literature exists regarding the differences in demographics, causes, comorbidities, presentation, and structural changes associated with cervical spine degeneration in patients from distinct geographic regions. The authors aimed to evaluate the demographic and clinical characteristics of patients with cervical spine degeneration admitted to a single center in Mexico. METHODS: This study enrolled patients with degenerative disease of the cervical spine. Clinical data were retrieved from medical records and retrospectively characterized. RESULTS: A total of 50 patients with cervical spine degeneration were included in the analysis. Of these, 26% were men with a median age of 54 years. Hypertension, depression, anxiety, obesity, and alcohol consumption were presented in about a quarter of the participants. In addition, we observed hypertriglyceridemia and hypercholesterolemia in 72% and 46% of participants, respectively. The median duration of symptoms was 11 months, including radicular arm/neck pain (80%), tingling (80%), reduced muscle strength (48%), and gait disturbances (48%). Forty percent of patients had 2 cervical segments radiologically involved, mainly at C5-C6, with changes such as disc herniation (88%), foraminal stenosis with nerve root compression (67%), reduced spinal canal-to-vertebral body ratio (38%), and ligamentum flavum hypertrophy (24%). Also, 22% of patients showed degenerative cervical myelopathy. Strikingly, 48% of enrolled individuals showed cervicolumbar tandem spinal stenosis, mainly in L4-L5 and L5-S1, who were generally older, had a longer duration of symptoms, and had a higher comorbidity burden, including hyperglycemia, hypertension, and depression. CONCLUSIONS: The demographic and clinical characteristics of degenerative cervical spine disease in Mexico differ with respect to other geographical regions by a younger age of diagnosis, a high frequency of cardiovascular, metabolic, and mental health comorbidities, and an increased prevalence of concomitant lumbar spinal stenosis. CLINICAL RELEVANCE: Our findings reveal a considerably high burden of cervicolumbar tandem spinal stenosis as a distinctive feature of Mexican patients with cervical spine degeneration.

[Transcultural adaptation and validation of the DASH questionnaire in Mexican healthy volunteers and patients with neurogenic disorders of the upper extremity]. / Adaptación transcultural y validación de la versión mexicana del cuestionario DASH en individuos sanos y pacientes con trastornos neurogénicos del miembro superior.

Background: The Disability of the Arm, Shoulder and Hand (DASH) questionnaire assesses the impact of upper extremity disorders on quality of life. However, its use in the Mexican population has not been formally validated. Objective: To conduct a cultural adaptation and validation of the DASH questionnaire to evaluate the perspective of patients with neurogenic disorders of the upper extremity regarding the impact on their quality of life. Method: We performed an adaptation of the Spanish version of the DASH questionnaire to the Mexican vocabulary and applied it to 478 volunteers. Ceiling effect, floor effect, item-total correlation, descriptive statistics of items and total score, internal consistency, precision, cross-sectional and longitudinal validity were estimated by comparing healthy controls and affected individuals with different disability levels. Results: Our DASH questionnaire version was equivalent to those previously approved and showed homogeneity of the items with respect to the total value of the questionnaire (Cronbach's alpha > 0.96). In addition, it showed an accuracy of 7.25 points and the crosssectional and longitudinal validity was documented with significant differences between groups and subgroups with distinct disability levels. Conclusions: The DASH questionnaire can be used with a high level of confidence in the Mexican population.

Antecedentes: El cuestionario de discapacidad de brazo, hombro y mano (DASH, Disabilities of the Arm, Shoulder and Hand) mide el impacto de patologías del miembro superior en la calidad de vida. Sin embargo, su uso en la población mexicana no ha sido formalmente validado. Objetivo: Realizar la adaptación cultural y validación del cuestionario DASH para conocer la perspectiva de pacientes con trastornos neurogénicos del miembro superior respecto al impacto en su calidad de vida. Método: Se realizó una adaptación al vocabulario mexicano de la versión española del cuestionario DASH y se aplicó en 478 voluntarios. Se estimaron el efecto techo, el efecto suelo, la correlación ítem-total, las medidas de tendencia central de ítems y el puntaje total, la consistencia interna, la precisión y la validez transversal y longitudinal mediante la comparación de individuos sanos y enfermos con diferente nivel de discapacidad. Resultados: Nuestra versión del cuestionario DASH resultó equivalente a las previamente aprobadas y mostró homogeneidad de los ítems respecto al valor total del cuestionario (alfa de Cronbach > 0.96). Además, tuvo una precisión de 7.25 puntos y se documentó la validez transversal y longitudinal con diferencias significativas entre grupos y subgrupos con diferente nivel de discapacidad. Conclusiones: El cuestionario DASH puede ser empleado con un nivel de confianza alto en la población mexicana.

Resection of a rare giant chondromesenchymal hamartoma of the scalp with intracranial blood supply in an adult woman: illustrative case.

BACKGROUND: Nasal chondromesenchymal hamartomas (NCMHs) are benign, slow-growing lesions formed by mesenchymal and cartilaginous components. They occur predominantly in male infants at the nasopharynx and orbit. Rare cases have been reported in adults. Ectopic NCMHs occurring in other head regions without the typical nasopharyngeal or orbital involvement have not been previously described. OBSERVATIONS: The authors presented the case of a 40-year-old woman with a giant mass in the left frontoparietal region that started to enlarge progressively after the patient's first pregnancy at the age of 21 years. The tumor caused intense headaches, nausea, vomiting, asthenia, and syncope. On admission, the neurological examination revealed no abnormalities. Brain magnetic resonance imaging showed a solid homogeneous tumor without intraaxial involvement extending inferiorly to the left zygomatic arch, with a significant mass effect on the adjacent bones but no infiltration. Remarkably, digital subtraction angiography demonstrated that the tumor received blood supply from superficial as well as intracranial branches of the left vertebral artery. After tumor resection, histopathological analysis revealed characteristics indistinguishable from an NCMH. LESSONS: The authors described a rare NCMH of the scalp with intracranial blood supply in an adult patient. A case with similar characteristics had not been reported before.

Nerve preservation during partial sacrectomy by two-stage anterior and posterior approach: illustrative case.

BACKGROUND: Preserving the neurological function of sacral nerves during total or partial sacrectomy is challenging. OBSERVATIONS: The authors describe a case of an osseous desmoplastic fibroma of the sacrum in a 51-year-old woman. The patient attended the authors' institution with loss of muscle strength and sensitivity impairment in both legs, gait instability, bowel constipation, urinary incontinence, and weight loss. Preoperative magnetic resonance imaging and positron emission tomography/computed tomography showed intrapelvic and posterior extension of the tumor but sparing of S1 and the sacroiliac and lumbosacral joints. After a multidisciplinary discussion of the case, a staged anterior-posterior approach to the sacrum was chosen. The abdominal approach allowed full mobilization of the uterus, ovaries, bladder, and colon and protection of iliac vessels. After tumor resection, a synthetic surgical mesh was placed over the sacrum to minimize soft tissue defects. Then, the posterior stage allowed the authors to perform a bicortical osteotomy, achieving wide tumor excision with minimal nerve root injury. Spinopelvic fixation was not necessary, because both sacroiliac and lumbosacral joints remained intact. A few days after the surgery, the patient restarted ambulation and recovered sphincter control. LESSONS: Multidisciplinary planning and a staged abdominal and posterior approach for partial sacrectomy were fundamental to preserve neurological function in this case.

The pterional approach for the surgical resection of an orbital cholesteatoma: a case report.

BACKGROUND: Cholesteatomas are benign tumors mainly composed of cholesterol crystals that rarely arise within the orbit. However, orbital cholesteatomas require a complete surgical resection due to their recidivating potential. Transcranial approaches offering a broad surgical exposure of the orbital cavity have been scarcely used for the management of these tumors. Here, we provide evidence of the benefits of the pterional craniotomy for the surgical resection of orbital tumors by sharing our experience in the surgical management of a cholesteatoma of the superotemporal orbital wall. CASE PRESENTATION: A 45-year-old Hispanic man with a 2-year history of progressive proptosis of the left eye attended to our center complaining of diplopia and migraine. At his arrival, physical examination revealed ptosis, palpebral edema, and exophthalmos of the left eye, as well as the abolishment of the ipsilateral photomotor and consensual responses. Fundoscopy showed mild optic atrophy, whereas a T2-weighted magnetic resonance imaging (MRI) of the head showed a hyperintense mass arising at the superotemporal wall of the orbit that was displacing the eyeball. The tumor was resected using a pterional craniotomy without postoperative complications. The histopathological analysis of the tumor revealed a cholesteatoma. The patient recovered the functionality of the left eye with no visual sensitive deficits nor tumor recurrence 1 year after the surgery. CONCLUSIONS: Our results support the use of the pterional craniotomy as a safe procedure for the surgical resection of cholesteatomas arising at the superotemporal walls of the orbit, with low postoperative morbidity.

Atypical Association of Autoimmune Limbic Encephalitis with Anti-NMDA Receptor Antibodies in a Young Male Patient: Clinical, Imaging, and Neuropsychological Characteristics.

The spectrum of autoimmune encephalitis (AE) encompasses several entities characterized by a variable frequency of psychiatric symptoms, cognitive dysfunction, focal deficits, and seizures. Although patients with AE can be categorized in specific syndromes, overlapping manifestations are also common. Furthermore, atypical correlations between clinical phenotypes and autoantibody profiles could occur in rare cases. Here, we report the rare case of a young adult man attending due to new-onset seizures and a history of memory loss, autonomic disturbances, headache, behavioral changes, and visual and olfactory hallucinations. The patient was subjected to a complete diagnostic approach that included a comprehensive laboratory workup, neuropsychological testing, electroencephalogram, cerebrospinal fluid (CSF) analysis, brain MRI, and positron emission tomography/computed tomography scan that revealed a functional and structural compromise of the bilateral medial temporal lobes. Together with the clinical manifestations of the patient, these findings were compatible with the diagnosis of autoimmune limbic encephalitis (ALE). Strikingly, further analysis of the CSF showed autoantibodies against the N-methyl-D-aspartate (NMDA) receptor. We found very few cases of the co-occurrence of anti-NMDA receptor antibodies and nonparaneoplastic ALE in the literature, especially in male patients. Our report exemplifies the complicated differential diagnosis of ALE and adds clinical information of the association with anti-NMDA receptor antibodies.

Chronic subclinical spondylotic myelopathy exacerbated by COVID-19: A case report.

INTRODUCTION: Besides typical respiratory symptoms, the coronavirus disease 2019, also known as COVID-19, is characterized by a wide range of neurological symptoms that result from the injury of the brain and peripheral nerves. Only a few reports have described the involvement of the spinal cord among COVID-19 patients. Furthermore, little is known about the risk of individuals with chronic degenerative conditions of the spine for acute neurological complications of COVID-19. CASE PRESENTATION: Here, we describe the case of a 73-year-old man with a subclinical cervical multifocal spondylotic myelopathy that manifested neurological symptoms of spinal cord injury only some days after getting infected with SARS-CoV-2. The patient did not show any data associated with respiratory involvement and improved clinically after decompressive spinal surgery and administration of steroids. CONCLUSIONS: This is the first reported case of an acute exacerbation of a chronic degenerative condition of the spine caused by COVID-19.

Beneficial effects of a multidomain cognitive rehabilitation program for traumatic brain injury-associated diffuse axonal injury: a case report.

BACKGROUND: Neuropsychological rehabilitation is a crucial component of medical care for patients with diffuse axonal injury (DAI). However, current cognitive intervention programs directed to favor the training of specific domains individually have shown controversial results. Here, we evaluated the effectiveness of a neuropsychological rehabilitation program directed to favor training of attention, memory, visuospatial abilities, and executive functioning together in a patient with severe traumatic brain injury (TBI)-associated DAI. CASE PRESENTATION: A 26-year-old Hispanic woman with a recent history of a severe TBI attended our center complaining of memory problems, dysarthria, and difficulty in planning. A comprehensive cognitive assessment revealed dysfunction in sustained, selective, and divided attention, alterations in memory, planning, and organization of executive behavior, as well as impairment of visuospatial cognitive functions. The patient underwent a 24-week neuropsychological rehabilitation program directed to favor attention, memory, visuospatial abilities, and executive functioning together. After the cognitive intervention, we observed a better patient's performance in tasks requiring sustained, selective, and divided attention, improvement of encoding and retrieval memory problems, use of spatial relationships, planning, and organization of behavior skills. We also observed generalization effects on other domains, such as learning, mental flexibility, inhibition functions, and language. CONCLUSIONS: In conclusion, our results suggest that neuropsychological rehabilitation programs favoring multiple domains together are useful in reestablishing cognitive deficits in patients with severe DAI.

Tau Protein Phosphorylated at Threonine-231 is Expressed Abundantly in the Cerebellum in Prion Encephalopathies.

BACKGROUND: Transmissible spongiform encephalopathies (TSEs) are rare neurodegenerative disorders that affect animals and humans. Bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeld-Jakob Disease (CJD) in humans belong to this group. The causative agent of TSEs is called "prion", which corresponds to a pathological form (PrPSc) of a normal cellular protein (PrPC) expressed in nerve cells. PrPSc is resistant to degradation and can induce abnormal folding of PrPC, and TSEs are characterized by extensive spongiosis and gliosis and the presence of PrPSc amyloid plaques. CJD presents initially with clinical symptoms similar to Alzheimer's disease (AD). In AD, tau aggregates and amyloid-ß protein plaques are associated with memory loss and cognitive impairment in patients. OBJECTIVE: In this work, we study the role of tau and its relationship with PrPSc plaques in CJD. METHODS: Multiple immunostainings with specific antibodies were carried out and analyzed by confocal microscopy. RESULTS: We found increased expression of the glial fibrillary acidic protein (GFAP) and matrix metalloproteinase (MMP-9), and an exacerbated apoptosis in the granular layer in cases with prion disease. In these cases, tau protein phosphorylated at Thr-231 was overexpressed in the axons and dendrites of Purkinje cells and the extensions of parallel fibers in the cerebellum. CONCLUSION: We conclude that phosphorylation of tau may be a response to a toxic and inflammatory environment generated by the pathological form of prion.

Phenotype of Peripheral NK Cells in Latent, Active, and Meningeal Tuberculosis.

The mechanisms underlying the immunopathology of tuberculous meningitis (TBM), the most severe clinical form of extrapulmonary tuberculosis (TB), are not understood. It is currently believed that the spread of Mycobacterium tuberculosis (Mtb) from the lung is an early event that occurs before the establishment of adaptive immunity. Hence, several innate immune mechanisms may participate in the containment of Mtb infection and prevent extrapulmonary disease manifestations. Natural killer (NK) cells participate in defensive processes that distinguish latent TB infection (LTBI) from active pulmonary TB (PTB). However, their role in TBM is unknown. Here, we performed a cross-sectional analysis of circulating NK cellCID="C008" value="s" phenotype in a prospective cohort of TBM patients (n = 10) using flow cytometry. Also, we addressed the responses of memory-like NK cell subpopulations to the contact with Mtb antigens in vitro. Finally, we determined plasma levels of soluble NKG2D receptor ligands in our cohort of TBM patients by enzyme-linked immunosorbent assay (ELISA). Our comparative groups consisted of individuals with LTBI (n = 11) and PTB (n = 27) patients. We found that NK cells from TBM patients showed lower absolute frequencies, higher CD69 expression, and poor expansion of the CD45RO+ memory-like subpopulation upon Mtb exposure in vitro compared to LTBI individuals. In addition, a reduction in the frequency of CD56brightCD16- NK cells characterized TBM patients but not LTBI or PTB subjects. Our study expands on earlier reports about the role of NK cells in TBM showing a reduced frequency of cytokine-producing cells compared to LTBI and PTB.

Corrigendum: CXCL17 Is a Specific Diagnostic Biomarker for Severe Pandemic Influenza A(H1N1) That Predicts Poor Clinical Outcome.

[This corrects the article DOI: 10.3389/fimmu.2021.633297.].

CXCL17 Is a Specific Diagnostic Biomarker for Severe Pandemic Influenza A(H1N1) That Predicts Poor Clinical Outcome.

The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.

Isolated agenesis of the corpus callosum and normal general intelligence development during postnatal life: a case report and review of the literature.

BACKGROUND: Agenesis of the corpus callosum can occur isolated or as part of a complex congenital syndrome. Patients with isolated agenesis of the corpus callosum may present with severe intellectual disability, although a proportion of affected individuals develop normal intelligence. However, even in patients with no apparent deficits, subtle neuropsychological alterations may occur as the cognitive demand increases with age. Hence, patients with this deffect require a strict follow-up during their postnatal life. Thus, physicians require a better knowledge of the cognitive features of agenesis of the corpus callosum to improve their approach to this cerebral malformation. Here, we report an illustrative case of a school-age child with isolated agenesis of the corpus callosum and normal intelligence. We also provide a literature review about the postnatal screening of neurocognitive deficits in patients with agenesis of the corpus callosum. CASE PRESENTATION: An 8-year-old Hispanic boy with total agenesis of the corpus callosum attended for medical follow-up. The defect was identified during the neonatal period by cranial ultrasonography and brain computed tomography scan. However, he did not present any craniofacial or non-cerebral malformation suggestive of a congenital syndrome. Furthermore, he showed no neuropsychiatric disorder or intellectual disability during his early childhood. At the age of 4, he was subjected to a control brain magnetic resonance imaging that showed total agenesis of the corpus callosum and colpocephaly. At his arrival, a neurological examination was normal with no signs of intracranial hypertension. His intelligence quotient was unaltered and he scored normal in the Mini-Mental State Examination test. The literature reviewed here suggested that patients with agenesis of the corpus callosum require a strict neurocognitive follow-up during postnatal life, as they may present neuropsychological deficits during adolescence, when development of the corpus callosum is completed and there is maximum reliance on this structure. Thus, our patient was scheduled for future annual neurocognitive testing. CONCLUSIONS: Isolated agenesis of the corpus callosum is not innocuous, and patients with this defect require a strict neurocognitive follow-up. We provide an informative reference tool useful for the postnatal neuropsychological screening of patients with isolated agenesis of the corpus callosum.

A Complete and State of the Art Pre-mortem Diagnostic Approach to Creutzfeldt-Jakob Disease: A Case Report.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal and rapidly progressive form of dementia caused by the spread of a prion protein within the brain. Its real incidence is unknown since its definitive diagnosis requires histopathological analysis of brain specimens. However, novel tests that detect prion proteins in cerebrospinal fluid samples, such as the real-time quaking-induced conversion (RT-QuIC) technique, now allow the pre-mortem diagnosis of sCJD. Here, we report the first case of sCJD confirmed by RT-QuIC in Latin America, providing evidence of its diagnostic performance and clinical correlation.

Neurological Aspects of SARS-CoV-2 Infection: Mechanisms and Manifestations.

The human infection of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern that has caused more than 16.8 million new cases and 662,000 deaths as of July 30, 2020. Although coronavirus disease 2019 (COVID-19), which is associated with this virus, mainly affects the lungs, recent evidence from clinical and pathological studies indicates that this pathogen has a broad infective ability to spread to extrapulmonary tissues, causing multiorgan failure in severely ill patients. In this regard, there is increasing preoccupation with the neuroinvasive potential of SARS-CoV-2 due to the observation of neurological manifestations in COVID-19 patients. This concern is also supported by the neurotropism previously documented in other human coronaviruses, including the 2002-2003 SARS-CoV-1 outbreak. Hence, in the current review article, we aimed to summarize the spectrum of neurological findings associated with COVID-19, which include signs of peripheral neuropathy, myopathy, olfactory dysfunction, meningoencephalitis, Guillain-Barré syndrome, and neuropsychiatric disorders. Furthermore, we analyze the mechanisms underlying such neurological sequela and discuss possible therapeutics for patients with neurological findings associated with COVID-19. Finally, we describe the host- and pathogen-specific factors that determine the tissue tropism of SARS-CoV-2 and possible routes employed by the virus to invade the nervous system from a pathophysiological and molecular perspective. In this manner, the current manuscript contributes to increasing the current understanding of the neurological aspects of COVID-19 and the impact of the current pandemic on the neurology field.

PHF-Core Tau as the Potential Initiating Event for Tau Pathology in Alzheimer's Disease.

Worldwide, around 50 million people have dementia. Alzheimer's disease (AD) is the most common type of dementia and one of the major causes of disability and dependency among the elderly worldwide. Clinically, AD is characterized by impaired memory accompanied by other deficiencies in the cognitive domain. Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) are histopathological lesions that define brains with AD. NFTs consist of abundant intracellular paired helical filaments (PHFs) whose main constituent is tau protein. Tau undergoes posttranslational changes including hyperphosphorylation and truncation, both of which favor conformational changes in the protein. The sequential pathological processing of tau is illustrated with the following specific markers: pT231, TG3, AT8, AT100, and Alz50. Two proteolysis sites for tau have been described-truncation at glutamate 391 and at aspartate 421-and which can be demonstrated by reactivity with the antibodies 423 and TauC-3, respectively. In this review, we describe the molecular changes in tau protein as pre-NFTs progress to extracellular NFTs and during which the formation of a minimal nucleus of the filament, as the PHF core, occurs. We also analyzed the PHF core as the initiator of PHFs and tau phosphorylation as a protective neuronal mechanism against the assembly of the PHF core.