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Spalt-like proteins are Zinc finger transcription factors from Caenorhabditis elegans to vertebrates, with critical roles in development. In vertebrates, four paralogues have been identified (SALL1-4), and SALL2 is the family's most dissimilar member. SALL2 is required during brain and eye development. It is downregulated in cancer and acts as a tumor suppressor, promoting cell cycle arrest and cell death. Despite its critical functions, information about SALL2 regulation is scarce. Public data indicate that SALL2 is ubiquitinated and phosphorylated in several residues along the protein, but the mechanisms, biological consequences, and enzymes responsible for these modifications remain unknown. Bioinformatic analyses identified several putative phosphorylation sites for Casein Kinase II (CK2) located within a highly conserved C-terminal PEST degradation motif of SALL2. CK2 is a serine/threonine kinase that promotes cell proliferation and survival and is often hyperactivated in cancer. We demonstrated that CK2 phosphorylates SALL2 residues S763, T778, S802, and S806 and promotes SALL2 degradation by the proteasome. Accordingly, pharmacological inhibition of CK2 with Silmitasertib (CX-4945) restored endogenous SALL2 protein levels in SALL2-deficient breast MDA-MB-231, lung H1299, and colon SW480 cancer cells. Silmitasertib induced a methuosis-like phenotype and cell death in SW480 cells. However, the phenotype was significantly attenuated in CRISPr/Cas9-mediated SALL2 knockout SW480 cells. Similarly, Sall2-deficient tumor organoids were more resistant to Silmitasertib-induced cell death, confirming that SALL2 sensitizes cancer cells to CK2 inhibition. We identified a novel CK2-dependent mechanism for SALL2 regulation and provided new insights into the interplay between these two proteins and their role in cell survival and proliferation.

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Colorectal cancer (CRC) is one of the most common malignant neoplasms and the second leading cause of death from tumors worldwide. Therefore, there is a great need to study new therapeutical strategies, such as effective immunotherapies against these malignancies. Unfortunately, many CRC patients do not respond to current standard immunotherapies, making it necessary to search for adjuvant treatments. Histone deacetylase 6 (HDAC6) is involved in several processes, including immune response and tumor progression. Specifically, it has been observed that HDAC6 is required to activate the Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor involved in immunogenicity, by activating different genes in these pathways, such as PD-L1. Over-expression of immunosuppressive pathways in cancer cells deregulates T-cell activation. Therefore, we focused on the pharmacological inhibition of HDAC6 in CRC cells because of its potential as an adjuvant to avoid immunotolerance in immunotherapy. We investigated whether HDAC6 inhibitors (HDAC6is), such as Nexturastat A (NextA), affected STAT3 activation in CRC cells. First, we found that NextA is less cytotoxic than the non-selective HDACis panobinostat. Then, NextA modified STAT3 and decreased the mRNA and protein expression levels of PD-L1. Importantly, transcriptomic analysis showed that NextA treatment affected the expression of critical genes involved in immunomodulatory pathways in CRC malignancies. These results suggest that treatments with NextA reduce the functionality of STAT3 in CRC cells, impacting the expression of immunomodulatory genes involved in the inflammatory and immune responses. Therefore, targeting HDAC6 may represent an interesting adjuvant strategy in combination with immunotherapy.

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Resumen Introducción: La Meningitis Bacteriana Aguda (MBA) corresponde a la inflamación de las leptomeninges por presencia de bacterias piógenas. La epidemiología es variable y depende multifactorial. A pesar de los avances en medicina la mortalidad de la MBA se ha mantenido estable, evidenciando la necesidad de estudiar esta patología para orientar estrategias de prevención y tratamiento. Objetivos: Determinar la prevalencia de los agentes etiológicos de MBA confirmadas en adultos en el Hospital San Martín de Quillota (HSMQ) entre los años 2012 y 2018. Establecer la tasa de resistencia a antibióticos. Determinar el perfil de los pacientes, y establecer la relación entre perfil, agente etiológico identificado y desenlace. Métodos: c muestra de 38 casos, se estableció la prevalencia de los patógenos involucrados y se realizó un análisis estadístico considerando los factores de riesgo, sus días de estadía y su condición al egreso hospitalario. Resultados: 15 casos en que no se aisló patógeno en LCR (líquido cefalorraquídeo), 13 MBA por neumococo, 4 por Haemophilus spp, 3 por meningococo, 2 por Staphylococcus spp y 1 por Mycobacterium tuberculosis. En el grupo sin agente aislado se observó un mejor pronóstico, valores de PCR (proteína C reactiva) en sangre menores y valores de glucorraquia mayores. Se registraron 6 fallecimientos por MBA. Conclusión: La prevalencia de los agentes etiológicos fue similar a la descrita en la literatura, con neumococo como el microorganismo más frecuente, no se reportaron casos de Listeria monocytogenes. Probablemente en el grupo sin agente aislado se incluyeron casos de meningitis virales.

Introduction: Acute bacterial meningitis (ABM) is denifed as the inflammation of leptomeninges due to the presence of pyogenic bacteriae. Epidemiology is variable and multifactorial. In spite of advance in medicine, ABM's mortality has remained stable, hence the need to study the causative microorganisms in order to guide prevention and treatment strategies. Objectives: To determine the prevalence of the etiological agents of ABM confirmed in adults in a medium complexity hospital located in Quillota, Chile, between 2012 and 2018, to establish the rate of resistance of these to antibiotics. Determine the profile of the patients and establish the relationship between profile, etiological agent identified and outcome. Methods: A sample of 38 cases with ABM was evaluated during, the prevalence of the pathogens involved was established and a statistical analysis was carried out considering the risk factors of patients, their days of in-hospital stay and their condition at hospital discharge. Results: We analyzed 38 cases, 15 without isolated pathogens, 13 of Streptococcus pneumoniae, 4 of Haemophilus spp., 3 of Neisseria meningitidis, 2 of Staphylococcus spp. and we obtained one case of Mycobacterium tuberculosis. In the group without isolated pathogens, a better prognosis was observed, lower blood CRP values and higher glucose on spinal fluid values. 6 deaths per ABM were recorded. Conclusion: The prevalence of etiological agents was similar to that described in the literature, with pneumococcus as the most frequent microorganism, no cases of Listeria monocytogenes were reported. Probably in the group in which no agent was isolated, cases of viral meningitis were included.

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Tetanus is a severe and potentially mortal disease, which affects the Nervous System, caused by the bacteria Clostridium tetani. It's endemic in developing countries, presenting in Chile with a rate of 0,02 cases per 100.000 habitants, but the antitetanic vaccine has reduced its incidence in developed countries. We present here a case report of a patient with generalized tetanus from our hospital. The clinical presentation was characterized by generalized increased muscle tone and trismus, and the patient was hospitalized in the Intensive Care Unit. The neurologic manifestations were important for a period of 3 weeks, but then they started decreasing until the patient was discharged, without complications and being able to sit and walk with assistance. In relation to this case, we will review the actualizations in the subject of Tetanus. The recommended treatment includes support therapy, prevention of complications, antibiotics, muscle relaxants and anti-tetanospasmin immunoglobulin; all therapies that our patient received partially. The disease has a mortality that reaches the 50 percent in some series, but the ones who survive have a good prognosis and full recovery. This is why the presentation of this case is important, being an infrequent disease that must be diagnosed timely and be treated adequately.

Introducción: El tétanos es una enfermedad grave y potencialmente mortal, que afecta al sistema nervioso y causada por la bacteria Clostridium tetani. Es endémica en países en desarrollo, teniendo en Chile el año 2007 una tasa de 0,02 casos por cien mil habitantes. La vacuna con el toxoide antitetánico ha disminuido ostensiblemente su incidencia en países desarrollados. Caso clínico: Se presenta el caso clínico de un paciente de 18 años con tétanos generalizado ingresado a nuestro hospital. Clínicamente se manifestó con un aumento del tono muscular generalizado y trismo. Se hospitalizó en la Unidad de Cuidados Intensivos. Los síntomas y signos neurológicos tuvieron una máxima intensidad de aproximadamente cuatro semanas; posteriormente fueron disminuyendo sin presentar complicaciones severas. Al alta el enfermo lograba sentarse y caminar con ayuda. Discusión: A propósito de este caso se hace una revisión de la literatura y actualización de esta grave enfermedad. El tratamiento recomendado incluye terapia de soporte, prevención de complicaciones, antibioterapia, relajantes musculares e inmunoglobulina antitetánica; terapias que este paciente recibió. Si bien esta enfermedad tiene una letalidad promedio de un 50 por ciento, los pacientes que sobreviven tienen buen pronóstico y recuperación completa. Por ello, la presentación de este caso clínico es importante, sobre todo siendo una condición poco frecuente, que debe diagnosticarse con prontitud y, así, recibir el tratamiento adecuado.

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Background: Central Pontine Myelinolysis (CPM) is the most severe neurological complication after liver transplantation and apparently is not related to changes in osmolarity. Aim: To report five transplanted patients with CPM. Patients and Methods: In a series of 27 patients subjected to liver transplantation between 2005 and 2008, we found five patients who developed CPM. Results: All patients presented a severe hepatic encephalopathy. In the absence of alterations in osmolality, they developed, between the second to seventh day after transplantation, a central quadriplegia, hyperreflexia and Babinski sign, with preservation of sensorium. Magnetic resonance imaging showed demyelination of the motor pathway only in the protuberance. Motor recovery first began in the fingers and hands, followed by forearms, toes, feet, arms and finally the legs, defining a somatotopic recovery of the cortico-spinal pathway. Conclusions: This form of regaining motility shows that the selective involvement of the pyramidal tract in CPM, is according to its location in the pons and suggests a local entrapment. It is due to the structural rigidity of the protuberance that limits the expansive requirements of cytotoxic and vasogenic edema, and only affects the long fibers of cortico-spinal tracts, sensitized by encephalopathy. The entrapment syndromes generally preserve the axons, injure myelin and have no inflammatory reactions.

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BACKGROUND: Central Pontine Myelinolysis (CPM) is the most severe neurological complication after liver transplantation and apparently is not related to changes in osmolarity. AIM: To report five transplanted patients with CPM. PATIENTS AND METHODS: In a series of 27 patients subjected to liver transplantation between 2005 and 2008, we found five patients who developed CPM. RESULTS: All patients presented a severe hepatic encephalopathy. In the absence of alterations in osmolality, they developed, between the second to seventh day after transplantation, a central quadriplegia, hyperreflexia and Babinski sign, with preservation of sensorium. Magnetic resonance imaging showed demyelination of the motor pathway only in the protuberance. Motor recovery first began in the fingers and hands, followed by forearms, toes, feet, arms and finally the legs, defining a somatotopic recovery of the cortico-spinal pathway. CONCLUSIONS: This form of regaining motility shows that the selective involvement of the pyramidal tract in CPM, is according to its location in the pons and suggests a local entrapment. It is due to the structural rigidity of the protuberance that limits the expansive requirements of cytotoxic and vasogenic edema, and only affects the long fibers of cortico-spinal tracts, sensitized by encephalopathy. The entrapment syndromes generally preserve the axons, injure myelin and have no inflammatory reactions.

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Clinically Lafora disease (LD) is an autosomal recessive form of progressive myoclonus epilepsy (PME). It develops due to mutations in gene that encodes laforin or malin, which may be involved in regulating the glycogen metabolism. Pathognomonic Lafora bodies are composed by dense aggregates of polyglucosans inclusions, found in brain and other organs. We describe 18 year old female with family history of myodonic epilepsy. She developed worsening myodonic seizures with correlative electroencephalogram abnormalities and a progressive mental deterioration. Diagnosis was confirmed with periodic acid-schiff (PAS) positive lafora bodies and ubiquitin-positive inmunohistochemical stain, which helped to distinguish from other PAS positive inclusions. This is the first case describe of Lafora disease in Chile.

Clínicamente, la enfermedad de Lafora es una forma de epilepsia mioclónica progresiva, autosómica recesiva. Se desarrolla debido a la mutación del gen que codifica para la laforina y/o la malina, las cuales están involucradas en la regulación del metabolismo del glicógeno. Los corpúsculos de Lafora que identifican la enfermedad están compuestos por agregados densos de poliglicano que se encuentran en inclusiones tanto en el cerebro, como en otros tejidos. Describimos una mujer de 18 años con una historia familiar de epilepsia mioclónica; ella desarrolló crisis mioclónicas que se correlacionaban con anormalidades electroencefalográficas, que empeoraron progresivamente, asociadas a un deterioro cognitivo. El diagnóstico fue confirmado con la presencia de corpúsculos de Lafora encontrados en las glándulas sudoríparas de una biopsia de piel, con tinciones de PAS e inmunohistoquímicas positivos para ubiquitina, lo que permitió distinguir estos corpúsculos de otras inclusiones PAS positivas. Este es el primer caso descrito de enfermedad de Lafora en Chile.

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We report the case of a 44-year-old slaughter-house operator with a skin lesion that had been present for two years on the back of his left hand. The lesion had increased progressively in size despite numerous topical treatments. Physical examination revealed an infiltrated erythematous-violet plaque with a verrucous surface featuring numerous orifices draining purulent material. Histologic study of the lesion disclosed tuberculoid granulomatous infiltrates at the dermoepidermal limit. Presence of Mycobacterium tuberculosis, together with other epidemiologic, clinical, histologic, and immunologic data, permitted a diagnosis of tuberculosis verrucosa cutis to be made. The excellent response of the patient to treatment confirmed this hypothesis. However, polychemotherapy withdrawal was temporarily needed due to analytical abnormalities.

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We report a healthy 16-year-old Caucasian boy, who consulted us for white, asymptomatic lesions in the mouth. The lesions were stable and had been present for 6 years. On physical examination, there were diffuse white, soft, corrugated plaques involving the buccal and labial mucosa, oral commissures, and floor of the mouth. No other mucosae were affected and there were no skin or nail abnormalities. The histologic findings revealed epidermal hyperplasia with parakeratosis and intracellular edema in the squamous cell layer. No nuclear atypia was observed. A differential diagnosis of three entities is proposed: white sponge nevus, leukoedema, and focal epithelial hyperplasia.

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A 12-year-old girl had a lesion located on the upper part of the scalp that was clinically interpreted as a melanocytic nevus and corresponded histologically to a basal cell carcinoma. At age 2 years she had been diagnosed as having acute lymphoblastic leukemia L1, for which she was treated with systemic chemotherapy. She also received telecobalt therapy to the whole cranium for prophylaxis of meningeal leukosis. Having rejected other possible causes that can favor the appearance of basal cell carcinoma during childhood (basal cell nevus syndrome, nevus sebaceus, albinism, etc.), we believe that this case should be added to the five previously reported in the literature as basal cell carcinoma developing at an early age in cranial radiation portals with megavoltage radiotherapy. We draw attention to the need to explore radiated areas of skin as part of the long-term follow-up of these patients, and to the advisability of obtaining a biopsy from any persistent lesion in these areas.

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A 2-month-old boy with an important hardening of the skin in the pubic and genital regions is presented. He was born prematurely at 31 weeks of gestation, and required a respirator during the first 72 h. The analytical explorations and abdominal ultrasound images were normal. Histological study had not shown significant changes. The patient did not receive any treatment and gradually experienced remission. Because of the location and spontaneous regression in a few months, the picture is very similar to the one described by Degos as 'Scléroedème génito-sus-pubien' of the newborn.

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BACKGROUND: Some mixed tumors of the apocrine variety also show characteristics of follicular and/or sebaceous differentiation. This can be explained because of the common embryologic origin of the three structures in the primary epithelial germ of the superficial ectoderm. METHODS: Twenty specimens of apocrine mixed tumors were studied by conventional microscopy. The specimens were evaluated searching for some features of folliculo-sebaceous differentiation. RESULTS: Certain features of folliculo-sebaceous differentiation were found in 45% of the samples examined. Additionally, different tumoral architectures were observed, resembling several well-characterized adnexal organoid neoplasms. In some tumors, there were also follicular structures of mesenchymal origin, similar to the dermal hair papilla and the arrector pili muscle. CONCLUSION: Apocrine mixed tumors of the skin illustrate the ability of pluripotential primordial cells to differentiate in different directions within an individual tumor. Moreover, mixed tumors appear as a compendium of different folliculo-sebaceous neoplasms. We suggest that these proliferations should be interpreted as "complex neoplasms of the primary epithelial germ."

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We report on a female aged 13 years, whose scalp hair began to disappear at the age of 9 years, leaving only sparse wispy hairs in the parietal-occipital region. Eyelashes, eyebrows and body hair were unaffected. There were no signs of ectodermal dysplasia on the skin, nails, teeth and eyes nor other congenital abnormalities. The family pedigree showed 15 relatives similarly affected according to an autosomal dominant mode of transmission. Clinical, genetic, histological and ultrastructural aspects led to a diagnosis of hereditary hypotrichosis simplex of the scalp (Toribio-Quiñones type).

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A 3-year-old boy had maculopapules on his face and neck since age 6 months. These were yellow-brown, asymptomatic, and clinically similar to flat warts. Histopathologic study revealed a fibrohistiocytic infiltrate in the superficial dermis. Ultrastructurally, comma-shaped bodies, desmosome-like junctions, and coated vesicles were seen; there were no lipid droplets or Birbeck granules. With these data, a diagnosis of benign cephalic histiocytosis was made. Twenty-five cases are reported in the literature: 17 males and 8 females (male:female ratio 2:1). Sixteen patients had lesions on parts of the body other than the head, neck, and shoulders.

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