Toxoplasmosis outbreak in São Paulo, Brazil: Epidemiology and visual outcome

ABSTRACT Purpose: To describe a 2019 acute toxoplasmosis outbreak in the city of São Paulo, Brazil, and to evaluate the laboratory serological profile for toxoplasmosis for three consecutive years. The ophthalmological manifestations of the patients involved in the outbreak were also studied. Methods: A cross-sectional descriptive study of a toxoplasmosis outbreak in São Paulo, Brazil, between February and May 2019. Epidemiological data were described, as were the observed ocular manifestations. As part of this study the number of patients with positive IgM toxoplasmosis serology was obtained from a large laboratory network (DASA) for three consecutive years, including the year of the outbreak (2018, 2019, 2020). Results: Eighty-three individuals were identified in the outbreak and two clusters were studied. The clinical picture of at least 77% of the patients, the epidemiological analysis, and the short incubation period (5-8 days) suggested contamination by oocysts. Serological laboratory data analysis revealed an increase of positive toxoplasmosis IgM in 2019 of 73% compared to the previous year. Ophthalmological examination revealed that at least 4.8% of the patients developed toxoplasmic retinochoroiditis, none of whom had been treated during the acute systemic disease. Conclusion: Our findings indicate vegetable contamination as the possible source of this outbreak, a high prevalence of toxoplasmosis in São Paulo during the outbreak period, and a drop in the number of tests during the COVID-19 pandemic. Retinochoroiditis was observed in at least 4.8% of the cases. We confirm the need to implement effective means for the prevention, diagnosis, and treatment of the disease. This may involve raising awareness among the population of the importance of vegetable hygiene, and improved quality control of food and water.

20% Autologous serum vs. 0.05% cyclosporine and preservative-free artificial tears in the treatment of Sjögren related dry eye / Soro autólogo a 20% versus ciclosporina a 0,05 e lubrificantes oculares sem conservantes no tratamento da síndrome do olho seco relacionada à Sjögren

ABSTRACT Purpose: To compare the 3-month results of treatment with 20% autologous serum or combination treatment with preservative-free artificial tears and 0.05% cyclosporine in patients with dry eye disease due to primary Sjögren's syndrome. Methods: A total of 130 eyes of 65 patients with newly diagnosed dry eye disease due to primary Sjögren's syndrome were included in the study. The patients were divided into two treatment groups: 66 eyes of 33 patients were assigned to the autologous serum treatment group, and 64 eyes of 32 patients were assigned to the combination treatment group. Schirmer test, tear break-up time and Ocular Surface Disease Index (OSDI) scores were recorded at pretreatment and at 3 months of treatment. Results: At 3 months of treatment, the mean Schirmer value and the mean tear break-up time were significantly higher in the combination treatment group (p<0.0001 and p=0.034, respectively). The OSDI score at 3 months was significantly lower in the autologous serum Group (p=0.004). When the two groups were evaluated separately, the improvements in Schirmer, tear break-up time test, and OSDI scores from before to after treatment were statistically significant: p<0.0001, p<0.001, and p<0.0001, respectively, for the authologus serum Group, and p<0.0001, p<0.001, and p<0.0001, respectively, for the combination treatment group. Conclusions: In short-term treatment of dry eye disease due to primary Sjögren's syndrome, treatment with autologous serum was significantly superior to -combination treatment with preservative-free artificial tears and 0.05% cyclosporine in terms of improvement in OSDI scores. Improvements in Schirmer test and tear break-up time scores were significantly superior in the group treated with preservative-free artificial tears and 0.05% cyclosporine.

RESUMO Objetivo: Comparar os resultados de 3 meses de soro autólogo a 20% com um tratamento combinado, ou seja, lubrificantes oculares sem conservantes e ciclosporina a 0,05% em pacientes com síndrome do olho seco devida à síndrome de Sjögren primária. Métodos: Foram incluídos no estudo 130 olhos de 65 pacientes recentemente diagnosticados com síndrome do olho seco devida à síndrome de Sjögren primária. Os pacientes foram divididos em dois grupos de tratamento, 66 olhos de 33 pacientes foram incluídos no grupo de tratamento com soro autólogo e 64 olhos de 32 pacientes foram incluídos no grupo de tratamento combinado com lubrificantes oculares sem conservantes e ciclosporina. Os resultados do teste de Schirmer e do tempo de ruptura do filme lacrimal e os índices de doença da superfície ocular (OSDI) foram registrados antes e depois de três meses de tratamento. Resultados: Três meses após o tratamento, o valor médio do teste de Schirmer foi mais alto com significância estatística no grupo do tratamento combinado com lubrificantes oculares sem conservantes e ciclosporina (p<0,0001) e o tempo de ruptura do filme lacrimal também foi significativamente maior nesse grupo (p=0,034). Também aos três meses, a doença da superfície ocular foi menor com significância estatística no grupo de tratamento com soro autólogo (p=0,004). Quando os dois grupos foram avaliados separadamente, a melhora no teste de Schirmer, o tempo de ruptura e a doença da superfície ocular antes e depois do tratamento tiveram diferenças estatisticamente significativas tanto no grupo de soro autólogo (p<0,0001, p<0,001 e p<0,0001, respectivamente) quanto no grupo de tratamento combinado (p<0,0001, p<0,001 e p<0,0001, respectivamente). Conclusões: No tratamento de curto prazo da síndrome do olho seco devida à síndrome de Sjögren primária, o tratamento com soro autólogo foi significativamente superior ao tratamento com lubrificantes oculares sem conservantes combinados com ciclosporina, em termos de melhora no doença da superfície ocular. As melhoras no teste de Schirmer e no tempo de ruptura do filme lacrimal foram significativamente maiores no grupo de tratamento combinado com lubrificantes oculares sem conservantes e ciclosporina.

Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population

Abstract Background In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants. Methods SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression. Results There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05). Conclusions Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA. Key Points Genetic variants of WNT9A were associated with the incidence and severity of TOA. Allele G of rs11588850 was associated with an increased transcriptional activity of WNT9A promoter. Allele G of rs11588850 may add to the risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.

Caracterización de los pacientes con cáncer bucal en el Hospital Provincial Docente Oncológico María Curie de Camagüey

Introducción: El cáncer bucal continúa siendo una de las neoplasias malignas en ascenso, de acuerdo con su incidencia y el importante número de muertes cada año. En este sentido, se han desarrollado programas de salud para la población que garantizan la pesquisa, la prevención y la atención de las enfermedades. Objetivo: Caracterizar a los pacientes con cáncer bucal en el Hospital Provincial Docente Oncológico María Curie de la provincia Camagüey durante el período 2018-2022. Métodos: Se realizó un estudio descriptivo transversal en el Hospital Provincial Docente Oncológico María Curie de la provincia Camagüey en un universo de 218 pacientes, que acudieron al Servicio de Cirugía de Cabeza y Cuello del año 2018 al 2022 y tuvieron como diagnóstico cáncer bucal. La muestra se delimitó a 113 pacientes que cumplieron con los criterios de inclusión y exclusión. Resultados: El cáncer bucal predominó en el sexo masculino con 89 (78,76 %) en los años 2019 y 2021. Hubo mayor frecuencia en pacientes de piel blanca con 97 (85,84 %) y el año 2021 mostró mayor número de estos enfermos. La lengua fue la más afectada con 43 (30,05 %) pacientes, seguida por el suelo de boca en 18 (15,92 %) y las encías en 17 (15,04 %) pacientes. Según el estadio existió un predominio del IV en 61 (53,98 %) enfermos, seguido por el III con un 18,58 % de pacientes diagnosticados. Conclusiones: Prevaleció del sexo masculino en el grupo de 60 a 79 años y los pacientes de piel blanca fueron los más afectados. La localización de las lesiones se manifestó con mayor incidencia en la lengua y los estadios IV y III de la enfermedad son los más representativos en el momento del diagnóstico.

Introduction: Oral cancer continues to be one of the malignant neoplasms on the rise, according to its incidence and the significant number of deaths each year. In this sense, health programs have been developed for the population that guarantee screening, prevention and care of the diseases. Objective: To characterize patients with oral cancer at the María Curie Oncological Teaching Provincial Hospital in Camagüey province during the period 2018-2022. Methods: A cross-sectional descriptive study was carried out in the María Curie Oncological Teaching Provincial Hospital of Camagüey province in a universe of 218 patients, who attended the Head and Neck Surgery Service from 2018 to 2022 and had oral cancer as diagnosis. The sample was limited to 113 patients who met the inclusion and exclusion criteria. Results: Oral cancer predominated in the male sex with 89 (78.76%) in the years 2019 and 2021. There was a higher incidence in patients with white skin with 97 (85.84%) and the year 2021 showed a higher number of these patients. The tongue was the most affected with 43 (30.05%) patients, followed by the floor of the mouth in 18 (15.92%) and the gums in 17 (15.04%) patients. According to stage there was a predominance of stage IV in 61 (53.98%) patients, followed by stage III with 18.58% of patients diagnosed. Conclusions: Male sex prevailed in the 60 to 79 years age group and white skin patients were the most affected. The location of the lesions manifested with greater incidence on the tongue and stages IV and III of the disease are the most representative at the time of diagnosis.

Analysis of the diagnosis and treatment experience and etiological characteristics of 119 cases of primary canaliculitis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the clinical features, diagnosis and treatment experience and the distribution characteristics of pathogenic microorganisms of primary canaliculitis, and provide reference for its diagnosis and treatment. METHODS: Retrospective clinical study. A total of 119 cases(120 eyes)diagnosed as primary canaliculitis in the department of ophthalmology of Wuxi No.2 People's Hospital from June 2019 to February 2023 were included. The treatment methods were mainly divided into conservative treatment(removing canaliculus stones through lacrimal punctum combined with injecting antibiotic eye ointment into the tube)and surgical treatment. The inspection methods of pathogenic microorganisms included secretion smear microscopy and microbial culture.RESULTS: Primary canaliculitis was more common in middle-aged and older female, mainly manifested by long-term red eye and increased secretion; however, the majority was not accompanied by tearing. Totally, 118 cases(99.2%)had monocular disease, while 63 cases(63 eyes; 52.5%)had inferior lacrimal canaliculus disease. Laboratory examination: Among 119 cases(120 eyes), 4 cases(4 eyes)did not undergo laboratory examination, and the other 115 cases(116 eyes)were as follows: Gram staining microscopy of secretion smear showed that Actinomyces were detected in 102 cases(103 eyes; 88.8%), while no fungus was detected; Microbial culture: 85 cases(86 eyes; 74.1%)were positive for bacterial culture. A total of 111 bacterial strains were cultured, which contained 26 types of bacteria. Among them, 32 strains were aerobic(28.8%); 26 strains were anaerobic(23.4%); and 53 strains were facultative anaerobic(47.7%). The most common bacteria were streptococcus(20 strains), staphylococcus(13 strains), Propionibacterium(10 strains), and capnocytophaga(10 strains). Only 4 cases(4 eyes; 3.4%)of microbial cultures were positive for Actinomyces. Fungus was negative in all microbial cultures. Treatment: Of the 119 cases(120 eyes), 114 cases(115 eyes; 95.8%)were cured by conservative treatment of removing lacrimal canaliculus stones through lacrimal punctum and intracanalicular ointment infiltration(IOI), while 5 cases(5 eyes)were not effective in conservative treatment; however, all of them were cured after surgical treatment, and the cure rate for primary canaliculitis was 100.0%.CONCLUSION: The incidence of primary canaliculitis is low, and it is prevalent in middle-aged and older female. Single lacrimal canaliculus is more common, which could be missed and misdiagnosed in clinic. Actinomyces is the major pathogen observed mostly in mixed infections, with heterogeneous strains, mainly anaerobic or facultative anaerobic bacteria. Streptococcus and Staphylococcus are the most common whereas fungal canaliculitis is rare. The cure rate of primary canaliculitis is high after diagnosis, and IOI method is recommended as the initial treatment of canaliculitis.

Percepción temporal de síntomas de disfagia en una cohorte de pacientes con disfagia orofaríngea neurogénica

Introducción: La disfagia resulta de varios mecanismos fisiopatológicos donde sus síntomas no son estáticos ni homogéneos en las personas, especialmente cuando existe disfagia orofaríngea neurogénica. Objetivo: Conocer la percepción y comportamiento en el tiempo de síntomas de disfagia mediante el instrumento Eating Assessment Tool-10 (EAT-10) en pacientes con disfagia orofaríngea neurogénica, con el fin de visualizar la dinámica clínica de esta forma de disfagia. Metodología: Estudio observacional tipo cohorte en pacientes con disfagia orofaríngea neurogénica de causas neurológicas y neuromusculares, con seguimiento a tres y seis meses y diligenciamiento del EAT-10 al momento basal, tercer y sexto mes. Resultados: Un total de 90 personas con evaluación basal, de las cuales el 56,7 % (51/90) lograron seguimiento al tercer mes y 25,6 % (23/90) al sexto mes. Los síntomas de disfagia con mayor autopercepción en los tres momentos fueron la dificultad para tragar sólidos, sensación de comida pegada en garganta y tos al comer. La odinofagia no fue un síntoma habitualmente percibido. La puntuación total del EAT-10 estuvo entre 16,61 ± 9 y 18,1 ± 9,5 puntos en general. En pacientes con seguimiento completo se observó variación en la autopercepción para tragar líquidos y pastillas. Se observó variación del puntaje al ajustarlo por recepción de terapias. Discusión: Las enfermedades neurológicas y neuromusculares impactan directamente la deglución con gravedad entre leve a profunda, donde la autopercepción de síntomas deglutorios es dinámica, pero con síntomas cardinales de disfagia orofaríngea en el tiempo. Conclusiones: El reconocimiento y seguimiento de síntomas de disfagia deben ser aspectos usuales en la atención de pacientes con enfermedades neurológicas y neuromusculares.

Introduction: Dysphagia results from several pathophysiological mechanisms where its symptoms are not static or homogeneous in people, especially when there is neurogenic oropharyngeal dysphagia. Objective: To know the perception and behavior over time of symptoms of dysphagia using the Eating Assessment Tool-10 (EAT-10) in patients with neurogenic oropharyngeal dysphagia to visualize the clinical dynamics of this form of dysphagia. Methodology: Observational cohort study in patients with neurogenic oropharyngeal dysphagia of neurological and neuromuscular causes with, follow-up at three and six months, and completion of the EAT-10 at baseline, third and sixth month. Results: A total of 90 people with baseline evaluation were included, of whom 56.7% (51/90) achieved follow-up at the third month and 25.6% (23/90) at the sixth month. Symptoms of dysphagia with greater self-perception at all three moments were difficulty swallowing solids, sensation of food stuck in the throat and coughing when eating. Odynophagia was not a commonly perceived symptom. The total score of the EAT-10 was between 16.61±9 and 18.1±9.5 points in general. In patients with complete follow-up, variation in self-perception of swallowing liquids and pills was observed. Variation of the score when adjusting for the reception of therapies. Discussion: Neurological and neuromuscular diseases directly impact swallowing with mild to profound severity, where self-perception of swallowing symptoms is dynamic, but with cardinal symptoms of oropharyngeal dysphagia over time. Conclusions: The recognition and monitoring of dysphagia symptoms should be usual aspects in the care of patients with neurological and neuromuscular diseases.

Caracterización de los aspectos etiológicos, fisiopatológicos, clínicos y terapéuticos de la sepsis y shock séptico / Characterization of the etiological, physiopathological, clinical and therapeutic aspects of sepsis and septic shock

La sepsis es un síndrome clínico basado en una compleja y dinámica interacción entre patógeno y huésped. La identificación de diferentes fenotipos y la heterogeneidad de la sepsis obligan a cambiar paradigmas en el diagnóstico-tratamiento. El shock séptico o septicémico se define como la hipotensión inducida por sepsis que persiste a pesar de la reanimación adecuada con fluidos, acompañada de alteraciones de la perfusión o disfunción de órganos. O la necesidad de fármacos vasoactivos para corregir la presión arterial. Es un tipo de shock distributivo, con reducción de las resistencias vasculares sistémicas y generalmente aumento del gasto cardíaco. En los últimos años, ha evolucionado la atención de la sepsis con especial enfoque shock séptico (SS) por su gravedad y su mayor morbimortalidad. En consideración a lo anterior, esta revisión tiene el propósito de realizar la caracterización de esta patología en los aspectos etiológicos, fisiopatológicos, clínicos y terapéuticos más importantes

Sepsis is a clinical syndrome based on a complex and dynamic interaction between pathogen and host. The identification of different phenotypes and the heterogeneity of sepsis requires a paradigm shift in its diagnosis and treatment. Septic shock is defined as a sepsis-induced hypotension that persists despite adequate fluid resuscitation, accompanied by perfusion abnormalities or organ dysfunction. It may also involve the need for vasopressor drugs to correct blood pressure. It is a type of distributive shock, characterized by reduced systemic vascular resistance and typically increased cardiac output. In recent years, the management of sepsis has evolved with a special focus on septic shock (SS) due to its severity and higher morbidity and mortality. Considering the above, this review aims to characterize this condition in terms of its etiological, pathophysiological, clinical, and therapeutic aspects

Detección molecular de patógenos en deposiciones en niños consultantes por diarrea aguda en Servicios de Urgencia

Introducción: La diarrea aguda continúa siendo una de las principales causas de morbilidad en niños; sin embargo, el diagnóstico etiológico presenta limitaciones dada la baja sensibilidad de los métodos tradicionales. Objetivo: Describir los microorganismos identificados en niños que acudieron al Servicio de Urgencia (SU) de un hospital universitario en Santiago, Chile, por diarrea aguda y a los que se le solicitó panel molecular gastrointestinal. Métodos: Se revisaron fichas clínicas y resultados de panel gastrointestinal realizados entre junio de 2017 y marzo de 2020. Resultados: Se incluyeron 198 pacientes, edad promedio de 54,5 meses y 60,6% (120/198) de sexo masculino. La positividad del panel fue de 78,8% (156/198) con 35,3% (55/156) de las muestras polimicrobianas. Se identificaron 229 microorganismos, de los cuales 72,9% (167/229) corresponden a bacterias, 25,8% (59/229) a virus y 1,3% (3/229) a parásitos. Destacaron Campylobacter spp. y Escherichia coli enteropatógena (ECEP) como las bacterias más frecuentemente identificadas. Los pacientes con detección de Campylobacter spp. presentaron con mayor frecuencia fiebre (p = 0,00). ECEP se aisló principalmente (82,5%) en muestras polimicrobianas. Discusión: Los resultados enfatizan el potencial que poseen los estudios moleculares para mejorar el diagnóstico etiológico de la diarrea, pero a la vez llevan a cuestionar el rol patogénico de algunos microorganismos identificados.

Background: Acute diarrhea continues to be one of the main causes of morbidity in children, however the etiologica diagnosis presents limitations given the low sensitivity of traditional methods. Aim: To describe the microorganisms identified in children who attended the emergency department (ED) in Santiago, Chile, due to acute diarrhea and to whom a gastrointestinal panel was requested as part of their study. Material and Methods: Clinical records and results of the gastrointestinal panel carried out between June 2017 and March 2020 were reviewed. Results: 198 patients were included, the average age was 54.5 months and 60.6% (120/198) were males. Positivity was 78.8% (156/198) with 35.3% (55/156) of the samples being polymicrobial. 229 microorganisms were identified, of which 72.9% (167/229) corresponded to bacteria, 25.8% (59/229) to viruses, and 1.3% (3/229) to parasites. Campylobacter spp. and enteropathogenic Escherichia coli (EPEC) were the most frequently identified bacteria. Patients with detection of Campylobacter spp. presented a higher frequency of fever (p = 0.00). EPEC was isolated in 82.5% of the cases in polymicrobial samples. Discussion: The results emphasize the potential of molecular studies to improve the etiological diagnosis of diarrhea and at the same time lead to question the pathogenic role of some microorganisms.

ACV isquémico en población joven: ¿existe un enfoque diferencial del riesgo?

Introducción: El ataque cerebrovascular isquémico en el adulto joven se define como aquel que ocurre en la población entre los 18 y los 55 años, y representa el 15-18 % de todos los ACV isquémicos. Los factores de riesgo en jóvenes son comunes a los encontrados en adultos mayores. El objetivo de este trabajo es describir las características clínicas y los factores de riesgo de una población menor de 55 años con ACV isquémico atendida en un centro de referencia hospitalario en Colombia. Materiales y métodos: Estudio descriptivo, retrospectivo de corte transversal en pacientes entre los 18 y los 55 años; se incluyeron 100 pacientes sobrevivientes a un primer ACV isquémico agudo confirmado por neuroimagen, atendidos entre enero de del 2019 y noviembre del 2021. Resultados: De 1023 pacientes con diagnóstico de ACV isquémico agudo, el 9,8 % fueron adultos jóvenes. La media de edad fue de 45 ± 8,7 años, y el 59 % de estos pacientes fueron hombres. Discusión: Los factores de riesgo "tradicionales" se presentan en la mayoría de los jóvenes con ACV isquémico. La hipertensión arterial se mantiene como el antecedente más frecuente. Las mujeres presentan eventos de mayor severidad y peor desenlace funcional. Conclusión: Los pacientes mayores de 45 años tienen un perfil de factores de riesgo similar a lo observado en adultos mayores con ACV, mientras que en los menores de 45 años se encuentra un perfil de factores de riesgo diferente que plantea un diagnóstico etiológico particular de esta población.

Introduction: Ischemic stroke in young adults is defined as occurring in individuals between the ages of 18 and 55, representing 15-18 % of all ischemic strokes. Risk factors in young adults are similar to those found in older adults. The objective of this study is to describe the clinical characteristics and risk factors of a population under 55 years of age with ischemic stroke treated at a hospital reference center in Colombia. Materials and methods: Descriptive, retrospective cross-sectional study in patients between 18 and 55 years old. A total of 100 patients between 18 and 55 years old who survived a first confirmed acute ischemic stroke, as confirmed by neuroimaging, were included. The study period was from January 2019 to November 2021. Results: Out of 1023 patients diagnosed with acute ischemic stroke, 9.8 % occurred in young adults. The mean age was 45 ± 8.7 years, of which 59 % were male. Discussion: "Traditional" risk factors are present in the majority of young adults with ischemic stroke. Hypertension remains the most common antecedent. Women experience more severe events and worse functional outcomes. Conclusion: Patients over 45 years old have a risk factor profile similar to what is observed in older adults with stroke, while in those under 45, a different risk factor profile is found, which poses a particular etio-logical diagnosis for this population.

Childhood Pneumonia: What’s Unchanged, and What’s New?

Childhood pneumonia is still a significant clinical and public health problem. India contributes the highest number of deaths due to pneumonia, accounts for about 20% of global mortality among under five children. Various etiologic agents including bacteria, viruses and atypical organism are responsible for childhood pneumonia. Recent studies suggest that viruses are one of the major causes of childhood pneumonia. Among viruses, respiratory syncytial virus has got great attention and several recent studies are reporting it as an important organism for pneumonia. Lack of exclusive breast feeding during first six months, improper timing of start and content of complimentary feeding, anemia, undernutrition, indoor pollution due to tobacco smoking and use of coal and wood for cooking food and lack of vaccinations are important risk factors. X-ray chest is not routinely performed to diagnose pneumonia while use of lung ultrasound is increasing to detect consolidation, pleural effusion, pneumothorax and pulmonary edema (interstitial syndrome). Role of C-reactive protein (CRP) and procalcitonin is similar, to differentiate between viral and bacterial pneumonia, however duration of antibiotics is better guided by procalcitonin. Newer biomarkers like IL-6, presepsin and triggering receptor expressed on myeloid cells 1 are needed to be evaluated for their use in children. Hypoxia is significantly associated with childhood pneumonia. Therefore, use of pulse oximetry should be encouraged for early detection and prompt treatment of hypoxia to prevent adverse outcomes. Among the available tools for risk of mortality assessment in children due to pneumonia, PREPARE score is the best but external validation will be needed.

Evaluation of IL-4, MIP-1α, and MMP-9 gene expression levels in peri-implant tissues in peri-implantitis

Abstract This case-control study evaluated the gene expression levels of interleukin (IL)-4, macrophage inflammatory protein type 1 alpha (MIP-1α), and metalloproteinase (MMP)-9, factors involved in the formation of giant cells in healthy peri-implant tissue and peri-implantitis. Thirty-five subjects (15 healthy and 20 with peri-implantitis), who met the inclusion and exclusion criteria, were included in this study. The peri-implant tissue biopsies were subjected to total RNA extraction, DNAse treatment, and cDNA synthesis. Subsequently, the reaction of real-time PCR was performed to evaluate the gene expression levels of IL-4, MIP-1α, and MMP-9 concerning the reference gene. IL-4 gene expression showed higher (18-fold) values in the Peri-Implantitis Group of Patients when compared with the Healthy (Control) Group (p<0.0001). Although MIP- 1α and MMP-9 gene expression levels were higher in diseased implants, they showed no significant differences (p=0.06 and p=0.2337), respectively. Within the limitations of this study, the results showed that in tissues affected by peri-implantitis, only levels of Il-4 were increased when compared with tissues in the control group.

Resumo Este estudo caso-controle teve como objetivo avaliar a expressão gênica dos níveis de interleucina (IL)-4, proteína inflamatória de macrófagos tipo alfa 1 (MIP-1α) e metalopreoteinase (MMP)-9, todos fatores envolvidos na formação de células gigantes em tecidos peri-implantares saudáveis e com peri-implantite. Trinta e cinco indivíduos (15 saudáveis e 20 com peri-implantite) foram incluídos nesse estudo seguindo os critérios de inclusão e exclusão. Os tecidos peri-implantares foram submetidos a extração do RNA total, tratamento de DNAse e síntese de cDNA. Subsequentemente, a reação de PCR em tempo real foi realizada para avaliar os níveis da expressão de IL-4, MIP-1α, e MMP-9 em relação ao gene de referência. O nível de expressão de IL-4 foi estatisticamwente maior (18 vezes) nos tecidos de pacientes com peri-implantite quando comparados aos pacientes saudáveis (grupo controle) (p<0,0001). Embora os níveis de expressão de MIP- 1α e MMP-9 apresentassem maiores valores nos implantes doentes, esses níveis não foram estatisticamente significantes (p=0.06 and p=0.2337) respectivamente. Dentro das limitações desse estudo, os resultados mostraram que nos tecidos afetados pela peri-implantite, apenas os nívies de IL-4 estavam aumentados quando comparados ao grupo controle.

El problema etiológico de los delirios en la esquizofrenia para la neuropsiquiatría actual / The Etiological Problem of Psychotic Delusions in Current Neuropsychiatry / O problema etiológico dos delírios na esquizofrenia para a neuropsiquiatria atual

Introducción: el delirio constituye uno de los síntomas más complejos y severos de la psicosis. Uno de los problemas más fundamentales que enfrenta la investigación en el campo de la neuropsiquiatría tiene que ver con el desafío de producir teorías explicativas para la producción de este tipo de estado mental, a lo que se denomina problema etiológico de los delirios psicóticos. Desarrollo: se analizan críticamente las principales alternativas dentro de la neuropsiquiatría contemporánea al problema etiológico en el contexto de la esquizofrenia. Conclusión: el análisis indica que las tres teorías fundamentales que conviven en la actualidad poseen problemas para avanzar en el desafío de explicar la etiología de los delirios. Por lo anterior, se propone la idea de que, a la luz del estado del debate reciente, la hibridación teórica podría perfilarse como el mejor candidato metodológico para generar progreso real en la disciplina

Introduction: Delusions constitute one of the most complex and severe symptoms of psychosis. One of the most fundamental problems within current research in neuropsychiatry has to do with the challenge of producing explanatory theories of the aetiology of the phenomenon. I call this the etiological problem of psychotic delusions. Development: The main alternatives to the etiological problem in schizophrenia in current neuropsychiatry are critically assessed. Conclusion: The three current co-existing approaches possess a number of problems to make real progress in the etiological debate. For this reason, I suggest that, in light of the current state of the art, theoretical hybridization could become the best methodologi- cal candidate to make progress within the target debate

Introdução: o delírio é um dos sintomas mais complexos e graves da psicose. Um dos problemas mais fundamentais enfrentados atualmente pelas pesquisas no campo da neuropsiquiatria diz respeito ao desafio de produzir teorias explicativas para a produção desse tipo de estado mental, que chamo de o problema etiológico dos delírios psicóticos. Desenvolvimento: são analisadas criticamente as principais alternativas da neuropsiquiatria contemporânea ao problema etiológico no contexto da esquizofrenia. Conclusão: a análise indica que as três teorias fundamentais que coexistem atualmente têm problemas para avançar no desafio de explicar a etiologia dos delírios. Portanto, propõe-se a ideia de que, à luz do estado atual do debate, a hibridação teórica poderia surgir como o melhor candidato metodológico para gerar um progresso real na disciplina.

Dependence of radioactive iodine-131 capture by the lacrimal ducts on the tear production level

Purpose: Secondary acquired lacrimal duct obstruction (SALDO) is one of the complications of radioiodine therapy. SALDO is formed a few months after therapy if there is a sufficient uptake of radioactive iodine by the nasolacrimal duct. To date, risk factors leading to SALDO are unclear. The objective was to determine the correlation between the tear production level and radioactive iodine?131 uptake in the lacrimal ducts.Methods: Basal and reflex tear production was studied in 64 eyes prior to the therapy with radioactive iodine?131 after drug?induced hypothyroidism. The condition of the ocular surface was assessed using the Ocular Surface Disease Index (OSDI) questionnaire. Seventy?two hours after the radioactive iodine therapy, scintigraphy was performed, which determined the presence or absence of iodine?131 in the lacrimal ducts. T?statistics and the Mann–Whitney criterion were used to identify the differences between the groups. The differences were considered significant at P ? 0.05. The current tear production level in patients receiving radioiodine therapy was determined using a mathematical model. Results: A statistically significant difference between the basal (p = 0.044) and reflex (p = 0.015) tear production levels was found in cases with and without iodine?131 uptake by the lacrimal ducts. The probable current tear production level corresponds to the sum of basal and 10–20% of reflex tear production. The uptake of iodine?131 was found regardless of the OSDI results.Conclusion: The probability of iodine?131 uptake by the lacrimal ducts rises as the tear production level increases.

Metastatic and aggressive renal cell carcinoma mimicking a unilateral choroidal tuberculoma / Carcinoma de células renais metastático grave mimetizando tuberculoma de coroide unilateral

ABSTRACT Ocular metastases from systemic tumors are uncommon. The choroid is the most frequent target, with a preference for elderly individuals. Lung cancer is the predominant primary tumor that metastasizes to the eyes in males, although other ocular conditions such as uveitis and retinal lesions can mimic secondary tumor implants in ocular tissues. On fundoscopy, choroidal metastasis resembles other infectious processes, especially choroidal tuberculoma. Therefore, patients presenting with choroidal masses should undergo detailed clinical examinations, especially if the mass is the first manifestation of a systemic and severe disease. In this report, we describe a young man with a metastatic choroidal tumor secondary to papillary renal cell carcinoma mimicking a unilateral choroidal tuberculoma.

RESUMO A disseminação metastática ocular de tumores sistêmicos é incomum, ocorrendo principalmente na coroide e em pacientes idosos. O câncer de pulmão é considerado o principal tumor metastático ocular em homens, contudo, outras doenças oculares, como as uveítes e lesões retinianas, podem mimetizar os implantes secundários tumorais nos tecidos oculares. O aspecto fundoscópico das neoplasias da coroide pode apresentar similaridade com outros processos infecciosos, especialmente o tuberculoma de coroide. Dessa forma, a investigação clínica detalhada é de grande importância no diagnóstico de pacientes com massas coroideanas, especialmente quando configuram a primeira manifestação de uma doença sistêmica e grave. Relatamos um caso raro de metástase coroideana como primeira manifestação clínica do carcinoma de células renais em um homem jovem, mimetizando um tuberculoma de coroide.

Study of Deliberate Self-Poisoning Among Adult Females in A Tertiary Care Hospital

Background: Poisoning is a common medico-social problem in our country causing around 300,000 episodes and around 2000 deaths per year. Attempted suicide among adult females are a major public health problem. The number of self-poisoning in females are increasing in our country day by day. The incidence, nature, etiology, age group affected and the outcome of self-poisoning in females of our country is different from that of the western world. Objective: The objective of the study was to analysis the socio-demographic profile & pattern of deliberate self-poisoning among adult females admitted in the Medicine Department, Dhaka Medical College Hospital. Material and Methods: This was a descriptive cross sectional study conducted in the Department of Medicine, Dhaka Medical College Hospital from January 2016 to June 2016. 100 admitted female participants were enrolled in this study as study population. A purposive sampling method was applied for sampling from study population. Results: The age of the participants were from 18 to 55 years with the mean age of 28.19 (± 9.84) years. Most number of the participants were in 21-29 year’s age group (42%) followed by ?20 year’s (29%). House wife (30%) was the most common occupation followed by student (25%). Most of the participants were from lower economic class (51%), followed by middle class (41%). 48% participants were in primary level, 24% in secondary level and 22% were illiterate. Most of the participants were married (51%), followed by unmarried (35%), divorced (9%) and widow (5%). 62% participants from rural and 38% from urban area. 75% were Muslim and 25% were Hindu. 55% were from the joint family and 45% were from the nuclear family. Most of the self-poisoning occurred between 6 am to 12 pm (42%), followed by 6 pm to 12 am (30%), 12 pm to 6 pm (20%) and 12 am to 6 am (8%). Insecticide was the most common poison materials (43%), followed by drug ingestion (30%), household detergent (13%), rodenticide (6%) and others (8%). Maximum participants reported the reason for self-poisoning was family disharmony (35%) followed by romantic disappointment (27%). 17% participants reported previous suicidal attempt and 11% had previous psychiatric disorder. Nearly half of the participants (43%) sought medical care within 2 hours and one fourth participants (31%) within 4 hours. About two-thirds of the participants (66%) received primary medical care from different govt. hospitals. Most of the female participants with self-poisoning were recovered completely (71%), while 20% participants recovered with complications and 9% participants died. In the study, fatality rate was found 33.3% in rodenticide and 16.3% in insecticide poisoning. Conclusions: As evident from the study, by intervene these problems by various measures might be helpful to prevent many of deliberate self-harm. Early diagnosis and prompt institution of appropriate treatment can make a favorable outcome in deliberate self-poisoning of female participants.

Effects of the epiretinal membrane on the outcomes of intravitreal dexamethasone implantation for macular edema secondary to branch retinal vein occlusion / Os efeitos de uma membrana epirretiniana nos resultados da implantação de dexametasona intravítrea para edema macular secundário à oclusão de ramo da veia retiniana

ABSTRACT Purpose: To investigate the effects of epiretinal membrane formation on the clinical outcomes of intravitreal dexamethasone implantation for macular edema secondary to branch retinal vein occlusion. Methods: This retrospective interventional case series includes the treatment of naive patients with macular edema secondary to non-ischemic branch retinal vein occlusion who underwent intravitreal dexamethasone implantation. The patients were divided into two groups as follows: Group 1 (n=25), comprised of patients with macular edema secondary to branch retinal vein occlusion without epiretinal membrane, and Group 2 (n=16), comprised of patients with macular edema secondary to branch retinal vein occlusion with an epiretinal membrane. Corrected visual acuity, central macular thickness, and central macular volume values were measured before and after treatment. The clinical outcomes of the groups were compared. Results: Mean age and male-to-female ratio were similar between the two groups (p>0.05, for both). The baseline and final corrected visual acuity values, central macular thickness, and central macular volumes of the groups were similar (p>0.05, for all). All the parameters were significantly improved after intravitreal dexamethasone implantation treatment (p<0.001, for all). The changes in central macular thickness and volume were also similar (p>0.05, for both). The mean number of intravitreal dexamethasone implantations was 2.1 ± 1.0 (range, 1-4) in Group 1 and 3.0 ± 1.2 (range, 1-5) in Group 2 (p=0.043). Conclusion: Epiretinal membrane formation had no effects on the baseline and final clinical parameters, including corrected visual acuity and central macular thickness and volume. The only parameter affected by the presence of epiretinal membrane formation is the number of intravitreal dexamethasone implantations, a greater number of which is needed for macular edema secondary to branch retinal vein occlusion with an epiretinal membrane.

RESUMO Objetivo: Investigar os efeitos da formação de uma membrana epirretiniana nos resultados clínicos da implantação intravítrea de dexametasona para edema macular secundário à oclusão de um ramo da veia retiniana. Métodos: Esta série retrospectiva de casos intervencionais inclui o tratamento de indivíduos com edema macular secundário à oclusão não isquêmica de um ramo da veia retiniana, sem tratamento prévio e que foram submetidos a implantação intravítrea de dexametasona. Os indivíduos foram divididos em dois grupos: Grupo 1 (n=25), composto por indivíduos com edema macular secundário à oclusão de um ramo da veia retiniana sem a presença de uma membrana epirretiniana, e Grupo 2 (n=16), composto por indivíduos com edema macular secundário à oclusão de um ramo da veia retiniana com a presença de uma membrana epirretiniana. Os valores da acuidade visual corrigida, espessura macular central e volume macular central foram obtidos antes e após o tratamento. Os resultados clínicos dos grupos foram comparados. Resultados: A média de idade e a proporção entre homens e mulheres foram semelhantes nos dois grupos (p>0,05 para ambos os valores). Os valores iniciais e finais da acuidade visual corrigida, espessura macular central e volume macular central foram semelhantes nos dois grupos (p>0,05 para todos os valores). Todos os parâmetros melhoraram significativamente após o tratamento com implante de dexametasona intravítrea (p<0,001 para todos os parâmetros) e as alterações na espessura macular central e no volume macular central também foram semelhantes (p>0,05 para ambos os valores). O número médio de implantações intravítreas de dexametasona foi 2,1 ± 1,0 (faixa de 1-4) no Grupo 1 e 3,0 ± 1,2 (faixa de 1-5) no Grupo 2 (p=0,043). Conclusão: A formação de uma membrana epirretiniana não tem efeitos sobre os parâmetros clínicos iniciais e finais, incluindo a acuidade visual corrigida, a espessura macular central e o volume macular central. O único parâmetro afetado pela formação de uma membrana epirretiniana é o número de implantações intravítreas de dexametasona, sendo necessário um número maior de implantações em casos de edema macular secundário à oclusão de um ramo da veia retiniana com a presença de uma membrana epirretiniana.

Patella cubiti - a continuing etiological mystery / Patella cubiti: un misterio etiológico continuo

SUMMARY: A sesamoid bone in the elbow joint is a rare anatomical variation described as a Patella cubiti. Although this variation has been known for centuries its exact etiology is still unclear. Congenital, developmental, and traumatic hypotheses have been proposed. It seldom causes clinical manifestations than elbow stiffness or hypomobility. Herein, we present a case of a 31-year-old patient admitted to our department with complaints of swelling and erythema in the right elbow. An X-ray image revealed a triangular accessory bone with rounded edges, which was diagnosed as a Patella cubiti in combination with olecranon bursitis. Knowledge of this rare elbow abnormality is paramount for orthopedic surgeons and roentgenologists in their daily medical practice.

Un hueso sesamoideo en la articulación del codo es una rara variación anatómica descrita como Patella cubiti. Aunque esta variación se conoce desde hace siglos, su etiología exacta aún no está clara. Se han propuesto hipótesis congénitas, de desarrollo y traumáticas. Rara vez causa manifestaciones clínicas que no sean rigidez o hipomovilidad del codo. Presentamos el caso de un paciente de 31 años que ingresó en nuestro servicio por presentar tumefacción y eritema en el codo derecho. Una imagen de rayos X reveló un hueso accesorio triangular con márgenes redondeados, que se diagnosticó como una Patella cubiti en combinación con bursitis del olécranon. El conocimiento de esta rara anomalía del codo es fundamental para los cirujanos ortopédicos y los médicos radiólogos en su práctica médica diaria.

Caracterización del dolor abdominal crónico en pacientes del Hospital Pediátrico Provincial Eduardo Agramonte Piña

Introducción: El dolor abdominal recurrente es un síntoma común en los niños y causa gran ansiedad a la familia. Representa hasta el 10 % de las consultas en pediatría, con frecuencia entre escolares y adolescentes, del 85 al 90 % de los casos la causa obedece a un trastorno de tipo funcional. Objetivo: Caracterizar el dolor abdominal recurrente en niños ingresados en el hospital pediátrico Eduardo Agramonte Piña de la provincia Camagüey. Métodos: Se realizó un estudio observacional, descriptivo, transversal, retrospectivo, cuyo universo de trabajo estuvo constituido por 122 pacientes ingresados con diagnóstico de dolor abdominal recurrente, durante el período de estudio. Para la obtención de la información se utilizó el análisis de documentos al revisar las historias clínicas del total de pacientes atendidos y los materiales bibliográficos. Resultados: De 122 pacientes estudiados el grupo más afectado correspondió al de 13-18 años de edad, seguido del grupo escolar de 7-12 años para un total de 73 y 45 casos, respectivamente. Entre los factores que aumentó la frecuencia estuvo la exposición mantenida a situaciones estresantes relacionadas con la disfunción del medio ambiente familiar y social del niño, expresados en los resultados, de 122 pacientes, 91 proceden de medios socio-ambientales disfuncionales, con predominio en las etapas escolares y de la adolescencia. Conclusiones: El número de pacientes con resultados de laboratorio negativos fue mayor que el de los positivos, por lo cual el dolor abdominal de origen funcional superó al de tipo orgánico.

Introduction: Recurrent abdominal pain (RAP) is a common symptom in children and causes great anxiety to the family. It represents up to 10% of pediatric consultations. It occurs frequently among schoolchildren and adolescents and in 85 to 90% of cases the cause is due to a functional disorder. Objective: To characterize the behavior of recurrent abdominal pain in children admitted to the Eduardo Agramonte Piña pediatric hospital in the province of Camagüey. Methods: An observational, descriptive, cross-sectional, retrospective study was carried out, whose universe of work consisted of 122 patients admitted with a diagnosis of recurrent abdominal pain, during the study period. To obtain the information, document analysis was used by reviewing the clinical histories of the total number of patients treated and the bibliographic materials. Results: Of a total of 122 patients studied, the most affected group corresponded to 13 to 18 years of age, followed by the school group of 7 to 12 years for a total of 73 and 45 cases, respectively. Among the factors that increased the frequency was sustained exposure to stressful situations related to the dysfunction of the child's family and social environment, expressed in the results: of 122 patients, 91 come from dysfunctional socio-environmental environments, with predominance in the schoolchildren and adolescents stages. Conclusions: The number of patients with negative laboratory results was greater than that of positive ones, that is why abdominal pain of functional origin exceeded that of organic origin.

Caracterización clínico epidemiológica de los pacientes con alteraciones bucomaxilofaciales en la provincia Camagüey

Introducción: Las personas con una deformación facial comúnmente están expuestas a las críticas o presión, colocando al individuo en situaciones embarazosas. El uso de prótesis es una solución eficiente a las deformidades faciales ya que evita complicaciones quirúrgicas y produce un buen resultado estético cuando no es posible la reconstrucción quirúrgica o se prefiere por el paciente. Objetivo: Caracterizar clínica y epidemiológicamente los pacientes con alteraciones bucomaxilofaciales en la provincia Camagüey. Métodos: Se realizó un estudio descriptivo de serie de casos en el periodo comprendido entre marzo y diciembre de 2022. Se tomó la información existente en las bases de datos y en los trabajos de terminación de la especialidad de Prótesis Estomatológica, realizados entre los años 2001 al 2019. Se utilizó para el análisis de la información, estadística descriptiva para distribución de frecuencias y los resultados finales se incluyeron en tablas. Resultados: La mayoría de los casos fueron pacientes masculinos, de edades entre 46 y 60; los defectos más frecuentes encontrados fueron los oculares. En cuanto al sexo fue evidente una mayor necesidad de prótesis bucomaxilofacial en los hombres y dentro de estas las prótesis oculares. Entre las principales causas de pérdida de estructuras se encontraron los traumatismos y las lesiones oncológicas. Conclusiones: Los defectos bucomaxilofaciales repercuten de forma negativa en la calidad de vida de quienes los padecen; las causas que generan los mismos, las regiones donde más se presentan, el sexo y la edad en que aparecen son elementos a tener en cuenta para un correcta prevención de dichas lesiones pero también permiten establecer pautas de trabajo encaminadas a brindar una atención multidisciplinaria para su rehabilitación protésica e integral.

Introduction: People with a facial deformity are commonly exposed to criticism or pressure, placing the individual in embarrassing situations. The use of prostheses is an efficient solution to facial deformities since it avoids surgical complications and produces a good aesthetic result when surgical reconstruction is not possible or is preferred by the patient. Objective: To characterize clinically and epidemiologically patients with oral and maxillofacial alterations in Camagüey province. Methods: A case report type study was carried out taking the results of the databases, completion works of the Dentistry Prosthesis specialty between the years 2001 and 2019. The study was carried out in the period between March and December 2022. The results were reflected in tables using descriptive statistics for them. Results: Most of the cases were male patients, aged between 46 and 60; the most frequent defects found were the ocular ones. Regarding gender, a greater need for oral and maxillofacial prostheses was evident in men, and within these, ocular prostheses. Among the main causes of loss of structures were traumatisms and oncological lesions. Conclusions: Oral and maxillofacial defects have a negative impact on the quality of life of those who suffer from them; the causes that generate them, the regions where they occur most, the sex and the age in which they appear are elements to take into account for a correct prevention of said injuries but also allow the establishment of work guidelines aimed at providing multidisciplinary care for their prosthetic and integral rehabilitation.

Changes in lung function in adolescents with substance use disorders: an exploratory study / Alterações da função pulmonar em adolescentes com transtornos relacionados ao uso de substâncias: estudo exploratório

ABSTRACT Objective: To compare lung function between adolescents with and without substance use disorder (SUD). Methods: This was an observational, cross-sectional exploratory study. The sample consisted of 16 adolescents with SUD and 24 age-matched healthy controls. The adolescents in the clinical group were recruited from a psychiatric inpatient unit for detoxification and rehabilitation; their primary diagnosis was SUD related to marijuana, cocaine, or polysubstance use. Questionnaires and pulmonary function tests were applied for clinical evaluation. Results: We found that FVC, FEV1, and their percentages of the predicted values were significantly lower in the adolescents with SUD than in those without. Those differences remained significant after adjustment for BMI and the effects of high levels of physical activity. The largest effect size (Cohen's d = 1.82) was found for FVC as a percentage of the predicted value (FVC%), which was, on average, 17.95% lower in the SUD group. In addition, the years of regular use of smoked substances (tobacco, marijuana, and crack cocaine) correlated negatively with the FVC%. Conclusions: This exploratory study is innovative in that it demonstrates the early consequences of smoked substance use for the lung health of adolescents with SUD.

RESUMO Objetivo: Comparar a função pulmonar de adolescentes com e sem transtornos relacionados ao uso de substâncias (TUS). Métodos: Trata-se de um estudo exploratório transversal observacional. A amostra foi composta por 16 adolescentes com TUS e 24 controles saudáveis emparelhados pela idade. Os adolescentes do grupo clínico foram recrutados em uma unidade de internação psiquiátrica para desintoxicação e reabilitação; seu diagnóstico primário era o de TUS (maconha, cocaína ou polissubstâncias). Foram aplicados questionários e testes de função pulmonar para a avaliação clínica. Resultados: A CVF, o VEF1 e seus valores em porcentagem do previsto foram significativamente mais baixos nos adolescentes com TUS do que naqueles sem TUS. Essas diferenças permaneceram significativas após os ajustes para levar em conta o IMC e os efeitos de altos níveis de atividade física. O maior tamanho de efeito (d de Cohen = 1,82) foi o observado em relação à CVF em porcentagem do previsto (CVF%), que foi, em média, 17,95% menor no grupo TUS. Além disso, os anos de uso regular de substâncias fumadas (tabaco, maconha e crack) correlacionaram-se negativamente com a CVF%. Conclusões: Este estudo exploratório é inovador na medida em que demonstra as consequências precoces do uso de substâncias fumadas para a saúde pulmonar de adolescentes com TUS.