RESUMO
OBJECTIVE: Paroxysmal non-epileptic events (PNEs) are a group of disorders that may be misdiagnosed as epilepsy. This study has aimed to assess the knowledge and practices of family physicians and pediatricians regarding the diagnosis, treatment, and follow-up of PNEs in children. METHODS: The study was designed as a prospective cross-sectional study that was conducted between March 1, 2022, and June 1, 2022, by reaching pediatric specialists and assistants, family physicians, subspecialty assistants, and subspecialists using a Google questionnaire. The survey consists of 26 questions. The questionnaire used by the researchers was prepared in accordance with the literature search and it included detailed questions on the diagnosis, treatment, and differential diagnosis of PNEs. RESULTS: A total of 37.3% worked as specialists. Most of the participants (41.3%) have worked in training and research hospitals, and 44.3% have been physicians for 6-10 years. The mean and standard deviation for the total score were 10.1 ± 2.6. The scores of family physicians were statistically lower than those of specialists, subspecialty assistants, and subspecialists. A total of 67.2% left the decision of whether the patient should stop taking their medication to another clinician. 45% of the doctors said that they were uncomfortable with the diagnosis. SIGNIFICANCE: The study findings emphasized the significant knowledge gap among healthcare providers regarding PNEs in children, highlighting the need for targeted educational interventions to improve their understanding and diagnostic skills in this area.
Assuntos
Epilepsia , Convulsões , Criança , Humanos , Convulsões/diagnóstico , Estudos Transversais , Estudos Prospectivos , Epilepsia/diagnóstico , Pessoal de Saúde , EletroencefalografiaRESUMO
Biotinidase deficiency (BD) is an autosomal recessive inherited metabolic disorder which results from the inability of biotin-dependent carboxylase enzymes to function due to the release and absorption of biotin, leading to neurological and cutaneous findings. In the present study, evaluation of demographic characteristics, clinical findings, laboratory results, molecular genetic characteristics, and genotype-phenotype correlations of cases with BD. Two hundred forty-seven cases were included in the study who were admitted to the Department of Pediatric Metabolism of Ankara Bilkent City Hospital after being identified with potential BD through the Newborn Screening Program (NBS), during family screening or based on suspicious clinical findings, or following the detection of a pathogenic variant in a BTD genetic analysis during the period of October 2020 and February 2022. The medical files of the cases were reviewed retrospectively. An analysis of the admission routes of all cases to our clinic revealed 89.5% NBS, 5.7% family screening, and 4.9% suspicious clinical findings suggestive of BD. Complete enzyme deficiency was identified in 19.8%, partial enzyme deficiency in 55.1%, and heterogenous enzyme deficiency in 9.7%. The most common pathogenic variants were c.1270G > C (p.Asp424His), c.410G > A (p.Arg137His), and c.38_44delGCGCTGinsTCC (p.Cys13Phefs*36) in BTD gene. The c.1270G > C variant was most common in patients with cutaneous symptoms. The c.410G > A and c.38_44delGCGCTGinsTCC variants were more common in the patients with neurological symptoms. The mean activity level in patients with the c.1270G > C homozygous variant was statistically significantly higher than the mean activity level in the c.1270G > C compound heterozygous patients and the activity level of patients without the c.1270G > C variant. The mean activity level in c.410G > A homozygous patients was statistically significantly lower than the mean activity level of the c.410G > A compound heterozygous patients and the activity level of patients without the c.410G > A variant. In the course of our study, four new pathogenic variants were detected, namely: c.190G > A (p.Glu64Lys), c.249 + 5G > T, c.228delA (p.Val77*), and c.682A > G (p.Ile228Val). Conclusions: The present study has determined the clinical and genetic spectrum of a large group of patients with BD in a single center. The frequent mutations in our study were similar to those reported in literature, and four novel variants were also described. What is Known: ⢠Biotinidase deficiency is an autosomal recessive, treatable inborn error of metabolism. Two hundred ninety-four pathogenic variants in the BTD gene have been identified and the c.1270G > C variant is the most frequent BTD gene mutation in both Turkey and around the world. What is New: ⢠Four new pathogenic variants (c.190G > A, p.Glu64Lys; c.249 + 5G > T; c.228delA, p.Val77*; and c.682A > G, p.Ile228Val) have been identified. It is believed that the c.38_44delGCGGCTGinsTCC variant is more commonly seen in individuals with ocular issues; however, further genotype-phenotype correlations are needed.
Assuntos
Deficiência de Biotinidase , Recém-Nascido , Humanos , Criança , Deficiência de Biotinidase/diagnóstico , Deficiência de Biotinidase/genética , Deficiência de Biotinidase/patologia , Biotinidase/genética , Biotinidase/metabolismo , Biotina/uso terapêutico , Biotina/genética , Estudos Retrospectivos , Mutação , Triagem Neonatal , Biologia MolecularRESUMO
BACKGROUND: Hypoxic ischemic encephalopathy (HIE) is a significant cause of mortality and short- and long-term morbidities. Therapeutic hypothermia (TH) has been shown to be the standard care for HIE of infants ≥36 weeks gestational age (GA), as it has been demonstrated to reduce the rates of mortality, and adverse neurodevelopmental outcomes. This study aims to determine the incidence of HIE in our country, to assess the TH management in infants with HIE, and present short-term outcomes of these infants. METHODS: The Turkish Hypoxic Ischemic Encephalopathy Online Registry database was established for this multicenter, prospective, observational, nationally-based cohort study to evaluate the data of infants born at ≥34 weeks GA who displayed evidence of neonatal encephalopathy (NE) between March, 2020 and April 2022. RESULTS: The incidence of HIE among infants born at ≥36 weeks GA (n = 965) was 2.13 per 1000 live births (517:242440), and accounting for 1.55% (965:62062) of all neonatal intensive care unit admissions. The rates of mild, moderate and severe HIE were 25.5% (n = 246), 58.9% (n = 568), and 15.6% (n = 151), respectively. Infants with severe HIE had higher rates of abnormal magnetic resonance imaging (MRI) findings, and mortality (p<0.001). No significant difference in mortality and abnormal MRI results was found according to the time of TH initiation (<3 h, 3-6 h and >6 h) (p>0.05). TH was administered to 85 (34.5%) infants with mild HIE, and of those born of 34-35 weeks of GA, 67.4% (n = 31) received TH. A total of 58 (6%) deaths were reported with a higher mortality rate in infants born at 34-35 weeks of GA (OR 3.941, 95% Cl 1.446-10.7422, p = 0.007). CONCLUSION: The incidence of HIE remained similar over time with a reduction in mortality rate. The timing of TH initiation, whether <3 or 3-6 h, did not result in lower occurrences of brain lesions on MRI or mortality. An increasing number of infants with mild HIE and late preterm infants with HIE are receiving TH; however, the indications for TH require further clarification. Longer follow-up studies are necessary for this vulnerable population.
Assuntos
Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Lactente , Humanos , Recém-Nascido , Estudos de Coortes , Hipóxia-Isquemia Encefálica/epidemiologia , Hipóxia-Isquemia Encefálica/terapia , Estudos Prospectivos , Recém-Nascido Prematuro , Hipotermia Induzida/métodos , Sistema de RegistrosRESUMO
AIM: The implementation of newborn screening programs for inborn errors of metabolism has advanced the diagnosis and management of affected infants and undoubtedly improved their outcomes. We aimed to determine out-of-pocket health expenditures of patients with inborn errors of metabolism during follow-up and treatment processes and to determine the economic burden on the families. MATERIALS AND METHODS: A total of 232 patients who voluntarily agreed to participate in the study and were regularly followed up in the Department of Pediatric Metabolism with the diagnosis of Inborn Errors of Metabolism between April 2022 and July 2022 were included. Questionnaires were asked about the demographic characteristics of patients, use of health services, follow-up, treatment procedures, frequency of controls and health expenditures. RESULTS: The average out-of-pocket expenditure of the households in the last month was 1039.22 ± 1030.08 (minimum: 20, maximum: 5000) Turkish Liras. When we consider the catastrophic health expenditure rate as expenditure exceeding 40% of household income, we found that 9.9% (23 people) of parents included in the study made catastrophic health expenditures. The rate of catastrophic expenditure of patients with a diagnosis of Amino Acid Metabolism Disorders was found to be higher than that of patients with a diagnosis of Vitamin and Cofactor Metabolism Disorders. Similarly, patients with a diagnosis of lysosomal storage diseases had more expenditures than patients with a diagnosis of vitamin and cofactor metabolism disorders. When we compared the rate of catastrophic health expenditure of the patients with urea cycle disorders and the patients with a diagnosis of vitamin and cofactor metabolism disorders, the former had more expenditure than the latter (p < 0.05). There was no significant difference between other disease groups in terms of catastrophic expenditure. The rate of catastrophic expenditures of the households living as large family type were higher than the families living as nuclear family type (p < 0.01). A statistically significant difference was found between the rates of catastrophic expenditures of the families living in Ankara and those who were admitted from other provinces for follow-up and treatment (p < 0.001). However, there was no difference between the rates of catastrophic expenditure of the patients who received any treatment and those who were followed up without treatment (p > 0.05). CONCLUSION: Due to the high rate of consanguineous marriages in our country, the development of newborn screening programs, the increase in awareness about metabolic diseases and the improvement in diagnostic methods, the frequency of metabolic diseases is increasing, and mortality and morbidity rates are significantly reduced with early diagnosis and treatment opportunities. It is necessary to carry out more comprehensive studies to determine and prevent the socioeconomic effects of out-of-pocket health expenditures of patients living with Inborn Errors of Metabolism.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Gastos em Saúde , Lactente , Recém-Nascido , Humanos , Criança , Características da Família , Financiamento Pessoal , Doença CatastróficaRESUMO
The coronavirus disease (COVID-19) is primarily disseminated through physical contact. As a precaution, it is recommended that indoor spaces have a limited number of people and at least one meter apart. This study proposes a real-time method for monitoring physical distancing compliance in indoor spaces using computer vision and deep learning techniques. The proposed method utilizes YOLO (You Only Look Once), a popular convolutional neural network-based object detection model, pre-trained on the Microsoft COCO (Common Objects in Context) dataset to detect persons and estimate their physical distance in real time. The effectiveness of the proposed method was assessed using metrics including accuracy rate, frame per second (FPS), and mean average precision (mAP). The results show that the YOLO v3 model had the most remarkable accuracy (87.07%) and mAP (89.91%). On the other hand, the highest fps rate of up to 18.71 was achieved by the YOLO v5s model. The results demonstrate the potential of the proposed method for effectively monitoring physical distancing compliance in indoor spaces, providing valuable insights for future use in other public health scenarios.
RESUMO
Introduction: Neuronal ceroid lipofuscinoses (NCLs) are a broad class of inherited lysosomal storage disorders. Known mutations in at least 13 different genes can result in NCL with variable ages of onset, symptoms, and pathologic findings. Generally, these patients experience cognitive and motor decline, seizures, visual impairment, and premature death. Pathologically, NCL patients display heterogeneous histologic abnormalities, but consistently exhibit neuronal loss, reactive gliosis, and lysosomal accumulation of autofluorescent storage material or lipopigment. Juvenile-onset NCL has been classically referred to as Batten disease. By far the most prevalent NCL is CLN3-associated disease. It is an autosomal recessive condition that is usually caused by mutations in the ceroid-lipofuscinosis, neuronal 3 (CLN3) gene. CLN3 encodes battenin, a ubiquitously expressed transmembrane protein of unknown function that is associated with cellular homeostasis and neuronal survival. The initial clinical symptom of CLN3-associated NCL is central vision loss, which is usually detected between 4 and 9 years of age. Seizures typically begin early in the second decade of life, and affected individuals rarely live beyond their mid-20ies. Case Presentation: Herein, we describe a 16-year-old patient with CLN3-related juvenile NCL with a preliminary diagnosis of Niemann Pick Type C disease. The proband showed characteristic clinical signs, including epilepsy, ataxia, psychomotor regression, dementia, and visual impairment with an unusual elevation of lyso-sphingomyelin-509 (Lyso-SM-509; 812 nmol/L, normal 1-33 nmol/L). A homozygous NM_001042432.2(CLN3):c.233dup (p.Thr80fs) variant was detected at exon 4 of CLN3. Diagnosis of NCL was difficult due to the pronounced elevation of LysoSM-509. Discussion: LysoSM-509 is a biomarker which is elevated especially in Niemann Pick Type C. We can consider that a high LysoSM-509 level might be also an indicator of NCL, especially NCL type 3.
RESUMO
As seen in the COVID-19 pandemic, one of the most important measures is physical distance in viruses transmitted from person to person. According to the World Health Organization (WHO), it is mandatory to have a limited number of people in indoor spaces. Depending on the size of the indoors, the number of persons that can fit in that area varies. Then, the size of the indoor area should be measured and the maximum number of people should be calculated accordingly. Computers can be used to ensure the correct application of the capacity rule in indoors monitored by cameras. In this study, a method is proposed to measure the size of a prespecified region in the video and count the people there in real time. According to this method: (1) predetermining the borders of a region on the video, (2) identification and counting of people in this specified region, (3) it is aimed to estimate the size of the specified area and to find the maximum number of people it can take. For this purpose, the You Only Look Once (YOLO) object detection model was used. In addition, Microsoft COCO dataset pre-trained weights were used to identify and label persons. YOLO models were tested separately in the proposed method and their performances were analyzed. Mean average precision (mAP), frame per second (fps), and accuracy rate metrics were found for the detection of persons in the specified region. While the YOLO v3 model achieved the highest value in accuracy rate and mAP (both 0.50 and 0.75) metrics, the YOLO v5s model achieved the highest fps rate among non-Tiny models.
RESUMO
BACKGROUND: Multiple myeloma (MM), characterized by extensive genomic instability and aberrant DNA damage repair, is a plasma cell malignancy due to the excessive proliferation of monoclonal antibody-producing plasma cells in the bone marrow. Despite the significant improvement in the survival of patients with the development of novel therapeutic agents, MM remains an incurable disease. Werner (WRN) helicase, a member of the RecQ helicase family that contributes to DNA replication, recombination, and repair, has been highlighted in cancer cell survival, yet the role and mechanism of WRN in MM remain unclear. METHODS AND RESULTS: Increased mRNA expression of WRN in newly diagnosed and relapsed CD138+ myeloma plasma cells than normal CD138+ plasma cells and their matched CD138- non-tumorigenic cells were detected by qPCR. Using NSC19630, a specific WRN helicase inhibitor, we further showed decreased cell viability, proliferation, and DNA repair and increased DNA damage and apoptosis in MM cells by MTT assay, cell cycle assay, apoptosis assay, and Western blotting. CONCLUSIONS: The results of the present study demonstrate that WRN is essential in MM cell viability, proliferation, and genomic stability, indicating its inhibition may enhance the efficacy of chemotherapy in MM.
Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/genética , Helicase da Síndrome de Werner/genética , Helicase da Síndrome de Werner/metabolismo , Exodesoxirribonucleases/genética , Reparo do DNA/genética , RecQ Helicases/genética , RecQ Helicases/metabolismo , Replicação do DNA , Dano ao DNA/genética , Proliferação de Células/genéticaRESUMO
BACKGROUND: People with spinal cord injury (SCI) frequently develop neuropathic pain (NP) that worsens disability and diminishes rehabilitation efficacy. Chronic NP is presently incurable due to poor understanding of underlying mechanisms. We hypothesized that multilocus neuroinflammation (NIF) might be a driver of SCI NP, and tested it by investigating whether NP coexisted with central NIF, neurotransmission (NTM), neuromodulation (NML) and neuroplasticity (NPL) changes post-SCI. METHODS: Female Sprague-Dawley rats (230-250 g) with T10 compression or laminectomy were evaluated for physical conditions, coordinated hindlimb functions, neurological reflexes, and mechanical/thermal sensitivity thresholds at 1 day post-injury (p.i.) and weekly thereafter. Eight weeks p.i., central nervous system tissues were histochemically and immunohistochemically characterized for parameters/markers of histopathology and NIF/NTM/NML/NPL. Also analyzed was the correlative relationship between levels of selected biomarkers and thermosensitivity thresholds via statistical linear regression. RESULTS: SCI impaired sensorimotor functions, altered reflexes, and produced spontaneous pain signs and hypersensitivity to evoked nociceptive, mechanical, and thermal inputs. Only injured spinal cords exhibited neural lesion, microglia/astrocyte activation, and abnormal expression of proinflammatory cytokines, as well as NIF/NTM/NML/NPL markers. Brains of SCI animals displayed similar pathophysiological signs in the gracile and parabrachial nuclei (GrN and PBN: sensory relay), raphe magnus nucleus and periaqueduct gray (RMN and PAG: pain modulation), basolateral amygdala (BLA: emotional-affective dimension of pain), and hippocampus (HPC: memory/mood/neurogenesis). SCI augmented sensory NTM/NPL (GrN and PBN); increased GAD67 (PAG) level; reduced serotonin (RMN) and fear-off neuronal NTR2 (BLA) expressions; and perturbed neurogenesis (HPC). CONCLUSION: T10 compression caused chronic hyperalgesia that coexisted with NIF/NTM/NML/NPL responses at multilevel neuroaxis centers. The data have provided multidimensional biomarkers as new mechanistic leads to profile SCI NP for therapeutic/therapy development.
Assuntos
Neuralgia , Traumatismos da Medula Espinal , Ratos , Animais , Feminino , Hiperalgesia/metabolismo , Ratos Sprague-Dawley , Neuralgia/metabolismo , Traumatismos da Medula Espinal/patologia , Inflamação/complicações , BiomarcadoresRESUMO
Objective: Peripheral T-cell lymphomas (PTCLs) are an uncommon and quite heterogeneous group of disorders, representing only 10%-15% of all non-Hodgkin lymphomas. Although both molecular and clinical studies have increased in recent years, we still have little knowledge regarding real-life practice with PTCLs. In this study, we aimed to investigate the clinical characteristics and treatment outcomes of a large population-based cohort of patients presenting with systemic non-cutaneous PTCL. Materials and Methods: We conducted a multicenter retrospective analysis of 190 patients consecutively diagnosed and treated with non-cutaneous PTCLs between 2008 and 2016. Results: Considering all first-line treatment combinations, the overall response rate was 65.9% with 49.4% complete remission (n=81) and 16.5% partial response (n=27). The 5-year overall survival and event-free survival rates were significantly different between the transplant and non-transplant groups (p<0.01, and p=0.033, respectively). Conclusion: The retrospective analysis of a large volume of real-life data on the Turkish experience regarding non-cutaneous PTCL patients showed consistent results compared to other unselected PTCL cohorts with some minor differences in terms of survival and transplantation outcomes. The long-term outcome of patients who receive autologous hematopoietic cell transplantation as part of upfront consolidation or salvage therapy is favorable compared to patients who are unable to receive high-dose therapy.
Assuntos
Hematologia , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/terapia , Estudos Retrospectivos , Transplante Autólogo , Resultado do TratamentoRESUMO
Objective: Achieving an early molecular response (EMR) is crucial for improving the prognosis of patients with chronic myeloid leukemia (CML). The halving time (HT) and reduction ratio (RR) of BCR::ABL1 transcript levels have recently emerged as additional prognostic indexes besides the BCR::ABL1 International Scale (IS). We aimed to investigate the prognostic role of BCR::ABL1 transcript levels, HT, and RR on molecular response kinetics at 3 months in patients with newly diagnosed chronic-phase (CP)-CML. Materials and Methods: Forty patients with CP-CML who received first-line imatinib treatment were included in this study. BCR::ABL1 transcript levels and molecular responses at baseline and at 3, 6, 12, and 24 months of treatment were evaluated retrospectively. Major molecular response (MMR) at 12 months and event-free survival (EFS) were determined as primary endpoints and the effects of treatment kinetics on these parameters were examined. Results: Of the 40 patients, BCR::ABL1 IS was ≤10% at 3 months in 72.5%, representing EMR. The rate of event occurrence was 45.5% in patients with BCR::ABL1 IS of >10%, whereas it was 6.9% in those with BCR::ABL1 IS of ≤10% (p=0.004). MMR was detected in 62.1% of the patients with EMR and in 9.1% of those without EMR (p=0.003). The cut-off value for achieving MMR was 24 days for HT and 0.04 for RR. Deep molecular response (DMR) at 24 months was associated with HT of ≤24 days and RR of ≤0.04. EFS was found to be significantly better in the group with BCR::ABL1 IS of ≤10% and HT of ≤24 days (p=0.001) and in the group with BCR::ABL1 IS of ≤10% and RR of ≤0.04 (p=0.007) compared to others. Conclusion: Our findings revealed that MMR could be predicted via EMR as well as by HT and RR. Additionally, HT of ≤24 days and RR of ≤0.04 were more important than BCR::ABL1 IS of ≤10% in achieving DMR at 24 months, and the combination of BCR::ABL1 IS of ≤10% with both HT of ≤24 days and RR of ≤0.04 has the best predictive value for EFS.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide de Fase Crônica , Doença Crônica , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos RetrospectivosRESUMO
Coronavirus disease-2019 continues to have a serious impact in countries with the effect of new variant viruses emerging with mutations. While the effectiveness and protection of the vaccine have been determined all over the world, some vaccine-related side effects can be detected in the form of cases. In our case, the patient was admitted to the emergency department of our hospital with complaints of weakness and progressive rash on his legs. Diffuse petechiae purpura on the legs of the patient was observed and complete blood count revealed thrombocytopenia. Peripheral blood smear supported the blood count test results with thrombocytopenia, secondary causes of thrombocytopenia were excluded, and the patient was diagnosed with vaccine-induced immune thrombocytopenia.
RESUMO
Acinar cystic transformation (ACT) of the pancreas is a rare non-neoplastic cystic lesion. It is most frequently observed in the head of the pancreas. Despite advances in radiologic imaging methods, preoperative diagnosis of acinar cystic transformation is difficult, it is often confused with other cystic lesions. Here, we report three cases of acinar cystic transformation, one of which showed diffuse involvement of the pancreas, and the remaining two were multilocular localized cystic lesions. We analyzed their histomorphologic and immunohistochemical features. The patients' ages ranged between 15 and 43 years and the ratio of females to males was 2:1. On microscopic examination, the cysts were lined by a single layer of flattened-cuboidal or columnar epithelial cells. The epithelial cells were diffusely positive with trypsin and keratin 7, but patchy with keratin 19. Due to its rarity and lack of radiologic and clinical awareness compared with other pancreatic cystic lesions, preoperative diagnosis of acinar cystic transformation is difficult and not definitive. All cases reported to date have been clinically benign and there is no evidence of recurrence or malignant transformation. The optimal treatment and whether to perform surgery remain controversial.
Assuntos
Cisto Pancreático , Neoplasias Pancreáticas , Adolescente , Adulto , Células Epiteliais/patologia , Feminino , Humanos , Masculino , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Pâncreas/cirurgia , Cisto Pancreático/diagnóstico , Cisto Pancreático/patologia , Cisto Pancreático/cirurgia , Neoplasias Pancreáticas/patologia , Adulto JovemRESUMO
BACKGROUND: Mucormycosis is an emerging aggressive mold infection. This study aimed to assess the outcome of hospitalized adults with rhino-orbito-cerebral mucormycosis (ROCM). The secondary objective was to identify prognostic factors in this setting. METHODS: This study was an international, retrospective, multicenter study. Patients' data were collected from 29 referral centers in 6 countries. All qualified as "proven cases" according to the EORTC/MSGERC criteria. RESULTS: We included 74 consecutive adult patients hospitalized with ROCM. Rhino-orbito-cerebral type infection was the most common presentation (n = 43; 58.1%) followed by rhino-orbital type (n = 31; 41.9%). Twenty (27%) had acquired nosocomial bacterial infections. A total of 59 (79.7%) patients (16 in combination) received appropriate antifungal treatment with high-doses of liposomal amphotericin B. Fifty-six patients (75.7%) underwent curative surgery. Thirty-five (47.3%) required intensive care unit admission (27; 36.5% under mechanical ventilation). Hospital survival was 56.8%, being reduced to 7.4% in patients with invasive mechanical ventilation. A multivariate binary backward logistic regression model identified confusion at admission (OR 11.48), overlapping hospital-acquired infection (OR 10.27), use of antifungal treatment before diagnosis (OR 10.20), no surgical debridement (OR 5.92), and the absence of prior sinusitis (OR 6.32) were independently associated with increased risk for death. CONCLUSION: Today, ROCM still has high mortality rate. Improving source control, rational therpy, and preventing nosocomial infections may improve survival in this severe infection.
Assuntos
Infecções Oculares Fúngicas , Mucormicose , Doenças Orbitárias , Adulto , Antifúngicos/uso terapêutico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Humanos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Doenças Orbitárias/diagnóstico , Doenças Orbitárias/tratamento farmacológico , Estudos RetrospectivosRESUMO
The transmembrane domain recognition complex (TRC) pathway is required for the insertion of C-terminal tail-anchored (TA) proteins into the lipid bilayer of specific intracellular organelles such as the endoplasmic reticulum (ER) membrane. In order to facilitate correct insertion, the recognition complex (consisting of BAG6, GET4 and UBL4A) must first bind to TA proteins and then to GET3 (TRC40, ASNA1), which chaperones the protein to the ER membrane. Subsequently, GET1 (WRB) and CAML form a receptor that enables integration of the TA protein within the lipid bilayer. We report an individual with the homozygous c.633 + 4A>G splice variant in CAMLG, encoding CAML. This variant leads to aberrant splicing and lack of functional protein in patient-derived fibroblasts. The patient displays a predominantly neurological phenotype with psychomotor disability, hypotonia, epilepsy and structural brain abnormalities. Biochemically, a combined O-linked and type II N-linked glycosylation defect was found. Mislocalization of syntaxin-5 in patient fibroblasts and in siCAMLG deleted Hela cells confirms this as a consistent cellular marker of TRC dysfunction. Interestingly, the level of the v-SNARE Bet1L is also drastically reduced in both of these models, indicating a fundamental role of the TRC complex in the assembly of Golgi SNARE complexes. It also points towards a possible mechanism behind the hyposialylation of N and O-glycans. This is the first reported patient with pathogenic variants in CAMLG. CAMLG-CDG is the third disorder, after GET4 and GET3 deficiencies, caused by pathogenic variants in a member of the TRC pathway, further expanding this novel group of disorders.
Assuntos
Retículo Endoplasmático , Bicamadas Lipídicas , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Glicosilação , Células HeLa , Humanos , Bicamadas Lipídicas/análise , Bicamadas Lipídicas/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas Qa-SNARE/metabolismo , Proteínas Qc-SNARE/análise , Proteínas Qc-SNARE/metabolismo , Ubiquitinas/metabolismoRESUMO
Uncertainties and risks play a central role in creating vulnerabilities for logistics service operations. Over the years, Logistic Service Providers (LSPs) have learned how to ensure resilience to confront uncertainties and risks triggered by adverse events. However, quite unlike any seen in recent times, the COVID-19 pandemic brings about unavoidable uncertainties and risks for the logistics industry. Yet, there is no common approach to contextualize how they interact together. We incorporate an empirical research design and make a threefold contribution: first, we identify uncertainties and risks that LSPs encounter during the COVID-19 pandemic and investigate their prominence. Second, we unveil intertwined schemes of afore-identified uncertainties and risks and augment the understanding of their cause-effect structure. Third, we provide an uncertainty and risk assessment guideline for LSPs affected by threats emerging from unforeseeable crises. In this study, we combine qualitative work and the fuzzy DEMATEL method. Qualitative thematic analysis of in-depth interviews reveals the most important uncertainties (COVID-19 measures, employee welfare, forecast horizon, demand change, and government regulations) and risks (COVID-19 risk, delivery delays, supply chain disruptions, financial failure, and product returns) for LSPs. The fuzzy DEMATEL method shows that COVID-19 measures and COVID-19 risk are highly prominent and influence other factors. The results indicate that demand change, government regulations, and supply chain disruptions are net causers, and employee welfare, financial failure, forecast horizon, delivery delays, and product returns are net receivers. Distinctly, employee welfare is the most affected factor, empirically confirming that major risks for LSPs are related to the human factor. More investigation in our results suggests that supply chain disruptions and demand change, two factors triggered by the COVID-19 pandemic, influence financial failure and forecast horizon, two factors associated with operational performance.
RESUMO
OBJECTIVES: This study aimed to investigate the frequency and status of depression and anxiety among mothers of children with inborn errors of metabolism (IEM) who were on a restricted diet and previously experienced metabolic crises. METHODS: This cross-sectional multicenter descriptive study included 93 children with IEM who were on restricted diet. The patients were divided into two groups: those who had experienced metabolic crises (n=44, urea cycle defect, organic acidemia, maple syrup urine disease, hereditary fructose intolerance) and those who had not experienced previous metabolic crises (n=49; phenylketonuria, galactosemia, and non-ketotic hyperglycinemia). The control group comprised 37 healthy children. The mothers of the patients and control participants answered a questionnaire about their and their children's demographic and clinical characteristics and completed the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI-S and STAI-T). RESULTS: The maternal BDI, STAI-S, and STAI-T scores were 6.3±5.2, 36.1±11.2, and 39.9±8.8, respectively, in the control group. The maternal BDI, STAI-S, and STAI-T scores of the children who had experienced (19.2±9.7; 44.0±12.4; 47.9±10.6) and those who had not experienced (13.9±9.1; 40.7 ±8.6; 45.3±8.3) a crisis were significantly higher than for the controls. The BDI score was significantly higher for the mothers of children who had experienced a crisis (p=0.011), whereas no significant difference was determined between the two patient groups regarding STAI-S and STAI-T scores. The mothers of four children who had experienced metabolic crises were on antidepressant therapy. CONCLUSION: Although their children were on a similar restricted diet, the mothers of children who previously experienced or who had the risk of experiencing metabolic crises had higher depression scores as compared with the mothers of children who did not experience a previous crisis. Early supportive therapy may be required for the families of these patients to lower the burden of stress.
Assuntos
Ansiedade/diagnóstico , Depressão/diagnóstico , Erros Inatos do Metabolismo/complicações , Mães/psicologia , Adulto , Ansiedade/epidemiologia , Ansiedade/psicologia , Criança , Efeitos Psicossociais da Doença , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Feminino , Humanos , Masculino , Erros Inatos do Metabolismo/psicologia , Mães/estatística & dados numéricos , Poder Familiar/psicologia , TurquiaRESUMO
NK (Natural Killer) cell-mediated adoptive immunotherapy has gained attention in hematology due to the progressing knowledge of NK cell receptor structure, biology and function. Today, challenges related to NK cell expansion and persistence in vivo as well as low cytotoxicity have been mostly overcome by pioneering trials that focused on harnessing NK cell functions. Recent technological advancements in gene delivery, gene editing and chimeric antigen receptors (CARs) have made it possible to generate genetically modified NK cells that enhance the anti-tumor efficacy and represent suitable "off-the-shelf" products with fewer side effects. In this review, we highlight recent advances in NK cell biology along with current approaches for potentiating NK cell proliferation and activity, redirecting NK cells using CARs and optimizing the procedure to manufacture clinical-grade NK and CAR NK cells for adoptive immunotherapy.
RESUMO
Oropharyngeal cancer (OPC), which is a common type of head and neck squamous cell carcinoma (HNSCC), is associated with tobacco and alcohol use, and human papillomavirus (HPV) infection. Underlying mechanisms and as a result prognosis of the HPV-positive and HPV-negative OPC patients are different. Like stem cells, the ability of self-renewal and differentiate, cancer stem cells (CSCs) have roles in tumor invasion, metastasis, drug resistance, and recurrence after therapy. Research revealed their roles to some extent in all of these processes but there are still many unresolved points to connect to CSC-targeted therapy. In this review, we will focus on what we currently know about CSCs of OPC and limitations of our current knowledge. We will present perspectives that will broaden our understanding and recent literature which may connect to therapy.