A case of cerebellar hypoplasia in a Chinese infant with osteogenesis imperfecta

We report a unique case of unilateral cerebellar hypoplasia in a young Chinese girl with osteogenesis imperfecta type IV. Magnetic resonance imaging showed mild basilar invagination and impression. Although unilateral cerebellar hypoplasia and osteogenesis imperfecta may have been coincidental diagnoses, we propose possible mechanisms for unilateral cerebellar hypoplasia secondary to osteogenesis imperfecta. For example, cerebellar hypoplasia may have been because of vascular disruption or direct compression to the posterior circulation in utero. Foetuses with osteogenesis imperfecta are more susceptible to the above risks compared to the normal foetus because of associated craniocervical anomalies and a poorly ossified skull.published_or_final_versio

The eyes do not see what the mind does not know : an underreported feature in mature cystic teratoma of the ovary

Mature cystic teratoma is the commonest ovarian germ cell tumour which accounts for 70% of all benign ovarian neoplasms in the reproductive age groups. Being a pluripotent germ cell tumour, mature cystic teratoma has at least two out of three mature embryonic germ cell components: ectoderm, mesoderm and endoderm. The presence of multiple cystic spaces within the tumour wall, also known as pneumatosis cystoides-like appearance is rarely described but a characteristic feature in cystic teratoma of the ovary. Currently, there is little information concerning the mechanism of its formation. Herein, we described an unusual case of ovarian mature cystic teratoma in a 31-year-old pregnant female with multiple sieve-like areas resembling pneumatosis cystoides of the intestine. Macroscopic and histological examination of the ovary revealed features diagnostic of mature cystic teratoma. Intriguingly, multiple cystic spaces of variable sizes were found within the cyst wall histologically. They were lined partially or completely by foamy histiocytes and foreign body type multinucleated giant cells, exhibiting strong CD68 immunoreactivity. Vascular endothelial markers (CD31 and CD34) and epithelial marker (cytokeratin AE1/AE3) were negative. A diagnosis of mature cystic teratoma with pneumatosis cystoides-like feature was rendered. The patient was discharged well with no signs and symptoms of early labour. The etiopathogenesis of this intriguing histological feature is briefly discussed in this article

Evaluation of imaging ordering by general practitioners in Australia, 2002–03 to 2011–12

Introdução: A deteção dos abusos contra crianças não é fácil para o médico, pois a história clínica recolhida é muitas vezes enganosa, os achados físicos são muitas vezes inespecíficos e os médicos, na maioria dos casos, não incluem o abuso no diagnóstico diferencial dos quadros clínicos com que se confrontam. Este diagnóstico é particularmente complexo no caso das queimaduras, cujas consequências, pelo menos do ponto de vista psicológico, são sempre graves. Daí a necessidade de cada vez se conhecerem mais profundamente estas situações, nas suas diversas vertentes, em cada país e comunidade, para que as medidas de detenção, diagnósticos e prevenção se possam adequar a cada realidade. Objetivo: Contribuir para conhecer melhor esta realidade e para reforçar a ideia da necessidade urgente da organização dos serviços em Angola, para que as equipas multidisciplinares possam existir e intervir adequada e atempadamente, para bem das vítimas, da comunidade e da justiça. Material e Métodos: Foram estudadas 230 crianças admitidas por queimaduras na Unidade de Queimados do Hospital Neves Bendinha, em Luanda. A ficha de recolha de dados foi preenchida durante o período de internamento das crianças, incluindo dados constantes do processo clínico hospitalar e outros obtidos através da entrevista de um dos progenitores ou representante legal da criança. Resultados e Discussão: As vítimas eram muito novas (50% até aos 5 anos; média de idade 7 anos), encontrando-se 99.6% a cargo dos familiares os quais, em apenas 69% dos casos, foram as pessoas que as levaram ao hospital; 57% não foram levadas ao hospital no dia do evento, sendo que em 77% dos casos este aconteceu em casa. Estes aspetos podem estar relacionados com a tentativa de ocultação dos cassos abusivos. De acordo com os registos clínicos, 47% das queimaduras associava-se a negligência, 33% a acidente e 20% a abuso. A queimadura provocada por imersão em água quente verificou-se em 75% dos casos alegadamente abusivos. Os locais mais atingidos foram os membros superiores (22%), tórax/mamas (22%) e membros inferiores (18%), para todos os casos, verificando-se que a região genital e nádegas sofreu mais queimaduras nas situações alegadamente abusivas (7%). As queimaduras figuradas, apesar de muito escassas no geral, surgiram em 50% dos casos de suspeita de abuso, bem como a distribuição bilateral e simétrica das lesões (em 57% destes casos), o que é altamente sugestivo de lesões intencionalmente infligidas. As queimaduras foram de 2º grau em 65% dos casos, sendo as mais graves nos casos supostamente devidos a abuso; no entanto, foi nestes casos que houve menos atingimento da área corporal (74% até 10% da área corporal), talvez porque a queimadura intencional foi aplicada a uma área concreta. Em 63% dos alegados abusos encontraram-se outras lesões distintas das queimaduras e em 28% cicatrizes de lesões (o que pode traduzir reiteração do abuso). A denúncia da suspeita de abuso foi apresentada em apenas 26% dos casos, o que está de acordo com a ocultação típica destes casos. Os supostos abusadores seriam maioritariamente familiares da vítima e do sexo feminino (58% e 56%), respetivamente, com idade média de 24 anos (20% menores de idade) e em 62% dos casos havia referência a consumo abusivo de álcool. Estes casos seriam melhor apoiados se conseguisse: (1) promover a sua deteção precoce pelos profissionais que trabalham com crianças; (2) incentivar a sinalização/denúncia da sua suspeita por esses mesmos profissionais; (3) a colaboração de especialistas em medicina legal para apoiar o diagnóstico mais seguro dos casos; (4) definir normas procedimentais e protocolos que apoiassem o diagnóstico por esses especialistas e a sua boa articulação com os outros profissionais os quais, no seu conjunto, deveriam constituir uma equipa multidisciplinar de intervenção nestes casos.Introduction: It is difficult for a doctor to detect a children abuse, due to the fact that the history about the event is sometimes not true, the physical findings are usually unspecific, frequently doctors don´t include the abuse in the differential diagnosis. This diagnosis is particularly difficult to perform in burns, which consequences, at least from the psychological point of view, are always severe. That´s why is important to know deeply this situations, in their several strands, in each country and community, so the detection measures, diagnosis and prevention can be adjust to each reality. Objective: To contribute to better understand this reality and to reinforce the necessity to organize the services in Angola, so that the multidisciplinary teams can exist and act in accordance and within a suitable way and schedule, for the welfare of the victims, community and justice. Material and Methods: 230 children were studied; they were admitted in the burn unit from the Hospital Neves Bendinha, in Luanda, Angola. The collection of data forms was fulfilled during the inpatient period; it includes information from their medical historical process and others collected through an interview to the children´s parents or their legal representative. Results and Discussion: The victims are very young (50% until the age of 5; average: 7 years-old), in 99.6% their relatives were in charge, and in only 69% of the cases, the relatives took the children to the hospital; 57% were not taken to the hospital in the day of the event, and in 77% of the cases the event happened at home. These aspects can be related with the attempt to hide these abusive cases. Accordingly to the clinic registrations, 47% of the burns were associated to neglecting acts, 33% to accidents and 20% to abuse. Burns caused by the immersion in hot water were showed in 75% of the alleged abusive cases. The body parts more affected were the upper limbs (22%), chest/breast (22%) and lower limbs (18%), for all the cases; the genital area and buttocks were the regions where more burns were suffered by the alleged abused children (7%). The patterned burns, in spite of being very rare, appeared in 50% of the suspected abuses cases, as well as the bilateral distribution and symmetrical of the burns (in 57% of these cases); these may suggest that the burns were intentional inflicted. The burns were of 2nd degree in 65% of the cases, being the more severe in the abuse cases; however, in these cases there was less body burn (74% until 10% of body area), maybe because the intentional burn was applied in a concrete area. In 63% of the alleged abuses there were other injuries and in 28% scars (that may suggest the reiteration of the abuse). The abuse complaints were presented in only 26% of the cases, which is in accordance with the attempt to hide them. The alleged abusers were mainly the victims’ relatives and the females (58% and 56%, respectively), with an average age of 24 years (20% minors) and in 62% of the cases there was a reference to an abusive alcohol consumption. These cases would be better supported if it was possible to: (1) promote the early detection by the professional that work with children; (2) promote the report of the professionals regarding these events; (3) obtain collaboration from the forensic doctors to support a more secure diagnosis in these cases; (4) set some procedure rules and protocols that can support the diagnosis performed by these physicians and their better cooperation with other professionals, creating together a multidisciplinary team for the intervention in these cases

Paclitaxel induces immunogenic cell death in ovarian cancer via TLR4/IKK2/SNARE-dependent exocytosis

Emerging evidence shows that the efficacy of chemotherapeutic drugs are reliant on their capability to induce immunogenic cell death (ICD), thus transforming dying tumor cells into antitumor vaccines. We wanted to uncover potential therapeutic strategies that target ovarian cancer by having a better understanding of the standard-of-care chemotherapy treatment. Here, we showed in ovarian cancer that paclitaxel induced ICD-associated DAMPs (i.e. damage-associated molecular patterns, such as CALR exposure, ATP secretion and HMGB1 release) in vitro and elicited significant antitumor responses in tumor vaccination assays in vivo. Paclitaxel-induced TLR4 signaling was essential to the release of DAMPs, which lead to the activation of NF-κB-mediated CCL2 transcription and IKK2-mediated SNARE-dependent vesicle exocytosis, thus exposing CALR on the cell surface. Paclitaxel induced ER stress, which triggered PERK activation and eIF2α phosphorylation independent of TLR4. Paclitaxel chemotherapy induced T cell infiltration in ovarian tumors of the responsive patients; CALR expression in primary ovarian tumors also correlated with patients' survival and patient response to chemotherapy. These findings suggest that the effectiveness of paclitaxel relied upon the activation of antitumor immunity through ICD via TLR4 and highlighted the importance of CALR expression in cancer cells as an indicator of response to paclitaxel chemotherapy in ovarian cancer

A Comparison Between Chinese Children Infected with Coronavirus Disease-2019 and with Severe Acute Respiratory Syndrome 2003

OBJECTIVES: To compare the clinical and laboratory features of severe acute respiratory syndrome 2003 (SARS) and coronavirus disease 2019 (COVID-19) in two Chinese pediatric cohorts, given that the causative pathogens and are biologically similar. , STUDY DESIGN: This is a cross-sectional study reviewing paediatric patients with SARS (n = 43) and COVID-19 (n=244) who were admitted to the Princess Margaret Hospital in Hong Kong and Wuhan Children's Hospital in Wuhan, respectively. Demographics, hospital length of stay, clinical and laboratory features were compared RESULTS: Overall, 97.7% of patients with SARS and 85.2% of patients with COVID-19 had epidemiological associations with known cases. Significantly more patients with SARS developed fever, chills, myalgia, malaise, coryza, sore throat, sputum production, nausea, headache, and dizziness than patients COVID-19. No SARS patients were asymptomatic at the time of admission. 29.1% and 20.9% COVID-19 patients were asymptomatic on admission and throughout their hospital stay, respectively. More SARS patients required oxygen supplementation than COVID-19 patients (18.6 vs. 4.7%, P = 004). Only 1.6% COVID-19 and 2.3% SARS patients required mechanical ventilation. Leukopenia (37.2% vs. 18.6%, p=0.008), lymphopenia (95.4% versus 32.6%, p<0.01), and thrombocytopenia (41.9% vs 3.8%, p<0.001) were significantly more common in SARS than COVID-19 patients. The duration between positive and negative nasopharyngeal aspirate and the length in hospital stay were similar in COVID-19 patients regardless of whether they were asymptomatic or symptomatic, suggesting a similar duration of viral shedding. CONCLUSIONS: Children with COVID-19 were less symptomatic and had more favorable hematological findings than children with SARS

Saliva Viral Load Better Correlates with Clinical and Immunological Profiles in Children with Coronavirus Disease 2019

BACKGROUND: Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking. METHODS: Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19. FINDINGS: 91 patients were included between March and August 2020. NPS and saliva viral loads were correlated (r=0.315, p=0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log10 NPS (r=-0.532, p<0.001) and saliva (r=-0.417, p<0.001) viral loads for all patients were inversely correlated with the days from symptom onset with statistical significance. Patients with cough, sputum, and headache had significantly higher saliva, but not NPS, viral loads. Higher saliva, but not NPS, viral loads were associated with total lymphopenia, CD3 and CD4 lymphopenia (all p<0.05), and were inversely correlated with total lymphocyte (r=-0.43), CD3 (r=-0.55), CD4 (r=-0.60), CD8 (r=-0.41), B (r=-0.482), and NK (r=-0.416) lymphocyte counts (all p<0.05). Interpretation: Saliva viral loads on admission in children correlated better with clinical and immunological profiles than NPS

EM23, a natural sesquiterpene lactone, targets thioredoxin reductase to activate JNK and cell death pathways in human cervical cancer cells

Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants and found to have potential anticancer activities. However, the intracellular molecular targets of SLs and the underlying molecular mechanisms have not been well elucidated. In this study, we observed that EM23, a natural SL, exhibited anti-cancer activity in human cervical cancer cell lines by inducing apoptosis as indicated by caspase 3 activation, XIAP downregulation and mitochondrial dysfunction. Mechanistic studies indicated that EM23-induced apoptosis was mediated by reactive oxygen species (ROS) and the knockdown of thioredoxin (Trx) or thioredoxin reductase (TrxR) resulted in a reduction in apoptosis. EM23 attenuated TrxR activity by alkylation of C-terminal redox-active site Sec498 of TrxR and inhibited the expression levels of Trx/TrxR to facilitate ROS accumulation. Furthermore, inhibition of Trx/TrxR system resulted in the dissociation of ASK1 from Trx and the downstream activation of JNK. Pretreatment with ASK1/JNK inhibitors partially rescued cells from EM23-induced apoptosis. Additionally, EM23 inhibited Akt/mTOR pathway and induced autophagy, which was observed to be proapoptotic and mediated by ROS. Together, these results reveal a potential molecular mechanism for the apoptotic induction observed with SL compound EM23, and emphasize its putative role as a therapeutic agent for human cervical cancer.published_or_final_versio

Contrasting genetic association of IL2RA with SLE and ANCA-associated vasculitis.

BACKGROUND: Autoimmune diseases are complex and have genetic and environmental susceptibility factors. The objective was to test the genetic association of systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibody (ANCA) - associated systemic vasculitis (AAV) with SNPs in the IL2RA region and to correlate genotype with serum levels of IL-2RA. METHODS: Using a cohort of over 700 AAV patients, two SLE case-control studies and an SLE trio collection (totalling over 1000 SLE patients), and a TaqMan genotyping approach, we tested 3 SNPs in the IL2RA locus, rs11594656, rs2104286 & rs41295061, each with a prior association with autoimmune disease; rs11594656 and rs41295061 with type 1 diabetes (T1D) and rs2104286 with multiple sclerosis (MS) and T1D. RESULTS: We show that SLE is associated with rs11594656 (P = 3.87 x 10-7) and there is some evidence of association of rs41295061 with AAV (P = 0.0122), which both have prior association with T1D. rs2104286, an MS and T1D - associated SNP in the IL2RA locus, is not associated with either SLE or AAV. CONCLUSION: We have confirmed a previous suggestion that the IL2RA locus is associated with SLE and showed some evidence of association with AAV. Soluble IL-2RA concentrations correlate with rs11594656 genotype in quiescent disease in both AAV and SLE. Differential association of autoimmune diseases and SNPs within the IL2RA locus suggests that the IL2RA pathway may prove to play differing, as yet undefined, roles in each disease