Prevention of insulin aggregation by dicarboxylic amino acids during prolonged infusion

The dicarboxylic amino acids, aspartic and glutamic acid, at their isoelectric pH, reduced aggregation of insulin solutions in vitro for 16 days during continuous agitation at 37 degrees C. Unprotected insulin solutions, when infused via a 14-day implantable infusion device in diabetic Chinese hamsters, controlled plasma glucose levels for only 2 days, followed by escape coincident with insulin aggregation. However, when insulin solutions were protected with glutamic acid, euglycemia was maintained for the 14-day life of the device.     

Blood Brain Barrier Injury in Diabetes: Unrecognized Effects on Brain and Cognition

Diabetes mellitus (DM) is a disorder due to the inability properly to metabolize glucose associated with dysregulation of metabolic pathways of lipids and proteins resulting in structural and functional changes of various organ systems. DM has detrimental effects on the vasculature, resulting in the development of various cardiovascular diseases and stemming from microvascular injury. The blood brain barrier (BBB) is a highly specialized structure protecting the unique microenvironment of the brain. Endothelial cells, connected by junctional complexes and expressing numerous transporters, constitute the main cell type in the BBB. Other components, including pericytes, basement membrane, astrocytes and perivascular macrophages, join endothelial cells to form the neurovascular unit (NVU) and contribute to the proper function and integrity of the BBB. The role of the BBB in the pathogenesis of diabetic encephalopathy and other diabetes-related complications in the central nervous system is apparent. However, the mechanisms, timing and consequences of BBB injury in diabetes are not well understood. The importance of further studies related to barrier dysfunction in diabetes is dictated by its potential involvement in the cognitive demise associated with DM. This review summarizes the impact of DM on BBB/NVU integrity and function leading to neurological and cognitive complications.     

Cross-Cultural Translation and Adaptation to Brazilian Portuguese of the Paediatric Pain Profile in Children With Severe Cerebral Palsy

ContextPain is a prevalent symptom in children with severe cerebral palsy (CSCP), mainly as a result of the progression of muscle contractures, bone deformities, gastroesophageal reflux, and recurrent infections. Considering the lack of verbal communication in this population, both pain diagnosis and assessment of the analgesic treatment are often neglected. Although the Paediatric Pain Profile (PPP), an instrument with 20 items, is used to assess behavior indicative of pain in CSCP, it is not validated in Brazil.ObjectivesTo translate, adapt, and evaluate the psychometric properties of the PPP to Brazilian Portuguese.MethodsThe study was carried out at a philanthropic institution for CSCP and a university hospital. The sample of CSCP unable to communicate through speech or any device, their respective parents or primary caregivers, and health professionals were included. First, the instrument was translated and then back translated, and its clarity was evaluated by parents, primary caregivers, and professionals. The psychometric properties of the final version were evaluated for internal consistency (Cronbach's α) and stability (test-retest).ResultsForty-five children with a mean (SD) chronological age of 16 (8.69) years, 26 of whom were male, were included in the study. A total of 150 applications of PPP were carried out: 30 to assess clarity and 120 to assess the psychometric properties. Each item of the translated version showed a median between 3.00 and 4.00, considered to be clear and very clear, respectively. The internal consistency of the items was α = 0.864, with no significant difference between test and retest (P = 0.271).ConclusionThe adapted version of the PPP in Brazilian Portuguese demonstrated good internal consistency (similar to the original instrument) and stability over time, decisive for the next step of clinical validation for CSCP.     

Differential prostaglandin formation induced by convulsions in the brain of mice susceptible (DBA/2J) and resistant (CFLP) to acoustic stimulation

Endogenous cerebral prostanoids possess anticonvulsant properties. This study investigates possible age-dependent anomalies of prostanoid synthesis in the brain of seizure-prone DBA/2J (DBA2) mice as compared to sound stimulus-resistant CFLP mice. Irrespective of the age of the animals, a large increase of prostaglandin (PG) D2 and E2 in the brain of CFLP mice was observed in response to pentylenetetrazol (PTZ)-, or electroshock (ES)-induced seizures. Significantly less PGD2 and PGE2 was formed in the brain of DBA2 mice at day 21 after birth when subjected to PTZ or ES convulsions. At 42 days of age, however, this deficit of cerebral PGD2 synthesis in DBA2 mice disappeared concomitantly with the age-related decrease in audiogenic seizure (AS) susceptibility, whereas the deficit of PGE2 formation persisted. These results suggest that a deficiency of cerebral PGD2 synthesis may be one of the factors responsible for the AS susceptibility of the DBA2 mice. In contrast to PTZ or ES convulsions, acoustically induced seizures of the DBA2 mice were not accompanied by cerebral prostanoid synthesis. This supports the view that the pathways involved in AS are different from those involved in PTZ or ES models of epilepsy.     

qSOFA score poorly predicts critical progression in COVID-19 patients

Wiener Medizinische Wochenschrift - In December 2019, the new virus infection coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)...     

12q14 microdeletion syndrome: A family with short stature and Silver-Russell syndrome (SRS)-like phenotype and review of the literature

We report here on the first family with short stature and Silver-Russell-like phenotype due to a microdeletion in 12q14.3. The Netchine-Harbison clinical scoring system was used for the clinical diagnosis of Silver-Russell syndrome (SRS). The three affected first-degree relatives (index patient, mother and brother) presented with prenatal and postnatal growth retardation, feeding difficulties, a prominent forehead and a failure to thrive, but did not show relative macrocephaly. In addition, our index patient showed dysmorphic facial features, periodically increased sweating, and scoliosis. Learning problems and cardiac arrhythmia presented as additional features of her brother. Using high-resolution array-CGH, heterozygosity for a 1.67?Mb deletion in 12q14.3 was detected in the index patient. The heterozygous loss was confirmed by MLPA in the index patient and the other two affected family members. The deletion includes the genes HMGA2, LLPH, TMBIM4, IRAK3, HELB, GRIP1, and the pseudogene RPSAP52. We conclude from these results and from the data of other patients reported in the literature that haploinsufficiency of HMGA2 leads to the short stature in this family.     

Levels of interleukin (IL)‐6 and IL‐8 are elevated in serum and bronchoalveolar lavage fluid of haematological patients with invasive pulmonary aspergillosis

Aspergillus spp. have been shown to induce T‐helper cell (Th) 1 and Th17 subsets resulting in elevated levels of several cytokines. The objective of this study was to analyse a bundle of cytokines in serum and bronchoalveolar lavage fluid (BALF) in patients with and without invasive pulmonary aspergillosis (IPA). This nested case‐control analysis included 10 patients with probable/proven IPA and 20 matched controls without evidence of IPA, out of a pool of prospectively enrolled (2014‐2017) adult cases with underlying haematological malignancies and suspected pulmonary infection. Serum samples were collected within 24 hours of BALF sampling. All samples were stored at ?70°C for retrospective determination of cytokines. IL‐6 and IL‐8 were significantly associated with IPA in both serum (P = .011 and P = .028) and BALF (P = .006 and P = .012, respectively), and a trend was observed for serum IL‐10 (P = .059). In multivariate conditional logistic regression analysis, IL‐10 remained a significant predictor of IPA in serum and IL‐8 among BALF cytokines. In conclusion, levels of IL‐6 and IL‐8 were significantly associated with probable/proven IPA, and a similar trend was observed for serum IL‐10. Future cohort studies should determine the diagnostic potential of these cytokines for IPA, and evaluate combinations with other IPA biomarkers/diagnostic tests.