Classical NF-κB activation impairs skeletal muscle oxidative phenotype by reducing IKK-α expression.

BACKGROUND: Loss of quadriceps muscle oxidative phenotype (OXPHEN) is an evident and debilitating feature of chronic obstructive pulmonary disease (COPD). We recently demonstrated involvement of the inflammatory classical NF-κB pathway in inflammation-induced impairments in muscle OXPHEN. The exact underlying mechanisms however are unclear. Interestingly, IκB kinase α (IKK-α: a key kinase in the alternative NF-κB pathway) was recently identified as a novel positive regulator of skeletal muscle OXPHEN. We hypothesised that inflammation-induced classical NF-κB activation contributes to loss of muscle OXPHEN in COPD by reducing IKK-α expression. METHODS: Classical NF-κB signalling was activated (molecularly or by tumour necrosis factor α: TNF-α) in cultured myotubes and the impact on muscle OXPHEN and IKK-α levels was investigated. Moreover, the alternative NF-κB pathway was modulated to investigate the impact on muscle OXPHEN in absence or presence of an inflammatory stimulus. As a proof of concept, quadriceps muscle biopsies of COPD patients and healthy controls were analysed for expression levels of IKK-α, OXPHEN markers and TNF-α. RESULTS: IKK-α knock-down in cultured myotubes decreased expression of OXPHEN markers and key OXPHEN regulators. Moreover, classical NF-κB activation (both by TNF-α and IKK-ß over-expression) reduced IKK-α levels and IKK-α over-expression prevented TNF-α-induced impairments in muscle OXPHEN. Importantly, muscle IKK-α protein abundance and OXPHEN was reduced in COPD patients compared to controls, which was more pronounced in patients with increased muscle TNF-α mRNA levels. CONCLUSION: Classical NF-κB activation impairs skeletal muscle OXPHEN by reducing IKK-α expression. TNF-α-induced reductions in muscle IKK-α may accelerate muscle OXPHEN deterioration in COPD.

Spaced taste avoidance conditioning in Lymnaea.

We succeeded in taste avoidance conditioning with sucrose as the conditional stimulus (CS) and an electrical stimulus (∼1000V, 80µA) as the unconditional stimulus (US). With 15 paired CS-US presentations on a single day, we were able to elicit both short-term memory (STM) and long-term memory (LTM) persisting for at least one week. However, while STM was elicited with 5, 8, 10, and 20 paired presentations of the CS-US on a single day, LTM was not. We found, however, that if we inserted a 3h interval between a first and a second set of CS-US pairings that both 8 and 20 paired CS-US presentations on a single day was now sufficient to cause LTM formation. Exposing snails to bryostatin before or during training enhanced LTM formation such that 8 paired presentations of the CS-US resulted in LTM.

The mitochondrial disease associated protein Ndufaf2 is dispensable for Complex-1 assembly but critical for the regulation of oxidative stress.

Deficiency in human mitochondrial Complex-1 has been linked to a wide variety of neurological disorders. Homozygous deletion of the Complex-1 associated protein, Ndufaf2, leads to a severe juvenile onset encephalopathy involving degeneration of the substantia nigra and other sub-cortical regions resulting in adolescent lethality. To understand the precise role of Ndufaf2 in Complex-1 function and its links to neurologic disease, we studied the effects on Complex-1 assembly and function, as well as pathological consequences at the cellular level, in multiple in vitro models of Ndufaf2 deficiency. Using both Ndufaf2-deficient human neuroblastoma cells and primary fibroblasts cultured from Ndufaf2 knock-out mice we found that Ndufaf2-deficiency selectively reduces Complex-1 activity. While Ndufaf2 is traditionally referred to as an assembly factor of Complex-1, surprisingly, however, Ndufaf2-deficient cells were able to assemble a fully mature Complex-1 enzyme, albeit with reduced kinetics. Importantly, no evidence of intermediate or incomplete assembly was observed. Ndufaf2 deficiency resulted in significant increases in oxidative stress and mitochondrial DNA deletion, consistent with contemporary hypotheses regarding the pathophysiology of inherited mutations in Complex-1 disorders. These data suggest that Ndufaf2, unlike other Complex-1 assembly factors, may be more accurately described as a chaperone involved in proper folding during Complex-1 assembly, since it is dispensable for Complex-1 maturation but not its proper function.

Budesonide versus prednisone with azathioprine for the treatment of autoimmune hepatitis in children and adolescents.

OBJECTIVE: To compare the effect of budesonide vs prednisone therapy both in combination with azathioprine in pediatric patients with autoimmune hepatitis (AIH). STUDY DESIGN: Forty-six patients with AIH (11 males and 35 females) aged 9-17 years were enrolled in a 6-month, prospective, double-blind, randomized, active-controlled, multicenter phase IIb study evaluating budesonide (n = 19; 3 mg twice or 3 times daily) vs prednisone (n = 27; 40 mg/day tapered to 10 mg/day), both with azathioprine (1-2 mg/kg/day), followed by a further 6 months of open-label budesonide therapy. The primary efficacy endpoint was complete biochemical remission (normal serum alanine aminotransferase and aspartate aminotransferase levels) without predefined steroid-specific side effects. RESULTS: We observed no statistically significant difference in the percentage of patients who met the primary endpoint between the budesonide (3 of 19; 16%) and prednisone groups (4 of 27; 15%) after 6 months, nor in the percentage of patients who experienced biochemical remission (budesonide, 6 of 19 [32%]; prednisone, 9 of 27 [33%]), lack of steroid-specific side effects (budesonide, 10 of 19 [53%]; prednisone, 10 of 27 [37%]). The mean weight gain was 1.2 ± 3.5 kg in the budesonide group and 5.1 ± 4.9 kg in the prednisone group (P = .006). A total of 42 patients received open-label budesonide treatment for another 6 months. After 12 months, 46% of these patients achieved complete remission. CONCLUSION: Oral budesonide with azathioprine can induce and maintain remission in pediatric patients with AIH and may be considered an alternative therapy to prednisone. The treatment causes fewer side effects and does not lead to weight gain; however, it may be less effective than prednisone in inducing remission.

Electroclinical features and long-term outcome of cryptogenic epilepsy in children with Down syndrome.

OBJECTIVE: To describe the electroclinical features and the long-term outcomes of epilepsy in a large cohort of males and females with Down syndrome who developed epilepsy in childhood. STUDY DESIGN: Subjects with Down syndrome and cryptogenic epilepsy with onset in childhood were identified retrospectively from the databases of 16 Italian epilepsy centers over a 40-year period. For each subject, age at onset of seizures, seizure semiology and frequency, electroencephalography characteristics, treatment with antiepileptic drugs, and long-term clinical and electroencephalography outcomes were analyzed. RESULTS: A total of 104 subjects (64 males [61.5%], 40 females [38.5%]) were identified. Seizure onset occurred within 1 year of birth in 54 subjects (51.9%), between 1 and 12 years in 42 subjects (40.4%), and after 12 years in 8 subjects (7.7%). Males had a younger age of seizure onset than females. Of the 104 subjects, 51 (49.0%) had infantile spasms (IS), 35 (33.7%) had partial seizures (PS), and 18 (17.3%) had generalized seizures (GS). Febrile seizures were recorded in 5 (4.8%) subjects. Intractable seizures were observed in 23 (22.1%) subjects, including 5 (9.8%) with IS, 8 (44.4%) with PS, and 10 (31.3%) with GS. CONCLUSION: Cryptogenic epilepsy in Down syndrome may develop during the first year of life in the form of IS or, successively, as PS or GS. Electroclinical features of IS resemble those of idiopathic West syndrome, with a favorable response to treatment with adrenocorticotropic hormone seen. Patients experiencing PS and GS may be resistant to therapy with antiepileptic drugs.

Time to menarche and final height after histrelin implant treatment for central precocious puberty.

OBJECTIVE: To compare final height, change in body mass index (BMI), and time from end of treatment until menarche in girls with central precocious puberty treated with the histrelin implant versus depot gonadotropin releasing hormone agonist injections. STUDY DESIGN: Chart review, interview, and final height measurements of 2 groups of girls with central precocious puberty; triptorelin depot (TD) group: 23 girls were treated from age 8.4 ± 0.3 with monthly injections of TD, for 26.7 ± 2.5 months; histrelin implant group: 11 girls were treated from age 8.7 ± 0.3 years for 28.4 ± 3.7 months, of whom 9 initially received monthly TD injections for 1.5-39 months. Final height, BMI (pretreatment vs recent), and time between either implant removal or last injection to menarche were compared. RESULTS: Time between removal of implant or last injection and menarche was 9.3 ± 1.5 (histrelin implant group) versus 16.1 ± 1.7 (TD group) months (P = .02). Predicted height at implant insertion was 156.8 ± 2.6 cm, and final height was 161.1 ± 2.0 cm (not significant [NS]). Predicted height for TD was 155.2 ± 1.9 cm and final height was 157.9 ± 1.7 cm (NS). Change from onset of treatment to final BMI-SDS for histrelin implant was -0.41 ± 0.3, and for TD was -0.03 ± 0.2 (NS). CONCLUSIONS: Menarche occurred sooner after implant removal. There was no difference in final height or BMI outcomes between the 2 treatment modalities.

Alteration of the sublingual microvascular glycocalyx in critically ill patients.

Glycocalyx degradation may contribute to microvascular dysfunction and tissue hypoperfusion during systemic inflammation and sepsis. In this observational study we evaluated the alteration of the sublingual microvascular glycocalyx in 16 healthy volunteers and 50 critically ill patients. Sidestream Dark Field images of the sublingual microcirculation were automatically analyzed by dedicated software. The Perfused Boundary Region (PBR) was calculated as the dimensions of the permeable part of the glycocalyx allowing the penetration of circulating red blood cells, providing an index of glycocalyx damage. The PBR was increased in ICU patients compared to healthy controls (2.7 [2.59-2.88] vs. 2.46 [2.37-2.59]µm, p<0.0001) and tended to be higher in the 32 septic patients compared to non-septics (2.77 [2.62-2.93] vs. 2.67 [2.55-2.75]µm, p=0.05), suggesting more severe glycocalyx alterations. A PBR of 2.76 showed the best discriminative ability towards the presence of sepsis (sensitivity: 50%, specificity: 83%; area under the receiver operating characteristic curve: 0.67, 95% CI 0.52-0.82, p=0.05). A weak positive correlation was found between PBR and heart rate (r=0.3, p=0.03). In 17 septic patients, a correlation was found between PBR and number of rolling leukocytes in post-capillary venules (RL/venule) (r=0.55, p=0.02), confirming that glycocalyx shedding enhances leukocyte-endothelium interaction.

Modulation of benzo[a]pyrene induced neurotoxicity in female mice actively immunized with a B[a]P-diphtheria toxoid conjugate.

Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also neurotoxic for mammalian species. To develop a prophylactic immune strategy against detrimental effects of B[a]P, female Balb/c mice immunized with a B[a]P-diphtheria toxoid (B[a]P-DT) conjugate vaccine were sub-acutely exposed to 2mg/kg B[a]P and behavioral performances were monitored in tests related to learning and memory, anxiety and motor coordination. mRNA expression of the NMDA receptor (NR1, 2A and 2B subunits) involved in the above behavioral functions was measured in 5 brain regions. B[a]P induced NMDA1 expression in three (hippocampus, amygdala and cerebellum) of five brain regions investigated, and modulated NMDA2 in two of the five brain regions (frontal cortex and cerebellum). Each one of these B[a]P-effects was reversed in mice that were immunized against this PAH, with measurable consequences on behavior such as anxiety, short term learning and memory. Thus active immunization against B[a]P with a B[a]P-DT conjugate vaccine had a protective effect and attenuated the pharmacological and neurotoxic effects even of high concentrations of B[a]P.

Using reactive hyperemia to assess the efficacy of local cooling on reducing sacral skin ischemia under surface pressure in people with spinal cord injury: a preliminary report.

OBJECTIVES: To investigate the efficacy of local cooling on reducing sacral skin ischemia in a weight-bearing position, and to identify the underlying physiological mechanisms using wavelet-based spectrum analysis of reactive hyperemia in people with spinal cord injury (SCI). DESIGN: Repeated-measures and before-after trial design. SETTING: University research laboratory. PARTICIPANTS: Wheelchair users with SCI with injury level between C4 and T5 (n=10) and able-bodied controls (n=10). INTERVENTIONS: Three protocols consisting of pressure without temperature changes, pressure with local cooling (Δt=-10°C), and pressure with local heating (Δt=+10°C) were tested. Each protocol consisted of a 10-minute baseline period, a 20-minute loading period at 60 mmHg, and a 20-minute recovery period (reactive hyperemia). A 30-minute washout period was allowed between protocols. MAIN OUTCOME MEASURES: A compound sensor head consisting of laser Doppler and heating and cooling probes was used to measure sacral skin blood flow and control skin temperature. Reactive hyperemic response to pressure and temperature stimuli was characterized in the time and frequency (metabolic [.0095-.02 Hz], neurogenic [.02-.05 Hz], and myogenic [.05-.15 Hz] components) domains. RESULTS: Pressure with local cooling resulted in a smaller reactive hyperemic response in both people with SCI and able-bodied controls as compared with pressure with local heating (P<.017) and pressure without temperature changes (P<.017), and the smaller hyperemia was attributed to reduced metabolic and neurogenic activities. People with SCI showed an attenuated response in reactive hyperemia (P<.017). CONCLUSIONS: This study supports the concept of using local cooling to reduce skin ischemia under surface pressure in people with SCI.

Hydroxypropyl-ß-cyclodextrin impacts renal and systemic hemodynamics in the anesthetized dog.

Hydroxypropyl-ß-cyclodextrin (HPßCD) is a complexation agent used to enhance drug solubilization and formulation stability. Although its toxicity is well characterized, its cardiovascular effects are less known. To investigate them, HPßCD was infused intravenously over 10 min in anesthetized dogs (10-40% (w/v, i.e. 200-800 mg/kg) in non-denervated animals and at 40% in denervated animals). HPßCD increased renal arteriolar resistance and decreased renal blood flow at all doses, almost immediately after infusion start, more drastically in females. A less pronounced increase in total peripheral resistance occurred in females only due to sex difference in sympathetic tone. Pulmonary hemodynamic parameters remained unaffected, suggesting that the renal effect was rather selective. As a consequence of the increased systemic blood pressure, heart rate decreased in normal animals without direct effect on cardiac conductance. This effect was abolished in denervated animals. This suggests that autonomous nervous feedback loops are functional in normal animals and that HPßCD has no direct chronotropic effect. In conclusion, systemic and renal hemodynamic changes should be considered as potential background effects at 200-400 mg/kg. At higher doses (800 mg/kg), changes are more pronounced and could mask/exacerbate hemodynamic response of drug candidate; such doses should be avoided in nonclinical safety studies.

Hypervascularized Large Vestibular Schwannomas: Single-Center Experience in a Series of Forty Cases.

Background: Vestibular schwannomas (VS) are usually hypovascularized benign tumors. Large VS (Koos grade IV) with unusual vascular architecture are defined as hypervascular (HVVS); the excessive bleeding during microsurgery has a negative impact on results. Methods: Forty consecutive patients were operated on for HVVS (group A). A tendency to bleed and adherence of capsule to nervous structures were evaluated by reviewing intraoperative video records. The cisternal facial nerve (FN) position was reported. Microsurgical removal was classified as total, near-total, subtotal, or partial and the MIB-1 index was evaluated in all. FN results were classified according to the House-Brackmann scale. Results: Results of Group A were compared with those of 45 patients operated on for large low-bleeding VS (group B). Mean tumor diameter was 3.81 cm in group A and 3.58 cm in group B; the mean age was 42.4 and 56.3 years, respectively. The mean American Society of Anesthesiologists Physical Status Scale class of group A was 1.67 versus 2.31 of group B (P < 0.01). Total or near-total resection was accomplished in 76.5% of group A versus 73.3% of group B. Tight capsule adhesion was observed in 67.5% of group A versus 57.8% of group B. Mean MIB-1 was 1.25% and 1.08%, respectively.FN anatomic preservation was possible in 84.6% of group A versus 95.5% of group B; 67.5% of group A had HB grade I or II FN outcome versus 93.3% of group B (P < 0.001). In group A, 8 patients (20.0%) experienced transient postoperative complications versus 4.4% of group B. Recurrence/regrowth was observed in 4 patients in group A versus 1 in group B. Conclusions: Intraoperative video for classification of HVVS was used. Microsurgery of large HVVS was associated with higher (usually transient) complications and recurrence/regrowth rates and poorer FN outcome, especially in patients with tight capsule adhesion.

MicroRNA Expression Profiling in Diabetic Kidney Disease.

The microRNAs (miRNAs) that can regulate diabetic kidney disease (DKD) have not been fully characterized. The aim of this study was to identify the miRNAs that affect DKD and could be used as specific biomarkers or therapeutic agents. First, kidney tissues from two DKD mouse models and control mice were screened for differences in miRNA expression by microarray analysis followed by quantitative real-time reverse transcription-PCR. Six miRNAs were differentially expressed from controls in both DKD mouse models. Among them, miRNA-125b-5p and miRNA-181b-5p were exclusively downregulated in the DKD mouse model. Next, we administered miRNA-181b-5p-mimic to DKD mice, which reduced the albuminuria and abnormal mesangial expansion. Pathway analysis and database research revealed that overexpression of miRNA-181b-5p significantly altered the expression of seven mRNAs in six known signaling pathways in the kidneys of DKD mice. Furthermore, the serum level of miRNA-125b-5p was significantly higher in patients with DKD (1.89±0.40-fold, P<0.05) compared with patients with other kidney diseases (0.94±0.13-fold) and healthy subjects (1.00±0.19-fold). Serum levels of miRNA-181b-5p were lower in patients with DKD (0.30±0.06-fold, P<0.05) compared with patients with other kidney diseases (1.06±0.20-fold) and healthy subjects (1.00±0.16-fold). These results suggest that miRNA-125b-5p and miRNA-181b-5p may represent novel diagnostic biomarkers and that miRNA-181b-5p may represent a therapeutic target for DKD.

Safety and Efficacy of Convalescent Plasma in Elderly COVID-19 Patients: The RESCUE Trial.

OBJECTIVE: To assess the safety and efficacy of convalescent plasma (CP) transfusion in elderly people with moderate to severe coronavirus disease 2019 (COVID-19) living in a long-term care facility (LTCF). PATIENTS AND METHODS: Twenty-two consecutive elderly patients with COVID-19 infection living in an LTCF in Lombardy, Italy, who were given CP during May 15 to July 31, 2020, were enrolled in a prospective cohort study. Their clinical, instrumental, and laboratory parameters were assessed following the CP treatment. The overall mortality rate in this group was compared with that recorded in other LTCFs in Lombardy during the 3-month period from March to May 2020. RESULTS: Of the 22 patients enrolled, 68.2% (n=15) received 1 CP unit, 27.3% (n=6) received 2 units, and 4.5% (n=1) received 3 units. Of the CP units transfused, 76.7% (23/30) had a neutralizing antibody titer of 1:160 or greater. No adverse reactions were recorded during or after CP administration. Improvements in clinical, functional, radiologic, and laboratory parameters during the 14 days after CP transfusion were observed in all 19 patients who survived. Viral clearance was achieved in all patients by the end of follow-up (median, 66 days; interquartile range, 48-80 days). The overall mortality rate was 13.6% (3/22), which compared favorably with that in the control group (38.3% [281/733]; P=.02) and corresponded to a 65% reduction in mortality risk. CONCLUSION: Early administration of CP with an adequate anti-severe acute respiratory syndrome coronavirus 2 antibody titer to elderly symptomatic patients with COVID-19 infection in an LTCF was safe and effective in eliminating the virus, restoring patients' immunity, and blocking the progression of COVID-19 infection, thereby improving patients' survival. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04569188.

Reversal of motor-skill transfer impairment by trihexyphenidyl and reduction of dorsolateral striatal cholinergic interneurons in Dyt1 ΔGAG knock-in mice.

DYT-TOR1A or DYT1 early-onset generalized dystonia is an inherited movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, or abnormal postures. The majority of the DYT1 dystonia patients have a trinucleotide GAG deletion in DYT1/TOR1A. Trihexyphenidyl (THP), an antagonist for excitatory muscarinic acetylcholine receptor M1, is commonly used to treat dystonia. Dyt1 heterozygous ΔGAG knock-in (KI) mice, which have the corresponding mutation, exhibit impaired motor-skill transfer. Here, the effect of THP injection during the treadmill training period on the motor-skill transfer to the accelerated rotarod performance was examined. THP treatment reversed the motor-skill transfer impairment in Dyt1 KI mice. Immunohistochemistry showed that Dyt1 KI mice had a significant reduction of the dorsolateral striatal cholinergic interneurons. In contrast, Western blot analysis showed no significant alteration in the expression levels of the striatal enzymes and transporters involved in the acetylcholine metabolism. The results suggest a functional alteration of the cholinergic system underlying the impairment of motor-skill transfer and the pathogenesis of DYT1 dystonia. Training with THP in a motor task may improve another motor skill performance in DYT1 dystonia.

Clec4e-Receptor Signaling in Myocardial Repair After Ischemia-Reperfusion Injury.

The bacterial C-type lectin domain family 4 member E (CLEC4E) has an important role in sterile inflammation, but its role in myocardial repair is unknown. Using complementary approaches in porcine, murine, and human samples, we show that CLEC4E expression levels in the myocardium and in blood correlate with the extent of myocardial injury and left ventricular (LV) functional impairment. CLEC4E expression is markedly increased in the vasculature, cardiac myocytes, and infiltrating leukocytes in the ischemic heart. Loss of Clec4e signaling is associated with reduced acute cardiac injury, neutrophil infiltration, and infarct size. Reduced myocardial injury in Clec4e -/- translates into significantly improved LV structural and functional remodeling at 4 weeks' follow-up. The early transcriptome of LV tissue from Clec4e -/- mice versus wild-type mice reveals significant upregulation of transcripts involved in myocardial metabolism, radical scavenging, angiogenesis, and extracellular matrix organization. Therefore, targeting CLEC4E in the early phase of ischemia-reperfusion injury is a promising therapeutic strategy to modulate myocardial inflammation and enhance repair after ischemia-reperfusion injury.

SGLT2 Inhibitor, Canagliflozin, Attenuates Myocardial Infarction in the Diabetic and Nondiabetic Heart.

The authors hypothesized that despite similar cardiovascular event rates, the improved cardiovascular survival from sodium glucose transporter 2 (SGLT2) inhibition, seen clinically, could be via a direct cytoprotective effect, including protection against myocardial ischemia/reperfusion injury. Langendorff-perfused hearts, from diabetic and nondiabetic rats, fed long-term for 4 weeks with canagliflozin, had lower infarct sizes; this being the first demonstration of canagliflozin's cardioprotective effect against ischemia/reperfusion injury in both diabetic and nondiabetic animals. By contrast, direct treatment of isolated nondiabetic rat hearts with canagliflozin, solubilized in the isolated Langendorff perfusion buffer, had no impact on infarct size. This latter study demonstrates that the infarct-sparing effect of long-term treatment with canagliflozin results from either a glucose-independent effect or up-regulation of cardiac prosurvival pathways. These results further suggest that SGLT2 inhibitors could be repurposed as novel cardioprotective interventions in high-risk cardiovascular patients irrespective of diabetic status.

Robot-assisted intravertebral augmentation corrects local kyphosis more effectively than a conventional fluoroscopy-guided technique.

OBJECTIVEIntravertebral augmentation (IVA) is a reliable minimally invasive technique for treating Magerl type A vertebral body fractures. However, poor correction of kyphotic angulation, the risk of cement leakage, and significant exposure to radiation (for the surgeon, the operating room staff, and the patient) remain significant issues. The authors conducted a study to assess the value of robot-assisted IVA (RA-IVA) for thoracolumbar vertebral body fractures.METHODSThe authors performed a retrospective, single-center study of patients who had undergone RA-IVA or conventional fluoroscopy-guided IVA (F-IVA) for thoracolumbar vertebral body fractures. Installation and operating times, guidance accuracy, residual local kyphosis, degree of restoration of vertebral body height, incidence of cement leakage, rate of morbidity, length of hospital stay, and radiation-related data were recorded.RESULTSData obtained in 30 patients who underwent RA-IVA were compared with those obtained in 30 patients who underwent F-IVA during the same period (the surgical indications were identical, but the surgeons were different). The mean ± SD installation time in the RA-IVA group (24 ± 7.5 minutes) was significantly shorter (p = 0.005) than that in the F-IVA group (26 ± 8 minutes). The mean operating time for the RA-IVA group (52 ± 11 minutes) was significantly longer (p = 0.026) than that for the F-IVA group (30 ± 11 minutes). All RA-IVAs and F-IVAs were Ravi's scale grade A (no pedicle breach). The mean degree of residual local kyphosis (4.7° ± 3.15°) and the percentage of vertebral body height restoration (63.6% ± 21.4%) were significantly better after RA-IVA than after F-IVA (8.4° ± 5.4° and 30% ± 34%, respectively). The incidence of cement leakage was significantly lower in the RA-IVA group (p < 0.05). The mean length of hospital stay after surgery was 3.2 days for both groups. No surgery-related complications occurred in either group. With RA-IVA, the mean radiation exposure was 438 ± 147 mGy × cm for the patient and 30 ± 17 mGy for the surgeon.CONCLUSIONSRA-IVA provided better vertebral body fracture correction than the conventional F-IVA. However, RA-IVA requires more time than F-IVA.

Effects of an early life experience on rat brain cannabinoid receptors in adolescence and adulthood.

Neonatal handling is an experimental model of early life experience associated with resilience in later life challenges, altering the ability of animals to respond to stress. The endocannabinoid system of the brain modulates the neuroendocrine and behavioral effects of stress, while this system is also capable of being modulated by stress exposure itself. The present study has addressed the question of whether neonatal handling in rats could affect cannabinoid receptors, in an age- and sex-dependent manner, using in situ hybridization and receptor binding techniques. Different effects of neonatal handling were observed in adolescent and adult brain on CB1 receptor mRNA and [3H]CP55,940 binding levels, which in some cases were sexually dimorphic. Neonatal handling interfered in the developmental trajectories of CB1 receptor mRNA levels in striatum and amygdaloid nuclei, as well as of [3H]CP55,940 binding levels in almost all regions studied. Adult handled rats showed reduced [3H]CP55,940 binding levels in the prefrontal cortex, striatum, nucleus accumbens and basolateral amygdala, while binding levels in prefrontal cortex of adolescent handled rats were increased. Finally, handling resulted in decreases in female [3H]CP55,940 binding levels in the striatum, nucleus accumbens, CA3 and DG of dorsal hippocampus and basolateral amygdala. Our results suggest that a brief and repeated maternal separation during the neonatal period induces changes on cannabinoid receptors differently manifested between adolescence and adulthood, male and female brain, which could be correlated to their stress response.

Schema therapy as treatment for adults with autism spectrum disorder and comorbid personality disorder: Protocol of a multiple-baseline case series study testing cognitive-behavioral and experiential interventions.

BACKGROUND: To our knowledge treatment of personality disorder (PD) comorbidity in adults with ASD is understudied and is still in its infancy. This study investigates the effectiveness of schema therapy for PD-psychopathology in adult patients with both ASD and PD. METHODS/DESIGN: Twelve adult individuals (age > 18 years) with ASD and at least one PD are given a treatment protocol consisting of 30 weekly offered sessions. A concurrent multiple baseline design is used with baseline varying from 4 to 9 weeks, after which weekly supportive sessions varying from 1 to 6 weeks start with the study therapist. After baseline and 1 to 6 supportive sessions, a 5-week exploration phase follows with weekly sessions during which current and past functioning, psychological symptoms, and schema modes are explored, and information about the treatment is given. This is followed by 15 weekly sessions with cognitive-behavioral interventions and 15 weekly sessions with experiential interventions: patients are vice versa and randomly assigned to the interventions. Finally, there is a 10-month follow-up phase with monthly booster sessions. Participants are randomly assigned to baseline length, and report weekly during treatment and monthly at follow-up on Belief Strength of negative core beliefs, and fill out SMI, SCL-90 and SRS-A 7 times during screening procedure (i.e. before baseline), after supportive sessions, after exploration, after cognitive and behavioral interventions, after experiential interventions, and after 5- and 10- month follow-up. The SCID-II is administered during screening procedure, at 5- and at 10-month follow-up. TRIAL REGISTRATION: The Netherlands National Trial Register NTR5788. Registered 01 April 2016.

Healthcare-associated infections in children: knowledge, attitudes and practice of paediatric healthcare providers at Tygerberg Hospital, Cape Town.

BACKGROUND: Healthcare (HC) providers' knowledge, attitudes and practices with regard to infection control (IC) may positively or adversely affect rates of institutional healthcare-associated infection (HAI). OBJECTIVES: To determine paediatric HC providers' knowledge, attitudes and practices regarding HAI and guide IC interventions in a resource-limited setting. METHODS: Paediatric HC providers at Tygerberg Children's Hospital, Cape Town, South Africa completed an anonymous, self-administered, 37-item questionnaire. RESULTS: Questionnaires (201, 66.6% participation rate) were completed by medical (90, 44.7%), allied health (16, 8%) and nursing providers (95, 47.3%). Median age was 34 years (IQR 27-43), and 84% were female. Knowledge scores were low [57% correct, mean (SD) 7.7 (1.7)/14 questions] but higher in the medical/allied category (P ≤ 0.001) and those qualified for ≥ 10 years (P = 0.008). Providers lacked knowledge of the main routes of infection transmission and misunderstood hand hygiene and terminal cleaning recommendations. Nurses scored higher for attitude questions [63% desired responses, mean 5 (1.2)/8 questions] (P = 0.02). Only 38% reported adequate undergraduate teaching on HAI and most (93%) wanted more in-service IC training. Providers agreed with punitive measures for colleagues ignoring IC recommendations (89%). Nurses scored higher for practice questions [53% desired responses, mean 3.2 (1.2)/6 questions] (P ≤ 0.001). Self-reported adherence to IC recommendations was high, 88% for hand hygiene and 74% for use of personal protective equipment. However, there was poor uptake of annual influenza vaccination (25%) and N95 respirator fit-testing (28%), and many felt obliged to report for work when sick (67%). DISCUSSION: Expanded in-service and undergraduate training in IC should emphasize methods of hand hygiene and routes of infection transmission. Paediatric providers support mandatory reporting of HAI events and stricter enforcement of IC recommendations.