A range of artificial molecular systems has been created that can exhibit controlled linear and rotational motion. In the further development of such systems, a key step is the addition of ...communication between molecules in a network. Here, we show that a two-dimensional array of dipolar molecular rotors can undergo simultaneous rotational switching when applying an electric field from the tip of a scanning tunnelling microscope. Several hundred rotors made from porphyrin-based double-decker complexes can be simultaneously rotated when in a hexagonal rotor network on a Cu(111) surface by applying biases above 1 V at 80 K. The phenomenon is observed only in a hexagonal rotor network due to the degeneracy of the ground-state dipole rotational energy barrier of the system. Defects are essential to increase electric torque on the rotor network and to stabilize the switched rotor domains. At low biases and low initial rotator angles, slight reorientations of individual rotors can occur, resulting in the rotator arms pointing in different directions. Analysis reveals that the rotator arm directions are not random, but are coordinated to minimize energy via crosstalk among the rotors through dipolar interactions.
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IJS, NUK, SBMB, UL, UM, UPUK
In three phase 3 trials, ixekizumab, an anti–IL-17A monoclonal antibody, was effective in the treatment of patients with moderate-to-severe plaque psoriasis. Adverse events included neutropenia, ...candida infections, and inflammatory bowel disease.
Psoriasis is a chronic inflammatory disease that is mediated by aberrant immune responses and driven by self-perpetuating cytokine networks.
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Advances in understanding the pathogenic cytokine network of psoriasis have led to the development of new treatments
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that provide greater efficacy in terms of complete skin clearance.
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The motivation to completely clear psoriasis plaques from the skin of patients has grown in response to accumulating evidence that residual skin disease can affect a patient’s health-related quality of life
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similar to that associated with chronic conditions such as type 2 diabetes.
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Ixekizumab, a recombinant, high-affinity, humanized, IgG4-κ monoclonal . . .
Although mammalian parent–offspring interactions during early life are primarily through the mother, there is increasing evidence for the impact of fathers on offspring development. A critical issue ...concerns the pathways through which this paternal influence is achieved. In the present review, we highlight the literature suggesting several of these routes of paternal effects in mammals. First, similar to mothers, fathers can influence offspring development through the direct care of offspring, as has been observed in biparental species. Second, there is growing evidence that, even in the absence of contact with offspring, fathers can transmit environmentally‐induced effects (i.e. behavioural, neurobiological and metabolic phenotypes induced by stress, nutrition and toxins) to offspring and it has been speculated that these effects are achieved through inherited epigenetic variation within the patriline. Third, fathers may also impact the quality of mother–infant interactions and thus achieve an indirect influence on offspring. Importantly, these pathways of paternal influence are not mutually exclusive but rather serve as an illustration of the complex mechanisms through which parental influence is achieved. These influences may serve to transmit traits across generations, thus leading to a transgenerational transmission of neurobiological and behavioural phenotypes.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The ultrafast ring-opening reaction of photochromic fulgides proceeds via conical intersections to the ground state isomers involving activation barriers in the excited state. The coherent ...oscillations observed in the femtosecond transient absorption signal of a methyl-substituted indolylfulgide were analysed in the framework of vibrational wavepackets to expose a dominant low-frequency mode at ∼80 cm(-1). The quantum chemical calculations in the relaxed excited state geometry of this fulgide revealed that the experimentally observed vibrational normal mode has a dominant contribution to the relevant ring-opening reactive coordinate.
Previous studies suggest that high protein intake in infancy leads to a higher body mass index (BMI) in later childhood. We examined the associations of total, animal and vegetable protein intake in ...early childhood with detailed measures of body composition at the age of 6 years.
This study was performed in 2911 children participating in a population-based cohort study. Protein intake at the age of 1 year was assessed with a validated food-frequency questionnaire and was adjusted for total energy intake. At the children's age of 6 years, we measured their anthropometrics and body fat (with dual-energy X-ray absorptiometry). We calculated age- and sex-specific s.d. scores for BMI, fat mass index (FMI) and fat-free mass index (FFMI).
After adjustment for confounders, a 10 g per day higher total protein intake at 1 year of age was associated with a 0.05 s.d. (95% confidence interval (CI) 0.00, 0.09) higher BMI at age 6. This association was fully driven by a higher FMI (0.06 s.d. (95%CI 0.01, 0.11)) and not FFMI (-0.01 s.d. (95%CI -0.06, 0.05)). The associations of protein intake with FMI at 6 years remained significant after adjustment for BMI at the age of 1 year. Additional analyses showed that the associations of protein intake with FMI were stronger in girls than in boys (P for interaction=0.03), stronger among children who had catch-up growth in the first year of life (P for interaction<0.01) and stronger for intake of animal protein (both dairy and non-dairy protein) than protein from vegetable sources.
Our results suggest that high protein intake in early childhood is associated with higher body fat mass, but not fat-free mass. Future studies are needed to investigate whether these changes persist into adulthood and to examine the optimal range of protein intake for infants and young children.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
As one of the leading causes of elderly patients' hospitalisation, proximal femur fractures (PFFs) will present an increasing socioeconomic problem in the near future. This is a result of the ...demographic change that is expressed by the increasing proportion of elderly people in society. Peri-operative management must be handled attentively to avoid complications and decrease mortality rates. To deal with the exceptional needs of the elderly, the development of orthogeriatric centres to support orthogeriatric co-management is mandatory. Adequate pain medication, balanced fluid management, delirium prevention and the operative treatment choice based on comorbidities, individual demands and biological rather than chronological age, all deserve particular attention to improve patients' outcomes. The operative management of intertrochanteric and subtrochanteric fractures favours intramedullary nailing. For femoral neck fractures, the Garden classification is used to differentiate between non-displaced and displaced fractures. Osteosynthesis is suitable for biologically young patients with non-dislocated fractures, whereas total hip arthroplasty and hemiarthroplasty are the main options for biologically old patients and displaced fractures. In bedridden patients, osteosynthesis might be an option to establish transferability from bed to chair and the restroom. Postoperatively, the patients benefit from early mobilisation and early geriatric care. During the COVID-19 pandemic, prolonged time until surgery and thus an increased rate of complications took a toll on frail patients with PFFs. This review aims to offer surgical guidelines for the treatment of PFFs in the elderly with a focus on pitfalls and challenges particularly relevant to frail patients. Keywords: Garden classification, Frailty, Surgical management, Delirium prevention
Background and purpose
Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome for which treatment response is generally assumed to be good. We aimed to determine the prevalence and ...prognostic risk factors for refractoriness of JME.
Methods
We systematically searched PubMed and EMBASE and included 43 eligible studies, reporting seizure outcome after antiepileptic drug (AED) treatment in JME cohorts. We defined refractory JME as persistence of any seizure despite AED treatment and performed a random‐effects meta‐analysis to assess the prevalence of refractory JME and of seizure recurrence after AED withdrawal in individuals with well‐controlled seizures. Studies reporting potential prognostic risk factors in relation to seizure outcome were included for subsequent meta‐analysis of risk factors for refractoriness.
Results
Overall, 35% (95% confidence interval, 29–41%) of individuals (n = 3311) were refractory. There was marked heterogeneity between studies. Seizures recurred in 78% (95% confidence interval, 52–94%) of individuals who attempted to withdraw from treatment after a period of seizure freedom (n = 246). Seizure outcome by publication year suggested that prognosis did not improve over time. Meta‐analysis suggested six variables as prognostic factors for refractoriness, i.e. having three seizure types, absence seizures, psychiatric comorbidities, earlier age at seizure onset, history of childhood absence epilepsy and praxis‐induced seizures.
Conclusion
One‐third of people with JME were refractory, which is a higher prevalence than expected. Risk factors were identified and can be used to guide treatment and counselling of people with JME.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Posterior fossa tumors are the most common pediatric brain tumors. MR imaging is key to tumor detection, diagnosis, and therapy guidance. We sought to develop an MR imaging-based deep learning model ...for posterior fossa tumor detection and tumor pathology classification.
The study cohort comprised 617 children (median age, 92 months; 56% males) from 5 pediatric institutions with posterior fossa tumors: diffuse midline glioma of the pons (
= 122), medulloblastoma (
= 272), pilocytic astrocytoma (
= 135), and ependymoma (
= 88). There were 199 controls. Tumor histology served as ground truth except for diffuse midline glioma of the pons, which was primarily diagnosed by MR imaging. A modified ResNeXt-50-32x4d architecture served as the backbone for a multitask classifier model, using T2-weighted MRIs as input to detect the presence of tumor and predict tumor class. Deep learning model performance was compared against that of 4 radiologists.
Model tumor detection accuracy exceeded an AUROC of 0.99 and was similar to that of 4 radiologists. Model tumor classification accuracy was 92% with an F
score of 0.80. The model was most accurate at predicting diffuse midline glioma of the pons, followed by pilocytic astrocytoma and medulloblastoma. Ependymoma prediction was the least accurate. Tumor type classification accuracy and F
score were higher than those of 2 of the 4 radiologists.
We present a multi-institutional deep learning model for pediatric posterior fossa tumor detection and classification with the potential to augment and improve the accuracy of radiologic diagnosis.
Mesenchymal stromal cell (MSC) derived exosomes mediate tissue protection and regeneration in many injuries and diseases by modulating cell protein production, protecting from apoptosis, inhibiting ...inflammation, and increasing angiogenesis. In the present study, daily intraperitoneal injection of MSC-derived exosomes protected alveolarization and angiogenesis in a newborn rat model of bronchopulmonary dysplasia (BPD) induced by 14 days of neonatal hyperoxia exposure (85% O2). Exosome treatment during hyperoxia prevented disruption of alveolar growth, increased small blood vessel number, and inhibited right heart hypertrophy at P14, P21, and P56. In vitro, exosomes significantly increased tube-like network formation by HUVEC, in part through a VEGF mediated mechanism. In summary, daily intraperitoneal injection of exosomes increased blood vessel number and size in the lung through pro-angiogenic mechanisms. MSC-derived exosomes therefore have both anti-inflammatory and pro-angiogenic mechanism to protect the lung from hyperoxia induced lung and heart disease associated with BPD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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