Shaken baby syndrome in Switzerland: results of a prospective follow-up study, 2002-2007

Since the incidence of shaken baby syndrome in Switzerland was not known, we conducted a nationwide prospective follow-up study for a 5-year period (from 2002 to 2007). The data were collected through the Swiss Pediatric Surveillance Unit. Inclusion criteria were the presence, in a child ≤6years of age, of 1) more than or equal to two clinical symptoms (altered consciousness, convulsions, respiratory irregularities, and bulging fontanel), 2) one eye finding (retinal hemorrhages, vitreous hemorrhages), 3) one MRI/CT finding (subdural hematoma, subarachnoid hematoma, and parenchymatous lesions), or 4) history of shaking. Exclusion criteria were age >6years or documented accident/disease explaining symptoms/findings. To describe outcome, we used the King's Outcome Scale for Childhood Head Injury (KOSCHI). 56 cases were reported from 13 of 26 Swiss cantons, representing 80% of the Swiss population; 49 cases met the inclusion criteria. Preponderance of male infants was high (31 male and 18 female); median age at admission was 4months (1-58). Clinical symptoms were present in 42 infants, retinal/vitreous hemorrhages in 39 infants, and pathological brain/head imaging in 46 infants. In 13 cases, the caregivers admitted shaking the child. Outcomes (KOSCHI 1-5; n = 47 patients) were death (KOSCHI 1) 8 (17.7%), vegetative state (KOSCHI 2) 0, severe disability (KOSCHI 3) 11 (22.2%), moderate disability (KOSCHI 4) 14 (31.1%), and good recovery (KOSCHI 5) 14 (28.8%). Based on these data, the incidence of shaken baby syndrome in Switzerland is 14 per 100 000 live births, which corresponds to the incidence in other Western countries. Demographic characteristics and outcomes of Swiss patients were comparable to published studie

Characteristics associated with maltreatment types in children referred to a hospital protection team

Objective: The aim of this paper is to describe characteristics associated with maltreatment types in children referred to the child protection team at the University Children's Hospital Zürich. Since 2003, the child protection team has registered data on each case in a standardized form. Methods: To examine differences in gender, age, nationality, and socioeconomic status by type of maltreatment, regression analyses were conducted for the 1,484 cases that were referred from 2003 to 2006. Results: The most common types of referred maltreatment were sexual (38%) and physical maltreatment (31%) with mean ages of 8.4 and 7years, respectively. Compared to physical maltreatment, where gender distribution was equal, there was a higher risk for girls to become victims of sexual maltreatment. Younger children were at higher risk for neglect (mean age 5years). Low socioeconomic status increased the risk for physical as compared to sexual maltreatment. However, whether the child was of Swiss or of foreign nationality was not associated with an increased risk for any type of maltreatment when controlling for socioeconomic status. Conclusion: As this study is one of a few to analyze characteristics in child maltreatment referred to a hospital child protection team, further research is needed. To improve international comparability, thorough documentation of the cases is encourage

The silent epidemic of falls from buildings: analysis of risk factors

This study wanted to search for potential risk factors associated with falls from windows and balconies in order to eventually improve prevention. All children under the age of 16years suffering from head injuries/multiple trauma due to falls from windows or balconies treated over the last 7years at the intensive care unit (ICU) of the University Children's Hospital Zürich were analysed retrospectively (group A). Fifty patients out of all children suffering from head injuries/multiple trauma due to other types of accidents in the same period were selected at random as controls (group B). Out of a total of 241 children with head injury and/or multiple trauma, 31 (13%) fell out of a building. Twenty-seven of these victims (87%) fell from the third floor or lower. Twenty-one of the falls (68%) occurred at home. Fifteen children (49%) climbed on a piece of furniture before falling. In almost 20% of the accidents dangerous balcony or house constructions led to the fall. Parents did not witness the fall, except for three cases (10%) with direct parental involvement (one mother jumped out with her child, two mothers threw their child out of the window). Two children (6%) attempted suicide. Children aged 0-5years were predominantly represented (84%), and all six children who died were in this age group. There were significantly more patients with foreign nationalities and lower socio-professional categories in group A than in group B. In both groups, the accidents concerned the youngest child of the family in approximately 50% and happened mostly during summer evenings. There were no significant differences in injured systems and in injury severity between the two groups. This study identified young age, an immigrant family setting, low socio-professional category of the parents, dangerous house constructions, inappropriate furniture placement, and summertime evenings as risk factors for serious building falls in children. This information may foster focused preventio

Podoplanin immunopositive lymphatic vessels at the implant interface in a rat model of osteoporotic fractures

Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of lymphocytes, macrophages, debris and the implants degradation products. Therefore the lymphatic vessels are involved in implant integration and fracture healing

Refining Humane Endpoints in Mouse Models of Disease by Systematic Review and Machine Learning-Based Endpoint Definition

Ideally, humane endpoints allow for early termination of experiments by minimizing an animal’s discomfort, distress and pain, while ensuring that scientific objectives are reached. Yet, lack of commonly agreed methodology and heterogeneity of cut-off values published in the literature remain a challenge to the accurate determination and application of humane endpoints. With the aim to synthesize and appraise existing humane endpoint definitions for commonly used physiological parameters, we conducted a systematic review of mouse studies of acute and chronic disease models, which used body weight, temperature and/or sickness scores for endpoint definition. In the second part of the study, we used previously published and unpublished data on weight, temperature and sickness scores from mouse models of sepsis and stroke and applied machine learning algorithms to assess the usefulness of this method for parameter selection and endpoint definition across models. Studies were searched for in two electronic databases (MEDLINE/Pubmed and Embase). Out of 110 retrieved full-text manuscripts, 34 studies were included. We found large intra- and inter-model variance in humane endpoint determination and application due to varying animal models, lack of standardized experimental protocols and heterogeneity of performance metrics (part 1). Machine learning models trained with physiological data and sickness severity score or modified DeSimoni neuroscore identified animals with a high risk of death at an early time point in both mouse models of stroke (male: 93.2% at 72h post-treatment; female: 93.0% at 48h post-treatment) and sepsis (96.2% at 24h post-treatment), thus demonstrating generalizability in endpoint determination across models (part 2)

Progressive Improvement of T

Testosterone deficiency leads to bone loss and testosterone treatment has a beneficial effect. This study investigated the effects of normalizing serum testosterone on bone mineral density in 45 men with osteoporosis, diagnosed with testosterone deficiency (serum testosterone levels <12.1 nmol/L, T-scores: (mean ± SD) −3.12 ± 0.45, minimum: −4.10, and maximum: −2.60). In a cumulative, prospective, registry study of hypogonadal men (mean age: 53 ± 7 years) they received parenteral testosterone undecanoate of 1000 mg/12 weeks for up to six years. After one year 44 men were included in the registry, after two years 36 men, after three years 32 men, after four years 25 men, after five years 10 men and after six years 4 men. The declining numbers do not reflect drop-out rates but are a result of the registry design. Over the 6 year period there was a significant and progressive improvement of the T-scores in these men. Normalizing of serum testosterone leads to an improvement of bone mineral density and this improvement was progressive with the time period of testosterone administration. In this study of 6-years many men with testosterone deficiency suffered from classical diagnoses (Klinefelter’s syndrome and testicular pathology) hitherto undiagnosed

Refined movement analysis in the staircase test reveals differential motor deficits in mouse models of stroke

Accurate assessment of post-stroke deficits is crucial in translational research. Recent advances in machine learning offer precise quantification of rodent motor behavior post-stroke, yet detecting lesion-specific upper extremity deficits remains unclear. Employing proximal middle cerebral artery occlusion (MCAO) and cortical photothrombosis (PT) in mice, we assessed post-stroke impairments via the Staircase test. Lesion locations were identified using 7 T-MRI. Machine learning was applied to reconstruct forepaw kinematic trajectories and feature analysis was achieved with MouseReach, a new data-processing toolbox. Lesion reconstructions pinpointed ischemic centers in the striatum (MCAO) and sensorimotor cortex (PT). Pellet retrieval alterations were observed, but were unrelated to overall stroke volume. Instead, forepaw slips and relative reaching success correlated with increasing cortical lesion size in both models. Striatal lesion size after MCAO was associated with prolonged reach durations that occurred with delayed symptom onset. Further analysis on the impact of selective serotonin reuptake inhibitors in the PT model revealed no clear treatment effects but replicated strong effect sizes of slips for post-stroke deficit detection. In summary, refined movement analysis unveiled specific deficits in two widely-used mouse stroke models, emphasizing the value of deep behavioral profiling in preclinical stroke research to enhance model validity for clinical translation.Peer Reviewe

Interaction of ARC and Daxx: a novel endogenous target to preserve motor function and cell loss after focal brain ischemia in mice

The aim of this study was to explore the signaling and neuroprotective effect of transactivator of transcription (TAT) protein transduction of the apoptosis repressor with CARD (ARC) in in vitro and in vivo models of cerebral ischemia in mice. In mice, transient focal cerebral ischemia reduced endogenousARCprotein in neurons in the ischemic striatum at early reperfusion time points, and in primary neuronal cultures, RNA interference resulted in greater neuronal susceptibility to oxygen glucose deprivation (OGD).TAT.ARC protein delivery led to a dose-dependent better survival after OGD. Infarct sizes 72 h after 60 min middle cerebral artery occlusion (MCAo) were on average 30±8% (mean±SD; p=0.005; T2-weighted MRI) smaller in TAT.ARC-treated mice (1ug intraventricularly during MCAo) compared with controls. TAT.ARC-treated mice showed better performance in the pole test compared with TAT.β-Gal-treated controls. Importantly, post-stroke treatment (3 h after MCAo) was still effective in affording reduced lesion volume by 20±7% (mean±SD; p˃0.05) and better functional outcome compared with controls. Delayed treatment in mice subjected to 30 min MCAo led to sustained neuroprotection and functional behavior benefits for at least 28 d. Functionally, TAT.ARC treatment inhibited DAXX–ASK1–JNK signaling in the ischemic brain. ARC interacts with DAXX in a CARD-dependent manner to block DAXX trafficking and ASK1–JNK activation. Our work identifies for the first time ARC–DAXX binding to block ASK1–JNK activation as an ARC-specific endogenous mechanism that interferes with neuronal cell death and ischemic brain injury. Delayed delivery of TAT.ARC may present a promising target for stroke therapy

Mixtures of organic micropollutants exacerbated in vitro neurotoxicity of prymnesins and contributed to aquatic toxicity during a toxic algal bloom

Prymnesins produced by an algal bloom of Prymnesium parvum led to the death of several hundred tons of freshwater fish in the Oder River in summer 2022. We investigated effects on aquatic life and human cell lines from exposure to extracts of contaminated water collected during the fish kill. We detected B-type prymnesins and &gt;120 organic micropollutants. The micropollutants occurred at concentrations that would cause the predicted mixture risk quotient for aquatic life to exceed the acceptable threshold. Extracts of water and filters (biomass and particulates) induced moderate effects in vivo in algae, daphnids and zebrafish embryos but caused high effects in a human neuronal cell line indicating the presence of neurotoxicants. Mixture toxicity modelling demonstrated that the in vitro neurotoxic effects were mainly caused by the detected B-type prymnesins with minor contributions by organic micropollutants. Complex interactions between natural and anthropogenic toxicants may underestimate threats to aquatic ecosystems