MRI-Based Prediction of Clinical Improvement Following Ventricular Shunt Placement for Normal Pressure Hydrocephalus (NPH): Development and Evaluation of an Integrated Multi-Sequence Machine Learning Algorithm.

BACKGROUND AND PURPOSE: Symptoms of normal pressure hydrocephalus (NPH) are sometimes refractory to shunt placement, with limited ability to predict improvement for individual patients. We evaluated an MRI-based artificial intelligence method to predict post-shunt NPH symptom improvement. MATERIALS AND METHODS: NPH patients who underwent magnetic resonance imaging (MRI) prior to shunt placement at a single center (2014-2021) were identified. Twelve-month post-shunt improvement in modified Rankin Scale (mRS), incontinence, gait, and cognition were retrospectively abstracted from clinical documentation. 3D deep residual neural networks were built on skull stripped T2-weighted and fluid attenuated inversion recovery (FLAIR) images. Predictions based on both sequences were fused by additional network layers. Patients from 2014-2019 were used for parameter optimization, while those from 2020-2021 were used for testing. Models were validated on an external validation dataset from a second institution (n=33). RESULTS: Of 249 patients, n=201 and n=185 were included in the T2-based and FLAIR-based models according to imaging availability. The combination of T2-weighted and FLAIR sequences offered the best performance in mRS and gait improvement predictions relative to models trained on imaging acquired using only one sequence, with AUROC values of 0.7395 [0.5765-0.9024] for mRS and 0.8816 [0.8030-0.9602] for gait. For urinary incontinence and cognition, combined model performances on predicting outcomes were similar to FLAIR-only performance, with AUROC values of 0.7874 [0.6845-0.8903] and 0.7230 [0.5600-0.8859]. CONCLUSIONS: Application of a combined algorithm using both T2-weighted and FLAIR sequences offered the best image-based prediction of post-shunt symptom improvement, particularly for gait and overall function in terms of mRS. ABBREVIATIONS: NPH = normal pressure hydrocephalus; iNPH = idiopathic NPH; sNPH = secondary NPH; AI = artificial intelligence; ML = machine learning; CSF = cerebrospinal fluid; AUROC = area under the receiver operating characteristic; FLAIR = fluid attenuated inversion recovery; BMI = body mass index; CCI = Charlson Comorbidity Index; SD = standard deviation; IQR = interquartile range.

Interobserver variation in tumor delineation of liver metastases using Magnetic Resonance Imaging.

Background and purpose: Magnetic Resonance Imaging (MRI) guided stereotactic body radiotherapy (SBRT) of liver metastases is an upcoming high-precision non-invasive treatment. Interobserver variation (IOV) in tumor delineation, however, remains a relevant uncertainty for planning target volume (PTV) margins. The aims of this study were to quantify IOV in MRI-based delineation of the gross tumor volume (GTV) of liver metastases and to detect patient-specific factors influencing IOV. Materials and methods: A total of 22 patients with liver metastases from three primary tumor origins were selected (colorectal(8), breast(6), lung(8)). Delineation guidelines and planning MRI-scans were provided to eight radiation oncologists who delineated all GTVs. All delineations were centrally peer reviewed to identify outliers not meeting the guidelines. Analyses were performed both in- and excluding outliers. IOV was quantified as the standard deviation (SD) of the perpendicular distance of each observer's delineation towards the median delineation. The correlation of IOV with shape regularity, tumor origin and volume was determined. Results: Including all delineations, average IOV was 1.6 mm (range 0.6-3.3 mm). From 160 delineations, in total fourteen single delineations were marked as outliers after peer review. After excluding outliers, the average IOV was 1.3 mm (range 0.6-2.3 mm). There was no significant correlation between IOV and tumor origin or volume. However, there was a significant correlation between IOV and regularity (Spearman's ρs = -0.66; p = 0.002). Conclusion: MRI-based IOV in tumor delineation of liver metastases was 1.3-1.6 mm, from which PTV margins for IOV can be calculated. Tumor regularity and IOV were significantly correlated, potentially allowing for patient-specific margin calculation.

Exposure-Response Analyses for Belzutifan to Inform Dosing Considerations and Labeling.

Belzutifan (Welireg, Merck & Co., Inc., Rahway, NJ, USA) is an oral, potent hypoxia-inducible factor-2α inhibitor, recently approved in the United States for the treatment of von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and other VHL disease-associated neoplasms. Safety and efficacy were investigated in two clinical studies: a Phase 1 dose escalation/expansion study in solid tumors and RCC and a Phase 2 study in VHL-RCC. A population pharmacokinetic model was used to estimate belzutifan exposures to facilitate exposure-response (E-R) analyses for efficacy and safety endpoints. Relationships between exposure and efficacy (overall response rate, disease control rate, progression-free survival, best overall tumor size response, and other endpoints), safety outcomes (Grade ≥3 anemia, Grade ≥3 hypoxia, and time to first dose reduction/dose interruption), and pharmacodynamic biomarkers (erythropoietin [EPO] and hemoglobin [Hgb]) were evaluated using various regression techniques and time-to-event analyses. Efficacy E-R was generally flat with non-significant positive trends with exposure. The safety E-R analyses demonstrated a lack of relationship for Grade ≥3 hypoxia and a positive relationship for Grade ≥3 anemia, with incidences also significantly dependent on baseline Hgb. Exposure-dependent reductions in EPO and Hgb were observed. Based on the cumulative benefit-risk assessment in VHL disease-associated neoplasms using E-R, no a priori dose adjustment is recommended for any subpopulation. These analyses supported the benefit-risk profile of belzutifan 120 mg once daily dosing in patients with VHL-RCC for labeling and the overall development program.

Paediatric hydrocephalus.

Hydrocephalus is classically considered as a failure of cerebrospinal fluid (CSF) homeostasis that results in the active expansion of the cerebral ventricles. Infants with hydrocephalus can present with progressive increases in head circumference whereas older children often present with signs and symptoms of elevated intracranial pressure. Congenital hydrocephalus is present at or near birth and some cases have been linked to gene mutations that disrupt brain morphogenesis and alter the biomechanics of the CSF-brain interface. Acquired hydrocephalus can develop at any time after birth, is often caused by central nervous system infection or haemorrhage and has been associated with blockage of CSF pathways and inflammation-dependent dysregulation of CSF secretion and clearance. Treatments for hydrocephalus mainly include surgical CSF shunting or endoscopic third ventriculostomy with or without choroid plexus cauterization. In utero treatment of fetal hydrocephalus is possible via surgical closure of associated neural tube defects. Long-term outcomes for children with hydrocephalus vary widely and depend on intrinsic (genetic) and extrinsic factors. Advances in genomics, brain imaging and other technologies are beginning to refine the definition of hydrocephalus, increase precision of prognostication and identify nonsurgical treatment strategies.

Characterization of HIV variants from paired Cerebrospinal fluid and Plasma samples in primary microglia and CD4+ T-cells.

Despite antiretroviral therapy (ART), HIV persistence in the central nervous system (CNS) continues to cause a range of cognitive impairments in people living with HIV (PLWH). Upon disease progression, transmigrating CCR5-using T-cell tropic viruses are hypothesized to evolve into macrophage-tropic viruses in the CNS that can efficiently infect low CD4-expressing cells, such as microglia. We examined HIV-1 RNA concentration, co-receptor usage, and CSF compartmentalization in paired CSF and blood samples from 19 adults not on treatment. Full-length envelope CSF- and plasma-derived reporter viruses were generated from 3 subjects and phenotypically characterized in human primary CD4+ T-cells and primary microglia. Median HIV RNA levels were higher in plasma than in CSF (5.01 vs. 4.12 log10 cp/mL; p = 0.004), and coreceptor usage was mostly concordant for CCR5 across the paired samples (n = 17). Genetically compartmentalized CSF viral populations were detected in 2 subjects, one with and one without neurological symptoms. All viral clones could replicate in T-cells (R5 T cell-tropic). In addition, 3 CSF and 1 plasma patient-derived viral clones also had the capacity to replicate in microglia/macrophages and, therefore have an intermediate macrophage tropic phenotype. Overall, with this study, we demonstrate that in a subset of PLWH, plasma-derived viruses undergo genetic and phenotypic evolution within the CNS, indicating viral infection and replication in CNS cells. It remains to be studied whether the intermediate macrophage-tropic phenotype observed in primary microglia represents a midpoint in the evolution towards a macrophage-tropic phenotype that can efficiently replicate in microglial cells and propagate viral infection in the CNS.

Continuing the conversation: a cross-sectional study about the effects of work-related adverse events on the mental health of Dutch (resident) obstetrician-gynaecologists (ObGyns).

BACKGROUND: Obstetrician-Gynaecologists (ObGyns) frequently face work-related adverse events such as severe obstetric complications and maternal or neonatal deaths. In 2014, the WATER-1 study showed that ObGyns are at risk of developing work-related posttraumatic stress disorder (PTSD), while many hospitals lacked a professional support system. The aim of the present study is to evaluate the current prevalence of work-related traumatic events and mental health problems among Dutch ObGyns, as well as to examine the current and desired support. METHODS: In 2022, an online questionnaire was sent to all members of the Dutch Society of Obstetrics and Gynaecology (NVOG), including resident and attending ObGyns. The survey included questions about experienced work-related events, current and desired coping strategies, and three validated screening questionnaires for anxiety, depression, and PTSD (HADS, TSQ, and PCL-5). RESULTS: The response rate was 18.8% and 343 questionnaires were included in the analysis. Of the respondents, 93.9% had experienced at least one work-related adverse event, 20.1% had faced a complaint from the national disciplinary board, and 49.4% had considered leaving the profession at any moment in their career. The prevalence rates of clinically relevant anxiety, depression, and psychological distress were 14.3, 4.4, and 15.7%, respectively. The prevalence of work-related PTSD was 0.9% according to DSM-IV and 1.2% according to DSM-5. More than half of the respondents (61.3%) reported the presence of a structured support protocol or approach in their department or hospital, and almost all respondents (92.6%) rated it as sufficient. CONCLUSIONS: The percentages of anxiety, depression, psychological distress and PTSD are comparable to the similar study performed in 2014. Most Dutch ObGyns experience adverse events at work, which can be perceived as traumatic and, in certain cases, may lead to the development of PTSD. Structured support after adverse work-related events is now available in almost two-thirds of workplaces, and was mostly experienced as good. Despite substantial improvements in the availability and satisfaction of professional support after work-related adverse events, the prevalence rates of mental problems remain considerable, and it is imperative to sustain conversation about the mental well-being of ObGyns.

Off-the-Shelf Synthetic Biodegradable Grafts Transform In Situ into a Living Arteriovenous Fistula in a Large Animal Model.

Current vascular access options require frequent interventions. In situ tissue engineering (TE) may overcome these limitations by combining the initial success of synthetic grafts with long-term advantages of autologous vessels by using biodegradable grafts that transform into autologous vascular tissue at the site of implantation. Scaffolds (6 mm-Ø) made of supramolecular polycarbonate-bisurea (PC-BU), with a polycaprolactone (PCL) anti-kinking-coil, are implanted between the carotid artery and jugular vein in goats. A subset is bio-functionalized using bisurea-modified-Stromal cell-derived factor-1α (SDF1α) derived peptides and ePTFE grafts as controls. Grafts are explanted after 1 and 3 months, and evaluated for material degradation, tissue formation, compliance, and patency. At 3 months, the scaffold is resorbed and replaced by vascular neo-tissue, including elastin, contractile markers, and endothelial lining. No dilations, ruptures, or aneurysms are observed and grafts are successfully cannulated at termination. SDF-1α-peptide-biofunctionalization does not influence outcomes. Patency is lower in TE grafts (50%) compared to controls (100% patency), predominantly caused by intimal hyperplasia. Rapid remodeling of a synthetic, biodegradable vascular scaffold into a living, compliant arteriovenous fistula is demonstrated in a large animal model. Despite lower patency compared to ePTFE, transformation into autologous and compliant living tissue with self-healing capacity may have long-term advantages.

Shifts in phytoplankton and zooplankton communities in three cyanobacteria-dominated lakes after treatment with hydrogen peroxide.

Cyanobacteria can reach high densities in eutrophic lakes, which may cause problems due to their potential toxin production. Several methods are in use to prevent, control or mitigate harmful cyanobacterial blooms. Treatment of blooms with low concentrations of hydrogen peroxide (H2O2) is a promising emergency method. However, effects of H2O2 on cyanobacteria, eukaryotic phytoplankton and zooplankton have mainly been studied in controlled cultures and mesocosm experiments, while much less is known about the effectiveness and potential side effects of H2O2 treatments on entire lake ecosystems. In this study, we report on three different lakes in the Netherlands that were treated with average H2O2 concentrations ranging from 2 to 5 mg L-1 to suppress cyanobacterial blooms. Effects on phytoplankton and zooplankton communities, on cyanotoxin concentrations, and on nutrient availability in the lakes were assessed. After every H2O2 treatment, cyanobacteria drastically declined, sometimes by more than 99%, although blooms of Dolichospermum sp., Aphanizomenon sp., and Planktothrix rubescens were more strongly suppressed than a Planktothrix agardhii bloom. Eukaryotic phytoplankton were not significantly affected by the H2O2 additions and had an initial advantage over cyanobacteria after the treatment, when ample nutrients and light were available. In all three lakes, a new cyanobacterial bloom developed within several weeks after the first H2O2 treatment, and in two lakes a second H2O2 treatment was therefore applied to again suppress the cyanobacterial population. Rotifers strongly declined after most H2O2 treatments except when the H2O2 concentration was ≤ 2 mg L-1, whereas cladocerans were only mildly affected and copepods were least impacted by the added H2O2. In response to the treatments, the cyanotoxins microcystins and anabaenopeptins were released from the cells into the water column, but disappeared after a few days. We conclude that lake treatments with low concentrations of H2O2 can be a successful tool to suppress harmful cyanobacterial blooms, but may negatively affect some of the zooplankton taxa in lakes. We advise pre-tests prior to the treatment of lakes to define optimal treatment concentrations that kill the majority of the cyanobacteria and to minimize potential side effects on non-target organisms. In some cases, the pre-tests may discourage treatment of the lake.

Clinical criteria for filum terminale resection in occult tethered cord syndrome.

OBJECTIVE: Tethered cord syndrome (TCS) comprises three symptom categories: back/leg pain, bowel/bladder, and neurological complaints. MRI typically reveals a low-lying conus medullaris, filum terminale (FT) pathology, or lumbosacral abnormalities. FT resection is established in TCS but not in radiologically occult TCS (OTCS). This study aims to identify patients with OTCS who are likely to benefit from FT resection. METHODS: The authors recruited 149 patients with OTCS (31 pediatric, 118 adult) treated with FT resection-including only cases with progressive TCS, negative spine MRI, and no concurrent neurological/urological conditions. A comprehensive questionnaire collected patient self-reported symptoms and clinical findings at the preoperative and at 3- and 12-month follow-up examinations. Based on questionnaire data, the authors extracted a 15-item symptoms and findings scale to represent the three TCS symptom categories, assigning 1 point for each item present. RESULTS: OTCS presents without radicular/segmental sensorimotor findings, but with leg/back pain and conus dysfunction, in addition to leg fatigue and spasticity; the latter indicating an upper motoneuron pathology. The 15-item scale showed clinical improvement in 89% of patients at the 3-month follow-up and 68% at the 12-month follow-up. Multivariate analysis of the scale revealed that it accurately predicts outcome of FT resection in 82% of cases. Patients with a preoperative score exceeding 6 points are most likely to benefit from surgery. CONCLUSIONS: By applying the study's inclusion criteria and incorporating the novel 15-item scale, surgeons can effectively select candidates for FT resection in patients with OTCS. The observed outcomes in these selected patients are comparable to those achieved in degenerative spine surgery.

Nonbinary 2D Distribution Tool Maps Autonomic Nerve Fiber Clustering in Lumbosacral Ventral Roots of Rhesus Macaques.

Neuromodulation of the peripheral nervous system (PNS) by electrical stimulation may augment autonomic function after injury or in neurodegenerative disorders. Nerve fiber size, myelination, and distance between individual fibers and the stimulation electrode may influence response thresholds to electrical stimulation. However, information on the spatial distribution of nerve fibers within the PNS is sparse. We developed a new two-dimensional (2D) morphological mapping tool to assess spatial heterogeneity and clustering of nerve fibers. The L6-S3 ventral roots (VRs) in rhesus macaques were used as a model system to map preganglionic parasympathetic, γ-motor, and α-motor fibers. Random and ground truth distributions of nerve fiber centroids were determined for each VR by light microscopy. The proposed tool allows for nonbinary determinations of fiber heterogeneity by defining the minimum distance between nerve fibers for cluster inclusion and comparisons with random fiber distributions for each VR. There was extensive variability in the relative composition of nerve fiber types and degree of 2D fiber heterogeneity between different L6-S3 VR levels within and across different animals. There was a positive correlation between the proportion of autonomic fibers and the degree of nerve fiber clustering. Nerve fiber cluster heterogeneity between VRs may contribute to varied functional outcomes from neuromodulation.

Role of patent ductus arteriosus in preterms in long-term outcome.

OBJECTIVE: This study aimed to determine long-term neurodevelopmental outcome and cerebral oxygenation in extremely preterm infants, comparing those with a hemodynamic significant patent ductus arteriosus (hsPDA) to those without. STUDY DESIGN: We included infants born before 28 weeks of gestation from 2008 to 2010 with routine echocardiography. Prior to echocardiography, regional cerebral oxygen saturation was measured. At 5 years of age, we evaluated neurodevelopmental outcomes using the Movement Assessment Battery for Children 2nd Dutch edition for motor skills and the Wechsler Preschool and Primary Scale of Intelligence 3rd Dutch edition for cognition. RESULTS: A total of 66 infants (gestational age 26.6 ± 0.9 weeks, birth weight 912 ± 176 g) were included, 34 infants with a hsPDA (including treatment). The group infants with hsPDA showed lower pre-closure cerebral saturation levels (58.2 % ±7.8 % versus 62.8 % ±7.0 %; p = 0.01). At 5 years, impaired motor outcome occurred more often in infants with hsPDA (17 (53 %) vs. 7 (23 %); p = 0.01). In multivariate analysis existence of hsPDA remained unfavourably related to the motor subdomain "aiming and catching". There were no potential effects of hsPDA on cognitive performance at 5 years of age. CONCLUSION: Treatment-receiving infants with hsPDA appear to exhibit motor deficits, specifically in "aiming and catching", by the age 5. Persistent ductal patency could be a contributing factor.

Omics Studies of Tumor Cells under Microgravity Conditions.

Cancer is defined as a group of diseases characterized by abnormal cell growth, expansion, and progression with metastasis. Various signaling pathways are involved in its development. Malignant tumors exhibit a high morbidity and mortality. Cancer research increased our knowledge about some of the underlying mechanisms, but to this day, our understanding of this disease is unclear. High throughput omics technology and bioinformatics were successful in detecting some of the unknown cancer mechanisms. However, novel groundbreaking research and ideas are necessary. A stay in orbit causes biochemical and molecular biological changes in human cancer cells which are first, and above all, due to microgravity (µg). The µg-environment provides conditions that are not reachable on Earth, which allow researchers to focus on signaling pathways controlling cell growth and metastasis. Cancer research in space already demonstrated how cancer cell-exposure to µg influenced several biological processes being involved in cancer. This novel approach has the potential to fight cancer and to develop future cancer strategies. Space research has been shown to impact biological processes in cancer cells like proliferation, apoptosis, cell survival, adhesion, migration, the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors, among others. This concise review focuses on publications related to genetic, transcriptional, epigenetic, proteomic, and metabolomic studies on tumor cells exposed to real space conditions or to simulated µg using simulation devices. We discuss all omics studies investigating different tumor cell types from the brain and hematological system, sarcomas, as well as thyroid, prostate, breast, gynecologic, gastrointestinal, and lung cancers, in order to gain new and innovative ideas for understanding the basic biology of cancer.

Long-term outcomes of young, node-negative, chemotherapy-naïve, triple-negative breast cancer patients according to BRCA1 status.

BACKGROUND: Due to the abundant usage of chemotherapy in young triple-negative breast cancer (TNBC) patients, the unbiased prognostic value of BRCA1-related biomarkers in this population remains unclear. In addition, whether BRCA1-related biomarkers modify the well-established prognostic value of stromal tumor-infiltrating lymphocytes (sTILs) is unknown. This study aimed to compare the outcomes of young, node-negative, chemotherapy-naïve TNBC patients according to BRCA1 status, taking sTILs into account. METHODS: We included 485 Dutch women diagnosed with node-negative TNBC under age 40 between 1989 and 2000. During this period, these women were considered low-risk and did not receive chemotherapy. BRCA1 status, including pathogenic germline BRCA1 mutation (gBRCA1m), somatic BRCA1 mutation (sBRCA1m), and tumor BRCA1 promoter methylation (BRCA1-PM), was assessed using DNA from formalin-fixed paraffin-embedded tissue. sTILs were assessed according to the international guideline. Patients' outcomes were compared using Cox regression and competing risk models. RESULTS: Among the 399 patients with BRCA1 status, 26.3% had a gBRCA1m, 5.3% had a sBRCA1m, 36.6% had tumor BRCA1-PM, and 31.8% had BRCA1-non-altered tumors. Compared to BRCA1-non-alteration, gBRCA1m was associated with worse overall survival (OS) from the fourth year after diagnosis (adjusted HR, 2.11; 95% CI, 1.18-3.75), and this association attenuated after adjustment for second primary tumors. Every 10% sTIL increment was associated with 16% higher OS (adjusted HR, 0.84; 95% CI, 0.78-0.90) in gBRCA1m, sBRCA1m, or BRCA1-non-altered patients and 31% higher OS in tumor BRCA1-PM patients. Among the 66 patients with tumor BRCA1-PM and ≥ 50% sTILs, we observed excellent 15-year OS (97.0%; 95% CI, 92.9-100%). Conversely, among the 61 patients with gBRCA1m and < 50% sTILs, we observed poor 15-year OS (50.8%; 95% CI, 39.7-65.0%). Furthermore, gBRCA1m was associated with higher (adjusted subdistribution HR, 4.04; 95% CI, 2.29-7.13) and tumor BRCA1-PM with lower (adjusted subdistribution HR, 0.42; 95% CI, 0.19-0.95) incidence of second primary tumors, compared to BRCA1-non-alteration. CONCLUSIONS: Although both gBRCA1m and tumor BRCA1-PM alter BRCA1 gene transcription, they are associated with different outcomes in young, node-negative, chemotherapy-naïve TNBC patients. By combining sTILs and BRCA1 status for risk classification, we were able to identify potential subgroups in this population to intensify and optimize adjuvant treatment.

The importance, consequences and treatment of psychosocial risk factors in heart disease: less conversation, more action!

Psychosocial factors play a significant role in the incidence and prognosis of cardiovascular disease with a rapidly increasing body of knowledge, as acknowledged by their inclusion in the European Society of Cardiology cardiovascular prevention guideline since 2012. Nevertheless, psychosocial risk is not consistently assessed, acknowledged and treated in daily clinical practice. Therefore, adopting a multidimensional approach that encompasses biological, psychological, and social factors is crucial for understanding the dynamic nature of cardiovascular health and disease, delivering patient-centred care, and developing effective interventions to ultimately enhance health and satisfaction with contemporary medicine and care. The current review summarises the state-of-the-art evidence for screening and treating psychological risk factors in coronary heart disease, heart failure, and atrial fibrillation in the context of cardiac rehabilitation, along with accompanying recommendations. The limited adoption of routine screening, despite longstanding recommendations, highlights the importance of prioritising the implementation and expansion of routine screening in primary and secondary prevention. To advance psychosocial treatment, a standardised and personalised approach including comprehensive education, physical exercise, and psychosocial support with a focus on patient-reported outcomes is crucial. Treating heart and mind together has the potential to decrease psychosocial risk while enhancing the prognosis and quality of life, therefore delivering true patient-centred care.

Therapeutic frameworks in integration sessions in substance-assisted psychotherapy: A systematised review.

Serotonergic psychedelics and related substances have been explored as potential adjuncts in substance-assisted psychotherapy (SAPT) for treating various disorders. SAPT can be divided into three phases: preparation, administration and integration. Integration is commonly defined as the comprehension and effective application of insights from psychedelic experiences into everyday life. However, there is limited research regarding the most appropriate therapeutic approach during SAPT. In this article, we discuss the current evidence for different therapeutic frameworks for integration sessions when serotonergic psychedelics and entactogens are used as adjuncts to psychotherapy. We conducted a systematised review of the literature following PRISMA guidelines and searched PsycINFO, MEDLINE and Cochrane Library databases. The final synthesis included 75 clinical trials, mixed-methods investigations, treatment manuals, study protocols, quasi-experiments, qualitative investigations, descriptive studies, opinion papers, reviews, books and book chapters, published until 11 November 2022. The effects that various therapeutic approaches for integration sessions have on therapeutic outcomes have not been investigated by means of rigorous research. Most of the available evidence we retrieved was not supported by empirical data, thus limiting any conclusive statements regarding appropriate therapeutic frameworks for integration sessions for SAPT. Current clinical studies have used a range of therapeutic frameworks with the majority drawing from the humanistic-experiential tradition. While integration is regarded as crucial for the safe application of SAPT, there is currently an insufficient evidence base to suggest that any type of therapy is effective for guiding integration sessions. A systematic investigation of different therapeutic frameworks for integration and additional therapy-related factors is needed.

Relationship of Morphometrics and Symptom Severity in Female Type I Chiari Malformation Patients with Biological Resilience.

In the present study we report the relationship among MRI-based skull and cervical spine morphometric measures as well as symptom severity (disability-as measured by Oswestry Head and Neck Pain Scale and social isolation-as measured by the UCLA Loneliness scale) on biomarkers of allostatic load using estrogen, interleukin-6, C-reactive protein, and cortisol in a sample of 46 CMI patients. Correlational analyses showed that McRae line length was negatively associated with interleukin-6 and C-reactive protein levels, and Analysis of Variance (ANOVA) showed joint effects of morphometric measures (McRae line length, anterior CSF space) and symptom severity (disability and loneliness) on estrogen and intereukin-6 levels. These results are consistent with allostatic load. That is, when the combination of CSF crowding and self-report symptom (disability and loneliness) severity exceed the capacity of biological resilience factors, then biomarkers such as neuroprotective estrogen levels drop, rather than rise, with increasing symptom severity.

The epidemiology of crib-related head injuries: A ten-year nationwide analysis.

INTRODUCTION: Falls from cribs resulting in head injury are understudied and poorly characterized. The purpose of this study was to advance current understanding of the prevalence, descriptive characteristics of injury victims, and the types of crib fall-related head injuries (CFHI) using queried patient cases from the National Electronic Injury Surveillance System (NEISS) database. METHODS: Using the US Consumer Product Safety Commission's System NEISS database, we queried all CFHIs among children from over 100 emergency departments (EDs). Patient information regarding age, race, sex, location of the incident, diagnoses, ED disposition, and sequelae were analyzed. The number of CFHI from all US EDs during each year was also collected from the database. RESULTS: There were an estimated 54,799 (95% CI: 30,228-79,369) total visits to EDs for CFHIs between 2012 and 2021, with a decrease in incidence of approximately 20% during the onset of the COVID-19 pandemic (2019: 5616 cases, 2020: 4459 cases). The annual incidence of injuries showed no significant trend over the 10-year study period. An available subset of 1782 cases of head injuries from approximately 100 EDs was analyzed, and 1442 cases were included in final analysis. Injuries were sorted into three primary categories: unspecified closed head injury (e.g., closed head injury, blunt head trauma, or traumatic brain injury), concussion, or open head injury and skull fracture. Unspecified closed head injuries were the most common of all head injuries (95.4%, 1376/1442). Open head injuries (14/1442, 0.97%) and concussions 3.6% (52/1442, 3.6%) were rare. Most injuries involved children under the age of 1 (42.6%) compared to children who were 1, 2, 3, or 4-years old. About a fourth of patients had other diagnoses in addition to their primary injury including scalp/forehead hematomas, emesis, and contusions. Female patients were more likely to present with other diagnoses in addition to their primary head injury (Difference: 12.3%, 95% CI: 9.87%-15.4%, p < .0001). CONCLUSION: Despite minimum rail height requirements set by the Consumer Safety Product Commission (CPSC), head injuries associated with crib falls are prevalent in the United States. However, most injuries were minor with a vast majority of patients being released following examination and treatment.

The harmful cyanobacterium Microcystis aeruginosa PCC7806 is more resistant to hydrogen peroxide at elevated CO2.

Rising atmospheric CO2 can intensify harmful cyanobacterial blooms in eutrophic lakes. Worldwide, these blooms are an increasing environmental concern. Low concentrations of hydrogen peroxide (H2O2) have been proposed as a short-term but eco-friendly approach to selectively mitigate cyanobacterial blooms. However, sensitivity of cyanobacteria to H2O2 can vary depending on the available resources. To find out how cyanobacteria respond to H2O2 under elevated CO2, Microcystis aeruginosa PCC 7806 was cultured in chemostats with nutrient-replete medium under C-limiting and C-replete conditions (150 ppm and 1500 ppm CO2, respectively). Microcystis chemostats exposed to high CO2 showed higher cell densities, biovolumes, and microcystin contents, but a lower photosynthetic efficiency and pH compared to the cultures grown under low CO2. Subsamples of the chemostats were treated with different concentrations of H2O2 (0-10 mg·L-1 H2O2) in batch cultures under two different light intensities (15 and 100 µmol photons m-2·s-1) and the response in photosynthetic vitality was monitored during 24 h. Results showed that Microcystis was more resistant to H2O2 at elevated CO2 than under carbon-limited conditions. Both low and high CO2-adapted cells were more sensitive to H2O2 at high light than at low light. Microcystins (MCs) leaked out of the cells of cultures exposed to 2-10 mg·L-1 H2O2, while the sum of intra- and extracellular MCs decreased. Although both H2O2 and CO2 concentrations in lakes vary in response to many factors, these results imply that it may become more difficult to suppress cyanobacterial blooms in eutrophic lakes when atmospheric CO2 concentrations continue to rise.