Patho-morphology of patellar instability in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Children and adolescents have the highest incidence of patellar instability among the population. We aimed to identify patho-morphological and epidemiological factors associated with patellar instability, and to identify factors predisposing to recurrence in children and adolescents. METHODS: Published and unpublished literature databases, conference proceedings and the reference lists of included studies were searched to the 14th of March 2024. Studies were eligible if they compared history characteristics, examination features and radiological parameters between patients with and without instability, or evaluated risk factors for instability recurrence. A random-effects meta-analysis was performed. Included studies were appraised using tools respective of study design. RESULTS: The evidence was moderate to low in quality. Forty-five studies (including 9000 patients) were eligible. Tibial tubercle - tibial groove (TT-TG) distance (weighted mean difference [WMD] 5.96 mm, 95% Confidence Interval [CI]: 4.94 to 6.99 mm), sulcus angle (WMD: 13.93˚, 95% CI: 9.1˚ to 18.8˚), and Insall-Salvati index (WMD: 0.2, 95% CI: 0.16 to 0.23) were greater in patients with patellar instability. Risk factors for recurrent dislocation included age less than 18 years (Odds ratio [OR]: 2.56, 95% CI: 1.63 to 4.0), skeletal immaturity (OR: 1.79, 95% CI: 1.21 to 2.64) and presence of trochlear dysplasia (OR: 3.37, 95% CI: 1.85 to 6.15). CONCLUSION: Knowledge of patho-morphological factors associated with patellar instability could help explain its pathophysiological processes, allowing for the design of treatment approaches and the identification of patients at risk.

Light at the end of the tunnel: Innovative opportunities for saving tropical biodiversity.

The expansion of roads into wilderness areas and biodiversity hotspots in the Global South seems inevitable and is predicted to bring about significant biodiversity loss. Even so, existing widespread strategies aiming to mitigate the direct and indirect impacts of roads on the environment have been of limited effectiveness. These tactics, including construction of fencing, wildlife crossings on paved roads, and establishment of protected areas along the roads, are unlikely to be sufficient for protecting diverse species assemblages from roadkill, habitat fragmentation, and anthropogenic activity in tropics. This indicates the need for integration of more ambitious approaches into the conservation toolkit, such as the constructing tunnels, covered ways, and elevated roads. Although these tools could significantly support conservation efforts to save tropical biodiversity, to date, they are rarely considered. Here, we discuss factors which determine the need for application of these approaches in the Global South. We highlight the often-overlooked long-term benefits associated with the application of the proposed tools. We also discuss the potential challenges and risks, and the ways to minimise them. Hopefully this article will encourage practitioners to integrate these strategies into conservation toolkits and allow policy-makers and investors to make informed decisions on sustainable road infrastructure development in the Global South.

Implementation of automated personalised breast radiotherapy planning techniques with scripting in Raystation.

OBJECTIVE: Implement scripted automatic breast planning (AP) for breast techniques within Raystation. METHODS: Manual plans (MPs) were re-planned and compared with AP plans for whole breast (WB), partial breast (PB), hybrid volumetric modulated arc therapy simultaneous integrated boost (VMAT SIB) and VMAT nodal plans. RESULTS: WB AP plans took 7 min comparing well to MP. One WB AP failed a mandatory dose constraint. Small statistically significant differences showed improved coverage for AP at expense of slightly hotter plans, however absolute differences were small (mean differences < 1% or D 0.5cc<0.2 Gy). PB AP plans took 9 min, showing improved coverage (V 24.7Gy97.6 vs 96.4 %). One PB AP case failed a mandatory constraint. Other dosimetric differences were non-significant. SIB AP plans took 14 min with one case failing a mandatory constraint with minor differences compared with MP except larger V 42.8Gy (3 vs 1.5 %) and more MU. VMAT AP plans took 12 min and were hotter for PTVp_4000 but had higher nodal coverage. Contra_Lung V 2.5Gy was higher (8.8 %) than MP plans (6.5 %). CONCLUSION: Automatic planning of modern breast techniques has been successfully introduced using a commercial planning system. AP plans are very similar to MP, requiring little manual interaction for most cases with significant timesaving potential. ADVANCES IN KNOWLEDGE: Scripted breast plans produced within minutes for WB, PB, SIB and VMAT. Successfully introduced into large busy department. Plans similar to manual plans, requiring little manual interaction.

Increasing rates of methamphetamine/amphetamine-involved overdose hospitalizations in Washington State, 2010-2017.

BACKGROUND AND AIMS: In the United States, overdose deaths resulting from methamphetamine and other amphetamine-type stimulants (METH/AMPH) have been increasing. We describe rates and characterize patients hospitalized after a METH/AMPH-involved overdose in Washington State, to guide prevention and control measures. DESIGN SETTING PARTICIPANTS: We conducted a trend analysis of hospitalized Washington State residents aged ≥15 years who received a METH/AMPH-involved overdose diagnosis in Washington's civilian hospitals and reported in the Comprehensive Hospital Abstract Reporting System. MEASUREMENTS: We used Joinpoint regression analysis to study trends in rates of hospitalized patients who received a METH/AMPH-involved overdose diagnosis during 2010-2017. We used 2016-2017 data to describe characteristics of patients with nonfatal and fatal outcomes and used chi-square test (for categorical variables) and Wilcoxon rank-sum test (for continuous variables) to compare characteristics of patients by outcome. FINDINGS: During 2010-2017, 3587 patients were hospitalized and received a METH/AMPH-involved overdose diagnosis. The age-adjusted rate for METH/AMPH-involved overdose hospitalization increased from 6.3/100,000 persons in 2010 to 8.5/100,000 persons in 2017. Patients aged ≥55 years had the greatest increase in rate of overdose hospitalizations. Among these patients, 86% also had a substance use disorder diagnosis involving substances other than METH/AMPH, and 35% experienced a polysubstance overdose. CONCLUSIONS: We observed increasing rates of METH/AMPH-involved overdose hospitalizations in Washington State, particularly among persons aged ≥55 years. Approximately a third of patients also experienced a polysubstance overdose, which can be considered when designing interventions to address increasing rates of overdose hospitalizations in Washington State.

Dendrites are dispensable for basic motoneuron function but essential for fine tuning of behavior.

Dendrites are highly complex 3D structures that define neuronal morphology and connectivity and are the predominant sites for synaptic input. Defects in dendritic structure are highly consistent correlates of brain diseases. However, the precise consequences of dendritic structure defects for neuronal function and behavioral performance remain unknown. Here we probe dendritic function by using genetic tools to selectively abolish dendrites in identified Drosophila wing motoneurons without affecting other neuronal properties. We find that these motoneuron dendrites are unexpectedly dispensable for synaptic targeting, qualitatively normal neuronal activity patterns during behavior, and basic behavioral performance. However, significant performance deficits in sophisticated motor behaviors, such as flight altitude control and switching between discrete courtship song elements, scale with the degree of dendritic defect. To our knowledge, our observations provide the first direct evidence that complex dendrite architecture is critically required for fine-tuning and adaptability within robust, evolutionarily constrained behavioral programs that are vital for mating success and survival. We speculate that the observed scaling of performance deficits with the degree of structural defect is consistent with gradual increases in intellectual disability during continuously advancing structural deficiencies in progressive neurological disorders.

Dscam1 is required for normal dendrite growth and branching but not for dendritic spacing in Drosophila motoneurons.

Down syndrome cell adhesion molecule, Dscam, serves diverse neurodevelopmental functions, including axon guidance and synaptic adhesion, as well as self-recognition and self-avoidance, depending on the neuron type, brain region, or species under investigation. In Drosophila, the extensive molecular diversity that results from alternative splicing of Dscam1 into >38,000 isoforms provides neurons with a unique molecular code for self-recognition in the nervous system. Each neuron produces only a small subset of Dscam1 isoforms, and distinct Dscam1 isoforms mediate homophilic interactions, which in turn, result in repulsion and even spacing of self-processes, while allowing contact with neighboring cells. While these mechanisms have been shown to underlie mushroom body development and spacing of mechanosensory neuron dendrites, here we report that Dscam1 plays no role in adult Drosophila motoneuron dendrite spacing, but is required for motoneuron dendritic growth. Targeted expression of Dscam-RNAi in an identified flight motoneuron did not impact dendrite spacing, but instead produced overgrowth. Increasing the knockdown strength severely reduced dendritic growth and branching. Similarly, Dscam mutant motoneurons in an otherwise control background (MARCM) were completely devoid of mature dendrites. These data suggest that Dscam1 is required cell autonomously for normal adult motoneuron dendrite growth in Drosophila. This demonstrates a previously unreported role of Drosophila Dscam1 in central neuron development, and expands the current understanding that Dscam1 operates as a cell adhesion molecule that mediates homophilic repulsion.

Environmental enrichment protects against the effects of chronic stress on cognitive and morphological measures of hippocampal integrity.

Chronic stress has detrimental effects on hippocampal integrity, while environmental enrichment (EE) has beneficial effects when initiated early in development. In this study, we investigated whether EE initiated in adulthood would mitigate chronic stress effects on cognitive function and hippocampal neuronal architecture, when EE started one week before chronic stress began, or two weeks after chronic stress onset. Adult male Sprague Dawley rats were chronically restrained (6h/d) or assigned as non-stressed controls and subdivided into EE or non-EE housing. After restraint ended, rats were tested on a radial arm water maze (RAWM) for 2-d to assess spatial learning and memory. The first study showed that when EE began prior to 3-weeks of chronic stress, EE attenuated chronic stress-induced impairments in acquisition, which corresponded with the prevention of chronic stress-induced reductions in CA3 apical dendritic length. A second study showed that when EE began 2-weeks after the onset of a 5-week stress regimen, EE blocked chronic stress-induced impairments in acquisition and retention at 1-h and 24-h delays. RAWM performance corresponded with CA3 apical dendritic complexity. Moreover, rats in EE housing (control or stress) exhibited similar corticosterone profiles across weeks, which differed from the muted corticosterone response to restraint by the chronically stressed pair-housed rats. These data support the interpretation that chronic stress and EE may act on similar mechanisms within the hippocampus, and that manipulation of these factors may yield new directions for optimizing brain integrity and resilience under chronic stress or stress related neuropsychological disorders in the adult.

Human podocytes possess a stretch-sensitive, Ca2+-activated K+ channel: potential implications for the control of glomerular filtration.

Podocytes express many proteins characteristic of smooth muscle, such as actin and myosin. They also express receptors to several vasoactive agents, including acetylcholine and angiotensin II; these phenotypic properties suggest that podocytes are not static entities but may respond to physiologic stimuli. The electrophysiologic properties of a conditionally immortalized human podocyte cell line that expresses the specific podocyte proteins nephrin, podocin, and synaptopodin were examined by patch clamp. Channels that were highly K(+)-selective and had a conductance of 224 +/- 11.5 pS in symmetrical 150 mM K(+) solutions were identified. Channel activity was Ca(2+)- and voltage-dependent, being increased with an increase in Ca(2+) or depolarization, and inhibited by penitrem A. The conductance and voltage- and Ca(2+)-dependence suggest that this is the large-conductance calcium-activated K(+) channel, BK (KCNMA1)-this was supported by reverse transcription-PCR experiments that showed the presence of the BK encoding mRNA, along with expression of KCNMB subunit types 3 and 4. In sections of human glomeruli, immunocytochemistry revealed that BK co-localizes with the podocyte-specific protein nephrin, indicating that these channels are present in native human podocytes. In whole-cell experiments, penitrem A inhibited outward currents to the same extent as tetra-ethyl ammonium (TEA) but did not affect the membrane potential. Channel activity was also increased by applying suction to the patch pipette or by dilution of the bathing medium, indicating that these channels are stretch sensitive. Thus, these channels do not contribute to the resting membrane potential but are activated by a rise in intracellular Ca(2+), membrane depolarization, cell swelling, or membrane stretch. By implication, these results suggest that podocytes may be able to respond to changes in the glomerular capillary pressure and modulate the GFR.