Effectiveness of braces designed using computer-aided design and manufacturing (CAD/CAM) and finite element simulation compared to CAD/CAM only for the conservative treatment of adolescent idiopathic scoliosis: a prospective randomized controlled trial

Purpose

Clinical assessment of immediate in-brace effect of braces designed using CAD/CAM and FEM vs. only CAD/CAM for conservative treatment of AIS, using a randomized blinded and controlled study design.

Methods

Forty AIS patients were prospectively recruited and randomized into two groups. For 19 patients (control group), the brace was designed using a scan of patient’s torso and a conventional CAD/CAM approach (CtrlBrace). For the 21 other patients (test group), the brace was additionally designed using finite element modeling (FEM) and 3D reconstructions of spine, rib cage and pelvis (NewBrace). The NewBrace design was simulated and iteratively optimized to maximize the correction and minimize the contact surface and material.

Results

Both groups had comparable age, sex, weight, height, curve type and severity. Scoliosis Research Society standardized criteria for bracing were followed. Average Cobb angle prior to bracing was 27° and 28° for main thoracic (MT) and lumbar (L) curves, respectively, for the control group, while it was 33° and 28° for the test group. CtrlBraces reduced MT and L curves by 8° (29 %) and 10° (40 %), respectively, compared to 14° (43 %) and 13° (46 %) for NewBraces, which were simulated with a difference inferior to 5°. NewBraces were 50 % thinner and had 20 % less covering surface than CtrlBraces.

Conclusion

Braces designed with CAD/CAM and 3D FEM simulation were more efficient and lighter than standard CAD/CAM TLSO’s at first immediate in-brace evaluation. These results suggest that long-term effect of bracing in AIS may be improved using this new platform for brace fabrication.

Trial registration

NCT02285621.

     

Neurokinin-1 and neurokinin-3 receptors in primate substantia nigra

Striatonigral axons co-release GABA and substance P (SP) at their target sites, but little is known about the action of SP at nigral level. Therefore, we studied immunohistochemically the cellular and subcellular localization of SP and its high affinity receptors neurokinin-1 (NK-1R) and neurokinin-3 (NK-3R) at nigral level in squirrel monkeys. Immunofluorescent studies revealed that, although SP+ fibers arborised more densely in the pars reticulata (SNr) than in the pars compacta (SNc), the two nigral divisions harbored numerous neurons expressing NK-1R and NK-3R. Confocal microscopic analyses showed that numerous SNr neurons and virtually all SNc dopaminergic neurons contained both NK-1R and NK-3R. At the electron microscope level, NK-1R and NK-3R were mainly associated with intracellular sites or located at extrasynaptic position on plasma membrane. A small proportion of SP+ boutons also showed NK-3R immunoreactivity. The distribution of NK-1R and NK-3R in SNr and SNc suggests that SP exerts its effect through postsynaptic receptors, as well as via presynaptic autoreceptors and heteroreceptors. These findings indicate that the excitatory peptide SP can modulate the inhibitory action of GABA at nigral level and suggest that the co-release of these two neuroactive substances should be taken into account when considering the functional organization of the basal ganglia.     

Cutaneous necrotizing vasculitis after low dose methotrexate therapy for rheumatoid arthritis: A possible manifestation of methotrexate hypersensitivity

Summary Large haemorrhagic and necrotic cutaneous lesions developed after two low dose (5mg) methotrexate injections in a patient suffering from long standing rheumatoid arthritis. Differential clinical diagnosis included factitia dermatitis, infectious processes, pyoderma gangrenosum, rheumatoid neutrophilic dermatitis, necrotizing arteritis and vasculitis. Histological and direct immunofluo-rescent examinations of skin biopsies supported the diagnosis of leucocytoclastic vasculitis. We discuss the respective roles of methotrexate and rheumatoid arthritis in the outbreak of leucocytoclastic vasculitis. Hypersensitivity is strongly suspected.     

A descending dopamine pathway conserved from basal vertebrates to mammals

Dopamine neurons are classically known to modulate locomotion indirectly through ascending projections to the basal ganglia that project down to brainstem locomotor networks. Their loss in Parkinson’s disease is devastating. In lampreys, we recently showed that brainstem networks also receive direct descending dopaminergic inputs that potentiate locomotor output. Here, we provide evidence that this descending dopaminergic pathway is conserved to higher vertebrates, including mammals. In salamanders, dopamine neurons projecting to the striatum or brainstem locomotor networks were partly intermingled. Stimulation of the dopaminergic region evoked dopamine release in brainstem locomotor networks and concurrent reticulospinal activity. In rats, some dopamine neurons projecting to the striatum also innervated the pedunculopontine nucleus, a known locomotor center, and stimulation of the dopaminergic region evoked pedunculopontine dopamine release in vivo. Finally, we found dopaminergic fibers in the human pedunculopontine nucleus. The conservation of a descending dopaminergic pathway across vertebrates warrants re-evaluating dopamine’s role in locomotion.Dopaminergic neurons represent a vital neuromodulatory component essential for vertebrate motor control, and their loss in neurodegenerative disease is devastating. The meso-diencephalic dopamine (DA) neurons are known to provide ascending projections to the basal ganglia, which, in turn, provide input to cortical structure in mammals but also project caudally to the mesencephalic locomotor region (MLR), a highly conserved structure that controls locomotion in all vertebrates investigated to date (1–7; for review, see ref. 8). A growing body of evidence supports the view that basal ganglia connectivity is highly conserved among vertebrates, from lampreys to mammals (9–11; for review, see ref. 12), with some interspecies differences recently highlighted (13). As such, the homology between DA cell populations remains to be resolved in vertebrates. As a general rule, DA neurons from the meso-diencephalon send projections to the striatum in all vertebrates. In lampreys and teleosts, those neurons are located only in the diencephalon (posterior tuberculum), but in tetrapods and cartilaginous fishes (14) they are located in both the diencephalon and the mesencephalon. An increasing number of authors seem to agree with the hypothesis that at least some of the meso-diencephalic DA neurons located in the diencephalon are homologous in all vertebrates, and thus, homologous to at least a portion of the mammalian substantia nigra pars compacta (SNc)/ventral tegmental area (VTA) (13, 15–19; for review, see ref. 20). Alternatively, it was suggested that the posterior tuberculum DA neurons projecting to the striatum in zebrafish are homologs of the mammalian DA neurons of the A11 group (21). This will be discussed below in light of the results of the present study.In lampreys, only a few meso-diencephalic DA neurons send ascending projections to the striatum (9, 22); the majority of DA neurons send a direct descending projection to the MLR (22, 23), where DA is released and increases locomotor output through D1 receptors (22). These results demonstrate that the descending dopaminergic pathway to the MLR is an important modulator of locomotor output, but it remains to be determined whether this pathway is conserved in higher vertebrates.The existence of a descending dopaminergic pathway that powerfully increases locomotor output has important implications for Parkinson’s disease, which involves the meso-diencephalic DA neurons. A loss of descending dopaminergic projections could play a role in the locomotor deficits systematically observed in that disease. Because of the highly conserved nature of both the dopaminergic system and brainstem locomotor circuitry in vertebrates, we hypothesized that a direct descending dopaminergic pathway to the MLR also exists in higher vertebrates. Previous anatomical (24, 25) and electrophysiological (26) studies in rats support the idea of a descending connection from the SNc to the pedunculopontine nucleus [PPN, considered part of the MLR (2)]. Moreover, dopaminergic terminals were found in the PPN of monkeys (27), but the origin of this projection is still unknown in mammals.Here, we investigated whether the direct descending projection from meso-diencephalic DA neurons to the MLR is present in two tetrapods, the salamander and the rat. Moreover, we supplement our analyses with anatomical data from human brain tissue. Using traditional and virogenetic axonal tracing, immunofluorescence, in vivo voltammetry, and calcium imaging of reticulospinal neurons, we provide anatomical and functional evidence strongly supporting a conserved role for the descending projections of meso-diencephalic DA neurons in the regulation of brainstem locomotor networks across the vertebrate subphylum.     

Psychosocial Functioning and Depressive Symptoms Among HIV-Positive Persons Receiving Care and Treatment in Kenya,Namibia, and Tanzania

In sub-Saharan Africa, the prevalence of depressive symptoms among people living with HIV (PLHIV) is considerably greater than that among members of the general population. It is particularly important to treat depressive symptoms among PLHIV because they have been associated with poorer HIV care-related outcomes. This study describes overall psychosocial functioning and factors associated with depressive symptoms among PLHIV attending HIV care and treatment clinics in Kenya, Namibia, and Tanzania. Eighteen HIV care and treatment clinics (six per country) enrolled approximately 200 HIV-positive patients (for a total of 3,538 participants) and collected data on patients’ physical and mental well-being, medical/health status, and psychosocial functioning. Although the majority of participants did not report clinically significant depressive symptoms (72 %), 28 % reported mild to severe depressive symptoms, with 12 % reporting severe depressive symptoms. Regression models indicated that greater levels of depressive symptoms were associated with: (1) being female, (2) younger age, (3) not being completely adherent to HIV medications, (4) likely dependence on alcohol, (5) disclosure to three or more people (versus one person), (6) experiences of recent violence, (7) less social support, and (8) poorer physical functioning. Participants from Kenya and Namibia reported greater depressive symptoms than those from Tanzania. Approximately 28 % of PLHIV reported clinically significant depressive symptoms. The scale-up of care and treatment services in sub-Saharan Africa provides an opportunity to address psychosocial and mental health needs for PLHIV as part of comprehensive care.     

Is parenting the mediator of change in behavioral parent training for externalizing problems of youth?

Change in parenting behavior is theorized to be the mediator accounting for change in child and adolescent externalizing problems in behavioral parent training (BPT). The purpose of this review is to examine this assumption in BPT prevention and intervention programs. Eight intervention and 17 prevention studies were identified as meeting all criteria or all but one criterion for testing mediation. Parenting behaviors were classified as positive, negative, discipline, monitoring/supervision, or a composite measure. Forty-five percent of the tests performed across studies to test mediation supported parenting as a mediator. A composite measure of parenting and discipline received the most support, whereas monitoring/supervision was rarely examined. More support for the mediating role of parenting emerged for prevention than intervention studies and when meeting all criteria for testing mediation was not required. Although the findings do not call BPT into question as an efficacious treatment, they do suggest more attention should be focused on examining parenting as a putative mediator in BPT.     

Impact of the Omicron variant on SARS-CoV-2 reinfections in France,March 2021 to February 2022

Since the first reports in summer 2020, SARS-CoV-2 reinfections have raised concerns about the immunogenicity of the virus, which will affect SARS-CoV-2 epidemiology and possibly the burden of COVID-19 on our societies in the future. This study provides data on the frequency and characteristics of possible reinfections, using the French national COVID-19 testing database. The Omicron variant had a large impact on the frequency of possible reinfections in France, which represented 3.8% of all confirmed COVID-19 cases since December 2021.