Translational Neuroscience Contributes to Understanding Neurodevelopmental Outcomes of Dostoyevsky's "Brothers Karamazov" With Treatment Implications.

Dostoyevsky's novels raise profound ethical, moral, philosophical and theological issues and, as a result, both he and his novels serve as fertile subjects of scholarly inquiry across a variety of academic disciplines. In particular, major characters in "The Brothers Karamazov" lend themselves to classical psychodynamic formulations, such as the influence of adverse childhood experiences on adult social and occupational outcomes, which in the case of Dmitry, the eldest son of Fyodor Pavlovich Karamazov, are considered in exquisitely fine detail. Prosecutor and defense attorney provide differing interpretations of how early traumas, largely due to paternal neglect and abuse, affected Dmitry's adult outcome in the climactic trial over his alleged patricide.

From Mouse to Man: N-Methyl-d-Aspartic Acid Receptor Activation as a Promising Pharmacotherapeutic Strategy for Autism Spectrum Disorders.

The BALB/c mouse displays hypersensitivity to behavioral effects of MK-801 (dizocilpine), a noncompetitive N-methyl-d-aspartic acid (NMDA) receptor "open-channel" blocker, and shows both no preference for an enclosed stimulus mouse over an inanimate object and reduced social interaction with a freely behaving stimulus mouse. NMDA receptor agonist interventions improved measures of social preference and social interaction of the BALB/c mouse model of autism spectrum disorder (ASD). A "proof of principle/proof of concept" translational 10-week clinical trial with 8-week of active medication administration was conducted comparing 20 DSM-IV-TR-diagnosed older adolescent/young adult patients with ASD randomized to once-weekly pulsed administration (50 mg/d) versus daily administration of d-cycloserine (50 mg/d).

Targeted NMDA Receptor Interventions for Autism: Developmentally Determined Expression of GluN2B and GluN2A-Containing Receptors and Balanced Allosteric Modulatory Approaches.

Various ASD risk alleles have been associated with impairment of NMDA receptor activation (i.e., NMDA Receptor Hypofunction) and/or disturbance of the careful balance between activation mediated by GluN2B-subtype and GluN2A-subtype-containing NMDA receptors.

Perineuronal Nets and Metal Cation Concentrations in the Microenvironments of Fast-Spiking, Parvalbumin-Expressing GABAergic Interneurons: Relevance to Neurodevelopment and Neurodevelopmental Disorders.

Because of their abilities to catalyze generation of toxic free radical species, free concentrations of the redox reactive metals iron and copper are highly regulated. Importantly, desired neurobiological effects of these redox reactive metal cations occur within very narrow ranges of their local concentrations. For example, synaptic release of free copper acts locally to modulate NMDA receptor-mediated neurotransmission.

Exposure to Low (≤10 cGy) Doses of 4He Particles Leads to Increased Social Withdrawal and Loss of Executive Function Performance.

Astronauts on the planned mission to Mars will be exposed to galactic cosmic radiation (GCR), with proton and He particles accounting (in approximately equal amounts) for ∼75% of the equivalent dose. Exposure to ≤15 cGy of space radiation ions with Z ≥ 15 particles has been shown to impair various executive functions, including attentional set shifting and creative problem-solving in rats. Executive functions also regulate social interactions and mood.

A De Novo Missense Variant of SCN2A: Implications and Limitations for Understanding Clinical Phenotype and Treatment Recommendations.

Autism spectrum disorder can be associated with a variety of genetic findings. We report a heterozygous de novo missense variant of SCN2A, the gene coding a voltage-gated sodium ion channel enriched in the axon initial segment and nodes of Ranvier of "immature" neocortical pyramidal neurons. With further understanding of the neurodevelopmental and functional effects of this missense variant on neuronal excitability and neocortical circuitry, there may be targeted pharmacotherapeutic interventions, potentially with "disease-modifying effects.

Psychotropic medication use for adults and older adults with intellectual disability; selective review, recommendations and future directions.

A growing expert consensus has emerged to guide prescribing behavior and monitoring of psychotropic medications in adults and older adults with intellectual disability (ID). However, there is little empirically-derived evidence to inform physician selection of specific categories of psychotropic medication for treatment of "challenging" behaviors in this vulnerable population (such as aggression to self, others and objects; self-injurious behaviors; repetitive stereotypic behaviors; and hyperactivity). Difficulties with application of formal definitional diagnostic criteria and reliable assignment of psychiatric diagnoses to adults with ID, which is often difficult due to their poor communication skills, contribute to confusion and uncertainty surrounding medication selection.

An Evolving Therapeutic Rationale for Targeting the α Nicotinic Acetylcholine Receptor in Autism Spectrum Disorder.

Abnormalities of cholinergic nuclei, cholinergic projections, and cholinergic receptors, as well as abnormalities of growth factors involved in the maturation and maintenance of cholinergic neurons, have been described in postmortem brains of persons with autism spectrum disorder (ASD). Further, microdeletions of the 15q13.3 locus that encompasses CHRNA7, the gene coding the α nicotinic acetylcholine receptor (α nAChR), are associated with a spectrum of neurodevelopmental disorders, including ASD.

Glycine transporter type 1 (GlyT1) inhibition improves conspecific-provoked immobility in BALB/c mice: Analysis of corticosterone response and glucocorticoid gene expression in cortex and hippocampus.

Stress reactivity and glucocorticoid signaling alterations are reported in mouse models of autism spectrum disorder (ASD). BALB/c mice display decreased locomotor activity in the presence of stimulus mice and spend less time exploring enclosed stimulus mice; this mouse strain has been validated as an ASD model. VU0410120, a glycine type 1 transporter (GlyT1) inhibitor, improved sociability in BALB/c mice, consistent with data that NMDA Receptor (NMDAR) activation regulates sociability, and the endogenous tone of NMDAR-mediated neurotransmission is altered in this strain.

PURL: Can vitamin D prevent acute respiratory infections?

A systematic review and meta-analysis says Yes, but the dosages used may not be what you'd expect.

Metabotropic functions of the NMDA receptor and an evolving rationale for exploring NR2A-selective positive allosteric modulators for the treatment of autism spectrum disorder.

NMDA receptors are widely distributed throughout the brain and major therapeutic challenges include targeting specific NMDA receptor subtypes while preserving spatial and temporal specificity during their activation. The NR2A-subunit containing NMDA receptor is implicated in regulating synchronous oscillatory output of cortical pyramidal neurons, which may be disturbed in clinical presentations of autism spectrum disorder (ASD). Because NR2A-selective positive allosteric modulators (PAMs) preserve spatial and temporal selectivity while activating this subpopulation of receptors, they represent a promising strategy to address neocortical circuit abnormalities in ASD.

PURL: First-time, mild diverticulitis: Antibiotics or watchful waiting?

Don't jump to antibiotic Tx for mild, uncomplicated diverticulitis, a recent RCT says. Observation may be just as effective.

Feasibility of Patient-Reported Outcomes Measurement Information System (PROMIS®) computerized adaptive tests in systemic lupus erythematosus outpatients.

Objective The aims of this study were to assess the feasibility of administering Patient-Reported Outcomes Measurement Information System (PROMIS®) computerized adaptive tests (CATs) to outpatients with systemic lupus erythematosus (SLE). Methods Adults with SLE were recruited during routine outpatient visits at an SLE Center of Excellence. Participants completed 14 PROMIS CATs and provided feedback on their experience.

Have large femoral heads reduced prosthetic impingement in total hip arthroplasty?

Background:: Prosthetic impingement is implicated in dislocation after total hip arthroplasty (THA). While use of larger diameter femoral heads reduces the incidence of dislocation, the effect of larger heads upon impingement rate is unknown. We assessed retrieved THA components for evidence of impingement to determine if large femoral heads reduced the rate of impingement in primary THA and what factors might influence impingement.

Feasibility, Validity, and Reliability of the 10-item Patient Reported Outcomes Measurement Information System Global Health Short Form in Outpatients with Systemic Lupus Erythematosus.

Objective: To assess the feasibility, validity, and reliability of the Patient Reported Outcomes Measurement Information System Global Health Short Form (PROMIS10) in outpatients with systemic lupus erythematosus (SLE).

Methods: SLE outpatients completed PROMIS10, Medical Outcomes Study Short Form-36 (SF-36), LupusQoL-US, and selected PROMIS computerized adaptive tests (CAT) at routine visits at an SLE Center of Excellence. Construct validity was evaluated by correlating PROMIS10 physical and mental health scores with PROMIS CAT, legacy instruments, and physician-derived measures of disease activity and damage.

Evaluation of peritalar subluxation in adult acquired flatfoot deformity using computed tomography and weightbearing multiplanar imaging.

Background: The aim of this study was to assess the inferior talus-superior talus (inf-tal-sup-tal) angle (previously proven reliable in multiplanar-weight bearing imaging (MP-WB)) on both computed tomography (CT) and MP-WB scans. We sought to compare the angle between the two modalities in both AAFD and control groups, as well as to compare the groups to each other.

Methods: Inf-tal-sup-tal angles were compared between a stage II AAFD group (n=38) with routine MP-WB and CT scans and a control group (n=20) with preoperative CT scans for lisfranc injuries and normal hindfoot alignment after healing.

Tarsometatarsal joint communication during fluoroscopy-guided therapeutic joint injections and relationship with patient age and degree of osteoarthritis.

Objective: Although the tarsometatarsal joints are separated into three distinct synovial compartments, communications between adjacent compartments are often noted during image-guided injections. This study aims to determine whether abnormal inter-compartment tarsometatarsal joint communication is associated with patient age or degree of tarsometatarsal osteoarthritis.

Materials And Methods: One hundred forty tarsometatarsal injections were retrospectively reviewed by two radiologists.

Total hip arthroplasty in young patients with post-traumatic arthritis of the hip.

Background: Post-traumatic arthritis of the hip is a degenerative condition that commonly affects young patients. In this study, we evaluate long-term implant survival and patient-reported outcomes after primary total hip arthroplasty (THA) in patients aged 35 or younger with post-traumatic arthritis of the hip.

Methods: We conducted a retrospective study with follow-up.

Validity and Reliability of Patient Reported Outcomes Measurement Information System Computerized Adaptive Tests in Systemic Lupus Erythematosus.

Objective: The aims of this study were to assess the construct validity and the test-retest reliability of Patient Reported Outcomes Measurement Information System (PROMIS) computerized adaptive tests (CAT) in patients with systemic lupus erythematosus (SLE).

Methods: Adults with SLE completed the Medical Outcomes Study Short Form-36, LupusQoL-US version ("legacy instruments"), and 14 selected PROMIS CAT. Using Spearman correlations, PROMIS CAT were compared with similar domains measured with legacy instruments.

Fretting and Corrosion at the Backside of Modular Cobalt Chromium Acetabular Inserts: A Retrieval Analysis.

Background: Adverse local tissue reaction formation has been suggested to occur with the Modular Dual Mobility (MDM) acetabular design. Few reports in the literature have evaluated fretting and corrosion damage between the acetabular shell and modular metal inserts in this modular system. We evaluated a series of 18 retrieved cobalt chromium MDM inserts for evidence of fretting and corrosion.

Sugarcoated Perineuronal Nets Regulate "GABAergic" Transmission: Bittersweet Hypothesis in Autism Spectrum Disorder.

Fast-spiking, parvalbumin-expressing "GABAergic" interneurons regulate synchronous oscillatory output of pyramidal neurons. Metabolic demands of these GABAergic projections are great because local ion concentrations must be optimally maintained; in addition, high rates of mitochondrial respiration necessitate exquisite redox regulation. Interestingly, only fast-spiking, parvalbumin-expressing basket cells coexpressing 3 metalloproteinases seem to be preferentially enwrapped in perineuronal nets (PNNs), a specialized lattice-like structure of the extracellular matrix.

Retrieval Analysis of Neck-Stem Coupling in Modular Hip Prostheses.

Background: Dual-taper modular stems have suffered from high revision rates caused by adverse local tissue reactions secondary to fretting and corrosion. We compared the fretting and corrosion behavior of a group of modular neck designs to that of a design that had been recalled for risks associated with fretting and corrosion at the modular neck junction.

Methods: We previously analyzed fretting and corrosion on 60 retrieved Rejuvenate modular neck-stem implants.

Patient Factors Associated With Higher Expectations From Foot and Ankle Surgery.

Background: Few authors have investigated patients' expectations from foot and ankle surgery. In this study, we aimed to examine relationships between patients' preoperative expectations and their demographic and clinical characteristics. We hypothesized that patients with more disability and those with anxiety or depressive symptoms would have greater expectations.