Postpartum Depression-Identifying Risk and Access to Intervention.

PURPOSE OF REVIEW: As maternal mortality climbs in the USA with mental health conditions driving these preventable deaths, the field of reproductive psychiatry must shift towards identification of women and other birthing individuals at risk and facilitating access. This review brings together recent studies regarding risk of perinatal depression and highlights important comorbidities that place individuals at higher vulnerability to poor perinatal outcomes. RECENT FINDINGS: Recent research suggests that identifying risk for perinatal depression including historical diagnoses of depression, anxiety, trauma, and comorbid substance use and intimate partner violence may move the field to focus on preventive care in peripartum populations. Emerging data shows stark health inequities in racial and ethnic minority populations historically marginalized by the health system and in other vulnerable groups such as LGBTQ+ individuals and those with severe mental illness. Innovative models of care using systems-level approaches can provide opportunities for identification and risk analyses of vulnerable peripartum patients and facilitate access to therapeutic or preventive interventions. Utilizing intergenerational approaches and leveraging multidisciplinary teams that thoughtfully target high-risk women and other birthing individuals could promote significant changes to population-level care in maternal health.

Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

A Comparison of Methods for the Estimation of Body Composition in Highly Trained Wheelchair Games Players.

The purpose of this study was to assess the agreement in body composition measurements of wheelchair athletes using skinfolds, bio-impedance analysis (BIA) and air displacement plethysmography (ADP) relative to dual-energy X-ray absorptiometry (DXA). A secondary objective was to develop new skinfold prediction equations to estimate %fat for this sample. 30 wheelchair games players were recruited and the body composition outcomes of BIA, ADP, and skinfolds were compared to the DXA outcomes by a paired-samples t-test (systematic bias), intraclass correlation (ICC, relative agreement) and Bland-Altman plots (absolute agreement). Regression models to predict the %fat as measured by DXA by the sum of skinfolds or BIA were calculated. Results showed that the predictions of %fat when using BIA, ADP or skinfolds systematically underestimated the %fat mass as measured by the DXA. All ICC values, except for the measurement of fat (kg) by ADP (ICC=0.702), were below 0.7. New prediction models found the ∑7 skinfolds and calf circumference as the best model to predict %fat (R(2)=0.84). In conclusion, BIA, ADP and existing skinfolds equations should be used with caution when estimating %fat of wheelchair athletes with substantial body asymmetry, lower body muscular atrophy and upper body muscular development.

Lipoprotein Particles in Adolescents and Young Women With PCOS Provide Insights Into Their Cardiovascular Risk.

CONTEXT: Adult women with polycystic ovarian syndrome (PCOS) have an increased risk for cardiovascular disease, but the evidence for this is controversial in adolescents and young women with PCOS. Measurement of low-density lipoprotein (LDL) particle number, measured by nuclear magnetic resonance spectroscopy is a novel technology to assess cardiovascular risk. OBJECTIVE: The objective of the study was to evaluate lipoprotein particle number and size in young women with PCOS and its relationship with insulin resistance and hyperandrogenism. DESIGN: This was a cross-sectional case control study. SETTING: The study was conducted at a clinical research center. PARTICIPANTS: Women with PCOS (n = 35) and normal controls (n = 20) participated in the study. INTERVENTIONS: Blood samples and anthropometric measures were obtained. MAIN OUTCOME MEASURES: LDL particle size and number were measured using nuclear magnetic resonance spectroscopy. A secondary outcome was to investigate the correlation of LDL particle number with high-sensitivity C-reactive protein, waist to hip ratio, hyperandrogenism, insulin resistance, and adiponectin. RESULTS: Women with PCOS had higher LDL particle number when compared with healthy controls (935 ± 412 vs 735 ± 264, P = .032); LDL particle number correlated strongly with high-sensitivity C-reactive protein (r = 0.37, P = .006) and waist-to-hip (r = 0.57, P = .0003). The higher LDL particle number was driven mainly due to differences in the small LDL particle number (sLDLp), with PCOS patients having more sLDLp (348 ± 305 vs 178 ± 195, P = .015). The sLDLp correlated with the Matsuda index (r = -0.51, P = .0001), homeostasis model assessment index of insulin resistance (r = 0.41, P = .002), and adiponectin (r = -0.46, P = .0004) but not with T. CONCLUSION: Adolescent and young women with PCOS have an atherogenic lipoprotein profile suggestive of increased cardiovascular risk that appears to be driven by the degree of visceral adiposity and insulin resistance.

Enhanced uptake and siRNA-mediated knockdown of a biologically relevant gene using cyclodextrin polyrotaxane.

Ideal cationic polymers for siRNA delivery could result in its enhanced cellular internalization, escape from endosomal degradation, and rapid release in cell cytoplasm, to facilitate knockdown of the target gene. In this study, we have investigated the ability of an in-house synthesized cationic polyrotaxane to bind siRNA into nanometric complexes. This polymer, which had earlier shown improved transfection of model siRNA (luciferase), was used to improve the cellular internalization of the siRNA molecule with therapeutic implications. In cellular assays, the polymer enhanced the knockdown of a gene involved in the pathogenesis of tuberculosis, when the nanocomplexes were compared with free siRNA. The efficacy and cellular non-toxicity of this polymer encourage its further exploitation in animal models of tuberculosis and other intracellular bacterial infections.

Not all glucocorticoid-induced obesity is the same: differences in adiposity among various diagnostic groups of Cushing syndrome.

The cAMP signaling pathway is implicated in bilateral adrenocortical hyperplasias (BAHs), which are often associated with ACTH-independent Cushing syndrome (CS). Although CS is invariably associated with obesity and is frequently associated with PKA signaling defects, we recently reported that its different forms appear to also present with variable weight gain and adiposity. The present study was aimed at characterizing further the phenotypic and molecular differences in periadrenal adipose tissue (PAT) among patients with subtypes of CS, by anthropometric/biochemical analyses and quantification of PKA expression and activity in BAHs in comparison to a non-CS group with aldosterone producing adenomas (APAs). Glucocorticoid levels, serum parameters, and BMI were analyzed among a larger patient cohort including those with different forms of CS, APAs, and Cushing disease. Abdominal CT scans were available for a small subset of patients examined for fat distribution. PAT collected during adrenalectomy was assayed for PKA activity, cAMP, and PKA expression. BMI and BMI z-score were lower in adults with PPNAD with PRKAR1A mutations and in pediatric patients with PPNAD with and without PRKAR1A mutations, respectively. Patients with PPNAD had higher cAMP levels in PAT and different fat distribution. Thus, PKA activity in PAT differed between CS diagnostic groups. Increased cAMP and PKA activity may have contributed to phenotypic differences among subtypes of CS. In agreement with the known roles of cAMP signaling in the regulation of adiposity, patients with PPNAD were less obese than other patients with CS.

Threat bias in mice with inactivating mutations of Prkar1a.

Anxiety disorders are associated with abnormalities in the neural processing of threat-related stimuli. However, the neurobiological mechanisms underlying threat bias in anxiety are not well understood. We recently reported that a Prkar1a heterozygote (Prkar1a(+/-)) mouse with haploinsufficiency for the main regulatory subunit (R1α) of protein kinase A (PKA) exhibits an anxiety-like phenotype associated with increased cAMP signaling in the amygdala. Prkar1a(+/-) mice provide a novel model to test the direct effect of altered PKA expression and subsequent anxiety-like behavioral phenotype on the response to threat. We hypothesized that Prkar1a(+/-)mice would exhibit a bias in threat detection since increased amygdala activity during emotional stimuli is associated with a maladaptive response. We measured behavior and PKA activity in brain areas after exposure to predator or control odor exposure in male Prkar1a(+/-) and wild-type (WT) littermates. Indeed, there were significant differences in the behavioral response to threat detection; WT mice showed the expected response of decrease in exploratory behavior during predator vs. control odor exposure, while Prkar1a(+/-) mice did not alter their behavior between conditions. Basal and total PKA activity was independently associated with genotype, with an interaction between genotype and threat condition. Prkar1a(+/-) mice had higher PKA activity in amygdala and ventromedial hypothalamus in response to predator odor. In contrast, WT mice had higher PKA activity in amygdala and orbitofrontal cortex after exposure to control odor. Dysregulated PKA activity in the amygdala-prefrontal cortex circuitry in Prkar1a(+/-) mice is associated with behavioral phenotype of anxiety and a bias for threat. This is likely related to a failure to inhibit the amydgala response, which is an effect of the genotype. These results suggest that the alteration in PKA signaling in Prkar1a(+/-) mice is not ubiquitous in the brain; tissue-specific effects of the cAMP/PKA pathway are related to threat detection and fear sensitization.

[Therapy of septic paraplegia]. / Therapie der septischen Querschnittlähmung.

The frequency of infectious diseases of the spine and associated spinal cord injury are constantly increasing. Affected are multimorbid and elderly patients, mostly after prolonged medical treatment. An acute spinal cord injury due to infection is an emergency. A rapid decision for treatment strategy and if at all possible subtle debridement of the infected tissue with decompression of the spinal cord is paramount. Additionally spinal cord injury necessitates specialized treatment and care of the infection. Spinal cord injured patients in general and these patients in particular are prone to complications and need especially trained nursing personnel. It is therefore recommended that patients with vertebral osteomyelitis associated with spinal cord injury should be transferred to dedicated centres of treatment as soon as possible.Just as in cases of spondylodiscitis without spinal cord injury inconsistent surgical or insufficient antibiotic treatment worsens the prognosis significantly. If it is possible to remit the infection, the prognosis for recovery of motor and sensory function is better than in cases with traumatic spinal cord injury. In many cases at least partial recovery can be observed.

Factors influencing the identification rate of the sentinel node in breast cancer.

Sentinel node biopsy is a widely accepted alternative to primary axillary lymph node dissection for ipsilateral nodal assessment in breast cancer. We have performed a retrospective chart review in 713 consecutive patients with primary, operable breast cancer who underwent sentinel node biopsy in order to identify factors that determine the sentinel node identification rate. Chi-squared test, univariate and multivariate analyses were used to evaluate the influence of different factors on the sentinel identification rate. Among the factors investigated, tumour size was correlated with sentinel lymph nodes detection rates (multiple logistic regression, P= 0.002). In addition, the patient's age showed to be a significant influencing factor (multiple logistic regression, P= 0.006). Body mass index and grade only exhibited a significant correlation with the identification rate in the univariate (P= 0.041, P= 0.025), but not in the multivariate analysis (P= not significant). All associations were found to be independent of the site of injection. Interestingly, surgeons with intermediate expertise (11-20 prior dissections) had the highest detection rates (P= 0.004). We conclude that sentinel identification rates are higher in larger tumours and in younger patients, independent of the injection site. Surgical experience in sentinel node dissection is not linearly correlated with higher identification rates.

The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes.

The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among pediatric patients with pituitary adenomas (PA). In this study, we screened children with PA for mutations in these genes; somatic GNAS mutations were also studied in a limited number of growth hormone (GH) or prolactin (PRL)-secreting PA. We studied 74 and 6 patients with either isolated Cushing disease (CD) or GH- or PRL-secreting PA, respectively. We also screened four pediatric patients with CD, and four with GH/PRL-secreting tumors who had some syndromic features. There was one AIP mutation (p.Lys103Arg) among 74 CD patients. Two MEN1 mutations that occurred in patients with recurrent or difficult-to-treat disease were found among patients with CD. There was one MEN1 and three AIP mutations (p.Gln307ProfsX104, p.Pro114fsX, p.Lys241X) among pediatric patients with isolated GH- or PRL-secreting PA and one additional MEN1 mutation in a patient with positive family history. There were no mutations in the PRKAR1A, CDKN1B, CDKN2C or GNAS genes. Thus, germline AIP or MEN1 gene mutations are frequent among pediatric patients with GH- or PRL-secreting PA but are significantly rarer in pediatric CD; PRKAR1A mutations are not present in PA outside of Carney complex.

The growth hormone receptor (GHR) polymorphism in growth-retarded children with Cushing disease: lack of association with growth and measures of the somatotropic axis.

Pediatric Cushing disease (CD) often presents with short stature, but we have observed significant inter-individual variability in the growth delay caused by endogenous hypercortisolism. Glucocorticoids cause growth retardation by affecting the growth hormone (GH) - insulin-like growth factor-1 (IGF 1) somatotropic axis, but also other, GH-independent sites. Recently, the GH receptor (GHR) gene was found to have a common polymorphism (P) that leads to a deletion (d3) or retention of exon 3. In this study, we tested the hypothesis that the GH receptor polymorphism (GHR-P) maybe one of the significant variants that determines the degree of growth delay among patients with CD. GHR genotyping was performed on 56 children with newly diagnosed CD (24 females, 32 males, mean age of 12.9+/-3.3 years) who were followed at our institution between the years 1997-2007. Correlation analysis included genotype, measures of growth and the somatotropic axis, and anthropometrics. Within the group, 31 (12 girls, 19 boys) expressed the full length GHR allele, 10 (4 girls, 6 boys) were d3-GHR homozygotes and 15 (7 girls, 8 boys) were d3-GHR heterozygotes. No significant differences were found between the GHR genotypes and patient's height and/or growth velocity, or any other measures that we evaluated. The presence of a well-studied and common GHR polymorphism does not appear to be responsible for the variability of growth delay observed in patients with Cushing disease.

Retroreflecting polarization spectroscopy enabling miniaturization.

We describe and characterize alternative configurations for Doppler-free polarization spectroscopy. The suggested apparatus enables complete pump/probe beam overlap and allows substantial miniaturization. Its utility and performance for narrow linewidth, high-stability frequency locking is discussed for the /5S(1/2)F=2>-->/5P(3/2)F(')>D(2) transition in (87)Rb.

First results on angular distributions of thermal dileptons in nuclear collisions.

The NA60 experiment at the CERN Super Proton Synchrotron has studied dimuon production in 158A GeV In-In collisions. The strong excess of pairs above the known sources found in the complete mass region 0.2

Posterior decompression and stabilization for metastatic compression of the thoracic spinal cord: is this procedure still state of the art?

STUDY DESIGN: Retrospective study utilizing the standard patient data documentation of a spinal cord injury (SCI) unit. OBJECTIVE: To examine the efficacy and outcome of posterior decompression and stabilization for metastatic cord compression. SETTING: Orthopedic university hospital with large SCI unit. METHODS: The 34 consecutive patients who had presented with symptoms of spinal cord compression due to metastatic disease and progressive neurologic deficit were treated using a uniform surgical approach (posterior decompression and stabilization). After surgery, all treatment options available in a full-featured SCI unit were applied as necessary and suitable. Outcome was rated concerning neurologic function (American Spinal Injury Association, ASIA), functional status (Functional Independence Measure) and pain. The results were compared to the published results, focusing on publications describing results of anterior surgical approaches to the spine. RESULTS: Evaluation of the results of the ASIA exams showed that progression of the neurologic deficit could be stopped in the majority of cases-however recovery of neurologic function was rare. The functional status could be improved markedly and good pain reduction was achieved. CONCLUSION: I mmediate surgery can be recommended if the general condition of the patient warrants surgical intervention. Using accepted standards of documentation for SCI, a clear perspective of the results that can be expected is provided. Comparing the results of this study with the current literature there is no evidence that anterior approaches are superior.

Evidence for radial flow of thermal dileptons in high-energy nuclear collisions.

The NA60 experiment at the CERN SPS has studied low-mass dimuon production in 158A GeV In-In collisions. An excess of pairs above the known meson decays has been reported before. We now present precision results on the associated transverse momentum spectra. The slope parameter Teff extracted from the spectra rises with dimuon mass up to the rho, followed by a sudden decline above. While the initial rise is consistent with the expectations for radial flow of a hadronic decay source, the decline signals a transition to an emission source with much smaller flow. This may well represent the first direct evidence for thermal radiation of partonic origin in nuclear collisions.

J/psi production in Indium-Indium collisions at 158 GeV/nucleon.

The NA60 experiment studies muon pair production at the CERN Super Proton Synchrotron. In this Letter we report on a precision measurement of J/psi in In-In collisions. We have studied the J/psi centrality distribution, and we have compared it with the one expected if absorption in cold nuclear matter were the only active suppression mechanism. For collisions involving more than approximately 80 participant nucleons, we find that an extra suppression is present. This result is in qualitative agreement with previous Pb-Pb measurements by the NA50 experiment, but no theoretical explanation is presently able to coherently describe both results.

First measurement of the rho spectral function in high-energy nuclear collisions.

We report on a precision measurement of low-mass muon pairs in 158 AGeV indium-indium collisions at the CERN SPS. A significant excess of pairs is observed above the yield expected from neutral meson decays. The unprecedented sample size of 360,000 dimuons and the good mass resolution of about 2% allow us to isolate the excess by subtraction of the decay sources. The shape of the resulting mass spectrum is consistent with a dominant contribution from pi+pi- -->rho -->mu+mu- annihilation. The associated space-time averaged spectral function shows a strong broadening, but essentially no shift in mass. This may rule out theoretical models linking hadron masses directly to the chiral condensate.

[Paraplegia in cases of septic diseases of the spine]. / Querschnittlähmung bei septischen Erkrankungen der Wirbelsäule.

BACKGROUND: Paraplegia of non-traumatic origin has an increasing incidence. Infection of the spine is a major contributor to the number of these cases. Besides adequate management of spinal cord injury, the treatment of these patients requires specific therapeutic techniques. PATIENTS AND METHODS: Eighteen patients with acute pyogenic infection of the spine and spinal cord injury were admitted to our facility in the years 1997-2000. All except two patients were treated by surgical debridement and internal stabilisation. RESULTS: The infections healed after surgical treatment in all cases. Neurological function improved and no patient showed neurological deterioration. Both patients who were not fit for surgery died during treatment. CONCLUSION: Surgical instrumentation and replacement of the destroyed vertebra, despite a pyogenic environment, resulted in permanent resolution of the infection. There is potential for neurological recovery but full recovery is rare.