Clinical correlates and symptom patterns of anxious depression among patients with major depressive disorder in STAR*D

BACKGROUND: Anxious depression, defined as Major Depressive Disorder (MDD) with high levels of anxiety symptoms, may represent a relatively common depressive subtype, with distinctive features. OBJECTIVE: The objective of this study was to determine the prevalence of anxious depression and to define its clinical correlates and symptom patterns. METHOD: Baseline clinical and sociodemographic data were collected on 1450 subjects participating in the STAR*D study. A baseline Hamilton Rating Scale for Depression (HAM-D) Anxiety/ Somatization factor score of > or =7 was considered indicative of anxious depression. The types and degree of concurrent psychiatric symptoms were measured using the Psychiatric Diagnostic Screening Questionnaire (PDSQ), by recording the number of items endorsed by study participants for each diagnostic category. MDD symptoms were assessed by clinical telephone interview with the 30-item Inventory of Depressive Symptomatology (IDS-C30). RESULTS: The prevalence of anxious depression in this population was 46 %. Patients with anxious MDD were significantly more likely to be older, unemployed, less educated, more severely depressed, and to have suicidal ideation before and after adjustment for severity of depression. As far as concurrent psychiatric symptoms are concerned, patients with anxious depression were significantly more likely to endorse symptoms related to generalized anxiety, obsessive compulsive, panic, post-traumatic stress, agoraphobia, hypochondriasis, and somatoform disorders before and after adjustment for severity of depression. Anxious-depression individuals were also significantly less likely to endorse IDS-C30 items concerning atypical features, and were significantly more likely to endorse items concerning melancholic/endogenous depression features. CONCLUSION: This study supports specific clinical and sociodemographic correlates of MDD associated with high levels of anxiety (anxious depression).     

CD40 ligand is a T cell growth factor

CD40 ligand (CD40L) is a 33-kDa type II membrane glycoprotein induced on T cells upon activation. CD40L has previously been shown to induce proliferation of resting B cells, immunoglobulin (Ig) secretion from B cells cultured with cytokines and cytokine secretion and tumoricidal activity from monocytes. In this report CD40L is shown to be stimulatory for human T cells, inducing CD25 (p55 IL-2R) and CD40L expression on resting peripheral blood T cells, enhanced expression of these molecules and CD69 on CD3-activated cells and secretion of interferon-y, tumor necrosis factor-a and interleukin (IL)-2 from T cells cultured in the presence of a sub-mitogenic concentration of phytohemagglutinin A (PHA). Furthermore, stimulation with CD40L induces proliferation of CD3- or PHA-activated T cells of blood, tonsillar or thymic origin. A similar proliferative response is observed with CD4^? and CD8⁺ T cells and this effect is largely IL-2 independent. A soluble construct of the extracellular domain of the CD40L has similar activity to that of membrane-expressed ligand in the induction of T cell surface antigens and proliferation. The results presented here taken together with the various activities ascribed for CD40L on B cells and monocytes demonstrate that CD40L has pleiotropic biological activity for cells of the hemopoietic lineage.     

Strategic control and medial frontal negativity: beyond errors and response conflict

Errors in timed choice tasks typically produce an error-related negativity (ERN) in the event-related potential (ERP). The error specificity of the ERN has been challenged by studies showing a correct response negativity (CRN). Forty-five participants engaged in a flanker task in which both compatibility between flankers and target and the probability of compatible flankers were manipulated. Correct responses elicited a CRN, the amplitude of which increased with the degree of mismatch between the presence of conflict and conflict probability, even on low-conflict (compatible) trials. The fronto-central N2 component was larger on high-conflict (incompatible) correct response trials. However, in contrast to some recent accounts, this N2 was largest for highly probable stimuli. These findings suggest revision to models of the effects of conflict on response-related negativity to account for strategic adjustments made in preparation for the response.     

Studies on epidermal growth factor receptor signaling in vertebrate limb patterning.

The epidermal growth factor receptor (EGFR) regulates multiple patterning events in Drosophila limb development, but its role in vertebrate limb morphogenesis has received little attention. The EGFR and several of its ligands are expressed in developing vertebrate limbs in manners consistent with potential patterning roles. To gain insight into functions of EGFR signaling in vertebrate limb development, we expressed a constitutively active EGFR in developing chick limbs in ovo. Expression of activated EGFR causes pre- and postaxial polydactyly, including mirror-image-type digit duplication, likely due to induction of ectopic expression and/or modulation of genes involved in anterior-posterior (AP) patterning such as Sonic hedgehog (Shh), dHand, Patched (Ptc), Gli3, Hoxd13, Hoxd11, bone morphogenetic protein 2 (Bmp2), Gremlin, and FGF4. Activation of EGFR signaling dorsalizes the limb and alters expression of the dorsal-ventral (DV) patterning genes Wnt7a, Lmx, and En1. Ectopic and/or extended FGF8 expressing apical ectodermal ridges (AERs) are also seen. Interdigital regression is inhibited and the digits fail to separate, leading to syndactyly, likely due to antiapoptotic and pro-proliferative effects of activated EGFR signaling on limb mesoderm, and/or attenuation of interdigital Bmp4 expression. These findings suggest potential roles for EGFR signaling in AP and DV patterning, AER formation, and cell survival during limb morphogenesis.     

Antigenic mapping of the envelope proteins of equine infectious anemia virus: identification of a neutralization domain and a conserved region on glycoprotein 90

Summary Monoclonal antibodies (MCAbs) were used to dissect the antigenic sites of the surface glycoproteins of the prototype cell-adapted Wyoming strain of equine infectious anemia virus (EIAV) Serologic reactivities of these MCAbs were determined by ELISA, additive ELISA, competitive ELISA, and Western blot assays. The results indicated that antigenic reactivity of gp90 was localized on at least four distinct epitopes, two of which were important in neutralization. Our studies also revealed that these epitopes were localized on overlapping antigenic sites on gp90. On the other hand, only two distinct non-overlapping epitopes were identified on gp45. Competitive binding studies of neutralizing MCAbs and reference EIA-positive horse serum delineated the presence of a neutralization domain on gp90 that appears to be immunodominant both in naturally infected horses and in mice immunized with EIAV. Limited proteolytic fragmentation of the gp90 component of several serologically distinct EIAV isolates produced common 12K immunoreactive fragments that contained a conserved epitope. These results indicate the occurrence of conserved antigenic regions on EIAV glycoproteins as well as a neutralization domain on gp90, which can be used as potential targets for vaccine development.     

Precision Tracing of Household Dengue Spread Using Inter- and Intra-Host Viral Variation Data,Kamphaeng Phet,Thailand

Dengue control approaches are best informed by granular spatial epidemiology of these viruses, yet reconstruction of inter- and intra-household transmissions is limited when analyzing case count, serologic, or genomic consensus sequence data. To determine viral spread on a finer spatial scale, we extended phylogenomic discrete trait analyses to reconstructions of house-to-house transmissions within a prospective cluster study in Kamphaeng Phet, Thailand. For additional resolution and transmission confirmation, we mapped dengue intra-host single nucleotide variants on the taxa of these time-scaled phylogenies. This approach confirmed 19 household transmissions and revealed that dengue disperses an average of 70 m per day between households in these communities. We describe an evolutionary biology framework for the resolution of dengue transmissions that cannot be differentiated based on epidemiologic and consensus genome data alone. This framework can be used as a public health tool to inform control approaches and enable precise tracing of dengue transmissions.     

The implementation of an infection control bundle within a Total Care Burns Unit

AimTo evaluate the impact of the implementation of a best practice infection prevention and control bundle on healthcare associated burn wound infections in a paediatric burns unit.BackgroundBurn patients are vulnerable to infection. For this patient population, infection is associated with increased morbidity and mortality, thereby representing a significant challenge for burns clinicians who care for them.MethodsAn interrupted time series was used to compare healthcare associated burn wound infections in paediatric burn patients before and after implementation of an infection prevention and control bundle. Prospective surveillance of healthcare associated burn wound infections was conducted from 2012 to 2014. Other potential healthcare associated infection rates were also reviewed over the study period, including urinary tract infections, pneumonia, upper respiratory tract infections and sepsis. An infection prevention and control bundle developed in collaboration between the paediatric burn unit and infection control clinicians was implemented in 2013 in addition to previous standard practice.ResultsDuring the study period a total of 626 patients were admitted to the paediatric burns unit. Healthcare associated burn wound infections reduced from 34 in 2012 to 0 in 2014 following the implementation of the infection prevention and control bundle. Pneumonia and sepsis also reduced to 0 in 2013 and 2014, however one upper respiratory tract infection occurred in 2013 and urinary tract infections persisted in 2013.ConclusionThe implementation of an infection prevention and control bundle was effective in reducing healthcare associated burn wound infections, pneumonia and sepsis within our paediatric burns unit. Urinary tract infections remain a challenge for future improvement.     

The interhemispheric fissure—surgical outcome of interhemispheric approaches

Neurosurgical Review - Exposure of the anterior skull base is challenging due to strategic structures. The interhemispheric approach (IHA) has turned out to be a feasible technique. We report our...     

Health-related quality of life,uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic

Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.