Children's unique experience of depression: Using a developmental approach to predict variation in symptomatology

<p>Abstract</p> <p>Background</p> <p>Current clinical knowledge suggests that children can have different types of depressive symptoms (irritability and aggression), but presents no theoretical basis for these differences. Using a developmental approach, the present study sought to test the relationship between developmental level (mental age) and expression of depressive symptoms. The primary hypothesis was that as children's mental age increased, so would the number of internalizing symptoms present.</p> <p>Methods</p> <p>Participants were 252 psychiatric inpatients aged 4 to 16 with a diagnosed depressive disorder. All children were diagnosed by trained clinicians using DSM criteria. Patients were predominantly male (61%) with varied ethnic backgrounds (Caucasian 54%; African American 22%; Hispanic 19%; Other 5%). Children were given an IQ test (KBIT or WISC) while within the hospital. Mental age was calculated by using the child's IQ score and chronological age. Four trained raters reviewed children's records for depressive symptoms as defined by the DSM-IV TR. Additionally, a ratio score was calculated to indicate the number of internalizing symptoms to total symptoms.</p> <p>Results</p> <p>Mental age positively correlated (<it>r </it>= .51) with an internalizing total symptom ratio score and delineated between several individual symptoms. Mental age also predicted comorbidity with anxiety and conduct disorders. Children of a low mental age were more likely to be comorbid with conduct disorders, whereas children with a higher mental age presented more often with anxiety disorders. Gender was independently related to depressive symptoms, but minority status interacted with mental age.</p> <p>Conclusion</p> <p>The results of this study indicate that a developmental approach is useful in understanding children's depressive symptoms and has implications for both diagnosis and treatment of depression. If children experience depression differently, it follows that treatment options may also differ from that which is effective in adults.</p

A feasibility study incorporating a pilot randomised controlled trial of oral feeding plus pre-treatment gastrostomy tube versus oral feeding plus as-needed nasogastric tube feeding in patients undergoing chemoradiation for head and neck cancer (TUBE trial): study protocol

Background There are 7000 new cases of head and neck squamous cell cancers (HNSCC) treated by the NHS each year. Stage III and IV HNSCC can be treated non-surgically by radio therapy (RT) or chemoradiation therapy (CRT). CRT can affect eating and drinking through a range of side effects with 90 % of patients undergoing this treatment requiring nutritional support via gastrostomy (G) or nasogastric (NG) tube feeding. Long-term dysphagia following CRT is a primary concern for patients. The effect of enteral feeding routes on swallowing function is not well understood, and the two feeding methods have, to date, not been compared to assess which leads to a better patient outcome. The purpose of this study is to explore the feasibility of conducting a randomised controlled trial (RCT) comparing these two options with particular emphasis on patient willingness to be randomised and clinician willingness to approach eligible patients. Methods/design This is a mixed methods multicentre study to establish the feasibility of a randomised controlled trial comparing oral feeding plus pre-treatment gastrostomy versus oral feeding plus as required nasogastric tube feeding in patients with HNSCC. A total of 60 participants will be randomised to the two arms of the study (1:1 ratio). The primary outcome of feasibility is a composite of recruitment (willingness to randomise and be randomised) and retention. A qualitative process evaluation investigating patient, family and friends and staff experiences of trial participation will also be conducted alongside an economic modelling exercise to synthesise available evidence and provide estimates of cost-effectiveness and value of information. Participants will be assessed at baseline (pre-randomisation), during CRT weekly, 3 months and 6 months. Discussion Clinicians are in equipoise over the enteral feeding options for patients being treated with CRT. Swallowing outcomes have been identified as a top priority for patients following treatment and this trial would inform a future larger scale RCT in this area to inform best practice

NR4A Gene Expression Is Dynamically Regulated in the Ventral Tegmental Area Dopamine Neurons and Is Related to Expression of Dopamine Neurotransmission Genes

The NR4A transcription factors NR4A1, NR4A2, and NR4A3 (also known as Nur77, Nurr1, and Nor1, respectively) share similar DNA-binding properties and have been implicated in regulation of dopamine neurotransmission genes. Our current hypothesis is that NR4A gene expression is regulated by dopamine neuron activity and that induction of NR4A genes will increase expression of dopamine neurotransmission genes. Eticlopride and γ-butyrolactone (GBL) were used in wild-type (+/+) and Nurr1-null heterozygous (+/−) mice to determine the mechanism(s) regulating Nur77 and Nurr1 expression. Laser capture microdissection and real-time PCR was used to measure Nurr1 and Nur77 mRNA levels in the ventral tegmental area (VTA). Nur77 expression was significantly elevated 1 h after both GBL (twofold) and eticlopride (fourfold). In contrast, GBL significantly decreased Nurr1 expression in both genotypes, while eticlopride significantly increased Nurr1 expression only in the +/+ mice. In a separate group of mice, haloperidol injection significantly elevated Nur77 and Nor1, but not Nurr1 mRNA in the VTA within 1 h and significantly increased tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA expression by 4 h. These data demonstrate that the NR4A genes are dynamically regulated in dopamine neurons with maintenance of Nurr1 expression requiring dopamine neuron activity while both attenuation of dopamine autoreceptors activation and dopamine neuronal activity combining to induce Nur77 expression. Additionally, these data suggest that induction of NR4A genes could regulate TH and DAT expression and ultimately regulate dopamine neurotransmission

A systematic review of task- shifting for HIV treatment and care in Africa

BACKGROUND: Shortages of human resources for health (HRH) have severely hampered the rollout of antiretroviral therapy (ART) in sub-Saharan Africa. Current rollout models are hospital- and physician-intensive. Task shifting, or delegating tasks performed by physicians to staff with lower-level qualifications, is considered a means of expanding rollout in resource-poor or HRH-limited settings. METHODS: We conducted a systematic literature review. Medline, the Cochrane library, the Social Science Citation Index, and the South African National Health Research Database were searched with the following terms: task shift*, balance of care, non-physician clinicians, substitute health care worker, community care givers, primary healthcare teams, cadres, and nurs* HIV. We mined bibliographies and corresponded with authors for further results. Grey literature was searched online, and conference proceedings searched for abstracts. RESULTS: We found 2960 articles, of which 84 were included in the core review. 51 reported outcomes, including research from 10 countries in sub-Saharan Africa. The most common intervention studied was the delegation of tasks (especially initiating and monitoring HAART) from doctors to nurses and other non-physician clinicians. Five studies showed increased access to HAART through expanded clinical capacity; two concluded task shifting is cost effective; 9 showed staff equal or better quality of care; studies on non-physician clinician agreement with physician decisions was mixed, with the majority showing good agreement. CONCLUSIONS: Task shifting is an effective strategy for addressing shortages of HRH in HIV treatment and care. Task shifting offers high-quality, cost-effective care to more patients than a physician-centered model. The main challenges to implementation include adequate and sustainable training, support and pay for staff in new roles, the integration of new members into healthcare teams, and the compliance of regulatory bodies. Task shifting should be considered for careful implementation where HRH shortages threaten rollout programmes

Carbon Stocks and Fluxes in Tropical Lowland Dipterocarp Rainforests in Sabah, Malaysian Borneo

Deforestation in the tropics is an important source of carbon C release to the atmosphere. To provide a sound scientific base for efforts taken to reduce emissions from deforestation and degradation (REDD+) good estimates of C stocks and fluxes are important. We present components of the C balance for selectively logged lowland tropical dipterocarp rainforest in the Malua Forest Reserve of Sabah, Malaysian Borneo. Total organic C in this area was 167.9 Mg C ha−1±3.8 (SD), including: Total aboveground (TAGC: 55%; 91.9 Mg C ha−1±2.9 SEM) and belowground carbon in trees (TBGC: 10%; 16.5 Mg C ha−1±0.5 SEM), deadwood (8%; 13.2 Mg C ha−1±3.5 SEM) and soil organic matter (SOM: 24%; 39.6 Mg C ha−1±0.9 SEM), understory vegetation (3%; 5.1 Mg C ha−1±1.7 SEM), standing litter (<1%; 0.7 Mg C ha−1±0.1 SEM) and fine root biomass (<1%; 0.9 Mg C ha−1±0.1 SEM). Fluxes included litterfall, a proxy for leaf net primary productivity (4.9 Mg C ha−1 yr−1±0.1 SEM), and soil respiration, a measure for heterotrophic ecosystem respiration (28.6 Mg C ha−1 yr−1±1.2 SEM). The missing estimates necessary to close the C balance are wood net primary productivity and autotrophic respiration

Long Tract of Untranslated CAG Repeats Is Deleterious in Transgenic Mice

The most frequent trinucleotide repeat found in human disorders is the CAG sequence. Expansion of CAG repeats is mostly found in coding regions and is thought to cause diseases through a protein mechanism. Recently, expanded CAG repeats were shown to induce toxicity at the RNA level in Drosophila and C. elegans. These findings raise the possibility that CAG repeats may trigger RNA-mediated pathogenesis in mammals. Here, we demonstrate that transgenic mice expressing EGFP transcripts with long CAG repeats in the 3′ untranslated region develop pathogenic features. Expression of the transgene was directed to the muscle in order to compare the resulting phenotype to that caused by the CUG expansion, as occurs in myotonic dystrophy. Transgenic mice expressing 200, but not those expressing 0 or 23 CAG repeats, showed alterations in muscle morphology, histochemistry and electrophysiology, as well as abnormal behavioral phenotypes. Expression of the expanded CAG repeats in testes resulted in reduced fertility due to defective sperm motility. The production of EGFP protein was significantly reduced by the 200 CAG repeats, and no polyglutamine-containing product was detected, which argues against a protein mechanism. Moreover, nuclear RNA foci were detected for the long CAG repeats. These data support the notion that expanded CAG repeat RNA can cause deleterious effects in mammals. They also suggest the possible involvement of an RNA mechanism in human diseases with long CAG repeats

CTL Escape Mediated by Proteasomal Destruction of an HIV-1 Cryptic Epitope

Cytotoxic CD8+ T cells (CTLs) play a critical role in controlling viral infections. HIV-infected individuals develop CTL responses against epitopes derived from viral proteins, but also against cryptic epitopes encoded by viral alternative reading frames (ARF). We studied here the mechanisms of HIV-1 escape from CTLs targeting one such cryptic epitope, Q9VF, encoded by an HIVgag ARF and presented by HLA-B*07. Using PBMCs of HIV-infected patients, we first cloned and sequenced proviral DNA encoding for Q9VF. We identified several polymorphisms with a minority of proviruses encoding at position 5 an aspartic acid (Q9VF/5D) and a majority encoding an asparagine (Q9VF/5N). We compared the prevalence of each variant in PBMCs of HLA-B*07+ and HLA-B*07- patients. Proviruses encoding Q9VF/5D were significantly less represented in HLA-B*07+ than in HLA-B*07- patients, suggesting that Q9FV/5D encoding viruses might be under selective pressure in HLA-B*07+ individuals. We thus analyzed ex vivo CTL responses directed against Q9VF/5D and Q9VF/5N. Around 16% of HLA-B*07+ patients exhibited CTL responses targeting Q9VF epitopes. The frequency and the magnitude of CTL responses induced with Q9VF/5D or Q9VF/5N peptides were almost equal indicating a possible cross-reactivity of the same CTLs on the two peptides. We then dissected the cellular mechanisms involved in the presentation of Q9VF variants. As expected, cells infected with HIV strains encoding for Q9VF/5D were recognized by Q9VF/5D-specific CTLs. In contrast, Q9VF/5N-encoding strains were neither recognized by Q9VF/5N- nor by Q9VF/5D-specific CTLs. Using in vitro proteasomal digestions and MS/MS analysis, we demonstrate that the 5N variation introduces a strong proteasomal cleavage site within the epitope, leading to a dramatic reduction of Q9VF epitope production. Our results strongly suggest that HIV-1 escapes CTL surveillance by introducing mutations leading to HIV ARF-epitope destruction by proteasomes

The elusive archaeology of Kongo urbanism: the case of Kindoki, Mbanza Nsundi (Lower Congo, DRC)

We present here results, analyses and an in-depth historical contextualisation of the fieldwork undertaken in 2012 and 2013 at the Kindoki site in the Lower Congo (DRC). This site is linked with Mbanza Nsundi, one of the Kongo Kingdom's provincial capitals, which turns out to be archaeologically 'elusive'. Pinpointing its location proved to be particularly challenging. To this end, a historically-informed excavation methodology was developed that was never implemented in Central Africa before. We combined a strategy of systematic test pits with a large-scale 50 m grid approach. A cemetery was identified on Kindoki Hill with distinct but contemporaneous quarters of a 16th-17thcenturies settlement on both sides. The cemetery itself contains mainly 18th-century burials, in all likelihood of successive Nsundi rulers. The foreign, especially Portuguese, ceramics excavated on the hilltop and the hundreds of Venetian and likely Bavarian beads found in the graves are indicative of Mbanza Nsundi's connection to trade routes linking the Atlantic coast with the Pool region. The most striking discovery is that of a previously unknown type of comb-impressed pottery, from a pit with a calibrated radiocarbon date AD 1294-1393 (2 sigma). This suggests that a settlement had been developing at Kindoki since at least the 14th century, which allows us, for the very first time, to spatially bridge Kongo history and 'prehistory'. For the entire Lower Congo region only three 14C dates posterior to AD 1000 were available before the start of the KongoKing project, twelve have been added for just Kindoki