Associations between hypothalamic-pituitary-adrenal axis system gene variants and cortisol reactivity in preschoolers: Main effects and gene-environment interactions

Exposure to stressful events during early development has consistently been shown to produce long lasting effects on the hypothalamic-pituitary-adrenal (HPA) axis, which may increase vulnerability to mood and anxiety disorders. Recently reported genetic association studies indicate that these disorders may be influenced, in part, by gene-environment interactions (GxE) involving polymorphisms within the corticotrophin-releasing hormone and monoaminergic system genes. However, little is known about how genetic variants and life stress work to shape children’s neuroendocrine reactivity and emerging symptoms. Therefore, the aim of this thesis is to examine main effects of candidate genes and GxE on the neuroendocrine stress response and internalizing symptoms in a community sample of 409 preschoolers. In Chapter 2 analyses show associations between variants of the CRHR1 and CRHBP genes and children’s cortisol responses to a standardized laboratory stress task. I also found evidence for GxE, where variants of the CRH system genes moderated the impact of childhood stress on early-emerging symptoms of depression and anxiety. A functional polymorphism of the catechol-O-methyltransferase (COMT) gene, the val158met, has been implicated in the etiology of stress-related mood disorders. Therefore, in Chapter 3, I examined links between the val158met polymorphism, cortisol reactivity to stress, and internalizing symptoms. I found evidence for association between the val158met genotype and cortisol reactivity to stress. Additionally, the val158met genotype moderated the link between childhood stress and emerging symptoms of anxiety. Due to the proposed role of dopamine and serotonin gene polymorphisms in research on GxE in internalizing disorders, in Chapters 4 and 5, I examined whether associations between dopaminergic and serotonin candidate gene polymorphisms and childhood cortisol reactivity and internalizing symptoms were moderated by childhood life stress. Analyses showed evidence for GxE predicting children’s symptoms. Specifically, polymorphisms of DRD2 and DAT1 genes moderated the effect of childhood stress on emerging symptoms of anxiety. With regard to serotonin pathway polymorphisms, I found associations between the serotonin transporter promoter polymorphism (5-HTTLPR) and children’s anxious symptoms. Additionally, consistent with previously reported findings, the interaction between MAOA 30bp VNTR and childhood stress predicted child anxiety symptoms. Limitations of this work include a relatively small sample size for genetic analyses, as well as the examination of a limited number of markers at each gene. Additionally, I did not correct for multiple statistical tests in some analyses due to the hypothesis-driven nature of the work. Taken together, the analyses show the complex underpinnings of individual differences in stress regulation, and highlight specific genetic vulnerabilities that influence early psychophysiological reactivity, that may in turn contribute to the development of stress-related disorders later in development

Clinical Considerations For The Use Of Cantilever Bridges

Replacement of missing dentition is one of the common reasons to attend a dental practice for individuals who wish to restore their aesthetics and function. There are a variety of treatment modalities for the replacement of a single missing tooth that is a removable of partial denture, a fixed partial denture or an implant supported restoration. Each of these treatment options have their own advantages and disadvantages. Adequate clinical experience becomes a most important factor for treatment planning in fixed and removable prosthodontics. The cantilever fixed partial denture is defined as a restoration having one or more abutments at one end while the other end of the restoration remains unsupported. Anterior teeth replacement can be effectively done using a short-span cantilevered fixed partial denture. Studies report that conventional cantilevered fixed prostheses of various designs have a survival rate of 82% over a 10 year period and cantilevered resin-retained prosthesis show survival rates 83 92% during a 5 year period. While treatment planning for fixed cantilever bridges, there are aesthetic, design and occlusal considerations that should be kept in mind to achieve successful treatment outcome. These are discussed in this paper. Also included, is a clinical case report of a patient that had fixed cantilever prosthesis replacing the maxillary left central incisor with good aesthetic and functional results. Geriatric patients prefer the comfort of a cantilever fixed partial denture to a removable partial denture, since less maintenance is required at subsequent appointments. However, with the rapid advancement in implant dentistry, the use of cantilever fixed partial dentures may be decreasing. This article outlines the basic clinical considerations which may be applied during treatment for fixed cantilever bridges. Key Words: Cantilever bridges; clinical treatment planning; tooth replacement; fixed prosthodontics

Prevalence of bilateral cataract blindness in persons ≥50 years of age in Pulwama district, Jammu & Kashmir, India

Rapid assessment of cataract blindness has been accepted as a robust tool to help planners in developing countries.Prevalence of cataract blindness can give important information about the impact of a cataract intervention programme. A study in this direction was carried out in Pulwama district of Jammu & Kashmir. Our results clearly showed that with the increase in age, the prevalence of bilateral cataract blindness increases manifold. However, gender did influence the prevalence of cataract in the present survey. The prevalence of bilateral cataract decreases considerably, with the increase in education of both the genders. Among both male and female respondents examined, 89 percent were having both eyes phakia. Similarly 79 percent of study population were not having lenticular opacity either in R/E or L/E in both males and females. Results show that the prevalence of bilateral cataract blindness in district Pulwama is 4.16 percent

It\u27s a precious gift, not to waste : Is routine cross matching necessary in orthopedics surgery?: Retrospective study of 699 patients in 9 different procedures

Background: Orthopedic surgeries are usually associated with excessive blood loss which leads surgeons to overestimate need for blood transfusions and over ordering of blood. The cross matched blood, when not used, leads to the wastage of blood bank resources in terms of time, money and manpower. The objective of this study was to investigate the compliance to previously proposed MSBOS and to provide updated recommendations for all orthopedic procedures. Methods: A retrospective analysis was conducted between 1st June 2015 and 31st May 2016. Patients admitted to the orthopedic surgery service for whom blood products were requested were included. Cross Match/Transfusion (CT) Ratio, Transfusion Index and Transfusion Probability were calculated. Values of \u3c 2.5, \u3e 0.5 and \u3e 30% respectively, were taken as standards. Maximum Surgical Blood Ordering Schedule (MSBOS) was proposed based upon these calculations using Mead\u27s criteria. Results: Six hundred and ninety-nine patients were sampled after implementing exclusion criteria. The overall CT ratio was 4.87, transfusion index was 0.55 and transfusion probability was 25%. A compliance rate of 24.6% was observed with the reference CT ratio of 2.5. Highest CT ratio was calculated for arthroscopic procedures while tumor resection had the lowest ratio. Age, procedure performed, ASA status and use of tourniquet were found to be significantly associated with CT ratio being greater or less than 2.5. Conclusion: Results showed significant wastage of blood products and non-compliance with blood ordering guidelines. Hence there is need for large scale prospective studies to establish MSBOS and ensure its compliance

Girls\u27 internalizing symptoms and white matter tracts in Cortico-Limbic circuitry

© 2019 The Authors Dysfunction in cortico-limbic circuitry is implicated in internalizing disorders (i.e., depressive and anxious disorders), but less is known about whether structural variations precede frank disorder and thus potentially mark risk. We therefore examined associations between white matter (WM) tract microstructure in cortico-limbic circuitry at age 7 and concurrent and longitudinal patterns of internalizing symptoms in 42 typically developing girls using Diffusion Tensor Imaging (DTI). Girls\u27 internalizing symptoms were concurrently associated with reduced fractional anisotropy (FA) in segments of the cingulum bundle (CB) and the uncinate fasciculus (UF), bilaterally. Moreover, latent profile analysis showed that girls with increasing internalizing symptoms, based on assessments at ages 3, 6, 7, and 8, had reduced FA in these segments compared to girls with stably low symptoms. These results point to a putative neural mechanism underlying the course of childhood internalizing symptoms

Fungal Sinusitis with Intracranial Extension in Immuno-competent Patients: Surgical Planning According to Relation to Eloquent Neurovascular Structures

AbstractObjectiveTo evaluate the results of combined neurosurgical and ENT surgical management for patients with fungal sinusitis with intracranial extension.MethodsWe managed 10 cases with fungal sinusitis with intracranial extension. This included 7 females and 3 males. Four patients presented with unilateral proptosis, 2 with deterioration of level of consciousness due to meningitis, 2 with chronic headache, one with epilepsy and one patient presented with trigeminal pain. All cases had long history of chronic headache and nasal obstruction. CT was done in all cases, MR in 8 patients, CT angiography and conventional cerebral angiography in one patient. Surgical intervention was decided according to the relation of the fungal granuloma to eloquent intracranial structures. Endonasal approach alone was used when the granuloma was not related to the optic nerve, internal carotid artery or cavernous sinus (n=3). Combined subfrontal and endonasal approach was used when the granuloma was closely related to one or more of these structures (n=5). Transcranial approach alone was done for 2 patients with isolated sphenoid fungal sinusitis that was associated with a mycotic internal carotid artery aneurysm in one patient and with a temporal lobe abscess in the other. In addition, antifungal treatment was used for 8-12 weeks. Patients were followed up clinically and radiologically for 6-36 month period.ResultsNo morbidity related to the operative procedures was recorded in the study group. One patient died two month post-operatively due to fungal meningitis. In survivors (n=9): headache and nasal obstruction improved, proptosis was corrected, epilepsy and trigeminal pain were controlled by medication. Follow-up CT showed eradication of the fungal granuloma in all survivors. Histopathological results showed mucormycosis (n=2), aspirgillosis (n=4), and no fungus (4 patients).ConclusionTeam work by ENT and neurosurgical staff and early diagnosis are mandatory in the management of fungal sinusitis with intracranial extension in immune-competent patients. Surgical planning according to the relation of fungal granuloma to eloquent neurovascular structures is the corner stone for save removal of granuloma

The serotonin transporter promoter polymorphism moderates the continuity of behavioral inhibition in early childhood.

Persistently elevated behavioral inhibition (BI) in children is a marker of vulnerability to psychopathology. However, little research has considered the joint influences of caregiver and child factors that may moderate the continuity of BI in early childhood, particularly genetic variants that may serve as markers of biological plasticity, such as the serotonin transporter linked polymorphic region (5-HTTLPR). We explored this issue in 371 preschoolers and their caregivers, examining whether parent characteristics (i.e., overinvolvement or anxiety disorder) and child 5-HTTLPR influenced the continuity of BI between ages 3 and 5. Measures were observational ratings of child BI, observational and questionnaire measures of parenting, and parent interviews for anxiety disorder history, and children were genotyped for the 5-HTTLPR. Parent factors did not moderate the association between age 3 and age 5 BI; however, child BI at age 3 interacted with children\u27s 5-HTTLPR variants to predict age 5 BI, such that children with at least one copy of the short allele exhibited less continuity of BI over time relative to children without this putative plasticity variant. Findings are consistent with previous work indicating the 5-HTTLPR short variant increases plasticity to contextual influences, thereby serving to decrease the continuity of BI in early childhood