Clinical Symptomology Research Articles

Ten years of enzyme replacement therapy in paediatric onset mucopolysaccharidosis II in England

The outcome of 110 patients with paediatric onset mucopolysaccharidosis II (MPS II) since the commercial introduction of enzyme replacement therapy (ERT) in England in 2007 is reported.Median length of follow up was 10 years 3 months (range = 1 y 2 m to 18 years 6 month). 78 patients were treated with ERT, 18 had no ERT or disease modifying treatment 7 had haematopoietic stem cell transplant, 4 experimental intrathecal therapy and 3 were lost to follow up. There is clear evidence of improved survival (median age of death of ERT treated (n = 16) = 15.13 years (range = 9.53 to 20.58 y), and untreated (n = 17) = 11.43 y (0.5 to 19.13 y) p = .0005). Early introduction of ERT improved respiratory outcome at 16 years, the median FVC (% predicted) of those in whom ERT initiated <8 years = 69% (range = 34–86%) and 48% (25–108) (p = .045) in those started >8 years. However, ERT appears to have minimal impact on hearing, carpal tunnel syndrome or progression of cardiac valvular disease. Cardiac valvular disease occurred in 18/46 (40%), with progression occurring most frequently in the aortic valve 13/46 (28%). The lack of requirement for neurosurgical intervention in the first 8 years of life suggests that targeted imaging based on clinical symptomology would be safe in this age group after baseline assessments. There is also emerging evidence that the neurological phenotype is more nuanced than the previously recognized dichotomy of severe and attenuated phenotypes in patients presenting in early childhood.

Multidisciplinary management of spinal aneurysmal bone cysts: A single-center experience.

The management of spinal aneurysmal bone cysts (ABCs) is complex and often requires multimodality therapy, including surgical intervention to stabilize the axial skeleton, and avoid neurologic injury or death. With en bloc resection, ABCs have a recurrence rate of 12%, which increases to >50% with subtotal resection. The use of doxycycline sclerotherapy has been reported to reduce the recurrence rate of non-spinal ABCs to 5% at >24 month follow-up. We retrospectively reviewed our institutional results for sodium tetradecyl sulfate (STS)/doxycycline sclerotherapy and surgical intervention for spinal ABCs, to assess our treatment paradigm for these tumors and inform our future approach to these lesions. Three cervical, two thoracic and two lumbar spine ABCs were treated in seven patients with spine-exclusive disease at our institution from 2011 to the present. The most common presenting complaint was pain. Each patient was retrospectively reviewed for clinical symptomology, number of treatments, technique and clinical follow-up. Qualitative assessment of improvement was based on the most recent clinical evaluation. The cohort underwent a mean of three treatment sessions (range 2-15). All were treated with STS and/or doxycycline. Five patients underwent surgical intervention at some point, either before or following sclerotherapy. After the last sclerotherapy session, four patients reported stable or improved pain symptoms, while two reported progressive pain that required surgical intervention for that indication. One patient, who underwent both multiple rounds of sclerotherapy and surgical resection, died due to acute on chronic cervical spine collapse with cord compression and inability to control disease. We report our experience in the treatment of spinal column ABCs. Stabilization or improvement in pain was seen in four patients, while the remainder had progressive disease. Our multidisciplinary approach allows patients to receive the most appropriate treatment at presentation and thereafter, for symptom amelioration or spinal stability. Important future goals are to quantitatively assess changes in symptoms over time and to incorporate a reproducible radiographic endpoint for the assessment of treatment efficacy.

O56. Model Systems in Mice to Study Peripheral Inflammation, Resulting in Neuroinflammation

The link between peripheral inflammation and neuropsychiatric disorders has gained momentum in the recent past. Although the sequalae of peripheral inflammation leading to clinical symptomology is unclear, it is becoming apparent that microglia and neuroinflammation play a critical role in the pathophysiology of such disorders. To model the consequences of elevated inflammation, we challenged mice peripherally with LPS and polyI:C to study effects on brain neuroinflammation.

Binge drinking: Prevalence, correlates, and expectancies of alcohol use among individuals with first-episode psychosis.

AimThis study examines the prevalence and correlates of binge drinking and its association with expectancies of alcohol use, within a sample of patients with first‐episode psychosis enrolled in the Early Psychosis Intervention Programme (EPIP) in Singapore's Institute of Mental Health.MethodsA total of 280 patients from the EPIP were recruited for an on‐going longitudinal study examining cigarette smoking and alcohol habits. Only baseline data were used, pertaining to socio‐demographics, alcohol use, clinical symptomology, quality of life, and expectancies of alcohol use.ResultsOverall 23.9% (N = 67) reported ever binge drinking in their lifetime, and 11.4% (N = 32) had binged in the past 2 weeks. Controlling for all other socio‐demographic and clinical factors, binge drinking was significantly associated with higher education levels, having children, current or past history of cigarette smoking, and lower negative symptom scores. Binge drinkers were also more likely to endorse statements relating to the themes of enhancement seeking (ie, using alcohol to alter or enhance experiences in a pleasurable way), coping with distress, and socializing‐related expectancies of alcohol use.ConclusionSimilar to past studies, the prevalence of binge drinking among our first‐episode sample was relatively high. Our findings suggest certain lifestyle and social factors associated with risky drinking behaviour that future prevention efforts may address. Additionally, the three motivations of enhancement seeking, coping, and socializing also suggest psychological processes and coping styles that could be targeted for interventions.

Left fimbria atrophy is associated with hippocampal metabolism in female major depressive disorder patients.

Despite the high incidence of major depressive disorder (MDD) in females, the detailed neurobiology mechanism remains not fully understood. Increasing evidence showed that MDD was associated with hippocampal volumetric abnormality with different subfields demonstrating various alteration features. However, the linkage between hippocampal atrophy with its biochemical information remains unclear. In this study, we aim to investigate the relationship between bilateral hippocampal subfields volumetric and metabolic information in female MDD patients, using a combined T1weighted magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-MRS) technology. There are 15 female MDD patients and 12 matched healthy controls involved in the study. We found a significant decrease in left fimbria volume in MDD group, which was negatively correlated with left hippocampal choline level. In addition, the left hippocampal creatine concentration in patients was negatively correlated with left fimbria volume. Moreover, the NAA level in left hippocampus was negatively correlated with MDD clinical symptomology including anxiety and depression scores. Our findings suggest that the altered coupling between hippocampal structural and metabolic features might contribute to the etiology of female MDD patients.

Outcomes from 18years of cervical spine surgery in MPS IVA: a single centre's experience.

This study examines the long-term outcomes of paediatric Morquio (MPS IVA) patients undergoing cervical spine surgery and evaluates the factors that impacting this. A retrospective review was performed on all MPS IVA patients undergoing cervical spine surgery, since the introduction of standardised neuroradiological screening. The impact of preoperative neurological status, growth, genotype and radiological status on outcome is assessed, whilst long-term surgical, radiological and neurological outcomes are documented. Twenty-six of the eighty-two MPS IVA patients (31%) reviewed underwent cervical spine surgery at a median age of 6.1years (range, 1.45 to 15.24). Preoperatively, cord signal change was seen in 11 patients with 5 being myelopathic; however, 6 clinically manifesting patients had no overt cord signal change. Postoperatively, none of the 14 preoperatively clinically asymptomatic patients followed long term progressed neurologically during a median follow-up of 77.5months (range = 18-161). Of the ten preoperatively clinically symptomatic patients who were followed up for the same duration, seven continued to deteriorate, two initially improved and one remained stable. Radiological follow-up performed for a median duration of 7years (range = 0.5-16) has shown a degree of stenosis at the level immediately caudal to the termination of the graft in 76% of patients, though only one has become clinically symptomatic and required revision. Once clinically elicitable neurological signs become evident in patients with MPS IVA, they tend to progress despite surgical intervention. Referring clinicians should also not be falsely reassured by the lack of T2 spinal cord signal change but should consider surgical intervention in the face of new clinical symptomology or radiological signs of progressive canal stenosis or instability.

Cystic Endometrial Hyperplasia-Pyometra Complex in a Bitch: A Case Report

Abstract An eight-year-old nulliparous Spitz bitch was presented to clinics with a complaint of persistent vomiting and anorexia since fifteen days. It had a history of purulent discharges from vulva one year back. Based on findings of clinical examination, radiography, ultrasonography and laboratory reports, the condition was diagnosed as cystic endometrial hyperplasia. The clinical symptomology, surgical outcome of the case along with histopathological and immunohistochemical studies of the affected uterus were discussed. Keywords: Endometrial hyperplasia, nulliparous, hemometra, hydrometra, ovariohysterectomy Cite this Article P. Ravi Kumar, B. Sailaja, Ch. Sudha Rani Chowdary. Cystic Endometrial Hyperplasia-pyometra Complex in a Bitch: A Case Report. Research & Reviews: Journal of Veterinary Science and Technology. 2016; 5(2): 1–4p.

4:03 PM Abstract No. 368 Nutcracker syndrome as a cause of recurrent symptoms in pelvic congestion syndrome patients who underwent gonadal vein embolization

Left renal vein compression by the SMA (nutcracker syndrome) prevents normal flow from the left renal vein into IVC and can divert flow into the left ovarian vein in women, resulting in pelvic congestion syndrome symptoms. In these patients, embolization of the left ovarian vein result in renal venous hypertension, which may predispose patients to new or recurrent symptoms. The purpose of this study was to investigate the clinical implications of left renal vein compression in patients who underwent left ovarian vein embolization. In this retrospective study, 79 patients underwent left ovarian vein embolization. Of these, 40 females (mean age 44.5 years) had a contrast-enhanced CT or MRI prior to the procedure and adequate clinical follow-up. Electronic medical records were reviewed to capture clinical symptomology before and after embolization. On preprocedural CT or MRI, the percent compression of the left renal vein (LRV) by the SMA was measured, as was the diameter of the left lumbar vein at the level of the LRV. Categorical variables were compared with the chi square test. Left ovarian vein embolization was performed due to pelvic pain in 33 patients. In 7 patients, embolization was performed due to leg pain, swelling, or varicosities without pelvic pain. Of the patients with pelvic pain, 75% had improvement in symptoms. Overall, 27 patients reported recurrent, new, or unimproved pelvic pain or flank pain at a median of 159 days. In patients with 60% or greater narrowing of the LRV at the level of the SMA, 80% had recurrent/new/unchanged symptoms compared to 28% in patients without LRV compression (p = 0.003). The presence of a prominent left lumbar vein was significantly associated with LRV compression (p<0.001). The presence of both LRV compression and a prominent left lumbar vein had a 100% positive predictive value for recurrent/new/unimproved symptoms. The presence of nutcracker syndrome correlated significantly with recurrent or new symptoms after left ovarian vein embolization. Assessing its presence prior to embolization may be important to optimize outcomes; an alternative therapy may be warranted.

Changes in Emotion Processing following Brief Augmented Psychodynamic Interpersonal Therapy for Functional Neurological Symptoms

Functional neurological symptoms (FNS) are considered non-volitional and often very disabling, but are not explainable by neurological disease or structural abnormalities. Brief Augmented Psychodynamic Interpersonal Therapy (BAPIT) was adapted to treat the putative emotion processing deficits thought to be central to FNS aetiology and maintenance. BAPIT for FNS has previously been shown to improve levels of distress and functioning, but it is unknown whether improvements on such measures correlate with changes in emotion processing ‒ which this treatment focuses on. To determine (a) whether the recently developed Emotional Processing Scale-25 can be used to demonstrate BAPIT-associated changes in patients with FNS, and (b) whether changes in the EPS-25 are associated with changes in previously validated outcome measures. 44 patients with FNS completed questionnaires including the EPS-25 and measures of clinical symptomology (health-related quality of life (SF-36), somatic symptoms (PHQ-15), psychological distress (CORE-10) and illness understanding (BIPQ)) pre- and post-therapy. At group level, emotion processing improved following therapy (p = .049). Some measures of clinical symptomology also improved, namely health-related quality of life (p = .02) and illness understanding (p = .01). Improvements in the EPS-25 correlated with improvements in mental health-related quality of life and psychological distress. Emotion processing and some measures of clinical symptomology improved in patients with FNS following BAPIT. The EPS-25 demonstrated changes that correlated with previously validated outcome measures. The EPS-25 is a suitable measure of psychotherapy-associated change in the FNS patient population.

The Neuropsychology (Broadly Conceived) of Multiple System Atrophy, Progressive Supranuclear Palsy, and Corticobasal Degeneration.

To review the cognitive and behavioral features of the different atypical parkinsonian syndromes in which motor symptoms dominate early clinical symptomology: multiple systems atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). The impact of cognitive and behavioral deficits on quality of life, associations between neuropsychological and neuropsychiatric findings and brain imaging, and cognitive and behavioral symptom management are also discussed. A review of the available MSA, PSP, and CBD literature was conducted, with emphasis given to studies investigating the cognitive and behavioral features of the syndromes. Although the three reviewed atypical parkinsonian syndromes share many similarities to each other and PD from a neuropsychological perspective, differences in prevalence and severity of cognitive impairment and patterns of performance on neuropsychological and neuropsychiatric measures exist in the research literature. Cognitive and behavioral features are early and pervasive aspects of MSA, PSP, and CBD.

Combined serum levels of multiple proteins in tPA-BDNF pathway may aid the diagnosis of five mental disorders

Mental disorders are severe, disabling conditions with unknown etiology and are commonly misdiagnosed when clinical symptomology criteria are solely used. Our previous work indicated that combination of serum levels of multiple proteins in tissue plasminogen activator (tPA)-brain-derived neurotrophic factor (BDNF) pathway improved accuracy of diagnosis of major depressive disorder (MDD). Here, we measured serum levels of tPA, plasminogen activator inhibitor-1 (PAI-1), BDNF, precursor-BDNF (proBDNF), tropomyosin-related kinase B (TrkB) and neurotrophin receptor p75 (p75NTR) in patients with paranoid schizophrenia (SZ, n = 34), MDD (n = 30), bipolar mania (BM, n = 30), bipolar depression (BD, n = 22), panic disorder (PD, n = 30), and healthy controls (HCs, n = 30) by Enzyme-linked immunosorbent assay kits. We used receiver operating characteristic (ROC) curve to analyze diagnostic potential of these proteins. We found, compared with HCs, that serum tPA and proBDNF were lower in SZ, BM and BD; TrkB was lower in SZ and BD; and p75NTR was declined in SZ and BM. ROC analysis showed that combined serum level of tPA, PAI-1, BDNF, proBDNF, TrkB and p75NTR was better than any single protein in accuracy of diagnosis and differentiation, suggesting that the combination of multiple serum proteins levels in tPA-BDNF pathway may have a potential for a diagnostic panel in mental disorders.

7 Changes in emotion processing associated with brief augmented psychodynamic interpersonal therapy for functional neurological symptoms

Objective The putative links between abnormal emotion processing and Functional Neurological Symptoms (FNS) suggest that this patient group might benefit from a psychotherapeutic intervention targeting the perception, naming, tolerance, and expression of emotions. Brief Augmented Psychodynamic Interpersonal Therapy, an intervention designed to address emotion processing difficulties, has previously been associated with improvements in health-related quality of life and psychological distress in patients with FNS. The objective of this study was therefore to determine whether improvements in clinical symptomology following Brief Augmented Psychodynamic Interpersonal Therapy, were associated with improvements in emotion processing. A second exploratory objective was to see if there were any identifying characteristics of patients who made a clinically significant improvement in emotion processing. Method battery of self-report questionnaires was administered to patients with FNS (n=44), prior to and following a course of Brief Augmented Psychodynamic Interpersonal Therapy. Emotion Processing was measured using the Emotion Processing Scale (EPS-25). The Short Form 36 (SF-36), Clinical Outcomes in Routine Evaluations (CORE 10), Patient Health Questionnaire (PHQ-15), and the Brief Illness Perception Questionnaire (BIPQ) measured health-related quality of life, psychological distress, somatic symptom severity, and illness perception respectively. Clinically significant improvements on the EPS-25 were identified using the Reliable Change Index. Patients were subsequently categorised as making a clinically significant improvement or not, and compared on all available demographic and clinical symptomology variables. Results We observed a significant reduction on the EPS-25 (p=0.049) following Brief Augmented Psychodynamic Interpersonal Therapy for FNS. Change scores on the EPS-25 correlated positively with improvements on the mental health subscale of the SF-36 (r=0.634) and the CORE-10 (r=0.673). BIPQ scores were significantly lower (p=0.013) and SF-36 scores were significantly higher (p=0.020) post-therapy. 22% of patients made a clinically significant improvement on the EPS-25. However, we were unable to identify any demographic or clinical symptomology variables which differed significantly between patients who made a clinically significant improvement in emotion processing and those who did not. Conclusion Emotion processing in patients with FNS improved following treatment with Brief Augmented Psychodynamic Interpersonal Therapy. This improvement was related to a reduction in psychological distress and improved mental health-related quality of life. Patients also perceived their symptoms as less threatening and experienced an improved health-related quality of life following intervention. Further work is required to establish characteristics which could identify patients who are particularly likely to improve in emotion processing with Brief Augmented Psychodynamic Interpersonal Therapy for FNS.

Evaluation of Visual-Evoked Cerebral Metabolic Rate of Oxygen as a Diagnostic Marker in Multiple Sclerosis.

A multiple sclerosis (MS) diagnosis often relies upon clinical presentation and qualitative analysis of standard, magnetic resonance brain images. However, the accuracy of MS diagnoses can be improved by utilizing advanced brain imaging methods. We assessed the accuracy of a new neuroimaging marker, visual-evoked cerebral metabolic rate of oxygen (veCMRO2), in classifying MS patients and closely age- and sex-matched healthy control (HC) participants. MS patients and HCs underwent calibrated functional magnetic resonance imaging (cfMRI) during a visual stimulation task, diffusion tensor imaging, T1- and T2-weighted imaging, neuropsychological testing, and completed self-report questionnaires. Using resampling techniques to avoid bias and increase the generalizability of the results, we assessed the accuracy of veCMRO2 in classifying MS patients and HCs. veCMRO2 classification accuracy was also examined in the context of other evoked visuofunctional measures, white matter microstructural integrity, lesion-based measures from T2-weighted imaging, atrophy measures from T1-weighted imaging, neuropsychological tests, and self-report assays of clinical symptomology. veCMRO2 was significant and within the top 16% of measures (43 total) in classifying MS status using both within-sample (82% accuracy) and out-of-sample (77% accuracy) observations. High accuracy of veCMRO2 in classifying MS demonstrated an encouraging first step toward establishing veCMRO2 as a neurodiagnostic marker of MS.

Effect of pharmacist intervention on improving antidepressant medication adherence and depression symptomology: A systematic review and meta-analysis.

Depression is a widespread disease with effective pharmacological treatments, but low medication adherence. Pharmacists play a key role in supporting medication adherence in patients with depression given their accessibility to patients. The aim of this review was to systematically evaluate the impact of pharmacist interventions on adherence to antidepressants and clinical symptomology among adult outpatients with depressive disorders. A systematic review of controlled trials (both randomized and non-randomized) was conducted. Studies were obtained through a search of PubMed, Academic Search Premier, and Cochrane Library databases. Studies which included a pharmacist intervention to improve medication adherence in outpatients age 17 and above with a depressive disorder diagnosis and antidepressant treatment were included. Twelve publications met inclusion criteria, representing a total of 15,087 subjects: 1379 (9%) intervention and 13,708 (91%) control. The interventions in each selected publication included some level of in-person counseling and education to promote antidepressant adherence. The pooled odds ratio for medication adherence at 6 months was 2.50 (95% CI 1.62 to 3.86). There were no significant differences noted in subgroup meta-analyses except study location (US, Middle East or Europe) and setting. Only one of the identified studies reported statistically significant impacts of the pharmacist intervention on patient depression symptoms. The findings suggest that pharmacist interventions can enhance patient adherence to antidepressant medication in adult outpatients. However, this review failed to demonstrate a positive effect of these interventions on clinical symptoms. Additional longitudinal research is recommended to investigate the multidimensional relationships between pharmacist interventions, patient adherence, and clinical outcomes. Pharmacists play a key role in supporting medication adherence in patients with depression given their accessibility to patients. The purpose of this review was to systematically evaluate the impact of pharmacist interventions on adherence to antidepressants and clinical symptomology among adult outpatients with depressive disorders. A systematic review of randomized and non-randomized controlled trials was conducted of the twelve studies which met inclusion criteria. The findings suggest that pharmacist interventions can enhance patient adherence to antidepressant medication in adult outpatients. However, this review failed to demonstrate a positive effect of these interventions on clinical symptoms.

Exploring the Intersections of Trauma, Structural Adversity, and Psychosis among a Primarily African-American Sample: A Mixed-Methods Analysis.

Traumatic life events (TLEs) have been associated with multiple psychiatric diagnoses, including anxiety disorders, major depression, PTSD, and psychosis. To advance our understanding of the complex interactions between forms of adversity as they manifest across the lifespan, psychosis, and symptom content, we undertook a mixed-methods investigation of TLEs and psychosis. Our research explored the association between cumulative exposures, type of TLE, and proximity to the traumatic event and psychosis; the association between TLEs and clinical symptomology including specific types of delusions and/or hallucinations; and how qualitative data further inform understanding of complex relationships and patterns of past trauma and symptoms as they unfold over time. There were a total of 97 participants in the quantitative study sample, 51 participants with present state psychosis and 46 non-clinical. There were a total of 34 qualitative study participants, all of whom were experiencing psychosis. The quantitative analysis showed that when comparing persons with psychosis to the non-clinical group, there were no group differences in the overall total score of TLEs. However, there was a significant difference in cumulative TLEs that “Happened,” demonstrating that as the number of TLEs increased, the likelihood of clinical psychosis also increased. We also found a correlation between lifetime cumulative TLEs that “Happened” and PANSS five-factor analysis: positive, excitement, depression, thought disorder, activation, and paranoia scores. The qualitative analysis further built on these finding by providing rich narratives regarding the timing of trauma-related onset, relationships between trauma and both trauma-related and religious–spiritual content, and trauma and hallucinatory modality. Analysis of participant narratives suggests the central role of localized cultural and sociopolitical influences on onset, phenomenology, and coping and contributes to a growing literature calling for strengths-based, client-driven approaches to working with distressing voices and beliefs that centers the exploration of the personal and social meaning of such experiences including links to life narratives. Findings also underscore the clinical importance of trauma assessment and trauma-informed care.

Testosterone deficiency in adults and corresponding treatment patterns across the globe.

The global prevalence of testosterone deficiency (TD) ranges from 10–40%. The actual diagnosis of TD is controversial, as a wide range of total testosterone (TT) thresholds are used for diagnosis (200–400 ng/dL), and physicians differ in their emphasis placed on clinical symptoms. There are also significant global differences in the prescription patterns of testosterone replacement therapy (TRT). In the United States, prescription of TRT is significantly higher than the rest of the world, increasing 3-fold over the last 10 years and more so in eugonadal men. The majority of treating physicians emphasizes clinical symptomology of TD over laboratory values, and up to one-fourth of their patients do not even have serum testosterone levels. There are significant inter-physician differences in willingness to prescribe TRT in the setting of prostate cancer. Data is scarce on testosterone prescribing patterns in Africa, Asia, and the Middle East. More literature is needed to better characterize how physicians from different regions diagnose TD.

Utility of home sleep apnea testing in high-risk veterans.

Many Veterans Affairs Medical Centers (VAMCs) have implemented home sleep apnea testing (HSAT) in lieu of traditional in-lab testing to establish a timely and cost-sensitive diagnosis of obstructive sleep apnea (OSA). However, concern remains for the sensitivity and specificity of said technology in this population as many veterans are at increased risk for many of the comorbid conditions that can limit the accuracy of HSAT results. Hence, the purpose of this study is to evaluate rate of incongruent outcomes (e.g., negative HSAT results despite high clinical symptomology) as well as differences in study quality metrics and predictors of OSA between veteran sleep patients and general sleep patients being evaluated by a home sleep test. A random sample of HSAT outcomes from 1500 veterans and 1500 general sleep clinic patients was retrieved from a repository of anonymized HSAT outcomes from 2009 to 2013. General sleep clinic data were from patients referred for home sleep testing from a variety of clinical practices across North America, whereas VAMC patients were tested using a central dissemination process. All patients were tested for OSA using the Apnea Risk and Evaluation System (ARES), an HSAT that simultaneously records airflow, pulse oximetry, snoring, accelerometry, and EEG. Sample differences and rates of comorbidities, HSAT outcomes, predictors of OSA, and pretest OSA risk information were evaluated between groups. The presence of OSA was defined as an apnea-hypopnea index (AHI; using 4% desaturation criterion) of ≥5 and ≥15 events per hour. Sample differences in predictors of OSA were evaluated using logistic multiple regression. Veterans (91.3% male) were more likely to report comorbidities, especially depression, insomnia, hypertension, diabetes, restless legs syndrome (RLS), and use of sleep and pain medications compared to general sleep clinic patients (57.1% male). Despite differences in the rate of medical comorbidities, no differences were observed between groups with regard to rates of positive studies, study integrity indicators, or predictors of OSA. Veterans, on average, had 30min less recording time compared to those in the general clinic sample (p<.01). However, these differences did not impact the amount of the record that was deemed valid nor were veterans more likely to have wakefulness after sleep onset. Predictors of OSA for both groups included advancing age, and increased measures of adiposity (neck circumference and BMI). Mean AHI and respiratory disturbance index (RDI) were statistically similar for both groups and were similar for sleep stage and position. Home sleep apnea testing for the diagnosis of OSA appears to yield similar results for VAMC patients deemed at high risk for OSA as it does with general sleep clinic patients.

Design, synthesis, and evaluation of (2S,4R)-Ketoconazole sulfonamide analogs as potential treatments for Metabolic Syndrome

Metabolic Syndrome, also referred to as ‘Syndrome X’ or ‘Insulin Resistance Syndrome,’ remains a major, unmet medical need despite over 30years of intense effort. Recent research suggests that there may be a causal link between this condition and abnormal glucocorticoid processing. Specifically, dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis leads to increased systemic cortisol concentrations. Cushing’ syndrome, a disorder that is also typified by a marked elevation in levels of cortisol, produces clinical symptomology that is similar to those observed in MetS, and they can be alleviated by decreasing circulating cortisol concentrations. As a result, it has been suggested that decreasing systemic cortisol concentration might have a positive impact on the progression of MetS. This could be accomplished through inhibition of enzymes in the cortisol synthetic pathway, 11β-hydroxylase (Cyp11B1), 17α‐hydroxylase‐C17,20‐lyase (Cyp17), and 21‐hydroxylase (Cyp21). We have identified a series of novel sulfonamide analogs of (2S,4R)-Ketoconazole that are potent inhibitors of these enzymes. In addition, selected members of this class of compounds have pharmacokinetic properties consistent with orally delivered drugs, making them well suited to further investigation as potential therapies for MetS.

Clinical Aspect of Diseases of Cornea in Ayurveda

Introduction: There are total seventy sixocular diseases described in Sushruta Samhita and 94 diseases in Astanga Sangrah &amp; Astanga Hridya. This concept of classification of ocular disorders is well buttressed by classifying the disease as Sandhigata (Diseases affecting junctional areas of eye), Vartamagata (Diseases of eyelids), Shuklagata (Diseases of Sclera plus Conjunctiva), Krishnagata (Diseases of Cornea), Sarvagata (Diseases affecting all parts of Eye), Drishtigata (Diseases of Lens). Material and Methods: Extensive literary review of various text of Ayurveda in order to carve out a possible comparison of Ayurvedic Corneal Ophthalmological disorders with modern counterpart. Aims: To establish clinical correlation between diseases of Krishna mandala to disease of the cornea. Discussion: Classifications of corneal diseases in classical Ayurvedic texts are sequential and progressive in nature viz. one condition progress to the next corresponding stage. Acharya Sushruta described 4 types of diseases of cornea while Vagbhatta has enumerated 5 types. A conscious endeavor is made to correlate the Ayurvedic and modern corneal disorders in a complimentary manner. Conclusion: The congruent behavior of corneal disorders of Ayurved and modern is justified by the clinical symptomology, progression of the disease, prognostic reasons and relevant intervention. The integrated disease approach, treatment application and predicting prognosis will suffice the resultant outcome of the disease in a more favorable perspective which will herald a better approach in managing preventable corneal blindness.Â

Separation anxiety in dogs: What progress has been made in our understanding of the most common behavioral problems in dogs?

Separation anxiety has long been recognized as an anxiety-related disorder in dogs that is only observed in the owner's real absence or perceived absence. Over the past four decades, this condition has been the most commonly discussed disorder in published studies, but etiology, treatment, and prevention remain elusive. A review of the literature indicates a lack of comparative studies. Little progress has been made to build a new understanding beyond the clinical symptomology. Future research employing more rigorous designs and systematically building upon a clearly defined research questions is needed to advance our knowledge of this most common behavioral problem in dogs.