Controlling Microbial Multicellular Behaviors With Saccharide Derivatives

Microbial multicellular behaviors like biofilm formation and swarming motility are known to increase their tolerance against antimicrobials. From microbial standpoint, nonmicrobicidal agents that do not impede growth are tolerable and therefore, there is a lower propensity to develop resistance against such agents as compared to microbicidal ones (antibiotics). This study describes a new antibiofilm approach of using nonmicrobicidal saccharide derivatives for controlling the multicellular behaviors of gram-negative bacteria, Pseudomonas aeruginosa and fungus, Candida albicans. Pseudomonas aeruginosa is known to secrete rhamnolipids, a class of biosurfactants that plays an important role in maintaining the architecture of its biofilm and promoting its swarming motility. Here we show the ability of certain synthetic nonmicrobicidal disaccharide derivatives (DSDs) to mimic the biofunctions of rhamnolipids. The rhlA mutant of P. aeruginosa is incapable of synthesizing rhamnolipids and also unable to swarm on semi-solid agar gel. When the natural ligands, rhamnolipids were externally added into the semi-solid agar gel in a concentration dependent manner, the swarming of the rhlA mutant reactivated at lower concentrations (10 μM) and then at relatively higher concentrations (15 μM), the swarming reactivation was reversed. When some active synthetic DSDs were tested on the rhlA mutant, the bacterial swarming first reactivated and then the activation reversed at higher DSD concentrations, similar to the effect of externally added rhamnolipids. Previously, a known bacterial signalling molecule has been shown to exhibit a similar concentration dependent activation and then activation reversal for light simulation by Vibrio fischeri. Some DSDs having disaccharide stereochemistries (cellobiose or maltose) and a bulky aliphatic tail (3, 7, 11-trimethyl-dodecanyl) caused swarming reactivation of the rhlA mutant at concentrations lower than that caused by the externally added rhamnolipids. The synthetic nonmicrobicidal DSDs were also very effective at inhibiting the adhesion of P. aeruginosa to polystyrene surface, and at inhibiting the bacterial biofilm formation. These DSDs were also potent dispersers of pre-formed biofilm of P. aeruginosa. The potent antibiofilm (inhibition and dispersion) activities were observed for those DSDs that possessed a disaccharide (cellobiose or maltose) stereochemistry and a bulky aliphatic chain such as 3, 7, 11-trimethyl-dodecanyl. These potent DSDs had half-maximal inhibitory concentrations for biofilm inhibition (IC50) and dispersion (DC50) comparable to those of known potent antibiofilm agents against P. aeruginosa. Gene-reporting assays indicate that the mechanism of action of such DSDs is not via the known las or rhl quorum sensing systems of P. aeruginosa but that the adhesin potein, pilin maybe a likely target of such molecules. Biofilms formed under natural settings are usually formed by both bacteria and fungus that co-reside in the same microenvironment. Therefore, agents that can prevent mixed biofilms are desirable from a therapeutic standpoint. Despite being nonmicrobicidal to both fungal blastospores and hyphae, the synthetic DSDs were able to inhibit the biofilm formation of fungus Candida albicans. Microscopic evaluation showed that most DSDs did not prevent the blastospores-to-hyphae morphogenesis. The DSDs were effective at inhibiting biofilm formation of Candida albicans when applied within five minutes of seeding the test surface with fungal cells. Using a surface based assay it was shown that one DSD dramatically reduced the surface adhesion of Candida albicans hyphae. The antibiofilm activity of such DSDs against Candida albicans is probably due to their ability to prevent hyphae surface adhesion

A study of intent of suicide in people with major depression

Background: Depression is most important underlying diagnosis among the cases of suicide. There is dearth of information regarding suicidal intent among people of depression and its relationship with hopelessness among Indians. Aims & Objective: To describe the intent of suicide in people with depression among the north Indian population. Material & Methods: This was a cross-sectional study at department of psychiatry, King George's Medical University, Lucknow. Subjects between age group of 18-60 years with major depressive disorder as per DSM-IV TR criteria were screened and included in the study. Each subject was assessed using Hamilton Depression Rating Scale (HRS), Beck’s Hopelessness Scale (BHS) and Suicide Intent Questionnaire (SIQ). Results: Suicidal intent was observed among 68.1% (n=49) of sample (n=72). There was no significant (p>0.05) association of suicidal intent with socio-demographic factors except domicile status. Suicidal intent was common among people with moderate to severe depression and those with hopelessness. The hopelessness was present among 70.8% of subjects. Conclusion: Suicidal intent is common among people with major depression. The authors emphasize the need of exploration of suicidal intent in people with depression

Adherence to highly active antiretroviral therapy and its correlates among HIV infected pediatric patients in Ethiopia

BACKGROUND: The introduction of combination antiretroviral therapy (ART) has resulted in striking reductions in HIV-related mortality. Despite increased availability of ART, children remain a neglected population. This may be due to concerns that failure to adhere appears to be related to continued viral replication, treatment failure and the emergence of drug-resistant strains of HIV. This study determines the rates and factors associated with adherence to Antiretroviral (ARV) Drug therapy in HIV-infected children who were receiving Highly Active Antiretroviral Therapy (HAART) in Addis Ababa, Ethiopia in 2008. METHODS: A cross-sectional study was conducted in five hospitals in Addis Ababa from February 18 - April 28, 2008. The study population entailed parents/caretaker and index children who were following ART in the health facilities. A structured questionnaire was used for data collection. RESULTS: A total of 390 children respondents were included in the study with a response rate of 91%. The majority, equaling 205 (52.6%) of the children, were greater than 9 years of age. Fifty five percent of the children were girls. A total of 339 children (86.9%) as reported by caregivers were adherent to antiretroviral drugs for the past 7 days before the interview. Numerous variables were found to be significantly associated with adherence: children whose parents did not pay a fee for treatment [OR = 0.39 (95%CI: 0.16, 0.92)], children who had ever received any nutritional support from the clinic [OR = 0.34 (95%CI: 0.14, 0.79)] were less likely to adhere. Whereas children who took co-trimoxazole medication/syrup besides ARVs [OR = 3.65 (95%CI: 1.24, 10.74)], children who did not know their sero-status [OR = 2.53 (95%CI: 1.24, 5.19)] and children who were not aware of their caregiver's health problem [OR = 2.45 (95%CI: 1.25, 4.81)] were more likely to adhere than their counterparts. CONCLUSION: Adherence to HAART in children in Addis Ababa was higher than other similar set-ups. However, there are still significant numbers of children who are non-adherent to HAART

Performance Evaluation of High-Resolution Ultrasound versus Magnetic Resonance Imaging in Diagnosing Peripheral Nerve Pathologies

Background High-resolution ultrasound (HRUS) and magnetic resonance neurography (MRN) are considered complementary to clinical and neurophysiological assessment for neuropathies. Aims The aim of our study was to compare the accuracy of HRUS and MRN for detecting various peripheral nerve pathologies, to choose the correct investigation to facilitate prompt patient management. Materials and Methods This prospective study was done using HRUS with 14 MHz linear-transducer and 3 or 1.5T MR in cases referred for the assessment of peripheral nerve pathologies. Image interpretation was done using a scoring system (score 0–3 confidence level) to assess for nerve continuity/discontinuity, increased nerve signal/edema, fascicular change, caliber change, and neuroma/mass lesion. We determined the accuracy, sensitivity, and specificity of these modalities compared with the diagnostic standard determined by surgical and/or histopathological, if not performed then clinical and/or electrodiagnostic evaluation. Results The overall accuracy of MRN was 89.3% (specificity: 66.6%, sensitivity: 92.6%, negative predictive value [NPV]: 57.1%, positive predictive value [PPV]: 95%) and that of HRUS was 82.9% (specificity: 100%, sensitivity: 80.4%, NPV: 42.8, PPV: 100). The confidence level for detecting nerve discontinuity and change in nerve caliber was found to be higher on ultrasonography than magnetic resonance imaging (MRI) (100 vs. 70% and 100 vs. 50%, respectively). Pathology of submillimeter caliber nerves was accurately detected by HRUS and these could not be well-visualized on MRI. Conclusion HRUS is a powerful tool that may be used as the first-line imaging modality for the evaluation of peripheral nerve pathologies, and a better means of evaluation of peripheral nerves with submillimeter caliber

Spondyloarthropathy - Is sacroiliac joint imaging sufficient? A study of 431 patients

Background: Sacroiliac (SI) joint involvement (sacroiliitis) is considered as major criteria for diagnosing Spondyloarthropathy (SpA), although involvement of spine and hip can also occur. The aim of our study was to assess the utility of including sagittal short-tau inversion recovery (STIR) sequence of dorsolumbar spine and coronal STIR/proton density (PD) fat saturated sequence through both hips, to routine SI joint magnetic resonance (MR) imaging protocol, in patients clinically suspected to have SpA. Material and Methods: A retrospective observational study was conducted between February 2013 and February 2018 on clinically suspected SpA patients referred to our department for imaging. The images obtained using this new SI joint protocol were evaluated for findings suggesting SpA diagnosis as per the Assessment of SpondyloArthritis international Society criteria. Other differentials for similar symptoms were also looked for. Results: Of the 431 patients (313 M and 118 F), 255 had features confirming the diagnosis of SpA and 176 had no radiological manifestations of SpA (56 were normal and 120 had other findings to suggest clinical symptoms; e.g., degenerative SpA, Pott’s spine, skeletal metastases, early AVN of hip, cysticercus, iliofemoral impingement). 19/255 patients had normal SI joints but other findings to suggest diagnosis of SpA, e.g. romanus lesions, costovertebritis/costotransversitis, pubic symphysitis, inflammatory hip arthropathy, enthesitis, iliofemoral/trochanteric bursitis. 33/61 patients with chronic sacroiliitis had disease activity in spine or hip. Conclusion: Inclusion of sections through dorsolumbar spine and both hips to routine SI joint protocol, helped in identifying: (a) early disease in 19 patients, who had normal SI joints and may have otherwise been missed with routine only SI joint imaging, (b) additional findings in SpA-related sacroiliitis, (c) disease activity in chronic sacroiliitis, and (d) other causes of low back pain and thus helped in further patient management

A cross-sectional study of cognitive functions and disability in schizophrenia from a tertiary care hospital in North India

Background: Cognitive functions are important predictors of day to day functioning. Cognitive functions are significantly affected in schizophrenia and various other psychiatric disorders. There are very few Indian studies studying the relationship between cognitive functions and disability. Aims and Objectives: The purpose of the present study was to assess the cognitive functions in stable patients of schizophrenia and compare them with normal controls and also to study the relationship between cognition and disability in these patients. Materials and Methods: Thirty stable patients of schizophrenia attending psychiatry outpatient clinic of a Tertiary Care Hospital of North India were included in the study. Thirty healthy volunteers with no psychiatric illness matched for age, gender, and education were also included cognitive functions were assessed using Brief Assessment of Cognition in Schizophrenia and disability was assessed using WHO Disability Assessment Schedule 2.0 (WHODAS 2.0). Results: Highly significant difference (P < 0.0001) was found between the cognitive functions of the schizophrenia group and healthy control group. The patients of schizophrenia had a maximum disability in the area of life activities followed by participation and cognition. There existed a significant negative correlation between cognition and mobility (r = −0.45, P < 0.05), getting along with people (r = −0.44, P < 0.05), life activities (r = −0.42, P < 0.05), participation (r = −0.39, P ≤ 0.05), and total scores on WHODAS 2.0 (r = −0.48, P ≤ 0.05). Conclusion: Cognitive functions are an important predictor of disability. Cognitive deficits exist even in the stable patients of schizophrenia which is significantly higher than the healthy group