In an investigation of the psychosocial correlates of suicidal ideation in adolescent inpatients, the Beck Scale for Suicide Ideation (BSI) was administered to 108 inpatients between 12 and 17 years of age who were diagnosed with mixed psychiatric disorders. A series of multiple regression analyses that controlled for gender, ethnicity, age, diagnosis of a mood disorder, and a history of a past suicide attempt were then used to examine the relationships of the Beck Depression Inventory, Anxiety Inventory, and Hopelessness Scale (BHS) with the BSI. Regardless of the series, the BHS contributed unique variance to the explanation of the BSI scores. The results are discussed as supporting the use of the BSI with adolescent inpatients and indicating that hopelessness is related to suicidal ideation when depression is controlled for.

Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound.

Cashew nut shell liquid (CNSL) has been used in traditional medicine for the treatment of a wide variety of pathophysiological conditions. To further define the mechanism of CNSL action, we investigated the effect of cashew nut shell extract (CNSE) on two matrix metalloproteinases, MMP-2/gelatinase A and MMP-9/gelatinase B, which are known to have critical roles in several disease states. We observed that the major constituent of CNSE, anacardic acid, markedly inhibited the gelatinase activity of 3T3-L1 cells. Our gelatin zymography studies on these two secreted gelatinases, present in the conditioned media from 3T3-L1 cells, established that anacardic acid directly inhibited the catalytic activities of both MMP-2 and MMP-9. Our docking studies suggested that anacardic acid binds into the MMP-2/9 active site, with the carboxylate group of anacardic acid chelating the catalytic zinc ion and forming a hydrogen bond to a key catalytic glutamate side chain and the C15 aliphatic group being accommodated within the relatively large S1Ј pocket of these gelatinases. In agreement with the docking results, our fluorescence-based studies on the recombinant MMP-2 catalytic core domain demonstrated that anacardic acid directly inhibits substrate peptide cleavage in a dosedependent manner, with an IC 50 of 11.11 M. In addition, our gelatinase zymography and fluorescence data confirmed that the cardol-cardanol mixture, salicylic acid, and aspirin, all of which lack key functional groups present in anacardic acid, are much weaker MMP-2/MMP-9 inhibitors. Our results provide the first evidence for inhibition of gelatinase catalytic activity by anacardic acid, providing a novel template for drug discovery and a molecular mechanism potentially involved in CNSL therapeutic action.

Multidrug-resistant community-acquired infections caused by the opportunistic human pathogen Pseudomonas aeruginosa are increasingly reported in India and other locations globally. Since this organism is ubiquitous in the environment, samples such as sewage and wastewater are rich reservoirs of P. aeruginosa bacteriophages. In this study, we report the isolation and characterization of a novel P. aeruginosa N4-like lytic bacteriophage, vB_Pae_AM.P2 (AM.P2), from wastewater in Kerala, India. AM.P2 is a double-stranded DNA podovirus that efficiently lyses the model strain, PAO1, at a multiplicity of infection as low as 0.1 phage per bacterium and resistance frequency of 6.59 × 10−4. Synergy in bactericidal activity was observed between AM.P2 and subinhibitory concentrations of the antibiotic ciprofloxacin. Genome sequencing of AM.P2 revealed features similar to those of the N4-like P. aeruginosa phages LUZ7 and KPP21. As judged by two independent assay methods, spot tests and growth inhibition, AM.P2 successfully inhibited the growth of almost 30% of strains from a contemporary collection of multidrug-resistant P. aeruginosa clinical isolates from South India. Thus, AM.P2 may represent an intriguing candidate for inclusion in bacteriophage cocktails developed for various applications, including water decontamination and clinical bacteriophage therapy. IMPORTANCE In India, multidrug resistance determinants are much more abundant in community-associated bacterial pathogens due to the improper treatment of domestic and industrial effluents. In particular, a high bacterial load of the opportunistic pathogen P. aeruginosa in sewage and water bodies in India is well documented. The isolation and characterization of bacteriophages that could target emerging P. aeruginosa strains, representing possible epicenters for community-acquired infections, could serve as a useful alternative tool for various applications, such as phage therapy and environmental treatment. Continuing to supplement the repertoire of broad-spectrum bacteriophages is an essential tool in confronting this problem.

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ObjectiveDiabetic retinopathy is one of the leading causes of visual impairment after cataract and uncorrected refractive error. It has major public health implications globally, especially in countries such as India where the prevalence of diabetes is high. With timely screening and intervention, the disease progression to blindness can be prevented, but several barriers exist. As compliance to diabetic retinopathy screening in people with diabetes is very poor in India, this study was conducted to explore understanding of and barriers to diabetic retinopathy screening from the perspectives of patients and healthcare providers.MethodsUsing qualitative methods, 15 consenting adult patients with diabetes were selected purposively from those attending a large tertiary care private eye hospital in southern India. Eight semistructured interviews were carried out with healthcare providers working in large private hospitals. All interviews were audiotaped, transcribed verbatim and analysed using the framework analytical approach.ResultsFour themes that best explained the data were recognising and living with diabetes, care-seeking practices, awareness about diabetic retinopathy and barriers to diabetic retinopathy screening. Findings showed that patients were aware of diabetes but understanding of diabetic retinopathy and its complications was poor. Absence of symptoms, difficulties in doctor–patient interactions and tedious nature of follow-up care were some major deterrents to care seeking reported by patients. Difficulties in communicating information about diabetic retinopathy to less literate patients, heavy work pressure and silent progression of the disease were major barriers to patients coming for follow-up care as reported by healthcare providers.ConclusionsEnhancing patient understanding through friendly doctor–patient interactions will promote trust in the doctor. The use of an integrated treatment approach including education by counsellors, setting up of patient support groups, telescreening approaches and use of conversation maps may prove more effective in the long run.

Members of the matrix metalloproteinase (MMP) family have biological functions that are central to human health and disease, and MMP inhibitors have been investigated for the treatment of cardiovascular disease, cancer and neurodegenerative disorders.

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