Psychosocial Correlates of the Experience of Caregiving Among Caregivers of Patients With Schizophrenia.

BACKGROUND: Family caregivers provide essential support to their loved ones with schizophrenia with profound outcomes for themselves. The caregiver burden fails to consider the entire caregiving experience, which also incorporates positive aspects of caring. Many potentially significant variables are associated with this. AIM: To examine the correlates of the experience of caregiving in caregivers of patients with schizophrenia. The specific objectives were to examine the socio-demographic variables of the patients and caregivers, clinical variables of the patient, caregivers' knowledge of illness, caregivers' perspectives of family functioning, caregiver coping, their social support, psychological distress, quality of life, and their spirituality, religiosity and personal beliefs and the associations of these variables with the caregivers' experience of caregiving. METHODS: This cross-sectional observational study was conducted between August 2018 and January 2021 at All India Institute of Medical Sciences, New Delhi, India. One hundred and fifty-eight dyads of patients with schizophrenia and their family caregivers were recruited using purposive sampling. Experience of Caregiving Inventory was used to evaluate the caregiving experience. The caregivers were also assessed on socio-demographics, knowledge of illness, family functioning, coping, social support, general mental health, quality of life, and spiritual, religious, and personal beliefs. Patient socio-demographics and clinical variables were also assessed. RESULTS: A negative experience of caregiving was reported by caregivers of patients who had higher positive or negative symptoms of schizophrenia. Impaired Communication, Roles, Affective Responsiveness, Affective Involvement, and General Functioning aspects of family functioning were associated with a negative experience of caregiving. Denial/blame and seeking social support as coping were also associated with a negative experience of caregiving. A negative experience of caregiving was significantly positively correlated with greater psychological distress and poorer quality of life. Greater inner peace was associated with a less negative experience of caregiving. Spiritual strength was associated with a more positive experience of caregiving. Knowledge of mental illness and caregiver social support were not significantly associated with the experience of caregiving. CONCLUSION: Experience of caregiving is a relevant construct, the understanding of which can help inform caregiver-directed interventions in the future. Specifically, family-based interventions, which include ameliorating patient symptomatology, improving the family environment, strengthening caregivers' coping strategies, attending to caregiver distress, and encouraging spirituality among caregivers, may lead to a less negative and more positive experience of caregiving; and a better quality of life for caregivers.

Changes in Psychosocial Variables Among Caregivers of Patients With Schizophrenia: A Short-Term Follow-Up Study.

BACKGROUND AND AIMS: Caring for a person with schizophrenia entails considerable effort. The caregiving experience while caring for a person with schizophrenia has been described as both stressful and enriching. The literature on changes in caregiving experience with time has been fairly limited. The present analysis looks at the change in the caregiving experience of caregivers of patients with schizophrenia. METHOD: This study had a sample of 50 caregivers of patients with schizophrenia who were followed up after a period of 6 to 10 months. Caregiving experience, knowledge of the mental illness, family functioning, coping, social support, psychological distress, quality of life, and spiritual, religious, and personal beliefs were assessed at the two time points. RESULTS: Among the negative caregiving experiences, caregivers' need for back-up and patient dependency reduced significantly at follow-up as compared to baseline, though total negative or positive experiences of caregiving did not show a significant difference. Knowledge about mental illness did not significantly increase at follow-up, though issues related to poor communication and affective involvement in family functioning reduced over the period of time. Coping and social support remained largely the same, while psychological distress was reduced. All domains of quality of life improved over the follow-up period, while the hope, optimism, and inner peace aspects of spiritual, religious, and personal beliefs improved with time. CONCLUSION: Some aspects of caregiving experiences may change with time. As caregivers become more adjusted to caregiving roles, their distress may reduce, and their quality of life may improve.

Transferability of laparoscopic skills acquired from three-dimensional high-definition and ultra-high definition endovision system to two-dimensional high-definition endovision system: an ex-vivo randomized study.

Three-dimensional high-definition (3D HD) and ultra-high-definition (4 K HD) endovision systems are rapidly adopted in academic setting. However, transferability of laparoscopic skills acquired from these systems to two-dimensional high-definition (2D HD) endovision system is not known. Forty stereo-enabled surgical residents were randomized into two groups. They performed three standardized surgical tasks, Task 1(Peg transfer), Task 2(Precision touch on uneven surface) and Task 3(Surgical knotting on rubber tube) for 15 repetitions using either 3D HD or 4 K HD. Both groups then performed the same tasks using 2D HD for 5 repetitions. Their performances were evaluated for execution time (speed) and error scores (safety). The residents in 3D HD group performed all three tasks significantly faster than residents in 4 K HD group with comparable error scores. The time taken to complete the tasks on 2D HD were comparable between residents trained in 3D HD and 4 K HD in two out of three tasks (p = 0.027, P = 0.115, p = 0.368 in task 1, 2 and 3 respectively). However, in two out of three tasks, residents trained on 3D HD committed significantly more errors than residents trained on 4 K HD (p < 0.0001, p < 0.001 in task 1 and task 2 respectively). Skill acquired on 4 K HD seems transferable to 2D HD environment. Participants trained in 3D HD made more errors while performing the tasks in 2D HD. It may be prudent to offer additional training on 2D HD to residents trained on 3D HD for safer laparoscopic surgical practice.

Effectiveness of smoking cessation intervention in opioid-dependent male subjects on buprenorphine maintenance treatment: An open-label trial.

Background: High prevalence (more than 80%) rates of tobacco smoking have been found both in, opioid-dependent subjects and among opioid-dependent subjects on opioid substitution treatment (OST) with buprenorphine or methadone. Aim: We aimed to explore the efficacy of combined nicotine replacement therapy (NRT) and individual counseling (IC) when compared to NRT alone in subjects on OST with buprenorphine. Methods: This study was carried out in a tertiary medical care center. It was an open-label randomized clinical trial. A total of 57 buprenorphine maintained smokers were recruited and randomized into two groups. They were assigned nicotine gum for 4 weeks plus either (1) a baseline IC session, and a second IC session after 1 week, or (2) simple advice to quit. In the first group, 31 subjects received NRT with IC and in the second group, 26 subjects received NRT plus simple advice to quit. The primary outcomes of this study were seven days point prevalence abstinence, biochemically confirmed by carbon monoxide (CO) breath analyzer, and reduction in smoking (mean no. of cigarettes or bidis/day). The smoking behavior during the 4 weeks follow-up period was assessed by the timeline follow-back (TLFB) method and confirmed by the CO breath analyzer. Results: The group of subjects who received NRT with IC showed higher rates of smoking cessation at the end of treatment (51%) as compared to the NRT and simple advice group where smoking cessation rates were around 8% (P < 0.001). Conclusion: A multi-component approach (pharmacotherapy and counseling) enhances treatment outcomes and enhances rates of abstinence from smoking.

Relapse during opioid use disorder treatment: A pilot study to understand the reasons for opioid use during treatment.

Background: Opioid use is a cause of concern in many parts of the world. About 2.1% Indians use opioids. Opioids are also the most common drugs used by injection drug users in India. Despite various treatment strategies used to manage opioid use disorders (OUDs), relapse is common. A good treatment program would make efforts to address lapses and prevent relapse. Hence, there is a need to understand the factors associated with relapse in OUD. Method: One hundred and twenty patients completed a baseline assessment that included socio-demographic details and the Maudsley Addiction Profile (MAP). They were followed up for three months and assessed using telephonic interview for opioid use. All those who relapsed were assessed using the Reasons for Relapse Questionnaire (RRQ). The patients who relapsed were compared with the patients who were abstinent. Relapse was defined as any use of opioid during follow-up. Results: Forty participants relapsed during the 90 days of the study period. Relapsed patients had a greater number of conflict days with family members, used a higher amount of heroin and cannabis at baseline, were less likely to be discharged on buprenorphine, and were more likely to drop out. Participants cited mood and social reasons more often than cue/craving and unwell domains of RRQ. Conclusion: Baseline treatment and prospective factors are associated with relapse in OUD. Addressing these factors can help in reducing relapse in OUD patients.

Performance of three-dimensional and ultra-high-definition (4K) technology in laparoscopic surgery: A systematic review and meta-analysis.

Background: The technology in the field of laparoscopy is rapidly evolving and is primarily focussed on increasing the quality of image and depth perception in the form of 4K and three-dimensional (3D) technology. There has been no conclusion yet regarding the better technology. Methods: A systematic search was performed independently by two authors across MEDLINE, Google Scholar and Embase using the PRISMA guidelines. All randomised control trials comparing 3D and 4K technologies were included. Meta-analysis was conducted using random-effects statistics for time taken for different tasks across the studies. Results: The search strategy revealed a total of 1835 articles, out of which nine studies were included. Three studies showed no superiority of 3D over 4K, while the remaining six did. Meta-analysis for the time taken for peg transfer favoured 3D over 4K (overall effect: Z = 2.12; P = 0.03). Forest plots for time taken for suturing (Z = 1.3; P = 0.19) and knot tying (Z = 1.7; P = 0.09) also favoured 3D over 4K; the results however were statistically insignificant. Path length was reported by two studies and was found to be lesser in the 3D group. Two studies measured the workload by NASA/Surg-TLX score, which was lower in the 3D group. Visual side effects were found to be higher in the 3D group. Conclusion: 3D technology is likely to result in a shorter operative time and better efficiency of movement as compared to the 4K technology by the virtue of its better depth perception.

Learning Pattern of Two-Dimensional, Three-Dimensional, and Ultra-High-Definition Endovision System on Standardized Phantom Tasks: An Ex Vivo Randomized Study.

Introduction: Three-dimensional (3D), high-definition (HD), and ultra-high-definition (4K HD) are recent additions over regular HD technology for laparoscopic surgery. The aim of this study was to evaluate the learning pattern of these systems on standardized phantom tasks. Methodology: Forty-five stereo-enabled resident doctors were randomly assigned into three groups. They performed three validated tasks, precision touch on flat surface, precision touch on uneven surface, surgical knot on rubber tube using either two-dimensional (2D) HD, 3D HD, or 4K HD Endovision systems. Each task was repeated 20 times. Data from four consecutive repetitions were pooled to make five blocks. Split group analysis by comparing the consecutive blocks in execution time and errors were made to see the learning pattern. A significant difference was accepted as continuous learning while no significant difference was accepted as learning stabilization. Result: Operating time was stabilized in two tasks after third block in 2D HD, one task after fourth block in 4K HD. There was continuous learning in all tasks with 3D HD. The 3D HD group was significantly faster than 2D HD and 4K HD in most of the tasks on fifth block. The error scores were similar between the consecutive blocks in 4K HD. It was stabilized after second block in 2D HD group and third block on 3D HD. Conclusion: The 3D HD Endovision system has more potential of faster execution of a task, but need more practice to reach similar safety profile. The 4K HD reached the safety plateau with minimal repetitions.

Hemocyte RNA-Seq analysis of Indian malarial vectors Anopheles stephensi and Anopheles culicifacies: From similarities to differences.

Anopheles stephensi and Anopheles culicifacies are dominant malarial vectors in urban and rural India, respectively. Both species carry significant biological differences in their behavioral adaptation and immunity, but the genetic basis of these variations are still poorly understood. Here, we uncovered the genetic differences of immune blood cells, that influence several immune-physiological responses. We generated, analyzed and compared the hemocyte RNA-Seq database of both mosquitoes. A total of 5,837,223,769 assembled bases collapsed into 7,595 and 3,791 transcripts, originating from hemocytes of laboratory-reared 3-4 days old naïve (sugar-fed) mosquitoes, Anopheles stephensi and Anopheles culicifacies respectively. Comparative GO annotation analysis revealed that both mosquito hemocytes encode similar proteins. Furthermore, while An. stephensi hemocytes showed a higher percentage of immune transcripts encoding APHAG (Autophagy), IMD (Immune deficiency pathway), PRDX (Peroxiredoxin), SCR (Scavenger receptor), IAP (Inhibitor of apoptosis), GALE (galactoside binding lectins), BGBPs (1,3 beta D glucan binding proteins), CASPs (caspases) and SRRP (Small RNA regulatory pathway), An. culicifacies hemocytes yielded a relatively higher percentage of transcripts encoding CLIP (Clip domain serine protease), FREP (Fibrinogen related proteins), PPO (Prophenol oxidase), SRPN (Serpines), ML (Myeloid differentiation 2-related lipid recognition protein), Toll path and TEP (Thioester protein), family proteins. However, a detailed comparative Interproscan analysis showed An. stephensi mosquito hemocytes encode proteins with increased repeat numbers as compared to An. culicifacies. Notably, we observed an abundance of transcripts showing significant variability of encoded proteins with repeats such as LRR (Leucine rich repeat), WD40 (W-D dipeptide), Ankyrin, Annexin, Tetratricopeptide and Mitochondrial substrate carrier repeat-containing family proteins, which may have a direct influence on species-specific immune-physiological responses. Summarily, our deep sequencing analysis unraveled that An. stephensi evolved with an expansion of repeat sequences in hemocyte proteins as compared to An. culicifacies, possibly providing an advantage for better adaptation to diverse environments.

Comparison of two-dimensional high-definition, ultra high-definition and three-dimensional endovision systems: an ex-vivo randomised study.

BACKGROUND: Two-dimensional high-definition (2D HD) endovision system is preferred for laparoscopic surgery. Recently, new generation three-dimensional (3D) HD and ultra-HD (4K) endovision systems are introduced to improve the safety and efficacy of laparoscopic surgery. There is limited evidence on superiority of one technology over the others. This experimental trial was designed to evaluate 2D HD, 3D HD and 4K HD endovision systems in performance of standardized tasks. METHODS: This was a randomized, cross-over experimental study. Twenty-one surgical residents who were exposed to laparoscopic surgery were enrolled. Participants were randomly assigned into three groups. Each group performed standardised tasks i.e. peg transfer, precision cutting, navigating in space and intra-corporeal suturing using 2D HD, 4K HD and 3D HD endovision systems on a box trainer. Procedures were recorded as 2D HD videos and analysed later. Participant's perceived workload was assessed using Surg-TLX questionnaire. Primary endpoints were execution time in seconds and error score. Secondary endpoint was workload assessment. RESULTS: The 3D HD had shorter execution time compared to 2D HD and 4K HD in all tasks except precision cutting (p = 0.004, 0.03, 0.001, 0.001 and p = 0.002, 0.191, 0.006, 0.005 in peg transfer, precision cutting, navigating in space and intra-corporeal suturing respectively). The 4K HD was significantly faster than 2D HD only in navigating in space task (p = 0.002). The error score between 3D HD and 4K HD were comparable in all tasks. The 2D HD had significantly more error scores compared to 4K HD, 3D HD in peg transfer task (p = 0.005, 0.014, respectively). 3D HD had significantly less workload than 2D HD and 4K HD in most of the dimensions of Surg-TLX CONCLUSIONS: 3D HD endovision system in comparison to 2D HD and 4K HD, may lead to faster execution without compromising safety of a task and is associated with less workload.

Is there enough naloxone to deter the diversion? Effect of concurrent administration of intravenous naloxone on opioid agonist effects of intravenous buprenorphine: A randomised, double-blind, within-subject, crossover study among opioid-dependent subjects.

INTRODUCTION AND AIMS: We aimed to evaluate and compare the effect of different intravenous doses of naloxone on reinforcing effect of intravenous buprenorphine (2 mg) in patients stabilised on sublingual buprenorphine. DESIGN AND METHODS: This is a double-blind, within-subject, randomised, crossover study. Opioid-dependent patients, with history of intravenous drug use, stabilised on buprenorphine maintenance treatment were included after informed consent (n = 14). We administered and assessed the reinforcing effects of six test conditions: buprenorphine and naloxone co-formulation (BNX) in 4:1, 2:1 and 1:1 dose ratio (i.e. buprenorphine 2 mg + naloxone 0.5, 1 and 2 mg, respectively), buprenorphine alone (2 mg), pheniramine maleate (45.5 mg) and saline at 24 hourly intervals. RESULTS: No significant opioid withdrawals were precipitated during any test conditions. Compared to buprenorphine alone, 4:1 BNX had comparable euphoria, drug recognition, subjective opiate sensations and drug liking (P > 0.05); 2:1 BNX condition had significantly different subjective euphoria (P = 0.001), opioid recognition (P = 0.002), subjective opioid sensations at 60 min (P = 0.027) and drug liking (P < 0.001), while 1:1 BNX had significantly different objective euphoria (P = 0.002), opioid recognition (P = 0.030), subjective opioid sensations (P < 0.001) and drug liking (P < 0.001). No significant difference was noted on sedation scores between buprenorphine alone and all three combinations of BNX. DISCUSSION AND CONCLUSIONS: The 4:1 BNX condition did not impact the reinforcing agonist effects of buprenorphine. None of the intravenous BNX combination ratios precipitated opioid withdrawals. Findings emphasise the need for exploring more abuse deterrent mechanisms.

Rates, knowledge and risk factors of non-fatal opioid overdose among people who inject drugs in India: A community-based study.

INTRODUCTION AND AIMS: Non-fatal opioid overdose (NFOO) predicts future fatal opioid overdose and is associated with significant morbidity. There is limited literature on the rates and risk factors for NFOO in people who inject drugs (PWID) from India. We aimed to study the rates of NFOO and documented risk factors for NFOO, as well as knowledge-level of NFOO among PWID from India. DESIGN AND METHODS: Community-based, cross-sectional and observational study. We interviewed 104 adult male participants receiving HIV prevention services. Drug use patterns, rates of NFOO and opioid overdose risk factors, knowledge about opioid overdose and its management were assessed. RESULTS: The mean age of the participants was 27.9 years. The most common opioid used for injecting was heroin followed by buprenorphine. About 45% (n = 47) participants had experienced an opioid overdose at least once in their lifetime. Around 25% (n = 26) participants had overdosed in the past year, while 21% (n = 22) participants had overdosed within the past 3 months. The majority had risk factors that could predispose them to NFOO. No participant was aware of the use of naloxone for opioid overdose. DISCUSSION AND CONCLUSION: The rates of NFOO as well as risk factors for overdose among PWID from India are high, with poor knowledge on overdose management. There is urgent need for a program to prevent and manage opioid overdose among PWID in India.

Prevalence and determinants of anxiety disorders among adolescents in a rural community from northern India.

INTRODUCTION: There is scarce data available on community based prevalence of Anxiety Disorders (ADs) amongst adolescents in north Indian settings. OBJECTIVE: To determine the prevalence of anxiety disorders, and associated factors amongst adolescents in a rural community of Ballabgarh block, district Faridabad, Haryana. METHODS: Participants (10-19 years) were enrolled through simple random sequence from a sampling frame of adolescents residing in 28 villages of Ballabgarh block using household survey technique. They were screened using Screen for Childhood Anxiety Related Emotional Disorders (SCARED) tool and then subjected to confirmatory diagnosis using Mini-International Neuropsychiatric Interview for Children/Adolescent (MINI KID). All adolescents with ADs were assessed for co-psychiatric morbidities using MINI-KID and functional impairment using Children Global Assessment Scale (CGAS). Prevalence and 95% Confidence intervals are reported. Additionally, socio-demographic factors were elicited using a semi-structured interview schedule and associations were determined using multivariable logistic regression analysis. RESULTS: A total of 678 adolescents participated in this study with mean age (SD) as 14.2 (2.5) years. The age adjusted prevalence of anxiety disorders was found to be 16.6% (95% CI: 16.0-17.2). The most prevalent anxiety disorder among participants was social anxiety disorders followed by specific phobias. Female sex and low socio-economic status were associated with anxiety disorders. Two third of adolescents with ADs had no functional impairment and almost one third were found to have one or more co-existing psychiatric co-morbidity. CONCLUSION: We found a high prevalence of ADs in rural north Indian community settings warranting adequate health system response at primary care level.

Psychological adaptation of Indian expeditioners during prolonged residence in Antarctica.

BACKGROUND: In view of the growing human activities in Antarctica and increasing exposure of humans to prolonged isolation under extreme conditions, such as space travel and deep sea diving, it is necessary to study the psychological adaptation to such an environment. The current study aimed to assess the psychological adaptation of Indian expeditioners to prolonged residence in Antarctica. MATERIALS AND METHODS: Twenty-four winter team members of 27th Indian Scientific Expedition to Antarctica were administered seven instruments 5 times during the expedition. The instruments measured cognition and memory, general psychological health and tobacco, and alcohol consumption. RESULTS: Alcohol consumption was maximum during the initial days of arrival on the continent and decreased thereafter, with another spike during the peak of the winter season. Externalized psychological reactions peaked during the midwinter period. Anxiety and insomnia peaked during the coldest period whereas depressive symptoms did not change throughout the expedition. Cognition was at its worst during the final phase of Antarctic residence. No significant change was noted in the third quarter of wintering. CONCLUSION: Each phase of Antarctic residence could be equated with a particular stage in psychological adaptation. There was no third quarter phenomenon.

Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness.

Patients with severe alcoholic hepatitis (SAH) not responding to glucocorticoid therapy have higher mortality, though they do not differ in their baseline clinical characteristics and prognostic scores from those who respond to therapy. We hypothesized that the baseline hepatic gene expression differs between responders (R) and non-responders (NR). Baseline liver transcriptome was compared between R and NR in Indian (16 each) and French (5 NR, 3 R) patients with SAH. There were differentially expressed genes (DEGs) between NR and R, in Indian (1106 over-expressed, 96 under-expressed genes) and French patients (65 over-expressed, 142 under-expressed genes). Indian NR had features of hepatocyte senescence and French NR exhibited under-expression of genes involved in cell division, indicating a central defect in the capacity of hepatocytes for self-renewal in both populations. Markers of hepatic progenitor cell proliferation were either very few (Indian patients) or absent (French patients). No DEGs were enriched in inflammatory pathways and there were no differences in nuclear receptor subfamily 3 group C member 1 (NR3C1) transcript expression and splicing between NR and R. Our results reveal that baseline hepatic transcriptome is reflective of subsequent glucocorticoid non-response and indicate impaired regenerative potential of the liver as an underlying phenomenon in NR.

Association of ankyrin repeats & kinase domain containing 1 (ANKK1) gene polymorphism with co-morbid alcohol & nicotine dependence: A pilot study from a tertiary care treatment centre in north India.

BACKGROUND & OBJECTIVES: The frequently encountered co-morbidity of alcohol dependence (AD) with nicotine dependence (ND) increases the risk for various diseases. Ankyrin repeats and kinase domain containing 1 (ANKK1) gene polymorphism is reported to be associated with both ND and AD. This study was undertaken to investigate the possible association of alcohol and tobacco use variables with ANKK1 polymorphism in co-morbid alcohol- and nicotine-dependent treatment seekers visiting a tertiary care centre in north India. METHODS: Seventy nine male participants (18-65 yr old) fulfilling diagnostic criteria for ND and AD were included in the study. The socio-demographic data, along with alcohol and tobacco use profile, was recorded and ANKK1 profiling was carried out. Both the allele groups, A1 and A2, were compared with respect to demographic and substance dependence profile. Univariate binary logistic regression analysis was performed to determine the risk of high nicotine and alcohol consumption with genotype. RESULTS: The A1 carrier group (n=33) reported a significantly higher amount of alcohol and tobacco consumed per day. The scores on parameters of ND were found to be significantly higher in this group. The logistic regression analysis revealed that participants with A1 genotype were 2.5 times more likely to report higher amount of alcohol and nicotine consumption than A2 carriers. INTERPRETATION & CONCLUSIONS: The study provides an indication for the association of ANKK1 polymorphism in the form of higher substance consumption among alcohol dependent smokers, who are A1 carriers and thus may require higher attention of the treatment provider.

Immune signature of urothelial cancer associated with grade, recurrence, and invasion.

BACKGROUND: Urothelial carcinoma (UC) is one of most common genitourinary malignancy and the spectrum of disease ranges from in situ lesions to muscle-invasive cancers. The non-muscle-invasive lesions have tendency to recur or progress to muscle-invasive disease. The study of the immune profile may identify immune determinants associated with high-grade, recurrence, and invasion in patients with UC. METHODS: Pathway-focused RT(2) profiler arrays were used to screen patients with UC for dysregulation of candidate genes of Th1-Th2-Th3 and NFκB pathways, which were then validated by real-time polymerase chain reaction on tumor samples and correlated with grade, recurrence, and invasion of tumors to identify their role in predicting behavior of the tumor. The cytokines found associated with recurrence were then validated in urine of patients with UC. RESULTS: IFNγ, IL2, IL4, IL10, IL17, CCL7, CTLA4, and SPP1 of the cytokine pathway and TLR4, TLR3, RELA, NFκB1, and MYD88 of the NFκB pathway were found differentially expressed in patients with urothelial cancer by array and quantative real-time polymerase chain reaction. Among these, IL10 and SPP1 were found consistently up-regulated in high-grade, invasive, and recurrent cases and up-regulated IL10 and CTLA4 were found associated with a short recurrence-free survival time (P = 0.001 and P = 0.065). Urinary IL10 concentration was significantly higher in both patients with cancer and cystitis compared with healthy controls, but the difference in concentration between patients with cancer and cystitis patients was not statistically significant. However, urinary CTLA4 concentrations were found to be significantly higher in urothelial cancer patients compared with healthy controls and cystitis cases and found to be associated with poor recurrence-free survival. CONCLUSION: The study indicates that high urinary CTLA4 concentration raises the index of suspicion of recurrence in a known case of urothelial cancer and may be used as a surveillance marker.

Is CXCL10/CXCR3 axis overexpression a better indicator of leprosy type 1 reaction than inducible nitric oxide synthase?

BACKGROUND & OBJECTIVES: Leprosy type 1 reactions (T1R) are acute episodes of immune exacerbation that are a major cause of inflammation and nerve damage. T1R are diagnosed clinically and supported by histopathology. No laboratory marker is currently available that can accurately predict a T1R. Increased plasma and tissue expression of inducible nitric oxide synthase (i-NOS) and chemokine CXCL10 have been demonstrated in T1R. We studied the gene expression and immunoexpression of i-NOS, CXCL10 and its receptor CXCR3 in clinically and histopathologically confirmed patients with T1R and compared with non-reactional leprosy patients to understand which biomarker has better potential in distinguishing reaction from non-reaction. METHODS: Gene expression of i-NOS, CXCL10 and CXCR3 was studied in 30 skin biopsies obtained from patients with borderline tuberculoid (BT), mid-borderline (BB) and borderline lepromatous (BL) leprosy with and without T1R by real-time PCR. Further validation was done by immunohistochemical expression on 60 borderline leprosy biopsies with and without T1R. RESULTS: Of the 120 patients histopathological evaluation confirmed T1R in 65 (54.2%) patients. CXCR3 gene expression was significantly (P<0.05) higher in BT- and BB-T1R patients compared to those without T1R. The CXCL10 gene expression was significantly higher (P<0.05) in BB leprosy with T1R but the difference was not significant in patients with BT with or without T1R. Immunoexpression for CXCR3 was significant in both BB-T1R and BB (P<0.001) and BT and BT-T1R (P<0.001). Immunoexpression of CXL10 was significant only in differentiating BB from BB-T1R leprosy (P<0.01) and not the BT cases. i-NOS immunoexpression was not useful in differentiating reactional from non-reactional leprosy. INTERPRETATION & CONCLUSIONS: Both CXCL10 and CXCR3 appeared to be useful in differentiating T1R reaction in borderline leprosy while CXCR3 alone differentiated BT from BT-T1R. CXCR3 may be a potentially useful immunohistochemical marker to predict an impending T1R.

Genomic alterations in breast cancer patients in betel quid and non betel quid chewers.

Betel Quid (BQ) chewing independently contributes to oral, hepatic and esophageal carcinomas. Strong association of breast cancer risk with BQ chewing in Northeast Indian population has been reported where this habit is prodigal. We investigated genomic alterations in breast cancer patients with and without BQ chewing exposure. Twenty six BQ chewers (BQC) and 17 non BQ chewer (NBQC) breast cancer patients from Northeast India were analyzed for genomic alterations and pathway networks using SNP array and IPA. BQC tumors showed significantly (P<0.01) higher total number of alterations, as compared with NBQC tumors, 48 ± 17% versus 32 ± 25 respectively. Incidence of gain in fragile sites in BQC tumors were significantly (P<0.001) higher as compared with NBQC tumors, 34 versus 23% respectively. Two chromosomal regions (7q33 and 21q22.13) were significantly (p<0.05) associated with BQC tumors while two regions (19p13.3-19p12 and 20q11.22) were significantly associated with NBQC tumors. GO terms oxidoreductase and aldo-keto reductase activity in BQC tumors in contrast to G-protein coupled receptor protein signaling pathway and cell surface receptor linked signal transduction in NBQC tumors were enriched in DAVID. One network "Drug Metabolism, Molecular Transport, Nucleic Acid Metabolism" including genes AKR1B1, AKR1B10, ETS2 etc in BQC and two networks "Molecular Transport, Nucleic Acid Metabolism, Small Molecule Biochemistry" and "Cellular Development, Embryonic Development, Organismal Development" including genes RPN2, EMR3, VAV1, NNAT and MUC16 etc were seen in NBQC. Common alterations (>30%) were seen in 27 regions. Three networks were significant in common regions with key roles of PTK2, RPN2, EMR3, VAV1, NNAT, MUC16, MYC and YWHAZ genes. These data show that breast cancer arising by environmental carcinogens exemplifies genetic alterations differing from those observed in the non exposed ones. A number of genetic changes are shared in both tumor groups considered as crucial in breast cancer progression.

Expression of androgen receptor in breast cancer & its correlation with other steroid receptors & growth factors.

BACKGROUND & OBJECTIVES: Breast cancer is the second most common malignancy in Indian women. Among the members of the steroid receptor superfamily the role of estrogen and progesterone receptors (ER and PR) is well established in breast cancer in predicting the prognosis and management of therapy, however, little is known about the clinical significance of androgen receptor (AR) in breast carcinogenesis. The present study was aimed to evaluate the expression of AR in breast cancer and to elucidate its clinical significance by correlating it with clinicopathological parameters, other steroid receptors (ER and PR) and growth factors receptors (EGFR and CD105). METHODS: Expression of AR, ER, PR, epidermal growth factor receptor (EGFR) and endoglin (CD105) was studied in 100 cases of breast cancer by immunohistochemistry (IHC). Risk ratio (RR) along with 95% confidence interval (CI) was estimated to assess the strength of association between the markers and clinicopathological characteristics. Categorical principal component analysis (CATPCA) was applied to obtain new sets of linearly combined expression, for their further evaluation with clinicopathological characteristics (n=100). RESULTS: In 31 cases presenting with locally advanced breast cancer (LABC), the expression of AR, ER, PR, EGFR and CD105 was associated with response to neoadjuvant chemotherapy (NACT). The results indicated the association of AR+ (P=0.001) and AR+/EGFR- (P=0.001) with the therapeutic response to NACT in LABC patients. The AR expression exhibited maximum sensitivity, specificity and likelihood ratio of positive and negative test. The present results showed the benefit of adding AR, EGFR and CD105 to the existing panel of markers to be able to predict response to therapy. INTERPRETATION & CONCLUSIONS: More studies on the expression profiles of AR+, AR+/CD105+ and AR+/EGFR- in larger set of breast cancer patients may possibly help in confirming their predictive role for therapeutic response in LABC patients.

Study on predictive role of AR and EGFR family genes with response to neoadjuvant chemotherapy in locally advanced breast cancer in Indian women.

Locally advanced breast cancer (LABC) remains a clinical challenge as the majority of patients with this diagnosis develop distant metastases despite appropriate therapy. We analyzed expression of steroid and growth hormone receptor genes as well as gene associated with metabolism of chemotherapeutic drugs in locally advanced breast cancer before and after neoadjuvant chemotherapy (NACT) to study whether there is a change in gene expression induced by chemotherapy and whether such changes are associated with tumor response or non-response. Fifty patients were included with locally advanced breast cancer treated with cyclophosphamide, adriamycin, 5-fluorouracil (CAF)-based neoadjuvant chemotherapy before surgery. Total RNA was extracted from 50 match samples of pre- and post-NACT tumor tissues. RNA expression levels of epidermal growth factor receptor family genes including EGFR, ERBB2, ERBB3, androgen receptor (AR), and multidrug-resistance gene 1 (MDR1) were determined by quantitative real-time reverse transcriptase-polymerase chain reaction. Responders show significantly high levels of pre-NACT AR gene expression (P = 0.016), which reduces following NACT (P = 0.008), and hence can serve as a useful tool for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with locally advanced breast carcinoma. Moreover, a significant post-therapeutic increase in the expression levels of EGFR and MDR1 gene in responders (P = 0.026 and P < 0.001) as well as in non-responders (P = 0.055, P = 0.001) suggests that expression of these genes changes during therapy but they do not have any impact on tumor response, whereas a post-therapeutic reduction was observed in AR in responders. This indicates an independent predictive role of AR with response to NACT.