"I wanted to close the chapter completely and I feel like that [carrying naloxone] would keep it open a little bit": Refusal to carry naloxone among newly-abstinent opioid users and 12-step identity.

BACKGROUND: 12-step programs aim to address drug-related harms, like opioid overdose, via abstinence. However, abstaining from opioids can diminish tolerance, which increases risk for overdose death upon resumption. A recent study found that desire to abstain from drugs inhibited willingness to participate in take-home naloxone programming, which was linked to perceptions of harm reduction strategies being tied to drug use. In the present study, we uncovered a similar phenomenon occurring among newly-abstinent participants who were refusing to carry naloxone. METHODS: This study is an analysis of broader qualitative data collected throughout Southern California among persons who use opioids, including those recently abstinent. Preliminary analysis revealed that those newly abstinent refused to accept naloxone at the end of interviews, and so we began probing about this (N=44). We used thematic analysis and author positionality to explicate the emergent phenomenon and applied social identity theory to conceptualize findings. RESULTS: Mechanisms underlying naloxone refusal included its tie to a drug-using identity that newly-abstinent participants were attempting to retire. Carrying naloxone was also viewed as pointless due to doubt of witnessing an overdose again. Furthermore, the thought of being equipped with naloxone was not believed to be congruent with an abstinent identity, e.g. "me carrying it [naloxone] is making me feel like I'm going to be hanging out with people that are doing it [using drugs]." CONCLUSION: Recent detoxification heightens vulnerability to overdose, which other newly-abstinent peers might be positioned to respond to as bonds are formed through 12-step identity formation. However, naloxone is often refused by this group due to perceived 12-step identity clash. While some treatment spaces distribute naloxone, 12-step identity associated behavioral expectations appear to conflict with this strategy. Reframing these disconnects is essential for expanding the lifesaving naloxone community safety net.

A direct comparison of women's perceptions and acceptability of micronised progesterone and medroxyprogesterone acetate in combination with transdermal oestradiol in the management of young postmenopausal women, under 45 years of age.

OBJECTIVE: To assess the acceptability and perception of postmenopausal women, to two different hormone replacement therapy regimens, in relation to the control of their symptoms and development of adverse effects. STUDY DESIGN: Prospectively recruited postmenopausal women, <45 years, were randomised to one of two treatment arms for 12-months: cyclical micronised progesterone or medroxyprogesterone acetate in combination with transdermal oestradiol. A self-reported questionnaire with matrix rating scales was completed and repeated after 3, 6 and 12-months. MAIN OUTCOME MEASURES: Symptom control and development of adverse effects. RESULTS: Seventy-one individuals were screened, with baseline data available for 67 subjects. A total of 190 questionnaires were returned. The most commonly reported symptoms were low energy levels, vasomotor symptoms and sexual dysfunction. The prevalence of adverse effects ranged between 57.89 and 87.50%, with a reduction seen in the transdermal oestradiol + micronised progesterone arm (73.91% at 3-months, decreasing to 57.89% at 12-months; p = 0.33), compared to the transdermal oestradiol + medroxyprogesterone acetate arm (76.92% at 3-months, increasing to 87.50% at 12-months; p = 0.69). The main reported adverse effects were bloating, weight change and psychological symptoms. A significant difference was documented between the groups after set intervals, with a greater proportion reporting breast tenderness after 3-months (p = 0.01), lower numbers reporting mood swings at 6-months (p = 0.01) and irritability at 12-months (p = 0.03) in the transdermal oestradiol + micronised progesterone arm compared to the transdermal oestradiol + medroxyprogesterone acetate arm. CONCLUSIONS: The acceptability of both regimens was high despite adverse effects, but tolerability of transdermal oestradiol combined with micronised progesterone appeared to be better with fewer women reporting psychological concerns.

Transitioning from pharmaceutical opioids: A discrete-time survival analysis of heroin initiation in suburban/exurban communities.

INTRODUCTION: Research identifying pathways to heroin use has typically been conducted among urban populations. This study examined heroin initiation following pharmaceutical opioid use in three suburban/exurban Southern California counties. METHODS: Interviewer-administered surveys collected data among 330 participants (65.9 % male; 63.9 % non-Hispanic white) whose initial use of any opioid was a pharmaceutical opioid. Retrospective discrete-time survival analysis identified predictors of heroin initiation, measured as self-reported age of first heroin use. RESULTS: Median age of first pharmaceutical opioid use was 17 years; 50.6 % initially acquired pharmaceutical opioids from an illicit source, 56.7 % first used pharmaceutical opioids for recreational purposes, and 86 % initiated heroin use. Average time from first pharmaceutical opioid use to first heroin use was 8.2 years. Drug/alcohol treatment (adjusted Hazard Ratio [aHR]: 0.67, 95 % CI: 0.50, 0.88) was associated with delayed time to heroin initiation. Obtaining opioids from non-medical sources (aHR: 2.21, 95 % CI: 1.55, 3.14) was associated with accelerated time to heroin initiation. Reporting supply problems with obtaining pharmaceutical opioids (e.g., unable to acquire pharmaceutical opioids) was associated with accelerated time to heroin initiation, but the magnitude of this effect was dependent on one's history of methamphetamine use (p < 0.05). CONCLUSIONS: Time to heroin initiation following pharmaceutical opioid use was accelerated among those reporting supply problems and delayed among those with exposure to substance use treatment. Interventions interrupting supply of opioids might benefit from coordination with evidence-based medication-assisted treatment to minimize the risk of transitioning to heroin use, particularly among those with a long history of non-prescribed pharmaceutical opioid use.

ICSI does not improve reproductive outcomes in autologous ovarian response cycles with non-male factor subfertility.

STUDY QUESTION: Does the method of fertilisation improve reproductive outcomes in poor ovarian response (POR) cycles when compared to all other ovarian response categories in the absence of male factor subfertility? SUMMARY ANSWER: ICSI does not confer any benefit in improving the clinical pregnancy or live birth (LB) outcome in autologous ovarian response cycles in the absence of male factor subfertility when compared to IVF. WHAT IS KNOWN ALREADY: ICSI is associated with an improved outcome when compared to IVF in patients with severe male factor subfertility. STUDY DESIGN, SIZE, DURATION: A retrospective study involving 1 376 454 ART cycles, of which 569 605 (41.4%) cycles fulfilled the inclusion and exclusion criteria for all autologous ovarian response categories: 272 433 (47.8%) IVF cycles and 297 172 (52.2%) ICSI cycles. Of these, the POR cohort represented 62 641 stimulated fresh cycles (11.0%): 33 436 (53.4%) IVF cycles and 29 205 (46.6%) ICSI cycles. PARTICIPANTS/MATERIALS, SETTING, METHOD: All cycles recorded on the anonymised Human Fertilisation and Embryology Authority (HFEA) registry database between 1991 and 2016 were analysed. All fresh cycles with normal sperm parameters, performed after 1998 were included: frozen cycles, donor oocyte and sperm usage, intrauterine insemination cycles, preimplantation genetic testing (PGT) for aneuploidies (PGT-A), PGT for monogenic/single gene defects (PGT-M), PGT for chromosomal structural arrangements (PGT-SR) cycles, where the reason for stimulation was for storage and unstimulated cycles were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: ICSI did not confer any benefit in improving the LB outcome when compared to conventional IVF per treatment cycle (PTC), when adjusted for female age, number of previous ART treatment cycles, number of previous live births through ART, oocyte yield, stage of transfer, method of fertilisation and number of embryos transferred in the POR cohort (adjusted odds ratio [a OR] 1.03, 99.5% confidence interval [CI] 0.96-1.11, P = 0.261) and all autologous ovarian response categories (aOR 1.00, 99.5% CI 0.98-1.02, P = 0.900). The mean fertilisation rate was statistically lower for IVF treatment cycles (64.7%) when compared to ICSI treatment cycles (67.2%) in the POR cohort (mean difference -2.5%, 99.5% CI -3.3 to -1.6, P < 0.001). The failed fertilisation rate was marginally higher in IVF treatment cycles (17.3%, 95% binomial exact 16.9 to 17.7%) when compared to ICSI treatment cycles (17.0%, 95% binomial exact 16.6 to 17.4%); however, this did not reach statistical significance (P = 0.199). The results followed a similar trend when analysed for all autologous ovarian response categories with a higher rate of failed fertilisation in IVF treatment cycles (4.8%, 95% binomial exact 4.7 to 4.9%) when compared to ICSI treatment cycles (3.2%, 95% binomial exact 3.1 to 3.3%) (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The quality of data is reliant on the reporting system. Furthermore, success rates through ART have improved since 1991, with an increased number of blastocyst-stage embryo transfers. The inability to link the treatment cycle to the individual patient meant that we were unable to calculate the cumulative LB outcome per patient. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest study to date which evaluates the impact of method of fertilisation in the POR patient and compares this to all autologous ovarian response categories. The results demonstrate that ICSI does not confer any benefit in improving reproductive outcomes in the absence of male factor subfertility, with no improvement seen in the clinical pregnancy or LB outcomes following a fresh treatment cycle. STUDY FUNDING/COMPETING INTEREST(S): The study received no funding. C.M.B. is a member of the independent data monitoring group for a clinical endometriosis trial by ObsEva. He is on the scientific advisory board for Myovant and medical advisory board for Flo Health. He has received research grants from Bayer AG, MDNA Life Sciences, Volition Rx and Roche Diagnostics as well as from Wellbeing of Women, Medical Research Council UK, the NIH, the UK National Institute for Health Research and the European Union. He is the current Chair of the Endometriosis Guideline Development Group for ESHRE and was a co-opted member of the Endometriosis Guideline Group by the UK National Institute for Health and Care Excellence (NICE). I.G. has received research grants from Bayer AG, Wellbeing of Women, the European Union and Finox. TRIAL REGISTRATION NUMBER: Not applicable.

Secondary sex ratio in assisted reproduction: an analysis of 1 376 454 treatment cycles performed in the UK.

STUDY QUESTION: Does ART impact the secondary sex ratio (SSR) when compared to natural conception? SUMMARY ANSWER: IVF and ICSI as well as the stage of embryo transfer does impact the overall SSR. WHAT IS KNOWN ALREADY: The World Health Organization quotes SSR for natural conception to range between 103 and 110 males per 100 female births. STUDY DESIGN SIZE DURATION: A total of 1 376 454 ART cycles were identified, of which 1 002 698 (72.8%) cycles involved IVF or ICSI. Of these, 863 859 (85.2%) were fresh cycles and 124 654 (12.4%) were frozen cycles. Missing data were identified in 14 185 (1.4%) cycles. PARTICIPANTS/MATERIALS SETTING METHODS: All cycles recorded in the anonymized UK Human Fertilisation and Embryology Authority (HFEA) registry database between 1991 and 2016 were analysed. All singleton live births were included, and multiple births were excluded to avoid duplication. MAIN RESULTS AND THE ROLE OF CHANCE: The overall live birth rate per cycle for all IVF and ICSI treatments was 26.2% (n = 262 961), and the singleton live birth rate per cycle was 17.1% (n = 171 399). The overall SSR for this study was 104.0 males per 100 female births (binomial exact 95% CI: 103.1-105.0) for all IVF and ICSI cycles performed in the UK recorded through the HFEA. This was comparable to the overall SSR for England and Wales at 105.3 males per 100 female births (95% CI: 105.2-105.4) from 1991 to 2016 obtained from the Office of National Statistics database. Male predominance was seen with conventional insemination in fresh IVF treatment cycles (SSR 110.0 males per 100 female births; 95% CI: 108.6-111.5) when compared to micro-injection in fresh ICSI treatment cycles (SSR 97.8 males per 100 female births; 95% CI: 96.5-99.2; odds ratio (OR) 1.16, 95% CI 1.12-1.19, P < 0.0001), as well as with blastocyst stage embryo transfers (SSR 104.8 males per 100 female births; 95% CI: 103.5-106.2) when compared to a cleavage stage embryo transfer (SSR 101.2 males per 100 female births; 95% CI: 99.3-103.1; OR 1.03, 95% CI 1.01-1.06, P = 0.011) for all fertilization methods. LIMITATIONS REASONS FOR CAUTION: The quality of the data relies on the reporting system. Furthermore, success rates through ART have improved since 1991, with an increased number of blastocyst stage embryo transfers. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest study to date evaluating the impact of ART on SSR. The results demonstrate that, overall, ART does have an impact on the SSR when assessed according to the method of fertilization (ICSI increased female births while IVF increased males). However, given the ratio of IVF to ICSI cycles at present with 60% of cycles from IVF and 40% from ICSI, the overall SSR for ART closely reflects the population SSR for, largely, natural conceptions in England and Wales. STUDY FUNDING/COMPETING INTERESTS: The study received no funding. C.M.B. is a member of the independent data monitoring group for a clinical endometriosis trial by ObsEva. He is on the scientific advisory board for Myovant and medical advisory board for Flo Health. He has received research grants from Bayer AG, MDNA Life Sciences, Volition Rx and Roche Diagnostics as well as from Wellbeing of Women, Medical Research Council UK, the NIH, the UK National Institute for Health Research and the European Union. He is the current Chair of the Endometriosis Guideline Development Group for ESHRE and was a co-opted member of the Endometriosis Guideline Group by the UK National Institute for Health and Care Excellence (NICE). I.G. has received research grants from Wellbeing of Women, the European Union and Finox. TRIAL REGISTRATION NUMBER: Not applicable.

Anorectal malformations: Role of MRI in preoperative evaluation.

PURPOSE: To evaluate the spectrum of magnetic resonance imaging (MRI) findings in pediatric patients with anorectal malformation (ARM) and compare the accuracy of MRI and distal cologram (DC) findings using surgery as reference standard. MATERIALS AND METHODS: Thirty pediatric patients of age less than 14 years (19 boys and 11 girls) with ARM underwent preoperative MRI. MRI images were evaluated for the level of rectal pouch in relation to the pelvic floor, fistula, and development of sphincter muscle complex (SMC). Associated spinal and other anomalies in lumbar region and pelvis were also evaluated. DC was done in 26 patients who underwent colostomy. Ultrasound of abdomen and pelvis was also done for associated anomalies. RESULTS: Overall accuracy of MRI and DC to detect the exact level of rectal pouch including cloacal malformation was 93.33% and 76.9% respectively. MRI and DC could correctly identify presence or absence of fistula in 76.6% and 76.9% cases respectively. MRI and DC correctly identified the anatomy of fistula in 76% and 65% cases respectively. On MRI, correlation of development of levator ani and puborectalis with the level of rectal pouch as found on surgery was significant (P = 0.008; 0.024 respectively). Subjective assessment of sphincter muscle development on MRI correlated well with the surgical assessment [P = 0.019 and 0.016 for puborectalis and external anal sphincter (EAS) respectively]. Lumbosacral spine anomalies were present in 33.3% of patients and were most common in high type of ARM. Vesicoureteric reflux and renal agenesis were the most common renal and urinary tract anomalies and were present in 40% of cases. CONCLUSION: MRI allows reliable preoperative evaluation of ARM and should be considered as a complementary imaging modality for preoperative imaging in ARM.

Measuring improvement in knowledge of drug policy reforms following a police education program in Tijuana, Mexico.

BACKGROUND: Mexico's 2009 "narcomenudeo reform" decriminalized small amounts of drugs, shifting some drug law enforcement to the states and mandating drug treatment diversion instead of incarceration. Data from Tijuana suggested limited implementation of this harm reduction-oriented policy. We studied whether a police education program (PEP) improved officers' drug and syringe policy knowledge, and aimed to identify participant characteristics associated with improvement of drug policy knowledge. METHODS: Pre- and post-training surveys were self-administered by municipal police officers to measure legal knowledge. Training impact was assessed through matched paired nominal data using McNemar's tests. Multivariable logistic regression was used to identify predictors of improved legal knowledge, as measured by officers' ability to identify conceptual legal provisions related to syringe possession and thresholds of drugs covered under the reform. RESULTS: Of 1750 respondents comparing pre- versus post training, officers reported significant improvement (p < 0.001) in their technical understanding of syringe possession (56 to 91%) and drug amounts decriminalized, including marijuana (9 to 52%), heroin (8 to 71%), and methamphetamine (7 to 70%). The training was associated with even greater success in improving conceptual legal knowledge for syringe possession (67 to 96%) (p < 0.001), marijuana (16 to 91%), heroin (11 to 91%), and methamphetamine (11 to 89%). In multivariable modeling, those with at least a high school education were more likely to exhibit improvement of conceptual legal knowledge of syringe possession (adjusted odds ratio [aOR] 2.6, 95% CI 1.4-3.2) and decriminalization for heroin (aOR 2.7, 95% CI 1.3-4.3), methamphetamine (aOR 2.2, 95% CI 1.4-3.2), and marijuana (aOR 2.5, 95% CI 1.6-4). CONCLUSIONS: Drug policy reform is often necessary, but not sufficient to achieve public health goals because of gaps in translating formal laws to policing practice. To close such gaps, PEP initiatives bundling occupational safety information with relevant legal content demonstrate clear promise. Our findings underscore additional efforts needed to raise technical knowledge of the law among personnel tasked with its enforcement. Police professionalization, including minimum educational standards, appear critical for aligning policing with harm reduction goals.

Approximation of functions in the generalized Zygmund class using Hausdorff means.

In this paper we investigate the degree of approximation of a function belonging to the generalized Zygmund class [Formula: see text] ([Formula: see text]) by Hausdorff means of its Fourier series. We also deduce a corollary and mention a few applications of our main results.

Myeloid translocation genes differentially regulate colorectal cancer programs.

Myeloid translocation genes (MTGs), originally identified as chromosomal translocations in acute myelogenous leukemia, are transcriptional corepressors that regulate hematopoietic stem cell programs. Analysis of The Cancer Genome Atlas (TCGA) database revealed that MTGs were mutated in epithelial malignancy and suggested that loss of function might promote tumorigenesis. Genetic deletion of MTGR1 and MTG16 in the mouse has revealed unexpected and unique roles within the intestinal epithelium. Mtgr1-/- mice have progressive depletion of all intestinal secretory cells, and Mtg16-/- mice have a decrease in goblet cells. Furthermore, both Mtgr1-/- and Mtg16-/- mice have increased intestinal epithelial cell proliferation. We thus hypothesized that loss of MTGR1 or MTG16 would modify Apc1638/+-dependent intestinal tumorigenesis. Mtgr1-/- mice, but not Mtg16-/- mice, had a 10-fold increase in tumor multiplicity. This was associated with more advanced dysplasia, including progression to invasive adenocarcinoma, and augmented intratumoral proliferation. Analysis of chromatin immunoprecipitation sequencing data sets for MTGR1 and MTG16 targets indicated that MTGR1 can regulate Wnt and Notch signaling. In support of this, immunohistochemistry and gene expression analysis revealed that both Wnt and Notch signaling pathways were hyperactive in Mtgr1-/- tumors. Furthermore, in human colorectal cancer (CRC) samples MTGR1 was downregulated at both the transcript and protein level. Overall our data indicates that MTGR1 has a context-dependent effect on intestinal tumorigenesis.

Pain Perception: Computerized versus Traditional Local Anesthesia in Pediatric Patients.

BACKGROUND: Local anesthetic injection is one of the most anxiety- provoking procedure for both children and adult patients in dentistry. A computerized system for slow delivery of local anesthetic has been developed as a possible solution to reduce the pain related to the local anesthetic injection. STUDY DESIGN: The present study was conducted to evaluate and compare pain perception rates in pediatric patients with computerized system and traditional methods, both objectively and subjectively. STUDY DESIGN: It was a randomized controlled study in one hundred children aged 8-12 years in healthy physical and mental state, assessed as being cooperative, requiring extraction of maxillary primary molars. Children were divided into two groups by random sampling - Group A received buccal and palatal infiltration injection using Wand, while Group B received buccal and palatal infiltration using traditional syringe. Visual Analog scale (VAS) was used for subjective evaluation of pain perception by patient. Sound, Eye, Motor (SEM) scale was used as an objective method where sound, eye and motor reactions of patient were observed and heart rate measurement using pulse oximeter was used as the physiological parameter for objective evaluation. RESULTS: Patients experienced significantly less pain of injection with the computerized method during palatal infiltration, while less pain was not statistically significant during buccal infiltration. Heart rate increased during both buccal and palatal infiltration in traditional and computerized local anesthesia, but difference between traditional and computerized method was not statistically significant. CONCLUSION: It was concluded that pain perception was significantly more during traditional palatal infiltration injection as compared to computerized palatal infiltration, while there was no difference in pain perception during buccal infiltration in both the groups.

Predictors of early neurological deterioration in patients with acute ischaemic stroke with special reference to blood urea nitrogen (BUN)/creatinine ratio & urine specific gravity.

BACKGROUND & OBJECTIVES: Early neurological deterioration (END) occurs in about 20 to 40 per cent of patients with acute ischaemic stroke and results in increased mortality and functional disability. In recent studies relative dehydration has been found to be associated with END in patients with acute ischaemic stroke. This study was conducted to identify factors useful for predicting END and to assess the role of blood urea nitrogen/creatinine ratio (BUN/creatinine) and urine specific gravity (USG) as predictors of END in patients with acute ischaemic stroke. METHODS: The present study was an observational prospective study. Various parameters comprising demographic, clinical, laboratory and radiological variables along with stroke severity were assessed and studied as predictors of early neurological deterioration in 114 consecutive patients presenting to the Emergency department during 2012. BUN/creatinine >15 and USG >1.010 were studied as markers of relative dehydration contributing to END. RESULTS: Of the 114 patients enrolled in the study, END was observed in 25 (21.9%) patients. National Institutes Health Stroke Scale score (NIHSS) ≥ 12 at admission was found to be an independent risk factor for END. Amongst markers of relative dehydration, BUN/creatinine >15 at admission was found to be an independent risk factor for END, as also USG >1.010. Also, cerebral oedema and size of hypodensity >1/3 rd of the middle cerebral artery territory on cranial CT were observed to be independent risk factors for END. INTERPRETATION & CONCLUSIONS: Our study findings highlighted a possible association of relative dehydration, as indicated by BUN/creatinine ratio >15, with END along with other parameters like stroke severity at presentation, extent of hypodensity >1/3 rd of the middle cerebral artery (MCA) territory and cerebral oedema. Dehydration being a treatable condition, the use of BUN/creatinine >15 as a marker of relative dehydration, can be helpful in detecting patients with dehydration early and thus play a role in preventing END.

Bordetella trematum bacteremia in an infant: a cause to look for.

Bordetella trematum spp. nov. has been isolated from wounds, ear infections and diabetic ulcers. We report a case of a 7-month-old infant with fever, vomiting and abnormal body movements with bacteremia caused by this novel species. The infant responded to fluoroquinolone and macrolide combination therapy.

Association of the Position of the Copper T 380A as Determined by the Ultrasonography Following its Insertion in the Immediate Postpartum Period with the Subsequent Complications: An Observational Study.

PURPOSE: Incorrectly placed copper T 380A leads to increased contraception failure. This study aimed to find an association between the ultrasonographic position of the copper T 380A in the immediate postpartum period and the adverse effects observed during the period of 6 months after its insertion. METHODS: This descriptive study was carried out in the Department of Obstetrics & Gynaecology of a tertiary-care-center of India from September 2011 to February 2013. The women eligible for immediate postpartum copper T 380A insertion with previous regular menstrual cycles for at least 6 months before the current pregnancy, and those who were willing for follow-up visits and had easy accessibility to the hospital, were recruited. A clinical evaluation and ultrasonographic assessment of Intra-Uterine-Contraceptive-Device (IUCD) after insertion was carried out after enrolment. The complications (expulsions, vaginal discharge, menstrual irregularity, and lower abdominal pain) were subsequently assessed during a 6-month follow-up period. The primary objective was the ultrasonographic assessment of the placement of IUCD immediately after insertion. The incidence of complications and their association with the presence of malposition was also studied. RESULTS: Hundred patients were evaluated during the study period. Forty-four (44 %) women were found to have malpositioned IUCDs on ultrasonographic evaluation done following insertion. The complications among the IUCD users included menstrual irregularity (27.17 %), pain in lower abdomen (20.65 %), vaginal discharge (7.6 %), and expulsions (9.7 %). The IUCD expulsions, menstrual irregularities, and pain were significantly more in patients with malpositions (p < 0.05). CONCLUSIONS: Malpositioning of IUCD is common immediately following insertion and is significantly associated with more complications during the follow-up.

Evaluation and Validation of Neo-Adjuvant Response Index (NRI) and It's Correlation with Various Predictive Biomarkers and RECIST in Locally Advanced Breast Cancer.

BACKGROUND: Response evaluation following neo-adjuvant chemotherapy in breast cancer is usually done without taking in to account the axillary response and the available tools like 'response evaluation criteria in solid tumors' (RECIST) have this limitation. These criteria rely solely on the response observed in the primary tumour. Neoadjuvant response index is one such attempt to have a comprehensive assessment of response both in the primary tumour and the axilla. METHODS: 30 cases of locally advanced breast cancer (LABC) were assessed for response using 'Neo-adjuvant Response Index'. The index always gives score between '0' (no response or progressive disease) and '1' (pathological complete response i.e. no invasive tumor in breast as well as axilla). This index includes axillary response as well and provides a spectrum of response rather than dividing patients into simply responders and non-responders . RESULTS: Mean reading of index was found to be 0.2925 in this study. Three patients achieved an index of 1. This index correlates significantly with the existing scales for assessing response. Hormone negative tumors were found to be more chemo responsive with higher rates of pathological complete response (pCR) while ER/PR + Her2- tumors showed a very poor response to NACT. CONCLUSIONS: Based on the observations of the present study it may be submitted that Neoadjuvant Response Index (NRI) is a reliable and simple tool that can serve as a comprehensive and accurate method of assessing response to neo-adjuvant chemotherapy as it takes in to consideration both the tumor and axillary response unlike the existing RECIST, binary system (responders are those with greater than 50 % reduction), RCB method and the available biomarkers. This study being first of it's kind in Indian population, in spite of it's limitations, could prove to be a launching ground for further reasearch and contribute substantially to the evidence base.

Central nervous system activity of an aqueous acetonic extract of Ficus carica L. in mice.

BACKGROUND: Ficus carica Linn. is reported to possess variety of activities, but its potential in CNS disorders is still to be explored. OBJECTIVE: The present study was carried out to evaluate the CNS depressant activity of aqueous acetonic extract of Ficus carica Linn on different models in mice. MATERIALS AND METHODS: The aerial parts of the plant Ficus carica L. were extracted with aqueous acetone and the solvent was removed by rotary vacuum evaporator under reduced pressure. A crude extract was given orally and its effects were tested on ketamine-induced sleeping time, muscle-coordination, anxiety (elevated-plus maze and Staircase test), convulsions [maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures], and nociception. In addition, we determined the levels of neurotransmitters, norepinephrine (NE) and 5-hydroxytryptamine (5-HT). RESULTS: RESULTS FROM THE EXPERIMENTAL MODELS TESTED SHOWED: (1) a delay on onset and prolongation of sleep of ketamine-induced sleeping time; (2) significant muscle relaxant activity; (3) a significant attenuation in the anxiety-response (4) a delay in the onset of seizures and reduction in duration of seizures and mortality induced by MES and PTZ; (5) a reduction in the licking time in nociception test and (6) increased levels of NE and 5-HT. CONCLUSION: This suggests that Ficus carica L. exerts its CNS depressive effect by modulating the neurotransmitters NE and 5-HT in the brain.

Evidence of presence of Mycobacterium tuberculosis in bovine tissue samples by multiplex PCR: possible relevance to reverse zoonosis.

Bovine tuberculosis, caused by Mycobacterium bovis, remains one of the most important zoonotic health concerns worldwide. The transmission of Mycobacterium tuberculosis from humans to animals also occurs especially in countries where there is close interaction of humans with the animals. In the present study, thirty bovine lung tissue autopsy samples from an organized dairy farm located in North India were screened for the presence of Mycobacterium tuberculosis complex by smear microscopy, histopathological findings and PCR. Differential diagnosis of M. tuberculosis and M. bovis was made based on the deletion of mce-3 operon in M. bovis. The present study found eight of these samples positive for M. tuberculosis by multiplex PCR. Sequencing was performed on two PCR-positive representative samples and on annotation, and BLAST analysis confirmed the presence of gene fragment specific to Mycobacterium tuberculosis. The presence of M. tuberculosis in all the positive samples raises the possibility of human-to-cattle transmission and possible adaptation of this organism in bovine tissues. This study accentuates the importance of screening and differential diagnosis of Mycobacterium tuberculosis complex in humans and livestock for adopting effective TB control and eradication programmes.