A Rare Cause of Acute on Chronic Liver Failure (ACLF): Bakuchi-Induced Liver Injury.

Psoralea corylifolia Linn (Bakuchi or Babchi), commonly known as purple fleabane, is a popular herb used in Ayurvedic traditional medicine. Its seeds, called Fructus Psoraleae, are traditionally used for treating leprosy, vitiligo, and psoriasis in the absence of empirical evidence. We report the first case of acute on chronic liver failure (ACLF) caused by Bakuchi, a well-documented hepatotoxic agent, in a middle-aged female. Her liver function deteriorated progressively which prompted us to go for a liver biopsy which was consistent with diagnosis of herb-induced liver injury after excluding all competing causes. Fortunately, the patient improved gradually after herb withdrawal and supportive care. Patients with underlying chronic liver disease (CLD) should be aware of risks in using untested herbal formulations. This case emphasizes the need for increased surveillance to formulate guidelines regarding the regulation and informed use of herbal supplements in patients with chronic liver disease.

Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial: Planned 10-Year Follow-up.

ABSTRACT: The CAPP2 trial investigated the long-term effects of aspirin and resistant starch on cancer incidence in patients with Lynch syndrome (LS). Participants with LS were randomized double-blind to 30 g resistant starch (RS) daily or placebo for up to 4 years. We present long-term cancer outcomes based on the planned 10-year follow-up from recruitment, supplemented by National Cancer Registry data to 20 years in England, Wales, and Finland. Overall, 463 participants received RS and 455 participants received placebo. After up to 20 years follow-up, there was no difference in colorectal cancer incidence (n = 52 diagnosed with colorectal cancer among those randomized to RS against n = 53 on placebo) but fewer participants had non-colorectal LS cancers in those randomized to RS (n = 27) compared with placebo (n = 48); intention-to-treat (ITT) analysis [HR, 0.54; 95% confidence interval (CI), 0.33-0.86; P = 0.010]. In ITT analysis, allowing for multiple primary cancer diagnoses among participants by calculating incidence rate ratios (IRR) confirmed the protective effect of RS against non-colorectal cancer LS cancers (IRR, 0.52; 95% CI, 0.32-0.84; P = 0.0075). These effects are particularly pronounced for cancers of the upper GI tract; 5 diagnoses in those on RS versus 21 diagnoses on placebo. The reduction in non-colorectal cancer LS cancers was detectable in the first 10 years and continued in the next decade. For colorectal cancer, ITT analysis showed no effect of RS on colorectal cancer risk (HR, 0.92; 95% CI, 0.62-1.34; P = 0.63). There was no interaction between aspirin and RS treatments. In conclusion, 30 g daily RS appears to have a substantial protective effect against non-colorectal cancer cancers for patients with LS. PREVENTION RELEVANCE: Regular bowel screening and aspirin reduce colorectal cancer among patients with LS but extracolonic cancers are difficult to detect and manage. This study suggests that RS reduces morbidity associated with extracolonic cancers. See related Spotlight, p. 557.

Impact of lymph node staging systems in predicting outcome in patients with ampullary cancer.

BACKGROUNDS/AIMS: Lymph node (LN) metastasis though, is a poor prognostic factor for ampullary carcinoma (APC), the impact of Lymph node ratio (LNR) and Logarithm odds of positive lymph node (LODDS) in the long-term survival remains controversial. We evaluated the factors affecting the long-term outcome in APC patients with emphasis on LNR and LODDS. METHODS: The prospectively collected data of 198 patients who underwent pancreatoduodenectomy for APC was analyzed after excluding 12 patients for various reasons. Factors affecting Disease specific survival (DSS) and Recurrence free survival (RFS) were analyzed with special reference to LN positivity, LNR and LODDS. RESULTS: Out of 186, 117 (62.9%) patients were alive at a median follow-up of 39.5 months and 72 (38.7%) developed recurrence. The overall 5-year DSS was 59.3% & RFS 54.9%. Univariate analysis showed T-stage, tumor differentiation, perineural invasion, LN positivity, LNR and LODDS was significantly affected DSS and RFS. On multivariate analysis, perineural invasion, LN positivity, LNR and LODDS lost its significance for DSS and RFS. AUC for prediction of DSS and RFS for LNR was 0.654 (p<0.001) & 0.629 (p=0.003) respectively and for LODDS, it was 0.697 (p<0.001) & 0.677 (p=0.001) respectively. Sensitivity and specificity of LNR (0.1) for DSS were 37.7% & 83.8% and for RFS were 36.1% & 83.3%; for LODDS (-1.00), sensitivity and specificity for DSS was 62.3% and 67.5% and for RFS it was 59.7% and 66.7% respectively. CONCLUSIONS: LNR and LODDS although independently seem to affect the RFS and DSS, albeit have a low sensitivity and specificity in predicting DSS and RFS.

Rate and risk factors of nocturnal enuresis in school going children.

PURPOSE: The purpose is to find out the rate of nocturnal enuresis in school going children (5-12 years) and the risk factors associated with it. MATERIALS AND METHODS: The parents of children aged between 5 and 12 years studying in two primary schools in Ahmedabad completed a self-administered semi-structured questionnaire comprising of enuresis, sociodemographic profiles, and risk factors. Children with enuresis and those without were compared on demographic characteristics and risk factors using Chi-square and t-test for categorical and quantitative data respectively. The data were analyzed using SPSS version 17. RESULTS: The response rate was 86.54% as 1904 responses were collected out of 2200. The overall rate of nocturnal enuresis was 6.7% (according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition definition of nocturnal enuresis). As the age increased, the rate of nocturnal enuresis declined. A positive family history was seen in 36.6% of children with enuresis. Enuresis was found to be more frequently in lower socioeconomic class. It was a neglected problem, only 20.6% of children received some kind of treatment. CONCLUSION: The rate of nocturnal enuresis was 6.7% in school going children. Strong correlation was found with family history. Although the rate was high, most of the children with enuresis were not treated.

Biofilm adaptation to iron availability in the presence of biotite and consequences for chemical weathering.

Bacteria in nature often live within biofilms, exopolymeric matrices that provide a favorable environment that can differ markedly from their surroundings. Biofilms have been found growing on mineral surfaces and are expected to play a role in weathering those surfaces, but a clear understanding of how environmental factors, such as trace-nutrient limitation, influence this role is lacking. Here, we examine biofilm development by Pseudomonas putida in media either deficient or sufficient in Fe during growth on biotite, an Fe rich mineral, or on glass. We hypothesized that the bacteria would respond to Fe deficiency by enhancing biotite dissolution and by the formation of binding sites to inhibit Fe leaching from the system. Glass coupons acted as a no-Fe control to investigate whether biofilm response depended on the presence of Fe in the supporting solid. Biofilms grown on biotite, as compared to glass, had significantly greater biofilm biomass, specific numbers of viable cells (SNVC), and biofilm cation concentrations of K, Mg, and Fe, and these differences were greater when Fe was deficient in the medium. Scanning electron microscopy (SEM) confirmed that biofilm growth altered the biotite surface, smoothing the rough, jagged edges of channels scratched by hand on the biotite, and dissolving away small, easy-to-access particles scattered across the planar surface. High-resolution magic angle spinning proton nuclear magnetic resonance (HRMAS 1 H NMR) spectroscopy showed that, in the Fe-deficient medium, the relative amount of polysaccharide nearly doubled relative to that in biofilms grown in the medium amended with Fe. The results imply that the bacteria responded to the Fe deficiency by obtaining Fe from biotite and used the biofilm matrix to enhance weathering and as a sink for released cation nutrients. These results demonstrate one mechanism by which biofilms may help soil microbes overcome nutrient deficiencies in oligotrophic systems.

Identification of a Bipotent Epithelial Progenitor Population in the Adult Thymus.

Thymic epithelial cells (TECs) are critically required for T cell development, but the cellular mechanisms that maintain adult TECs are poorly understood. Here, we show that a previously unidentified subpopulation, EpCam(+)UEA1(-)Ly-51(+)PLET1(+)MHC class II(hi), which comprises <0.5% of adult TECs, contains bipotent TEC progenitors that can efficiently generate both cortical (c) TECs and medullary (m) TECs. No other adult TEC population tested in this study contains this activity. We demonstrate persistence of PLET1(+)Ly-51(+) TEC-derived cells for 9 months in vivo, suggesting the presence of thymic epithelial stem cells. Additionally, we identify cTEC-restricted short-term progenitor activity but fail to detect high efficiency mTEC-restricted progenitors in the adult thymus. Our data provide a phenotypically defined adult thymic epithelial progenitor/stem cell that is able to generate both cTECs and mTECs, opening avenues for improving thymus function in patients.

Foxn1 Is Dynamically Regulated in Thymic Epithelial Cells during Embryogenesis and at the Onset of Thymic Involution.

Thymus function requires extensive cross-talk between developing T-cells and the thymic epithelium, which consists of cortical and medullary TEC. The transcription factor FOXN1 is the master regulator of TEC differentiation and function, and declining Foxn1 expression with age results in stereotypical thymic involution. Understanding of the dynamics of Foxn1 expression is, however, limited by a lack of single cell resolution data. We have generated a novel reporter of Foxn1 expression, Foxn1G, to monitor changes in Foxn1 expression during embryogenesis and involution. Our data reveal that early differentiation and maturation of cortical and medullary TEC coincides with precise sub-lineage-specific regulation of Foxn1 expression levels. We further show that initiation of thymic involution is associated with reduced cTEC functionality, and proportional expansion of FOXN1-negative TEC in both cortical and medullary sub-lineages. Cortex-specific down-regulation of Foxn1 between 1 and 3 months of age may therefore be a key driver of the early stages of age-related thymic involution.

Chromosomal abnormalities in couples with repeated fetal loss: An Indian retrospective study.

BACKGROUND: Recurrent pregnancy loss is a common occurrence and a matter of concern for couples planning the pregnancy. Chromosomal abnormalities, mainly balanced rearrangements, are common in couples with repeated miscarriages. PURPOSE: The purpose of this study is to evaluate the contribution of chromosomal anomalies causing repeated spontaneous miscarriages and provide detailed characterization of a few structurally altered chromosomes. MATERIALS AND METHODS: A retrospective cytogenetic study was carried out on 4859 individuals having a history of recurrent miscarriages. The cases were analyzed using G-banding and fluorescence in situ hybridization wherever necessary. RESULTS: Chromosomal rearrangements were found in 170 individuals (3.5%). Translocations were seen in 72 (42.35%) cases. Of these, reciprocal translocations constituted 42 (24.70%) cases while Robertsonian translocations were detected in 30 (17.64%) cases. 7 (4.11%) cases were mosaic, 8 (4.70%) had small supernumerary marker chromosomes and 1 (0.6%) had an interstitial microdeletion. Nearly, 78 (1.61%) cases with heteromorphic variants were seen of which inversion of Y chromosome (57.70%) and chromosome 9 pericentromeric variants (32.05%) were predominantly involved. CONCLUSIONS: Chromosomal analysis is an important etiological investigation in couples with repeated miscarriages. Characterization of variants/marker chromosome enable calculation of a more precise recurrent risk in a subsequent pregnancy thereby facilitating genetic counseling and deciding further reproductive options.

Effect of sleep deprivation on NREM sleep ERPs and related activity at sleep onset.

This research assessed the impact of one night of sleep deprivation on the amplitudes of NREM-sleep event-related potentials (NREM ERPs) and on the frequency of occurrence of related electroencephalogram activity including sleep spindles, arousals, K-complexes, and vertex sharp waves (VSWs). The NREM ERPs identified included P220, N350, P450, N550 and P900. During a pre-deprivation night, ten subjects took two 20-min naps separated by a 20-min break at their normal bedtime. Brief tones were presented at three intensity levels (60, 75 and 90 dB) with a 5-s interstimulus interval. Following these naps, subjects were kept awake until their normal bedtime the following day. At that time, they repeated the two-nap procedure. The ERPs obtained for each tone and wake/sleep state for pre- and post-deprivation conditions were analyzed using repeated measures statistical procedures. As anticipated, NREM ERP amplitudes recorded both pre- and post-deprivation increased with tone intensity and with approaching sleep. Also, sleep deprivation was associated with more rapid sleep onset, reduced arousability, and greater spindle production. While sleep deprivation had no effect on the amplitude of P220. Post-deprivation amplitudes of N350, N550 and P900 were greater, especially following the 90-dB tone. There was a corresponding increase in VSWs and K-complexes. These findings are inconsistent with the view that NREM ERPs reflect arousal. The underlying mechanism(s) may facilitate initiation and maintenance of sleep.

P300 and sleep-related positive waveforms (P220, P450, and P900) have different determinants.

Stimulus factors known to influence the amplitude of the well known endogenous event-related potential (ERP) component P300 were manipulated to determine whether they have the same, or a different, influence on the amplitude of positivities of the sleep ERPs identified as P220, P450, and P900. Behavioral responsiveness and ERPs were recorded as subjects moved from wakefulness to sleep while performing an oddball task. The task consisted of sequential presentation of target and non-target tone stimuli with instructions to respond to targets with a finger--lift response. The probability of the target and non-target stimuli was varied (0.2/0.8, 0.5/.05 and 0.8/0.2) across three test conditions. While subjects were awake, P300 was maximal parietally with amplitude inversely related to the relative probability of the evoking stimulus and directly related to its task relevance. Positive waveforms (P220, P450, P900) recorded in sleep were largest at frontal and central recording sites. P220 and P900 amplitudes were inversely related to stimulus probability. P220 was smaller following target relative to non-target stimuli. Processes underlying P220, P450, and P900 sleep-related waveforms are different from those underlying the P300 component seen in alert wakefulness. The sleep positivities may be state-related waveforms subject to modulation by psychological processes.

Low cerebrospinal fluid hypocretin levels found in familial narcolepsy.

OBJECTIVE: This report describes abnormal hypocretin neurotransmission in a case of familial narcolepsy. BACKGROUND: Narcolepsy is a chronic, often-disabling central nervous system disorder characterized by excessive daytime sleepiness and abnormal rapid eye movement (REM) sleep features including cataplexy, a loss of muscle tone triggered by emotion. The cause of human narcolepsy is unknown. Several familial cases have been described, but most cases are sporadic (95%). An abnormality of hypocretin neurotransmission has been found in a majority of sporadic cases. METHODS: Hypocretin-1 levels were measured in the cerebrospinal fluid of the narcoleptic proband of a family with several affected members. RESULTS: The proband was found to have a hypocretin-1 deficiency. CONCLUSION: Abnormal hypocretin neurotransmission is found in familial, as well as sporadic, narcolepsy.

Night-time sleep and daytime sleepiness in narcolepsy.

This report describes night-time sleep and daytime sleepiness in a large (N=530) sample of patients meeting the International Classification of Sleep Disorders criteria for diagnosis of narcolepsy. Sleep data were obtained from polysomnographic recordings on two consecutive nights. Sleepiness was assessed using the Multiple Sleep Latency Test, the Maintenance of Wakefulness Test and the Epworth Sleepiness Scale. Analysis revealed that sleep was mild to moderately disturbed on both recording nights. A first-night effect was suggested by decreased REM latency and increased percentage REM and slow-wave sleep on the second night. Sleepiness and sleep disturbance varied across patient subgroups created based on patient ethnicity and on the presence/absence of cataplexy, sleep apnoea, and periodic limb movements. Covariation of sleep and sleepiness measures across patients was significant but weak. Strong association was found between subgroup means of sleep and sleep disturbance measures. The findings reported here show that sleepiness and sleep disturbance vary across patient subgroups and that sleep disturbance is related to, although unable to account, for the pathological sleepiness of narcolepsy.

Long-term efficacy and safety of modafinil (PROVIGIL((R))) for the treatment of excessive daytime sleepiness associated with narcolepsy.

Objectives: To assess the long-term efficacy and safety of modafinil in patients with excessive daytime sleepiness (EDS) associated with narcolepsy.Background: Modafinil has been shown to be effective and well tolerated for treating EDS associated with narcolepsy in two large-scale, well-controlled, 9-week clinical trials.Methods: Four hundred and seventy eight adult patients with a diagnosis of narcolepsy who had completed one of two 9-week, double-blind, placebo-controlled, multicenter, clinical trials of modafinil were enrolled in two 40-week, open-label, extension studies. A flexible-dose regimen (i.e. 200, 300, or 400 mg daily) was followed in one study. In the second study, patients received 200 mg/day for 1 week, followed by 400 mg/day for 1 week. Investigators then prescribed either 200- or 400-mg doses for the duration of the study. Efficacy was evaluated using Clinical Global Impression of Change (CGI-C) scores, the Epworth Sleepiness Scale (ESS), and the 36-item Medical Outcomes Study health survey (SF-36). Adverse events were recorded. Data from the two studies were combined.Results: The majority of patients ( approximately 75%) received 400 mg of modafinil daily. Disease severity improved in >80% of patients throughout the 40-week study. At weeks 2, 8, 24, and 40, disease severity was 'much improved' or 'very much improved' in 49, 58, 59, and 58% of patients, respectively. The mean (+/-SEM) ESS score improved significantly from 16.5+/-0.2 at open-label baseline to 12.4+/-0.2 at week 2 and remained at that level through week 40 (P<0.001). Quality of life scores at weeks 4, 8, 24, and 40 were significantly improved versus open-label baseline scores for six of the eight SF-36 domains (P<0.001). The most common treatment-related adverse events were headache (13%), nervousness (8%), and nausea (5%). Most adverse events were mild to moderate in nature. A total of 341 patients (71%) completed the studies. Forty-three patients (9.0%) discontinued treatment because of adverse events.Conclusions: Modafinil is effective for the long-term treatment of EDS associated with narcolepsy and significantly improves perceptions of general health. Modafinil is well tolerated, with no evidence of tolerance developing during 40 weeks of treatment.

Information processing and coping style during the wake/sleep transition.

Information processing of meaningful events (subject's own name, neutral name and tones) was studied during the transition from wakefulness to sleep in two groups of subjects with opposing information processing styles, Monitors and Blunters. In two experimental sets, subjects were instructed to execute a fingerlift response to a predetermined stimulus type. Subject's own name produced the greatest number of K-complexes and arousals relative to other name and tones. A task relevance effect was found for arousals but not for K-complexes. The overall P3 amplitude was larger for Monitors than for Blunters, whereas Blunters showed a larger N350 to target stimuli than Monitors. The findings suggest that higher level processing continues during light sleep and that N350 may reflect a process related to sleep maintenance.

ERP and behavioral changes during the wake/sleep transition.

Event-related potentials (ERPs) following infrequent and frequent stimuli were studied as subjects moved from wakefulness to sleep. Subjects were instructed to respond to the infrequent "target" stimuli (attend condition) or to ignore the stimuli (ignore condition). Parietal P300, prominent following target ERPs in wakefulness under the attend condition, disappeared in association with reduced behavioral responsiveness and emergence of a central negativity (N350). The N350 and preceding and following positivities (P220 and P450) became the dominant feature of both target and nontarget ERPs under both attend and ignore conditions. The P220-N350-P450 complex was larger and peak latencies were shorter under the attend condition. Peak amplitudes tended to be larger following targets, especially under the attend condition. The findings suggest that, although the processes underlying P300 are less likely to be engaged, processing of stimulus deviance and task relevance continues in sleepiness and sleep, and is reflected by variance in N350 and related activity.

Effects of DNA polymer length on its adsorption to soils.

Three different DNA fragments ranging size from 2.69 kbp (1.75 MDa) to 23 kbp (14.95 MDa) were used as tracers to study the adsorption of polydisperse solutions of calf thymus DNA to eight model soils. The adsorption of the three tracers to all soils was described by the Freundlich adsorption model, with adsorption coefficients (K) ranging from 1.1 for acid-washed sand to over 300 for one soil. An inverse relationship between tracer size and K was observed with six of the eight soils, indicating that smaller fragments are sorbed preferentially versus larger fragments in these soils. No significant correlation between K and the organic carbon contents, clay contents, pHs, or cation exchange capacities of the model soils was observed.

Supercritical fluid extraction of 2,4-D from soils using derivatization and ionic modifiers.

Supercritical fluid extraction (SFE) with CO(2), a clean and rapid alternative to conventional organic solvent extraction techniques, was investigated for the extraction of 2,4-D from soils using a variety of pre-extraction soil treatments to enhance extraction recoveries. Initial experiments with silylation, ion-pairing, methyl esterification, and ionic displacement are reported. Methyl esterification and ionic displacement during SFE proved to be the most promising approaches for quantitative extraction. Although the SFE procedures were not fully optimized, comparison between SFE and a standard Soxhlet extraction method demonstrated the potential for improving analytical measurement for highly polar pesticides in soil by modifying SFE-CO(2) extraction with derivatizing reagents and ionic solutions.

An examination of leadership style and its relevance to shift work in an organizational setting.

Results form the present research suggest that leadership style may be different for day and night and shifts, the relationship between leadership and job satisfaction is different for night and day shift employees, and the relationship between leadership and performance appraisal is not different for day and night shift workers. Implications for shift workers and further research questions are discussed.

Bright light effects on body temperature, alertness, EEG and behavior.

The immediate psychophysiological and behavioral effects of photic stimulation on humans [bright light (BL) of 5K lux or dim light (DL) of 50 lux] were assessed in male subjects (N = 43) under four different conditions. For one condition the same subjects (N = 16) received alternating 90-min blocks of BL and DL during the nighttime h (2300-0800 h) under sustained wakefulness conditions. A second condition was similar to the first except that subjects (N = 8) received photic stimulation during the daytime hours. For the third and fourth conditions different subjects received either continuous BL (N = 10) or continuous DL (N = 9) during the nighttime hours. For the nighttime alternating condition body temperature decreased under DL but either increased or maintained under BL. For the continuous light condition, body temperature dropped sharply across the night under DL but dropped only slightly under BL. Sleepiness was considerably greater under DL than under BL, and the difference became larger as the night progressed. Similarly, alertness, measured by EEG beta activity, was greater under BL, and nighttime performance on behavioral tasks was also generally better. There were no differential effects between BL and DL on any measure during the daytime. These data indicate that light exerts a powerful, immediate effect on physiology and behavior in addition to its powerful influence on circadian organization.