Light Sensitive Liposomes: A Novel Strategy for Targeted Drug Delivery.

Light-sensitive liposomes have emerged as a promising platform for drug delivery, offering the potential for precise control over drug release and targeted therapy. These lipid-based nanoparticles possess photoresponsive properties, allowing them to undergo structural changes or release therapeutic payloads upon exposure to specific wavelengths of light. This review presents an overview of the design principles, fabrication methods, and applications of light-sensitive liposomes in drug delivery. Further, this article also discusses the incorporation of light-sensitive moieties, such as azobenzene, spiropyran, and diarylethene, into liposomal structures, enabling spatiotemporal control over drug release. The utilization of photosensitizers and imaging agents to enhance the functionality and versatility of light-sensitive liposomes is also highlighted. Finally, the recent advances, challenges, and future directions in the field, emphasizing the potential for these innovative nanocarriers to revolutionize targeted therapeutics, are also discussed.

Dynamical independence: Discovering emergent macroscopic processes in complex dynamical systems.

We introduce a notion of emergence for macroscopic variables associated with highly multivariate microscopic dynamical processes. Dynamical independence instantiates the intuition of an emergent macroscopic process as one possessing the characteristics of a dynamical system "in its own right," with its own dynamical laws distinct from those of the underlying microscopic dynamics. We quantify (departure from) dynamical independence by a transformation-invariant Shannon information-based measure of dynamical dependence. We emphasize the data-driven discovery of dynamically independent macroscopic variables, and introduce the idea of a multiscale "emergence portrait" for complex systems. We show how dynamical dependence may be computed explicitly for linear systems in both time and frequency domains, facilitating discovery of emergent phenomena across spatiotemporal scales, and outline application of the linear operationalization to inference of emergence portraits for neural systems from neurophysiological time-series data. We discuss dynamical independence for discrete- and continuous-time deterministic dynamics, with potential application to Hamiltonian mechanics and classical complex systems such as flocking and cellular automata.

Hypothesis awareness confounds asynchronous control conditions in indirect measures of the rubber hand illusion.

Reports of changes in experiences of body location and ownership following synchronous tactile and visual stimulation of fake and real hands (rubber hand (RH) effects) are widely attributed to multisensory integration mechanisms. However, existing control methods for subjective report measures (asynchronous stroking and control statements) are confounded by participant hypothesis awareness; the report may reflect response to demand characteristics. Subjective report is often accompanied by indirect (also called 'objective' or 'implicit') measures. Here, we report tests of expectancies for synchronous 'illusion' and asynchronous 'control' conditions across two pre-registered studies (n = 140 and n = 45) for two indirect measures: proprioceptive drift (a change in perceived hand location) and skin conductance response (a measure of physiological arousal). Expectancies for synchronous condition measures were greater than for asynchronous conditions in both studies. Differences between synchronous and asynchronous control condition measures are therefore confounded by hypothesis awareness. This means indirect measures of RH effects may reflect compliance, bias and phenomenological control in response to demand characteristics, just as for subjective measures. Valid control measures are required to support claims of a role of multisensory integration for both direct and indirect measures of RH effects.

Trait phenomenological control predicts experience of mirror synaesthesia and the rubber hand illusion.

In hypnotic responding, expectancies arising from imaginative suggestion drive striking experiential changes (e.g., hallucinations) - which are experienced as involuntary - according to a normally distributed and stable trait ability (hypnotisability). Such experiences can be triggered by implicit suggestion and occur outside the hypnotic context. In large sample studies (of 156, 404 and 353 participants), we report substantial relationships between hypnotisability and experimental measures of experiential change in mirror-sensory synaesthesia and the rubber hand illusion comparable to relationships between hypnotisability and individual hypnosis scale items. The control of phenomenology to meet expectancies arising from perceived task requirements can account for experiential change in psychological experiments.

Conscious perception and the modulatory role of dopamine: no effect of the dopamine D2 agonist cabergoline on visual masking, the attentional blink, and probabilistic discrimination.

RATIONALE: Conscious perception is thought to depend on global amplification of sensory input. In recent years, striatal dopamine has been proposed to be involved in gating information and conscious access, due to its modulatory influence on thalamocortical connectivity. OBJECTIVES: Since much of the evidence that implicates striatal dopamine is correlational, we conducted a double-blind crossover pharmacological study in which we administered cabergoline-a dopamine D2 agonist-and placebo to 30 healthy participants. Under both conditions, we subjected participants to several well-established experimental conscious-perception paradigms, such as backward masking and the attentional blink task. RESULTS: We found no evidence in support of an effect of cabergoline on conscious perception: key behavioral and event-related potential (ERP) findings associated with each of these tasks were unaffected by cabergoline. CONCLUSIONS: Our results cast doubt on a causal role for dopamine in visual perception. It remains an open possibility that dopamine has causal effects in other tasks, perhaps where perceptual uncertainty is more prominent.

Prior expectations facilitate metacognition for perceptual decision.

The influential framework of 'predictive processing' suggests that prior probabilistic expectations influence, or even constitute, perceptual contents. This notion is evidenced by the facilitation of low-level perceptual processing by expectations. However, whether expectations can facilitate high-level components of perception remains unclear. We addressed this question by considering the influence of expectations on perceptual metacognition. To isolate the effects of expectation from those of attention we used a novel factorial design: expectation was manipulated by changing the probability that a Gabor target would be presented; attention was manipulated by instructing participants to perform or ignore a concurrent visual search task. We found that, independently of attention, metacognition improved when yes/no responses were congruent with expectations of target presence/absence. Results were modeled under a novel Bayesian signal detection theoretic framework which integrates bottom-up signal propagation with top-down influences, to provide a unified description of the mechanisms underlying perceptual decision and metacognition.

A comparative study of electrical potential sensors and Ag/AgCl electrodes for characterising spontaneous and event related electroencephalagram signals.

BACKGROUND: Electroencephalography (EEG) is still a widely used imaging tool that combines high temporal resolution with a relatively low cost. Ag/AgCl metal electrodes have been the gold standard for non-invasively monitoring electrical brain activity. Although reliable, these electrodes have multiple drawbacks: they suffer from noise, such as offset potential drift, and usability issues, for example, difficult skin preparation and cross-coupling of adjacent electrodes. NEW METHOD: In order to tackle these issues a prototype Electric Potential Sensor (EPS) device based on an auto-zero operational amplifier was developed and evaluated. The EPS is a novel active ultrahigh impedance capacitively coupled sensor. The absence of 1/f noise makes the EPS ideal for use with signal frequencies of ∼10Hz or less. A comprehensive study was undertaken to compare neural signals recorded by the EPS with a standard commercial EEG system. RESULTS: Quantitatively, highly similar signals were observed between the EPS and EEG sensors for both free running and evoked brain activity with cross correlations of higher than 0.9 between the EPS and a standard benchmark EEG system. COMPARISON WITH EXISTING METHOD(S): These studies comprised measurements of both free running EEG and Event Related Potentials (ERPs) from a commercial EEG system and EPS. CONCLUSIONS: The EPS provides a promising alternative with many added benefits compared to standard EEG sensors, including reduced setup time and elimination of sensor cross-coupling. In the future the scalability of the EPS will allow the implementation of a whole head ultra-dense EPS array.

Effect of coenzyme Q10 alone and its combination with metformin on streptozotocin-nicotinamide-induced diabetic nephropathy in rats.

OBJECTIVES: This study was aimed to investigate the therapeutic potential of coenzyme Q10 and its combination with metformin on streptozotocin (STZ)-nicotinamide-induced diabetic nephropathy (DN). MATERIALS AND METHODS: Type 2 diabetes in rats was induced with STZ-nicotinamide. The diabetic rats were treated with coenzyme Q10 (10 mg/kg, p.o.) alone or coenzyme Q10 + metformin. Various parameters of renal function tests such as serum creatinine, urea, uric acid, and markers of oxidative stress such as renal malondialdehyde (MDA) level, superoxide dismutase (SOD), and catalase (CAT) activities were measured. Tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) activity, transforming growth factor-ß (TGF-ß), and nitrite content were estimated in renal tissues. All treated animal were subjected to histopathological changes of kidney. RESULT: Diabetic rats showed a significant reduction in renal function, which was reflected with an increase in serum urea, serum creatinine, uric acid. In addition, STZ-nicotinamide caused renal tubular damage with a higher MDA level, depletion of SOD and CAT activity and glutathione (GSH) level. Moreover, TNF-α, MPO activity, TGF-ß, and nitrite content were significantly increased in diabetic rats, while treatment with coenzyme Q10 or metformin or their combination ameliorate STZ-nicotinamide induced renal damage due to improvement in renal function, oxidative stress, suppression of TNF-α, MPO activity, TGF-ß and nitrite content along with histopathological changes. CONCLUSIONS: This finding suggests that the treatment with coenzyme Q10 or metformin showed significant renoprotective effect against STZ-nicotinamide-induced DN. However, concomitant administration of both showed a better renoprotective effect than coenzyme Q10 or metformin alone treatment.

Modes and models in disorders of consciousness science.

The clinical assessment of non-communicative brain damaged patients is extremely difficult and there is a need for paraclinical diagnostic markers of the level of consciousness. In the last few years, progress within neuroimaging has led to a growing body of studies investigating vegetative state and minimally conscious state patients, which can be classified in two main approaches. Active neuroimaging paradigms search for a response to command without requiring a motor response. Passive neuroimaging paradigms investigate spontaneous brain activity and brain responses to external stimuli and aim at identifying neural correlates of consciousness. Other passive paradigms eschew neuroimaging in favour of behavioural markers which reliably distinguish conscious and unconscious conditions in healthy controls. In order to furnish accurate diagnostic criteria, a mechanistic explanation of how the brain gives rise to consciousness seems desirable. Mechanistic and theoretical approaches could also ultimately lead to a unification of passive and active paradigms in a coherent diagnostic approach. In this paper, we survey current passive and active paradigms available for diagnosis of residual consciousness in vegetative state and minimally conscious patients. We then review the current main theories of consciousness and see how they can apply in this context. Finally, we discuss some avenues for future research in this domain.

The Enactive Torch: A New Tool for the Science of Perception.

The cognitive sciences are increasingly coming to terms with the embodied, embedded, extended, and experiential aspects of the mind. Exemplifying this shift, the enactive approach points to an essential role of goal-directed bodily activity in the generation of meaningful perceptual experience, i.e., sense-making. Here, building on recent insights into the transformative effects of practical tool-use, we make use of the enactive approach in order to provide a definition of an enactive interface in terms of augmented sense-making. We introduce such a custom-built interface, the Enactive Torch, and present a study of its experiential effects. The results demonstrate that the user experience is not adequately captured by any standardly assumed perceptual modality; rather, it is a new feeling that is mediated by the design of the device and shaped by the overall situation of the task. Taken together these findings show that there is much to be gained by synergies between engineering and the cognitive sciences in the creation of new experience-centered technology. We suggest that the guiding principle should be the design of interfaces that serve as a transparent medium for augmenting our natural skills of interaction with the world, instead of requiring conscious attention to the interface as an opaque object in the world.

A study on knowledge, beliefs and attitude towards leprosy in students of Jaipur, Rajasthan.

The objective of this study was to determine the knowledge, beliefs and attitudes regarding leprosy in school students of Jaipur district. A cross-sectional study was conducted from August 2010 to February 2011 on 1199 students (rural and urban) studying in class 10th and above. The findings of this study showed fair knowledge in students about cause, signs and symptoms of leprosy but less knowledge about prevention and treatment of the disease. Myths and beliefs were more prevalent in rural students as compared to urban ones. Both the groups showed positive attitude toward leprosy with 30-50% students showing neutral approach but negative reaction was more in rural students. In conclusion the study highlights to emphasize on health education in students and improving knowledge to develop positive attitude towards leprosy.

Determination of Doxazosin Mesylate in Tablets by RP-HPLC.

A simple, precise and rapid RP-HPLC method was developed for the determination of doxazosin mesylate in pharmaceutical formulations. The method was carried out on a Chromolith RP-C(18) column using a mixture of potassium phosphate buffer and methanol (40:60 v/v) and detection was done at 251 nm. The linearity range was 1-5 µg/ml. The retention time of the drug was 3.8 min. The LOD and LOQ were found to be 0.1 µg/ml and 0.5 µg/ml, respectively.

The WW domain containing E3 ubiquitin protein ligase 1 upregulates ErbB2 and EGFR through RING finger protein 11.

The WW domain containing E3 ubiquitin protein ligase 1 (WWP1) is a homologous to the E6-associated protein C terminus-type E3 ligase frequently overexpressed in human prostate and breast cancers due to gene amplification. Previous studies suggest that WWP1 promotes cell proliferation and survival; however, the mechanism of WWP1 action is still poorly understood. Here, we showed that WWP1 upregulates and maintains erythroblastic leukemia viral oncogene homolog 2 (ErbB2) and epithelial growth factor receptor (EGFR) in multiple cell lines. WWP1 depletion dramatically attenuates the EGF-induced ERK phosphorylation. WWP1 forms a protein complex with RING finger protein 11 (RNF11), a negative regulator of ErbB2 and EGFR. The protein-protein interaction is through the first and third WW domains of WWP1 and the PY motif of RNF11. Although WWP1 is able to ubiquitinate RNF11 in vitro and in vivo, WWP1 neither targets RNF11 for degradation nor changes RNF11's cellular localization. Importantly, inhibition of RNF11 can rescue WWP1 siRNA-induced ErbB2 and EGFR downregulation and growth arrest. Finally, we demonstrated that RNF11 is overexpressed in a panel of prostate and breast cancer cell lines with WWP1 expression. These findings suggest that WWP1 may promote cell proliferation and survival partially through suppressing RNF11-mediated ErbB2 and EGFR downregulation.

Epidemiological and clinical profile of irritable bowel syndrome in India: report of the Indian Society of Gastroenterology Task Force.

AIMS: To study the profile of irritable bowel syndrome (IBS), and the frequency of such symptoms among the general population, in India. METHODS: In this prospective, multi-center study, data were obtained from 2785 patients with chronic lower gastrointestinal symptoms (complainants) with no alarm feature and negative investigations for organic causes visiting physicians at 30 centers, and from 4500 community subjects (non-complainants), using separate questionnaires. RESULTS: Most complainants were middle-aged (mean age 39.4 years) and male (1891; 68%). The common symptoms were: abdominal pain or discomfort (1958; 70%), abdominal fullness (1951; 70%); subjective feeling of constipation (1404 of 2656; 53%), or diarrhea (1252 of 2656, 47%), incomplete evacuation (2134; 77%), mucus with stools (1506; 54%), straining at stools (1271; 46%), epigastric pain (1364; 49%) and milk intolerance (906; 32%). Median stool frequency was similar in patients who felt they had constipation or those who felt they had diarrhea. Information to subtype symptoms using standard criteria was available in 1301 patients; of these, 507 (39%) had constipation-predominant IBS ( 3 3 stools/day) and 744 (57%) had indeterminate symptoms. Among non-complainants, most subjects reported daily defecation frequency of one (2520 [56%]) or two (1535 [34%]). Among non-complainants, 567 (12.6%) reported abdominal pain, 503 (11%) irregular bowel, 1030 (23%) incomplete evacuation, 167 (4%) mucus and 846 (18%) straining at stools; a combination of abdominal pain or discomfort relieved by defecation, and incomplete evacuation was present in 189/4500 (4.2%) community subjects. CONCLUSIONS: Most patients with IBS in India are middle-aged men, and have a sense of incomplete evacuation and mucus with stools. Abdominal pain or discomfort is frequent but not universal. Importantly, stool frequency was similar irrespective of whether the patients felt having constipation or diarrhea. Most (90%) non-complainant subjects had 1 or 2 stools per day; symptoms complex suggestive of IBS was present in 4.2% of community subjects.

Protein-c deficiency presenting with subacute intestinal obstruction due to mesenteric vein thrombosis.

We describe a patient with protein C deficiency who presented with subacute intestinal obstruction due to ischaemic small bowel stricture. The patient also had left sided ileofemoral thrombosis. Venous thrombosis at unusual sites especially if associated with deep vein thrombosis of lower limb warrants a thorough screen for underlying thrombophilia. This, however, is a rare cause for ischaemic small bowel stricture.

Risk Factors of Hepatotoxicity During Anti-tuberculosis Treatment.

BACKGROUND: Antituberculosis treatment (ATT) induced hepato-toxicity is common, but risk factors predicting its development are poorly understood. The present study evaluates the clinical risk factors predicting the development of hepatotoxicity in Indian patients with tuberculosis on antituberculosis treatment. METHODS: Three groups of patients were studied at three service hospitals over a 3 year period from 2000-2002. Patients given ATT were followed up with monthly LFTs. Consecutive patients who developed Liver dysfunction (rise in SGPT > 5 times upper limit of normal) were studied, along with matched controls who did not. Markers for hepatitis B were also noted in these patients once in 6 months. A third group of patients who did not receive ATT but were HBsAg positive, were also similarly followed up. The possible association of age and sex of the patient, alcoholism, unrecognized chronic liver disease, hepatitis B virus carrier status and nutritional status with ATT-induced hepatitis was assessed. Statistical analysis was carried out by Chi square test/Fisher's exact test using WHO provided software Epi Info 6. Sixty-nine patients with ATT-induced hepatotoxicity were prospectively studied. In addition 128 patients on anti-tuberculosis drugs without hepatotoxicity and 39 HBsAg carriers not on ATT were followed up for 1 year. RESULTS: Age, Sex, history of alcohol intake and BMI were not found to be related to development of hepatotoxicity. Presence of HBV infection or an underlying silent chronic liver disease were found to significantly increase the risk of development of ATT-induced hepatotoxicity. Continuation of ATT after development of jaundice was associated with a high fatality rate. It was possible to re-introduce isoniazid in 96% and rifampicin in 88% of patients with ATT induced hepatotoxicity. CONCLUSION: ATT-induced hepatitis is common and is potentially fatal. It is likely to occur in those with underlying silent chronic liver disease, HBV infection and have been given ATT without a definite evidence of tuberculosis. Discontinuation of ATT leads to rapid recovery in most cases and drugs can safely be introduced after recovery in a majority of cases.

Should one vaccinate patients with chronic liver disease for hepatitis A virus in India?

BACKGROUND: Hepatitis A virus (HAV) vaccination is recommended worldwide for patients with chronic liver disease to prevent decompensation due to superinfection with HAV. India being endemic for HAV, the prevalence of pre-existing antibodies against HAV due to subclinical exposure to the virus in childhood among patients with chronic liver disease may be high and, therefore, vaccination may not be needed. However, little data are available on the prevalence of HAV antibody among patients with chronic liver disease in India. METHODS: All patients with chronic liver disease seen at Gastroenterology Center, Army Hospital R and R, New Delhi during the year 2002 and diagnosed to have either chronic liver disease were tested for the presence of IgG anti-HAV antibody in their sera (using a commercial ELISA kit). All patients with acute exacerbation or rapid deterioration of a preexisting chronic liver disease were separately studied for presence of IgM anti-HAV. In addition, a matched number of patients who attended the center due to diseases other than liver disease were also studied as controls. RESULTS: One hundred and eighty seven patients of chronic liver disease and 89 controls were studied. Mean age of these two groups was 38.6 and 42.1 years and 153 (81.8%) and 78 (87.6%) of them were males respectively. Etiology of chronic liver disease was HBV infection in 91(48.7%), HCV infection in 62 (33.2%), autoimmune chronic hepatitis in 3 (1.6%), PBC in seven (3.7%) and cryptogenic 24 (12.8%). Of these 179 (95.7%) patients tested positive for IgG anti-HAV. A total of 37 hospitalisations in 29 patients were noted during the study period due to acute exacerbation of pre-existing chronic liver disease. None of these were positive for IgM anti-HAV, while 28 were positive for IgG anti-HAV. Among the controls, 87 controls (94.6%) were positive IgG anti-HAV. The prevalence of anti-HAV positivity was similar among patients with various etiologies. CONCLUSION: Vaccination against HAV is not routinely required among patients with chronic liver disease in India as there is a very high prevalence of pre-existing antibodies in these patients. HAV superinfection as a cause of acute exacerbation of chronic liver disease was not seen in this.

Reversible segmental portal hypertension--an unusual presentation of abdominal tuberculosis in a renal transplant recipient.

Infections are the commonest cause of morbidity and mortality in renal transplant recipients. In India, tuberculosis is a one such common infection in these patients and presents with protean manifestations. We report here a case of pyrexia of unknown origin (PUO) and segmental portal hypertension in a renal transplant recipient. Search for the cause of portal hypertension revealed abdominal tubercular lymphadenitis. Treatment with anti-tubercular therapy caused regression of segmental portal hypertension.

Role of Biopsy from Gastric Corpus in Diagnosis of Helicobacter pylori Infection in Patients on Acid Suppression Therapy.

There are reports of migration of Helicobacter pylori from the gastric antrum to the proximal stomach following acid suppression therapy. The diagnosis of H pylori infection is usually based on rapid urease test and histology of gastric antral biopsies. 50 consecutive patients of peptic ulcer, 22 on proton pump inhibitors and 28 on histamine-2 receptor antagonists for at least 4 weeks were subjected to biopsies from the gastric corpus in addition to the antrum at the time of upper gastrointestinal endoscopy. H pylori infection was detected in 42 (84%) patients. The diagnosis was established from both antral and corpus biopsies in 34 (68%) and only antrum in 4 (8%). In 4 patients, 3 on proton pump inhibitors and one on H-2 receptor antagonists, H pylori was isolated only from the corpus. The rapid urease test was positive at a mean time of 67.6 minutes from the antrum as compared to 234.6 minutes from the corpus. Testing for H pylori from the antrum alone and not the corpus would have resulted in a false negative result in 8% patients. Biopsy from the gastric antrum should always be combined with biopsy from gastric corpus for the diagnosis of H pylori infection in patients with dyspepsia on acid suppression therapy.