Dissociable Contributions of Basolateral Amygdala and Ventrolateral Orbitofrontal Cortex to Flexible Learning Under Uncertainty.

Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including the highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, the unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach particularly before and after the first reversal that introduces new uncertainty. Here, we examined the roles of ventrolateral OFC (vlOFC) and BLA during reversal learning. Male and female rats were prepared with inhibitory designer receptors exclusively activated by designer drugs targeting projection neurons in these regions and tested on a series of deterministic and probabilistic reversals during which they learned about stimulus identity or side (left or right) associated with different reward probabilities. Using a counterbalanced within-subject design, we inhibited these regions prior to reversal sessions. We assessed initial and pre-/post-reversal changes in performance to measure learning and adjustments to reversals, respectively. We found that inhibition of the ventrolateral orbitofrontal cortex (vlOFC), but not BLA, eliminated adjustments to stimulus-based reversals. Inhibition of BLA, but not vlOFC, selectively impaired action-based probabilistic reversal learning, leaving deterministic reversal learning intact. vlOFC exhibited a sex-dependent role in early adjustment to action-based reversals, but not in overall learning. These results reveal dissociable roles for BLA and vlOFC in flexible learning and highlight a more crucial role for BLA in learning meaningful changes in the reward environment.

Predicting intracranial involvement: Unveiling perineural spread in COVID-19-associated mucormycosis, a novel phenomenon.

This study aimed to investigate the risk factors associated with intracranial involvement in COVID-19-associated mucormycosis (CAM) and to develop a nomogram model for predicting the risk of intracranial involvement, with a specific focus on perineural spread. An ambispective analysis was conducted on 275 CAM patients who received comprehensive treatment. Univariable and multivariable logistic regression analyses were performed to identify independent risk factors, and a nomogram was created based on the results of the multivariable analysis. The performance of the nomogram was evaluated using a receiver operating characteristic (ROC) curve, and the discriminatory capacity was assessed using the area under the curve (AUC). The model's calibration was assessed through a calibration curve and the Hosmer Lemeshow test. In the results, the multivariable logistic regression analysis revealed that age (OR: 1.23, 95% CI 1.06-3.79), HbA1c (OR: 7.168, 95% CI 1.724-25.788), perineural spread (OR: 6.3, 95% CI 1.281-19.874), and the disease stage were independent risk factors for intracranial involvement in CAM. The developed nomogram demonstrated good discriminative capacity with an AUC of 0.821 (95% CI 0.713-0.909) as indicated by the ROC curve. The calibration curve showed that the nomogram was well-calibrated, and the Hosmer Lemeshow test yielded a P-value of 0.992, indicating a good fit for the model. In conclusion, this study found that CAM particularly exhibits perineural spread, which is a predictive factor for intracranial involvement. A nomogram model incorporating age, HbA1c, disease stage, and perineural spread was successfully developed for predicting intracranial involvement in CAM patients in both in-patient and out-patient settings.

Discovery of perineural spread in COVID-19-associated mucormycosis reveals a new predictive model for intracranial complications which is crucial for early intervention.

Assessing the trophic ecology and migration on the exposure of cape petrels and Wilson's storm petrels from Antarctica to perfluoroalkylated substances, trace and major elements.

Chemical pollution is a global concern as contaminants are transported and reach even the remote regions of Antarctica. Seabirds serve as important sentinels of pollution due to their high trophic position and wide distribution. This study examines the influence of migration and trophic ecology on the exposure of two Antarctic seabirds, Wilson's storm petrel (Oceanites oceanicus - Ooc), and Cape petrel (Daption capense - Dca), to chemical elements and perfluoroalkyl substances (PFAS). Our methodology involved assessing the concentration of these pollutants in feather samples obtained from carcasses, offering a practical means for monitoring contamination. Trace and major element concentrations were comparable in both species, suggesting that migratory patterns have a minimal impact on exposure levels. However, Ooc had higher concentration of PFAS compared to Dca (mean, ng g-1dry weight, PFOA: Ooc:0.710, Dca:0.170; PFTrDA: Ooc:0.550, Dca:0.360, and PFTeDA: Ooc:1.01, Dca:0.190), indicating that migration to the more polluted Northern Hemisphere significantly affects PFAS exposure. Furthermore, while no strong associations were found between either trace elements or PFAS and the three stable isotopes (δ13C, δ15N, and δ34S), a negative association was observed between PFUnDA and δ15N, hinting at potential biodilution. The research concludes that the migratory patterns of these seabird species affect their PFAS exposure, underscoring the critical need for further exploration and understanding of these relationships to better inform conservation strategies.

Comparison of depth of electrode insertion between cochleostomy and round window approach: a cadaveric study.

INTRODUCTION: Round window approach and cochleostomy approach can have different depth of electrode insertion during cochlear implantation which itself can alter the audiological outcomes in cochlear implant. OBJECTIVE: The current study was conducted to determine the difference in the depth of electrode insertion via cochleostomy and round widow approach when done serially in same temporal bone. METHODOLOGY: This is a cross-sectional study conducted in the Department of Otorhinolaryngology in conjunction with Department of Anatomy and Department of Diagnostic and Interventional Radiology over a period of 1 year. 12-electrode array insertion was performed via either approach (cochleostomy or round window) in the cadaveric temporal bone. HRCT temporal bone scan of the implanted temporal bone was done and depth of insertion and various cochlear parameters were calculated. RESULT: A total of 12 temporal bones were included for imaging analysis. The mean cochlear duct length was 32.892 mm; the alpha and beta angles were 58.175° and 8.350°, respectively. The mean angular depth of electrode insertion via round window was found to be 325.2° (SD = 150.5842) and via cochleostomy 327.350 (SD = 112.79) degree and the mean linear depth of electrode insertion via round window was found to be 18.80 (SD = 4.4962) mm via cochleostomy 19.650 (SD = 3.8087) mm, which was calculated using OTOPLAN 1.5.0 software. There was a statically significant difference in linear depth of insertion between round window and cochleostomy. Although the angular depth of insertion was higher in CS group, there was no statistically significant difference with round window type of insertion. CONCLUSION: The depth of electrode insertion is one of the parameters that influences the hearing outcome. Linear depth of electrode insertion was found to be more in case of cochleostomy compared to round window approach (p = 0.075) and difference in case of angular depth of electrode insertion existed but not significant (p = 0.529).

Sialic acid blockade in dendritic cells enhances CD8+ T cell responses by facilitating high-avidity interactions.

Sialic acids are negatively charged carbohydrates that cap the glycans of glycoproteins and glycolipids. Sialic acids are involved in various biological processes including cell-cell adhesion and immune recognition. In dendritic cells (DCs), the major antigen-presenting cells of the immune system, sialic acids emerge as important regulators of maturation and interaction with other lymphocytes including T cells. Many aspects of how sialic acids regulate DC functions are not well understood and tools and model systems to address these are limited. Here, we have established cultures of murine bone marrow-derived DCs (BMDCs) that lack sialic acid expression using a sialic acid-blocking mimetic Ac53FaxNeu5Ac. Ac53FaxNeu5Ac treatment potentiated BMDC activation via toll-like receptor (TLR) stimulation without affecting differentiation and viability. Sialic acid blockade further increased the capacity of BMDCs to induce antigen-specific CD8+ T cell proliferation. Transcriptome-wide gene expression analysis revealed that sialic acid mimetic treatment of BMDCs induces differential expression of genes involved in T cell activation, cell-adhesion, and cell-cell interactions. Subsequent cell clustering assays and single cell avidity measurements demonstrated that BMDCs with reduced sialylation form higher avidity interactions with CD8+ T cells. This increased avidity was detectable in the absence of antigens, but was especially pronounced in antigen-dependent interactions. Together, our data show that sialic acid blockade in BMDCs ameliorates maturation and enhances both cognate T cell receptor-MHC-dependent and independent T cell interactions that allow for more robust CD8+ T cell responses.

Unequal lives: a sociodemographic analysis of COVID-19 transmission and mortality in India.

OBJECTIVES: Existing socio-economic inequalities shape, in very particular and measurable ways, the differential impact that a disease has on different sections of the same society. This is particularly true of COVID-19, which has rapidly exhausted the public health system in India, and magnified the gradient of vulnerability in an underserved populace. Using publicly available data, we have aimed to deconstruct this gradient into individual variables of inequality and quantify their impact on the transmission and mortality outcomes of COVID-19 in India. STUDY DESIGN: Sociodemographic analysis. METHODS: We quantify doubling times and case fatality ratios for all districts in India, then correlate them to 20 variables of socio-economic vulnerability and demographic structure. Variables that exhibit persistent correlation are then analysed using multivariate beta regression models to validate their impact on COVID-19 outcomes in India. RESULTS: The transmission of COVID-19 in India is enhanced by the lack of access to indoor latrines, drainage facilities, electricity, and proximate sources of drinking water. Transmission is slowed by the presence of an elderly population. Fatality rates relate negatively to an area's medical infrastructure and the presence of a college-educated populace. CONCLUSIONS: An interactive matrix of social inequalities, cultural practices, and behavioural patterns determines the path of COVID-19 through a community. Specific variables exhibit patterns of persistent vulnerability; others indicate a resistance to infection and mortality. This body of evidence, when incorporated into policy design, may lead to localised, need-sensitive models of intervention, both for preventive measures and medical care.

Bioremediation: an alternative approach for detoxification of polymers from the contaminated environment.

The industries and metropolitan wastes produced by anthropogenic activities are of great concern for nature as it causes soil contamination and deteriorate the environment. Plastic utilization is rapidly enhancing globally with passing days that last for a more extended period in the environment due to slow decomposition and natural degradation. Excessive use of polymer has risked the life of both marine, freshwater and terrestrial organisms. Lack of proper waste management and inappropriate disposal leads to environmental threats. Bioremediation processes involve microbes such as fungi, bacteria, etc. which contribute a crucial role in the breakdown of plastics. Extremophiles secrete extremozymes that are functionally active in extreme conditions and are highly crucial for polymer disaggregation in those conditions.

Thalamohippocampal atrophy in focal epilepsy of unknown cause at the time of diagnosis.

BACKGROUND AND PURPOSE: Patients with chronic focal epilepsy may have atrophy of brain structures important for the generation and maintenance of seizures. However, little research has been conducted in patients with newly diagnosed focal epilepsy (NDfE), despite it being a crucial point in time for understanding the underlying biology of the disorder. We aimed to determine whether patients with NDfE show evidence of volumetric abnormalities of subcortical structures. METHODS: Eighty-two patients with NDfE and 40 healthy controls underwent magnetic resonance imaging scanning using a standard clinical protocol. Volume estimation of the left and right hippocampus, thalamus, caudate nucleus, putamen and cerebral hemisphere was performed for all participants and normalised to whole brain volume. Volumes lower than two standard deviations below the control mean were considered abnormal. Volumes were analysed with respect to patient clinical characteristics, including treatment outcome 12 months after diagnosis. RESULTS: Volume of the left hippocampus (p(FDR-corr)  = 0.04) and left (p(FDR-corr)  = 0.002) and right (p(FDR-corr)  = 0.04) thalamus was significantly smaller in patients relative to controls. Relative to the normal volume limits in controls, 11% patients had left hippocampal atrophy, 17% had left thalamic atrophy and 9% had right thalamic atrophy. We did not find evidence of a relationship between volumes and future seizure control or with other clinical characteristics of epilepsy. CONCLUSIONS: Volumetric abnormalities of structures known to be important for the generation and maintenance of focal seizures are established at the time of epilepsy diagnosis and are not necessarily a result of the chronicity of the disorder.

Assessment of heavy metal status and identification of source in soils under intensive vegetable growing areas of Brahmaputra valley, North East India.

This study investigated the content of Cd, Pb, Cr, and Ni in the soils of intensive vegetable growing areas of the Brahmaputra valley, North East India, to assess their status and detect any buildup of metals due to long-term and continuous application of agrochemicals and organic manures. The content of heavy metals was determined in eighty composite surface soil samples (0-20 cm) collected from eight different locations of the valley having a history of more than forty years of vegetable production. This finding is novel as no comprehensive investigation has been done till date in respect of the content of heavy metals in the intensive vegetable growing areas of Brahmaputra valley. The locations are considered free from any pollution caused by industrial effluent or urbanization processes. The investigational data showed that the content of Cd, Pb, Cr, and Ni in the soils ranged from 0.43 to 3.24, 6.00 to 22.90, 3.00 to 15.24, and 3.30 to 14.30 mg kg-1, respectively. The overall mean values of the heavy metals showed a decreasing order of Pb (14.79 mg kg-1) > Cr (8.87 mg kg-1) > Ni (8.37 mg kg-1) > Cd (1.43 mg kg-1). The findings of the study indicated significant enrichment of the metals in the surface soils over the local background values of the elements measured in the C horizon. Though the concentrations of Pb, Cr, and Ni of the soils were well below the reference levels used in different countries, Cd showed distinctly higher value with maximum enrichment level. The soils were categorized as slightly to moderately polluted based on different pollution indices. Based on the ecological risk index, soils were in the low-risk category, but in respect of Cd, most of the soils fell under the moderately risky category. Multivariate analysis suggested the predominance of lithogenic influence on the content of Pb, Ni, and Cr while Cd content bears a distinct signature of the anthropogenic source. The buildup of Cd in the studied soils is a matter of critical concern and needs proper monitoring and management strategies to avoid any potential detrimental effect on soil, crop, and human health.

Is four-dimensional CT angiography as effective as digital subtraction angiography in the detection of the underlying causes of intracerebral haemorrhage: a systematic review.

PURPOSE: To determine whether the sensitivity and specificity of four-dimensional CTA (4D-CTA) are equivalent to digital subtraction angiography (DSA) in the detection of underlying vascular abnormalities in patients with intracerebral haemorrhage (ICH). METHODS: A systematic review of studies comparing 4D-CTA with DSA in the detection of the underlying structural causes of ICH was performed on the literature published between 1998 and 2019. RESULTS: We identified a total of 237 articles from PubMed, SCOPUS and Web of Science using the following Medical Subject Headings (MeSH) terms: primary intracerebral haemorrhage, 4D-CTA, DSA, cerebral haemorrhage, angiography, digital subtraction, arteriovenous malformations, 4D, CTA, dynamic-CTA and time-resolved CTA. Following the removal of duplicate publications and articles failing to meet our inclusion criteria, there were four articles potentially viable for analysis. Therefore, there were not sufficient studies to provide a statistically meaningful meta-analysis. CONCLUSION: The review of current literature has demonstrated that there are few published studies comparing 4D-CTA with DSA in spontaneous ICH, with only four suitable studies identified for potential analysis. However, due to the restricted number of patients and high sensitivity and specificity of 3 studies (100%), performing a meta-analysis was not meaningful. Qualitative analysis of the data concluded that 4D-CTA has the diagnostic potential to replace invasive DSA in certain cases with vascular abnormalities. However, further research studies directly comparing 4D-CTA with DSA using larger prospective patient cohorts are required to strengthen the evidence base.

Modeling the effect of area deprivation on COVID-19 incidences: a study of Chennai megacity, India.

OBJECTIVES: Socio-economic inequalities may affect coronavirus disease 2019 (COVID-19) incidence. The goal of the research was to explore the association between deprivation of socio-economic status (SES) and spatial patterns of COVID-19 incidence in Chennai megacity for unfolding the disease epidemiology. STUDY DESIGN: This is an ecological (or contextual) study for electoral wards (subcities) of Chennai megacity. METHODS: Using data of confirmed COVID-19 cases from May 15, 2020, to May 21, 2020, for 155 electoral wards obtained from the official website of the Chennai Municipal Corporation, we examined the incidence of COVID-19 using two count regression models, namely, Poisson regression (PR) and negative binomial regression (NBR). As explanatory factors, we considered area deprivation that represented the deprivation of SES. An index of multiple deprivations (IMD) was developed to measure the area deprivation using an advanced local statistic, geographically weighted principal component analysis. Based on the availability of appropriately scaled data, five domains (i.e., poor housing condition, low asset possession, poor availability of WaSH services, lack of household amenities and services, and gender disparity) were selected as components of the IMD in this study. RESULTS: The hot spot analysis revealed that area deprivation was significantly associated with higher incidences of COVID-19 in Chennai megacity. The high variations (adjusted R2: 72.2%) with the lower Bayesian Information Criteria (BIC) (124.34) and Akaike's Information Criteria (AIC) (112.12) for NBR compared with PR suggests that the NBR model better explains the relationship between area deprivation and COVID-19 incidences in Chennai megacity. NBR with two-sided tests and P <0.05 were considered statistically significant. The outcome of the PR and NBR models suggests that when all other variables were constant, according to NBR, the relative risk (RR) of COVID-19 incidences was 2.19 for the wards with high housing deprivation or, in other words, the wards with high housing deprivation having 119% higher probability (RR = e0.786 = 2.19, 95% confidence interval [CI] = 1.98 to 2.40), compared with areas with low deprivation. Similarly, in the wards with poor availability of WaSH services, chances of having COVID-19 incidence was 90% higher than in the wards with good WaSH services (RR = e0.642 = 1.90, 95% CI = 1.79 to 2.00). Spatial risks of COVID-19 were predominantly concentrated in the wards with higher levels of area deprivation, which were mostly located in the northeastern parts of Chennai megacity. CONCLUSIONS: We formulated an area-based IMD, which was substantially related to COVID-19 incidences in Chennai megacity. This study highlights that the risks of COVID-19 tend to be higher in areas with low SES and that the northeastern part of Chennai megacity is predominantly high-risk areas. Our results can guide measures of COVID-19 control and prevention by considering spatial risks and area deprivation.

An Open Label Prospective Study on Evaluation of Safety and Efficacy of Cilnidipine Over Amlodipine in Stage 1 Hypertensive Patients.

Background Calcium channel blockers are considered the first line drug over renin-angiotensinaldosterone system inhibitor in black population and with renin-angiotensinaldosterone system inhibitor in non-black population with Hypertension. Amlodipine has longer biological half life and lower potential to stimulate SNS. But, is associated with reflex tachycardia and pedal oedema. Cilnidipine has potent inhibitory both on voltage gated L-type and N-type calcium channels with better anti-proteinuric effect and good tolerability. Hence, our study compared the efficacy, safety and compliance of cilnidipine over amlodipine in Stage 1 hypertensive subjects. Objective To find out antihypertensive and renoprotective effect of cilnidipine. Method The study was open-label, single centre, prospective, parallel design, randomized controlled was done in Outdoor Patient Department (OPD) of Medicine and Department of Pharmacology in Burdwan Medical College and Hospital (BMCH). Patients with stage 1 HTN received cilnidipine while the other group received amlodipine. There were 4 follow-up visits for each participant consisting of baseline, 1 week, 6 weeks and after 12 weeks. Clinical parameters including pulse rate, blood pressure and ankle oedema noted also laboratory investigations were done. Safety parameters with adverse events and compliance by traditional pill count method. Result Blood pressure was effectively decreased by both amlodipine and cilnidipine. Cilnidipine significantly decreased Pulse Rate while amlodipine increased it and the difference in Pulse Rate comparing both the groups was statistically significant. None of the ADRs were statistically significant except pedal oedema. Pedal oedema was noted only in amlodipine arm and was statistically significant. Compliance to both the drugs was excellent. Total cost of therapy was higher with cilnidipine. Conclusion Though amlodipine is preferred drug, cilnidipine should be a better alternative when we consider subjects with sympathetic over activity, proteinuria or pedal oedema.

Post-chemotherapy target volumes are safe as boost volume for intact breast radiotherapy in locally advanced breast cancer.

PURPOSE: The purpose of our study is to evaluate the challenges in identification of postoperative complexes (POC), the utility of clips in delineation of clinical target volume for boost in LABC downstaged with neoadjuvant chemotherapy (NACT) and to correlate this with patterns of recurrence. METHODS AND MATERIALS: LABC patients who underwent NACT followed by BCS and radiotherapy (2007-2014) were the subject of our analysis. The data on visibility and characteristics of postoperative cavity (POC), concordance of its volume with clip volume on radiation planning scan were retrieved. A 1 cm margin beyond POC was delineated as a clinical target volume (CTV). Postoperative whole breast and supraclavicular radiotherapy (50 Gy/25fractions/5wk or 42.4 Gy/16#/3 wk) followed by boost (10-16 Gy/5-8#/1-1.5wk) were delivered. Patterns of recurrence were evaluated. RESULTS: Out of 60 patients, 28.3% patients had stage II disease and 71.7% had stage III disease. 25% patients achieved pathological CR (complete response). The median POC volume was 30 cc and the median clip volume was 40 cc. The concordance of POC volume with clip volume was seen in 80%. Clips served as a good surrogate for POC in 80% of patients. At a median follow-up of 65 months (IQ range 32-84 months), and a lost to follow-up rate of 11.6 %, 3.3% (n = 2) patients had local recurrence (LR) and 8.3% (n = 5) had regional recurrence (LRR) in the supraclavicular region. CONCLUSIONS: Delineation of post NACT excision cavity as POC for boost radiotherapy is safe. Clips serve as a good surrogate for CTV delineation in 75% patients.

Correction: Determining pathogenicity of genetic variants in hypertrophic cardiomyopathy: importance of periodic reassessment.

When this article was published, the Supplementary Material was omitted. The files are now provided in the online version of the article. The publisher regrets the error.

Argon plasma coagulation is an effective treatment for chronic radiation proctitis in gynaecological malignancy: an observational study.

AIM: Chronic radiation proctitis (CRP) develops in 5-15% of patients after pelvic radiation therapy, with rectal bleeding being the main symptom. Reports suggest that argon plasma coagulation (APC) can be an effective therapy for CRP following radiotherapy for prostate cancer, but there is less information about how useful it is after radiotherapy for gynaecological malignancy. The aim of this work therefore was to study the efficacy of APC for CRP after radiotherapy for gynaecological malignancy. METHOD: This was a prospective study of consecutive patients with CRP following radiotherapy for gynaecological malignancy at IPGME&R, SDLD, Kolkata, India; symptoms included rectal bleeding grade (RBG) ≥ 2. APC was performed at monthly intervals to a maximum of four treatment sessions. Severity of disease at baseline was graded (endoscopically) by the total colonoscopic severity score (TCSS) and treatment response was assessed by reduction in RBG from ≥ 2 to ≤ 1 measured at > 6 months after cessation of APC. RESULTS: Seventy patients [90% with cervical cancer, 10% with endometrial cancer; mean age 51.93 ± 9.15 years; median RBG 3 (range 2-4)] received APC. Seven patients died due to underlying malignancy and seven patients were lost to follow-up. Fifty-six (85.7%) patients responded to therapy after a median of 2 (range 1-4) treatment sessions. Multivariate analysis demonstrated that a lower haemoglobin at the start of treatment predicted failure of therapy (P < 0.05). CONCLUSION: APC is an effective management option for CRP in female patients with gynaecological malignancy. However, the more anaemic the patient the less likely it is to be successful.

Neuroradiological findings in patients with "non-lesional" focal epilepsy revealed by research protocol.

AIM: To evaluate whether a dedicated epilepsy research protocol with expert image re-evaluation can increase identification of patients with lesions and to attempt to ascertain the potential reasons why lesions were not identified previously on earlier clinical magnetic resonance imaging (MRI). MATERIALS AND METHODS: Forty-three patients (26 female) with focal refractory epilepsy who had failed at least two trials of anti-epileptic drug treatments were studied. Patients were recruited prospectively into the study if previous clinical MRI was deemed to be "non-lesional" by the clinicians involved in the initial assessment. Three-dimensional (3D) T1-weighted (T1W), T2-weighted (T2W), T2 fluid-attenuated inversion recovery (T2-FLAIR) sequences, and two-dimensional (2D) coronal T1-/T2W FLAIR were assessed by a neuroradiologist, including the previous clinical MRI of individual patients. RESULTS: Twenty-nine or 43 (67%) patients remained MRI-negative after scanning with the epilepsy-dedicated protocol and image reappraisal by expert consultant neuroradiologists; however, 14/43 (33%) patients were found to have potentially epileptogenic brain lesions. The lesion that most frequently escaped the attention of clinicians was hippocampal sclerosis (nine cases, of which two had an additional focal cortical dysplasia, FCD), followed by single FCDs (two cases), and others including gliosis, encephalocoele, and amygdala enlargement (one case each). Eleven of the 14 (79%) previously "non-lesional" patients had electroencephalogram (EEG) imaging-concordant localisation features, rendering them potential candidates for resective surgery. CONCLUSIONS: The primary factors explaining the newly identified lesions were the choice of MRI sequences, imaging parameters, data quality, lesion not reported (human factor), and loss of information through incomplete documentation. It is important for all clinicians to proceed meticulously in the detailed assessment of epilepsy-dedicated in-vivo MRI and discuss difficult patient cases in multidisciplinary team meetings.

Interaction of α-crystallin with some small molecules and its effect on its structure and function.

BACKGROUND: α-Crystallin acts like a molecular chaperone by interacting with its substrate proteins and thus prevents their aggregation. It also interacts with various kinds of small molecules that affect its structure and function. SCOPE OF REVIEW: In this article we will present a review of work done with respect to the interaction of ATP, peptide generated from lens crystallin and other proteins and some bivalent metal ions with α-crystallin and discuss the role of these interactions on its structure and function and cataract formation. We will also discuss the interaction of some hydrophobic fluorescence probes and surface active agents with α-crystallin. MAJOR CONCLUSIONS: Small molecule interaction controls the structure and function of α-crystallin. ATP and Zn+2 stabilize its structure and enhance chaperone function. Therefore the depletion of these small molecules can be detrimental to maintenance of lens transparency. However, the accumulation of small peptides due to protease activity in the lens can also be harmful as the interaction of these peptides with α-crystallin and other crystallin proteins in the lens promotes aggregation and loss of lens transparency. The use of hydrophobic probe has led to a wealth of information regarding the location of substrate binding site and nature of chaperone-substrate interaction. Interaction of surface active agents with α-crystallin has helped us to understand the structural stability and oligomeric dissociation in α-crystallin. GENERAL SIGNIFICANCE: These interactions are very helpful in understanding the mechanistic details of the structural changes and chaperone function of α-crystallin. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.

Effect of Curcumin Addition on the Adsorption and Transport of a Cationic Dye across DPPG-POPG Liposomes Probed by Second Harmonic Spectroscopy.

The effect of addition of curcumin on the adsorption and transport characteristics of a cationic dye, LDS+, across negatively charged bilayers composed of POPG and DPPG lipids were investigated by the interface selective second harmonic (SH) spectroscopic technique. Curcumin induced changes in the SH electric field signal of the LDS+ ions (E2ω (LDS+)) were observed to depend critically on the bilayer acyl chain saturation/unsaturation ratio (S/U). Following earlier works, the increase in the E2ω (LDS+) signal is attributed to the release of the Na+ counterions present in the head group region of the bilayer by curcumin and the decay of the E2ω (LDS+) signal is attributed to the bilayer intercalated state of curcumin. While the changes observed in the E2ω (LDS+) signal in the presence of POPG liposomes were consistent with our earlier study ( Varshney, G. K. et al. Langmuir , 2016 , 32 , 10415 - 10421 ), they were significantly different for DPPG liposomes, following curcumin addition. While the increase in the E2ω (LDS+) signal in the presence of POPG liposomes, is marginal (∼10-20%) and instantaneous (<1 s) followed by a rapid decay (completed within ∼100 s), in the presence of DPPG liposomes it was observed to increase slowly and at saturation shows a substantial increase (100-200%), following curcumin addition. When liposomes consisting of a mixture of POPG and DPPG lipids are used, curcumin induced kinetic characteristics of the E2ω (LDS+) signal showed a mixture of the individual kinetic characteristics observed for the unsaturated (POPG) and saturated (DPPG) liposomes. The observed kinetic trends of the E2ω (LDS+) signal following curcumin addition are explained on the basis of the relative strength of the Na+-POPG and Na+-DPPG interaction. Higher ordering of the lipid acyl chain region in DPPG liposome makes the Na+-DPPG interaction much stronger than the Na+-POPG interaction. Further, it is proposed that, in POPG-DPPG liposomes, individual domains of POPG and DPPG lipids exist at low temperature as suggested by the observed temperature dependent kinetic characteristics of the E2ω (LDS+) signal following curcumin addition. These domains are dependent on the S/U ratio and phase state of the bilayer. The gel phase was observed to be more conducive for individual domain formation. Results presented in this work not only support the notion that biological activity of curcumin is associated with its bilayer altering properties, but more interestingly it provides a qualitative insight about how bilayer phase separation can be achieved by modulating the hydrophobic interactions between the lipid acyl chains.

Expression dynamics of HSP70 during chronic heat stress in Tharparkar cattle.

Six male Tharparkar cattle aged 2-3 years were selected for the study. The animals were acclimatized in the psychrometric chamber at thermoneutral zone (TNZ) for 15 days and then exposed to 42 °C temperature up to 23 days followed by 12 days of recovery period. Physiological responses were estimated, and peripheral blood mononuclear cells (PBMCs) were isolated at TNZ on day 1, day 5, and day 12; after 6 h of heat stress exposure on day 16 to day 20, day 25, day 30, day 32, day 34, day 36, and day 38; and a recovery period on day 45 and day 50. The PBMCs were cultured to study the effect of thermal challenge on HSP70 messenger RNA (mRNA) expression pattern at different temperature-time combinations. The mRNA and protein expression of HSP70 in PBMCs along with serum extracellular HSP70 (eHSP70) was increased (P < 0.05) and showed two peaks on day 17 and day 32 (2nd and 17th days of thermal challenge, respectively). The HSP70 mRNA expression was increased (P < 0.05) in a temperature- and time-dependent manner in heat stress challenge treatment as compared to control in cultured PBMCs. HSP70 expression was found to be higher (P < 0.05) after 10 days of heat exposure (corresponds to chronic heat stress) as compared to the first 5 days of heat stress (corresponds to short-term heat stress) and control period at TNZ. The present findings indicate that HSP70 is possibly involved in heat stress adaptive response in Tharparkar cattle and the biphasic expression pattern may be providing a second window of protection during chronic heat stress.

Effect of Bilayer Partitioning of Curcumin on the Adsorption and Transport of a Cationic Dye Across POPG Liposomes Probed by Second-Harmonic Spectroscopy.

The effect of Curcumin partitioning into the bilayer during the adsorption and transport of a cationic dye, LDS, across a negatively charged POPG bilayer was investigated by the interface-selective second-harmonic (SH) spectroscopic technique. The intensity of SH electric field (E2ω) arising due to LDS adsorbed on the outer bilayer of the POPG liposome was observed to increase instantaneously (<1 s) following the addition of Curcumin. The fractional increase in the SH electric field (Ef2ω) and the bilayer transport rates (kT) of LDS were studied with respect to the pH of the solution and also with the Curcumin content in the lipid bilayer. Results obtained indicate that compared with the anionic form of the drug, its neutral form is more conducive of increasing the Ef2ω of LDS. With increasing Curcumin content in the lipid bilayer, two distinct regimes could be observed in terms of Ef2ω and kT values of LDS. For Curcumin:Lipid (C/L) ratio ≤0.02, the Ef2ω of LDS increases rapidly, while kT remains unchanged; and for C/L ratio ≥0.02, the Ef2ω values remains more or less constant, while there is a significant (∼40 times) increase followed by a modest increase in the kT values of LDS. The observed results support an earlier two-state binding model of Curcumin with the POPG bilayer. In addition, it is further proposed that at low C/L ratio Curcumin binds to the surface of the bilayer replacing the counterions (Na+) bound to the lipid head groups, which changes the bilayer surface charge density, thereby causing more LDS cations to adsorb on the bilayer surface. At high C/L ratio, Curcumin intercalates within the hydrophobic domain of the bilayer, altering its hydrophobicity and inducing enhanced transport of the LDS cation. Results presented in this work provide further insights into how Curcumin alters bilayer properties when it partitions from the aqueous to the bilayer phase.