Comparison of Clinical Outcomes of Implantation of Foldable Hydrophobic Acrylic Intraocular Lens With and Without Heparin Surface Modification in Indian Diabetic Patients.

Background This study aimed to compare the clinical outcomes of a heparin surface-modified (HSM) hydrophobic acrylic foldable intraocular lens (IOL) (CT LUCIA 601PY) and non-heparin-modified hydrophobic acrylic foldable IOL (AcrySof IQ SN60WF) in diabetic patients undergoing phacoemulsification. Methodology This randomized, single-surgeon, double-masked controlled trial was conducted at Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi. In this randomized controlled trial, 100 eyes of 100 diabetic patients with or without mild-to-moderate diabetic retinopathy were enrolled (HSM IOL, n = 50; non-HSM IOL, n = 50). Outcome measures were aqueous flare, visual acuity, and anterior chamber depth (ACD). These were measured preoperatively as well as one day, one week, one month, three months, six months, and one year postoperatively. Results The HSM IOL group had significantly lower anterior chamber aqueous flare values (photon count/ms) than the non-HSM IOL group on postoperative day one (9.97 ± 5.2 vs. 17.56 ± 11.3, p < 0.001), postoperative week one (11.47 ± 7.78 vs. 17.06 ± 9.4, p = 0.02), and postoperative month three (7.7 ± 4.1 vs. 12.5 ± 5.6, p = 0.004) of phacoemulsification. The corrected distance visual acuity (CDVA) was significantly better in the HSM IOL group on postoperative day one (uncorrected distance visual acuity: p = 0.022; CDVA; p = 0.005), but there was no significant difference at any other follow-ups. ACD was significantly longer in the HSM IOL group at all follow-ups. Conclusions The implantation of HSM IOL resulted in significantly lower inflammatory reactions in the early postoperative period in diabetics.

A Recruitment Maneuver After Apnea Testing Improves Oxygenation and Reduces Atelectasis in Organ Donors After Brain Death.

BACKGROUND: Hypoxemia is the main modifiable factor preventing lungs from being transplanted from organ donors after brain death. One major contributor to impaired oxygenation in patients with brain injury is atelectasis. Apnea testing, an integral component of brain death declaration, promotes atelectasis and can worsen hypoxemia. In this study, we tested whether performing a recruitment maneuver (RM) after apnea testing could mitigate hypoxemia and atelectasis. METHODS: During the study period, an RM (positive end-expiratory pressure of 15 cm H2O for 15 s then 30 cm H2O for 30 s) was performed immediately after apnea testing. We measured partial pressure of oxygen, arterial (PaO2) before and after RM. The primary outcomes were oxygenation (PaO2 to fraction of inspired oxygen [FiO2] ratio) and the severity of radiographic atelectasis (proportion of lung without aeration on computed tomography scans after brain death, quantified using an image analysis algorithm) in those who became organ donors. Outcomes in RM patients were compared with control patients undergoing apnea testing without RM in the previous 2 years. RESULTS: Recruitment maneuver was performed in 54 patients after apnea testing, with a median immediate increase in PaO2 of 63 mm Hg (interquartile range 0-109, p = 0.07). Eighteen RM cases resulted in hypotension, but none were life-threatening. Of this cohort, 37 patients became organ donors, compared with 37 donors who had apnea testing without RM. The PaO2:FiO2 ratio was higher in the RM group (355 ± 129 vs. 288 ± 127, p = 0.03), and fewer had hypoxemia (PaO2:FiO2 ratio < 300 mm Hg, 22% vs. 57%; p = 0.04) at the start of donor management. The RM group showed less radiographic atelectasis (median 6% vs. 13%, p = 0.045). Although there was no difference in lungs transplanted (35% vs. 24%, p = 0.44), both better oxygenation and less atelectasis were associated with a higher likelihood of lungs being transplanted. CONCLUSIONS: Recruitment maneuver after apnea testing reduces hypoxemia and atelectasis in organ donors after brain death. This effect may translate into more lungs being transplanted.

Early automated cerebral edema assessment following endovascular therapy: impact on stroke outcome.

BACKGROUND: Cerebral edema (CED) is associated with poorer outcome in patients with acute ischemic stroke (AIS). The aim of the study was to investigate the factors contributing to greater early CED formation in patients with AIS who underwent endovascular therapy (EVT) and its association with functional outcome. METHODS: We conducted a multicenter cohort study of patients with an anterior circulation AIS undergoing EVT. The volume of cerebrospinal fluid (CSF) was extracted from baseline and 24-hour follow-up CT using an automated algorithm. The severity of CED was quantified by the percentage reduction in CSF volume between CT scans (∆CSF). The primary endpoint was a shift towards an unfavorable outcome, assessed by modified Rankin Scale (mRS) score at 3 months. Multivariable ordinal logistic regression analyses were performed. The ∆CSF threshold that predicted unfavorable outcome was selected using receiver operating characteristic curve analysis. RESULTS: We analyzed 201 patients (mean age 72.7 years, 47.8% women) in whom CED was assessable for 85.6%. Higher systolic blood pressure during EVT and failure to achieve modified Thrombolysis In Cerebral Infarction (mTICI) 3 were found to be independent predictors of greater CED. ∆CSF was independently associated with the probability of a one-point worsening in the mRS score (common odds ratio (cOR) 1.05, 95% CI 1.03 to 1.08) after adjusting for age, baseline mRS, National Institutes of Health Stroke Scale (NIHSS), and number of passes. Displacement of more than 25% of CSF was associated with an unfavorable outcome (OR 6.09, 95% CI 3.01 to 12.33) and mortality (OR 6.72, 95% CI 2.94 to 15.32). CONCLUSIONS: Early CED formation in patients undergoing EVT was affected by higher blood pressure and incomplete reperfusion. The extent of early CED, measured by automated ∆CSF, was associated with worse outcomes.

Cholesterol Absorption Inhibition by Some Nutraceuticals.

Hyperlipidemia, characterized by elevated levels of lipids in the blood, represents a major risk factor for cardiovascular diseases, a leading cause of morbidity and mortality worldwide. Conventional pharmacological interventions have been effective in managing hyperlipidemia, but concerns about side effects and long-term use have prompted interest in alternative approaches, particularly the use of nutraceuticals. This comprehensive review aims to summarize and critically evaluate the current body of knowledge surrounding the role of nutraceuticals in the management of hyperlipidemia. We provide an overview of the different classes of nutraceuticals, including plant sterols, omega-3 fatty acids, soluble fiber, antioxidants, and various herbal extracts, which have been investigated for their lipid-lowering properties. The mechanisms of action of these nutraceuticals are discussed, highlighting their ability to modulate lipid metabolism, reduce oxidative stress, and promote cardiovascular health. Furthermore, we review the results of clinical trials and epidemiological studies that have assessed the efficacy of nutraceutical interventions in lowering cholesterol levels, improving lipid profiles, and reducing the risk of cardiovascular events. In addition to their lipid-lowering effects, we examine the safety profile, dosage recommendations, and potential interactions of nutraceuticals with conventional lipid-lowering medications. We also address the importance of patient adherence to dietary and lifestyle modifications in conjunction with nutraceutical supplementation. While nutraceuticals offer a promising avenue for managing hyperlipidemia, we emphasize the need for further research to establish evidence-based guidelines for their use in clinical practice. Challenges related to standardization, quality control, and regulatory considerations are also discussed. In conclusion, this comprehensive review provides valuable insights into the potential of nutraceuticals as adjunctive or alternative therapies for managing hyperlipidemia. While further research is needed, the accumulating evidence suggests that nutraceuticals can play a valuable role in promoting cardiovascular health and reducing the burden of hyperlipidemia- related diseases.

Rho GTPase signaling and mDia facilitate endocytosis via presynaptic actin.

Neurotransmission at synapses is mediated by the fusion and subsequent endocytosis of synaptic vesicle membranes. Actin has been suggested to be required for presynaptic endocytosis but the mechanisms that control actin polymerization and its mode of action within presynaptic nerve terminals remain poorly understood. We combine optical recordings of presynaptic membrane dynamics and ultrastructural analysis with genetic and pharmacological manipulations to demonstrate that presynaptic endocytosis is controlled by actin regulatory diaphanous-related formins mDia1/3 and Rho family GTPase signaling in mouse hippocampal neurons. We show that impaired presynaptic actin assembly in the near absence of mDia1/3 and reduced RhoA activity is partly compensated by hyperactivation of Rac1. Inhibition of Rac1 signaling further aggravates impaired presynaptic endocytosis elicited by loss of mDia1/3. Our data suggest that interdependent mDia1/3-Rho and Rac1 signaling pathways cooperatively act to facilitate synaptic vesicle endocytosis by controlling presynaptic F-actin.

Regio- and Stereoselective Intermolecular 1,2-Difunctionalization of Terminal Alkynes: An Approach to Access (Z)-ß-Amidovinylsulfones.

We have developed the first I2/base-catalyzed regio- and stereoselective intermolecular ß-amidosulfonylation of terminal alkynes using sodium sulfinates and quinoxalinone derivatives. The present methodology is compatible with a broad spectrum of various heterocyclic amides, terminal alkynes, and sodium sulfinates. It provides rapid access to valuable (Z)-ß-amidovinyl sulfones at mild conditions. Moreover, the synthetic application of this methodology was demonstrated by the late-stage functionalization of numerous bioactive molecules.

Feasibility of mitigation measures for agricultural greenhouse gas emissions in the UK. A systematic review.

The UK Government has set an ambitious target of achieving a national "net-zero" greenhouse gas economy by 2050. Agriculture is arguably placed at the heart of achieving net zero, as it plays a unique role as both a producer of GHG emissions and a sector that has the capacity via land use to capture carbon (C) when managed appropriately, thus reducing the concentration of carbon dioxide (CO2) in the atmosphere. Agriculture's importance, particularly in a UK-specific perspective, which is also applicable to many other temperate climate nations globally, is that the majority of land use nationwide is allocated to farming. Here, we present a systematic review based on peer-reviewed literature and relevant "grey" reports to address the question "how can the agricultural sector in the UK reduce, or offset, its direct agricultural emissions at the farm level?" We considered the implications of mitigation measures in terms of food security and import reliance, energy, environmental degradation, and value for money. We identified 52 relevant studies covering major foods produced and consumed in the UK. Our findings indicate that many mitigation measures can indeed contribute to net zero through GHG emissions reduction, offsetting, and bioenergy production, pending their uptake by farmers. While the environmental impacts of mitigation measures were covered well within the reviewed literature, corresponding implications regarding energy, food security, and farmer attitudes towards adoption received scant attention. We also provide an open-access, informative, and comprehensive dataset for agri-environment stakeholders and policymakers to identify the most promising mitigation measures. This research is of critical value to researchers, land managers, and policymakers as an interim guideline resource while more quantitative evidence becomes available through the ongoing lab-, field-, and farm-scale trials which will improve the reliability of agricultural sustainability modelling in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s13593-023-00938-0.

Genome-wide association studies for earliness, MYMIV resistance, and other associated traits in mungbean (Vigna radiata L. Wilczek) using genotyping by sequencing approach.

Yellow mosaic disease (YMD) remains a major constraint in mungbean (Vigna radiata (L.)) production; while short-duration genotypes offer multiple crop cycles per year and help in escaping terminal heat stress, especially during summer cultivation. A comprehensive genotyping by sequencing (GBS)-based genome-wide association studies (GWAS) analysis was conducted using 132 diverse mungbean genotypes for traits like flowering time, YMD resistance, soil plant analysis development (SPAD) value, trichome density, and leaf area. The frequency distribution revealed a wide range of values for all the traits. GBS studies identified 31,953 high-quality single nucleotide polymorphism (SNPs) across all 11 mungbean chromosomes and were used for GWAS. Structure analysis revealed the presence of two genetically distinct populations based on ΔK. The linkage disequilibrium (LD) varied throughout the chromosomes and at r2 = 0.2, the mean LD decay was estimated as 39.59 kb. Two statistical models, mixed linear model (MLM) and Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) identified 44 shared SNPs linked with various candidate genes. Notable candidate genes identified include FPA for flowering time (VRADI10G01470; chr. 10), TIR-NBS-LRR for mungbean yellow mosaic India virus (MYMIV) resistance (VRADI09G06940; chr. 9), E3 ubiquitin-protein ligase RIE1 for SPAD value (VRADI07G28100; chr. 11), WRKY family transcription factor for leaf area (VRADI03G06560; chr. 3), and LOB domain-containing protein 21 for trichomes (VRADI06G04290; chr. 6). In-silico validation of candidate genes was done through digital gene expression analysis using Arabidopsis orthologous (compared with Vigna radiata genome). The findings provided valuable insight for marker-assisted breeding aiming for the development of YMD-resistant and early-maturing mungbean varieties.

CSF-Based Volumetric Imaging Biomarkers Highlight Incidence and Risk Factors for Cerebral Edema After Ischemic Stroke.

BACKGROUND: Cerebral edema has primarily been studied using midline shift or clinical deterioration as end points, which only captures the severe and delayed manifestations of a process affecting many patients with stroke. Quantitative imaging biomarkers that measure edema severity across the entire spectrum could improve its early detection, as well as identify relevant mediators of this important stroke complication. METHODS: We applied an automated image analysis pipeline to measure the displacement of cerebrospinal fluid (ΔCSF) and the ratio of lesional versus contralateral hemispheric cerebrospinal fluid (CSF) volume (CSF ratio) in a cohort of 935 patients with hemispheric stroke with follow-up computed tomography scans taken a median of 26 h (interquartile range 24-31) after stroke onset. We determined diagnostic thresholds based on comparison to those without any visible edema. We modeled baseline clinical and radiographic variables against each edema biomarker and assessed how each biomarker was associated with stroke outcome (modified Rankin Scale at 90 days). RESULTS: The displacement of CSF and CSF ratio were correlated with midline shift (r = 0.52 and - 0.74, p < 0.0001) but exhibited broader ranges. A ΔCSF of greater than 14% or a CSF ratio below 0.90 identified those with visible edema: more than half of the patients with stroke met these criteria, compared with only 14% who had midline shift at 24 h. Predictors of edema across all biomarkers included a higher National Institutes of Health Stroke Scale score, a lower Alberta Stroke Program Early CT score, and lower baseline CSF volume. A history of hypertension and diabetes (but not acute hyperglycemia) predicted greater ΔCSF but not midline shift. Both ΔCSF and a lower CSF ratio were associated with worse outcome, adjusting for age, National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT score (odds ratio 1.7, 95% confidence interval 1.3-2.2 per 21% ΔCSF). CONCLUSIONS: Cerebral edema can be measured in a majority of patients with stroke on follow-up computed tomography using volumetric biomarkers evaluating CSF shifts, including in many without visible midline shift. Edema formation is influenced by clinical and radiographic stroke severity but also by chronic vascular risk factors and contributes to worse stroke outcomes.

Limited exposure to preserve stability and achieve complete excision of limited dorsal myeloschisis - the "Skip-Hop Laminectomy" technique: a technical note.

OBJECTIVE: The fibroneural stalk of an LDM has variable thickness, complexity, and length, which can span 5 to 6 vertebral segments from its skin attachment to its "merge point" with the dorsal spinal cord. Therefore, complete resection may require extensive multi-level laminotomies. In this technical note, a modification of the procedure is presented that avoids long segment laminectomies while ensuring complete excision of long LDM stalks. RESULTS: An illustrative case of resection of LDM is presented using skip laminectomies. The technique ensures complete removal of the stalk, thus reducing the risk of future intradural dermoid development, while at the same time minimizes the risk for delayed kyphotic deformity. CONCLUSIONS: A technique of "skip-hop" proximal and distal short segment laminectomies in cases of LDM optimizes the objectives of complete stalk resection with preservation of spinal integrity.

Unveiling Diversity for Quality Traits in the Indian Landraces of Horsegram [Macrotyloma uniflorum (Lam.) Verdc.].

Horsegram (Macrotyloma uniflorum [Lam.] Verdc.) is an underutilized pulse crop primarily cultivated in South Asian countries like India, Nepal, and Sri Lanka. It offers various nutraceutical properties and demonstrates remarkable resilience to both biotic and abiotic stresses. As a result, it has emerged as a promising crop for ensuring future food and nutritional security. The purpose of this study was to assess the nutritional profile of 139 horsegram germplasm lines obtained from 16 Indian states that were conserved at the National Gene Bank of India. Standard analytical methods, including those provided by the Association of Official Analytical Chemists (AOAC), were used for this investigation. The study revealed substantial variability in essential nutrients, such as protein (ranging from 21.8 to 26.7 g/100 g), starch (ranging from 26.2 to 33.0 g/100 g), total soluble sugars (TSSs) (ranging from 0.86 to 12.1 g/100 g), phenolics (ranging from 3.38 to 11.3 mg gallic acid equivalents (GAEs)/g), and phytic acid content (ranging from 1.07 to 21.2 mg/g). Noteworthy correlations were observed, including a strong positive correlation between sugars and phenols (r = 0.70) and a moderate negative correlation between protein and starch (r = -0.61) among the studied germplasm lines. Principal component analysis (PCA) highlighted that the first three principal components contributed to 88.32% of the total variability, with TSSs, phytates, and phenols emerging as the most significant contributors. The cluster analysis grouped the accessions into five clusters, with cluster III containing the accessions with the most desirable traits. The differential distribution of the accessions from north India into clusters I and III suggested a potential geographical influence on the adaptation and selection of genes. This study identified a panel of promising accessions exhibiting multiple desirable traits. These specific accessions could significantly aid quality breeding programs or be directly released as cultivars if they perform well agronomically.

First contact investigations and compliance to treatment in patients with uveitis.

AIM: To ascertain the pattern of investigations at first contact in uveitic patients and evaluate compliance to treatment. METHODS: An observational study comprised of 201 uveitic patients presenting for the first time to our centre from January 2019 to June 2020. Detailed information regarding systemic investigations undertaken by specialists at the time of first contact and the cost of these investigations were reviewed on the first visit to our centre. Compliance with the treatment was determined and reasons behind non-compliance were evaluated on the first follow-up in patients who had no improvement in clinical signs and symptoms. RESULTS: The mean age of the study group was 35.35±14.1y and gender composition was 59.7% males and 40.3% females. Anterior uveitis was observed in 45.3% of patients, intermediate uveitis in 31.8% of patients, posterior uveitis in 14.9% of patients and panuveitis in 8.0% of patients. Association with a systemic disease was evident in 17.9% of patients. When compared with standard guidelines and uveitis patterns, systemic investigations were identified to be relevant only in 38.3% of patients. Non-compliance to treatment was documented in 22.4% of patients. Common reasons for non-compliance were inadequate counselling by the treating physician about treatment in 26.7% of patients and a busy schedule at work/school in 22.2% of patients. CONCLUSION: Significant number of investigations performed at first contact is found to be contrary to standard guidelines and are not contributory to the care. About a quarter of patients in this study are found to be non-compliant with the treatment. Compliance is more challenging to achieve in school-going children and working adults. The availability of comprehensive, periodically updated, evidence-based guidelines on the role of investigations and the use of trained counsellors may help to channelize proper evaluation and improve compliance to treatment, respectively, in patients with uveitis.

Tailored mesoporous γ-WO3 nanoplates: unraveling their potential for highly sensitive NH3 detection and efficient photocatalysis.

Herein, the monoclinic phase of tungsten oxide (γ-WO3) was successfully obtained after annealing hydrothermally synthesised WO3 powder at 500 °C. As per the result obtained from the N2 adsorption-desorption isotherm, the material has been identified as mesoporous with a specific surface area of 3.71 m2 g-1 from BET (Brunauer-Emmett-Teller) analysis. Moreover, the average pore size (49.52 nm) and volume (0.050 cm3 g-1) were also determined by the BJH (Barrett-Joyner-Halenda) method. FE-SEM (field emission scanning electron microscopy) and HR-TEM (high resolution transmission electron microscopy) have confirmed the formation of nanoplates with an average diameter of approximately 274 nm. Raman spectroscopy has shown peaks at the lower wavenumber region (270 cm-1 and 326 cm-1) and the higher wavenumber region (713 cm-1 and 806 cm-1) for O-W-O bending modes and stretching modes, respectively. The combined effect of relative humidity (RH-11%-RH-95%-RH-11%) and NH3 (150 ppm, 300 ppm, 450 ppm, 600 ppm, 700 ppm, and 800 ppm) was investigated in this reported work. The synthesised γ-WO3 has shown highly responsive behaviour for humidity of 96.5% (RH-11%-95%) and NH3 sensing (under humidity) of 97.4% (RH-11%-95% with 800 ppm NH3). The response and recovery time were calculated as 15 s and 52 s, and 16 s and 54 s for humidity, and NH3 under humidity, respectively. The experimental findings demonstrated that the resistance of the sensor depends on the concentration of NH3 and humidity. Moreover, γ-WO3 has been investigated as a promising catalyst for the dye degradation of methylene blue (MB) with a degradation efficiency of 72.82% and methyl orange (MO) with a degradation efficiency of 53.84% under visible light exposure. This dye degradation occurred within 160 min in the presence of a catalyst under visible light irradiation.

NOMA cooperative VLC systems: design and performance analysis with OOK and L-PPM modulation.

Visible light communication (VLC) allows white LEDs to communicate while lighting, which improves resource consumption. Multiple relay approaches can be employed in conjunction with cooperative communications to achieve large gains in spatial diversity, expand the coverage, and possibly boost system capacity. In this paper, the nonorthogonal multiple access (NOMA) cooperative techniques for VLC systems using on-off keying (OOK) and L-pulse-position modulation (L-PPM) are proposed. The maximum ratio combining (MRC) schemes is adopted at the receiving node to combine the signals received from cooperative transmissions. Further, the decode-and-forward relaying protocol is considered for cooperation. The proposed system is analyzed for a multiuser scenario that is followed by a two- and three-user scenario for detailed analysis. This study calculates the bit error probability (BEP) of an OOK/L-PPM modulated NOMA cooperative VLC system under perfect and imperfect successive interference cancellation. Simulation results are presented to validate the produced analytical BEP results.

DOPA decarboxylase is an emerging biomarker for Parkinsonian disorders including preclinical Lewy body disease.

The diagnosis of Parkinsonian disorders is currently based on clinical criteria, which have limited sensitivity until most dopaminergic neurons are lost. Here we show that cerebrospinal fluid levels of DOPA decarboxylase (DDC) (also known as aromatic L-amino acid decarboxylase) can accurately identify patients with Lewy body disease (LBD) (area under the curve (AUC) = 0.89; PFDR = 2.6 × 10-13) and are associated with worse cognitive performance (P < 0.05). We also found that DDC can detect preclinical LBD stages in clinically unimpaired individuals with a positive seed amplification α-synuclein assay (AUC = 0.81, P = 1.0 × 10-5) and that this biomarker could predict progression to clinical LBD over a 3-year period in preclinical cases (hazard ratio = 3.7 per s.d. change, confidence interval = 1.1-12.7). Moreover, DDC levels were also increased in atypical Parkinsonian disorders but not in non-Parkinsonian neurodegenerative disorders. These cerebrospinal fluid results were replicated in an independent cohort, where we also found that DDC levels in plasma could identify both LBD and atypical Parkinsonian disorders (AUC = 0.92, P = 1.3 × 10-14). Our results show that DDC might have a future role in clinical practice as a biomarker of dopaminergic dysfunction to detect Parkinsonian disorders even during the preclinical disease stages and predict their progression to clinical LBD.

Neuroinflammation, autoinflammation, splenomegaly and anemia caused by bi-allelic mutations in IRAK4.

We describe a novel, severe autoinflammatory syndrome characterized by neuroinflammation, systemic autoinflammation, splenomegaly, and anemia (NASA) caused by bi-allelic mutations in IRAK4. IRAK-4 is a serine/threonine kinase with a pivotal role in innate immune signaling from toll-like receptors and production of pro-inflammatory cytokines. In humans, bi-allelic mutations in IRAK4 result in IRAK-4 deficiency and increased susceptibility to pyogenic bacterial infections, but autoinflammation has never been described. We describe 5 affected patients from 2 unrelated families with compound heterozygous mutations in IRAK4 (c.C877T (p.Q293*)/c.G958T (p.D320Y); and c.A86C (p.Q29P)/c.161 + 1G>A) resulting in severe systemic autoinflammation, massive splenomegaly and severe transfusion dependent anemia and, in 3/5 cases, severe neuroinflammation and seizures. IRAK-4 protein expression was reduced in peripheral blood mononuclear cells (PBMC) in affected patients. Immunological analysis demonstrated elevated serum tumor necrosis factor (TNF), interleukin (IL) 1 beta (IL-1ß), IL-6, IL-8, interferon α2a (IFN-α2a), and interferon ß (IFN-ß); and elevated cerebrospinal fluid (CSF) IL-6 without elevation of CSF IFN-α despite perturbed interferon gene signature. Mutations were located within the death domain (DD; p.Q29P and splice site mutation c.161 + 1G>A) and kinase domain (p.Q293*/p.D320Y) of IRAK-4. Structure-based modeling of the DD mutation p.Q29P showed alteration in the alignment of a loop within the DD with loss of contact distance and hydrogen bond interactions with IRAK-1/2 within the myddosome complex. The kinase domain mutation p.D320Y was predicted to stabilize interactions within the kinase active site. While precise mechanisms of autoinflammation in NASA remain uncertain, we speculate that loss of negative regulation of IRAK-4 and IRAK-1; dysregulation of myddosome assembly and disassembly; or kinase active site instability may drive dysregulated IL-6 and TNF production. Blockade of IL-6 resulted in immediate and complete amelioration of systemic autoinflammation and anemia in all 5 patients treated; however, neuroinflammation has, so far proven recalcitrant to IL-6 blockade and the janus kinase (JAK) inhibitor baricitinib, likely due to lack of central nervous system penetration of both drugs. We therefore highlight that bi-allelic mutation in IRAK4 may be associated with a severe and complex autoinflammatory and neuroinflammatory phenotype that we have called NASA (neuroinflammation, autoinflammation, splenomegaly and anemia), in addition to immunodeficiency in humans.

Regio- and Stereoselective Intermolecular Oxysulfonylation of Alkynes with 1,3-Diketones to Access (Z)-ß-Sulfonated Enethers.

The first multicomponent regio- and stereoselective difunctionalization of alkynes via concomitant C-O and C-S bond formation using 1,3-diketones and sodium sulfinate has been developed for the synthesis of various sulfonated enethers. The viability of this strategy is unveiled by gram-scale, various synthetic modifications and late-stage functionalization. This transformation does not require any prefunctionalization, metal catalysts, and oxidants. The present operationally simple, efficient, and sustainable approach provides various functionalized olefins in a one-pot protocol with high Z-selectivity.

ASSESSMENT OF QUALITY AND ADEQUACY OF PANRETINAL PHOTOCOAGULATION IN PROLIFERATIVE DIABETIC RETINOPATHY USING ULTRA-WIDEFIELD IMAGING.

PURPOSE: To assess the characteristics of completed panretinal photocoagulation (PRP), using ultra-widefield imaging in proliferative diabetic retinopathy. METHODS: Quantitative assessment of ultra-widefield imaging images of 133 patients with proliferative diabetic retinopathy with completed PRP was made using ImageJ software. The parameters assessed included distance of laser spots from the optic disk, foveal center, superior and inferior arcades, and extent of the maximum width of laser. Areas assessed were total area of the image, area of the inner limit within which laser spots are restricted, minimum areas of unlasered patches, total area lasered, and ideal area to be covered by PRP. RESULTS: Two hundred one images were assessed for the final analysis. The mean distance of laser spots was 4.2 ± 2.4 mm from the optic disk (nasal) and 6.6 ± 2.5 mm from the foveal center (temporal). The mean distance of laser spots from the superior arcade vessel was 3.2 ± 1.9 mm and 6.2 ± 4.4 mm from the inferior arcade. The mean area of the retina that should have been ideally lasered was found to be 900 ± 267 mm 2 , and the actual area lasered was found to be 681 ± 254.4 mm 2 . CONCLUSION: Approximately one-quarter area of the retina continues to remain ischemic because of the lack of inadequate coverage of PRP. Further longitudinal studies are recommended, using ultra-widefield imaging to objectively assess the adequacy of PRP and its role in modulating the course of progression of the retinopathy.

TBAI-Catalyzed Regioselective Hydroxyperoxidation of 1-Aryl/Alkyl-1,3-dienes.

An efficient, mild, and economical approach for regioselective synthesis of 4-aryl/alkyl-1-peroxy-but-3-en-2-ols from 1-substituted-1,3-butadienes using hydroperoxides and catalyzed by TBAI has been developed. This method can be executed in a simple operation with no dry conditions required and having tolerance to a wide range of substrates to access corresponding hydroxyperoxidates in good yields. Thus, an excellent regioselective orthogonal dioxygenation in a diene system has been achieved.

Strategies adopted by gastric pathogen Helicobacter pylori for a mature biofilm formation: Antimicrobial peptides as a visionary treatment.

Enormous efforts in recent past two decades to eradicate the pathogen that has been prevalent in half of the world's population have been problematic. The biofilm formed by Helicobacter pylori provides resistance towards innate immune cells, various combinatorial antibiotics, and human antimicrobial peptides, despite the fact that these all are potent enough to eradicate it in vitro. Biofilm provides the opportunity to secrete various virulence factors that strengthen the interaction between host and pathogen helping in evading the innate immune system and ultimately leading to persistence. To our knowledge, this review is the first of its kind to explain briefly the journey of H. pylori starting with the chemotaxis, the mechanism for selecting the site for colonization, the stress faced by the pathogen, and various adaptations to evade these stress conditions by forming biofilm and the morphological changes acquired by the pathogen in mature biofilm. Furthermore, we have explained the human GI tract antimicrobial peptides and the reason behind the failure of these AMPs, and how encapsulation of Pexiganan-A(MSI-78A) in a chitosan microsphere increases the efficiency of eradication.