Vis-NIR spectroscopy based rapid and non-destructive method to quantitate microplastics: An emerging contaminant in farm soil.

Microplastics (MPs) is the second most important environmental issue and can potentially enter into food chain through farmland contamination and other means. There are no standardized extraction methods for quantification of MPs in soil. The embedded errors and biases generated serious problems regarding the comparability of different studies and leading to erroneous estimation. To address this gap, present study was formulated to develop an efficient method for MPs analysis suitable for a wide range of soil and organic matrices. A method based on Vis-NIR (Visible-Near Infra Red) spectroscopy is developed for four different soil belonging to Alfisol, Inceptisol, Mollisol and Vertisol and two organic matter matrices (FYM and Sludge). The developed method was found as rapid, reproducible, non-destructive and accurate method for estimation of all three-density groups of MPs (Low, Medium and High) with a prediction accuracy ranging from 1.9 g MPs/kg soil (Vertisol) to 3.7 g MPs/kg soil (Alfisol). Two different regression models [Partial Least Square Regression (PLSR) and Principal Component Regression (PCR)] were assessed and PLSR was found to provide better information in terms of prediction accuracy and minimum quantification limit (MQL). However, PCR performed better for organic matter matrices than PLSR. The method avoids any complicated sample preparation steps except drying and sieving thus saving time and acquisition of reflectance spectrum for single sample is possible within 18 s. Owing to have the minimum quantification limit ranging from 1.9-3.7 g/kg soil, the vis-NIR based method is perfectly suitable for estimation of MPs in soil samples collected from plastic pollution hotspots like landfill sites, regular based sludge amended farm soils. Additionally, the method can be adapted by small scale compost industries for assessing MPs load in product like city compost which are applied at agricultural fields and will be helpful in quantifying possible MPs at the sources itself.

Targeted inhibition of colorectal cancer proliferation: The dual-modulatory role of 2,4-DTBP on anti-apoptotic Bcl-2 and Survivin proteins.

The anti-apoptotic proteins, Bcl-2 and Survivin, are consistently overexpressed in numerous human malignancies, notably in colorectal cancer. 2,4-Di-tert-butylphenol (2,4-DTBP) is a naturally occurring phenolic compound known for its diverse biological activities, including anti-cancer properties. The mechanism behind 2,4-DTBP-induced inhibition of cell proliferation and apoptosis in human colorectal cancer cells, specifically regarding Bcl-2 and Survivin, remains to be elucidated. In this study, we employed both in silico and in vitro methodologies to underpin this interaction at the molecular level. Molecular docking demonstrated a substantial binding affinity of 2,4-DTBP towards Bcl-2 (ΔG = -9.8 kcal/mol) and Survivin (ΔG = -5.6 kcal/mol), suggesting a potential inhibitory effect. Further, molecular dynamic simulations complemented by MM-GBSA calculations confirmed the significant binding of 2,4-DTBP with Bcl-2 (dGbind = -54.85 ± 6.79 kcal/mol) and Survivin (dGbind = -32.36 ± 1.29 kcal/mol). In vitro assays using HCT116 colorectal cancer cells revealed that 2,4-DTBP inhibited proliferation and promoted apoptosis in both a dose- and time-dependent manner. Fluorescence imaging and scanning electron microscopy illustrated the classical features associated with apoptosis upon 2,4-DTBP exposure. Cell cycle analysis through flow cytometry highlighted a G1 phase arrest and apoptosis assay demonstrated increased apoptotic cell population. Notably, western blotting results indicated a decreased expression of Bcl-2 and Survivin post-treatment. Considering the cytoprotective roles of Bcl-2 and Survivin through the inhibition of mitochondrial dysfunction, our findings of disrupted mitochondrial bioenergetics, characterized by reduced ATP production and oxygen consumption, further accentuate the functional impairment of these proteins. Overall, the integration of in silico and in vitro data suggests that 2,4-DTBP holds promise as a therapeutic agent targeting Bcl-2 and Survivin in colorectal cancer.

Stable RNA G-Quadruplex in the 5'-UTR of Human cIAP1 mRNA Promotes Translation in an IRES-Independent Manner.

RNA G-quadruplex (rG4) structures can influence the fate and functions of mRNAs, especially the translation process. The presence of rG4 structures in 5'-untranslated regions (5'-UTRs) of mRNAs generally represses translation. However, rG4 structures can also promote internal ribosome entry site (IRES)-mediated translation as one of its determinants. Here, we report the identification of an evolutionary conserved rG4-forming sequence motif at the extreme 5'-end of the unusually long 5'-UTR (1.7 kb) in the transcript of human cIAP1 gene encoding the cellular inhibitor of apoptosis protein-1 that promotes cell survival by suppressing apoptosis and is overexpressed in various cancer cells. Expectedly, NMR study, CD spectroscopy, and UV melting assay confirm the formation of a potassium ion-dependent intramolecular and parallel rG4 structure at the sequence stretch. Moreover, the G4-RNA-specific precipitation using biotin-linked biomimetic BioCyTASQ validates the formation of the rG4 structure in the cIAP1 5'-UTR in cells. Interestingly, disruption of the rG4 structure in the cIAP1 5'-UTR results in a dramatic reduction in translation of the downstream luciferase reporter in cells, suggesting a translation-promoting effect of the rG4 structure, contrary to many earlier reports. Furthermore, enhancement of translation by the cIAP1 rG4 structure occurs in an IRES-independent manner.

Characterization of field isolates of Fusarium spp. from eggplant in India for species complexity and virulence.

Eggplant wilt, despite emerging as a severe disease in India, the etiology must be better studied for its species' complexity and variability. The identity of fungal isolates associated with eggplants of India was established morphologically followed by sequencing and phylogenetic analysis. Three species, Fusarium falciforme, Fusarium incarnatum and Fusarium proliferatum, were observed for the first time in India. The isolates were tested for pathogenicity. Though all of them were pathogenic, the isolates displayed varying degrees of virulence. In further studies, the genetic relatedness of the isolates for virulence was assessed with candidate avirulent (SIX effectors), virulent (Fow1 and Fow2) and SSR markers. The SIX effector genes could not delineate the virulent isolates and were expressed in some non-F. oxysporum isolates for the first time. Likewise, the virulent genes, Fow1 for expression across the isolates and Fow2 for random expression across the isolates, were unsuitable markers for identifying the virulent groups. Hence, the F. oxysporum and F. solani isolates were genotyped with SSR markers. Though the clustering did not correlate with their virulence levels, the dendrogram grouping revealed variability among the F. oxysporum and F. solani isolates. This study concludes that although multiple species of Fusarium are associated with eggplant wilt in India, only F. oxysporum and F. solani are widespread in the surveyed areas. Though the three markers could not delineate the race specificity of the isolates, only the SSR makers could identify the genetic variability and hence, would help screen eggplant germplasm for fusarium wilt resistance.

Assessing the efficacy of phyllospheric growth-promoting and antagonistic bacteria for management of black rot disease of cauliflower incited by Xanthomonas campestris pv. campestris.

The study aimed to assess the potential of phyllospheric bacterial strains isolated from cauliflower plants as biocontrol agents against black rot disease caused by Xanthomonas campestris pv. campestris, through both in vitro and in vivo evaluations. A total of 46 bacterial strains were isolated from healthy and infected cauliflower leaves of both resistant and susceptible plants, and evaluated them for various traits, including plant growth-promoting activities and in vitro antagonistic activity against Xanthomonas campestris pv. campestris. Further, a pot experiment was conducted with the susceptible cauliflower genotype (Pusa Sharad) and 10 selected phyllospheric bacterial isolates to assess their biocontrol efficacy against the disease. The results showed that 82.60% of phyllospheric bacterial isolates were positive for phosphate solubilization, 63.04% for ammonia production, 58.69% for HCN production, 36.95% for siderophore production, and 78.26% had the capacity to produce IAA. Out of the 46 isolates, 23 exhibited in vitro antagonistic activity against X. campestris pv. campestris and 10 isolates were selected for a pot experiment under glasshouse conditions based on their good plant growth-promoting activities and antagonistic assay. The results revealed that bacterial isolate CFLB-27 exhibited the highest biocontrol efficiency (65.41%), followed by CFLB-24 (58.30%), CFLB-31 (47.11%), and CFLB-26 (46.03%). These four isolates were identified as Pseudomonas fluorescens CFLB-27, Bacillus velezensis CFLB-24, Bacillus amyloliquefaciens CFLB-31, and Stenotrophomonas rhizophila CFLB-26. This study provides valuable insights into the potential of phyllospheric bacteria as an effective tool for disease management in sustainable agriculture.

Facet-Dependent Photoelectrochemistry on Single Crystal Organic-Inorganic Halide Perovskite Electrodes.

Organometallic halide perovskites have garnered significant attention in various fields of material science, particularly solar energy conversion, due to their desirable optoelectronic properties and compatibility with scalable fabrication techniques. It is often unclear, however, how carrier generation and transport within complex polycrystalline films are influenced by variations in local structure. Elucidating how distinct structural motifs within these heterogeneous systems affect behavior could help guide the continued improvement of perovskite-based solar cells. Here, we present studies applying scanning electron microscopy (SECCM) to map solar energy harvesting within well-defined model systems of organometallic halide perovskites. Methylammonium lead bromide (MAPbBr3) single crystals were prepared via a low-temperature solution-based route, and their photoelectrochemical properties were mapped via SECCM using p-benzoquinone (BQ) in dichloromethane as a redox mediator. Correlated SECCM mapping and electron microscopy studies enabled facet-to-facet variations in photoelectrochemical performance to be revealed and carrier transport lengths to be evaluated. The photoelectrochemical behavior observed within individual single crystals was quite heterogeneous, attributable to local variations in crystal structure/orientations, intrafacet junctions, and the presence of other structural defects. These observations underscore the significance of controlling the microstructure of single perovskite crystals, presenting a promising avenue for further enhancement of perovskite-based solar cells.

Design and Additive Manufacturing of Acetabular Implant with Continuously Graded Porosity.

Porous structured metallic implants are preferable as bone graft substitutes due to their faster tissue integration mediated by bone in-growth and vascularization. The porous scaffolds/implants should also mimic the graded structure of natural bone to ensure a match of mechanical properties. This article presents a method for designing a graded porous structured acetabular implant and identifies suitable parameters for manufacturing the model through additive manufacturing. The design method is based on slice-wise modification to ensure continuity of gradation. Modification of the slices was achieved through the binary image processing route. A geodesic dome-type design was adopted for developing the acetabular cup model from the graded porous structure. The model had a solid shell with the target porosity and pore size gradually changing from 65% and 950 µm, respectively, in the inner side to 75% and 650 µm, respectively, towards the periphery. The required dimensions of the unit structures and the combinations of pore structure and strut diameter necessary to obtain the target porosity and pore size were determined analytically. Suitable process parameters were identified to manufacture the model by Direct Metal Laser Sintering (DMLS) using Ti6Al4V powder after carrying out a detailed experimental study to minimize the variation of surface roughness and warping over different build angles of the strut structures. Dual-contour scanning was implemented to simplify the scan strategy. The minimum diameter of struts that could be manufactured using the selected scanning strategy and scanning parameters was found to be 375 µm. Finally, the model was built and from the micro-CT data, the porosities and pore sizes were found to be closely conforming to the designed values. The stiffness of the structures, as found from compression testing, was also found to match with that of human trabecular bone well. Further, the structure exhibited compliant bending-dominated behaviour under compressive loading.

Translational regulation of δ-tubulin through its 5'-untranslated region.

BACKGROUND: δ-tubulin - a member of tubulin superfamily, is found in a subset of eukaryotes including human where it has a role in centriole maturation. The mutation in the gene results in a disorganized microtubule triplet arrangement leading to formation of defective centriole. Since centriole maturation is a periodic event, it will be interesting to see if δ-tubulin is also regulated in a cell cycle dependent manner. METHODS AND RESULTS: In this regard we show that the abundance of δ-tubulin mRNA remains unchanged throughout the cell cycle. However, the protein level varies periodically with a significantly higher expression in S-phase, implying regulation at the level of translation. Sequence analysis establishes the presence of a 90-base long conserved region, including a consensus motif of nine residues in the 5´-untranslated region (5´-UTR) of δ-tubulin transcript. The deletion analysis of the conserved region using luciferase reporter assay system confirms its strong inhibitory effect on translation. Interestingly, microtubule associated protein 4 (MAP4) is found to interact specifically with the 90-base long conserved region in the 5´-UTR and possibly responsible, at least partially, for the translation inhibitory activity of the UTR. Remarkably, MAP4 interacts with δ-tubulin in a periodic manner at protein level also. CONCLUSION: The results reported here show that δ-tubulin protein expression is regulated at posttranscriptional level and strongly suggest the role of MAP4 in modulation of both abundance and function of δ-tubulin.

Antibody Immobilization on Sulfated Cellulose Nanocrystals.

Exploiting cellulose nanocrystals' high aspect ratio and tailorable surface for immunological biosensors has been hindered by the relatively limited research on using commonly available sulfated cellulose nanocrystals (CNCs) for antibody immobilization and by the low hydrolytic stability of dried assemblies produced from sulfated CNCs. Herein, we report a reaction scheme that enables both hydrolytic stability and antibody immobilization through 3-aminopropyl-triethoxysilane and glutaric anhydride chemistry. Immobilization was demonstrated using three model antibodies used in the detection of the cancer biomarkers: alpha-fetoprotein, prostate-specific antigen, and carcinoembryonic antigen. Thermogravimetric analysis coupled with Fourier-transform infrared spectroscopy provided evidence of CNC modification. Quartz crystal microbalance with dissipation monitoring was used to monitor binding during each step of the immobilization scheme as well as binding of the corresponding antigens. The general reaction scheme was tested using both aqueous CNC dispersions and CNC films. Film modification is slightly simpler as it avoids centrifugation and washing steps. However, modifying the dispersed CNCs provides access to their entire surface area and results in a greater capacity for antigen binding.

Prenatal exposure to alcohol impairs responses of cerebral arterioles to activation of potassium channels: Role of oxidative stress.

BACKGROUND: Potassium channels play an important role in the basal tone and dilation of cerebral resistance arterioles in response to many stimuli. However, the effect of prenatal alcohol exposure (PAE) on specific potassium channel function remains unknown. The first goal of this study was to determine the influence of PAE on the reactivity of cerebral arterioles to activation of ATP-sensitive potassium (KATP ) and BK channels. Our second goal was to determine whether oxidative stress contributed to potassium channel dysfunction of cerebral arterioles following PAE. METHODS: We fed Sprague-Dawley dams a liquid diet with or without alcohol (3% EtOH) for the duration of their pregnancy (21 to 23 days). We examined in vivo responses of cerebral arterioles in control and PAE male and female offspring (14 to 16 weeks after birth) to activators of potassium channels (Iloprost [BK channels] and pinacidil [KATP channels]), before and following inhibition of oxidative stress with apocynin. RESULTS: We found that PAE impaired dilation of cerebral arterioles in response to activation of potassium channels with iloprost and pinacidil, and this impairment was similar in male and female rats. In addition, treatment with apocynin reversed the impaired vasodilation to iloprost and pinacidil in PAE rats to levels observed in control rats. This effect of apocynin also was similar in male and female rats. CONCLUSIONS: PAE induces dysfunction in the ability of specific potassium channels to dilate cerebral arterioles which appears to be mediated by an increase in oxidative stress. We suggest that these alterations in potassium channel function may contribute to the pathogenesis of cerebral vascular abnormalities and/or behavioral/cognitive deficits observed in fetal alcohol spectrum disorders.

On-Demand Electrochemical Fabrication of Ordered Nanoparticle Arrays using Scanning Electrochemical Cell Microscopy.

Well-ordered nanoparticle arrays are attractive platforms for a variety of analytical applications, but the fabrication of such arrays is generally challenging. Here, it is demonstrated that scanning electrochemical cell microscopy (SECCM) can be used as a powerful, instantly reconfigurable tool for the fabrication of ordered nanoparticle arrays. Using SECCM, Ag nanoparticle arrays were straightforwardly fabricated via electrodeposition at the interface between a substrate electrode and an electrolyte-filled pipet. By dynamically monitoring the currents flowing in an SECCM cell, individual nucleation and growth events could be detected and controlled to yield individual nanoparticles of controlled size. Characterization of the resulting arrays demonstrate that this SECCM-based approach enables spatial control of nanoparticle location comparable with the terminal diameter of the pipet employed and straightforward control over the volume of material deposited at each site within an array. These results provide further evidence for the utility of probe-based electrochemical techniques such as SECCM as tools for surface modification in addition to analysis.

Reconstruction of the Posterolateral Corner of the Knee Using LaPrade and Modified Larson Technique: A Prospective Study.

BACKGROUND: Posterolateral corner (PLC) injuries of the knee are often overlooked for its complex anatomy, and frequent association with cruciate ligament injuries. Overlooked injuries lead to reconstruction failure of cruciate ligaments, chronic knee pain and early arthritic changes. Many reconstruction methods are described, but the best treatment still remains elusive. In this study, we have treated grade-III PLC injuries by the 'anatomic LaPrade' technique and the 'fibula-based Modified Larson' technique, and evaluated their outcomes. Our hypothesis was that both the groups will have similar improvements after surgery. METHODS: An open-label prospective comparative study was done with a total of 28 patients from August 2013 to July 2019. Patients were treated alternatively by LaPrade or Modified Larson technique using hamstring autografts. Follow-up visits were done at sixth week and subsequently at 3, 6, 12, 18 and 24 months postoperatively. Outcomes were measured by Dial Test, side-to-side difference in lateral opening on varus stress radiographs, Lysholm score and IKDC subjective score. RESULTS: During analysis, we considered 25 patients only as three patients were lost to follow-up. Both the groups had comparable improvements in rotational stability, lateral opening on varus stress, Lysholm score and IKDC subjective score. CONCLUSION: Both LaPrade and Modified Larson technique showed good clinical results in restoring varus and rotational stability of knee in grade-III posterolateral corner injury of the knee. LEVEL OF EVIDENCE: II (prospective, comparative study).

Prenatal exposure to alcohol: mechanisms of cerebral vascular damage and lifelong consequences.

Alcohol is a well-known teratogen, and prenatal alcohol exposure (PAE) leads to a greater incidence of many cardiovascular-related pathologies. Alcohol negatively impacts vasculogenesis and angiogenesis in the developing fetal brain, resulting in fetal alcohol spectrum disorders (FASD). Ample preclinical evidence indicates that the normal reactivity of cerebral resistance arterioles, which regulate blood flow distribution in response to metabolic demand (neurovascular coupling), is impaired by PAE. This impairment of dilation of cerebral arteries may carry implications for the susceptibility of the brain to cerebral ischemic damage well into adulthood. The focus of this review is to consolidate findings from studies examining the influence of PAE on vascular development, give insights into relevant pathological mechanisms at the vascular level, evaluate the risks of ethanol-driven alterations of cerebrovascular reactivity, and revisit different preventive interventions that may have promise in reversing vascular changes in preclinical FASD models.

Constrictor responses of cerebral resistance arterioles in male and female rats exposed to prenatal alcohol.

While it is known that dilation of cerebral arterioles to NOS-dependent agonists is impaired in rats exposed to prenatal alcohol, no studies have examined the influence of prenatal alcohol on constrictor response of cerebral arterioles. Our goal was to determine whether constrictor responses of cerebral resistance arterioles are altered by prenatal exposure to alcohol and if any changes differed as a function of age or sex. We fed Sprague-Dawley rat dams a liquid diet with or without alcohol (3% ethanol) for the duration of their pregnancy. We then examined reactivity of cerebral arterioles to thromboxane (U-46619; 0.01 and 0.1 µM), arginine vasopressin (0.1 and 1 nM), and angiotensin II (1 and 10 µM) in four groups of offspring: control male and female, and prenatal alcohol male and female at two different ages (adolescent: 4-6 weeks old and adult: 14-16 weeks old). Constriction of cerebral arterioles to U-46619 and AVP were similar in male and female rats regardless of exposure to prenatal alcohol and age. Similarly, adolescent male and female rats showed no difference to angiotensin II following prenatal exposure to alcohol. However, alcohol-exposed females exhibited an unexpected dilation to the high concentration of angiotensin II in adulthood, which was absent in males. We suggest that the findings from these studies may have implications regarding the susceptibility of the brain to cerebral ischemic damage. We speculate that impaired vasodilation, coupled with preserved vasoconstriction, can lead to a scenario favoring a decrease in cerebral blood flow during times of increased metabolic demand.

Marker-Assisted Pyramiding of Downy Mildew-Resistant Gene Ppa3 and Black Rot-Resistant Gene Xca1bo in Popular Early Cauliflower Variety Pusa Meghna.

Cauliflower is an important extensively grown cool season vegetable in India. Black rot and downy mildew are major devastating diseases reducing yield and quality of the crop. To tackle these through host plant resistance, a marker-assisted backcross breeding method was followed to pyramid a black rot-resistant gene (Xca1bo) and a downy mildew-resistant gene (Ppa3) from donors BR-161 and BR-2, respectively, into the background of Pusa Meghna cauliflower cultivar. Marker-assisted backcross breeding was followed up to BC2 generation using SCAR marker ScOPO-04833 and SSR marker BoGMS0624 for black rot and downy mildew resistance genes in foreground selection, respectively. In background selection, at each stage of backcrossing, 47 parental polymorphic SSR markers were used. The graphical genotyping of the five two-gene (Xca1boXca1boPpa3Ppa3) homozygous BC2F2 plants showed an average recovery of 85.44% of the Pusa Meghna genome with highest genome recovery of 91.7%. The genome contribution of donor parents (BR-161 and BR-2) was 8.26 with 6.34% of residual heterozygousity. The backcross derived pyramided lines BC2F2:3-7-16 and BC2F2:3-7-33 showed high resistance to both the diseases and exhibited higher yield and vitamin C content as compared with recipient parent Pusa Meghna. It is, therefore, evident from this study that resistant genes can be introgressed successfully into a Pusa Meghna cultivar without any yield penalty, benefitting farmers with reduced input cost and consumers with chemical residue free produce. Besides, the pyramided lines carrying dominant resistant genes can be exploited in a hybridization programme to develop hybrid(s) in cauliflower.

Genome wide comparison of Leishmania donovani strains from Indian visceral leishmaniasis and para-kala-azar dermal leishmaniasis patients.

Visceral leishmaniasis (VL) or Kala-azar, primarily caused by Leishmania donovani, is a major health concern in many countries including India. Growing unresponsiveness among the parasites toward the available drugs is alarming, and so, it is necessary to decipher the underlying mechanism of such development for designing new therapeutics. Moreover, even after successful treatment, some VL patients develop apparently harmless skin lesions known as post-kala-azar dermal leishmaniasis (PKDL) which may serve as a reservoir of the parasite in the transmission cycle. Furthermore, recent reports of para-kala-azar dermal leishmaniasis (para-KDL) cases having PKDL manifestation with concomitant VL, emphasize the necessity of more attention to address complex nature of the parasite for eradicating the disease effectively. In the present study, whole genome sequencing is performed with sodium stibogluconate (SSG) sensitive and resistant L. donovani strains along with SSG sensitive para-KDL strains, derived from the clinical isolates of Indian patients to identify the genomic variations among them. Notably, the analyses of chromosome somy values and genome wide mutation profile in the coding regions reveal distinct clustering of the para-KDL strains with 24 genes being mutated uniquely in this group. Such distinguishing genomic changes among the para-KDL strains could be significant for the parasites to become dermatotropic. Overall, the study reveals a possible correlation of the development of SSG resistance and the transition towards the manifestation of PKDL with chromosome aneuploidy and non-synonymous genetic variations in the coding sequences of the L. donovani strains from Indian patients.

Rosiglitazone restores nitric oxide synthase-dependent reactivity of cerebral arterioles in rats exposed to prenatal alcohol.

BACKGROUND: Prenatal exposure to alcohol leads to a greater incidence of many cardiovascular-related diseases, presumably via a mechanism that may involve increased oxidative stress. An agonist of peroxisome proliferator-activated receptor gamma (PPARγ; rosiglitazone) has been shown to suppress alcohol-induced neuroinflammation and oxidative stress. The goal of this study was to determine whether acute and chronic treatment with rosiglitazone could restore or prevent impaired nitric oxide synthase (NOS)-dependent responses of cerebral arterioles in male and female adult (14-16 weeks old) rats exposed to alcohol in utero. METHODS: We fed Sprague-Dawley dams a liquid diet with or without 3% ethanol for the duration of their pregnancy (21-23 days). In the first series of studies, we examined the reactivity of cerebral arterioles to eNOS- (ADP), nNOS-dependent (NMDA), and NOS-independent agonists in male and female adult rats before and during acute (1 hour) topical application of rosiglitazone (1 µM). In a second series of studies, we examined the influence of chronic treatment with rosiglitazone (3 mg/kg/day in drinking water for 2-3 weeks) on the responses of cerebral arterioles in male and female adult rats exposed to alcohol in utero. RESULTS: We found that in utero exposure to alcohol similarly reduced responses of cerebral arterioles to ADP and NMDA, but not to nitroglycerin in male and female adult rats. In addition, acute treatment of the male and female adult rats with rosiglitazone similarly restored this impairment in cerebral vascular function to that observed in controls. We also found that chronic treatment with rosiglitazone prevented impaired vascular function in male and female adult rats that were exposed to alcohol in utero. CONCLUSIONS: PPARγ activation may be an effective and relevant treatment to reverse or prevent cerebral vascular abnormalities associated with prenatal exposure to alcohol.

A phylogenetic analysis of Momordica (Cucurbitaceae) in India based on karyo-morphology, nuclear DNA content and rDNA ITS1-5.8S-ITS2 sequences.

The infrageneric delimitation of Momordica, a medicinally important genus of Cucurbitaceae, is ill-defined until date. Momordica chromosomes are extremely small and are difficult to stain and visualize because of the dense cytoplasmic background. We have conducted karyomorphometric analysis by EMA method in five Indian Momordica species, and the nuclear genome sizes were estimated by flow cytometry for the first time. The somatic chromosome numbers ranged from 2n = 18 to 56 in the species. We have resolved previously disputed chromosome numbers in M. cymbalaria and M. dioica as 2n = 18 (lowest) and 2n = 56, respectively. Chromosome counts in the other species were re-confirmed as 2n = 22 in M. charantia, 2n = 28 in M. cochinchinensis and 2n = 56 in M. subangulata. The largest genome size was recorded in M. cymbalaria (3.74 pg 2C-1), while the smallest size (0.72 pg 2C-1) was detected in M. charantia var. charantia. The nuclear genome sizes were analysed in comparison to chromosome numbers and total chromosome lengths of the species. Karyomorphometric indices showed comparable symmetric karyotypes in the species except in M. cymbalaria having tendency towards asymmetry. The UPGMA phenogram and principle component analysis based on nuclear DNA contents and karyomorphometric parameters demonstrated interspecies differences, intraspecific distinction within M. charantia varieties and highlighted distinction of M. cymbalaria. This study was further supported by the rDNA ITS sequence-based phylogenetic analysis which revealed the monophyletic origin of the Indian members of Momordica and clarified the intraspecies relationship among the studied members. As a whole, the study brought out new insights on species diversification within the genus Momordica in India and would benefit further studies on biosystematics and plant breeding programmes.

Hypotension Prediction Index for Prevention of Hypotension during Moderate- to High-risk Noncardiac Surgery.

BACKGROUND: The Hypotension Prediction Index is a commercially available algorithm, based on arterial waveform features, that predicts hypotension defined as mean arterial pressure less than 65 mmHg for at least 1 min. We therefore tested the primary hypothesis that index guidance reduces the duration and severity of hypotension during noncardiac surgery. METHODS: We enrolled adults having moderate- or high-risk noncardiac surgery with invasive arterial pressure monitoring. Participating patients were randomized to hemodynamic management with or without index guidance. Clinicians caring for patients assigned to guidance were alerted when the index exceeded 85 (range, 0 to 100) and a treatment algorithm based on advanced hemodynamic parameters suggested vasopressor administration, fluid administration, inotrope administration, or observation. Primary outcome was the amount of hypotension, defined as time-weighted average mean arterial pressure less than 65 mmHg. Secondary outcomes were time-weighted mean pressures less than 60 and 55 mmHg. RESULTS: Among 214 enrolled patients, guidance was provided for 105 (49%) patients randomly assigned to the index guidance group. The median (first quartile, third quartile) time-weighted average mean arterial pressure less than 65 mmHg was 0.14 (0.03, 0.37) in guided patients versus 0.14 (0.03, 0.39) mmHg in unguided patients: median difference (95% CI) of 0 (-0.03 to 0.04), P = 0.757. Index guidance therefore did not reduce amount of hypotension less than 65 mmHg, nor did it reduce hypotension less than 60 or 55 mmHg. Post hoc, guidance was associated with less hypotension when analysis was restricted to episodes during which clinicians intervened. CONCLUSIONS: In this pilot trial, index guidance did not reduce the amount of intraoperative hypotension. Half of the alerts were not followed by treatment, presumably due to short warning time, complex treatment algorithm, or clinicians ignoring the alert. In the future we plan to use a lower index alert threshold and a simpler treatment algorithm that emphasizes prompt treatment.

Monomer release from direct and indirect adhesive restorations: A comparative in vitro study.

OBJECTIVES: Indirect dental restorations produced by computer-aided design and computer-aided manufacturing (CAD/CAM) are relatively new in daily dental practice. The aim of the present study was to compare the monomer release between direct composite restorations and indirect CAD/CAM produced restorations (composite, ceramic and hybrid). METHODS: Identical crown restorations were prepared from three indirect materials (Cerasmart, Vitablocs Mark II and Vita Enamic) and one composite material (Clearfil AP-X). For each restoration, eight crown restorations were luted onto tooth samples and immersed into 2.5mL of an aqueous extraction solvent. Additionally, three nonluted crowns of each restoration type were also immersed in the extraction solvent, and served as controls. Every week, the extraction solvent was collected and refreshed, during a period of 8 weeks. The released monomers were quantified using ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: Indirect restorations release significantly lower quantities of residual monomers than direct restorations, and the monomers released by the luted indirect restorations are mainly derived from the composite material used for cementation. The quantity of monomers released by direct restorations greatly depended on the time of light polymerization. SIGNIFICANCE: In terms of monomer release, indirect restorations are a good alternative to direct restorations to limit patient exposure to residual monomers. It is important to ideally design the fit of indirect restoration so that the cement layer is as thin as possible and the monomer release from this cement layer remains as low as possible.