Dinuclear gold(I) complexes based on carbene and diphosphane ligands: bis[2-(dicyclohexylphosphano)ethyl]amine complex inhibits the proteasome activity, decreases stem cell markers and spheroid viability in lung cancer cells.

Three new dinuclear gold(I) complexes (1-3) containing a carbene (1,3-Bis(2,6-di-isopropylphenyl)imidazol-2-ylidene (IPr)) and diphosphane ligands [bis(1,2-diphenylphosphano)ethane (Dppe), bis(1,3-diphenylphosphano)propane (Dppp) and bis[2-(dicyclohexylphosphano)ethyl]amine (DCyPA)], were synthesized and characterized by elemental analysis and, ESI-MS, mid FT-IR and NMR spectroscopic methods. The structures of complexes 2 and 3 were determined by X-ray crystallography, which revealed that the complexes are dinuclear having gold(I) ions linearly coordinated. The anticancer activities of the complexes (1-3) were evaluated in lung (A549), breast (MC-F7), prostate (PC-3), osteosarcoma (MG-63) and ovarian (A2780 and A2780cis) cancer models. Growth inhibition by the new complexes was higher than cisplatin in all cell lines tested. The mechanism of action of complex 3 was investigated in A549 cells using 2-dimensional (2D) models and 3D-multicellular tumor spheroids. Treatment of A549 cells with complex 3 caused: the induction of apoptosis and the generation of reactive oxygen species; the cell cycle arrest in the G0/G1 phase; the inhibition of both the proteasome and the NF-kB activity; the down-regulation of lung cancer stem cell markers (NOTCH1, CD133, ALDH1 and CD44). Complex 3 was more active than cisplatin also in 3D models of A549 lung cancer cells.

Assessment of carbon footprint of milk production and identification of its major determinants in smallholder dairy farms in Karnataka, India.

Indian dairy enterprise is dominated by smallholder dairy farms that contribute 72% of the country's total milk production. These smallholder dairy farms are often considered to emit substantial greenhouse gases (GHG) but are poor in productive performances. Therefore, it is crucial to estimate the carbon footprint (CF) of milk production of the smallholder Indian dairy farms. The primary objectives of the study were (1) Assessing the CF of milk production of smallholder dairy farms through life cycle analysis in south-interior Karnataka, India; (2) Identifying the hotspots of GHG emissions and significant factors influencing the CF of milk production in smallholder dairy production system. The study accounted GHG emissions from different sources and considered multiple functions of the smallholder production system. Estimations were made based on primary data collected from 47 farms and associated secondary data. For estimating the CF of milk production, the emissions of carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) on a CO2-equivalent (CO2-eq) basis from feed production, enteric fermentation, manure management, transport and energy usage were allocated to fat- and protein-corrected milk (FPCM) based on mass balance, price (crop byproducts and residues) and feed digestibility. Principal component analysis and stepwise linear regression analysis were performed to identify the major factors influencing the CF. The average total GHG emissions (kg CO2-eq yr-1 farm-1) attributable to milk production based on mass, economic, and digestibility allocations were 8,936, 8,641, and 8,759, respectively. The contributions of CH4, N2O, and CO2 to the total farm GHG emission were 70.6%, 20.5%, and 7.69%, respectively. The major emission hotspots were CH4 emission from enteric fermentation (66.8%) and GHG emission from feed production (23.0%). The average CF of cradle-to-dairy cooperative milk production varied from 1.45 to 1.81 kg CO2-eq kg FPCM-1. The CF of milk production was more than 2-fold greater, when milk yield was below 3,500 kg lactating cow-1 yr-1. The FPCM yield 100 kg body weight-1, dry matter intake, and CH4 emission from manure management were the strongest determinants of the CF and explained 83.4% of the observed variation. The study emphasized the importance of considering multiple functions of a mixed crop-livestock-based dairy production system for estimating CF per unit of product. The results suggest that maintaining high-yielding dairy animals and adopting appropriate feeding strategies for better feed utilization are the possible effective interventions for reducing the CF of milk production.

Effect of silkworm (Bombyx mori) pupae oil supplementation on enteric methane emission and methanogens diversity in sheep.

In vitro and in vivo studies were conducted to examine the effect of silkworm pupae oil on methane (CH4) emission and methanogens diversity. Five graded levels (2, 4, 6, 8 and 10%) of silkworm pupae oil were tested in vitro. Eighteen Mandya adult sheep were divided into three groups. All the animals were fed on similar basal diet except the oil supplementation in test groups. Oil level for supplementation was decided on the basis of in vitro study. In vitro study indicated a reduction of 22% in CH4 production with 2% oil supplementation. Animals in test groups were supplemented with oil (2%) either daily (CON) or intermittently (INT) on every alternate week for all the seven days. A significant reduction of 17-20% in enteric CH4 emission (g/d) was achieved due to oil supplementation in sheep. However, No variation was established between test groups CON and INT. In present study, Methanobrevibacter was major genus contributed ∼90% of the total rumen methanogens; whilst Methanobrevibacter gottschalkii was the most abundant methanogens species. Abundance of Methanobrevibacter ruminantium was affected with the oil supplementation. It can be concluded that the silkworm pupae oil at 2% can decrease CH4 emission by 15-20%.

Country-wide distribution of bluetongue virus with expanding host spectrum and evidence of vector competence in Hungary.

Following the introduction of bluetongue virus type 4 (BTV-4) in 2014, country-wide monitoring of bluetongue (BT) disease was performed to see whether the virus has become enzootic in Hungary. To analyse the epizootiology of BT, over 110,000 samples collected from domestic and wild ruminants were screened for the presence of BTV RNA and virus-specific antibodies using real-time RT-PCR assay and commercial ELISA kit, respectively. During laboratory analysis, specimens collected from 333 (0.8%) cattle, 79 (2.2%) sheep, 4 (0.9%) goats, and 1 (2.3%) mouflon were found to be positive by viral RNA-detection assay. In addition, antibody to BTV was detected in 5.5% (3158/57,250) of cattle, 10.1% (517/5120) of sheep, 40% (116/290) of goat, and 5.6% (16/284) of buffalo origin samples. The majority of positive samples originated from south-western counties; however, 18 out of 19 counties reported cases or antibody prevalence in the examined animals. Genome sequencing of a representative BTV-4 strain from 2015 was also performed. When comparing this strain with the isolate BTV4-HUN2014 detected only a year earlier in Hungary, mutations at 14 sites were identified within the amplified and sequenced genome. Our findings reinforce the need for continued surveillance of BT disease in Hungary. Keywords: reoviridae; orbivirus; cattle; sheep; goat; biting midge.

Near-White Light Emission from Lead(II) Metal-Organic Frameworks.

Reaction of bpy (bpy = 4,4'-bipyridine) with Pb(OAc)2·3H2O in DMF (DMF = dimethylformamide) afforded a metal-organic framework (MOF), [Pb2(µ-bpy)(µ-O2CCH3)2(µ-O2CCH3)2]·H2O (1). Reaction of bpy with Pb(O2CCF3)2 in a methanol and chloroform mixture furnished another MOF, [Pb(µ-bpy)(µ-O2CCF3)2]·1/2CHCl3 (2). However, the reaction of bpy with Pb(OAc)2·3H2O in the presence of trifluoroacetic acid in a similar reaction condition yielded a hydrogen-bonded zwitter-ionic complex of Pb(II), [Pb(bpy-H)2(O2CCF3)4] (3). All compounds have been characterized by single crystal X-ray crystallography, FT-IR, and 1H NMR spectroscopies. Compound 1 forms four heptacoordinated Pb(II) joined by (OCCH3)-O- linkages, resulting in a 3D noninterpenetrated MOF net with a four-connected uninodal sra (SrAl2) topology. However, in 2, tetra-connected Pb4(O2CCF3)8 cluster units are linked further through eight bpy ligands to furnish a doubly interpenetrated MOF with a new topology but having the very similar connectivity of 1, whereas 3 forms a zigzag hydrogen-bonded chain structure. The variation of carboxylate anions, pH of the reaction medium, and the ratio of the reactants profoundly affected the final topological structure of the compounds synthesized. The solid-state photoluminescence of 1-3 was investigated at room temperature. Interestingly 1, 2, and 3 achieved close to white light emission when excited at 329, 376, and 330 nm, respectively. The systematic understanding of the photophysical properties of analogous Pb-based compounds may open new perspectives for developing single-phase white-light-emitting materials using Pb(II) based MOFs.

Association between the intima-media thickness of the extracranial carotid arteries and metabolic syndrome in ethnic Kyrgyzs.

BACKGROUND: It is known that atherosclerosis is the leading cause of cardiovascular disease. We aimed to study the correlation between components of metabolic syndrome (MS) and subclinical carotid atherosclerosis in a group of ethnic Kyrgyzs. METHODS: In а descriptive study we assessed 144 ethnic Kyrgyzs (69 males, 75 females) aged 36-73 years (average age 51.03 ± 8.2). All participants underwent a clinical investigation and an anthropometric evaluation (weight, height, waist circumference (WC)). Abdominal obesity (АО) was confirmed at WC ≥ 94 cm in males and ≥ 88 cm in females. Fasting plasma glucose and lipid spectrum tests were performed. An ultrasound assessment of carotid intima-media thickness (IMT) was performed using a 7.5 MHz transducer (Phillips-SD 800). RESULTS: MS was revealed in 61 (42.4%; 47.8% in men and 37.3% in women) of the investigated patients. IMT was significantly increased with the presence of MS components in males (no components vs 2 components of MS: 0.67 ± 0.007 and 0.81 ± 0.009 respectively; р < 0.05) and females (no components vs 3 components of MS: 0.63 ± 0.007 and 0.76 ± 0.01 respectively; р < 0.01). IMT trended towards an increase in the presence of a greater number of MS components in patients with and without AO (р < 0.01). In order to identify independent factors affecting IMT we carried out a multifactorial logistic regression analysis. Arterial hypertension was found to have the greatest influence on the development of MS (OR = 3.81, p < 0.0001). CONCLUSION: In the group of ethnic Kyrgyzs, a greater number of MS components, with AO or without AO, is associated with higher carotid IMT.

Replication kinetics of neuropathogenic and non-neuropathogenic equine herpesvirus type 1 (EHV-1) strains in primary murine neurons and ED cell line.

Equine herpesvirus type 1 (EHV-1) causes respiratory infections, abortion and neurological disorders in horses. Molecular epidemiology studies have demonstrated that a single-point mutation in DNA polymerase gene, resulting in an amino acid variation (N752/D752), is significantly associated with the neuropathogenic potential of EHV-1 strains. The aim of the study was to elucidate if there are any differences between neuropathogenic (EHV-1 26) and non-neuropathogenic (Jan-E and Rac-H) EHV-1 strains in their ability to infect neuronal cells. For the tested EHV-1 strains, cytopathic effect (CPE) was manifested by changed morphology of cells, destruction of actin cytoskeleton and nuclei degeneration, which led to focal degeneration. Moreover, EHV-1 26 strain caused fusion of the infected cells to form syncytia in culture. Real-time PCR analysis demonstrated that both neuropathogenic and non-neuropathogenic EHV-1 strains replicated in neurons and ED cells (equine dermal cell line) at a similar level. We can assume that a point mutation in the EHV-1 polymerase does not affect viral replication in this cell type.

Quest for highly connected metal-organic framework platforms: rare-earth polynuclear clusters versatility meets net topology needs.

Gaining control over the assembly of highly porous rare-earth (RE) based metal-organic frameworks (MOFs) remains challenging. Here we report the latest discoveries on our continuous quest for highly connected nets. The topological exploration based on the noncompatibility of a 12-connected RE polynuclear carboxylate-based cluster, points of extension matching the 12 vertices of the cuboctahedron (cuo), with 3-connected organic ligands led to the discovery of two fascinating and highly connected minimal edge-transitive nets, pek and aea. The reduced symmetry of the employed triangular tricarboxylate ligand, as compared to the prototype highly symmetrical 1,3,5-benzene(tris)benzoic acid guided the concurrent occurrence of nonanuclear [RE9(µ3-OH)12(µ3-O)2(O2C-)12] and hexanuclear [RE6(OH)8(O2C-)8] carboxylate-based clusters as 12-connected and 8-connected molecular building blocks in the structure of a 3-periodic pek-MOF based on a novel (3,8,12)-c trinodal net. The use of a tricarboxylate ligand with modified angles between carboxylate moieties led to the formation of a second MOF containing solely nonanuclear clusters and exhibiting once more a novel and a highly connected (3,12,12)-c trinodal net with aea topology. Notably, it is the first time that RE-MOFs with double six-membered ring (d6R) secondary building units are isolated, representing therefore a critical step forward toward the design of novel and highly coordinated materials using the supermolecular building layer approach while considering the d6Rs as building pillars. Lastly, the potential of these new MOFs for gas separation/storage was investigated by performing gas adsorption studies of various probe gas molecules over a wide range of pressures. Noticeably, pek-MOF-1 showed excellent volumetric CO2 and CH4 uptakes at high pressures.

Pharmacokinetics of Monoclonal Antibodies Throughout Pregnancy: A Systematic Literature Review.

BACKGROUND AND OBJECTIVE: Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for various indications. The aim of this systematic literature review was to characterize the PK of mAbs throughout pregnancy. METHODS: A systematic literature search was carried out in PubMed and Embase on 21 April 2023. Articles were included when information on PK or exposure parameters of mAbs in pregnant women was available. RESULTS: A total of 42 relevant articles were included, of which eight discussed adalimumab, three certolizumab pegol, five eculizumab, one golimumab, 12 infliximab (IFX), two natalizumab, one canakinumab, one omalizumab, five tocilizumab, eight ustekinumab, and five vedolizumab. One of the 42 studies reported information on clearance (CL) and volume of distribution (VD) of IFX; all other studies only reported on serum concentrations in the pre-pregnancy state, different trimesters, and the postpartum period. For all of the assessed mAbs except IFX, serum concentrations were similar to concentrations in the pre-pregnancy state or modestly decreased. In contrast, IFX trough concentrations generally increased in the second and third trimesters in comparison to the non-pregnant state. CONCLUSION: Available information suggests that the anatomical and physiological changes throughout pregnancy may have meaningful effects on the PK of mAbs. For most mAbs (not IFX), modestly higher dosing (per mg) maybe needed during pregnancy to sustain a similar serum exposure compared to pre-pregnancy.

Hyperprolactinemia in antipsychotic-naive patients with first-episode psychosis.

BACKGROUND: Hyperprolactinemia is frequent in patients with schizophrenic psychoses. It is usually regarded as an adverse effect of antipsychotics but has recently also been shown in patients without antipsychotic medication. Our objective was to test whether hyperprolactinemia occurs in antipsychotic-naive first-episode patients (FEPs). METHOD: In the framework of the European First Episode Schizophrenia Trial (EUFEST), 249 out of 498 FEPs were eligible for this study, of whom 74 were antipsychotic naive. All patients were investigated regarding their serum prolactin levels with immunoassays standardized against the 3rd International Reference Standard 84/500. RESULTS: Twenty-nine (39%) of the 74 antipsychotic-naive patients showed hyperprolactinemia not explained by any other reason, 11 (50%) of 22 women and 18 (35%) of 52 men. CONCLUSIONS: Hyperprolactinemia may be present in patients with schizophrenic psychoses independent of antipsychotic medication. It might be stress induced. As enhanced prolactin can increase dopamine release through a feedback mechanism, this could contribute to explaining how stress can trigger the outbreak of psychosis.

A phase II study of metformin plus pemetrexed and carboplatin in patients with non-squamous non-small cell lung cancer (METALUNG).

Immune checkpoint inhibitors (ICIs) ± chemotherapy is the standard treatment for driver mutation-negative non-small cell lung cancer (NSCLC). However, accessibility to ICIs in LMICs is limited due to high cost, and platinum-based chemotherapy remains the mainstay of treatment. Metformin has anticancer properties, and studies suggest synergism between metformin and pemetrexed. Based on preclinical evidence, this combination may be more beneficial for STK11-mutated NSCLC, a subgroup, inherently resistant to ICIs. In this Simon two-stage, single-arm phase 2 trial, we investigated metformin with pemetrexed-carboplatin (PC) in patients with treatment-naive stage IV non-squamous NSCLC. The primary outcome was 6-month progression-free survival (PFS) rate. Secondary outcomes were safety, overall survival (OS), overall response rate (ORR), proportion of STK11 mutation, and effect of STK11 mutation on 6-month PFS rate. The study was terminated for futility after interim analysis. The median follow-up was 34.1 months. The 6-month PFS rate was 28% (95% CI 12.4-0.46). The median PFS and OS were 4.5 (95% CI 2.2-6.1) and 7.4 months (95% CI 5.3-15.3), respectively. The ORR was 72%. Gastrointestinal toxicities were the most common. No grade 4/5 toxicities were reported. Targeted sequencing was possible in nine cases. Two patients had STK11 mutation and a poor outcome (PFS < 12 weeks). We could not demonstrate the benefit of metformin with CP in terms of improvement in 6-month PFS rate; however, the combination was safe (CTRI/2019/02/017815).

Unveiling meta-Alkyloxy/-Silyloxy-Substituted N-Aryl PNP Ligands for Efficient Cr-Catalyzed Ethylene Tetramerization.

Novel N-aryl-functionalized PNP ligands (1-4) bearing m-alkyloxy/-silyloxy substituents were prepared and evaluated for chromium-catalyzed ethylene oligomerization using MMAO-3A as an activator. The selected Cr/PNP system under optimized condition exhibited high 1-octene-selective (up to 70 wt %) ethylene tetramerization at a remarkable rate (over 3000 kg gCr-1 h-1). More importantly, the undesirable polyethylene selectivity was restricted to a minimum level of ∼1-2 wt % for pre-catalysts derived with ligands 1 and 2. Employing chlorobenzene as a reaction medium yielded best productivity in conjunction to the total α-olefin (1-C6 + 1-C8) selectivity (∼88 wt %). N-aryl PNP ligands (3 and 4) incorporating m-silyloxy substituents in the phenyl ring exhibited relatively poorer tetramerization performance while yielding higher PE fraction as compared to their m-alkyloxy derivatives. A detailed molecular structure of the best-performing pre-catalyst 1-Cr was established by single-crystal X-ray diffraction analysis. The stability of 1/Cr-based catalyst system was investigated for a reaction time of up to 2 h under optimized condition.

Scale-up and manufacturing of clinical-grade self-inactivating γ-retroviral vectors by transient transfection.

The need for γ-retroviral (gRV) vectors with a self-inactivating (SIN) design for clinical application has prompted a shift in methodology of vector manufacturing from the traditional use of stable producer lines to transient transfection-based techniques. Herein, we set out to define and optimize a scalable manufacturing process for the production of gRV vectors using transfection in a closed-system bioreactor in compliance with current good manufacturing practices (cGMP). The process was based on transient transfection of 293T cells on Fibra-Cel disks in the Wave Bioreactor. Cells were harvested from tissue culture flasks and transferred to the bioreactor containing Fibra-Cel in the presence of vector plasmid, packaging plasmids and calcium-phosphate in Dulbecco's modified Eagle's medium and 10% fetal bovine serum. Virus supernatant was harvested at 10-14 h intervals. Using optimized procedures, a total of five ecotropic cGMP-grade gRV vectors were produced (9 liters each) with titers up to 3.6 × 10(7) infectious units per milliliter on 3T3 cells. One GMP preparation of vector-like particles was also produced. These results describe an optimized process for the generation of SIN viral vectors by transfection using a disposable platform that allows for the generation of clinical-grade viral vectors without the need for cleaning validation in a cost-effective manner.

Critical variables affecting clinical-grade production of the self-inactivating gamma-retroviral vector for the treatment of X-linked severe combined immunodeficiency.

Patients with X-linked severe combined immunodeficiency (SCID-X1) were successfully cured following gene therapy with a gamma-retroviral vector (gRV) expressing the common gamma chain of the interleukin-2 receptor (IL2RG). However, 5 of 20 patients developed leukemia from activation of cellular proto-oncogenes by viral enhancers in the long-terminal repeats (LTR) of the integrated vector. These events prompted the design of a gRV vector with self-inactivating (SIN) LTRs to enhance vector safety. Herein we report on the production of a clinical-grade SIN IL2RG gRV pseudotyped with the Gibbon Ape Leukemia Virus envelope for a new gene therapy trial for SCID-X1, and highlight variables that were found to be critical for transfection-based large-scale SIN gRV production. Successful clinical production required careful selection of culture medium without pre-added glutamine, reduced exposure of packaging cells to cell-dissociation enzyme, and presence of cations in wash buffer. The clinical vector was high titer; transduced 68-70% normal human CD34(+) cells, as determined by colony-forming unit assays and by xenotransplantation in immunodeficient NOD.CB17-Prkdc(scid)/J (nonobese diabetic/severe combined immunodeficiency (NOD/SCID)) and NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NOD/SCID gamma (NSG))) mice; and resulted in the production of T cells in vitro from human SCID-X1 CD34(+) cells. The vector was certified and released for the treatment of SCID-X1 in a multi-center international phase I/II trial.

Cut off values for abdominal obesity as a criterion of metabolic syndrome in an ethnic Kyrgyz population (Central Asian region).

BACKGROUND: People of different racial and ethnic backgrounds have a distinct pattern of central fat deposition, thus making it necessary to devise a race based approach for the diagnosis and evaluation of abdominal obesity (AO). This is the first study to determine the optimal waist circumference (WC) cutoff values for definition of AO in an ethnic Kyrgyz population. METHODS: 323 persons of Kyrgyz ethnicity (183 women and 140 men), with a mean age of 51.8 ± 9.5 years old were included in the study. Measurement of blood pressure (BP), anthropometric data (including body mass index calculation and WC measurement), fasting blood sugar, serum lipid parameters and insulin were performed in all examined individuals. Insulin resistance (IR) was considered as HOMA index (insulin × fasting glucose/22.5) ≥ 2.77. Sensitivity and specificity for the presence of IR or two other criteria of MS (according to the international classification, 2009) were calculated by using receiver operating characteristic (ROC) curves for men and women separately. RESULTS: The optimal sensitivity and specificity obtained from the ROC curves for IR were 88 cm in women (sensitivity of 0.85, 95%CI (0.72-0.93), specificity of 0.58, 95%CI (0.49-0.66)) and 94 cm for men (sensitivity of 0.8, 95% CI (0.65-0.91), specificity of 0.61, 95% CI (0.51-0.71)). The data from the ROC curve for any two other MS criteria confirmed the results and the WC 88 cm in women (sensitivity of 0.82, 95% CI (0.72-0.9), specificity of 0.72, 95% CI (0.62-0.8)) and 94 cm in men (sensitivity of 0.74, 95% CI (0.62-0.84), specificity of 0.73, 95% CI (0.61-0.83)) were corresponded to the optimal sensitivity and specificity. CONCLUSION: WC ≥ 88 cm and ≥ 94 cm should be used as a criterion for the diagnosis of AO for Kyrgyz women and men respectively based on these results.

Paediatric aesthetic dentistry: a review.

AIM: A number of conditions can lead to aesthetically unacceptable dentitions like dental caries, discoloration, trauma, early loss of teeth, misalignment and any abnormality of shape and size. Today we have a large number of solutions available for aesthetic problems in paediatric dentistry. But the biggest dilemma is: How to choose what is best for a particular patient and that situation? Through this review we try to precisely highlight the various options for aesthetic restorations along with their indications, advantages and disadvantages. METHODS: A search and analysis of international works on aesthetics in paediatric dentistry is presented. RESULTS: A considerable number of studies have shown that people are more concerned about missing anterior teeth and their replacement than about posterior ones as aesthetics seems to be more important than function. CONCLUSION: Dental caries, although not life threatening, causes nagging pain and physical as well as psychological discomfort. Nevertheless, it is clear that the condition is complex and multifactorial and hence it is important to review the various approaches available to restore the lost aesthetics.

Applicability of Demirjian's method of age assessment in a North Indian female population.

AIM: This study was conducted to determine whether the standards of dental maturation given by Demirjian et al. are applicable to North Indian children and to assess the relationship between dental age and chronological age. METHODS: In this study OPGs of 100 females of 8-14 years were taken, and dental age was calculated according to the Demirjian method. Chronological age was recorded and compared to dental age. STATISTICAL ANALYSIS: Collected data was statistically analysed. Pearson's correlation coefficient was used to correlate the dental and chronological age of the 100 girls. The statistical analysis was done by using SPSS version 10.0 software (SPSS Inc., Chicago IL). For all tests the p-value of <0.05 was considered for statistical significance. RESULTS: A strong correlation was found between chronological and dental ages. CONCLUSION: In the present pilot work it was concluded that the Demirjian method of dental age assessment showed high accuracy when applied to North Indian paediatric population.

Diversity of rumen microbiota using metagenome sequencing and methane yield in Indian sheep fed on straw and concentrate diet.

An in vivo study aiming to investigate the rumen methanogens community structure was conducted in Mandya sheep fed on straw and concentrate diet. The ruminal fluid samples were collected and processed for unravelling the rumen microbiota and methanogens diversity. Further, the daily enteric methane emission and methane yield was also quantified using the SF6 tracer technique. Results indicated that the Bacteroidetes (∼57%) and Firmicutes (25%) were two prominent affiliates of the bacterial community. Archaea represented about 2.5% of the ruminal microbiota. Methanobacteriales affiliated methanogens were the most prevalent in sheep rumen. The study inveterate that the ruminal archaea community in sheep is composed of 9 genera and 18 species. Methanobrevibacter represented the largest genus of the archaeome, while methylotrophs genera constituted only 13% of the community. Methanobrevibacter gottschalkii was the prominent methanogen, and Methaobrevibacter ruminantium distributed at a lower frequency (∼2.5%). Among Methanomassiliicoccales, Group 12 sp. ISO4-H5 constituted the most considerable fraction (∼11%). KEGG reference pathway for methane metabolism indicated the formation of methane through hydrogenotrophic and methylotrophic pathways, whereas the acetoclastic pathway was not functional in sheep. The enteric methane emission and methane yield was 19.7 g/d and 20.8 g/kg DMI, respectively. Various species of Methanobrevibacter were differently correlated, and the distribution of hydrogenotrophic methanogens mainly explained the variability in methane yield between the individual sheep. It can be inferred from the study that the hydrogenotrophic methanogens dominate the rumen archaeal community in sheep and methylotrophic/aceticlastic methanogens represent a minor fraction of the community. Further studies are warranted for establishing the metabolic association between the prevalent hydrogenotrophs and methylotrophs to identify the key reaction for reducing methane emission.

Physical Constraint in Pediatric Dentistry: The Lived Experience of Parents.

BACKGROUND: The use of physical constraint in pediatric dentistry is highly controversial. Papoose boards in particular, which envelop and immobilize children during treatment procedures, have been described as barbaric devices even though their goal is to protect the patient. In this debate, the voice of parents is important but still missing in the scientific literature. AIM: To understand how parents or caregivers experienced physical constraint and the use of the papoose board on their children during regular dental treatment. DESIGN: We conducted qualitative research rooted in interpretive phenomenology. Accordingly, we performed in-depth individual interviews with a purposive sample of 7 parents or caregivers. The interviews took place in Montréal, Canada, after the children had been treated with a papoose board for nonemergency dental treatments. The discussions were audio recorded, transcribed, and thematically analyzed. RESULTS: Two perspectives emerged among participants. Some explained that the papoose board calmed their children, helped the dentist to complete the procedures, and made their experience less stressful. For others, the papoose board was a horrible and traumatizing experience, leading to feelings of guilt toward their children. They expressed anger toward the dentists for not allowing them enough time to decide and for imposing use of the device. CONCLUSION: Our study raises serious ethical concerns about this practice. We believe that using a papoose board should remain an extraordinary measure and, more generally, that dental professionals should reflect on the place of children and their families in clinical encounters. KNOWLEDGE TRANSFER STATEMENT: The findings of this study should encourage policy makers, dental professionals and ethicists to consider the following points: 1) the traumatizing experiences described by parents raise serious ethical concerns about the use of papoose boards; 2) the dental profession should reflect on the place of children and their families in the clinical encounter and grapple with the importance of consent and how to ensure consent in encounters involving children and their parents.

Highly Efficient Ethylene Tetramerization Using Cr Catalysts Constructed with Trifluoromethyl-Substituted N-Aryl PNP Ligands.

Tetramerization of ethylene by chromium catalysts stabilized with functionalized N-aryl phosphineamine ligands C6H4(m-CF3)N(PPh2)2 (1), C6H4(p-CF3)N(PPh2)2 (2), C6H4(o-CF3)N=PPh2-PPh2 (3), and C6H3(3,5-bis(CF3))N(PPh2)2 (4) was evaluated. The parameter optimization includes temperature, co-catalyst, and solvent. Upon activation with MMAO-3A, the new catalyst system especially with m-functional PNP ligand (1) exhibited high 1-octene selectivity and productivity while giving minimum undesirable polyethylene and C10 + olefin by-products. Using PhCl as a solvent at 75 °C led to a remarkable α-olefin (1-C6 + 1-C8) selectivity (>90 wt %) at a reaction rate of 2000 kg·gCr -1·h-1. Under identical conditions, analogous PNP ligands bearing -CH3, -Et, and -Cl functional moieties at the meta position of the N-phenyl ring displayed significantly lower reactivity. The catalyst with p-functional ligand (2) exhibited lower activity and comparable selectivities, while the Cr/PPN (with ligand 3) system gave no noticeable reactivity. The molecular structure of the precatalyst (1-Cr), exhibiting a monomeric structural feature, was elucidated with the aid of single-crystal X-ray diffraction study.