Tocilizumab in COVID-19 interstitial pneumonia.

BACKGROUND: Published reports on tocilizumab in COVID-19 pneumonitis show conflicting results due to weak designs or heterogeneity in critical methodological issues. METHODS: This open-label trial, structured according to Simon's optimal design, aims to identify factors predicting which patients could benefit from anti-IL6 strategies and to enhance the design of unequivocal and reliable future randomized trials. A total of 46 patients with COVID-19 pneumonia needing of oxygen therapy to maintain SO2 > 93% and with recent worsening of lung function received a single infusion of tocilizumab. Clinical and biological markers were measured to test their predictive values. Primary end point was early and sustained clinical response. RESULTS: Twenty-one patients fulfilled pre-defined response criteria. Lower levels of IL-6 at 24 h after tocilizumab infusion (P = 0.049) and higher baseline values of PaO2/FiO2 (P = 0.008) predicted a favourable response. CONCLUSIONS: Objective clinical response rate overcame the pre-defined threshold of 30%. Efficacy of tocilizumab to improve respiratory function in patients selected according to our inclusion criteria warrants investigations in randomized trials.

Blame It on the Metabolite: 3,5-Dichloroaniline Rather than the Parent Compound Is Responsible for the Decreasing Diversity and Function of Soil Microorganisms.

Pesticides are key stressors of soil microorganisms with reciprocal effects on ecosystem functioning. These effects have been mainly attributed to the parent compounds, while the impact of their transformation products (TPs) has been largely overlooked. We assessed in a meadow soil (soil A) the transformation of iprodione and its toxicity in relation to (i) the abundance of functional microbial groups, (ii) the activity of key microbial enzymes, and (iii) the diversity of bacteria, fungi, and ammonia-oxidizing microorganisms (AOM) using amplicon sequencing. 3,5-Dichloroaniline (3,5-DCA), the main iprodione TP, was identified as a key explanatory factor for the persistent reduction in enzymatic activities and potential nitrification (PN) and for the observed structural changes in the bacterial and fungal communities. The abundances of certain bacterial (Actinobacteria, Hyphomicrobiaceae, Ilumatobacter, and Solirubrobacter) and fungal (Pichiaceae) groups were negatively correlated with 3,5-DCA. A subsequent study in a fallow agricultural soil (soil B) showed limited formation of 3,5-DCA, which concurred with the lack of effects on nitrification. Direct 3,5-DCA application in soil B induced a dose-dependent reduction of PN and NO3--N, which recovered with time. In vitro assays with terrestrial AOM verified the greater toxicity of 3,5-DCA over iprodione. "Candidatus Nitrosotalea sinensis" Nd2 was the most sensitive AOM to both compounds. Our findings build on previous evidence on the sensitivity of AOM to pesticides, reinforcing their potential utilization as indicators of the soil microbial toxicity of pesticides in pesticide environmental risk analysis and stressing the need to consider the contribution of TPs in the toxicity of pesticides on the soil microbial community.IMPORTANCE Pesticide toxicity on soil microorganisms is an emerging issue in pesticide risk assessment, dictated by the pivotal role of soil microorganisms in ecosystem services. However, the focus has traditionally been on parent compounds, while transformation products (TPs) are largely overlooked. We tested the hypothesis that TPs can be major contributors to the soil microbial toxicity of pesticides using iprodione and its main TP, 3,5-dichloroaniline, as model compounds. We demonstrated, by measuring functional and structural endpoints, that 3,5-dichloroaniline and not iprodione was associated with adverse effects on soil microorganisms, with nitrification being mostly affected. Pioneering in vitro assays with relevant ammonia-oxidizing bacteria and archaea verified the greater toxicity of 3,5-dichloroaniline. Our findings are expected to advance environmental risk assessment, highlighting the potential of ammonia-oxidizing microorganisms as indicators of the soil microbial toxicity of pesticides and stressing the need to consider the contribution of TPs to pesticide soil microbial toxicity.

Assessment of the impact of three pesticides on microbial dynamics and functions in a lab-to-field experimental approach.

The toxicity of pesticides on soil microorganisms is as an emerging area of concern. Novel and well-standardized tools could be now used to provide a robust assessment of the ecotoxicity of pesticides on soil microorganisms. We followed a tiered lab-to-field approach to assess the toxicity of three pesticides, widely used at EU level, (chlorpyrifos (CHL), isoproturon (IPU) and tebuconazole (TBZ)) on (i) the abundance of 11 microbial taxa and 8 functional microbial groups via q-PCR and (ii) the activity of enzymes involved in biogeochemical cycles via fluorometric analysis. Correlation of microbial measurements with the concentration of pesticides, and their transformation products (TPs) in soil enabled the identification of the compounds driving the effects observed. At lab tests (×1, ×2 and ×10 the recommended dose), CHL and TBZ significantly reduced the relative abundance of ammonia-oxidizing bacteria (AOB) and archaea (AOA) which recovered by the end of the study, while all pesticides induced a persistent reduction in the relative abundance of sulfur-oxidizing bacteria (SOB). The two demethylated metabolites of IPU (MD-IPU and DD-IPU) adversely affected P-cycling enzymes and leucine aminopeptidase (Leu). At field tests (×1, ×2 and ×5 the recommended dose), a persistent reduction on the relative abundance of AOA was induced by all pesticides, but only CHL and its hydrolysis product 3,5,6 trichloro-2-pyridynol (TCP) soil levels were negatively correlated with AOA relative abundance. Our findings suggest that ammonia-oxidizing microorganisms constitute the most responsive microbial group to pesticides and could be potential candidates for inclusion in pesticide risk assessment.

Correction to: Point shear wave ultrasound elastography with Esaote compared to real-time 2D shear wave elastography with supersonic imagine for the quantification of liver stiffness.

Unfortunately, in the first sentence under the section head "Point shear wave elastography", the transducer name was misspelled as CA541 (rather than CA451).

Point shear wave ultrasound elastography with Esaote compared to real-time 2D shear wave elastography with supersonic imagine for the quantification of liver stiffness.

PURPOSE: Different shear wave elastography (SWE) machines able to quantify liver stiffness (LS) have been recently introduced by various companies. The aim of this study was to investigate the agreement between point SWE with Esaote MyLab Twice (pSWE.ESA) and 2D SWE with Aixplorer SuperSonic (2D SWE.SSI). Moreover, we assessed the correlation of these machines with Fibroscan in a subgroup of patients. METHODS: A total of 81 liver disease patients and 27 subjects without liver disease accessing the ultrasound lab were considered. Exclusion criteria were liver nodules, BMI >35, and severe comorbidities. LS was sampled from the same intercostal space with both pSWE.ESA and 2D SWE.SSI and values were tested with Lin's analysis and Bland-Altman analysis (B&A). Agreement between each SWE machine and Fibroscan was assessed in 26 liver disease patients with Spearman correlation. RESULTS: Precision and accuracy between pSWE.ESA and 2D SWE.SSI were, respectively, 0.839 and 0.999. B&A showed a mean of only -0.2 kPa, with no systematic deviation between the techniques and limits of agreement at -11.6 and 11.3 kPa. Spearman's rho correlation versus Fibroscan was 0.849 for pSWE.ESA and 0.878 for 2D SWE.SSI. The relationship became less strict in the higher range of LS (≥15.2 kPa), corresponding to cirrhosis. CONCLUSION: The overall degree of concordance of pSWE.ESA and 2D SWE.SSI in measuring LS resulted remarkable, also when compared with Fibroscan. The less strict correlation for patients with LS in the higher range would not affect the staging of disease as such patients are anyhow classified as cirrhotic.

Investigation of orthologous pathogen recognition gene-rich regions in solanaceous species.

Pathogen receptor proteins such as receptor-like protein (RLP), receptor-like kinase (RLK), and nucleotide-binding leucine-rich repeat (NLR) play a leading role in plant immunity activation. The genome architecture of such genes has been extensively investigated in several plant species. However, we still know little about their elaborate reorganization that arose during the plant speciation process. Using recently released pepper and eggplant genome sequences, we were able to identify 1097 pathogen recognition genes (PRGs) in the cultivated pepper Zunla-1 and 775 in the eggplant line Nakate-Shinkuro. The retrieved genes were analysed for their tendency to cluster, using different methods to infer the means of grouping. Orthologous relationships among clustering loci were found, and interesting reshuffling within given loci was observed for each analysed species. The information obtained was integrated into a comparative map to highlight the evolutionary dynamics in which the PRG loci were involved. Diversification of 14 selected PRG-rich regions was also explored using a DNA target-enrichment approach. A large number of gene variants were found as well as rearrangements of sequences encoding single protein domain and changes in chromosome gene order among species. Gene duplication and transposition activity have clearly influenced plant genome R-gene architecture and diversification. Our findings contribute to addressing several biological questions concerning the parallel evolution that occurred between genomes of the family Solanaceae. Moreover, the integration of different methods proved a powerful approach to reconstruct the evolutionary history in plant families and to transfer important biology findings among plant genomes.

Isolation and genetic analysis of pure cells from forensic biological mixtures: The precision of a digital approach.

Latest genotyping technologies allow to achieve a reliable genetic profile for the offender identification even from extremely minute biological evidence. The ultimate challenge occurs when genetic profiles need to be retrieved from a mixture, which is composed of biological material from two or more individuals. In this case, DNA profiling will often result in a complex genetic profile, which is then subject matter for statistical analysis. In principle, when more individuals contribute to a mixture with different biological fluids, their single genetic profiles can be obtained by separating the distinct cell types (e.g. epithelial cells, blood cells, sperm), prior to genotyping. Different approaches have been investigated for this purpose, such as fluorescent-activated cell sorting (FACS) or laser capture microdissection (LCM), but currently none of these methods can guarantee the complete separation of different type of cells present in a mixture. In other fields of application, such as oncology, DEPArray™ technology, an image-based, microfluidic digital sorter, has been widely proven to enable the separation of pure cells, with single-cell precision. This study investigates the applicability of DEPArray™ technology to forensic samples analysis, focusing on the resolution of the forensic mixture problem. For the first time, we report here the development of an application-specific DEPArray™ workflow enabling the detection and recovery of pure homogeneous cell pools from simulated blood/saliva and semen/saliva mixtures, providing full genetic match with genetic profiles of corresponding donors. In addition, we assess the performance of standard forensic methods for DNA quantitation and genotyping on low-count, DEPArray™-isolated cells, showing that pure, almost complete profiles can be obtained from as few as ten haploid cells. Finally, we explore the applicability in real casework samples, demonstrating that the described approach provides complete separation of cells with outstanding precision. In all examined cases, DEPArray™ technology proves to be a groundbreaking technology for the resolution of forensic biological mixtures, through the precise isolation of pure cells for an incontrovertible attribution of the obtained genetic profiles.

A novel mutation in BCS1L associated with deafness, tubulopathy, growth retardation and microcephaly.

UNLABELLED: We report a novel homozygous missense mutation in the ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene in two consanguineous Turkish families associated with deafness, Fanconi syndrome (tubulopathy), microcephaly, mental and growth retardation. All three patients presented with transitory metabolic acidosis in the neonatal period and development of persistent renal de Toni-Debré-Fanconi-type tubulopathy, with subsequent rachitis, short stature, microcephaly, sensorineural hearing impairment, mild mental retardation and liver dysfunction. The novel missense mutation c.142A>G (p.M48V) in BCS1L is located at a highly conserved region associated with sorting to the mitochondria. Biochemical analysis revealed an isolated complex III deficiency in skeletal muscle not detected in fibroblasts. Native polyacrylamide gel electrophoresis (PAGE) revealed normal super complex formation, but a shift in mobility of complex III most likely caused by the absence of the BCS1L-mediated insertion of Rieske Fe/S protein into complex III. These findings expand the phenotypic spectrum of BCS1L mutations, highlight the importance of biochemical analysis of different primary affected tissue and underline that neonatal lactic acidosis with multi-organ involvement may resolve after the newborn period with a relatively spared neurological outcome and survival into adulthood. CONCLUSION: Mutation screening for BCS1L should be considered in the differential diagnosis of severe (proximal) tubulopathy in the newborn period. WHAT IS KNOWN: • Mutations in BCS1L cause mitochondrial complex III deficiencies. • Phenotypic presentations of defective BCS1L range from Bjornstad to neonatal GRACILE syndrome. What is New: • Description of a novel homozygous mutation in BCS1L with transient neonatal acidosis and persistent de Toni-Debré-Fanconi-type tubulopathy. • The long survival of patients with phenotypic presentation of severe complex III deficiency is uncommon.

Molecular structure and elastic properties of thermotropic liquid crystals: integrated molecular dynamics--statistical mechanical theory vs molecular field approach.

The connection between the molecular structure of liquid crystals and their elastic properties, which control the director deformations relevant for electro-optic applications, remains a challenging objective for theories and computations. Here, we compare two methods that have been proposed to this purpose, both characterized by a detailed molecular level description. One is an integrated molecular dynamics-statistical mechanical approach, where the bulk elastic constants of nematics are calculated from the direct correlation function (DCFs) and the single molecule orientational distribution function [D. A. McQuarrie, Statistical Mechanics (Harper & Row, New York, 1973)]. The latter is obtained from atomistic molecular dynamics trajectories, together with the radial distribution function, from which the DCF is then determined by solving the Ornstein-Zernike equation. The other approach is based on a molecular field theory, where the potential of mean torque experienced by a mesogen in the liquid crystal phase is parameterized according to its molecular surface. In this case, the calculation of elastic constants is combined with the Monte Carlo sampling of single molecule conformations. Using these different approaches, but the same description, at the level of molecular geometry and torsional potentials, we have investigated the elastic properties of the nematic phase of two typical mesogens, 4'-n-pentyloxy-4-cyanobiphenyl and 4'-n-heptyloxy-4-cyanobiphenyl. Both methods yield K3(bend) >K1 (splay) >K2 (twist), although there are some discrepancies in the average elastic constants and in their anisotropy. These are interpreted in terms of the different approximations and the different ways of accounting for the structural properties of molecules in the two approaches. In general, the results point to the role of the molecular shape, which is modulated by the conformational freedom and cannot be fully accounted for by a single descriptor such as the aspect ratio.

Understanding the distinctive elastic constants in an oxadiazole bent-core nematic liquid crystal.

The splay and bend elastic constants of the bent-core oxadiazole material [C5-Ph-ODBP-Ph-OC12] have been investigated as a function of temperature across the nematic phase. The bend constant K(33) is found to take values of ~3.0 pN and to be almost temperature independent, whereas, the splay constant K(11) increases monotonically from ~3.5 pN close to the isotropic phase transition to values of ~9 pN deep in the nematic phase. No pretransitional divergence is observed in either K(11) or K(33) at temperatures approaching the underlying phase. This behavior of the elastic constants is distinct from that observed in rodlike liquid crystal systems but appears to share characteristics with the few other bent-core nematic systems studied to date. We discuss the interdependence of the elastic constants, the birefringence, and the order parameter to allow a comparison of the observed behavior with theory. We show that calculations of the elastic constants via molecular-field theory and atomistic modeling are in excellent qualitative as well as good quantitative (within 2 pN) agreement with the measurements across the temperature range, offering a deeper understanding of the elasticity in bent-core nematic materials than has been, hitherto, available.

Application of the whole-transcriptome shotgun sequencing approach to the study of Philadelphia-positive acute lymphoblastic leukemia.

Although the pathogenesis of BCR-ABL1-positive acute lymphoblastic leukemia (ALL) is mainly related to the expression of the BCR-ABL1 fusion transcript, additional cooperating genetic lesions are supposed to be involved in its development and progression. Therefore, in an attempt to investigate the complex landscape of mutations, changes in expression profiles and alternative splicing (AS) events that can be observed in such disease, the leukemia transcriptome of a BCR-ABL1-positive ALL patient at diagnosis and at relapse was sequenced using a whole-transcriptome shotgun sequencing (RNA-Seq) approach. A total of 13.9 and 15.8 million sequence reads was generated from de novo and relapsed samples, respectively, and aligned to the human genome reference sequence. This led to the identification of five validated missense mutations in genes involved in metabolic processes (DPEP1, TMEM46), transport (MVP), cell cycle regulation (ABL1) and catalytic activity (CTSZ), two of which resulted in acquired relapse variants. In all, 6390 and 4671 putative AS events were also detected, as well as expression levels for 18 315 and 18 795 genes, 28% of which were differentially expressed in the two disease phases. These data demonstrate that RNA-Seq is a suitable approach for identifying a wide spectrum of genetic alterations potentially involved in ALL.

Administration of botanicals with the diet regulates gene expression in peripheral blood cells of Sarda sheep during ACTH challenge.

The aim of the present research was to investigate the regulation of gene expression in ovine blood leukocytes during ACTH-induced cortisol release and the effect of dietary administration of botanicals to counteract the evoked response in polymorphonucleate cells (PMNCs). Thirty-six homogeneous Sarda sheep (age, 18±4.1 mo; BW, 38.7±1.3 kg) were allotted to six groups of six sheep each. One group was used as a negative control (Saline) and five groups were treated, every 12 h for 48 h, with 0.5 mL of ACTH agonist (250 µg/mL of tetracosactrin). Before ACTH treatment, four of the five ACTH-treated groups were separated and fed for 22 d with a basal diet supplemented with extracts from Echinacea angustifolia roots (PO+ACTH), Echinacea angustifolia flowers (EA+ACTH), Andrographis paniculata (AP+ACTH), and the bark of Larix decidua milled (LB+ACTH). Control groups (Saline and ACTH) were fed with the same basal diet without botanicals. Total RNA was extracted from blood samples collected before (T0) and after 3 h (T3) and 51 h (T51) from the first ACTH injection, and transcriptome analysis was performed using a custom oligoarray, designed from 12,194 Ovis aries UniGenes on a CombiMatrix platform. At T3, treatment with ACTH caused down-regulation of transcripts (P<0.001) involved in "response to stress" (GADD45A, GADD45B, WRNIP1, and XRCC6) and in "innate immune response" (MAPK3 and NFkBIB). At T51, treatment with ACTH caused down-regulation (P<0.001) of genes involved in "immune response" (IFNG and IL2) and up-regulation (P<0.001) of NF-κB1 and TP53. Each botanical produced a different (P<0.001) molecular signature for these genes at T3 and T51. The most active botanical in modulating transcriptome modifications in PMNCs after ACTH-induced cortisol release was Larix decidua Mill bark followed by Polinacea roots. These botanicals can be viewed as promising feed supplements in ruminants to cope with conditions associated with increased concentrations of plasma cortisol.

Phase behavior and properties of the liquid-crystal dimer 1'',7''-bis(4-cyanobiphenyl-4'-yl) heptane: a twist-bend nematic liquid crystal.

The liquid-crystal dimer 1'',7''-bis(4-cyanobiphenyl-4'-yl)heptane (CB7CB) exhibits two liquid-crystalline mesophases on cooling from the isotropic phase. The high-temperature phase is nematic; the identification and characterization of the other liquid-crystal phase is reported in this paper. It is concluded that the low-temperature mesophase of CB7CB is a new type of uniaxial nematic phase having a nonuniform director distribution composed of twist-bend deformations. The techniques of small-angle x-ray scattering, modulated differential scanning calorimetry, and dielectric spectroscopy have been applied to establish the nature of the nematic-nematic phase transition and the structural features of the twist-bend nematic phase. In addition, magnetic resonance studies (electron-spin resonance and (2)H nuclear magnetic resonance) have been used to investigate the orientational order and director distribution in the liquid-crystalline phases of CB7CB. The synthesis of a specifically deuterated sample of CB7CB is reported, and measurements showed a bifurcation of the quadrupolar splitting on entering the low-temperature mesophase from the high-temperature nematic phase. This splitting could be interpreted in terms of the chirality of the twist-bend structure of the director. Calculations using an atomistic model and the surface interaction potential with Monte Carlo sampling have been carried out to determine the conformational distribution and predict dielectric and elastic properties in the nematic phase. The former are in agreement with experimental measurements, while the latter are consistent with the formation of a twist-bend nematic phase.

A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.

Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.

Neurological complications of celiac disease and autoimmune mechanisms: preliminary data of a prospective study in adult patients.

Antibodies to gangliosides and Purkinje cells have been reported in patients with celiac disease (CD) with neuropathy and ataxia, respectively. Whether these antibodies are pathogenic is not clear. The response of neurological symptoms and antibody titers to a gluten-free diet is still controversial. The objective of our study was to assess whether neurological manifestations in CD patients correlate with antibody titers and a gluten-free diet.Thirty-five CD patients (9 males, 26 females, mean age 37.1 +/- 12.6 yrs) were followed prospectively. At initial evaluation, 23 were on a gluten-free diet, 12 were not. At recruitment and during follow-up, patients underwent neurological and electrophysiological evaluation. IgG, IgM, and IgA anti-ganglioside antibodies were assayed by ELISA; anti-neuronal antibodies were assessed by immunohistochemistry and Western blot. Four patients, all males, had electrophysiological evidence of neuropathy; three had been on a gluten-free diet for several months, and one was newly diagnosed. One had reduced tendon reflexes; another complained of distal paresthesias. With regard to anti-ganglioside antibodies, three patients had a moderate increase in antibodies without symptoms or signs of neuropathy. No patients had ataxia or cerebellar dysfunction, although in four patients reactivity to neuronal antigens was found. In 17 patients, an electrophysiological follow-up (mean duration of follow-up, 9 months) showed no changes. In conclusion, the preliminary results of this prospective study indicate that neuropathy, usually subclinical, may accompany CD. Antibody titers do not seem to correlate with neurological symptoms/signs or diet. Ongoing follow-up will help confirm these data and clarify the role, if any, of antibodies in neurological involvement in CD.

Molecular theory of dielectric relaxation in nematic dimers.

This paper reports a theory for the dielectric relaxation of dimeric mesogenic molecules in a nematic liquid crystal phase. Liquid crystal dimers consist of two mesogenic groups linked by a flexible chain. Recent experimental studies [D. A. Dunmur, G. R. Luckhurst, M. R. de la Fuente, S. Diez, and M. A. Perez Jubindo, J. Chem. Phys. 115, 8681 (2001)] of the dielectric properties of polar liquid crystal dimers have found unexpected results for both the static (low frequency) and variable frequency dielectric response of these materials. The theory developed in this paper provides a quantitative model with which to understand the observed experimental results. The mean-square dipole moments of alpha,omega-bis[(4-cyanobiphenyl-4'-yl]alkanes in a nematic phase have been calculated using both the rotational isomeric state model and a full torsional potential for the carbon-carbon bonds of the flexible chain. The orienting effect of the nematic phase is taken into account by a parametrized potential of mean torque acting on the mesogenic groups and the segments in the flexible chain. Results of calculations using the full torsional potential are in excellent agreement with experimental results for comparable systems. The probability density p(eq)(beta(A),beta(B)) for the orientation of the mesogenic groups (A,B) along the nematic director is also calculated. The resultant potential of mean torque is a surface characterized by four deep energy wells or sites equivalent to alignment of the terminal groups A and B approximately parallel and antiparallel to the director; of course, the reversal of the director leads to equivalent sites. This potential energy surface provides the basis for a kinetic model of dielectric relaxation in nematic dimers. Solution of the Fokker-Planck equation corresponding to this four-site model gives the time dependence of the site populations, and hence the time-correlation functions for the total dipole moment along the director. In this model the end-over-end rotation of the molecule, corresponding to simultaneous reversal of both mesogenic groups, is excluded because the activation energy is too large. Results are presented for a number of cases, in which a dipole is located on one or both of the mesogenic groups, and additionally where the groups differ in size. For the latter, under particular conditions, the correlation function exhibits a biexponential decay, which corresponds to two low frequency absorptions in the dielectric spectrum. This is exactly what has been observed for nonsymmetric nematic dimers having different groups terminating a flexible chain. Experimental results over a range of temperature for the nonsymmetric dimer alpha-[(4-cyanobiphenyl)-4'-yloxy]-omega-(4-decylanilinebenzylidene-4'-oxy)nonane can be fitted precisely to the theory, which provides new insight into the orientational and conformational dynamics of molecules in ordered liquid crystalline phases.

Two new cases of Barraquer-Simons syndrome.

Barraquer-Simons syndrome is a rare form of partial lipodystrophy, mainly characterized by loss of subcutaneous tissue, starting from the face and spreading to the upper part of the body. Occasional functional anomalies such as deafness, epilepsy, and mental retardation can be associated with the condition; nephropathy and myopathy have been observed occasionally. Here we report on two new sporadic cases, who show at the moment only a facial involvement, without any associated anomalies and/or medical complications.