We examine the impact of the 2008-2009 Crisis on two dimensions of manufacturing firms in Eastern Europe and Central Asia, i.e., receivables collection (whether the customers pay after the delivery ...rather than before or on the date of delivery) and financing of manufacturing firms’ fixed asset purchases (what type of financing they used before and after the 2008-2009 Crisis). We use the Business Environment and Enterprise Performance Survey (BEEPS), i.e., BEEPS IV and BEEPS V data to represent the pre-Crisis and post-Crisis periods respectively. Our analysis indicates that the percentage of purchases paid by the customers of the manufacturing firms significantly decline from the pre-Crisis to the post-Crisis period. This finding suggests that manufacturing firms tighten their payment policies and are not as lenient with their customers post-Crisis. In addition, we find that the percentage of manufacturing firms’ fixed asset purchases paid for by internal financing significantly increases, whereas the percentage of fixed asset purchases paid for by owner’s contribution and supplier credit significantly decline post-Crisis. These findings suggest that as a result of the 2008-2009 Crisis, manufacturing firms in these countries seem to rely more on internal funding which may be due to tighter availability of external sources or drainage of shareholders funds (not enough cash) post-Crisis.
Delayed administration of vascular endothelial growth factor (VEGF) promotes functional recovery after focal cerebral ischemia. However, early intravenous injection of VEGF increases blood–brain ...barrier (BBB) leakage, hemorrhagic transformation and infarct volume whereas its application to cortical surface is neuroprotective. We have investigated whether or not early intracerebroventricular administration of VEGF could replicate the neuroprotective effect observed with topical application and the mechanism of action of this protection. Mice were subjected to 90 mins middle cerebral artery (MCA) occlusion and 24 h of reperfusion. Vascular endothelial growth factor (8 ng, intracerebroventricular) was administered 1 or 3 h after reperfusion. Compared with the vehicle-treated (intracerebroventricular) group, VEGF decreased the infarct volume along with BBB leakage in both treatment groups. Neurologic disability scores improved in parallel to the changes in infarct volume. Independently of the decrease in infarct size, VEGF also reduced the number of TUNEL-positive apoptotic neurons. Phospo-Akt levels were significantly higher in ischemic hemispheres of the VEGF-treated mice. Contrary to intracerebroventricular route, intravenous administration of VEGF (15 μg/kg) enhanced the infarct volume as previously reported for the rat. In conclusion, single intracerebroventricular injection of VEGF protects brain against ischemia without adversely affecting BBB permeability, and has a relatively long therapeutic time window. This early neuroprotective action, observed well before recovery-promoting actions such as angiogenesis, possibly involves activation of the PI-3-Akt pathway.
Objective
To identify causes of the autosomal‐recessive malformation, diencephalic‐mesencephalic junction dysplasia (DMJD) syndrome.
Methods
Eight families with DMJD were studied by whole‐exome or ...targeted sequencing, with detailed clinical and radiological characterization. Patient‐derived induced pluripotent stem cells were derived into neural precursor and endothelial cells to study gene expression.
Results
All patients showed biallelic mutations in the nonclustered protocadherin‐12 (PCDH12) gene. The characteristic clinical presentation included progressive microcephaly, craniofacial dysmorphism, psychomotor disability, epilepsy, and axial hypotonia with variable appendicular spasticity. Brain imaging showed brainstem malformations and with frequent thinned corpus callosum with punctate brain calcifications, reflecting expression of PCDH12 in neural and endothelial cells. These cells showed lack of PCDH12 expression and impaired neurite outgrowth.
Interpretation
DMJD patients have biallelic mutations in PCDH12 and lack of protein expression. These patients present with characteristic microcephaly and abnormalities of white matter tracts. Such pathogenic variants predict a poor outcome as a result of brainstem malformation and evidence of white matter tract defects, and should be added to the phenotypic spectrum associated with PCDH12‐related conditions. Ann Neurol 2018;84:646–655
Alternative splicing plays a critical role in mouse neurodevelopment, regulating neurogenesis, cortical lamination, and synaptogenesis, yet few human neurodevelopmental disorders are known to result ...from pathogenic variation in splicing regulator genes. Nuclear Speckle Splicing Regulator Protein 1 (NSRP1) is a ubiquitously expressed splicing regulator not known to underlie a Mendelian disorder.
Exome sequencing and rare variant family-based genomics was performed as a part of the Baylor-Hopkins Center for Mendelian Genomics Initiative. Additional families were identified via GeneMatcher.
We identified six patients from three unrelated families with homozygous loss-of-function variants in NSRP1. Clinical features include developmental delay, epilepsy, variable microcephaly (Z-scores -0.95 to -5.60), hypotonia, and spastic cerebral palsy. Brain abnormalities included simplified gyral pattern, underopercularization, and/or vermian hypoplasia. Molecular analysis identified three pathogenic NSRP1 predicted loss-of-function variant alleles: c.1359_1362delAAAG (p.Glu455AlafsTer20), c.1272dupG (p.Lys425GlufsTer5), and c.52C>T (p.Gln18Ter). The two frameshift variants result in a premature termination codon in the last exon, and the mutant transcripts are predicted to escape nonsense mediated decay and cause loss of a C-terminal nuclear localization signal required for NSRP1 function.
We establish NSRP1 as a gene for a severe autosomal recessive neurodevelopmental disease trait characterized by developmental delay, epilepsy, microcephaly, and spastic cerebral palsy.
Rapid initiation of antiretroviral therapy (ART) reduces the transmission of HIV infection in the community. This study aimed to determine whether rapid ART initiation is effective compared to ...standard ART treatment in our country.
Patients were grouped based on time to treatment initiation. HIV RNA levels, CD+4 T cell count, CD4/CD8 ratio, and ART regimens were recorded at baseline and follow-up visits for 12 months.
There were 368-ART naive adults (treatment initiated at the time of HIV diagnosis; 143 on the first day, 48 on the second-seventh day, and 177 after the seventh day). Although virological suppression rates at 12
months were higher in all groups, over 90% on average, there were no statistically significant differences in HIV-1 RNA suppression rates, CD+4 T cell count, and CD4/CD8 ratio normalization in the studied months but in multivariate logistic regression analysis; showed a significant correlation between both virological and immunological response and those with CD4+ T <350 cells/mL at 12th month in total patients.
Our findings support the broader application of recommendations for rapid ART initiation in HIV patients.
The structural, magnetic, and magnetocaloric properties of the Pr
2
Fe
17-x
Ti
x
(
x
= 0, 0.2, 0.4, 0.6) intermetallic compounds prepared by the arc-melting process were investigated. X-ray analyses ...indicated that all samples are single phase with the rhombohedral Th
2
Zn
17
-type structure. The unit-cell volume was determined to increase with the increasing Ti content. The magnetic measurements revealed that the Curie temperature increases with Ti content from 286 K for
x
= 0 to 337 K for
x
= 0.6. The maximum value of |ΔSm| tends to decrease from 5.63 J/kg.K for
x
= 0 to 4.28 J/kg.K for
x
= 0.6 with increasing Ti content at 5 T magnetic field change. At the same magnetic field change, the relative cooling power (RCP) ranges from 425.17 J/Kg for
x
= 0 to 385.62 J/Kg for
x
= 0.6. The critical exponents (
β
,
γ
, and
δ
) determined from magnetocaloric data for
x
< 0.2 belong to mean-field model with long-range ferromagnetic interaction. A small deviation in the critical exponents of
γ
and
δ
for
x
> 0.4 samples was attributed to inhomogeneous magnetic state of the samples. From the phase analysis, it was concluded that all samples showed a second-order magnetic phase transition.
Summary Introduction Botulinum toxin injections are previously reported to be a noninvasive alternative method for treating masseteric hypertrophy. However, there is a debate on finding an ideal ...place for injection. The aim of this study is to document the anatomical landmarks for defining the motor nerve entry points (MNEPs) of the masseteric nerve in the masseter for effective botulinum toxin injections. Materials and methods Twelve sides from six adult fixed cadavers were used for this study. The MNEPs of the masseteric nerve were defined according to standard landmark lines including the orbitomeatal line (OML) and the line (VL), which intersects the mid-distance of the OML to the tip of the angle of the mandible. Results All MNEPs were located 4.4 cm inferior to the OML. In addition, the average anterior distance of the MNEPs to the VL was 1.4 cm and the average posterior distance was 0.6 cm. Conclusion The ideal site of Botox injection into the masseter is a rectangular area: 5 cm inferior to the OML, 1 cm anterior and posterior to the VL, and just above the periosteum. Based on the data of our study, injections to the parotid gland and branches of the facial nerve such as the marginal mandibular and buccal can be avoided. The masseteric nerve can easily be found approximately 1.0–1.5 cm inferior to the zygomatic arch, 1 cm medial to the temporomandibular joint capsule, and 1 cm superior to mandibular notch, which makes its use for facial reanimations more efficient.
Objective: We aimed to evaluate the clinical and laboratory features and MEFV allele distribution in Crimean Tatar familial Mediterranean fever patients and to compare them with Turkish familial ...Mediterranean fever patients and healthy controls. Materials and Methods: All newly diagnosed familial Mediterranean fever patients with Crimean Tatar nationality (n = 18) in Children’s Regional Hospital in Simferopol were enrolled in the study and were compared to 40 familial Mediterranean fever cases followed up at Hacettepe University, Ankara, Turkey. The distribution of MEFV alleles was assessed in the 127 unrelated healthy Crimean Tatar adults aged 20 years or more from different parts of the Crimea peninsula. Results: Age and gender distribution, the frequency of colchicine resistance, and colchicine intolerance were similar between Turkish and Crimean Tatar children with familial Mediterranean fever. The duration of familial Mediterranean fever attack was shorter in Turkish patients than in Crimean Tatar (2.0 vs. 3.0 days, P < .001). Chest pain was more frequent in Turkish familial Mediterranean fever patients, whereas arthralgia, arthritis, and erysipeloid rash were more common in Crimean TatarT. MEFV allele distribution in Crimean Tatar was M694V-81%, M680I and V726A 9.5% both, and 68.6%, 14.3%, and 12.9% in Turkish, consequently. Homozygous carriers were 11%, compound-heterozygous was 6%, and heterozygous was 83%, compared to Turkish being 45%, 30%, and 25%, respectively. The allele distribution in healthy Crimean Tatar and Turkish was 10.2% and M694V was 7.1%, M680I was 1.6%, and V726A was 1.6%. Conclusion: The similar MEFV allele prevalence in both populations suggests the high prevalence of familial Mediterranean fever and the high number of undiagnosed patients in the Crimea peninsula. Younger age at onset, shorter duration of attacks, the prevalence of articular involvement, and erysipeloid rash were distinctive features of familial Mediterranean fever in Crimean Tatar.
Background:
Genetic profiling of resected tumor or biopsy samples is increasingly used for cancer diagnosis and therapy selection for thyroid and other cancer types. Although mutations occur in cell ...DNA and are typically detected using DNA sequencing, recent attempts focused on detecting pathogenic variants from RNA. The aim of this study was to determine the completeness of capturing mutations using RNA sequencing (RNA-Seq) in thyroid tissue and fine-needle aspiration (FNA) samples.
Methods:
To compare the detection rate of mutations between DNA sequencing and RNA-Seq, 35 tissue samples were analyzed in parallel by whole-exome DNA sequencing (WES) and whole-transcriptome RNA-Seq at two study sites. Then, DNA and RNA from 44 thyroid FNA samples and 47 tissue samples were studied using both targeted DNA sequencing and RNA-Seq.
Results:
Of 162 genetic variants identified by WES of DNA in 35 tissue samples, 77 (48%) were captured by RNA-Seq, with a detection rate of 49% at site 1 and 46% at site 2 and no difference between thyroid and nonthyroid samples. Targeted DNA sequencing of 91 thyroid tissue and FNA samples detected 118 pathogenic variants, of which 57 (48%) were identified by RNA-Seq. For DNA variants present at >10% allelic frequency (AF), the detection rate of RNA-Seq was 62%, and for those at low (5–10%) AF, the detection rate of RNA-Seq was 7% (
p
< 0.0001). For common oncogenes (
BRAF
and
RAS
), 94% of mutations present at >10% AF and 11% of mutations present at 5–10% AF were captured by RNA-Seq. As expected, none of
TERT
promoter mutations were identified by RNA-Seq. The rate of mutation detection by RNA-Seq was lower in FNA samples than in tissue samples (32% vs. 49%,
p
= 0.02).
Conclusions:
In this study, RNA-Seq analysis detected only 46–49% of pathogenic variants identifiable by sequencing of tumor DNA. Detection of mutations by RNA-Seq was more successful for mutations present at a high allelic frequency. Mutations were more often missed by RNA-Seq when present at low frequency or when tested on FNA samples. All
TERT
mutations were missed by RNA-Seq. These data suggest that RNA-Seq does not detect a significant proportion of clinically relevant mutations and should be used with caution in clinical practice for detecting DNA mutations.
Résumé
Dans cette analyse sur l'évolution de l'écart salarial entre hommes et femmes, l'autrice évalue le rôle de la variation du rendement salarial des compé‐tences professionnelles «cérébrales» ...(cognitives et interpersonnelles) et «physiques» (compétences motrices et force musculaire). Utilisant une série harmonisée sur six pays européens et des données comparables sur les États‐Unis, elle montre que l'effet du prix des compétences professionnelles est très variable selon les pays. Toutefois, dans tous les pays de l'échantillon, une proportion considérable de l'évo‐lution de l'écart de rémunération entre hommes et femmes reste inexpliquée par l'évolution de ce prix.
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