Distinct Effects of Antidepressants in Association With Mood Stabilizers and/or Antipsychotics in Unipolar and Bipolar Depression.
There is a dearth of studies comparing the clinical outcomes of patients with treatment-resistant unipolar (TRD) depression and depression in bipolar disorder (BD) despite similar treatment strategies. We aimed to evaluate the effects of the pharmacological combinations (antidepressants [AD], mood stabilizers [MS], and/or antipsychotics [AP]) used for TRD and BD at the McGill University Health Center. We reviewed health records of 206 patients (76 TRD 130 BD) with TRD and BD treated with similar augmentation strategies including AD with MS (AD+MS) or AP (AD+AP) or combination (AD+AP+MS). Clinical outcomes were determined by comparing changes on the 17-time Hamilton Depression Rating Scale (HAMD-17), Quick Inventory of Depressive Symptomatology, and Clinical Global Impression-Severity of Illness at the beginning (T0) and after 3 months of an unchanged treatment (T3). Baseline HAMD-17 scores in TRD were higher than in BD (P < 0.001), but TRD patients had a greater improvement at end point (P = 0.003). Antidepressants with AP generated greater reductions in HAMD-17 in TRD compared with BD (P = 0.02). Importantly, in BD patients, the addition of AD compared with other treatment strategies failed to improve the outcome. The limitations of this study include possibly unrepresentative subjects from tertiary care settings, incomplete matching of BD and TRD subjects, nonrandomized treatment with unmatched agents, doses, and times, unknown treatment adherence, and nonblinded retrospective outcome assessments. Nevertheless, the findings may reflect real-world interactions of clinically selected pharmacotherapies. Combination of augmentation strategies such as AD+AP and/or MS showed a better clinical improvement in patients with TRD compared with BD suggesting a limited evidence for AD potentiation in BD.


Classification and Characterization of Tire-Road Wear Particles in Road Dust by Density.
Tire treads are abraded by friction with the road surface, producing tire tread wear particles (TWPs). TWPs combined with other particles on the road such as road wear particles (RWPs) and mineral particles (MPs), forming tire-road wear particles (TRWPs). Dust on an asphalt pavement road is composed of various components such as TRWPs, asphalt pavement wear particles (APWPs), MPs, plant-related particles (PRPs), and so on. TRWPs have been considered as one of major contaminants produced by driving and their properties are important for study on real abrasion behaviors of tire treads during driving as well as environmental contamination. Densities of the TRWPs are totally dependent on the amount of the other components deposited in the TWPs. In this study, a classification method of TRWPs in the road dust was developed using density separation and the classified TRWPs were characterized using image analysis and pyrolytic technique. Chloroform was used to remove APWPs from mixture of TRWPs and APWPs. TRWPs were found in the density range of 1.20-1.70 g/cm3. By decreasing the particle size of the road dust, the TRWP content in the road dust increased and its density slightly tended to increase. Aspect ratios of the TRWPs varied and there were many TRWPs with low aspect ratio below 2.0. The aspect ratio range was 1.2-5.2. Rubber compositions of the TRWPs were found to be mainly NR/SBR biblend or NR/BR/SBR triblend.


Cucurbit[8]uril-mediated supramolecular photoswitching for self-preservation of mesoporous silica nanoparticle delivery system.
In this study, a novel UV-responsive drug carrier based on mesoporous silica nanoparticles (MSNs) has been designed. A 'self' peptide was introduced onto the MSN surface through a supramolecular photoswitchable heteroternary complexation of cucurbit[8]uril, azobenzene and 4,4'-dipyridyl derivative. The light-induced isomerization of azobenzene contributed to the formation of intelligent cucurbit[8]uril based self-preserving MSNs (CSMSNs). In vitro studies demonstrated that the CSMSNs were effectively shielded against macrophages by the peptide protective layer. Doxorubicin hydrochloride (DOX·HCl) could be well encapsulated in the CSMSNs and exhibit low toxicity without UV-irradiation. After reaching the tumor tissue, the peptide camouflage was removed upon UV-irradiation, which enabled the target ligand mediated cell uptake of the drug carrier and the accelerated drug release.


Desmoplastic ameloblastoma: report of a unique case and review of literature.
Desmoplastic Ameloblastoma is a rare variant of ameloblastoma. 90 cases of desmoplastic ameloblastoma have been reported so far in literature. We are presenting a rare case of desmoplastic ameloblastoma in the ramus region of mandible with regards to its clinical and radiographical viewpoints. Only one other case of desmoplastic ameloblastoma has been reported in the ramus region of mandible of the 90 cases that we have reviewed. Review of literature has revealed the tumour to most commonly occur in the 3rd to 5th decade of life with a high preponderance of Japanese males. The anterior region of either jaw was most commonly found to be affected. Radiological appearance was most commonly of a mixed radio-lucent/radio-opaque type with a high incidence of poorly defined borders. However our case differed from the reviewed cases as it was found to be a unilocular lesion with well defined borders. Histopathological findings of our case were consistent with the hisotpathological appearance of the reviewed cases and showed extensive stromal desmoplasia and small tumour nests of odontogenic epithelium scattered in stroma.


The pro-apoptotic actions of 2-methoxyestradiol against ovarian cancer involve catalytic activation of PKCδ signaling.
2-methoxyestradiol (2MeOE2) is a natural metabolite of estradiol, which is generated by the action of CYP1A1 enzyme in the liver. We have previously shown that a flaxseed-supplemented diet decreases both the incidence and severity of ovarian cancer in laying hens, also induces CYP1A1 expression in liver. Recently, we have shown that as a biologically derived active component of flax diet, 2MeOE2 induces apoptosis in ovarian cancer cells which is partially dependent on p38 MAPK. The objective of this study was to elucidate the molecular mechanism of actions of 2MeOE2, a known microtubule disrupting agent, in inducing apoptosis in ovarian tumors. 2MeOE2 induces γH2Ax expression and apoptotic histone modifications in ovarian cancer cells, which are predicted downstream targets of protein kinase Cδ (PKCδ) during apoptosis. Overexpressing full length PKCδ alone does not induce apoptosis but potentiates 2MeOE2-mediated apoptosis. C3-domain mutated dominant-negative PKCδ (PKCδDN) significantly reduces 2MeOE2-induced caspase-3 cleavage and apoptotic histone modification. Silencing PKCδ diminishes 2MeOE2-mediated apoptosis. The catalytic fragment of PKCδ (PKCδCAT) evokes pro-apoptotic effects which are principally dependent on p38 MAPK phosphorylation. The pro-apoptotic actions of 2MeOE2 are in part dependent on catalytic activation of PKCδ. Catalytic activation of PKCδ accelerates the 2MeOE2-induced apoptotic cascade. This study describes a novel molecular action of flaxseed diet in ovarian cancer.


Outcomes of stereotactic radiosurgery for large vestibular schwannomas: a systematic review and meta-analysis.
Large vestibular schwannomas (VS) pose a treatment challenge for both microsurgery (MS) and stereotactic radiosurgery (SRS). Technical developments have allowed for safer irradiation of large tumors. It remains unclear if SRS can achieve appropriate tumor control and acceptable cranial nerve toxicities. In this study, we assess outcomes of irradiation for large VS. PubMed MEDLINE, EMBASE, Web of Science, and Cochrane were searched for all the studies assessing SRS outcome in large VS. Primary endpoints included clinical and radiographic tumor control, need for salvage surgery, serviceable hearing, cranial nerve V and VII impairment, presence of hydrocephalus requiring shunting, and presence of vertigo/dizziness. Twenty-two studies were identified that met selection criteria for analysis from an initial pool of 1272 reports. They were evaluated according to treatment protocol: 1) single-dose SRS (13 studies, 483 patients), 2) combination of MS and SRS (7 studies, 182 patients), and 3) fractionated SRS (3 studies, 82 patients). Tumor control was achieved in 89%, 94%, and 91% of patients, respectively. Odds ratios (ORs) of post- over pretreatment serviceable hearing were 0.42 (P < .01), 0.47 (P = .05), and 0.60 (P = .22); for facial nerve impairment, these ORs were 1.08 (P = .69), 3.45 (P = .28), and 0.87 (P = .71), respectively. The management of large VS remains challenging. All treatment modalities resulted in high tumor control rates and worsening of pretreatment hearing. None, however, caused significant facial nerve impairment, suggesting that management strategies incorporating focal irradiation can be successful.


Protein-losing Enteropathy Complicated with Primary Intestinal Follicular Lymphoma.
Protein-losing enteropathy (PLE) is a rare syndrome characterized by hypoproteinemia due to gastrointestinal (GI) protein loss. Primary intestinal follicular lymphoma (PIFL), a specific variant of follicular lymphoma with essential only GI involvement, has not been reported as an etiology of PLE. We herein report a case of PLE complicated with PIFL that was successfully treated with rituximab, resulting in rapid improvement of PLE and a complete response of PIFL. Macroscopic findings of ulcerative lesions with diffuse involvement, which were precisely described by capsule and double-balloon enteroscopy at the diagnosis, also improved following the treatment. This case provides a clue suggesting factors that promote PLE in PIFL.


Meiotic chromosome structure. Kinetochores and chromatid cores in standard and B chromosomes of Arcyptera fusca (Orthoptera) revealed by silver staining.
The behaviour of two chromosome structures in silver-stained chromosomes was analyzed through the first meiotic division in spermatocytes of the acridoid species Arcyptera fusca. Results showed that at diakinesis kinetochores and chromatid cores are individualized while they associate in bivalents of metaphase I; only kinetochores and distal core spots associate in the sex chromosome. Metaphase I is characterized by morphological and localization changes of both kinetochores and cores which define the onset of anaphase I. These changes analyzed in both autosomes and in the sex chromosome allow us to distinguish among three different substages in metaphase I spermatocytes. B chromosomes may be present as univalents, bivalents, or trivalents. Metaphase I B univalents are characterized by separated cores except at their distal ends and individualized and flat sister kinetochores. At anaphase I sister kinetochores of lagging B chromatids remain connected through a silver-stained strand. The behaviour of cores and kinetochores of B bivalents is identical with that found in the autosomal bivalents. The differences in the morphology of kinetochores of every chromosome shown by B trivalents at metaphase I may be related to the balanced forces acting on the multivalent. The results show dramatic changes in chromosome organization of bivalents during metaphase I. These changes suggest that chromatid cores are not involved in the maintenance of bivalents. Moreover, the changes in morphology of kinetochores are independent of the stage of meiosis but correlate with the kind of division (amphitelic-syntelic) that chromosomes undergo.


Preparation of Carbon Nanowall and Carbon Nanotube for Anode Material of Lithium-Ion Battery.
Carbon nanowall (CNW) and carbon nanotube (CNT) were prepared as anode materials of lithium-ion batteries. To fabricate a lithium-ion battery, copper (Cu) foil was cleaned using an ultrasonic cleaner in a solvent such as trichloroethylene (TCE) and used as a substrate. CNW and CNT were synthesized on Cu foil using plasma-enhanced chemical vapor deposition (PECVD) and water dispersion, respectively. CNW and CNT were used as anode materials for the lithium-ion battery, while lithium hexafluorophosphate (LiPF6) was used as an electrolyte to fabricate another lithium-ion battery. For the structural analysis of CNW and CNT, field emission scanning electron microscope (FE-SEM) and Raman spectroscopy analysis were performed. The Raman analysis showed that the carbon nanotube in composite material can compensate for the defects of the carbon nanowall. Cyclic voltammetry (CV) was employed for the electrochemical properties of lithium-ion batteries, fabricated by CNW and CNT, respectively. The specific capacity of CNW and CNT were calculated as 62.4 mAh/g and 49.54 mAh/g. The composite material with CNW and CNT having a specific capacity measured at 64.94 mAh/g, delivered the optimal performance.


Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms.
Despite their importance in tissue homeostasis and renewal, human pituitary stem cells (PSCs) are incompletely characterized. We describe a human single nucleus RNA-seq and ATAC-seq resource from pediatric, adult, and aged postmortem pituitaries (snpituitaryatlas.princeton.edu) and characterize cell-type-specific gene expression and chromatin accessibility programs for all major pituitary cell lineages. We identify uncommitted PSCs, committing progenitor cells, and sex differences. Pseudotime trajectory analysis indicates that early-life PSCs are distinct from the other age groups. Linear modeling of same-cell multiome data identifies regulatory domain accessibility sites and transcription factors that are significantly associated with gene expression in PSCs compared with other cell types and within PSCs. We identify distinct deterministic mechanisms that contribute to heterogeneous marker expression within PSCs. These findings characterize human stem cell lineages and reveal diverse mechanisms regulating key PSC genes and cell type identity.


Basement membrane proteins in the space of Disse: a reappraisal.
The distribution of two major basement membrane components, type IV collagen and laminin, was studied within the perisinusoidal space of Disse in normal human liver using (i) an immunoperoxidase method for light microscopy and (ii) immunogold labelling for ultrastructural localisation. Although immunoreactivity depended on the mode of tissue fixation, both proteins could be identified at this site using a panel of affinity purified antibodies. These findings indicate that these proteins are normal constituents of the perisinusoidal extracellular matrix, and refute the hypothesis that capillarization of the sinusoids in chronic liver disease results from neo-expression of laminin in the space of Disse.


A case of resistance to thyroid hormone with thyroid cancer.
Resistance to thyroid hormone (RTH) is an autosomal dominant hereditary disorder that is difficult to diagnose because of its rarity and variable clinical features. The magnitude of RTH is caused by mutations in the thyroid hormone receptor beta (TR beta) gene. We recently treated a 38-yr-old woman with RTH who had incidental papillary thyroid carcinoma. She presented with goiter and displayed elevated thyroid hormone levels with an unsuppressed TSH. She was determined to harbor a missense mutation of M310T in exon 9 of the TR beta gene, and diagnosed with generalized RTH. This mutation has not yet been reported in Korea. RTH is very rare and easily overlooked, but should be considered in patients who present with goiter and elevated thyroid hormone levels with an unsuppressed TSH. The association between thyroid cancer and RTH needs further study.


[Maternal mortality in Peru].
The author investigates maternal mortality in Peru using data from the second Demographic and Family Health Survey (ENDES-II) carried out in 1991-1992. "The inclusion of a module about adult mortality in the questionnaire of the ENDES II [made it possible] to estimate maternal mortality using a set of questions about the sisters of the women interviewed. The study highlights the inverse relation between levels of maternal mortality and education, [especially] the relevance of formal education for decreasing the incidence of maternal mortality." (SUMMARY IN ENG)


[Simultaneous determination of 38 limited colorants in cosmetics by high performance liquid chromatography].
A method has been established for the simultaneous determination of 38 limited colorants in cosmetics by high performance liquid chromatography (HPLC). The samples were extracted by ultrasonic with tetrahydrofuran, methanol, ammonium acetate solution as extraction solvents. After centrifugation, nitrogen blow and redissolved in turn, the extracts were separated on an Agilent zorbax SB-Aq column (150 mm x 3.0 mm, 3.5 µm) using a gradient elution program with acetonitrile and 30 mmol/L ammonium acetate containing 0.075% (v/v) formic acid as mobile phases. The detection wavelengths were set at 254, 416, 484, 514, 590 and 620 nm. The linear ranges of the 38 target compounds were all in the range of 1 to 10 mg/L with correlation coefficients more than 0.999. The limits of quantification (LOQs) for the 38 colorants were in the range of 5-50 µg/g. The average recoveries at two spiked levels ranged from 93.2% to 107.6% with the relative standard deviations (RSDs) less than 10% (n = 6). This method is accurate, simple, sensitive and reliable, and can be used for the analysis of the 38 limited colorants in cosmetics.


Searching for common sequence patterns among distantly related proteins.
We have developed a program Gap Allowing Pattern Explorer (GAPE) to extract amino acid sequence motifs conserved among distantly related proteins. The GAPE program is designed to allow gaps in the sequences. First, this program generates all possible amino acid patterns comprising up to five amino acids. Sequences containing the amino acid residues in the same order as a generated pattern are selected as subsequences, where the differences in the distances between two consecutive amino acids are ignored. Next, the motifs are extracted from the subsequences under conditions in which all four distances between the five amino acids are fixed. At this stage, motifs with gaps in their subsequence are also found by relaxing one of the four fixed distances. The statistical significance for a motif obtained is calculated based on the amino acid composition of the sequences under consideration. When the GAPE program was applied to 59 pyridoxal-phosphate-related sequences and 64 ATP (AMP-forming)-related sequences, motifs extracted with a low expectation of occurrence contained some of the amino acid residues chemically proved to be involved in the ligand recognition.


Behavior of accessory abducens and abducens motoneurons during eye retraction and rotation in the alert cat.
1. The activity of both accessory abducens (Acc Abd) and abducens (Abd) motoneurons (Mns) was recorded in the alert cat during eye retraction and rotational eye movements. Cats were fitted with two scleral coils, one measured rotational eye movements directly and the other retraction by distinguishing the translational component. 2. Acc Abd and Abd Mns were identified following antidromic activation from electrical stimulation of the ipsilateral VIth nerve. 3. In response to corneal air puffs, bursts of spikes were produced in all (n = 30) Acc Abd Mns. The burst began 7.2 +/- 1.2 (SD) ms after onset of the air puff and 8.9 +/- 1.9 ms before eye retraction. 4. Acc Abd Mns were silent throughout all types of rotational eye movements, and tonic activity was not observed during intervals without air-puff stimulation. 5. In contrast, all (n = 50) identified Abd Mns exhibited a burst and/or pause in activity preceding and during horizontal saccades as well as a tonic activity proportional to eye position. 6. Only 10% of Abd Mns fired a weak burst of spikes in response to air-puff stimulation. 7. We conclude that Acc Abd Mns are exclusively involved in eye retraction in the cat and that only a few Abd Mns have an eye-retraction signal added to their eye position and velocity signals. Thus any rotational eye-movement response described in retractor bulbi muscle must result from innervation by Mns located in the Abd and/or the oculomotor nuclei. 8. The organization of the prenuclear circuitry and species variation are discussed in view of the nictiating membrane extension response measured in associative learning.


Human biodistribution and dosimetry of iodine-123-fluoroalkyl analogs of beta-CIT.
Two new N-omega-fluoroalkyl analogs of [123I]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I]beta-CIT), the fluoroethyl and fluoropropyl compounds ([123I]FE-CIT and [123I]FP-CIT, respectively), have been shown to have faster kinetics and better selectivity for the dopamine transporter than [123I]beta-CIT. We examined the organ biodistribution and radiation safety of these two compounds in six healthy volunteers who received an injection with each of the two compounds 2 weeks apart. Data were obtained on the Strichman 860 whole-body scanner. Transmission scans were obtained in all subjects prior to the injection of the radiotracer with a line source and used to derive organ-specific attenuation correction factors. Whole-body planar images were acquired every hour for the first 6 h, and at 24 h. Attenuation-corrected regional conjugate counts were converted into units of activity using a calibration factor obtained for each subject by dividing whole-body conjugate decay-corrected counts from the first acquisition by the injected activity. Radiation dose estimates were on average higher for [123I]CIT-FE than for [123I]CIT-FP, with the lower large intestine receiving the highest exposure: 0.15+/-13% mGy/MBq (mean +/-COV) and 0.12+/-14% mGy/MBq for [123I]FE-CIT and [123I]FP-CIT, respectively, followed by the upper large intestine and the spleen.


Less dropout from prolonged exposure sessions prescribed at least twice weekly: A meta-analysis and systematic review of randomized controlled trials.
Trauma-focused psychotherapies, such as prolonged exposure (PE), are strongly recommended to treat posttraumatic stress disorder due to their effects in reducing symptoms. However, such therapies may also suffer from high dropout rates. To investigate how clients might benefit from trauma-focused therapy while minimizing dropout, we conducted a meta-analysis of 1,508 adults from 35 randomized controlled trials (RCTs) of outpatient PE programs to evaluate treatment frequency as a predictor of dropout. When an RCT prescribed PE sessions at least twice weekly compared to less frequently, the dropout rate was significantly lower at 21.0%, 95% CI [13.9%, 30.4%], compared to 34.0%, 95% CI [28.9%, 39.4%], OR = 0.52, 95% CI [0.30, 0.89], p = .018. It was not possible to draw causal conclusions, as only one RCT compared two PE treatment frequencies head-to-head. Nonetheless, the findings remained significant after controlling for study characteristics. These data invite reconsideration of the common practice of weekly psychotherapy in favor of twice-weekly sessions in standard outpatient treatment.


The relation between school entrance age and school achievement during primary schooling: evidence from Croatian primary schools.
Compulsory school entrance age and admission policies differ across countries and educational systems, and there is a continuing debate on the question whether and how the age at school entry affects various student outcomes. This study explored the relation between school entrance age and school achievement among students attending fourth (ages 10-11) and eighth (ages 14-15) grade of Croatian primary schools. Participants were 44,479 fourth- and 43,338 eighth-grade students from all Croatian primary schools. Students were divided into groups of younger and older school entrants based on the difference between the year of birth and the year of school entry. Differences in school achievement between students who were younger and those who were older when they entered school in subjects covered by the curriculum for respective grades were examined among fourth- and eighth-grade students. Two achievement measures were used for each subject-objective test results obtained during a national examination and final school marks appointed by teachers. Among fourth-grade students, older school entrants on average performed slightly better than the younger ones in all the subjects, irrespective of the achievement measure used. However, these differences in achievement are very small, and the effect of school entrance age on achievement is very weak. In the eighth-grade sample, younger and older school entrants did not differ in their achievement in the majority of subjects. Students who are older when they enter school perform slightly better than their older classmates in the lower grades of primary school, but these differences in achievement are very small and are probably no longer present by the end of primary schooling.


The role of long-chain fatty acyl-CoA esters in beta-cell signal transduction.
Glucose-induced insulin secretion is associated with inhibition of free fatty acid (FFA) oxidation, increased esterification and complex lipid formation by pancreatic beta-cells. Abundant evidence favors a role for cytosolic long-chain acyl-CoA (LC-CoA), including the rapid rise in malonyl CoA, the inhibitory effect of hydroxycitrate or acetyl CoA carboxylase knockout, both of which prevent malonyl CoA formation, and the stimulatory effect of exogenous FFA. On the other hand, some evidence opposes the concept, including the fall in total LC-CoA levels in response to glucose, the stimulatory effect of LC-CoA on K(ATP) channels and the lack of inhibition of glucose-stimulated secretion either by overexpression of malonyl CoA decarboxylase, which markedly lowers malonyl CoA levels, or by triacsin C, which blocks FFA conversion to LC-CoA. Alternative explanations for these data are presented. A revised model of nutrient-stimulated secretion involving two arms of signal transduction that occur simultaneously is proposed. One arm depends on modulation of the K(ATP) channel evoked by changes in the ATP/ADP ratio. The other arm depends upon anaplerotic input into the tricarboxylic acid cycle, generation of excess citrate, and increases in cytosolic malonyl-CoA. Input from this arm is increased LC-CoA. Signaling through both arms would be required for normal secretion. LC-CoA esters and products formed from them are potent regulators of enzymes and channels. It is hypothesized that their elevations directly modulate the activity of enzymes, genes and various beta-cell functions or modify the acylation state of key proteins involved in regulation of ion channels and exocytosis.


Prolongation of epidural analgesia using solid lipid nanoparticles as drug carrier for lidocaine.
Solid lipid nanoparticles (SLNs), as a drug carrier, are a very attractive strategy for sustained and controlled drug release. In this study, we investigated the feasibility of SLNs to prolong the action of lidocaine for potential application in epidural anesthesia and analgesia. Lidocaine-loaded SLNs were prepared with different lipids, including monostearin (MS), glyceryl palmitostearate (GP), and stearic acid (SA). The morphology and crystallinity were characterized with transmission electron microscopy and powder x-ray diffraction. In vitro release studies were carried in phosphate buffer solution of pH 7.4 using cellulose dialysis membrane. The in vivo efficacy of epidural anesthesia was evaluated in rats. Lidocaine was successfully incorporated in SLNs prepared with MS, GP, and SA, respectively. The particle sizes of lidocaine-loaded SLNs were 143 to 388 nm with polydispersity index of 0.29 to 0.45. Powder x-ray diffraction analysis showed that lidocaine was mainly dispersed in SLNs in an amorphous state. The in vitro release within 48 hrs showed that lidocaine released from SLNs was 80% with MS SLNs, 69% with GP SLNs, and 89% with SA SLNs. The epidural efficacy was compared with that of aqueous lidocaine HCl. Single injection of lidocaine SLN suspension produced epidural block for more than 8 hrs with MS SLNs, 12 hrs with GP SLNs, and 4 hrs with SA SLNs. ]The same dose of lidocaine in aqueous solution lasted for less than 2 hrs. Solid lipid nanoparticles can be exploited as a promising drug carrier for extending the action of lidocaine.


Indoor Air Quality and Health.
In the last few decades, Indoor Air Quality (IAQ) has received increasing attention from the international scientific community, political institutions, and environmental governances for improving the comfort, health, and wellbeing of building occupants.[...].


Multiple bowel intussusceptions from metastatic localized malignant pleural mesothelioma: a case report.
Localized malignant pleural mesothelioma (LMPM) is a rare occurrence, and gastrointestinal intra-luminal metastases have not previously been reported. Herein, we report a patient with LMPM who presented with a local recurrence 10 mo after initial en bloc surgical resection. Abdominal computed tomography was performed for intractable, vague abdominal pain with episodic vomiting, which showed a "target sign" over the left lower quadrant. Laparotomy revealed several intra-luminal metastatic tumors in the small intestine and colon and a segmental resection of metastatic lesions was performed. Unfortunately, the patient died of sepsis despite successful surgical intervention. Though local recurrence is more frequent in LMPM, the possibility of distant metastasis should not be ignored in patients with non-specific abdominal pain.


Biallelic loss-of-function in NRAP is a cause of recessive dilated cardiomyopathy.
Familial dilated cardiomyopathy (DCM) is typically a monogenic disorder with dominant inheritance. Although over 40 genes have been linked to DCM, more than half of the patients undergoing comprehensive genetic testing are left without molecular diagnosis. Recently, biallelic protein-truncating variants (PTVs) in the nebulin-related anchoring protein gene (NRAP) were identified in a few patients with sporadic DCM. We determined the frequency of rare NRAP variants in a cohort of DCM patients and control patients to further evaluate role of this gene in cardiomyopathies. A retrospective analysis of our internal variant database consisting of 31,639 individuals who underwent genetic testing (either panel or direct exome sequencing) was performed. The DCM group included 577 patients with either a confirmed or suspected DCM diagnosis. A control cohort of 31,062 individuals, including 25,912 individuals with non-cardiac (control group) and 5,150 with non-DCM cardiac indications (Non-DCM cardiac group). Biallelic (n = 6) or two (n = 5) NRAP variants (two PTVs or PTV+missense) were identified in 11 unrelated probands with DCM (1.9%) but none of the controls. None of the 11 probands had an alternative molecular diagnosis. Family member testing supports co-segregation. Biallelic or potentially biallelic NRAP variants were enriched in DCM vs. controls (OR 1052, p<0.0001). Based on the frequency of NRAP PTVs in the gnomAD reference population, and predicting full penetrance, biallelic NRAP variants could explain 0.25%-2.46% of all DCM cases. Loss-of-function in NRAP is a cause for autosomal recessive dilated cardiomyopathy, supporting its inclusion in comprehensive genetic testing.


Plasmid pC present in Salmonella enterica serovar Enteritidis PT14b strains encodes a restriction modification system.
Salmonella enterica serovar Enteritidis (S. Enteritidis) possesses plasmids of different sizes and roles. Besides the serovar-specific virulence plasmid present in most field strains, S. Enteritidis can harbour plasmids of low molecular mass whose biological role is poorly understood. We therefore sequenced plasmid pC present in S. Enteritidis strains belonging to phage type PT14b. The size of plasmid was determined to be 5,269 bp and it was predicted to encode four open reading frames (ORFs). The first two ORFs were found (initial 3,230 bp) to be highly homologous to rom and mbeA genes of ColE1 plasmid of Escherichia coli. Proteins encoded by the other two ORFs were 99% homologous to a restriction methylase and restriction endonuclease encoded by plasmid pECO29 of a field strain of E. coli. Using insertional mutagenesis we confirmed experimentally that the plasmid pC-encoded restriction modification system was functional and could explain the high resistance of S. Enteritidis PT14b strains to phage infection.


Growth problems in children with asthma.
Growth problems are often seen in children with asthma. Rarely, these problems may be caused by poor asthma control. Negatively-deviating growth curves in asthmatic boys aged 8-15 years are often associated with a chronic delay in growth and puberty. Daily treatment with any dose of systemic corticosteroids suppresses the growth rate for as long as the treatment is maintained. The risk of growth rate suppression due to inhaled corticosteroids depends on the dose, administration regimen and delivery device. The risk becomes significant with > or =800 microg budesonide from a metered-dose inhaler with a spacer, and with > or =400 microg budesonide or fluticasone propionate from a dry-powder inhaler. Regardless of the treatment modality applied, all children with asthma should have their height growth measured at least every 6 months, and indications for endocrine work-up should follow general criteria for a growth-insufficient child.


Comparison of two regimens for patients with thyroid-associated ophthalmopathy receiving intravenous methyl prednisolone: A single center prospective randomized trial.
Intravenous (i.v.) glucocorticoid is recommended for active moderate-to-severe thyroid-associated ophthalmopathy (TAO). However, the details of the treatment schedule are still debatable. The present prospective randomized trial was performed to compare clinical outcomes and serum cytokines between the two regimens. A cohort of 90 patients with active moderate-to-severe TAO was randomized to receive i.v. methyl prednisolone on a weekly protocol or daily scheme. The response rate was evaluated at the 12-week follow-up visit. Serum interleukin (IL)-2, IL-6 and IL-17 levels were measured in 160 patients with TAO, 60 patients with isolated Graves' disease (GD) and 60 normal control (NC) at baseline, as well as patients with active moderate-to-severe TAO at the 12th week after treatment. The daily scheme had a higher response rate than the weekly protocol without a significant difference (77.8 vs. 63.6%, P>0.05). No major adverse events were recorded under either regimen. Overall, minor events were more common on the daily scheme (11.36 vs. 4.35%, P<0.05)than on the weekly protocol, whereas the deterioration of eye symptoms (two patients) was only reported on the weekly protocol. At baseline, the IL-17 level in the TAO group was higher than that in the isolated GD and NC groups (P<0.05). In addition, the IL-17 level in the active TAO group was higher than that in the inactive TAO group (P<0.05). Furthermore, the IL-17 level had significantly decreased under the two regimens at the 12-week visit (P<0.05). In conclusion, for patients with active moderate-to-severe TAO, daily i.v. glucocorticoid therapy has a relative higher response rate than the weekly protocol with a few more minor adverse events. These two regimens have their own merits with regard to adverse effects. IL-17 has the potential to be a biomarker for evaluating TAO activity and treatment effects.


[Study of chemically modified hemoglobin as an artificial oxygen carrier in the model of hemorrhagic shock in dogs].
Hemodynamic and gas-transporting properties of the chemically modified hemoglobin solution have been studied on the model of hemorrhagic shock in dog. It has been shown that the polymerized hemoglobin solution exerts the hemodynamic action just as the plasma substitute "polyglucin" does. However, in contrast to the latter, polyhemoglobin circulating in the vascular bed for a prolonged period of time increases the blood oxygen capacity and oxygen delivery to tissues with the resultant increase in body total oxygen taking-up.


[Effectiveness of tolfenamic acid in the prevention of migraine].
The migraine prophylactic effect of tolfenamic acid 300 mg versus pizotifen 1.5 was evaluated in a prospective, randomized, double-blind, parallel group study. 192 patients were included with a frequency of 4-8 moderate to severe migraine attacks monthly, with or without aura, fulfilling the diagnostic criteria for migraine as defined by the International Headache Society. A four-week baseline period without medication was followed by 12 weeks of treatment with tolfenamic acid 300 mg or pizotifen 1.5 mg. In both periods patients were allowed to take escape medication (paracetamol and codeine) if the treatment was inefficient. All the patients had a headache diary before and during treatment. The primary criterion of efficacy was reduction in attack frequency per 4 weeks. Also reduction in intensity or duration of migraine attacks in hours at the end of 12 weeks treatment compared to the baseline period was measured. Both groups exhibited significant reduction in attack frequency (p < 0.001). Tolfenamic acid significantly reduced severity compared to the run-in period (p = 0.009). Patients treated with pizotifen needed more escape medication when compared to the run-in period (p < 0.01). Tolerance, especially weight gain, was a major drawback with pizotifen. Because of its high efficacy, excellent tolerability and low cost, tolfenamic acid is an interesting option for migraine prophylaxis.


Design, synthesis and biological evaluation of pyridine-chalcone derivatives as novel microtubule-destabilizing agents.
Further optimization of the trimethoxyphenyl scaffold of parent chalcone compound (2a) by introducing a pyridine ring afforded a series of novel pyridine-chalcone derivatives as potential anti-tubulin agents. All the target compounds were evaluated for their antiproliferative activities. Among them, representative compound 16f exhibited the most potent activity with the IC50 values ranging from 0.023 to 0.045 μM against a panel of cancer cell lines. Further mechanism study results demonstrated that compound 16f effectively inhibited the microtubule polymerization by binding to the colchicine site of tubulin. Moreover, cellular mechanism studies disclosed that 16f caused G2/M phase arrest, induced cell apoptosis and disrupted the intracellular microtubule network. Also, 16f reduced the cell migration and disrupted the capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). Importantly, 16f significantly inhibited tumor growth in H22 xenograft models without apparent toxicity, which was stronger than the reference compound CA-4, indicating that it is worthy to investigate 16f as a potent microtubule-destabilizing agent for cancer therapy.


In vitro glycation of human serum albumin by dihydroxyacetone and dihydroxyacetone phosphate.
Amino groups in proteins can non-enzymatically react with reducing sugars to generate a structurally diverse group of compounds referred to as advanced glycation end products (AGEs). The in vivo formation of AGEs contributes to some of the complications of diabetes including atherosclerosis, cataract formation, and renal failure. The formation of AGEs is dependent on both sugar and protein concentrations. Increases in temperature, pH, and exposure time of sugars to the proteins also play a significant role in the rate of AGE formation. This study focuses on the use of a combination of analytical techniques to study the in vitro AGE formation of HSA with dihydroxyacetone phosphate (DHAP), a ketose generated during glycolysis, and its dephosphorylated analog, dihydroxy acetone (DHA), commonly used as a browning reagent in skin tanning preparations. The extent of AGE formation was affected by DHAP and DHA concentrations and by the duration of HSA exposure to these glycating agents. Increases in temperature and pH sped the glycation process and enhanced the formation of the AGEs of HSA. MALDI-TOF mass spectroscopic data provided a reliable result to evaluate the extent of the AGE formation.


13,14-Dihydro-15-keto prostaglandin F2α release in response to oxytocin challenge early post-partum in anoestrous Nelore cows submitted to temporary calf removal and progesterone priming.
The study evaluated, in early post-partum anoestrous Nelore cows, if the increase in plasma oestradiol (E2) concentrations in the pre-ovulatory period and/or progesterone priming (P4 priming) preceding ovulation, induced by hormonal treatment, reduces the endogenous release of prostaglandin PGF(2)α and prevents premature lysis of the corpus luteum (CL). Nelore cows were subjected to temporary calf removal for 48 h and divided into two groups: GPE/eCG group (n = 10) and GPG/eCG group (n = 10). Animals of the GPE/eCG group were treated with a GnRH agonist. Seven days later, they received 400 IU of eCG, immediately after PGF(2)α treatment, and on day 0, 1.0 mg of oestradiol benzoate (EB). Cows of the GPG/eCG group were similarly treated as those of the GPE/eCG group, except that EB was replaced with a second dose of GnRH. All animals were challenged with oxytocin (OT) 9, 12, 15 and 18 days after EB or GnRH administration and blood samples were collected before and 30 min after OT. Irrespective of the treatments, a decline in P4 concentration on day 18 was observed for cows without P4 priming. However, animals exposed to P4 priming, treated with EB maintained high P4 concentrations (8.8 ± 1.2 ng/ml), whereas there was a decline in P4 on day 18 (2.1 ± 1.0 ng/ml) for cows that received GnRH to induce ovulation (p < 0.01). Production of 13,14-dihydro-15-keto prostaglandin F(2)α (PGFM) in response to OT increased between days 9 and 18 (p < 0.01), and this increase tended to be more evident in animals not exposed to P4 priming (p < 0.06). In conclusion, the increase in E2 during the pre-ovulatory period was not effective in inhibiting PGFM release, which was lower in P4-primed than in non-primed animals. Treatment with EB promoted the maintenance of elevated P4 concentrations 18 days after ovulation in P4-primed animals, indicating a possible beneficial effect of hormone protocols containing EB in animals with P4 priming.


Identifying elemental genomic track types and representing them uniformly.
With the recent advances and availability of various high-throughput sequencing technologies, data on many molecular aspects, such as gene regulation, chromatin dynamics, and the three-dimensional organization of DNA, are rapidly being generated in an increasing number of laboratories. The variation in biological context, and the increasingly dispersed mode of data generation, imply a need for precise, interoperable and flexible representations of genomic features through formats that are easy to parse. A host of alternative formats are currently available and in use, complicating analysis and tool development. The issue of whether and how the multitude of formats reflects varying underlying characteristics of data has to our knowledge not previously been systematically treated. We here identify intrinsic distinctions between genomic features, and argue that the distinctions imply that a certain variation in the representation of features as genomic tracks is warranted. Four core informational properties of tracks are discussed: gaps, lengths, values and interconnections. From this we delineate fifteen generic track types. Based on the track type distinctions, we characterize major existing representational formats and find that the track types are not adequately supported by any single format. We also find, in contrast to the XML formats, that none of the existing tabular formats are conveniently extendable to support all track types. We thus propose two unified formats for track data, an improved XML format, BioXSD 1.1, and a new tabular format, GTrack 1.0. The defined track types are shown to capture relevant distinctions between genomic annotation tracks, resulting in varying representational needs and analysis possibilities. The proposed formats, GTrack 1.0 and BioXSD 1.1, cater to the identified track distinctions and emphasize preciseness, flexibility and parsing convenience.


Relationship between wine composition and temperature: Impact on Bordeaux wine typicity in the context of global warming-Review.
Weather conditions throughout the year have a greater influence than other factors (such as soil and cultivars) on grapevine development and berry composition. Temperature affects gene expression and enzymatic activity of primary and secondary metabolism which determine grape ripening and wine characteristics. In the context of the climate change, temperatures will probably rise between 0.3°C and 1.7°C over the next 20 years. They are already rising and the physiology of grapevines is already changing. These modifications exert a profound shift in primary (sugar and organic acid balance) and secondary (phenolic and aromatic compounds) berry metabolisms and the resulting composition of wine. For example, some Bordeaux wines have a tendency toward reduced freshness and a modification of their ruby color. In this context it is necessary to understand the impact of higher temperatures on grape development, harvest procedures, and wine composition in order to preserve the typicity of the wines and to adapt winemaking processes.


Functional maturation of mouse CD4+CD8- thymocytes induced by medullary-type thymus epithelial cells.
Murine CD4+CD8-(CD4SP) thymocyte subset is a heterogeneous population, in which the Qa-2- cells are less functional, whereas the Qa-2+ cells are fully functional. Evidence is provided here that the transition from Qa-2- to Qa-2+ CD4SP thymocytes is an intrathymic process of differentiation induced by thymic medullary-type epithelial cells. The separated Qa-2-CD4SP could be induced to express Qa-2 molecules up to 84%-89% of the total viable cells after cocultured for 3 d with MTEC1 cells, a murine thymic medullary type epithelial cell line established in our laboratory. Kinetic study showed that both the percentage of Qa-2+ cells and the density of the expressed Qa-2 molecules on CD4SP thymocytes induced by MTEC1 were progressively increasing in 72-h cultures. The MTEC1-induced Qa-2+CD4SP thymocytes were fully functional, which exhibited capabilities of proliferation and cytokine secretion in response to Con A stimulation as high as those of freshly isolated Qa-2+CD4SP thymocytes. The profile of cytokines secreted by MTEC1-induced Qa-2+CD4SP thymocytes was Thy 0 type specified by the production of IL-2, IL-4 and IL-6. The results suggest that Qa-2-CD4SP thymocytes may give rise to the Qa-2+CD4SP thymocytes, and acquire fully functional competence in thymic medulla under the foster of local epithelial cells.


Massive Pulmonary Embolism: Extracorporeal Membrane Oxygenation and Surgical Pulmonary Embolectomy.
Massive pulmonary embolism (PE) refers to large emboli that cause hemodynamic instability, right ventricular failure, and circulatory collapse. According to the 2016 ACCP Antithrombotic Guidelines, therapy for massive PE should include systemic thrombolytic therapy in conjunction with anticoagulation and supportive care. However, in patients with a contraindication to systemic thrombolytics or in those who fail the above interventions, extracorporeal membrane oxygenation (ECMO) and/or surgical embolectomy may be used to improve oxygenation, achieve hemodynamic stability, and successfully treat massive PE. Randomized controlled human trials evaluating ECMO in this context have not been done, and its role has not been well-defined. The European Society of Cardiology 2014 acute PE guidelines briefly mention that ECMO can be used for massive PE as a method for hemodynamic support and as an adjunct to surgical embolectomy. The 2016 CHEST Antithrombotic Therapy for venous thromboembolism Disease guidelines do not mention ECMO in the management of massive PE. However, multiple case reports and small series cited benefit with ECMO for massive PE. Further, ECMO may facilitate stabilization for surgical embolectomy. Unfortunately, ECMO requires full anticoagulation to maintain the functionality of the system; hence, significant bleeding complicates its use in 35% of patients. Contraindications to ECMO include high bleeding risk, recent surgery or hemorrhagic stroke, poor baseline functional status, advanced age, neurologic dysfunction, morbid obesity, unrecoverable condition, renal failure, and prolonged cardiopulmonary resuscitation without adequate perfusion of end organs. In this review, we discuss management of massive PE, with an emphasis on the potential role for ECMO and/or surgical embolectomy.


UV-vis spectroscopy and dynamic light scattering study of gold nanorods aggregation.
Gold nanorods (AuNRs) were used as spectroscopic sensing elements to detect specific DNA sequences with a single-base mismatch sensitivity. The assay was based on the observation that the stabilizing repulsive forces between CTA(+)-coated AuNRs can be removed by citrate ions, which causes aggregation among AuNRs; whereas nucleic acids of different structures[ i.e., peptide nucleic acid (PNA), single-stranded DNA (ssDNA), PNA-DNA complex, and double-stranded DNA (dsDNA)] can retard the aggregation. Moreover, the dsDNA PNA-DNA duplexes provide larger retardation than that by unhybridized ssDNA and PNA probe. This assay can differentiate single-base mismatched targets with base substitution at different locations (center and end) with AuNRs of a larger aspect ratio. Besides ultraviolet-visable spectroscopy measurement of particle assembly-induced plasmonic coupling that in turn provides a spectroscopic detection of the specific DNA, dynamic light scattering and transmission electron microscope (TEM) were used to measure smaller degree of aggregation that can reveal sodium citrate- and dsDNA-AuNRs interactions in fine detail.


The information content of electron flow through adsorbed molecular monolayers.
We point to the ability of noncontact measurements of electron transport via self-assembled monolayers to provide chemical, A-resolved information about the underlying molecule. A conceptual framework is presented to model a current flow of soft electrons through a molecular monolayer to a substrate and explore the information content of this and other emerging noncontact measurements. A numerical scheme is developed where advantage is taken of the split-operator formalism to propagate the incident electronic wave function over a suitable periodic potential energy surface representing the self-assembled monolayer. The (experimentally observable) potential difference introduced by the transmitted electrons is extracted from the time-averaged electron density using the Poisson equation of classical electrostatics.


Serum bactericidal and inhibitory titres in the management of melioidosis.
A retrospective evaluation of the relationship between serum bactericidal and inhibitory titres and treatment outcome in 195 adult Thai patients with severe melioidosis was conducted. Drug regimens included ceftazidime (52% of patients), co-amoxiclav (24%), imipenem (11%) or the conventional four-drug combination (11%). Pre- and 1 h post-dose serum samples were collected after 48-72 h of therapy, and serum inhibitory and bactericidal titrations determined. Median post-dose titres were: bactericidal 1:8 (range 0-1:128) and inhibitory 1:16 (range 0-1:128). Overall mortality was 26% and outcome was not influenced by either inhibitory or bactericidal titres. Pre-dose titres correlated with renal function; renal function was the most important predictor of mortality. Determination of serum inhibitory or bactericidal titres is unhelpful in the management of severe melioidosis.


A general dealloying route to synthesize nanoporous non-noble metals.
At present, most studies focus upon the synthesis of nanoporous noble metals such as Au, Ag, Pt and Pd. Here we show that the dealloying route can be generally used to fabricate nanoporous non-noble metals like Bi, Ga and Sn, and rapidly solidified Mg-based (Mg-Bi, Mg-Ga and Mg-Sn) precursors were utilized. The microstructure of the as-obtained nanoporous metals has been characterized using X-ray diffraction, scanning electron microscopy and energy dispersive X-ray analysis. These nanoporous metals show a three-dimensional bicontinuous ligament-channel structure. It has been found that the more active Mg atoms were selectively etched away during dealloying, and the residual elements (Bi, Ga and Sn) diffused and agglomerated to form the nanoporous structure.


A Corticocortical Circuit Directly Links Retrosplenial Cortex to M2 in the Mouse.
Retrosplenial cortex (RSC) is a dorsomedial parietal area involved in a range of cognitive functions, including episodic memory, navigation, and spatial memory. Anatomically, the RSC receives inputs from dorsal hippocampal networks and in turn projects to medial neocortical areas. A particularly prominent projection extends rostrally to the posterior secondary motor cortex (M2), suggesting a functional corticocortical link from the RSC to M2 and thus a bridge between hippocampal and neocortical networks involved in mnemonic and sensorimotor aspects of navigation. We investigated the cellular connectivity in this RSC→M2 projection in the mouse using optogenetic photostimulation, retrograde labeling, and electrophysiology. Axons from RSC formed monosynaptic excitatory connections onto M2 pyramidal neurons across layers and projection classes, including corticocortical/intratelencephalic neurons (reciprocally and callosally projecting) in layers 2-6, pyramidal tract neurons (corticocollicular, corticopontine) in layer 5B, and, to a lesser extent, corticothalamic neurons in layer 6. In addition to these direct connections, disynaptic connections were made via posterior parietal cortex (RSC→PPC→M2) and anteromedial thalamus (RSC→AM→M2). In the reverse direction, axons from M2 monosynaptically excited M2-projecting corticocortical neurons in the RSC, especially in the superficial layers of the dysgranular region. These findings establish an excitatory RSC→M2 corticocortical circuit that engages diverse types of excitatory projection neurons in the downstream area, suggesting a basis for direct communication from dorsal hippocampal networks involved in spatial memory and navigation to neocortical networks involved in diverse aspects of sensorimotor integration and motor control. Corticocortical pathways interconnect cortical areas extensively, but the cellular connectivity in these pathways remains largely uncharacterized. Here, we show that a posterior part of secondary motor cortex receives corticocortical axons from the rostral retrosplenial cortex (RSC) and these form monosynaptic excitatory connections onto a wide spectrum of excitatory projection neurons in this area. Our results define a cellular basis for direct communication from RSC to this medial frontal area, suggesting a direct link from dorsal hippocampal networks involved in spatial cognition and navigation (the "map") to sensorimotor networks involved the control of movement (the "motor").


Prediction of complications in gamma knife radiosurgery of arteriovenous malformation.
The incidence of complications following radiosurgical treatment of arteriovenous malformations (AVM) is presented. A simple relationship exists between average dose and risk of complications, and on this basis a model is presented that gives a qualitatively correct description of this relationship. The parameters of the model have been determined using a clinical material of 862 AVM treatments to give a quantitatively correct description of the risk of complications. The dose-response curve is described by a double-exponential function. An accurate description of the dose-response curve at high dose levels is shown to be very important in radiosurgery.


Biotransformation of formaldehyde in cultured human bronchus.
Biotransformation of formaldehyde to formic acid was studied to investigate the capacity of human bronchial epithelial cells to detoxicate formaldehyde. Normal human bronchial explants and normal primary bronchial epithelial cells were grown in medium containing 0.5 to 5 mM formaldehyde for up to 48 h. Formic acid was quantitated by analytical isotachophoresis. Explants were cultured with up to 5 mM formaldehyde for 48 h with approximately linear turnover, but at 5 mM the cells showed reduced biotransformation relative to the lower concentrations. The mean K(m) values for explants were 1.4 and 5.1 mM for cells and the mean V(max) values were 3.3 nmol/mg protein.min for the explants and 6.1 nmol/mg protein.min for the cells. By using the same technique with hepatocytes we found K(m) 1.25 mM and V(max) 4.2 nmol/mg protein.min, indicating that human bronchial epithelium cells have formaldehyde biotransforming activity similar to that of hepatocytes. Our results indicate that human bronchial epithelial cells oxidize formaldehyde at a relatively fast rate at concentrations up to 3 mM formaldehyde in the medium over a period up to 48 h.


Progress after one year of a pseudorabies eradication program for large swine herds.
Six large farrow-to-finish swine herds quarantined for pseudorabies in Illinois participated in the USDA-initiated Large Herd Cleanup Study. These herds were monitored for antibodies to pseudorabies virus (PRV) for 1 year after the initiation of an intensive eradication program. Herd size ranged between 425 and 1,500 females of breeding age. Gene-deleted modified-live virus vaccines were used on all farms, with 3 of the 6 herds receiving a vaccine with a deletion of the gene for glycoprotein-I and the other 3 herds receiving a vaccine with a deletion of the gene for glycoprotein-X. The breeding herd and growing pigs were vaccinated on each farm. Each herd produced its own replacement gilts. In addition, management changes emphasizing all-in, all-out pig flow were initiated. One year after initiation of the vaccination program, sera for the measurement of PRV antibodies were obtained from sows and heavy finishing pigs (> 70 kg) from each of the farms. Prevalence of PRV antibodies attributable to wild-type virus infection ranged from 7 to 63% (median, 33%) for sows and from 0 to 42% (median, 4%) for finishers, as determined by the appropriate vaccine differential test. For each sow herd, there was a large decrease in the PRV seroprevalence rate after 1 year of the program (range, -21 to -68%; median, -42%). Examination of PRV prevalence rates by parity indicated decreased seroprevalences in the lower parities (< 2) in 3 of the herds, suggesting that vaccination reduced the spread of PRV.(ABSTRACT TRUNCATED AT 250 WORDS)


Alterations in chemokine receptor CCR5 expression on blood dendritic cells correlate with acute graft-versus-host disease.
Dendritic cells (DC) are important in the development of acute graft-versus-host disease (GVHD) after allogeneic hemopoietic cell transplantation (alloHCT). The trafficking of immature DC from blood to GVHD target organs is likely to be regulated by chemokine receptors. We performed flow cytometry to document the expression of chemokine receptors on circulating DC and correlated the findings after alloHCT with occurrence of acute GVHD. In normal individuals, plasmacytoid DC (pDC) expressed high levels of CCR5, whereas the major CD16 myeloid DC subpopulation lacked CCR5. However, its expression on CD16 cells was induced by culture in allogeneic mixed lymphocyte reaction supernatant, an effect largely mediated by interferon-γ. CCR5 was expressed on a significant proportion of CD16 DC in 42 alloHCT patients, whereas it was down-regulated on pDC. The maximum percentage of CCR5CD16 DC, at any time after transplantation, correlated with acute GVHD, whereas the minimum CCR5 on pDC showed a similar correlation. Before developing signs of GVHD, the maximum percentage CCR5CD16 DC was higher in patients with GVHD grades II to IV than in GVHD grades 0 and I, whereas the minimum percentage CCR5 on pDC was lower in GVHD grades II to IV than in GVHD grades 0 and I. CCR5 levels more than 20.5% on CD16 myeloid DC and less than 22.6% on CD123 pDC correlated with subsequent GVHD grades II to IV with high sensitivities and specificities. These observations may reflect DC activation and altered homing during the alloimmune response and could allow early diagnosis and therapeutic intervention before the clinical diagnosis of GVHD.


Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors.
Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS). Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as "complex I bypass." In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology.


An optimized animal model for partial and total skin thickness burns studies.
Development of an improved animal model for studying skin burns in rats. Twenty-four male Wistar rats were randomly assigned to four groups (n=6): G1-Control, G2- T100°C, G3-T150°C and G4-T200°C. Two 10 x 10 mm squares were outlined with a sterile surgical marker on each side and along the vertebral column using a prepared template positioned between the anterior and posterior limbs. G2-G4 rats were subjected to 100°C, 150°C and 200ºC thermal burns, respectively. G1 rats served as controls. Burns were inflicted by applying a copper plate connected to an electronic temperature controlling device to the dorsal skin of anesthetized rats. Four burns were produced on each animal (total area: 4 cm²/animal) leaving about 1 cm of undamaged skin between burn areas. Analgesia was administered during 24 h after burn injury by adding 30 mg codeine phosphate hemihydrate to 500 ml tap water. The application of 100°C and 150ºC resulted in partial thickness skin burns with central reepithelialization of the burned area only at 100°C. In G4 group the whole thickness of the skin was injured without central reepithelialization. However, there was marginal reepithelialization in all groups. The model studied is inexpensive and easily reproducible, enabling the achievement of controlled burns with partial or total impairment of the skin in experimental animals.


Saline acclimation and water and sodium transport across avian small intestine.
The uptake of sodium and water across everted sacs of the jejunum and ileum of Pekin ducklings, nestling Glaucous-winged gulls, and adult Japanese quail was measured in both freshwater- and saltwater-acclimated birds to assess the importance of the avian small intestine in salt and water balance after a salt load. The jejunum and ileum together were divided into segments I-V in ducklings and gulls and segments I-IV in Japanese quail. Acclimation to sodium chloride solutions increased the uptake of sodium and water, per unit dry weight of tissue, across segments II and IV in larger ducklings, although no significant differences were observed in smaller ducklings. Sodium and water transport were significantly greater across the posterior region of the small intestine of saltwater-acclimated gulls. In Japanese quail acclimated to sodium chloride solutions, mean values for sodium and water uptake were decreased, compared with fresh-water-acclimated birds, but were not statistically significantly different. Increased uptake of water and sodium after saline acclimation appears to be correlated with the presence of functional salt glands.


Australian rural medical students' perceived readiness for work as a junior doctor: A cross-sectional national survey.
To report self-perceived readiness for work as a junior doctor in a national cohort of rural clinical school students. Cross-sectional study using a self-report questionnaire. Independent variables included 14 individual readiness items related to clinical and professional tasks, sociodemographic data and reported experience of rural clinical school (RCS) training. Participants were 668 medical students (55.3% females) completing a full academic year in rural Australia. Multivariable analysis explored factors associated with overall readiness for work as a junior doctor. 86% agreed that RCS experience prepared them to undertake the roles and responsibilities of a junior doctor. Self-ratings for specific clinical and professional tasks varied from a mean score of 5.9-8.0 out of 10, and 13 of the 14 items were associated with the outcome (p-value <0.001, except for performing spirometry). Lowest readiness scores were seen for some aspects including raising concerns about a colleague (mean score 6.1) or responding to workplace bullying (mean score 6.0). Aspects of the RCS experience that were strongly associated with overall readiness included: feeling a valued team-member (OR 9.28, 95%CI 2.43-35.39), feeling well-supported academically (OR 6.64, 95%CI 3.39-13.00), having opportunity for unsupervised but supported clinical practice (OR 4.67, 95%CI 1.45-15.00), having a rural mentor (OR 3.38, 95%CI 1.89-6.06) and having a previous health professional qualification (OR 2.7, 95%CI 1.32-5.54). Most RCS students felt ready for work as a junior doctor. Important aspects of RCS experience are likely to include students feeling integrated within the clinical team and having opportunities for authentic clinical roles. There remains a significant challenge for medical school curricula to address professional areas where graduates felt less prepared.


Enhanced Biological Imaging via Aggregation-Induced Emission Active Porous Organic Cages.
Porous organic cages (POCs) have many advantages, including superior microenvironments, good monodispersity, and shape homogeneity, excellent molecular solubility, high chemical stability, and intriguing host-guest chemistry. These properties enable POCs to overcome the limitations of extended porous networks such as metal-organic frameworks (MOFs) and covalent organic frameworks (COFs). However, the applications of POCs in bioimaging remain limited due to the problems associated with their rigid and hydrophobic structures, thus leading to strong aggregation-caused quenching (ACQ) in aqueous biological media. To address this challenge, we report the preparation of aggregation-induced emission (AIE)-active POCs capable of stimuli responsiveness for enhanced bioimaging. We rationally design a hydrophilic, structurally flexible tetraphenylethylene (TPE)-based POC that is almost entirely soluble in aqueous solutions. This POC's conformationally flexible superstructure allows the dynamic rotation of the TPE-based phenyl rings, thus endowing impressive AIE characteristics for responses to environmental changes such as temperature and viscosity. We employ these notable features in the bioimaging of living cells and obtain good performance, demonstrating that the present AIE-active POCs are suitable candidates for further biological applications.


Ozone-Induced Reduction in Quantity of Ribulose-1,5-bisphosphate Carboxylase in Alfalfa Foliage.
The concentration of ribulose-1,5-bisphosphate carboxylase was measured in the foliage of ;Moapa 69,' ;Ladak,' and ;Vernal' cultivars of alfalfa (Medicago sativa L.) after plants were exposed to 0.25 or 0.30 microliters per liter ozone for 2 hours. The quantity of ribulose-1,5-bisphosphate carboxylase decreased 80%, 68%, and 36% in leaves which did not exhibit ozone symptoms and to undetectable levels, 99% and 79% in symptomatic foliage for each cultivar, respectively.


Expression levels of stress protein gp96 are not limiting for major histocompatibility complex class I-restricted antigen presentation.
Immunization of mice with gp96 induces CTL with specificity for proteins that are expressed in the cells from which gp96 was isolated (Arnold et al., J. Exp. Med. 1995. 182: 885, Udono et al., Proc. Natl. Acad. Sci. USA 1994. 91: 3077). Recently, it has been shown that gp96 from cells transfected with vesicular stomatitis virus (VSV) nucleocapsid protein as well as gp96 loaded in vitro with peptides containing an epitope of this protein are taken up by phagocytic cells which obtain thereby the capacity for stimulating VSV-specific cytotoxic T lymphocytes (Suto and Srivastava, Science 1995. 269: 1585). The immunization experiments together with the peptide transfer from gp96/peptide complexes to major histocompatibility complex (MHC) class I molecules of phagocytic cells are consistent with the hypothesis that the endoplasmic reticulum-resident protein gp96 plays a crucial role in the antigen presentation of a cell (Srivastava et al., Immunogenetics 1994. 29: 93). To examine the involvement of gp96 in class I-restricted antigen presentation, we reduced gp96 RNA and protein levels by transfecting P13.1 cells with a vector containing part of gp96 cDNA in antisense orientation to the promotor. We found that antisense clones expressing strongly reduced levels of gp96 mRNA and gp96 protein show normal levels of MHC class I molecules on the cell surface and are recognized by T cells to the same extent as wild-type cells. Thus, our results show that normal levels of gp96 expression in a cell are not limiting for class I-restricted antigen presentation.


Hydrogen Sulfide Alleviates Postharvest Senescence of Grape by Modulating the Antioxidant Defenses.
Hydrogen sulfide (H2S) has been identified as an important gaseous signal in plants. Here, we investigated the mechanism of H2S in alleviating postharvest senescence and rotting of Kyoho grape. Exogenous application of H2S released from 1.0 mM NaHS remarkably decreased the rotting and threshing rate of grape berries. H2S application also prevented the weight loss in grape clusters and inhibited the decreases in firmness, soluble solids, and titratable acidity in grape pulp during postharvest storage. The data of chlorophyll and carotenoid content suggested the role of H2S in preventing chlorophyll breakdown and carotenoid accumulation in both grape rachis and pulp. In comparison to water control, exogenous H2S application maintained significantly higher levels of ascorbic acid and flavonoid and total phenolics and reducing sugar and soluble protein in grape pulp. Meanwhile, H2S significantly reduced the accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion (O2 (∙-)) in grape pulp. Further investigations showed that H2S enhanced the activities of antioxidant enzymes ascorbate peroxidase (APX) and catalase (CAT) and decreased those of lipoxygenase (LOX) in both grape peels and pulp. In all, we provided strong evidence that H2S effectively alleviated postharvest senescence and rotting of Kyoho grape by modulating antioxidant enzymes and attenuating lipid peroxidation.


[Analysis of a pedigree affected with congenital dysfibrinogenemia due to a novel Gly31Glu mutation of FGA gene].
To analyze the phenotype and genotype of a pedigree affected with congenital dysfibrinogenemia. Liver and kidney functions of the proband and her relatives were determined. Coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time(TT), fibrin(ogen) degradation products (FDPs), D-dimer(D-D) and the calibration experiment of protamine sulfate of against plasma TT were detected in the proband and her predigree members. The activity and antigen of fibrinogen (Fg) in plasma were measured by Clauss method and immunonephelometry method, respectively. All of the exons and exons-intron boundaries of the three fibrinogen genes (FGA, FGB and FGG) were subjected to PCR amplification and Sanger sequencing. Potential influence of the suspected mutations were analyzed with bioinformatics software including PolyPhen-2, SIFT and Mutation Taster. The proband had normal PT, APTT, FDPs, D-D and prolonged TT (31.8 s). The activity of fibrinogen (Fg) in plasma was significantly decreased but the antigen was normal. Genetic analysis revealed a heterozygous c.92G>A (p.Gly31Glu) mutation in exon 2 of the FGA gene. Family studies revealed that the mother carried the same mutation. Bioinformatic analysis suggested that the mutation may affect the function of Fg Protein. The dysfibrinogenemia was probably caused by the novel Gly31Glu mutation of the FGA gene.


Correlation between right atrial venous blood gasometry and cardiac index in cardiac surgery postoperative period.
To determine, even during postoperative period, the confiability of the cardiac index correlate with the data data given by a central atrial venous blood gasometry in patients who underwent cardiac surgery. From the sample of arterial and venous blood of right atrium gathered in postoperative of cardiac surgery, it was determinated the hemoglobin concentration and the gasometric study through what was observed of the venous oxygen saturation (SvO2) and the partial pressure of oxygen from venous blood gathered in right atrium (PvO2), add to the calculation of artery-venous difference of the oxygen content--radial artery / right atrium (C( a-v )O2). Afterwards, these parameters were compared with the cardiac index determined by thermodilution. There was good correlation between SvO2, C(av)O2 of the venous right atrial blood and cardiac index measured by thermodilution method, with sensibility and specificity good and high positive predict value and negative predict value. The PvO2 demonstrated poor sensibility in the estimative of low output. In cardiac surgery postoperative, the SvO2 and the C(a-v)O2 were safe parameters correlated with low cardiac output. The PvO2 demonstrated poor sensibility in the estimative of low output in postoperative cardiac surgery.


Violence, insecurity, and the risk of polio: A systematic analysis.
Since the introduction of polio vaccines in the 1950's and 60's, eradication of poliovirus from the world has been technically feasible. Progress towards this goal, however, has been uneven and influenced by social and political factors that challenge the implementation of robust immunization programs. While violence and insecurity are often cited as barriers to eradication, current global risk models are largely based on virologic and immunologic indicators measured at national levels. In this manuscript, we quantify the relevance of indicators of violence and insecurity on the risk of polio spread. Using logistic regression models and public data sources, we evaluate the relationship between measures of violence and instability and the location of poliomyelitis cases between 2006 and 2015 at the country-level, both individually and after controlling for more proximal determinants of disease, such as nearby circulating poliovirus and vaccination rates. We found that increases in a country's Fragile States Index (FSI) and Global Peace Index (GPI), aggregate indicators of violence and instability, were associated with the occurrence of poliovirus cases in the subsequent year (p< 0.01), even after controlling for established risk factors. These effects of violence and insecurity must be mediated through immunity and exposure to poliovirus, coarse measures of which are included in our model. This also implies that in our study, and in risk models in general, the interpretation depends on the quality and granularity of available data. National virologic and immunologic indicators understate the risk of poliovirus spread in areas with violence and insecurity, and the inclusion of such factors improves precision. In addition, the link between violence and incidence of disease highlights the broader challenge of implementing health interventions in conflict areas. We discuss practical implications of this work in understanding and measuring the risks to polio eradication and other global health initiatives, and the policy implications of the need to reach vulnerable populations in conflict zones.


[Leukocyte migration inhibitory factor and basophil degranulation in drug reactions].
We performed a prospective study in patients with a medical history of adverse reaction to drugs with the purpose of rule out allergy. We included 31 patients who were attended in the Allergy Service. We compared the sensibility and specificity of the test of inhibition factor of leucocytes migration and degranulation basophil against the exposition. After the statistical analysis, we concluded: the laboratory test, we have already mentioned, have little sensibility and specificity so the exposition test in the quickest, useful, and more simple method to determine drugs allergy, but more dangerous.


Analysis of transcription factor mRNAs in identified oxytocin and vasopressin magnocellular neurons isolated by laser capture microdissection.
The oxytocin (Oxt) and vasopressin (Avp) magnocellular neurons (MCNs) in the hypothalamus are the only neuronal phenotypes that are present in the supraoptic nucleus (SON), and are characterized by their robust and selective expression of either the Oxt or Avp genes. In this paper, we take advantage of the differential expression of these neuropeptide genes to identify and isolate these two individual phenotypes from the rat SON by laser capture microdissection (LCM), and to analyze the differential expression of several of their transcription factor mRNAs by qRT-PCR. We identify these neuronal phenotypes by stereotaxically injecting recombinant Adeno-Associated Viral (rAAV) vectors which contain cell-type specific Oxt or Avp promoters that drive expression of EGFP selectively in either the Oxt or Avp MCNs into the SON. The fluorescent MCNs are then dissected by LCM using a novel Cap Road Map protocol described in this paper, and the purified MCNs are extracted for their RNAs. qRT-PCR of these RNAs show that some transcription factors (RORA and c-jun) are differentially expressed in the Oxt and Avp MCNs.


Protective effect of ischemic preconditioning on testis injury following transient focal cerebral ischemia in diabetic rats.
We aim to evaluate the effect of ischemic preconditioning (IPreC) on testicular tissue after transient middle cerebral artery occlusion (MCAo) in Streptozotocin-induced diabetic (STZ) and non-diabetic rats. Testis injury and alterations of testosterone levels were evaluated histologically.. Testicular damage was detected by using hematoxylin- eosin and periodic acid- schiff staining and apoptosis was identified by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL). Total mean serum testosterone levels decreased in all diabetic groups (p < 0.05) although remote ischemia and IPreC did not have any effect. Serious testicular tubular damage was observed in both, diabetic and ischemic groups (p 0.05). Otherwise, remote IPreC induced MNAC instead of any changes in histopathological architecture. Moreover, remote IPreC reduced the tubular degeneration against synergistic damage of both ischemia and diabetes (p < 0.05). It can be suggested that remote ischemic preconditioning prevents testicular damage by improving histopathological alterations and inducing apoptosis, probably temporarily, after focal transient middle cerebral artery occlusion in both, diabetic and non-diabetic rats. This is the first report demonstrating protective effects of ischemic preconditioning on remote testis injury after transient middle cerebral artery occlusion in diabetic rats (Fig. 6, Ref. 23).


[Acute rhinosinusitis in adults--EPOS 2012 Part II].
Rhinosinusitis (RS) is an inflammatory disorder of the mucous membranes of the nose and paranasal sinuses, which are almost always affected concurrently. The EPOS2012 position paper initiated by the European Rhinologic Society and the European Academy of Allergy and Clinical Immunology is a recent comprehensive source on this common disease affecting approximately 20% of the population worldwide. Inflammation, not infection, is considered the cornerstone of RS, which is considered a temporal and pathophysiologic disease continuum with various subtypes. Acute rhinosinusitis is diagnosed, if typical symptoms last less than 12 weeks. It affects approximately 10% of the European population. Acute RS is further subdivided into acute viral, acute postviral and acute bacterial RS. Acute viral RS lasts less than 10 days with decreasing symptom intensity, while acute postviral RS is characterized by longer duration or a sudden increase of symptom severity around the 5th day ('double sickening'). Acute bacterial RS is assumed if 3 of the following 5 criteria are additionally met: Discoloured discharge (with unilateral predominance), severe local pain (with unilateral predominance), fever (>38ºC), elevated ESR/CRP, and 'double-sickening'. For the treatment of acute viral RS, nasal saline irrigations and OTC cold remedies are advised. In acute postviral RS, additional topical steroids are suggested. Advantages and disadvantages of antibiotic treatment in acute bacterial RS are detailed. Overall, the new EPOS position paper infers a reorientation in this area of high medical, pharmaceutical and economic relevance.


Characterizing the Landscape of Safety Net Programs and Policies in California during the COVID-19 Pandemic.
The COVID-19 pandemic prompted rapid and innovative policymaking around the world at the national, regional, and local levels. There has been limited work to systematically document and characterize new and expanded local U.S. pandemic-era policies, which is imperative to better understand the policy variation and resulting health impacts during this unprecedented time. California, the most populous U.S. state, provides a case example of a particularly active policy response. The aim of this Brief Report is to summarize the creation and potential areas of application of a newly created publicly available California- and US-based COVID-19 policy database. We generated an extensive list of California and US policies that were modified or created in response to the COVID-19 pandemic. From July-November 2021, we searched current and historical California and federal government websites, press releases, social media, and news sources and recorded detailed information on these policies, including coverage dates, eligibility criteria, and benefit amounts. This comprehensive dataset includes 39 public health, economic, housing, and safety net programs and policies implemented at both federal and state levels and provides details of the complex and multifaceted policy landscape in California from March 2020 to November 2021. Our database is publicly available. Future investigators can leverage the information systematically recorded in this database to rigorously assess the short- and long-term effects of these policies, which will in turn inform future preparedness response plans in California and beyond.


The human tyrosine kinase gene (FER) maps to chromosome 5 and is deleted in myeloid leukemias with a del(5q).
A novel member of the SRC tyrosine kinase gene family was recently isolated and characterized (Hao et al., 1989). This FES/FPS-related gene, named FER, lacks the transmembrane and extracellular domains which characterize tyrosine kinases with receptor function. Expression of FER in a wide range of cell types indicates a general role in intracellular signalling or differentiation processes. We have now mapped FER to chromosome 5q14----q23 using in situ hybridization techniques and suggest a more precise location within bands 5q21----q22. This region lies adjacent to a complex domain of growth factors and receptors, many involved in regulation of haematopoiesis. FER maps within a critical segment frequently deleted from chromosome 5 in patients with acute myeloid leukemia or myelodysplastic syndromes and was shown to be deleted in two such patients. It also maps close to the familial polyposis coli locus at 5q22.


Deep burns caused by far-infrared rays in a chiropractic sales centre.
We report the case of a patient who sustained a deep burn in the right ankle as a result of using far-infrared rays for the management of chronic pain in that site. The burn was sustained in a chiropractic sales centre. We recommend medical supervision in such centres and strict adherence to safety precautions.


Practical asymmetric conjugate alkynylation of Meldrum's acid-derived acceptors: access to chiral beta-alkynyl acids.
The enantioselective conjugate addition of alkynyl nucleophiles has been a long-standing challenge in synthetic chemistry. This paper describes a highly practical asymmetric conjugate alkynylation of Meldrum's acid-derived acceptors using cinchonidine (<$100/kg) as the chiral mediator. The process provides practical access to chiral beta-alkynyl acids. Noteworthy attributes of the method are its broad scope, high functional-group compatibility, and ease of scalability.


Effect of Dietary Fish Oil on Semen Quality and Reproductive Performance of Iranian Zandi Rams.
The current study was conducted to evaluate the effect of dietary fish oil on the semen quality and fertility potential of Zandi rams. For this purpose, a total of 15 Iranian Zandi rams were randomly assigned into three equal groups. The first group was a negative control and were fed without oil supplement. The second group was a positive control, and their diet contained palm oil, and the last group had a diet containing fish oil. All the diets were isocaloric and isonitrogenous. The rams were fed for 70 days, and the semen smaples were collected every 10 days. In experiment I, the evaluated parameters included semen volume, sperm concentration, motility, membrane integrity, and viability. In experiment II, 210 Iranian Zandi rams received CIDR for 12 days and 400 IU of equine chorionic gonadotropin at the time of CIDR removal. Then, they were assigned into three equal groups and artificially inseminated with semen samples. According to the obtained results, the supplementation of ram diet with fish oil as a source of omega-3 fatty acids improved the semen volume, sperm concentration, total motility, progressive motility, viability, membrane integrity, pregnancy rate, parturition rate, and lambing rate of the rams (P≤0.05). In conclusion, fish oil as a dietary supplement for rams could be an effective strategy to improve the semen quality of rams for artificial insemination and other goals.


[Decomposition of the differences in life expectancies].
"This study decomposes the differences between average life expectancies at age x by double standardization into effect of differences in the mortality structure by causes of death, and into effect of differences in the average life expectancies of those deceased due to certain causes of death, relying on abridged life tables by causes of death as for Belgium and Hungary in 1984.... The mortality structure by causes of death is more favourable in the case of females in both countries, but it contributes less to the rather significant differences in general mortality level. It is worth mentioning that the differences in the mortality level of males and females presents itself more definitely in Hungary than in Belgium." (SUMMARY IN ENG AND RUS)


Immunomodulatory Properties of Polysaccharide-Rich Young Green Barley (Hordeum vulgare) Extract and Its Structural Characterization.
Young green barley (YGB) water extract has revealed a beneficial impact on natural killer (NK) cells' ability to recognize and eliminate human colon cancer cells, without any side effects for normal colon epithelial cells. The direct anticancer effect of the tested compounds has been also shown. The mixture of oligosaccharides found in this extract was characterized by chemical analyses and via FT-IR spectroscopy and MALDI-TOF MS techniques. The YGB preparation contained 26.9% of proteins and 64.2% of sugars, mostly glucose (54.7%) and fructose (42.7%), with a small amount of mannose (2.6%) and galactose (less than 0.5%). Mass spectrometry analysis of YGB has shown that fructose oligomers contained from 3 to 19 sugar units. The number of fructans was estimated to be about 10.2% of the dry weight basis of YGB. The presented results suggest the beneficial effect of the consumption of preparations based on young barley on the human body, in the field of colon cancer prevention.


Transcriptional landscape of circulating platelets from patients with COVID-19 reveals key subnetworks and regulators underlying SARS-CoV-2 infection: implications for immunothrombosis.
Thrombosis and coagulopathy are pervasive pathological features of coronavirus disease 2019 (COVID-19), and thrombotic complications are a sign of severe COVID-19 disease and are associated with multiple organ failure and increased mortality. Platelets are essential cells that regulate hemostasis, thrombus formation and inflammation; however, the mechanism underlying the interaction between platelets and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. The present study performed RNA sequencing on the RNA isolated from platelets obtained from 10 COVID-19 patients and eight healthy donors, and discovered that SARS-CoV-2 not only significantly altered the coding and non-coding transcriptional landscape, but also altered the function of the platelets, promoted thrombus formation and affected energy metabolism of platelets. Integrative network biology analysis identified four key subnetworks and 16 risk regulators underlying SARS-CoV-2 infection, involved in coronavirus disease-COVID-19, platelet activation and immune response pathways. Furthermore, four risk genes (upstream binding transcription factor, RNA polymerase II, I and III subunit L, Y-box binding protein 1 and yippee like 2) were found to be associated with COVID-19 severity. Finally, a significant alteration in the von Willebrand factor/glycoprotein Ib-IX-V axis was revealed to be strongly associated with platelet aggregation and immunothrombosis. The transcriptional landscape and the identification of critical subnetworks and risk genes of platelets provided novel insights into the molecular mechanisms of immunothrombosis in COVID-19 progression, which may pave the way for the development of novel therapeutic strategies for preventing COVID-19-associated thrombosis and improving the clinical outcome of COVID-19 patients.


Dizygotic twin pregnancies after medically assisted reproduction and after natural conception: maternal and perinatal outcomes.
To compare maternal and perinatal outcomes in dizygotic twin pregnancies conceived after medically assisted reproduction (MAR) with outcomes after natural conception (NC). Nationwide registry based study. Academic medical center. Primiparous women who delivered opposite sex twins between January 2000 and December 2012 in the Netherlands, comprising dizygotic twin pregnancies: 6,694 women, 470 after ovulation induction (OI), 511 after intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), 2,437 after in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI), and 3,276 after NC. None. Multivariable logistic regression and generalized linear mixed models to evaluate differences in outcomes: maternal outcomes of hypertension, preeclampsia, preterm delivery, hemorrhage, and delivery mode, perinatal outcomes including small for gestational age (SGA) with birth weight <10th percentile, birth weight <1,500 g, 5-minute Apgar score <7, admission to neonatal intensive care unit, congenital anomalies, and perinatal mortality. We found no statistically significant differences in maternal or perinatal outcomes after OI compared with NC. Women pregnant after IVF-ICSI had a lower risk for hypertension (adjusted odds ratio [aOR] 0.74; 95% confidence interval [CI], 0.66-0.83) compared with women pregnant after NC. After IUI-COH more children had Apgar scores <7 (adjusted odds ratio (aOR) 1.38; 95% confidence interval (CI) 1.05-1.81) and perinatal mortality rates were higher (aOR 1.56; 95% CI, 1.04-2.33) compared with NC. We found no differences in perinatal outcomes after IVF-ICSI compared with NC. Overall, maternal and perinatal risks other than those due to multiplicity are similar for twin pregnancies conceived after MAR and after NC.


Role of spectral counting in quantitative proteomics.
Spectral count, defined as the total number of spectra identified for a protein, has gained acceptance as a practical, label-free, semiquantitative measure of protein abundance in proteomic studies. In this review, we discuss issues affecting the performance of spectral counting relative to other label-free methods, as well as its limitations. Possible consequences of modifications, which are commonly applied to raw spectral counts to improve abundance estimations, are considered. The use of spectral counting for different types of quantitation studies is explored and critiqued. Different statistical methods and underlying frameworks that have been applied to spectral count analysis are described and compared, and problem areas that undermine confident statistical analysis are considered. Finally, the issue of accurate estimation of false-discovery rates is addressed and identified as a major current challenge in quantitative proteomics.


Short-term infusion of a fish oil-based lipid emulsion modulates fatty acid status, but not immune function or (anti)oxidant balance: a randomized cross-over study.
Studies suggest clinical benefits of parenteral fish oil (FO), rich in n-3 polyunsaturated fatty acids (PUFAs), over soyabean oil (SO), rich in n-6 PUFAs, in patients with pro-inflammatory conditions such as sepsis and trauma. Because the mechanisms behind these observations remain unclear, the present study explored the effects of intravenous infusion of FO and SO on fatty acid incorporation, immune functions and (anti)oxidant balance in healthy human volunteers. Saline, a SO emulsion and a FO emulsion were administered for one hour on three consecutive days at a rate of 0·2 g/kg BW/h to eight subjects in a randomized cross-over design with a 3-week interval between treatments. Plasma phospholipid and peripheral blood mononuclear cell (PBMC) fatty acid compositions, and leucocyte counts and functions were assessed prior to the first infusion (T = 0, baseline) and 1 day (T = 4, early effects) and 8 days (T = 11, late effects) after the third infusion. Fish oil infusion significantly increased n-3 PUFA proportions and decreased n-6 PUFA proportions in plasma phospholipids and PBMCs. There were no differences in immune functions or (anti)oxidant balance between treatments at any time. The present lipid infusion protocol appears to be safe and well tolerated and provides significant incorporation of n-3 PUFAs into plasma phospholipids and PBMCs. In the absence of overt inflammation, no direct effects of FO were observed on immune function or (anti)oxidant balance. This model may be useful to evaluate effects of parenteral lipids in other settings, for example in individuals displaying an inflammatory state.


Evaluation of Deep Neural Network Compression Methods for Edge Devices Using Weighted Score-Based Ranking Scheme.
The demand for object detection capability in edge computing systems has surged. As such, the need for lightweight Convolutional Neural Network (CNN)-based object detection models has become a focal point. Current models are large in memory and deployment in edge devices is demanding. This shows that the models need to be optimized for the hardware without performance degradation. There exist several model compression methods; however, determining the most efficient method is of major concern. Our goal was to rank the performance of these methods using our application as a case study. We aimed to develop a real-time vehicle tracking system for cargo ships. To address this, we developed a weighted score-based ranking scheme that utilizes the model performance metrics. We demonstrated the effectiveness of this method by applying it on the baseline, compressed, and micro-CNN models trained on our dataset. The result showed that quantization is the most efficient compression method for the application, having the highest rank, with an average weighted score of 9.00, followed by binarization, having an average weighted score of 8.07. Our proposed method is extendable and can be used as a framework for the selection of suitable model compression methods for edge devices in different applications.