Three new remarkable amphipod species (Crustacea: Gammaridae) from springs and subterranean waters of Central Asia.
Three new species of the family Gammaridae-Gammarus troglomorphus, sp. n., G. parvioculatus, sp. n. from Lebap Province of Turkmenistan and Tadzocrangonyx alaicus, sp. n. from Batken Region of Kyrgyzstan are described and illustrated. Morphological studies of a closely related Turkmenistan population of G. cf. subaequalis-Garlyk, probably conspecific with Gammarus subaequalis Martynov, 1935 was provided. The affinity of new species to concerned taxa is discussed. To define phylogenetic position of mentioned species DNA barcode data are obtained. Gammarus troglomorphus and G. parvioculatus are close neighbors but exceedingly different morphologically. Gammarus troglomorphus is a troglobiont; G. parvioculatus is an eutroglophile, but with exception of slightly smaller eyes, not troglomorph. Both found only within small areas in the extreme East of Turkmenistan. Gammarus cf. subaequalis-Garlyk seems to extend from the same region far into the eastern Kyrgyzstan.


Transcriptome analysis of pancreatic cancer cell response to treatment with grape seed proanthocyanidins.
Grape seed proanthocyanidins (GSPs) have been demonstrated to exhibit potential chemotherapeutic efficacy against various cancer types. To determine the underlying molecular mechanisms involved in GSP-induced apoptosis, the present study prepared pancreatic cancer (PC) cells samples, S3, S12 and S24, which were treated with 20 µg/ml GSPs for 3, 12 and 24 h, respectively. Control cell samples, C3, C12 and C24, were also prepared. Using RNA-sequencing, transcriptome comparisons were performed, which identified 966, 3,543 and 4,944 differentially-expressed genes (DEGs) in S3 vs. C3, S12 vs. C12 and S24 vs. C24, respectively. Gene Ontology analysis of the DEGs, revealed that treatment with GSPs is associated with disruption of the cell cycle (CC) in PC cells. Additionally, disruption of transcription, DNA replication and DNA repair were associated with GSP-treatment in PC cells. Network analysis demonstrated that the common DEGs involved in the CC, transcription, DNA replication and DNA repair were integrated, and served essential roles in the control of CC progression in cancer cells. In summary, GSPs may exhibit a potential chemotherapeutic effect on PC cell proliferation.


Parental Post-traumatic Stress Disorder Symptoms Are Related to Successful Aging in Offspring of Holocaust Survivors.
A fascinating, yet underexplored, question is whether traumatic events experienced by previous generations affect the aging process of subsequent generations. This question is especially relevant for offspring of Holocaust survivors (OHS), who begin to face the aging process. Some preliminary findings point to greater physical dysfunction among middle-aged OHS, yet the mechanisms behind this dysfunction need further clarification. Therefore, the current studies assess aging OHS using the broad-scoped conceptualization of successful aging, while examining whether offspring successful aging relates to parental post-traumatic stress disorder (PTSD) symptoms and offspring's secondary traumatization symptoms. In Study 1, 101 adult offspring (mean age = 62.31) completed measures of parental PTSD, secondary traumatization, as well as successful aging indices - objective (medical conditions, disability and somatic symptoms) and subjective (perceptions of one's aging). Relative to comparisons and OHS who reported that none of their parents suffered from probable PTSD, OHS who reported that their parents suffered from probable PTSD had lower scores in objective and subjective measures of successful aging. Mediation analyses showed that higher level of secondary traumatization mediated the relationship between parental PTSD and less successful aging in the offspring. Study 2 included 154 dyads of parents (mean age = 81.86) and their adult offspring (mean age = 54.48). Parents reported PTSD symptoms and offspring reported secondary traumatization and completed measures of objective successful aging. Relative to comparisons, OHS whose parent had probable PTSD have aged less successfully. Once again, offspring secondary traumatization mediated the effect. The findings suggest that parental post-traumatic reactions assessed both by offspring (Study 1) and by parents themselves (Study 2) take part in shaping the aging of the subsequent generation via reactions of secondary traumatization in the offspring. The studies also provide initial evidence that these processes can transpire even when offspring do not have probable PTSD or when controlling offspring anxiety symptoms. Our findings allude to additional behavioral and epigenetic processes that are potentially involved in the effect of parental PTSD on offspring aging, and further imply the need to develop interdisciplinary interventions aiming at promoting successful aging among offspring of traumatized parents.


MicroRNAs-based Therapy: A Novel and Promising Strategy for Cancer Treatment.
MicroRNAs are short non-coding RNAs involved in critical biological processes. In the past decade, the deregulation of miRNAs has been well-documented in a wide range of human diseases, including cancer. Overexpression and downregulation of miRNAs affect cellular pathways that contribute to carcinogenesis and tumor progression. This evidence makes miRNAs a suitable candidate for therapeutic applications and leads to developing strategies to manipulate their expression. Consistently, in vitro and in vivo studies show that Let-7, miR-10b, miR-21, miR-34, miR-155 and miR-221 are promising targets to develop miRNAs-based therapy for human malignancies. The purpose of this review is to discuss the different approaches that can be used to restore or reduce miRNAs expression in human cancer and the therapeutic implications.


The effect of carbon irradiation is associated with greater oxidative stress in mouse intestine and colon relative to γ-rays.
Carbon irradiation due to its higher biological effectiveness relative to photon radiation is a concern for toxicity to proliferative normal gastrointestinal (GI) tissue after radiotherapy and long-duration space missions such as mission to Mars. Although radiation-induced oxidative stress is linked to chronic diseases such as cancer, effects of carbon irradiation on normal GI tissue have not been fully understood. This study assessed and compared chronic oxidative stress in mouse intestine and colon after different doses of carbon and γ radiation, which are qualitatively different. Mice (C57BL/6J) were exposed to 0.5 or 1.3 Gy of γ or carbon irradiation, and intestinal and colonic tissues were collected 2 months after irradiation. While part of the tissues was used for isolating epithelial cells, tissue samples were also fixed and paraffin embedded for 4 µm thick sections as well as frozen for biochemical assays. In isolated epithelial cells, reactive oxygen species and mitochondrial status were studied using fluorescent probes and flow cytometry. We assessed antioxidant enzymes and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in tissues and formalin-fixed tissue sections were stained for 4-hydroxynonenal, a lipid peroxidation marker. Data show that mitochondrial deregulation, increased NADPH oxidase activity, and decreased antioxidant activity were major contributors to carbon radiation-induced oxidative stress in mouse intestinal and colonic cells. When considered along with higher lipid peroxidation after carbon irradiation relative to γ-rays, our data have implications for functional changes in intestine and carcinogenesis in colon after carbon radiotherapy as well as space travel.


Simple, Amplified, and Multiplexed Detection of MicroRNAs Using Time-Gated FRET and Hybridization Chain Reaction.
The hybridization chain reaction (HCR) is a simple and sensitive method for quantifying nucleic acids. Current approaches cannot combine a washing-free sensing format with multiplexed target quantification at low concentrations, which would be highly desirable for detection both in solution and in situ. Here, we demonstrate the implementation of time-gated Förster resonance energy transfer (TG-FRET) between terbium donors and dye acceptors into HCR for multiplexed quantification of microRNAs (miR-20a and miR-21) and their DNA analogues. HCR-TG-FRET provided washing-free nucleic acid quantification with very low limits of detection down to 240 amol (1.7 pM) of microRNA and 123 amol (0.88 pM) of DNA. Efficient distinction from very homologous microRNAs demonstrated high target specificity. Multiplexing with a single measurement, a single excitation wavelength, and a single FRET pair allowed for a simultaneous quantification of miR-20a and miR-21 at concentrations between 30 and 300 pM from the same sample. HCR-TG-FRET showed similar performance for serum-free and serum-containing samples without the use of RNase inhibitors. Our results present a significant improvement in current HCR approaches regarding simplicity, sensitivity, and multiplexing. The versatile diagnostic performance of HCR-TG-FRET even in challenging biological environments presents an important advantage for advanced nucleic acid biosensing.


[Abnormal antithrombin III: abnormalities of heparin or protease binding domain].
Two patients with abnormal antithrombin III manifested abnormality in heparin binding activity (abnormal antithrombin III "Toyma") or protease binding activity (abnormal antithrombin III "Aomori"). Antithrombin III "Toyama" is hereditarily homozygous with Arg47 to Cys47 (TGC-->TGT) mutation, and antithrombin III "Aomori" is hereditarily heterozygous with Arg393 to His393 (CGT-->CAT). The former is classified as type II-c, and the latter as type II-b according to Lane's classification2). Both patients showed cerebral thrombosis after age 20. Heparin cofactor II activity in the former case was slightly higher than normal. Oral anticoagulant therapy was used in the both cases. These cases were examined by biological and immunological assay, heparin sepharose column chromatography, binding activity to cultured porcine endothelial cells, restriction fragment length polymorphysm and polymerase chain reaction. The authors developed an antithrombin III assay method to be able to estimate real activity without the influence of heparin cofactor II activity11), and to apply the low molecular weight heparin to prevent relapse of thrombosis, and finally to find an anticoagulant substance in an interesting case of hepatocellular carcinoma (Edmondson type 1) producing normal antithrombin III30).


A controlled trial of GL enzyme in the treatment of acute myocardial infarction.
GL enzyme (hyaglosidase) is a highly purified component enzyme of hyaluronidase. A therapeutic trial was carried out in the treatment of suspected myocardial infarction among 1,488 patients presenting within 6 h of the onset of symptoms. No significant reduction in mortality at 6 months was observed in the GL group (15.7%) compared with the placebo group (16.4%). Mortality at 2 weeks was also unaffected by treatment (GL 10.3%; placebo 10.9%).


The dominant negative thyroid hormone receptor beta-mutant {Delta}337T alters PPAR{alpha} signaling in heart.
PPARalpha and TR independently regulate cardiac metabolism. Although ligands for both these receptors are currently under evaluation for treatment of congestive heart failure, their interactions or signaling cooperation have not been investigated in heart. We tested the hypothesis that cardiac TRs interact with PPARalpha regulation of target genes and used mice exhibiting a cardioselective Delta337T TRbeta1 mutation (MUT) to reveal cross-talk between these nuclear receptors. This dominant negative transgene potently inhibits DNA binding for both wild-type (WT) TRalpha and TRbeta. We used UCP3 and MTE-1 as principal reporters and analyzed gene expression from hearts of transgenic (MUT) and nontransgenic (WT) littermates 6 h after receiving either specific PPARalpha ligand (WY-14643) or vehicle. Interactions were determined through qRT-PCR analyses, and the extent of these interactions across multiple genes was determined using expression arrays. In the basal state, we detected no differences between groups for protein content for UCP3, PPARalpha, TRalpha2, RXRbeta, or PGC-1alpha. However, protein content for TRalpha1 and the PPARalpha heterodimeric partner RXRalpha was diminished in MUT, whereas PPARbeta increased. We demonstrated cross-talk between PPAR and TR for multiple genes, including the reporters UCP3 and MTE1. WY-14643 induced a twofold increase in UCP3 gene expression that was totally abrogated in MUT. We demonstrated variable cross-talk patterns, indicating that multiple mechanisms operate according to individual target genes. The non-ligand-binding TRbeta1 mutation alters expression for multiple nuclear receptors, providing a novel mechanism for interaction that has not been previously demonstrated. These results indicate that therapeutic response to PPARalpha ligands may be determined by thyroid hormone state and TR function.


Effect of the geometry of confining media on the stability and folding rate of α -helix proteins.
Protein folding in confined media has attracted wide attention over the past 15 years due to its importance to both in vivo and in vitro applications. It is generally believed that protein stability increases by decreasing the size of the confining medium, if the medium's walls are repulsive, and that the maximum folding temperature in confinement is in a pore whose size D 0 is only slightly larger than the smallest dimension of a protein's folded state. Until recently, the stability of proteins in pores with a size very close to that of the folded state has not received the attention it deserves. In a previous paper [L. Javidpour and M. Sahimi, J. Chem. Phys. 135, 125101 (2011)], we showed that, contrary to the current theoretical predictions, the maximum folding temperature occurs in larger pores for smaller α-helices. Moreover, in very tight pores, the free energy surface becomes rough, giving rise to a new barrier for protein folding close to the unfolded state. In contrast to unbounded domains, in small nanopores proteins with an α-helical native state that contain the β structures are entropically stabilized implying that folding rates decrease notably and that the free energy surface becomes rougher. In view of the potential significance of such results to interpretation of many sets of experimental data that could not be explained by the current theories, particularly the reported anomalously low rates of folding and the importance of entropic effects on proteins' misfolded states in highly confined environments, we address the following question in the present paper: To what extent the geometry of a confined medium affects the stability and folding rates of proteins? Using millisecond-long molecular dynamics simulations, we study the problem in three types of confining media, namely, cylindrical and slit pores and spherical cavities. Most importantly, we find that the prediction of the previous theories that the dependence of the maximum folding temperature T f on the size D of a confined medium occurs in larger media for larger proteins is correct only in spherical geometry, whereas the opposite is true in the two other geometries that we study. Also studied is the effect of the strength of the interaction between the confined media's walls and the proteins. If the walls are only weakly or moderately attractive, a complex behavior emerges that depends on the size of the confining medium.


Crystal structure of tubulin tyrosine ligase-like 3 reveals essential architectural elements unique to tubulin monoglycylases.
Glycylation and glutamylation, the posttranslational addition of glycines and glutamates to genetically encoded glutamates in the intrinsically disordered tubulin C-terminal tails, are crucial for the biogenesis and stability of cilia and flagella and play important roles in metazoan development. Members of the diverse family of tubulin tyrosine ligase-like (TTLL) enzymes catalyze these modifications, which are part of an evolutionarily conserved and complex tubulin code that regulates microtubule interactions with cellular effectors. The site specificity of TTLL enzymes and their biochemical interplay remain largely unknown. Here, we report an in vitro characterization of a tubulin glycylase. We show that TTLL3 glycylates the β-tubulin tail at four sites in a hierarchical order and that TTLL3 and the glutamylase TTLL7 compete for overlapping sites on the tubulin tail, providing a molecular basis for the anticorrelation between glutamylation and glycylation observed in axonemes. This anticorrelation demonstrates how a combinatorial tubulin code written in two different posttranslational modifications can arise through the activities of related but distinct TTLL enzymes. To elucidate what structural elements differentiate TTLL glycylases from glutamylases, with which they share the common TTL scaffold, we determined the TTLL3 X-ray structure at 2.3-Å resolution. This structure reveals two architectural elements unique to glycyl initiases and critical for their activity. Thus, our work sheds light on the structural and functional diversification of TTLL enzymes, and constitutes an initial important step toward understanding how the tubulin code is written through the intersection of activities of multiple TTLL enzymes.


DISMISS: detection of stranded methylation in MeDIP-Seq data.
DNA methylation is an important regulator of gene expression and chromatin structure. Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) is commonly used to identify regions of DNA methylation in eukaryotic genomes. Within MeDIP-Seq libraries, methylated cytosines can be found in both double-stranded (symmetric) and single-stranded (asymmetric) genomic contexts. While symmetric CG methylation has been relatively well-studied, asymmetric methylation in any dinucleotide context has received less attention. Importantly, no currently available software for processing MeDIP-Seq reads is able to resolve these strand-specific DNA methylation signals. Here we introduce DISMISS, a new software package that detects strand-associated DNA methylation from existing MeDIP-Seq analyses. Using MeDIP-Seq datasets derived from Apis mellifera (honeybee), an invertebrate species that contains more asymmetric- than symmetric- DNA methylation, we demonstrate that DISMISS can identify strand-specific DNA methylation signals with similar accuracy as bisulfite sequencing (BS-Seq; single nucleotide resolution methodology). Specifically, DISMISS is able to confidently predict where DNA methylation predominates (plus or minus DNA strands - asymmetric DNA methylation; plus and minus DNA stands - symmetric DNA methylation) in MeDIP-Seq datasets derived from A. mellifera samples. When compared to DNA methylation data derived from BS-Seq analysis of A. mellifera worker larva, DISMISS-mediated identification of strand-specific methylated cytosines is 80 % accurate. Furthermore, DISMISS can correctly (p <0.0001) detect the origin (sense vs antisense DNA strands) of DNA methylation at splice site junctions in A. mellifera MeDIP-Seq datasets with a precision close to BS-Seq analysis. Finally, DISMISS-mediated identification of DNA methylation signals associated with upstream, exonic, intronic and downstream genomic loci from A. mellifera MeDIP-Seq datasets outperforms MACS2 (Model-based Analysis of ChIP-Seq2; a commonly used MeDIP-Seq analysis software) and closely approaches the results achieved by BS-Seq. While asymmetric DNA methylation is increasingly being found in growing numbers of eukaryotic species and is the predominant pattern observed in some invertebrate genomes, it has been difficult to detect in MeDIP-Seq datasets using existing software. DISMISS now enables more sensitive examinations of MeDIP-Seq datasets and will be especially useful for the study of genomes containing either low levels of DNA methylation or for genomes containing relatively high amounts of asymmetric methylation.


[Clinical Characteristics of Mild-Moderate COVID-19 Patients and Risk Factors for the Development of Pneumonia].
Limited data exists to date on the predictors for the development of pneumonia in patients with mild and moderate coronavirus (COVID-19). In this study, it was aimed to evaluate the demographic characteristics and clinical findings of mild and moderate COVID-19 and to determine the risk factors for the development of COVID-19 pneumonia in patients admitted to the pandemic outpatient clinic of a university hospital. A total of 414 patients with laboratory confirmed COVID-19 were included. Of these, 220 (53.1%) were male, the mean age was 38.3 ± 12.7. Median duration of hospital admission from the onset of symptoms was three days (0-11). Of the confirmed COVID-19 cases, 154 (37.2%) had a history of family contact and the most common symptoms were weakness (68.4%), myalgia (61.8%), headache (56.5%), loss of smell (45.2%), loss of taste (43.2%) and anorexia (42.8%). Among females, weakness (p= 0.016), headache (p= 0.008), sore throat (p= 0.032), nausea (p= 0.003), anorexia (p= 0.045), loss of taste (p= 0.005) and loss of smell (p<0.001) were more common. Loss of taste (47.6% vs. 25%, p<0.001) and loss of smell (50% vs. 26.3%, p<0.001) were more common in patients with under the age of 50 and cough (43.4% vs. 29.3%, p= 0.003) was more common in patients with above the age of 40. Among 46 (11.1%) patients with asymptomatic COVID-19, there was no significant difference (p= 0.500) between the genders. Pneumonia was detected in 150 (43.8%) of 339 patients who underwent thorax computed tomography. In the univariate analysis; advanced age (p<0.001, odds ratio (OR)= 1.44), obesity (p<0.001 OR= 2.5), not being actively smoking (p<0.001, OR= 6.19), fever at first admission (p= 0.002, OR= 2.02), cough (p<0.001, OR= 3.26), shortness of breath (p<0.001, OR= 23.37), weakness (p= 0.042, OR= 1.63), anorexia (p= 0.009, OR= 1.79) and elevation of D-dimer (p= 0.014, OR= 1.92) were associated with the development of pneumonia. In multivariate analysis, obesity (p= 0.005, OR= 2.69), not being actively smoking (p<0.001, OR= 5.43), cough at first admission p= 0.017, OR= 2.16) and shortness of breath (p= 0.008, OR= 16.22) was determined as an independent risk factor for the development of pneumonia. CRP (p<0.001), D-dimer (p<0.001), ferritin (p<0.001) values among 108 (26.1%) patients with a body-mass index(BMI) >30 were high, and 60.9% of the patients had pneumonia (p<0.001) . CRP (p<0.001), D-dimer (p= 0.010) values were low, lymphocyte count (p= 0.001) was high among 106 (25.6%) active smokers, and 15.6% of the patients had pneumonia (p<0.001). Of the patients reported with persistent symptoms, 25.9% had loss of smell, 25% had weakness, and 23.1% had loss of taste on the seventh day; 21.1% had loss of smell, 21.1% had myalgia, and 19.7% had loss of taste on the 14th day. During their follow-up, the COVID-19 polymerase chain reaction (PCR) test was studied in 286 patients for control purposes. The median time of being negative for COVID-19 PCR test was eight days (3-56). In conclusion, symptoms may last longer than 14 days in 20- 30% of patients presenting with mild-moderate clinical findings. In addition, obesity should be considered as an important risk factor for COVID-19 pneumonia.


Reaction Mechanisms of Well-Defined Metal-N4 Sites in Electrocatalytic CO2 Reduction.
Electrocatalytic CO2 reduction to CO emerges as a potential route of utilizing emitted CO2 . Metal-N-C hybrid structures have shown unique activities, however, the active centers and reaction mechanisms remain unclear because of the ambiguity in true atomic structures for the prepared catalysts. Herein, combining density-functional theory calculations and experimental studies, the reaction mechanisms for well-defined metal-N4 sites were explored using metal phthalocyanines as model catalysts. The theoretical calculations reveal that cobalt phthalocyanine exhibits the optimum activity for CO2 reduction to CO because of the moderate *CO binding energy at the Co site, which accommodates the *COOH formation and the *CO desorption. It is further confirmed by experimental studies, where cobalt phthalocyanine delivers the best performance, with a maximal CO Faradaic efficiency reaching 99 %, and maintains stable performance for over 60 hours.


Chest wall injuries due to cardiopulmonary resuscitation and the effect on in-hospital outcomes in survivors of out-of-hospital cardiac arrest.
This study aimed to assess the prevalence of chest wall injuries due to cardiopulmonary resuscitation for out-of-hospital cardiac arrest (OHCA) and to compare in-hospital outcomes in patients with versus without chest wall injuries. A retrospective cohort study of all intensive care unit (ICU)-admitted patients who underwent cardiopulmonary resuscitation for OHCA between January 1, 2007, and December 2019 was performed. The primary outcome was the occurrence of chest wall injuries, as diagnosed on chest computed tomography. Chest wall injury characteristics such as rib fracture location, type, and dislocation were collected. Secondary outcomes were in-hospital outcomes and subgroup analysis of patients with good neurological recovery to identify those who could possibly benefit from the surgical stabilization of rib fractures. Three hundred forty-four patients were included, of which 291 (85%) sustained chest wall injury. Patients with chest wall injury had a median of 8 fractured ribs (P25-P75, 4-10 ribs), which were most often undisplaced (on chest computed tomography) (n = 1,574 [72.1%]), simple (n = 1,948 [89.2%]), and anterior (n = 1,785 [77.6%]) rib fractures of ribs 2 to 7. Eight patients (2.3%) had a flail segment, and 136 patients (39.5%) had an anterior flail segment. Patients with chest wall injury had fewer ventilator-free days (0 days [P25-P75, 0-16 days] vs. 13 days [P25-P75, 2-22 days]; p = 0.006) and a higher mortality rate (n = 102 [54.0%] vs. n = 8 [22.2%]; p < 0.001) than those without chest wall injury. For the subgroup of patients with good neurological recovery, the presence of six or more rib fractures or a single displaced rib fracture was associated with longer hospital and ICU length of stay, respectively. Cardiopulmonary resuscitation-related chest wall injuries in survivors of OHCA and especially rib fractures are common. Patients with chest wall injury had fewer ventilator-free days and a higher mortality rate. Patients with good neurological recovery might represent a subgroup of patients who could benefit from surgical stabilization of rib fractures. Therapeutic, level IV; Epidemiological, Level IV.


Cohort profile of the largest health & demographic surveillance system (Dibrugarh-HDSS) from North-East India.
Dibrugarh Health and Demographic Surveillance System (Dibrugarh-HDSS), was started in the year 2019 with the objective to create the health and demographic database of a population from a defined geographical area and a surveillance system for providing technical assistance for the implementation of programmes and formulating intervention strategies for reducing disease morbidities and mortalities in the population. Dibrugarh-HDSS adopted a panel design and covered 60 contiguous villages and 20 tea gardens. Line listing of all the households was conducted and a unique identification number detailing State, district, village/tea garden and serial number was provided along with geotagging. Detailed sociodemographic variables, anthropometric measurements (subjects ≥five years) and blood pressure data (subjects ≥18 yr), disease morbidity and mortality were collected. All data were collected in pre-designed and pre-tested questionnaires using a mobile application package developed for this purpose. Dibrugarh-HDSS included a total of 106,769 individuals (rural: 46,762, tea garden: 60,007) with 52,934 males (49.6%) and 53,835 females (50.4%). The number of females per thousand males were significantly higher (1042 in tea garden vs. 985 in rural populations) in the tea-garden community as compared to the village population. More than one-third (35.1%) of tea populations were illiterate compared to the rural population (17.1%). Villagers had significantly higher body mass index than the tea-garden community. The overall prevalence of hypertension (adjusted for age) was 29.4 vs. 28.2 per cent, respectively, for the village and tea-garden population. For both these communities, males (village=30.8%, tea garden=31.1%) showed a higher prevalence of hypertension (adjusted for age) than females (village=28.2%, tea garden=25.8%). The findings of the present study give an insight into the profile of the native rural and tea-garden populations that will help to identify risk factors of different health problems, review the effectiveness of different ongoing programmes, implement intervention strategies for reducing morbidity and mortality and assist the State health authorities in prioritizing their resource allocation and implementation strategies.


Low Frequency of Cardiomyopathy Using Cardiac Magnetic Resonance Imaging in an Acromegaly Contemporary Cohort.
Left ventricular hypertrophy (LVH) and myocardial fibrosis are considered common findings of the acromegaly cardiomyopathy in echocardiography studies. To evaluate the frequency of LVH, systolic dysfunction and myocardial fibrosis was undertaken in patients with acromegaly using cardiac magnetic resonance imaging (CMRi) before and after 12 months of octreotide long-acting repeatable treatment. Consecutive patients with active acromegaly submitted to biochemical analysis and CMRi before and after 12 months of treatment. Additionally, echocardiography was performed before treatment. Forty consecutive patients were evaluated using CMRi at baseline and 30 patients were reevaluated after 12 months of treatment. Additionally, 29 of these patients were submitted to echocardiography. Using CMRi, the frequency of LVH was 5%. The mean left ventricular mass index (LVMi) was 61.73 ± 18.8 g/m(2). The mean left ventricular ejection fraction (LVEF) was 61.85 ± 9.2%, and all patients had normal systolic function. Late gadolinium enhancement was present in five patients (13.5%), and one patient (3.5%) had an increased extracellular volume. After treatment, 12 patients (40%) had criteria for disease control. No clinically relevant differences in cardiac variables before and after treatment were observed. Additionally, there was no difference in LVMi and LVEF among patients with and without disease control. Using echocardiography, 31% of the patients had LVH, mean LVMi was 117.8 ± 46.3 g/m(2) and mean LVEF was 67.3 ± 4.4%. All patients had normal systolic function. We demonstrated by CMRi, the gold-standard method, that patients with active acromegaly might have a lower prevalence of cardiac abnormalities than previously reported.


Imprints of log-periodicity in thermoacoustic systems close to lean blowout.
In the context of statistical physics, critical phenomena are accompanied by power laws having a singularity at the critical point where a sudden change in the state of the system occurs. In this work we show that lean blowout (LBO) in a turbulent thermoacoustic system is accompanied by a power law leading to finite-time singularity. As a crucial discovery of the system dynamics approaching LBO, we unravel the existence of the discrete scale invariance (DSI). In this context, we identify the presence of log-periodic oscillations in the temporal evolution of the amplitude of the dominant mode of low-frequency oscillations (A_{f}) existing in pressure fluctuations preceding LBO. The presence of DSI indicates the recursive development of blowout. Additionally, we find that A_{f} shows a faster-than-exponential growth and becomes singular when blowout occurs. We then present a model that depicts the evolution of A_{f} based on log-periodic corrections to the power law associated with its growth. Using the model, we find that blowouts can be predicted even several seconds earlier. The predicted time of LBO is in good agreement with the actual time of occurrence of LBO obtained from the experiment.


Arterial mechanical impedance is a sensitive stress response monitor during general anesthesia.
Arterial mechanical impedance is a characteristic of arterial dynamics that is determined by photoplethysmographic amplitude and direct arterial pressure, while mechanical impedance is indicated by stiffness, viscosity, and inertia. We compared the parameters of mechanical impedance and photoplethysmographic amplitude to estimate the magnitude of stress response in patients undergoing general anesthesia by measuring direct arterial pressure. After sedating each patient with propofol, photoplethysmographic amplitude and mechanical impedance were measured as baseline control values, then 3 min after fentanyl administration (2 microg kg(-1)), the parameters were measured again as post-fentanyl values. Thereafter, a direct laryngoscopy procedure was performed and post-laryngoscopy values for the parameters were determined. The magnitudes of response to each event were compared by using the ratio of the measurements from the preceding event. Then, comparisons of the magnitudes were performed after coordinating each response in the same direction. Our results showed that both stiffness and viscosity of mechanical impedance had greater variations than photoplethysmographic amplitude. In conclusion, we propose stiffness and viscosity derived from arterial mechanical impedance as sensitive parameters to monitor stress responses during general anesthesia.


Identification of a novel peptide ligand of human transfrrin receptor 1 for targeted tumor delivery drug.
Human transferrin receptor 1 (TfR1) is expressed on malignant cells at levels several fold higher than those on normal cells and its expression can be correlated with tumor stage or cancer progression. It is a potentially rational target for drug delivery. To identify novel ligands which can recognize the TfR1 specifically, a random phage displayed 12-mer peptide library was screened and two consensus motifs of the peptides which are displayed by the positive phages RXR and RXXXR (x is any amino acid) were yield. The phage displaying peptide SPRPRHTLRLSL (designated as B18) exhibited the highest affinity to TfR1 in phage ELISA and B18 could bind to TfR1 specifically in a dose dependent manner. The flow cytometry assay and immunocellularchemistry assay showed that the B18 could bind to TfR1 positive carcinoma cells with specificity. In addition, the biodistribution assay indicated that B18 could home to TfR1 positive tumor tissue specifically. Our study suggests that the peptide exhibited by B18 is a potentially promising targeting peptide for tumor diagnosis and treatment.


Cyclin-dependent kinase 9 may as a novel target in downregulating the atherosclerosis inflammation (Review).
Inflammation is a key component of atherosclerosis. Genes coding for inflammatory or anti-inflammatory molecules are considered good candidates for estimating the risk of developing atherosclerosis. Cyclin-dependent kinase 9 (CDK9), the kinase of positive transcription elongation factor b (P-TEFb), is crucial in the cell cycle and apoptosis. Previous studies have focused on its inhibition of immune cells for the resolution of inflammation. Considering the effects of inflammation in the pathogenicity of atherosclerosis, decreasing inflammation through the inhibition of CDK9 may be useful for the prognosis of atherosclerosis. The aim of this review was to examine whether inhibition of the CDK9 monocyte may affect the process of inflammation by acting on the cytokine secretion and interacting with endothelial cells (ECs). Thus, CDK9 may be a novel target for the diagnosis and therapy of atherosclerosis.


Cytoplasmic localization of FTS (facteur thymique sérique) in thymic epithelial cells. An immunoelectronmicroscopical study.
This study was concerned with the localization of the facteur thymique sérique (FTS) by immunoelectronmicroscopy in cultured thymic epithelial cells. The FTS antibodies labelled differently sized cytoplasmic vacuoles containing a substance of variable density. This substance occurs occasionally in crystalline structures which reacted strongly with purified FTS antibodies. On the ultrastructural level the FTS-positive cells were demonstrated to fix specifically keratin antibodies and to contain tonofilaments. Some of these cells originated from the thymic medulla proved by the presence of microvilli-forming cytoplasmic vacuoles. The existence of FTS-positive crystalline inclusions confirmed the hypothesis of a storage process in the cytoplasm of thymic epithelial cells in vitro or in pathological conditions.


Environmental assessment of trace element bioaccumulation in sipunculan from seagrass and wetland sediments.
This study is the first measurement of trace elements in sipunculan and their surrounding sediments. The bioaccumulation characteristics of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), and zinc (Zn) were analyzed and compared in two sipunculan species, Sipuncula nudus and Siphonosoma vastum, which were collected from seagrass beds and wetlands in Taiwan. The sipunculan and sediment samples were analyzed using an inductively coupled plasma mass spectrometer. Both sipunculan in the wetlands and seagrass beds had a high Cu bioaccumulation mechanism. Multivariate analysis, principle component analysis, and partial least squares for discriminant analysis of trace element levels and bioaccumulation factors were used to distinguish the element distributions that corresponded to the two habitats (seagrass beds and wetlands). Different levels of certain trace elements in these two sipunculan species may result not only from the environmental factors of various habitats but also from the accumulation characteristics of various species. The As, Cd, Cr, Cu, Hg, and Zn concentrations were markedly lower in sipunculan than in other invertebrates from the adjacent polluted regions. The public health issues regarding the consumption of sipunculan are also discussed.


Induction of immunoglobulin transcription factor 2 and resistance to MEK inhibitor in melanoma cells.
Primary or acquired resistance to MEK inhibitors has been a barrier to successful treatment with MEK inhibitors in many tumors. In this study, we analyzed genome-wide gene expression profiling data from 6 sensitive and 6 resistant cell lines to identify candidate genes whose expression changes are associated with responses to a MEK inhibitor, selumetinib (AZD6244). Of 62 identified differentially expressed genes, we selected Immunoglobulin Transcription Factor 2, also known as transcription factor 4 as a potential drug resistance marker for further analysis. This was because the ITF-2 expression increase in resistant cell lines was relatively high and a previous study has suggested that ITF-2 functions as an oncogene in human colon cancers. We also established an AZD6244 resistant cell line (M14/AZD-3) from an AZD6244 sensitive M14 cell line. The expression of the ITF-2 was elevated both in primary AZD6244 resistant cell line, LOX-IMVI and acquired resistant cell line, M14/AZD-3. Targeted silencing of ITF-2 by siRNA significantly enhanced susceptibility to AZD6244 in resistant cells. Wnt/β-catenin pathway was activated through direct interaction of p-ERK and GSK3β. Our results suggest that up-regulation of the ITF-2 gene expression is associated with cellular resistance to MEK inhibitors, and activation of Wnt signaling pathway through interaction of p-ERK and GSK3β seems to be a mechanism for increase of ITF-2.


Tetanus toxoid IgE may be useful in predicting allergy during childhood.
Hypersensitivity reactions after immunization with tetanus toxoid are occasionally observed in atopic and non-atopic individuals. High IgE levels in infancy may predict subsequent allergy. The aims of this study were: i) to evaluate the role of specific IgE to tetanus toxoid in children in response to tetanus immunization and the possible factors associated with specific IgE levels, and ii) to investigate the correlation between specific IgE levels to tetanus toxoid and the late development of allergy (up to 12 years). Initially, 278 healthy infants (152 males and 126 females, aged 12 months) living in an urban city were screened for serum total IgE and specific IgE to tetanus toxoid, after having obtained informed consent from parents. After 12 years, 151 children could be evaluated. Total IgE summed with tetanus specific IgE were significantly associated with allergy at 12 years. In conclusion, this study demonstrates that serum total IgE and tetanus specific IgE may be predictive of subsequent allergy onset.


Screening a strain of Aspergillus niger and optimization of fermentation conditions for degradation of aflatoxin B₁.
Aflatoxin B₁, a type of highly toxic mycotoxin produced by some species belonging to the Aspergillus genus, such as Aspergillus flavus and Aspergillus parasiticus, is widely distributed in feed matrices. Here, coumarin was used as the sole carbon source to screen microorganism strains that were isolated from types of feed ingredients. Only one isolate (ND-1) was able to degrade aflatoxin B₁ after screening. ND-1 isolate, identified as a strain of Aspergillus niger using phylogenetic analysis on the basis of 18S rDNA, could remove 26.3% of aflatoxin B₁ after 48 h of fermentation in nutrient broth (NB). Optimization of fermentation conditions for aflatoxin B₁ degradation by selected Aspergillus niger was also performed. These results showed that 58.2% of aflatoxin B₁ was degraded after 24 h of culture under the optimal fermentation conditions. The aflatoxin B₁ degradation activity of Aspergillus niger supernatant was significantly stronger than cells and cell extracts. Furthermore, effects of temperature, heat treatment, pH, and metal ions on aflatoxin B₁ degradation by the supernatant were examined. Results indicated that aflatoxin B₁ degradation of Aspergillus niger is enzymatic and this process occurs in the extracellular environment.


Fenofibrate inhibits intestinal Cl- secretion by blocking basolateral KCNQ1 K+ channels.
Fibrates are peroxisome proliferator-activated receptor-alpha (PPARalpha) ligands in widespread clinical use to lower plasma triglyceride levels. We investigated the effect of fenofibrate and clofibrate on ion transport in mouse intestine and in human T84 colonic adenocarcinoma cells through the use of short-circuit current (I(sc)) and ion flux analysis. In mice, oral administration of fenofibrate produced a persistent inhibition of cAMP-stimulated electrogenic Cl(-) secretion by isolated jejunum and colon without affecting electroneutral fluxes of (22)Na(+) or (86)Rb(+) (K(+)) across unstimulated colonic mucosa. When applied acutely to isolated mouse intestinal mucosa, 100 microM fenofibrate inhibited cAMP-stimulated I(sc) within 5 min. In T84 cells, fenofibrate rapidly inhibited approximately 80% the Cl(-) secretory responses to forskolin (cAMP) and to heat stable enterotoxin STa (cGMP) without affecting the response to carbachol (Ca(2+)). Both fenofibrate and clofibrate inhibited cAMP-stimulated I(sc) with an IC(50) approximately 1 muM, whereas other PPARalpha activators (gemfibrozil and Wy-14,643) were without effect. Membrane permeabilization experiments on T84 cells indicated that fenofibrate inhibits basolateral cAMP-stimulated K(+) channels (putatively KCNQ1/KCNE3) without affecting Ca(2+)-stimulated K(+) channel activity, whereas clofibrate inhibits both K(+) pathways. Fenofibrate had no effect on apical cAMP-stimulated Cl(-) channel activity. Patch-clamp analysis of HEK-293T cells confirmed that 100 microM fenofibrate rapidly inhibits K(+) currents associated with ectopic expression of human KCNQ1 with or without the KCNE3 beta-subunit. We conclude that fenofibrate inhibits intestinal cAMP-stimulated Cl(-) secretion through a nongenomic mechanism that involves a selective inhibition of basolateral KCNQ1/KCNE3 channel complexes. Our findings raise the prospect of fenofibrate as a safe and effective antidiarrheal agent.


Effects of palmitoyl carnitine and structural analogs on arterial blood pressure in the rat. A comparison with platelet-activating factor.
Palmitoyl carnitine and lysophosphatidylcholine have been implicated in the generation of cardiac arrhythmias in the ischemic myocardium. These amphiphilic compounds are structurally similar to platelet-activating factor (PAF). The present study compared the hypotensive effect of these compounds to PAF in the anesthetized rat. Palmitoyl carnitine was about 1000 times less potent than PAF in lowering the blood pressure. Lysophosphatidylcholine and other structurally related compounds, in dosages similar to that of palmitoyl carnitine, had no significant hypotensive action. CV 3988, a PAF antagonist, blocked the hypotensive action of PAF but had no effect on the hypotensive action of palmitoyl carnitine. This suggested the effect of palmitoyl carnitine was not associated with the same site or mechanism as PAF. The results also ruled out the involvement of prostaglandin formation and of the sympathetic nervous system since indomethacin, phenoxybenzamine and propranolol did not affect the hypotensive action of palmitoyl carnitine. In addition, it is unlikely that palmitoyl carnitine exerted its effect by a direct membrane-perturbing action because lysophosphatidylcholine, which possesses similar amphiphilic properties, does not share the same hypotensive effect.


Optimal Diagnostic Yield Achieved With On-site Pathology Evaluation of Fine-Needle Aspiration-Assisted Core Biopsies for Pediatric Osseous Lesions: A Single-Center Experience.
- Image-guided, fine-needle aspiration-assisted core needle biopsy with an on-site evaluation by a pathologist (FNACBP) of osseous lesions is not a common practice in pediatric institutions. - To evaluate the diagnostic adequacy and accuracy of FNACBP for pediatric osseous lesions and to compare the adequacy with procedures that do not use fine-needle aspiration. - Six-year, retrospective review of 144 consecutive children biopsied for osseous lesions with and without fine-needle aspiration assistance. - Pathologic diagnosis was achieved in 79% (57 of 72) of the core biopsies without an on-site evaluation, 78% (32 of 41) of the open biopsies (9 with intraoperative consultation), and 97% (30 of 31) of the FNACBPs as the initial diagnostic procedure. Three FNACBP cases were preceded by nondiagnostic open biopsies. Among 34 lesions sampled by FNACBP, 33 (97%) succeeded with diagnostic tissue, with most (30 of 33; 91%) being neoplasms, including 16 malignant (48%), 13 benign (39%), and 1 indeterminate (3%) lesions. The most-common diagnoses were osteosarcoma (9 of 33; 27%) and Langerhans cell histiocytosis (7 of 33; 21%). In cases with follow-up information available, 93% (28 of 30) of the FNACBP-rendered diagnoses were clinically useful, allowing initiation of appropriate therapy. The FNACBP procedure had 100% specificity, sensitivity, and positive predictive value for all 14 malignant lesions, with the sensitivity being 88% in benign lesions. Most FNACBP procedures (32 of 34; 94%) yielded adequate material for ancillary testing. A gradual upward trend was observed for the choice of FNACBP as an initial diagnostic procedure for osseous lesions. - The FNACBP procedure yields sufficient material for diagnosis and ancillary studies in pediatric, osseous lesions and may be considered an initial-diagnostic procedure of choice.


Ovarian follicular dynamics during the estrous cycle in heifers monitored by real-time ultrasonography.
It is not clear whether the turnover of ovarian follicles during the estrous cycle in cattle is continuous and independent of the phase of the cycle, or whether waves of follicular growth occur at specific times of the cycle. To clarify this controversy, the pattern of growth and regression of ovarian follicles was characterized during a complete estrous cycle in ten heifers by daily ultrasonographic examinations. Follicles greater than or equal to 5 mm were measured and their relative locations within the ovary were determined in order to follow the sequential development of each individual follicle. Results indicated the presence of either two (n = 2 heifers), three (n = 7), or four (n = 1) waves of follicular growth per cycle. Each wave was characterized by the development of one large (dominant) follicle and a variable number of smaller (non-dominant) follicles. In the most common pattern observed (three waves/cycle), the first, second, and third waves started on Days 1.9 +/- 0.3, 9.4 +/- 0.5, and 16.1 +/- 0.7 (X +/- SEM), respectively. The dominant follicle in the third wave was the ovulatory follicle. The maximal size and the growth rate of the dominant follicle in the second wave were significantly lower than in the other waves, but no significant difference was observed between the first and third waves. For the two heifers that had two follicular waves/cycle, the waves started on Days 2 and 11, whereas in the remaining heifer (four waves/cycle), the waves began on Days 2, 8, 14, and 17, respectively. At 0, 1, 2, 3, and 4 days before estrus, the ovulatory follicle was the largest follicle in the ovaries in 100%, 95%, 74%, 35%, and 25% of follicular phases monitored, respectively. The relative size of the preovulatory follicle at the completion of luteolysis (progesterone less than 1 ng/ml) was negatively correlated (r = -0.90; p less than 0.0001) with the interval of time between the end of luteolysis and the luteinizing hormone surge, suggesting that the length of proestrus is determined by the size of the pre-ovulatory follicle at the beginning of proestrus. In conclusion, this study shows that the development of ovarian follicles greater than or equal to 5 mm in heifers occurs in waves and that the most common pattern is three waves per estrous cycle.


Prospects of bacteriophage collections in disinfectant applications.
The search and development of disinfectants is promising worldwide. However, there are currently no international regulations governing the testing and registration of germicidal agents. Moreover, the number of safety requirements for disinfectants for human, animal, and environmental health has increased. This research aimed to evaluate the prospects of using a collection of bacteriophages for disinfectant purposes. The objects of research were bacteriophages isolated from a total of 129 environmental samples obtained from seven sources in and around livestock buildings: (1) Feed residues from feeders and automatic drinkers; (2) washouts from floors, walls, and posts; (3) soil from underneath floors; (4) bedding; (5) sewage; (6) ponds; and (7) soil from paddocks. The corresponding strains were used as indicator test cultures for bacteriophages. The authors employed the following methods to work with bacteriophages: (a) Bacteriophage isolation methods, (b) the Appelman method (i.e., serial dilutions), (c) the Grazia method (i.e., agar layers), (d) phage titration on solid media, and (e) the bacterial phagotyping method. The results of the analysis on the bacteria of the Enterobacteriaceae family isolated 11 bacteriophages; one bacteriophage is specific to Pseudomonas aeruginosa, and another one is specific to Brucella abortus. The results also indicate that all bacteriophage strains of the Enterobacteriaceae family demonstrate lysis at a pH of 7.0. In addition, this polyphage lyses all strains of sensitive bacterial cultures. The optimum temperature for the cultivation of bacteriophages is 35°C. While using electron microscopy to study the consortium of bacteriophages, clearly distinguishable virions of bacteriophages were found in the microscope field of view. The main parameters for the production of polyphages include the ratio of the bacteriophage and its corresponding bacteriophage-sensitive culture, the pH of the cultivation medium, and the cultivation time of the bacteriophage system as well as the sensitive bacterium. With regard to the aforementioned parameters, the results indicate that the average value for all bacteriophages is 1:2, and the average cultivation medium pH is 7.0 for all bacteriophages. The average cultivation time for all bacteriophages is 18-24 h.


Liver Transplantation Modern techniques in donor and recipient operations.
Pacific Transplant Institute, California Pacific Medical Center, San Francisco Orthotopic hepatic transplantation provides hope for patients with irreversible liver disease, and the operation is becoming more accepted by the medical community and the public in general. Still, the operation is difficult and the postoperative and long-term management can be rather complex. Unlike pancreas, kidney and heart transplantation, liver transplantation lacks a back-up system, such as Insulin, dialysis or a ventricular support device, if graft failure occurs. Therefore, the Slightest error in the management of the patient after hepatic transplantation may prove fatal. Complications during the post-operative period often originate from the time of the procurement and/or transplantation operations. Thus, good techniques are crucial for a satisfactory outcome.


Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex.
Nuclear pore complexes (NPCs) are multiprotein channels connecting the nucleus with the cytoplasm. NPCs have been shown to have tissue-specific composition, suggesting that their function can be specialized. However, the physiological roles of NPC composition changes and their impacts on cellular processes remain unclear. Here we show that the addition of the Nup210 nucleoporin to NPCs during myoblast differentiation results in assembly of an Mef2C transcriptional complex required for efficient expression of muscle structural genes and microRNAs. We show that this NPC-localized complex is essential for muscle growth, myofiber maturation, and muscle cell survival and that alterations in its activity result in muscle degeneration. Our findings suggest that NPCs regulate the activity of functional gene groups by acting as scaffolds that promote the local assembly of tissue-specific transcription complexes and show how nuclear pore composition changes can be exploited to regulate gene expression at the nuclear periphery.


Joint alignment of multispectral images via semidefinite programming.
In this paper, we introduce a novel feature-point-matching based framework for achieving an optimized joint-alignment of sequential images from multispectral imaging (MSI). It solves a low-rank and semidefinite matrix that stores all pairwise-image feature-mappings by minimizing the total amount of point-to-point matching cost via a convex optimization of a semidefinite programming formulation. This unique strategy takes a complete consideration of the information aggregated by all point-matching costs and enables the entire set of pairwise-image feature-mappings to be solved simultaneously and near-optimally. Our framework is capable of running in an automatic or interactive fashion, offering an effective tool for eliminating spatial misalignments introduced into sequential MSI images during the imaging process. Our experimental results obtained from a database of 28 sequences of MSI images of human eye demonstrate the superior performances of our approach to the state-of-the-art techniques. Our framework is potentially invaluable in a large variety of practical applications of MSI images.


Quantification and comparison of psychiatric distress in African patients with albinism and vitiligo: a 5-year prospective study.
Vitiligo and albinism are two disorders of pigmentation that make the affected African highly visible and strikingly different from their peers. Both pose considerable management challenges, attract significant stigma and profound impairment of quality of life. To determine and compare psychiatric distress in vitiligo and albinism using the Hospital Anxiety and Depression Scale (HADS). Participants were 87 albinos and 102 vitiligo adult patients seen at an urban tertiary hospital in Nigeria between 2004 and 2009. Prevalence of psycho morbidity was 59% (60/102) in vitiligo compared with 26% (23/87) in the albinos. The mean anxiety score was estimated to be 2.55 points lower for albino patients (95% CI: 1.47 to 3.64), and the mean depression score 2.76 points lower (95% CI: 1.84 to 3.68), after adjustment for age, sex and marital status. However, significant differences were not observed when comparing the vitiligo patients with the subset of albino patients with skin cancer. Older patients had significantly higher anxiety and depression scores. Females had significantly higher anxiety scores (but not depression scores) compared to males. Genital involvement in vitiligo was significantly associated with anxiety but not depression. We found that the African with vitiligo suffers significantly higher psychiatric distress than the African albino on average. Clinical evaluation of these patients would be incomplete without assessment of their psycho morbidity. There is need for increased focus on cancer prevention strategies in the African albino.


Calycosin attenuates renal ischemia/reperfusion injury by suppressing NF-κB mediated inflammation via PPARγ/EGR1 pathway.
Renal ischemia reperfusion injury (IRI) is a leading and common cause of acute kidney injury (AKI), and inflammation is a critical factor in ischemic AKI progression. Calycosin (CAL), a major active component of Radix astragali, has been reported to have anti-inflammatory effect in multiple organs. However, whether CAL can alleviate renal IRI and its mechanism remain uncertain. In the present study, a renal IRI model is established by bilateral renal pedicles occlusion for 35 min in male C57BL/6 mice, and the effect of CAL on renal IRI is measured by serum creatinine and pathohistological assay. Hypoxia/reoxygenation (H/R) stimulated human renal tubular epithelial cells HK-2 were applied to explore the regulatory mechanisms of CAL. Luciferase reporter assay and molecular docking were applied to identify the CAL's target protein and pathway. In the mice with renal IRI, CAL dose dependently alleviated the renal injury and decreased nuclear factor kappa B (NF-κB) mediated inflammatory response. Bioinformatics analysis and experiments showed that early growth response 1 (EGR1) increased in mice with renal IRI and promoted NF-κB mediated inflammatory processes, and CAL dose-dependably reduced EGR1. Through JASPAR database and luciferase reporter assay, peroxisome proliferator-activated receptor γ (PPARγ) was predicted to be a transcription factor of EGR1 and repressed the expression of EGR1 in renal tubular epithelial cells. CAL could increase PPARγ in a dose dependent manner in mice with renal IRI and molecular docking predicted CAL could bind stably to PPARγ. In HK-2 cells after H/R, CAL increased PPARγ, decreased EGR1, and inhibited NF-κB mediated inflammatory response. However, PPARγ knockdown by siRNA transfection abrogated the anti-inflammation therapeutic effect of CAL. CAL produced a protective effect on renal IRI by attenuating NF-κB mediated inflammatory response via PPARγ/EGR1 pathway.


DNA methylation is not involved in dietary restriction induced lifespan extension in adult Drosophila.
Dietary restriction (DR) is widely regarded as a viable intervention to extend lifespan and healthspan in diverse organisms. The precise molecular regulatory mechanisms are largely unknown. Epigenetic modifications are not stable upon DR and also keep changing with age. Here, we employed whole genome bisulfite sequencing to determine the DNA methylation changes upon DR in adult Drosophila. Our results indicate that although a low level of DNA methylation exists in the adult Drosophila genome, there is no significant difference in DNA methylation levels upon DR when compared to unrestricted flies. This suggests that other epigenetic components such as histone modifications might be altered by DR.


Overexpression of redox-active protein thioredoxin-1 prevents development of chronic pancreatitis in mice.
Chronic pancreatitis (CP) is considered to result from repetitive pancreatic injury, and sustained production of various proinflammatory cytokines and chemokines are closely involved in its pathogenesis. Monocyte chemoattractant protein 1 (MCP-1), a member of the CC chemokine family, is believed to contribute to the progression of CP through monocyte/macrophage recruitment. This study aimed to clarify the protective role of thioredoxin-1 (TRX-1), a redox-regulating protein with antioxidative activity, in MCP-1 production and pancreatic fibrosis using a CP model in transgenic mice overexpressing TRX-1 (TRX-1-TG mice) and wildtype C57BL/6 mice. Experimental CP was induced by repeated administration of cerulein and lipopolysaccharide for 6 weeks. In TRX-1-TG mice, pancreatic atrophy was ameliorated, and histologically detectable inflammatory cell infiltration, glandular atrophy, and pseudotubular complex formation were suppressed. Overexpression of TRX-1 also attenuated pancreatic fibrosis and suppressed the activation of pancreatic stellate cells. Serum levels of MCP-1 and pancreatic expression of transforming growth factor-beta, platelet-derived growth factor, and MCP-1 were reduced in TRX-1-TG mice compared with levels in wild-type mice. Overexpression of TRX-1 also reduced H(2)O(2)-induced MCP-1 production in isolated pancreatic acinar cells. These results indicate that TRX-1 can potentially attenuate pancreatic fibrosis via the suppression of oxidative stress and MCP-1-mediated chronic inflammation.


[Immunohistochemical findings in intrathoracic tumors. II. Demonstration of alpha 1-antitrypsin in tumor tissue].
Immunohistological investigations for demonstration of alpha 1-antitrypsin were undertaken in different intrathoracic tumors. 60% of them showed deposits of alpha 1-antitrypsin in tumor tissue. Among different histological types, bronchial carcinomas showed the highest percentage of positive findings (= 75%). Negative findings were observed in carcinoid tumors and different neurogenic tumors.


Quality of Life and Related Factors in β-Thalassemia Patients.
The β-thalassemias are a group of genetic disorders defined by decreased levels of functional hemoglobin (Hb). In light of pivotal improvements in patient survival, the load of consistent treatment harms patients' quality of life (QOL). This study aimed to determine the QOL in patients with β-thalassemia (β-thal) in Iran and identify associated factors. This cross-sectional study was conducted among 1240 patients with β-thal. Data for this study were obtained from the General, the TranQol (Transfusion-dependent QoL) Standard, and the Multidimensional Scale of Perceived Social Support (MSPSS) questionnaires. The univariate and multivariable linear regression was used in STATA version 14 to identify factors related to QOL. Overall, the QOL score was 103 ± 21.96, and adults had a higher score than children under 15 years old. Emotional health had the highest score (39.96 ± 11.54), and sexual activity in adults (1.87 ± 2.08) and activities related to education in children (10.43 ± 7.46) had the lowest. The multivariable linear regression analysis showed that the age, gender, age of blood transfusion initiation, Hb level, number of underlying diseases, and social support level by family and community significantly impact QOL. In exchange for an increase in comorbidities, patients' QOL decreased by 86.0% [odds ratio (OR) = 0.14, 95% confidence interval (95% CI): 0.04-0.45]. Many factors affecting the QOL can be controlled, so social support, increased Hb levels, regular and timely blood transfusions, and treatment can improve the thalassemia patients' QOL.


Bubble Rupture and Bursting Velocity of Complex Fluids.
We analyzed bubble rupture and hole opening dynamics in a non-Newtonian fluid by investigating the retraction process of thin films after inflation at different blowing rates. The experiments were modeled through a dimensional analysis, with the aim of establishing a general approach on the bubble rupture dynamics and discerning the role of viscous, elastic, surface, and inertial forces on the opening velocity, according to the nature of the specific fluid. A new mathematical model, which includes all possible contributions to the hole opening dynamics, was proposed, to the best of our knowledge for the first time. The experimental evidence on the opening velocity as a function of the inflation rate was found to be in good agreement with the prediction of the model. The sensitivity of our modeling was tested by comparing our results with the existing models of retracting velocity.


Extent of social inequalities in disability in the elderly: results from a population-based study of British men.
Little is known about social inequalities in disability in the elderly. We examined the extent and determinants of socioeconomic inequalities in disability and functional limitation in elderly men in Britain. Disability was ascertained as problems with activities of daily living (ADLs) and instrumental ADL in a socioeconomically representative sample of 3,981 men from 24 British towns who were between 63 to 82 years of age in 2003. We also examined functional limitation. Measures of socioeconomic position were social class, age at leaving full-time education, and car and house ownership. Men in lower social classes had greater risks of both ADL and instrumental ADL disability and functional limitation compared with higher social classes; odds ratios (95% CI) for social class V compared with I were 3.13 (1.64-5.97), 2.87 (1.49-5.51), and 2.65 (1.31-5.35), respectively. Behavioral risk factors (smoking, body mass index, physical activity) and particularly co-morbidity attenuated these differences; together, they reduced relative risks to 1.11 (0.49-2.51), 1.01 (0.45-2.25), and 1.05 (0.46-2.42). Age at leaving full-time education had no relation to functional limitations after taking social class into account. Men who were not house or car owners had greater odds of functional limitation and ADL disability compared with house or car owners, independent of behavioural risk factors, comorbidities and social class. Strong socioeconomic inequalities in disability exist in the elderly, which were considerably explained by behavioral factors and comorbidity. Policy efforts are needed to reduce the social disparities in disability in the elderly.


Ellagitannins of Davidia involucrata. I. Structure of Davicratinic Acid A and Effects of Davidia Tannins on Drug-Resistant Bacteria and Human Oral Squamous Cell Carcinomas.
We isolated a new ellagitannin, davicratinic acid A (5), together with four known ellagitannins, davidiin (1), granatin A (2), pedunculagin (3), and 3-O-galloylgranatin A (4), from an aqueous acetone extract of dried Davidia involucrata leaves. The known ellagitannins were identified based on spectroscopic data. The structure of davicratinic acid A (5), a monomeric ellagitannin possessing a unique, skew-boat glucopyranose core, was established based on spectroscopic data. Additionally, we examined the effects of several tannins with good yields from this plant on drug-resistant bacteria and human oral squamous cell carcinomas, and found that davidiin (1) exhibited the most potent antibacterial and antitumor properties among the tannins examined.


Estimates of Soil Ingestion in a Population of Chinese Children.
China's soil pollution poses serious health risks. However, data regarding the soil ingestion rate (SIR) of the Chinese population, which is critical to assessing associated health risks, are lacking. We estimated soil ingestion of 177 Chinese children from Guangdong, Hubei, and Gansu Provinces. We conducted this investigation by employing a tracer mass-balance method. We collected a duplicate of all food consumed and all feces and urine excreted on 1 d (n=153) and over 3 consecutive d (n=24), as well as soil samples from play areas and drinking-water samples. We analyzed concentrations of the tracer elements Al, Ba, Ce, Mn, Sc, Ti, V, and Y in these samples using ICP-AES and ICP-MS and estimated the SIR for each subject. The estimated SIR data based on each tracer element were characterized by a skewed distribution, as well as higher inter-tracer and inter-subject variation, with several outliers. After removing the outliers, daily SIR median (range) values in milligrams per day were Al, 27.8 (−42.0 to 257.3); Ba, 36.5 (−230.3 to 412.7); Ce, 35.3 (−21.2 to 225.8); Mn, 146.6 (−1259.4 to 1827.7); Sc, 54.8 (−4.5 to 292.0); Ti, 36.7 (−233.7 to 687.0); V, 92.1 (10.4 to 308.0); and Y, 59.1 (−18.4 to 283.0). Daily SIR median/95th percentile (range) values based on the best tracer method (BTM) were 51.7/216.6 (−9.5 to 297.6) mg/d. Based on the BTM, recommended SIR values for the general population of Chinese children (2.5 to 12 years old) are 52 mg/d for the central tendency and 217 mg/d for the upper percentile. We did not differentiate between outside soil and indoor dust. Considering the lower concentration of tracer elements in indoor dust than outside soil, actual soil and dust ingestion rates could be higher. https://doi.org/10.1289/EHP930.


Effects of Cinnamoyloxy-mammeisin from Geopropolis on Osteoclast Differentiation and Porphyromonas gingivalis-Induced Periodontitis.
Bone-loss-related diseases such as rheumatoid arthritis, osteomyelitis, osteoporosis, and periodontitis are associated with high rates of morbidity worldwide. These disorders are characterized by an imbalance between the formation and activity of osteoblasts and osteoclasts, leading to bone loss. In this context, we evaluated the effect of cinnamoyloxy-mammeisin (CNM), an anti-inflammatory coumarin found in Melipona scutellaris geopropolis, on key targets related to bone remodeling. In the present study we investigated the in vitro effects of CNM on osteoclast differentiation and M-CSF+RANKL-induced osteoclastogenic marker expression. Additionally, the interference of CNM treatment on osteoclast activity was evaluated by zymography and resorption area. Finally, we assessed the capacity of the compound to mitigate alveolar bone loss in vivo in experimental murine periodontitis induced by Porphyromonas gingivalis. We observed that treatment with CNM impaired osteoclast differentiation, as evidenced by a reduced number of tartrate-resistant acid-phosphatase-positive multinucleated cells (TRAP+) as well as the expression of osteoclastogenic markers upon M-CSF+RANKL-induced stimulation. Similarly, we observed reduced gelatinolytic and resorption capacity in M-CSF+RANKL-induced cells in vitro. Lastly, CNM attenuated alveolar bone loss in an experimental murine periodontitis model. These findings indicate that CNM may be considered a promising treatment for bone loss diseases.


Levels of benzo[a]pyrene (BaP) in "mozzarella di bufala campana" cheese smoked according to different procedures.
The content of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon, was determined by HPLC-FL in "mozzarella di bufala campana" cheese, a stretched cooked cheese, either experimentally smoked according to traditional procedures, using straw, cardboard, and wood shavings or aromatized with smoke flavoring. The BaP residues, researched also in cheese samples sold at retail, were detected in the rind, in the core, and in the slice (outer and inner parts). In the cheeses experimentally smoked with straw and cardboard the BaP levels, ranging from 0.38 to 2.12 microg kg(-1) and from 0.46 to 2.40 microg kg(-1), respectively, were statistically higher than those of the cheeses smoked with wood shavings and aromatized with liquid smoke (from 0.19 to 0.80 microg kg(-1) and from 0.18 to 0.50 microg kg(-1), respectively). However the cheeses treated with liquid smoke flavor showed a BaP content exceeding the level allowed by the European Union. In the samples sold at retail, smoked with straw, values were lower than those obtained from samples smoked experimentally with the same combustible. This is probably due to different smoking technologies among the several provinces of the Protected Designation of Origin (PDO) area. PDO is a term used to characterize foodstuffs produced and prepared in a given geographical region by the means of a recognized process. A standardization of the traditional smoking procedures and an improvement of liquid smoke purification treatments are recommended for mozzarella cheese.


Clinical Application of Matrix-Assisted Laser-Resolved Ionization Time-Of-Flight Mass Spectrometry for Rapid Detection of Blood-Borne Pathogens.
To evaluate the performance of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in the identification of clinical pathogenic microorganisms. Blood culture-positive specimens were collected from inpatients in our hospital from March to December 2022 and identified using VITEK 2XL (biochemical), VITEK MS (colony), VITEK MS (bacterial membrane) and VITEK MS (separating gel) methods, respectively, to compare the compliance rate and identification values of the four methods. A total of 280 strains were included in the analysis, including 155 (55.36%) Gram-negative and 125 (44.64%) Gram-positive strains. 279 (99.64%) of the 280 strains were identified by VITEK 2XL (biochemical), including 154 (99.35%) Gram-negative and 125 (100%) Gram-positive strains. VITEK MS (colony) identified 278 (99.29%) strains, including 153 (98.71%) Gram-negative and 125 (100%) Gram-positive. 261 (93.21%) strains were identified in VITEK MS (bacterial membrane), including 148 (95.48%) Gram-negative and 113 (90.40%) Gram-positive strains. VITEK MS (separating gel) identified 232 (82.86%) strains, including 136 (87.74%) Gram-negative and 96 (76.80%) Gram-positive strains. MALDI-TOF MS findings are highly consistent with traditional culture identification methods in terms of identification accuracy, and the VITEK MS (bacterial membrane) and VITEK MS (separating gel) identification methods significantly reduce the turnaround time for identification in the laboratory.


Variation of self-imaging length in multimode waveguides beyond the paraxial approximation.
We demonstrate the precise variation of self-imaging distance with width of a Gaussian input, centrally fed into a symmetric dielectric slab waveguide of width ∼20λ0. The width of the Gaussian is varied from the paraxial to completely nonparaxial domain. Unlike the paraxial case, the self-imaging distance is found to depend on the beam width and change with the number of excited modes in the waveguide. These features should be useful in designing devices that exploit self-imaging for improved efficiency, especially in nanophotonic circuits.


Euthanasia: Global Scenario and Its Status in India.
The legal and moral validity of euthanasia has been questioned in different situations. In India, the status of euthanasia is no different. It was the Aruna Ramachandra Shanbaug case that got significant public attention and led the Supreme Court of India to initiate detailed deliberations on the long ignored issue of euthanasia. Realising the importance of this issue and considering the ongoing and pending litigation before the different courts in this regard, the Ministry of Health and Family Welfare, Government of India issued a public notice on May 2016 that invited opinions from the citizens and the concerned stakeholders on the proposed draft bill entitled The Medical Treatment of Terminally Ill Patients (Protection of Patients and Medical Practitioners) Bill. Globally, only a few countries have legislation with discreet and unambiguous guidelines on euthanasia. The ongoing developments have raised a hope of India getting a discreet law on euthanasia in the future.


Effect of lip closure on early maxillary growth in patients with cleft lip and palate.
Debate continues about the cause of midfacial growth disturbance in patients with facial clefts. To evaluate the functional effect of surgical closure of the lip before palatal closure according to the technique by Delaire on early maxillary growth in patients with complete unilateral cleft lip and palate. Twenty-two patients with unilateral cleft lip and palate were studied using plaster casts obtained at the time of cheilorhinoplasty and 6 months later before palatal closure. The interrupted lateral muscles were anatomically repositioned using the surgical technique by Delaire. No patients had received preoperative orthodontic treatment or a passive palatal plate. Cast analyses were performed using a digital caliper. Landmark positioning was performed 3 times by 2 different examiners to define intraobserver and interobserver differences. The final maxilla dimensions were recorded as the distances between the mean landmark positions. Using the t test, dimensions obtained before palatal closure were compared with dimensions obtained before lip closure. The method allowed good reproducibility. Functional closure of the lip significantly narrowed the transverse anterior cleft areas by -2.36 mm (P < .05). Sagittal variables were increased by 1.68 mm on the nonaffected side and by 1.48 mm on the affected side (P < .05 for both). Functional closure according to the technique by Delaire narrows the transverse dimensions of the maxilla, while simultaneously preserving initial sagittal growth. 4.


Towards a more physiological representation of vegetation phosphorus processes in land surface models.
Contents Summary 1223 I. Introduction 1223 II. Photosynthesis and respiration 1224 III. Biomass growth 1224 IV. Carbon allocation 1225 V. Plant internal P redistribution 1226 VI. Plant P uptake 1227 VII. Conclusion 1227 Acknowledgements 1228 References 1228 SUMMARY: Our ability to understand the effect of nutrient limitation on ecosystem productivity is key to the prediction of future terrestrial carbon storage. Significant progress has been made to include phosphorus (P) cycle processes in land surface models (LSMs), but these efforts are focused on the soil component of the P cycle. Incorporating the soil component is important to estimate plant-available P, but does not necessarily address the vegetation response to P limitation or plant-soil interactions. A more detailed representation of plant P processes is needed to link nutrient availability and ecosystem productivity. We review physiological and biochemical evidence for vegetation responses to P availability, and recommend ways to move towards a more physiological representation of vegetation P processes in LSMs.


Influence of silymarin and its flavonolignans on H(2)O(2)-induced oxidative stress in human keratinocytes and mouse fibroblasts.
The administration of antioxidants has been shown to enhance repair and healing processes in cutaneous tissue. Silymarin, an extract from Silybum marianum has been reported to be beneficial in the treatment of chemically-induced oxidative stress in mouse. In this study, we investigated the protective effects of silymarin, its flavonolignans silybin and dehydrosilybin and flavonoids quercetin and taxifolin against hydrogen peroxide-induced damage to human keratinocytes and mouse fibroblasts. The results showed that the cytotoxicity of hydrogen peroxide was dose-dependent in both cell lines. Pre-treatment with test compounds decreased oxidative injury. Dehydrosilybin and quercetin were the most powerful protectants. Silymarin was comparable to silybinin, its main component. This correlates with the antioxidant potential of the compounds. Our findings suggest that silymarin, flavonolignans and flavonoids may be useful as agents for improving skin tissue regeneration.


Dengue viruses cleave STING in humans but not in nonhuman primates, their presumed natural reservoir.
Human dengue viruses emerged from primate reservoirs, yet paradoxically dengue does not reach high titers in primate models. This presents a unique opportunity to examine the genetics of spillover versus reservoir hosts. The dengue virus 2 (DENV2) - encoded protease cleaves human STING, reducing type I interferon production and boosting viral titers in humans. We find that both human and sylvatic (reservoir) dengue viruses universally cleave human STING, but not the STING of primates implicated as reservoir species. The special ability of dengue to cleave STING is thus specific to humans and a few closely related ape species. Conversion of residues 78/79 to the human-encoded 'RG' renders all primate (and mouse) STINGs sensitive to viral cleavage. Dengue viruses may have evolved to increase viral titers in the dense and vast human population, while maintaining decreased titers and pathogenicity in the more rare animals that serve as their sustaining reservoir in nature.


Salmonella meningitis: report of three cases in adults and literature review.
Salmonella meningitis is an unusual complication of Salmonella sepsis and occurs almost exclusively in infants and young children. One case of Salmonella meningitis and two cases of cerebrospinal fluid (CSF) pleocytosis in adult patients with Salmonella bacteremia were studied and the literature was reviewed. On a retrospective review of the charts of 100 sequential patients with Salmonella typhi and S. paratyphi-positive blood cultures, we found one patient with fulminant Salmonella meningitis and two others with CSF pleocytosis. All three patients survived. The patient with Salmonella meningitis had significant residual neurologic sequela. Salmonella encephalopathy occurred in six other patients who presented with headache and were confused or drowsy. Cases of meningitis in adults do occur and are associated with a high morbidity and mortality. Newer cephalosporn antibiotics may be the therapy of choice in these infections.


Aura-like features and photophobia in sightless migraine patients.
Migraine is a central nervous system disorder frequently expressed with paroxysmal visual dysfunctions. To test the hypothesis that normal visual input is vital for the migrainous aura and photophobia. We studied the migraine-related visual disturbances in 8 sightless migraineurs identified among 200 visually impaired subjects. The main findings were the visual aura and photophobia disappearance along with blindness development, the oddness of aura - too short, colourful (e.g. blue or fire-like), auditory in nature or different in shape (round forms) - and the lack of photophobia. We propose that the aura duration should be accepted as shorter in visually impaired subjects. The changes in aura phenotype observed in our patients may be the result of both cerebral plasticity induced by the visual impairment and/or the lack of visual input per se. Integrity of visual pathways plays a key role in migraine visual aura and photophobia.


Score for neonatal acute physiology-II and neonatal pain predict corticospinal tract development in premature newborns.
Premature infants are at risk for adverse motor outcomes, including cerebral palsy and developmental coordination disorder. The purpose of this study was to examine the relationship of antenatal, perinatal, and postnatal risk factors for abnormal development of the corticospinal tract, the major voluntary motor pathway, during the neonatal period. In a prospective cohort study, 126 premature neonates (24-32 weeks' gestational age) underwent serial brain imaging near birth and at term-equivalent age. With diffusion tensor tractography, mean diffusivity and fractional anisotropy of the corticospinal tract were measured to reflect microstructural development. Generalized estimating equation models examined associations of risk factors on corticospinal tract development. The perinatal risk factor of greater early illness severity (as measured by the Score for Neonatal Acute Physiology-II [SNAP-II]) was associated with a slower rise in fractional anisotropy of the corticospinal tract (P = 0.02), even after correcting for gestational age at birth and postnatal risk factors (P = 0.009). Consistent with previous findings, neonatal pain adjusted for morphine and postnatal infection were also associated with a slower rise in fractional anisotropy of the corticospinal tract (P = 0.03 and 0.02, respectively). Lessening illness severity in the first hours of life might offer potential to improve motor pathway development in premature newborns.


Sulfonated 1,3-bis-(4-pyrid-yl)propane.
In the title compound, 4-[3-(3-sulfonato-pyridin-1-ium-4-yl)prop-yl]pyridin-1-ium-3-sulfonate, C(13)H(14)N(2)O(6)S(2), the mol-ecule is zwitterionic, with the sulfonic acid proton transfered to the basic pyridine N atom. Also, the structure adopts a butterfly-like conformation with the sulfonate groups on opposite sides of the 'wings'. The dihedral angle between the two pyridinium rings is 83.56 (7)°, and this results in the mol-ecule having a chiral conformation and packing. There is strong inter-molecular hydrogen bonding between the pyridinium H and sulfonate O atoms of adjoining mol-ecules. In addition, there are weaker inter-molecular C-H⋯O inter-actions.


The perceived needs of practicing optometrists in geriatric continuing education.
A survey of American Optometric Association members in the states of Kentucky and Illinois was undertaken to determine the perceived need areas for continuing education in the field of optometric geriatrics and gerontology. The membership was surveyed on which of a 23 possible courses were of the most interest and need. A total of 332 questionnaires were returned and analyzed. The respondents were largely younger practitioners (mean age 41) who had not taken a specific course in geriatrics during optometry school (56 percent). A large majority (79 percent) indicated that they would attend courses with geriatric content at regional and state continuing education. Courses with heavy optometric content were preferred over those with more general gerontology content. The most desired courses were in geriatric pharmacology and ocular disease. Coursework in medical epidemiology and systemic conditions affecting the older adult were the most needed in the area of general gerontology.


Vectorial delivery of newly-synthesized secretory proteins by human tracheal gland cells in culture.
The polarized secretion of newly-synthesized proteins of human tracheal submucosal gland cells was studied. Human tracheal gland cells were cultured on permeable filter supports allowing a separate biochemical analysis of apical and basal secretion. By transmission electron microscopy, confluent filter-grown cells were seen to form a continuous sheet of both multilayer and monolayer epithelial cells. Junctional complexes between adjacent cells were observed. On immunofluorescence microscopy, human tracheal gland cells in cultured exhibited characteristics of epithelial and secretory cells, including cytoplasmic staining for cytokeratin and for two secretory protein markers specific to the glandular serous type cell: lysozyme and antileucoprotease. [35S]methionine metabolic labelling experiments demonstrated that at least 90% of newly-synthesized secretory proteins were recovered in the apical medium. Moreover, lysozyme secretion was strongly polarized since 85% was released into the apical medium. Conversely, antileucoprotease secretion was more bidirectional since nearly 40% of released antileucoprotease was present in the basal medium. The fact that these two secretory proteins are released with differing relative polarity emphasizes that human tracheal gland cells exhibit at least two different exocytotic routing operations.


The effect of UV-A (352 nm) stress on chlorophyll fluorescence, chlorophyll a content, thickness of upper cortex and determinate DNA damage in Physcia semipinnata.
In the present study, Physcia semipinnata samples were exposed to UV-A (352 nm) in 20 J m(-2) for 24 h, 48 h and 72 h to seek the alterations in the PSII photosynthetic quantum yield, thallus anatomy and DNA mutation rate in response to radiation. The Fv/Fm ratio decreased in P. semipinnata following exposure to UV-A for 24h, 48 h and 72 h. The data of the present study reported that Chla degradation occurred by exposition of UV-A for 24 h, 48 h and 72 h. Photobiont size and thickness of upper cortex layer also showed a gradually decrease in P. semipinnata thallus sections during 24 h, 48 h and 72 h. The thickness of the upper cortex layer, exposed to UV-A for 72 h, of P. semipinnata thallus reduced 64%, compared with control. The random amplified polymorphic DNA (RAPD) technique was used to detect DNA damage. The main changes observed in the RAPD profiles resulted in both appearance and disappearance of different bands and variation of their intensity. According to RAPD assay, the genetic distance between the control group and 24h , 48 h and 72 h UV-A exposed, groups was found 56%, 78% and 84%, respectively.


Effect of fluid resuscitation on acute lung injury in a rat model of sepsis.
Sepsis is a systemic infection reaction and intravascular volume therapy plays a crucial role in it's treatment. Acute respiratory distress syndrome (ARDS) occurs in the lungs, the most affected organ. This study aimed to investigate the different effects of fluid therapy on ARDS caused by sepsis. To form a sepsis model, cecal ligation and puncture (CLP) procedure were performed on 44 adult rats. Divided into six groups; normal, CLP group, those treated with 40 ml/kg 0.9 % NaCl, 3 % NaCl (hypertonic saline), Ringer Lactate and Hydroxyethyl starch. After 24 hours treatments, histopathological examination of the lungs were done, and the plasma levels of CRP, TNF-α and IL-6 and paO2 were measured. The scores of all histological parameters of the group treated with hypertonic saline were significantly lower than of the other groups (p < 0.001). Likewise, according to the arterial blood gas results, paO2 was significantly higher (p < 0.01) in the hypertonic saline group compared to the other groups, and paCO2 was significantly lower (p < 0.01). CRP, TNF-α and IL-6 levels of inflammatory markers were also significantly lower in hypertonic saline groups compared to other groups (p < 0.001). Our study shows that treatment with hypertonic saline reduces the progression of ARDS in sepsis (Tab. 3, Fig. 4, Ref. 49).


Preformulation and formulation of newly synthesized QNT3-18 for development of a skin whitening agent.
New molecules having the structure of (E)-2-(4-tert-butylbenzylidene) hydrazinecarbothioamide (QNT3-18) or 4-tert-butylphenylthiourea (QNT3-20) was synthesized and presupposed to inhibit melanogenesis through the inhibition of tyrosinase, which is involved in melanin formation. Therefore, we seek to develop these new molecules as skin whitening agents in topical formulations based on preformulation studies. QNT3-18 or QNT3-20 showed a strong single endothermic peak at 159.34°C with 10.79 μm-sized or at 150.69°C with 9.0 μm-sized aggregated particles, respectively. Both QNT3-18 and QNT3-20 did not show cytotoxicity at effective concentration range (0.4 µM) against keratinocyte cells and QNT3-18 was more retained than QNT3-20 in the skin instead of permeating through the skin. QNT3-18 or QNT3-20 was practically insoluble in water; the aqueous solubility was 3.8 ± 0.37 or 130.6 ± 2.52 μg/mL, respectively. Also, the partition coefficient value (log P) corresponding to the quotient between aqueous and octanol concentration of the molecule was 3.9 or 2.6, respectively. The skin retention amount of QNT3-18 was 1.7-fold higher than that of QNT3-20. When the optimal SLN cream (J3 formulation) containing 4 μM QNT3-18 was applied on the backs of hairless rats for 4 days after UV irradiation for 7 days and the skin color was checked by reflectance spectrophotometer, the rat skin treated with SLN cream with QNT3-18 quickly recovered to normal compared to skin treated with SLN cream without QNT3-18. Taken together, this study suggests that topical formulations such as creams including SLNs with QNT3-18 might be appropriate carriers for skin whitening agents.


Development of a drug risk analysis and assessment system and its application in signal excavation and analysis of 263 cases of fluoroquinolone-induced adverse reactions.
Background: Adverse drug reaction (ADR) signal mining is essential for assessing drug safety. However, the currently available methods for this are rather cumbersome. Objective: We aimed to develop a drug risk analysis and assessment system using Java language and conduct pharmacovigilance data mining for fluoroquinolones at our hospital. Methods: We used ADR data reported by Shandong Provincial Third Hospital between July 2007 and August 2021. The signal detection methods included proportional reporting ratio (PRR), reporting odds ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), Medicines and Healthcare products Regulatory Agency (MHRA). The BCPNN method was used as the reference standard for comparing the remaining three signal detection methods based on sensitivity, specificity, positive predictive value, negative predictive value, and Jorden index. Results: The hospital database contained a total of 2,621 ADR reports, among which 263 were attributed to fluoroquinolones. There were 391 fluoroquinolone-ADR pairs. Using the PRR, ROR, MHRA, and BCPNN method, we detected 13 signals, 13 signals, 10 signals, and 11 weak signals, respectively. After signal detection, levofloxacin and moxifloxacin were shown to induce high risk signals for mental and sleep disorders, with the signal intensity of moxifloxacin being the most significant. Compared with BCPNN, the PRR and ROR methods showed better sensitivity, whereas the MHRA method showed better specificity. Conclusion: We developed a drug risk analysis and assessment system that can help hospitals and other medical institutions to detect and analyse ADR signals in the self-reporting system database, and thus improve drug safety. Further, it indicates that the central nervous system damage caused by fluoroquinolones should be monitored closely, and thus provides a reference for the clinical application of these drugs.


An Egyptian HPAI H5N1 isolate from clade 18.104.22.168 is highly pathogenic in an experimentally infected domestic duck breed (Sudani duck).
The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause major problems in poultry and can, although rarely, cause human infection. Being enzootic in domestic poultry, Egyptian isolates are continuously evolving, and novel clades vary in their pathogenicity in avian hosts. Considering the importance of domestic ducks as natural hosts of HPAI H5N1 viruses and their likelihood of physical contact with other avian hosts and humans, it is of utmost importance to characterize the pathogenicity of newly emerged HPAI strains in the domestic duck. The most recently identified Egyptian clade 184.108.40.206 HPAI H5N1 viruses have been isolated from naturally infected pigeons, turkeys and humans. However, essentially nothing is known about their pathogenicity in domestic ducks. We therefore characterized the pathogenicity of an Egyptian HPAI H5N1 isolate A/chicken/Faquos/amn12/2011 (clade 184.108.40.206) in Sudani duck, a domestic duck breed commonly reared in Egypt. While viral transcription (HA mRNA) was highest in lung, heart and kidney peaking between 40 and 48 hpi, lower levels were detected in brain. Weight loss of infected ducks started at 16 hpi and persisted until 120 hpi. The first severe clinical signs were noted by 32 hpi and peaked in severity at 72 and 96 hpi. Haematological analyses showed a decline in total leucocytes, granulocytes, platelets and granulocyte/lymphocyte ratio, but lymphocytosis. Upon necropsy, lesions were obvious in heart, liver, spleen and pancreas and consisted mainly of necrosis and petechial haemorrhage. Histologically, lungs were the most severely affected organs, whereas brain only showed mild neuronal degeneration and gliosis at 48 hpi despite obvious neurological clinical signs. Taken together, our results provide first evidence that this HPAI H5N1 isolate (clade 18.104.22.168) is highly pathogenic to Sudani ducks and highlight the importance of this breed as potential reservoir and disseminator of HPAI strains from this clade.


Palatal Swelling: Exploring an Elusive Diagnostic Dilemma.
Mucoepidermoid carcinoma is a locally invasive tumor of the major and minor salivary glands. A 29-year-old male patient reported a complaint of slow-growing, painless, non-ulcerated palatal swelling. On clinical evaluation, the swelling appeared benign; hence, the complete excision of the lesion was carried out under general anesthesia, with closure by reconstruction with a partial-thickness flap. Healing was uneventful. The histopathological evaluation revealed low-grade mucoepidermoid carcinoma. This case report aims to highlight the importance of proper clinical and histopathological evaluation to rule out malignancy, as mucoepidermoid carcinoma can have variable presentations and mimic various benign salivary gland lesions, similar to the occurrence in the present case.


Purification and characterization of thermostable α-amylase from germinating Sword bean (Canavalia gladiata (Jacq.) DC.) seeds.
The thermostable α-amylase from germinating sword bean (Canavalia gladiata (Jacq.) DC.) seeds (CgAmy) was successfully purified by a combination of ammonium sulphate fractionation and Epoxy-activated Sepharose 6B affinity chromatography. The purified α-amylase showed 507.8 fold with a specific activity of 750.0 U/mg. SDS-PAGE of the purified enzyme revealed a single protein band of 50.0 kDa. Purified enzyme was confirmed as α-amylase type by LC-MS/MS analysis and activity on specific substrate of ethylidene-pNP-G7. The CgAmy revealed extreme activity at a high temperature of 50.0-70.0°C with optimum activity at 70.0°C. The optimal pH of enzyme activity was observed at 6.0. The CgAmy exhibited stability in pH range of 5.0-8.0 and highly thermostable with a temperature of 40.0-60.0°C. The kinetic parameters K m for hydrolysis of starch were found to be 3.12 mg/ml. The α-amylase activity was enhanced in the presence of Co2+ and β-mercaptoethanol. While, Na2+, K2+, Ca2+, Mg2+, Zn2+, Ba2+, Fe2+ and Cd2+ slightly inhibited α-amylase activity. Interestingly, the CgAmy displayed stability towards some organic solvents and detergents. Stability at high temperature and some metal ions, organic solvents and detergents indicated that this enzyme has potential for various applications.