Alterations in the protein kinase C signaling activated by a parthenogenetic agent in oocytes from reproductively old mice.
To investigate the effect of female age on oocyte developmental competence, we focused on protein kinase C (PKC), a major component of the signalling pathway involved in oocyte activation, and put forward the hypothesis that, as it occurs in many organs and tissues, aging affects PKC function in mouse oocytes. Biochemical activity of PKC along with the expression and subcellular distribution of some PKC isoforms were monitored in young and old mouse oocytes parthenogenetically activated by SrCl(2). We found that PKC activity increased reaching a level that was lower in old compared to young oocytes in association with an incomplete translocation of PKCbetaI to the plasma membrane. Moreover, old oocytes exhibited a reduced expression of PKCbeta1 and PKCalpha at the protein level, without significant effects on the expression of the Ca(2+)-independent PKCdelta. Detectable amounts of PKCbeta1 mRNA were observed in young and old oocytes at GV stage with no difference between the two groups of age. When meiotic progression to anaphase II up to first cleavage were analyzed, a delay in meiosis resumption and significantly lower rates of pronuclei formation and first cleavage were observed in old compared to young oocytes. Moreover, we found that, in contrast to SrCl(2), PMA (12-O-tetradecanoyl phorbol-13-acetate), a PKC agonist, was ineffective in activating old oocytes. Present findings provide evidence that aging affects the correct storage and activation of some PKCs, functional components of the machinery involved in oocyte activation, and suggest that these changes may negatively influence the activation competence of old oocytes.


[Cutaneous manifestations of thrombocythaemia associated with myelofibrosis in a patient suffering from psoriasis and treated by PUVA (author's transl)].
Cutaneous manifestations of thrombocythaemia are caused by vascular lesions, either haemorrhagic or thrombotic, affecting above all the microcirculation of the extremities. The authors report a case of thrombocythaemia associated with myelofibrosis discovered by ischaemic lesions on the toes which appeared at the beginning of PUVA therapy for psoriasis. The type of vascular lesions generally depends on the platelet count. In the presence of these cutaneous manifestations, the determination of both platelet counts and functions may orient the diagnosis toward a myeloproliferative syndrome.


A 90-day subchronic toxicological assessment of dioscin, a natural steroid saponin, in Sprague-Dawley rats.
Dioscin is the major active compound in many traditional Chinese medicines (TCMs), while safety evaluation of this natural product has not yet been investigated. Therefore, the aim of this study was to evaluate the 90-day subchronic toxicity of dioscin in rats. The rats were divided into four groups and dioscin was administered orally at doses of 0, 75, 150 and 300 mg/kg/day, respectively. The toxicity of dioscin was evaluated based on clinical observations, ophthalmic examination, body weight, food and water consumption, urinalysis, hematology, clinical biochemistry and pathology. The results showed that dioscin had no subchronic toxicity in female rats and had slight subchronic toxicity in male rats. However, male rats in the 300 mg/kg/day group showed slight gastro-intestinal tract distension during the treatment period and hemolytic anemia in the hematology assessment. Compared with the control group, body weight gain was significantly decreased in male rats. Other significant changes were not associated with dioscin in the male and female groups. In conclusion, the no-observed-adverse-effect level (NOAEL) and the lowest-observed-adverse-effect level (LOAEL) of dioscin are estimated to be 300 mg/kg/day for female and male rats, respectively. Our work provides useful data for further research and new drug exploration of dioscin.


Description of Kibdelosporangium banguiense sp. nov., a novel actinomycete isolated from soil of the forest of Pama, on the plateau of Bangui, Central African Republic.
A novel actinomycete strain F-240,109(T) from the MEDINA collection was isolated from a soil sample collected in the forest of Pama, on the plateau of Bangui, Central African Republic. The strain was identified according to its 16S rRNA gene sequence as a new member of the genus Kibdelosporangium, being closely related to Kibdelosporangium aridum subsp. aridum (98.6 % sequence similarity), Kibledosporangium phytohabitans (98.3 %), Kibdelosporangium aridum subsp. largum (97.7 %), Kibdelosporangium philippinense (97.6 %) and Kibledosporangium lantanae (96.9 %). In order to resolve its precise taxonomic status, the strain was characterised through a polyphasic approach. The strain is a Gram-stain positive, aerobic, non-motile and catalase-positive actinomycete characterised by formation of extensively branched substrate mycelia and sparse brownish grey aerial mycelia with sporangium-like globular structures. The chemotaxonomic characterisation of strain F-240,109(T) corroborated its affiliation into the genus Kibdelosporangium. The peptidoglycan contains meso-diaminopimelic acid; the major menaquinone is MK-9(H4); the phospholipid profile contains high amounts of phosphatidylethanolamine, hydroxyphosphatidylethanolamine, diphosphatidylglycerol and an unidentified phospholipid; and the predominant cellular fatty acid methyl esters are iso-C16:0, iso-C14:0, iso-C15:0 and 2OH iso-C16:0. However, some key phenotypic differences regarding to its close relatives and DNA-DNA hybridization values indicate that strain F-240,109(T) represents a novel Kibdelosporangium species, for which the name Kibdelosporangium banguiense sp. nov. is proposed. The type strain is strain F-240,109(T) (=DSM 46670(T), =LMG 28181(T)).


Further improvements in the hepatocyte primary culture DNA repair test for carcinogens: detection of carcinogenic biphenyl derivatives.
DNA repair in hepatocyte primary cultures was induced by simultaneous treatment with the carcinogen and [3H] thymidine for 18 h beginning immediately after attachment of cells. The unscheduled DNA synthesis elicited by carcinogens was determined by counting grains with an automatic grain counter. In 5 biphenyl derivatives, a correlation was found between carcinogenicity and the ability to induce DNA repair. Hence, the method offers promise as a means of screening chemical carcinogens.


Epigenetics of colon cancer.
Accumulation of genetic and epigenetic alterations transforms normal colonic epithelial cells to adenocarcinoma cells. Genetic alterations include mutations in tumor suppressor genes and oncogenes, whereas epigenetic mechanisms are defined as heritable alterations in gene expression that is independent of changes in the primary DNA sequence. Role of epigenetic mechanisms in development and maintenance of organ- and tissue-specific gene expression is now realized. Disturbances in epigenetic landscape can lead to malignant cellular makeover, and these heritable changes are maintained through various cycles of cell division that renders cells to have discrete identity with similar genetic information. Epigenetic alterations in colorectal cancer (CRC) that transform colonic epithelial cells into adenocarcinoma cells include aberrant DNA methylation, chromatin modifications, and noncoding RNAs, especially microRNA expression. CpG island DNA methylation and aberrant methylation of genes drive the initiation and progression of CRC. Histone modifications impinge on chromatin structure and gene expression and thus play an important role in gene silencing in CRC. DNA hypermethylation also leads to downregulation and inappropriate expression of certain microRNAs that act like tumor suppressor genes. Determining the causes and roles of epigenetic instability in CRC pathogenesis will lead to effective prevention and therapeutic strategies for patients with CRC. Epigenetic drugs that underscore the reversible nature of epigenetic events have led the possibility of epigenetic therapy as a treatment option in CRC.


Utilization of date syrup as a tablet binder, comparative study.
The aim of this study was to investigate the possibility of using dates syrup as a tablet binder. Dates syrup (40%, 50%, 60% w/w dates syrup:water) was utilized for the granulation of sodium bicarbonate and calcium carbonate as examples for water-soluble and water-insoluble materials; correspondingly. Those two materials represent examples of bulky drugs as well. Starch paste (10% w/w starch in water) and sucrose syrup (50% w/w sucrose in water), the well-known tablet binders, were used in the granulation of the same materials for the sake of comparison. The granulations were evaluated with regard to particle size and particle size distribution, granule strength, bulk density, flowability, moisture content and compression behavior. In addition, tablets prepared and evaluated from these granules. Taste and flavor of the prepared tablet have been tested by seven healthy volunteers. Within the scope of this work, dates syrup showed excellent properties as a tablet binder in comparison to starch paste or sucrose syrup for the granulation of both water-soluble and water-insoluble materials. Also, better flavoring and masking taste have been noticed from an evaluation by human volunteers demonstrating the usefulness of the date syrup as sweetener and flavoring the tablets in addition to its use as binder.


Matrix metalloproteinases-1 and -2, and tissue inhibitor of metalloproteinase-2 production is abnormal in bone marrow stromal cells of multiple myeloma patients.
We have investigated the production of metalloproteinases (MMP-1, MMP-2, MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in bone marrow stromal cells (BMSCs) of patients with multiple myeloma (MM) and a healthy control. The new findings of this paper is that BMSCs of the MM patients exhibited intrinsic MMP-1, MMP-2 and TIMP-2 overproduction. Production of MMP-1, TIMP-2 and activation of MMP-2 was additionally enhanced in co-cultures of BMSCs with RPMI8226 cells. The ratio between MMP-2 and TIMP-2 was significantly higher in BMSCs of the MM patients than in control. BMSCs of both the control and the MM patients exhibited the presence of MMP-9 latent form, but in co-cultures RPMI8226 cells were the main producers of this metalloproteinase.


Expediting rare disease diagnosis: a call to bridge the gap between clinical and functional genomics.
Approximately 400 million people throughout the world suffer from a rare disease. Although advances in whole exome and whole genome sequencing have greatly facilitated rare disease diagnosis, overall diagnostic rates remain below 50%. Furthermore, in cases where accurate diagnosis is achieved the process requires an average of 4.8 years. Reducing the time required for disease diagnosis is among the most critical needs of patients impacted by a rare disease. In this perspective we describe current challenges associated with rare disease diagnosis and discuss several cutting-edge functional genomic screening technologies that have the potential to rapidly accelerate the process of distinguishing pathogenic variants that lead to disease.


Improving the accuracy of genomic prediction for meat quality traits using whole genome sequence data in pigs.
Pork quality can directly affect customer purchase tendency and meat quality traits have become valuable in modern pork production. However, genetic improvement has been slow due to high phenotyping costs. In this study, whole genome sequence (WGS) data was used to evaluate the prediction accuracy of genomic best linear unbiased prediction (GBLUP) for meat quality in large-scale crossbred commercial pigs. We produced WGS data (18,695,907 SNPs and 2,106,902 INDELs exceed quality control) from 1,469 sequenced Duroc × (Landrace × Yorkshire) pigs and developed a reference panel for meat quality including meat color score, marbling score, L* (lightness), a* (redness), and b* (yellowness) of genomic prediction. The prediction accuracy was defined as the Pearson correlation coefficient between adjusted phenotypes and genomic estimated breeding values in the validation population. Using different marker density panels derived from WGS data, accuracy differed substantially among meat quality traits, varied from 0.08 to 0.47. Results showed that MultiBLUP outperform GBLUP and yielded accuracy increases ranging from 17.39% to 75%. We optimized the marker density and found medium- and high-density marker panels are beneficial for the estimation of heritability for meat quality. Moreover, we conducted genotype imputation from 50K chip to WGS level in the same population and found average concordance rate to exceed 95% and r2 = 0.81. Overall, estimation of heritability for meat quality traits can benefit from the use of WGS data. This study showed the superiority of using WGS data to genetically improve pork quality in genomic prediction.


The Finnmark Study. A prospective population study of the social support buffer hypothesis, specific stressors and mental distress.
According to the buffer hypothesis, social support or social network may affect mental health by buffering the negative effect of stress on mental health. Previous studies have mostly been cross-sectional or have been done on selected populations, and the results have been conflicting. The buffer hypothesis was tested in three population-based health surveys which took place in 1987, 1990 and 1993 in five coastal municipalities in Finnmark, Norway. All persons aged 40-62 years and a random sample of those aged 20-39 years were invited, and 77%, 74% and 70% attended the three health surveys, respectively. Those who had attended the health surveys more than once and had answered the key questions about mental health and social network, social support (measured both as instrumental support as well as emotional support) and stress were included in the analyses. Stress was divided into acute stress, (somatic stress, civil stress and work stress) and chronic stress (having a chronic disease, disability pension, being a single parent or providing long term nursing care for someone in the family). Growth curve analyses using mental distress as the dependent variable were used, analysing the interactional effects of various types of stressors and social network or social support. When all possible stressors and the sum of social network/social support were taken into consideration, total social support/network buffered the deteriorating effect of total stressor score upon mental health. The effect was weak but significant, and stronger for women than men. When each stressor was analysed separately, only a significant buffer effect of social network could be detected for work stress. For one of the chronic stressors, receiving a disability pension, a buffer effect could be demonstrated for both social network and instrumental support. The results provide some support for the buffer hypothesis, and indication of specificity in the interactions between stressor and social network/social support was found.Women, in general, had a larger buffering effect from their social network than men.


Identification of sleep-disordered breathing in children: variation with event definition.
To determine the effect of varying approaches to the measurement of the respiratory disturbance index (RDI) on identification of sleep disordered breathing (SDB) in children. Cross-sectional study of SDB in a well-characterized birth cohort (stratified for term and preterm birth) participating in longitudinal studies of cognition and behavior. Community-based; overnight studies conducted in participant's homes. 433 children, ages 8-11 years, un-referred for clinical assessment of SDB. N/A. Participants underwent unattended overnight in-home recording of respiratory inductance plethysmography, pulse oximetry, body position, and heart rate. The relationships among RDIs derived from various definitions of apnea and hypopneas and thresholds for frequency of events were assessed. Median RDI varied by more than 20-fold for definitions using the more liberal criteria for event definition (all respiratory events; i.e., central or obstructive events and hypopneas with no requirement for associated desaturation) to the most conservative definition (using obstructive apneas only or obstructive apnea and hypopneas requiring a 5% associated desaturation). Prevalence estimates for SDB based on RDIs that included central apneas were 40% to 140% higher than those that excluded central apneas. Different approaches for quantifying RDI contribute to substantial variability in identification and classification of SDB in children and will lead to discrepant estimates of its presence and severity.


Toward Ecofriendly Piezoelectric Ceramics-Reduction of Energy and Environmental Footprint from Conceptualization to Deployment.
Piezoelectric materials are widely used in electromechanical coupling components including actuators, kinetic sensors, and transducers, as well as in kinetic energy harvesters that convert mechanical energy into electricity and thus can power wireless sensing networks and the Internet of Things (IoT). Because the number of deployed energy harvesting powered systems is projected to explode, the supply of piezoelectric energy harvesters is also expected to be boosted. However, despite being able to produce green electricity from the ambient environment, high-performance piezoelectrics (i.e., piezoelectric ceramics) are energy intensive in research and manufacturing. For instance, the design of new piezoceramics relies on experimental trials, which need high process temperatures and thus cause high consumption and waste of energy. Also, the dominant element in high-performance piezoceramics is hazardous Pb, but substituting Pb with other nonhazardous elements may lead to a compromise of performance, extending the energy payback time and imposing a question of trade-offs between energy and environmental benefits. Meanwhile, piezoceramics are not well recycled, raising even more issues in terms of energy saving and environmental protection. This paper discusses these issues and then proposes solutions and provides perspectives to the future development of different aspects of piezoceramic research and industry.


Getting to the root of hydrocephalus.
The blood-borne lipid lysophosphatidic acid and its receptor contribute to fetal-onset hydrocephalus, a severe neurological disorder of newborns.


Metal ion assistant transformation strategy to synthesize catechol-based metal-organic frameworks from Ti3C2Tx precursors.
Chemical transformation strategy is capable of fabricating nanomaterials with well-defined structures and fascinating performance via controllable crystallization kinetics in the phase transformation. V2CTx MXene has been used as precursors to fabricate vanadium porphyrin metal-organic frameworks (V-PMOFs) via the coordination of deprotonated carboxylic acid ligands. However, the rational and in-depth exploration of synthesis mechanism with the aim of enriching the variety of MXene (i.e., Ti3C2Tx) and organic ligands (i.e., catechol-based) to design new MOFs is rarely reported. Herein, we have first developed a metal ion assistant transformation strategy to synthesize three-dimensional catechol-based TiCu-HHTP (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) MOFs with a non-interpenetrating SrSi2 (srs) framework using two-dimensional Ti3C2Tx as precursors. The unique synergetic transformation mechanism involves the electron transfer from Ti3C2Tx to electrostatically adsorbed Cu2+ ion for redox reaction, the subsequent Ti-C bond rupture for Ti4+ ion release, and the continuous chelation coordination between Ti4+/Cu2+ and HHTP. Ti3C2Tx precursors and auxiliary metal ion could be rationally substituted by V2CTx and Mn+ (e.g., Ni2+, Co2+, Mn2+, and Zn2+), respectively. This strategy lays the foundation for the design and synthesis of innovative and multifarious MOFs derived from MXene or other unconventional metal precursors.


Flow dynamics in a stenosed carotid bifurcation model--Part II: Derived indices.
Basic velocity measurements from the previous study in this issue of modelled carotid artery bifurcation disease are post-processed to derive indices potentially useful for clinical diagnosis. Selected parameters are based upon ultrasound pulse Doppler velocity measurements made at sites +/- 0.625 radius at axial distances of 0, 1, 3, 5, and 10 diameters downstream of smooth, axially symmetric constrictions of 0, 20, 40, 60, and 80% diameter reduction. Indices based on single point velocity measurements include: (a) the center-line velocity index (CVI) at the throat of the constrictor which is sensitive to all degrees of constriction (p less than 0.05), and (b) various measures of velocity disturbance (VDI1-VD14) which show greatest sensitivity when measured at one-fourth diameter from the tube wall. Cross-sectional indices include: (a) the maximum slope index (MSI) which separates constrictions of less than 60% diameter reduction from those having greater than or equal to 60% diameter reduction (p less than 0.05), and (b) the cross-sectional profile index (CPI) which separates constrictions of less than or equal to 20% diameter reduction from those having greater than 20% diameter reduction (p less than 0.05). A field profile index (FPI) utilizes data from all available sites up to 5 diameters downstream and is able to separate all constrictor groups (p less than 0.05). Presence of constrictions produces characteristic flow patterns which can be quantified using indices based on the downstream velocity spectra. Specifically, locally increased velocity is very sensitive to degree of constriction and is best detected along the center line. Disturbance effects, while less pronounced, are complementary to changes in velocity magnitude and are first seen off-axis. Multiple point profile measures (cross sectional and full field) are also sensitive to degree of constriction and are best evaluated at 1 diameter and over 5 diameters, respectively, downstream of the constriction. All of the nondimensional indices offer the advantages of reduced probe and angle dependence and particular approaches may be implemented according to the data collection capability of the instrument used.


New synthesis and evaluation of enantiomers of 7-methyl-2-exo-(3'-iodo-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane as stereoselective ligands for PET imaging of nicotinic acetylcholine receptors.
A simple and efficient synthesis of nAChR antagonist (+/-)-7-methyl-2-exo-(3'-iodo-5'-pyridinyl)-7-azabicyclo[2.2.1]-heptane ((+/-)-NMI-EPB) has been developed. Both enantiomers of (+/-)-NMI-EPB were separated by semi-preparative chiral HPLC. The enantiomers manifested a substantial difference in their inhibition binding affinities ((+)-NMI-EPB, K(i)=2310, 1680 pM; (-)-NMI-EPB, K(i)=55, 68 pM). The enantiomers were stereoselectively radiolabeled with (11)C. In the distribution studies in the rodent brain [(11)C](-)-NMI-EPB specifically labeled nAChR whereas [(11)C](+)-NMI-EPB exhibited little specific binding. In the baboon PET study [(11)C](-)-NMI-EPB did not reach steady-state within 90 min post-injection suggesting that the radioligand may have some limitations for quantitative imaging.


The beneficial effects of vortioxetine on BDNF, CREB, S100B, β amyloid, and glutamate NR2b receptors in chronic unpredictable mild stress model of depression.
Depression, one of the most significant mental disorders, is still poorly understood in terms of its pathogenetic mechanisms despite its well-recognized association with stress. The current study's goal was to ascertain how the novel antidepressant drug vortioxetine (VOR) affected the BDNF (brain-derived neurotrophic factor), S100, amyloid β (Aβ), CREB (cAMP response element-binding protein), and NR2B, as well as its impact on depression-like behaviors, and tissue damage in an experimental rodent model of depression caused by chronic unpredictable stress. We employed twenty-eight Wistar albino male rats, and we randomly divided them into four groups, each consisting of 7 rats: control, CUMS (chronic unpredictable mild stress), CUMS+vortioxetine (CUMS+VOR), and CUMS+fluoxetine (CUMS+FLU). Sucrose preference and forced swimming tests (SPT and FST, respectively), PCR, ELISA, and histopathological and immunohistochemical evaluation were made on brains. The behaviors of reduced immobility in the FST and increased sucrose preference were observed in the CUMS group and they improved in the groups treated with VOR and FLU. Compared with the control group, the group exposed to CUMS showed increased Aβ and decreased BDNF, CREB, and S-100 expressions, as well as neuronal degeneration (p<0.001). VOR and FLU treatment ameliorate the findings. This study demonstrated significant ameliorative effects of VOR in an experimental model of chronic unpredictable depression to reduce brain tissue damage and depression-like behaviors in rats. Effects of CUMS on the brain and possible effects of VOR.


[Effect of preoperative biliary drainage on the immediate and long-term results after duodeno-cephalo-pancreatectomy for peri-ampullar neoplasia].
Pancreaticoduodenectomy has a primary role in the treatment of patients with periampullary carcinoma. Several series have reported encouraging operative mortality and survival after resection. Controversies exist regarding the impact of preoperative biliary drainage on immediate and long-term results.


Cytokine-induced monocyte adhesion to endothelial cells involves platelet-activating factor: suppression by conjugated linoleic acid.
Monocyte-endothelium interaction is key to many acute and chronic inflammatory diseases. We have investigated the factors regulating monocyte attachment to cytokine-activated human umbilical vein endothelial cells (HUVEC) and the modulatory effect of the polyunsaturated fatty acid (PUFA), conjugated linoleic acid (CLA) in this process. Both TNF-alpha and IL-1beta induced HUVEC platelet-activating factor (PAF) production and PAF was required for subsequent firm THP-1 monocyte adhesion since it was inhibited by both PAF receptor antagonists (BN-52021 or CV-6209) and a PAF synthesis inhibitor (sanguinarine). CLA inhibited the binding of both THP-1 and isolated human peripheral blood monocytes to HUVEC by up to 40% with the CLA t10,c12 isomer suppressing adhesion dose-dependently. Investigation into the mechanism involved demonstrated that with IL-1beta, VCAM-1 and ICAM-1 levels and pro-inflammatory cytokine expression were largely unaffected by CLA. Through the use of PAF receptor antagonists and PAF synthesis inhibitors, CLA was shown to inhibit cytokine-induced binding by suppressing PAF production. Direct assay of PAF levels confirmed this result. We conclude that endothelial-generated PAF plays a central role in cytokine-induced monocyte adherence to endothelium and that the anti-inflammatory action of PUFAs such as CLA in suppressing monocyte-endothelial interaction is mediated through attenuation of pro-inflammatory phospholipids such as PAF.


Experience of virtual commissioning of a process control system for the production of high-paraffin oil.
This work describes the experience in developing and testing software for oil industry automation control systems based on the simulation of technological processes and control systems combined in virtual reality, this approach is called virtual commissioning and is widely used in the world both to create automated process control systems and to simulate interactions between different systems.


[Image-based guidance in shoulder traumatology. Initial clinical experience].
Computer-assisted systems are used frequently in pelvis and spine surgery but are still rare in general trauma and hardly ever used in shoulder surgery. The major limitation is the use of rigid markers and the problem of obtaining navigable images in the complex shoulder region. The aim of this study was to evaluate the use of a new image-based guidance system in shoulder traumatology. The system was used to implant a tightrope system in Tossy III lesions of the AC joint (n=7) and compared to the conventional method (n=8). Outcome parameters were duration of surgery, number of trials for perfect positioning of the guide wire, C-arm shots used till K-wire position is accepted, duration of radiation and surgeon's comment on usability and benefit. The new system did not shorten the surgical procedure significantly (45 vs 49 min, p=0.6) but reduced the average overall radiation time from 152 to 90 s (p=0.3). The number of shots to implant the guide-wire could be reduced significantly from 8 to 5 (p=0.01). The number of trials to implant the guide wire was less in the image-guided group compared to the conventional group (1 vs 2, p=0.02). For the first time image-based guidance was used in shoulder traumatology. The system holds high potential to assist surgeons without disturbing the workflow in assuring guide wire positioning, reduce the number of dangerous mistrials and reduce the emission of radiation.


Organic and inorganic nitrogen removals by an ureolytic heterotrophic nitrification and aerobic denitrification strain Acinetobacter sp. Z1: Elucidating its physiological characteristics and metabolic mechanisms.
Although heterotrophic nitrification-aerobic denitrification (HN-AD) is promising in nitrogen removal, it remains unclear for most HN-AD strains in physiological characteristics and metabolic mechanisms. In this study, a newly isolated strain Acinetobacter sp. Z1 converted not only inorganic nitrogen, but also organic nitrogen to N2. Among them, urea was the preferential nitrogen substrate. Single-factor experiments showed that efficient HN-AD process occurred with acetate as carbon source, C/N ratios of 12 for NH4+-N and 15 for NO3--N, pH 8, 30 °C, DO of ∼5.8 mg/L and salinity less than 1.5 %. Subsequently, response surface analysis was applied to predict the optimal growth conditions. Its complete genome annotation in combination with enzymatic activity assay and nitrogen balance calculation showed that at least four pathways involved in nitrogen metabolism. This work indicates that ureolytic strain Z1 could be prepared as bacterial agents with other HN-AD strains to treat urea-containing wastewater like urine from urban community.


Adeno-associated virus-mediated expression of kallistatin suppresses local and remote hepatocellular carcinomas.
The current treatments for hepatocellular carcinoma (HCC) are poor, particularly for metastatic HCC. Intraportal transfusion of adeno-associated virus (AAV) leads to long-term and persistent transgenic expression in livers. Kallistatin, a novel angiogenesis inhibitor, exhibits anti-tumor activity. The aim of the study was to investigate whether intraportal injection of AAV-kallistatin could suppress local and metastatic HCC in mice. An AAV vector encoding kallistatin was constructed, and its transduction efficiency by intraportal transfusion in livers was examined by RT-PCR, immunohistochemical and Western blotting analysis. The anti-tumor activity was tested in three HCC models including hepatic and subcutaneous human Hep3B HCC tumors in BALB/c athymic (nu/nu) mice, and subcutaneous mouse BNL HCC tumors in BALB/c mice. Tumor cell proliferation in situ was examined by anti-Ki-67 staining, and apoptosis by TUNEL. Gene transfection by rAAV-kallistatin inhibited proliferation of human umbilical vein endothelial cells and HCC cells in vitro. Intraportal injection of rAAV-kallistatin resulted in persistent and specific expression of kallistatin in livers detected by RT-PCR and immunohistochemical analysis, and kallistatin protein in circulation detected by Western blotting analysis. Intraportal injection of rAAV-kallistatin significantly suppressed angiogenesis and growth of hepatic Hep3B tumors. The kallistatin released by hepatocytes into the circulation suppressed remote Hep3B and BNL tumors established subcutaneously. The rAAV-kallistatin gene therapy significantly inhibited tumor cell proliferation and induced apoptosis. Intraportal injection of rAAV-kallistatin suppressed hepatic and subcutaneous HCC tumors, relying on its anti-angiogenic and anti-proliferative activities.


DNA synthesis in gametocytes of Plasmodium falciparum.
The DNA content of Plasmodium falciparum gametocytes during intra-erythrocytic development and during gametogenesis was established by cytophotometric methods. Intraerythrocytic micro- and macrogametocytes (Stage I-Stage VB) contain about twice the amount of DNA of haploid sporozoites and ringstages, indicating that DNA is synthesized during transformation of ringforms into Stage I gametocytes. Microgametocytes, after activation at pH 8, rapidly duplicate their genome several times, while the DNA content of macrogametocytes remains constant during gametogenesis.


Presentation, disease progression and outcomes of adrenal gland metastases.
Data on the presentations and outcomes of patients with adrenal gland metastases are limited. Our objectives were to characterize the prevalence of adrenal metastases subtypes and investigate how varying clinical presentations affect disease progression, development of primary adrenal insufficiency (PAI) and mortality. Single institution tertiary centre, retrospective cohort study from 1997 to 2020. Adult patients with adrenal metastases. Clinical, radiologic and biochemical presentations and outcomes were reviewed. Of 579 patients (62.3% men, median age 67 years [range 25-92]) with adrenal metastases (median tumour size of 30 mm [range 5-200]), 339 (58.5%) were discovered during cancer staging, 210 (36.3%) were found incidentally, and 29 (5.0%) based on symptoms. Tumours originated from the lung (226, 39.0%), genitourinary (GU) (160, 27.6%), gastrointestinal (GI) (79, 13.6%) and other (114, 19.7%) organ systems. Bilateral metastases were found in 140 (24.2%) patients at the time of initial diagnosis, and 249 (43.0%) had bilateral disease throughout the study course. PAI developed in 12.4% of patients with bilateral disease and was associated with larger tumour size. Median follow-up time was 14 months (range 0-232), and 442 (76.3%) patients died. Higher mortality was independently associated with older age, adrenal metastases originating from the lung, bilateral disease, and the absence of adrenalectomy. Adrenal gland metastases originated most commonly from lung, GU and GI malignancies. Bilateral adrenal metastases occurred in 43% of patients, and PAI occurred in 12.4% of those with bilateral disease, warranting further case detection strategies.


MYD88 L265P MUTATION DETECTION IN THE AQUEOUS HUMOR OF PATIENTS WITH VITREORETINAL LYMPHOMA.
To detect the presence of MYD88 L265P mutation in the aqueous humor of patients with cytologically proven vitreoretinal lymphoma. Eight consecutive patients with bilateral vitreoretinal lymphoma (16 eyes) were prospectively evaluated. Genomic DNA was extracted from aqueous samples after paracentesis and vitreous humor samples after diagnostic vitrectomy. MYD88 codon 265 mutation was investigated by both amplification-refractory mutation system polymerase chain reaction approach and pyrosequencing assay in the aqueous humor of all patients and in the vitreous of 6 patients. A control group of 8 age-matched patients with established diagnosis of noninfectious uveitis was also tested for the presence of MYD88 L265P mutation in the aqueous humor. Eight patients (three men, five women) with mean age of 69.5 years (range 50-85 years) were considered. All the patients tested for MYD88 L265P in the vitreous (six) were positive, and this result was consistent with cytological examination in all samples but one. The MYD88 L265P mutation was found in the aqueous of 6 patients (75%), and in 3 of them, the mutation was present in both eyes. Results of MYD88 L265P mutation in aqueous and vitreous sample were consistent in 7 of the 8 eyes with available samples. The aqueous humor of the noninfectious uveitis control group was negative for the detection of MYD88 L265P mutation. MYD88 mutation was detected in the aqueous humor of 75% of patients with cytologically proven vitreoretinal lymphoma. This technique may be considered as an additional diagnostic tool in the detection of the disease.


Plasmodium malariae infections as a cause of febrile disease in an area of high Plasmodium falciparum transmission intensity in Eastern Uganda.
Plasmodium falciparum is responsible for the vast majority of (severe) clinical malaria cases in most African settings. Other Plasmodium species often go undiagnosed but may still have clinical consequences. Here, five cases of Plasmodium malariae infections from Eastern Uganda (aged 2-39 years) are presented. These infections were all initially mistaken for P. falciparum, but Plasmodium schizonts (up to 2080/µL) were identified by microscopy. Clinical signs included history of fever and mild anaemia. These findings highlight the importance of considering non-falciparum species as the cause of clinical malaria. In areas of intense P. falciparum transmission, where rapid diagnostic tests that detect only P. falciparum antigens are commonly used, non-falciparum malaria cases may be missed.


Molecular linkage of the human CTLA4 and CD28 Ig-superfamily genes in yeast artificial chromosomes.
CD28 and CTLA4 are structurally homologous single-V-domain molecules of the Ig superfamily, the genes of which comap on the same chromosomal bands in mouse and man. Using polymerase chain reactions, we isolated six yeast artificial chromosome (YAC) clones positive for CTLA4 and/or CD28 from a human-DNA-containing YAC library. Two double-positive clones, 365 and 550 kb long, respectively, were further studied. Detailed restriction enzyme maps showed that one of these YACs was nested in the other, that they both bore the same CD28- and CTLA4-hybridizing fragments, that similar fragments were seen in genomic DNA, and that the distance between the CD28 and CTLA4 genes was at most 150 kb and at least 25 kb. A CpG island was found between these genes. These results provide a high-resolution estimate of the physical distance between the CD28 and CTLA4 genes and constitute a basis for the isolation of neighboring structures.


Multispectroscopic studies on the molecular interactions between bovine γ-globulin and borohydride-capped silver nanoparticles.
Interactions between bovine γ-globulin (BGG) and borohydride-capped silver nanoparticles (BAgNPs) were studied using dynamic light scattering (DLS) and spectroscopic techniques such as UV-vis spectroscopy, fluorescence, and circular dichroism. The results were compared with earlier reported interactions between γ-globulin and citrate-coated AgNPs (CAgNPs). BAgNPs were synthesized and characterized. Irrespective of the coating on AgNPs, nanoparticles had formed ground-state complexes with the protein. CAgNPs, as well as BAgNPs had caused static quenching of tryptophan (Trp) fluorescence of the protein. The change in the capping agent from citrate to borohydride weakened the binding of nanoparticles with the protein. But the same change in capping agent had increased the fluorescence quenching efficiency of AgNPs. Hydrogen bonding and van der Waals interactions were involved in BGG-BAgNPs complex similar to the CAgNPs complex with γ-globulin. Polarity of the Trp microenvironment in BGG was not altered using BAgNPs as opposed to CAgNPs, as supported using synchronous and three-dimensional fluorescence. Resonance light scattering experiments also suggested nano-bio conjugation. Far-UV and near-UV circular dichroism (CD) spectra respectively pointed towards changes in the secondary and tertiary structure of BGG by BAgNPs, which was not observed for CAgNPs.


[Impacted maxillary cuspid. IV. Periodontal aspects].
Treatment goal of the maxillary impacted cuspid should include health periodontal end results. This clinical and radiographic study reveals in 75% of the cases a satisfying periodontal condition.


Anorectal Crohn's Disease.
Medical treatment remains the mainstay of perianal disease management for CD; however, aggressive surgical management should be considered for severe or recurrent disease. In all cases of perianal CD, medical and surgical treatments should be used in tandem by a multidisciplinary team. Significant development has been made in the treatment of Crohn's-related fistulas, particularly minimally invasive options with recent clinical trials showing success with mesenchymal stem cell applications. Inevitably, some patients with severe refractory disease may require fecal diversion or proctectomy. When considering reversal of a diverting or end ileostomy, cessation of proctitis is the most important factor.


Fibrinogen metabolism and disseminated intravascular coagulation in dengue hemorrhagic fever.
In 29 patients with dengue hemorrhagic fever (DHF), 12 with grade 2 and 17 with grades 3 and 4, fibrinogen metabolism was studied by using 125I-fibrinogen; 11 of these patients were studied during shock. Hemostatic studies were also performed to search for evidence of disseminated intravascular coagulation (DIC). Increased intravascular coagulation, as judged by rapid T1/2 of 125I-fibrinogen, as well as evidence of DIC by hemostatic patients with DHF grade 2 had rapid T1/2 and only 17% had DIC. Of the 11 patients studied during shock, 91% had both rapid T1/2 and evidence of DIC, whereas 63% of the 18 patients without shock had rapid T1/2 and only 11% of this latter group had DIC. A correlation between the increased fibrinogen consumption as judged by rapid T1/2 of 125I-fibrinogen, DIC, clinical severity, and shock was demonstrated. The role of DIC in the pathogenesis of DHF is discussed, and heparin is suggested for patients with prolonged shock and severe acidosis when DIC becomes clinically apparent.


A mixed-methods, population-based study of a syndemic in Soweto, South Africa.
A syndemic has been theorized as a cluster of epidemics driven by harmful social and structural conditions wherein the interactions between the constitutive epidemics drive excess morbidity and mortality. We conducted a mixed-methods study to investigate a syndemic in Soweto, South Africa, consisting of a population-based quantitative survey (N = 783) and in-depth, qualitative interviews (N = 88). We used ethnographic methods to design a locally relevant measure of stress. Here we show that multimorbidity and stress interacted with each other to reduce quality of life. The paired qualitative analysis further explored how the quality-of-life impacts of multimorbidity were conditioned by study participants' illness experiences. Together, these findings underscore the importance of recognizing the social and structural drivers of stress and how they affect the experience of chronic illness and well-being.


Antioxidant effects of propofol on tourniquet-induced ischemia-reperfusion injury: an experimental study.
This experimental study aimed to investigate the antioxidant effects of propofol anesthesia at induction doses in a rat skeletal muscle ischemia/reperfusion injury model. Twenty-six rats were randomly divided into three groups to receive one of the following interventions: sham operation (n = 6), ischemia/reperfusion (I/R) injury (n = 10), or propofol administration in addition to I/R injury (n = 10). I/R injury was attained by 2-h clamping of femoral artery followed by 3-h perfusion. Then blood and tissue samples were collected for biochemical analysis and histopathologic examination. Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) enzyme activities and nitric oxide (NO) and malondialdehyde (MDA) levels were measured in both plasma and muscle tissue. In addition, catalase (CAT) activity and protein carbonyl (PC) content were measured in muscle tissue. I/R group had significantly higher SOD activity (9.05 versus 5.63 and 6.18 U/mL, P < 0.05) and NO level (46.77 versus 30.62 and 33.90 μmol/L, P < 0.05) compared with sham-operated group and I/R plus propofol group. In addition, GSH-Px activity of the I/R group was significantly higher than sham-operated group (1.26 versus 1.05 U/mL, P < 0.05). I/R group had significantly higher tissue activities of CAT (0.11 versus 0.06 and 0.04 k/g protein, P < 0.05) and SOD (0.12 versus 0.08 and 0.07 U/mg protein, P < 0.05) compared with the sham and I/R plus propofol group. Histopathologic examination showed that I/R plus propofol group had significantly lower degeneration (P = 0.021) and inflammation (P = 0.028) scores compared with I/R group. Propofol anesthesia seems to enhance the antioxidant capacity against tourniquet induced ischemia-reperfusion injury.


In silico prediction of 3D structure of Mn superoxide dismutase of Scylla serrata and its binding properties with inhibitors.
In the present study, we used computational methods to model crab and rat MnSOD using the crystal structure of MnSOD from Homo sapiens (PDB code: 1MSD) as template by comparative modeling approach. We performed molecular dynamics simulations to study dynamic behavior of the crab MnSOD. The modeled proteins were validated and subjected to molecular docking analyses. Molecular docking tool was used to elucidate a comparative binding mode of the crab and rat SOD with potent inhibitors of SOD such as hydrogen peroxide (H2O2), potassium cyanide (KCN) and sodium dodecyl sulphate (SDS). The predicted valid structure of crab MnSOD did not show any interaction with KCN but close interaction with H2O2 and SDS. A possible inhibitory mechanism of SDS and H2O2 due to their interaction with the amino acids present in the active site of the MnSOD of the above two animals are elucidated. This allowed us to predict the binding modes of the proteins to elucidate probable mode of action and sites of interference.


Templated xerogels as platforms for biomolecule-less biomolecule sensors.
We report on a new sensor strategy that we have termed protein imprinted xerogels with integrated emission sites (PIXIES). The PIXIES platform is completely self-contained, and it achieves analyte recognition without a biorecognition element (e.g., antibody). The PIXIES relies upon sol-gel-derived xerogels, molecular imprinting, and the selective installation of a luminescent reporter molecule directly within the molecularly imprint site. In operation the templated xerogel selectively recognizes the target analyte, the analyte binds to the template site, and binding causes a change in the physicochemical properties within the template site that are sensed and reported by the luminescent probe molecule. We report the PIXIES analytical figures of merit for and compare these results to a standard ELISA. For human interleukin-1 the PIXIES-based sensor elements exhibited the following analytical figures of merit: (i) approximately 2 pg/mL detection limits; (ii) <2 min response times; (iii) >85 selectivity; (iv) <6% R.S.D. long term drift over 16 weeks of ambient storage; (v) >95% reversibility after more than 25 cycles; and (vi) >85% recoveries on spiked samples.


Left ventricle automatic pacing threshold management in CRT systems: A comprehensive review.
Modern cardiac resynchronization therapy (CRT) device-based threshold detection enables capture management and voltage output adjusting to combine consistent left ventricular (LV) pacing with acceptable battery drainage. The current technologies available for LV capture automatic confirmation in most cases require the evoked response, as well as "LV pace to right ventricular sense" algorithms. The LV pacing percentage counter may overestimate the CRT delivery which may be reduced due to pacing inhibition (by sensed LV activation) or inadequate capture due to subthreshold current or pacing into refractory tissue. Moreover, the LV threshold at implant and its behavior over time (as a marker of electrical viability) and the ineffective CRT issues (subthreshold stimulation or concealed loss of capture) are discussed. The purpose of the present review is to explore these new challenges regarding LV pacing automatic management.


[Therapy for unilateral vocal fold palsy].
The main symptom of unilateral vocal fold palsy is hoarseness, which can cause considerable disturbance to the patient depending on its extent and the patient's individual situation. Therapy aims at the restitution of a tuneful and resilient voice, which can be achieved by surgical or conservative means, improving the glottal closure and synchronizing the vocal fold vibrations during phonation. Vocal therapy is a common conservative method that may be supported by psychotherapeutic or physical procedures. In surgical therapy, there is a distinction between techniques of endoscopic augmentation by injecting different materials into the vocal folds and transcutaneous laryngeal framework surgery, i.e., transferring the paralyzed vocal fold to the glottal midline. Particularly apt for injection are biocompatible materials amount and position whose can easily be controlled. However, the inevitable resorption of many materials causes deterioration in voice quality. Furthermore, the change of vocal fold morphology obstructs regular phonatory vibration. On the other hand, medialization thyroplasty leads to permanent voice amelioration without a substantial complication rate when performed by experienced surgeons.


An integrated analysis of microRNAs regulating DNA damage response in triple-negative breast cancer.
Triple-negative breast cancer (TNBC) remains a clinical challenge due to its aggressive phenotype and limited treatment options for the patients. Many TNBC patients show an inherent defect in the DNA repair capacity primarily by acquiring germline mutations in BRCA1 and BRCA2 genes leading to Homologous Recombination Deficiency (HRD). Epigenetic modifications such as BRCA1 promoter methylation and miRNA expression targeting DNA repair pathway genes have contributed to the HRD phenotype in TNBC. Hence, we aimed to identify microRNAs that are associated with HRD status in the TCGA-BRCA project. We implemented a miRNA prediction strategy for identifying miRNAs targeting HR pathway genes using an in silico predicted and experimentally validated list from published literature for their association with genomic instability and factors affecting HRD. In silico analysis was performed to study miRNA expression patterns regulated by DNA methylation and TMB status in the TNBC patients from TCGA-BRCA project. Finally, we analysed selected miRNA expression with immune cell infiltration pattern in the TNBC patient cohort. Our study identified miRNAs associated with HRD, tumour mutation burden (TMB), and immune cell infiltration. Identified miRNA signatures were associated with the miR-17 ~ 92 cluster, miR-106b ~ 25 cluster, and miR-200b ~ 429 cluster. Pathway analysis of selected miRNAs suggested their association with altered immune cell infiltration in TNBC. Our study identified 6 'HRD associated miRNAs' such as miR-106b, miR-93, miR-17, miR-20a, miR-200b, and miR-429 as novel miRNA-based signatures associated with HR deficiency in TNBC.


A novel tribasic Golgi export signal directs cargo protein interaction with activated Rab11 and AP-1-dependent Golgi-plasma membrane trafficking.
The reovirus fusion-associated small transmembrane (FAST) proteins comprise a unique family of viral membrane fusion proteins dedicated to inducing cell-cell fusion. We recently reported that a polybasic motif (PBM) in the cytosolic tail of reptilian reovirus p14 FAST protein functions as a novel tribasic Golgi export signal. Using coimmunoprecipitation and fluorescence resonance energy transfer (FRET) assays, we now show the PBM directs interaction of p14 with GTP-Rab11. Overexpression of dominant-negative Rab11 and RNA interference knockdown of endogenous Rab11 inhibited p14 plasma membrane trafficking and resulted in p14 accumulation in the Golgi complex. This is the first example of Golgi export to the plasma membrane that is dependent on the interaction of membrane protein cargo with activated Rab11. RNA interference and immunofluorescence microscopy further revealed that p14 Golgi export is dependent on AP-1 (but not AP-3 or AP-4) and that Rab11 and AP-1 both colocalize with p14 at the TGN. Together these results imply the PBM mediates interactions of p14 with activated Rab11 at the TGN, resulting in p14 sorting into AP1-coated vesicles for anterograde TGN-plasma membrane transport.


Inconsistent Classification of "Outpatient" Surgeries Leads to Different Outcomes Following Total Hip Arthroplasty in Medicare Beneficiaries: A Critical Analysis.
With rising utilization of outpatient total hip arthroplasty (THA) in older patients including Medicare beneficiaries, the objective was to compare differences in definition including (1) patient demographics; (2) lengths of stay (LOS); and (3) outcomes of "outpatient" (stated status) versus "same-day discharge" (SDD) (actual LOS = 0 days) utilizing a nationwide database. A national database from 2015 to 2019 was queried for Medicare-aged patients undergoing outpatient THA. Total outpatient THAs (N = 6,072) were defined in one of 2 ways: either "outpatient" by the hospital (N = 2,003) or LOS = 0 days (N = 4,069). Demographics, LOS, discharge destinations, and complications were compared between groups. Logistic regression models computed odds ratios (ORs) for factors leading to complications, readmissions, and nonhome discharges. P values < .008 were significant. Women (OR: 1.19, P = .002), diabetes mellitus (OR: 1.31, P = .003), general anesthesia (OR: 1.24, P = .001), and longer operative times (≥95 minutes) (OR: 1.82, P < .001) were associated with 'outpatient' designation versus SDD. Within the hospital-defined 'outpatient' cohort, 49.1% (983 of 2,003) were discharged the same day (LOS = 0 days), and 21.8% had LOS 2 or more days. The hospital-defined 'outpatient' cohort had greater odds of nonhome discharges (6.3 versus 2.8%; OR: 1.88, P < .001) compared to SDD surgeries. The incidence was higher for any complication among hospital-defined 'outpatient' designated patients compared to SDD (5.5 versus 3.9%, P = .007). Outpatient surgeries may be misleading and often do not correlate with SDD, as over 20% remain in the hospital 2 or more days. Investigators should quantitatively define the "outpatient" status by actual LOS to allow standardization and results comparison. III.


Relapsing Exophiala jeanselmei phaeohyphomycosis in a lung-transplant patient.
Dematiaceous fungi are a cause of a variety of human infections, including phaeohyphomycosis, that may affect patients with solid organ or bone marrow transplants. Exophiala jeanselmei, the most common cause of the pheomycotic cyst/subcutaneous phaeohyphomycosis in the United States, has been shown to cause disease in transplant recipients. We report a lung-transplant patient with relapsing and invasive E. jeanselmei phaeohyphomycosis, who previously had a pheomycotic cyst excised and treated with oral fluconazole. The patient was subsequently treated with re-excision and an 8-month course of oral itraconazole without relapse as to date.


The Role of Nrf2 on the Cognitive Dysfunction of High-fat Diet Mice Following Lead Exposure.
Lead (Pb) exposure can induce the severe deleterious damage on the central nervous system (CNS). High-fat diet also has been suggested that it had some adverse effects on learning and memory, cognitive function, but there is lack of study on Pb and high-fat diet co-exposure on the CNS damage. In this study, the goal was to explore the effect of Pb on the cognitive function of mice with high-fat diet and to investigate whether Nrf2 signaling pathway acts in the cerebral cortex. C57BL/6J mice were randomly divided into control, high-fat diet, Pb (drinking water with 250 mg/L lead acetate), and high-fat diet with Pb (drinking water with 250 mg/L lead acetate) co-exposure groups for 12 weeks. Experiment data showed that learn memory and exploration ability of mice obviously decreased in Pb and high-fat diet, and reactive oxygen species (ROS) increased; then, the protein expressions of Nrf2, heme oxygenase-1, NADP(H):dehydrogenase quinone 1, and superoxide dismutase 2 were lower significantly compared with those in the control group. This study suggested that down-expressed Nrf2 signaling pathway possibly related to the cognitive dysfunction induced by Pb and high-fat diet co-exposure.


Matter, spacetime and the vacuum.
We distinguish three historical and scientific views of matter, spacetime, and the relationship between them: the absolute approach of Newton, the relational approach most often associated with Mach, and a third, geometrical approach which inspired Einstein and continues to drive efforts toward a unified theory of fundamental interactions today. Which is correct? We suggest that this is, to a large extent, an "ill-posed question," reminiscent of the wave/particle debate in earlier times. The boundary between matter and spacetime is no longer easy to draw, and it is likely that they are complementary aspects of the same reality. There is no clearer illustration of this than the modern view of the vacuum. We review the importance of this concept in cosmology, and explore the extent to which the old idea of an "empty" vacuum might still be maintained. If the real cosmological vacuum is far from empty, as observations now suggest, then it may be possible to achieve an even simpler goal: a Universe with a net energy of zero.


The interaction of aurein 2.5 with fungal membranes.
Aurein 2.5 (GLFDIVKKVVGAFGSL-NH2) is an antimicrobial peptide, which was seen to have activity against Stachybotris chartarum, Penicillium roseopurpureum and Aspergillus flavus with minimum fungicidal concentrations in the range 250-500 μM. S. chartarum showed enhanced susceptibility to lysis as compared to P. roseopurpureum and A. flavus, (44, 26 and 28 % respectively). Monolayers formed from lipid membrane extracts derived from S. chartarum, P. roseopurpureum and A. flavus showed maximal surface pressure changes of 13.5, 10.3 and 10.2 mN m(-1) respectively. However, aurein 2.5 adopted similar levels of α-helical structure (circa 45 %) in the presence of vesicles formed from membrane lipid extracts derived from all three fungi. These data imply that differential activity is not due to targeting and membrane association but linked to the ability of the bound peptide to lyse the cells. At sterol levels mimetic of eukaryotic systems, high levels of α-helical structure (circa 50 %) were also observed and hence similar binding. However, enhanced sterol levels (>0.6) led to a reduction in monolayer membrane interaction, suggesting that the sterols influence efficacy. Consistent with this suggestion, thermodynamic analysis showed that the peptide was able to destabilise model fungal monolayers, as indicated by negative values of ∆Gmix.


A case series of facial depigmentation associated with low fluence Q-switched 1,064 nm Nd:YAG laser for skin rejuvenation and melasma.
In recent years, "laser toning" using low fluence, large spot size, multiple passed Q-switched 1,064 nm Nd:YAG laser has gained much popularity in Asian countries for non-ablative skin rejuvenation and the treatment of melasma. This case series highlights one of the complications associated with laser toning, which is facial depigmentation. Fourteen patients with laser toning-associated facial depigmentation were assessed with cross-polarized and ultraviolet (UV) photographic images. The laser toning regimens received by these patients, as well as the treatment given for depigmentation, were analyzed retrospectively. All 14 patients were Chinese females, 9 of whom received laser toning for non-ablative skin rejuvenation and the other 5 for melasma. The treatment regimens received by these patients were highly variable. The total number of treatments received ranged from 6 to 50 (mean 22.07). In all cases, UV photographic images demonstrated facial mottled depigmentation. Laser toning failed to significantly improve melasma in all five patients. Five patients received targeted narrowband UVB for depigmentation with good clinical results. Laser toning with low fluence Q-switched 1,064 nm Nd:YAG laser for skin rejuvenation and melasma can be associated with mottled depigmentation. With laser toning being frequently performed, this complication may become more commonly encountered in clinical practice. The depigmentation can appear after only a few treatment sessions, and can cause much disfigurement, especially in cases with background melasma. Further studies on laser toning are needed with the view to optimizing efficacy and minimizing side-effects.


Immunohistochemical estimation of cell cycle phase in laryngeal neoplasia.
We previously developed an immunohistochemical method for estimating cell cycle state and phase in tissue samples, including biopsies that are too small for flow cytometry. We have used our technique to examine whether primary abnormalities of the cell cycle exist in laryngeal neoplasia. Antibodies against the markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67, and putative markers of cell cycle phase, cyclin D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis) were applied to paraffin-embedded sections of normal larynx (n = 8), laryngeal dysplasia (n = 10) and laryngeal squamous cell carcinoma (n = 10). Cells expressing each marker were determined as a percentage of total cells, termed the labelling index (LI), and as a percentage of Mcm-2-positive cells, termed the labelling fraction (LF). The frequency of coexpression of each putative phase marker was investigated by confocal microscopy. There was a correlation between Mcm-2 and Ki67 LIs (rho = 0.93) but Mcm-2 LIs were consistently higher. All cells expressing a phase marker coexpressed Mcm-2, whereas Ki67 was not expressed in a proportion of these cells. The putative phase markers showed little coexpression. Labelling index values increased on progression from normal larynx through laryngeal dysplasia to squamous cell carcinoma for Mcm-2 (P = 0.001), Ki67 (P = 0.0002), cyclin D1 (P = 0.015), cyclin A (P = 0.0001) and cyclin B1 (P = 0.0004). There was no evidence of an increase in the LF for any phase marker. Immunohistochemistry can be used to estimate cell cycle state and phase in laryngeal biopsies. Our data argues against primary cell cycle phase abnormalities in laryngeal neoplasia.


Competitive interactions limiting the number of species in rock pools: experiments with Sigara nigrolineata.
Rock-pool corixids (Hemiptera) Arctocorisa carinata and Callicorixa producta were excluded from small rock pools. First-stage larvae of Sigara nigrolineata, separately or together with larvae of either of the rock-pool species, were then introduced daily at a rate simulating reproduction by typical populations. In all three treatments, the survival of S. nigrolineata larvae was high at the beginning of experiment, 0.39-0.83 between the 1st and 5th stages, but later high mortality was observed. C. producta adults tended to invade experimental rock pools and towards the end of the experiment larvae of this species were dominant. Oviposition rates and developmental rates of the three species are comparable. In laboratory tests, young larvae of S. nigrolineata were more vulnerable to interspecific predation than those of the rock-pool species, and older larvae proved to be less efficient predators. In rock pools, there are no environmental factors preventing successful reproduction by S. nigrolineata. However, competition and predation by the two other rock-pool species seem to prevent successful reproduction. Dispersal in S. nigrolineata is too slow for efficient colonization of rapidly changing rock-pool environments.


Capillary electrochromatographic analysis of barbiturates in serum.
A capillary electrochromatographic method was developed for the separation of barbiturates. The separation was optimized in a 75 microm ID capillary, packed with 3-(1,8-naphthalimido)propyl-modified silyl silica gel (NAIP), studying the effect of buffer pH, buffer concentration, and mobile phase composition. Using an applied voltage of 20 kV and the short-end injection method (9 cm capillary effective length), the mobile phase of 1.0 mM citrate buffer (pH 5.0) containing 40% methanol provided the baseline separation of barbital, phenobarbital, secobarbital, and thiopental (internal standard) in less than 4.5 min. The method was successfully applied to the analysis of barbiturates in human serum. Under the optimal conditions, good repeatability and linearity were obtained in the range of 2.90-43.29 microg/mL for barbital, phenobarbital, and secobarbital.


Tumor-derived death receptor 6 modulates dendritic cell development.
Studies in murine models of cancer as well as in cancer patients have demonstrated that the immune response to cancer is often compromised. This paradigm is viewed as one of the major mechanisms of tumor escape. Many therapies focus on employing the professional antigen presenting dendritic cells (DC) as a strategy to overcome immune inhibition in cancer patients. Death receptor 6 (DR6) is an orphan member of the tumor necrosis factor receptor superfamily (TNFRSF21). It is overexpressed on many tumor cells and DR6(-/-) mice display altered immunity. We investigated whether DR6 plays a role in tumorigenesis by negatively affecting the generation of anti-tumor activity. We show that DR6 is uniquely cleaved from the cell surface of tumor cell lines by the membrane-associated matrix metalloproteinase (MMP)-14, which is often overexpressed on tumor cells and is associated with malignancy. We also demonstrate that >50% of monocytes differentiating into DC die when the extracellular domain of DR6 is present. In addition, DR6 affects the cell surface phenotype of the resulting immature DC and changes their cytokine production upon stimulation with LPS/IFN-gamma. The effects of DR6 are mostly amended when these immature DC are matured with IL-1beta/TNF-alpha, as measured by cell surface phenotype and their ability to present antigen. These results implicate MMP-14 and DR6 as a mechanism tumor cells can employ to actively escape detection by the immune system by affecting the generation of antigen presenting cells.


Rapid analysis of barley straw before and after dilute sulfuric acid pretreatment by photoluminescence.
The fluorescence intensities (FIs) of raw and pretreated barley straws were measured by fluorescence microscopy, and the difference in the fluorescence intensity of barley straw before and after dilute acid pretreatment was analyzed by investigation of the major compounds of barley straw. The difference in fluorescence intensity was due to the difference in xylan content. Barley straw was pretreated using dilute sulfuric acid at various conditions and the correlation between the fluorescence intensity and glucose yield of barley straw was investigated. The coefficient of determination (R(2)) of the correlation was found to be 72.28%. Also the calibration of fluorescence intensity with the xylan content was performed. In addition, the absorption and emission spectra of the raw and the pretreated barley straw were examined to verify the proposed method. The absorption and emission wave lengths were 550 nm and 665 nm, respectively.


Comparisons of glandular breast dose between digital mammography, tomosynthesis and breast CT based on anthropomorphic patient-derived breast phantoms.
To evaluate the bias to the mean glandular dose (MGD) estimates introduced by the homogeneous breast models in digital breast tomosynthesis (DBT) and to have an insight into the glandular dose distributions in 2D (digital mammography, DM) and 3D (DBT and breast dedicated CT, BCT) x-ray breast imaging by employing breast models with realistic glandular tissue distribution and organ silhouette. A Monte Carlo software for DM, DBT and BCT simulations was adopted for the evaluation of glandular dose distribution in 60 computational anthropomorphic phantoms. These computational phantoms were derived from 3D breast images acquired via a clinical BCT scanner. g·c·s·T conversion coefficients based on homogeneous breast model led to a MGD overestimate of 18% in DBT when compared to MGD estimated via anthropomorphic phantoms; this overestimate increased up to 21% for recently computed DgNDBT conversion coefficients. The standard deviation of the glandular dose distribution in BCT resulted 60% lower than in DM and 55% lower than in DBT. The glandular dose peak - evaluated as the average value over the 5% of the gland receiving the highest dose - is 2.8 times the MGD in DM, this factor reducing to 2.6 and 1.6 in DBT and BCT, respectively. Conventional conversion coefficients for MGD estimates based on homogeneous breast models overestimate MGD by 18%, when compared to MGD estimated via anthropomorphic phantoms. The ratio between the peak glandular dose and the MGD is 2.8 in DM. This ratio is 8% and 75% higher than in DBT and BCT, respectively.


Genetic toxicology in industry: perspectives and initiatives.
Recent studies support the view that, incidents apart, synthetic chemicals in general present only an industrial hygiene problem. It is also apparent that, if performed well, the Salmonella assay plus a genetically independent eukaryotic assay will be sufficient to detect genotoxins in vitro, while the in vivo micronucleus assay, linked to a liver genotoxicity assay, will alert to significant carcinogens. Some 'carcinogens' are not genotoxic, are weak and are usually species/organ specific in their action; they should be recognized as different and treated separately. Cancer bioassays could probably be discontinued except in special cases. Current protocols for such assays often yield misleading data and are unnecessarily expensive. When seeking significant environmental carcinogens and mutagens it would be profitable to turn away from industrial chemicals, despite the fact that they are readily available. In summary, it is suggested that there now exist short-term methods from the results of which it is possible to decide, with a high level of certainty, whether a compound will be a rodent carcinogen at dose levels that may be relevant to man.


Significant impact of cachexia index on the outcomes after hepatic resection for colorectal liver metastases.
The purpose of this study was to investigate the relation between preoperative cachexia index (CXI) and long-term outcomes in patients with colorectal liver metastases (CRLM) after hepatic resection. In all,118 patients who underwent hepatic resection for CRLM were analyzed retrospectively. The relationship between CXI and the long-term outcomes in patients after hepatic resection was investigated. CXI was calculated based on preoperative skeletal muscle index, serum albumin level, and neutrophil-lymphocyte ratio. The multivariate analysis showed that extrahepatic lesion (hazard ratio [HR] 2.86, 95% confidence interval [CI] 1.48-5.53, P < .01) and high CXI (HR 0.44, 95% CI 0.20-0.98, P = .04) were independent and significant predictors of disease-free survival. Moreover, extrahepatic lesion (HR 2.32, 95% CI 1.03-5.22, P = .04), high CXI (HR 0.17, 95% CI 0.05-0.57, P < .01), and curability R 1 or 2 (HR 3.29, 95% CI 1.23-8.78, P = .02) were independent and significant predictors of overall survival. CXI is a useful prognostic factor for disease-free survival and overall survival after hepatic resection in CRLM patients.


Neutrophil fluorescence in clozapine users is attributable to a 14kDa secretable protein.
Clozapine is the only antipsychotic agent with demonstrated efficacy in refractory schizophrenia. However, use of clozapine is hampered by its adverse effects, including potentially fatal agranulocytosis. Recently, we showed an association between neutrophil autofluorescence and clozapine use. In this study, we evaluated the subcellular localization of clozapine-associated fluorescence and tried to elucidate its source. Neutrophils of clozapine users were analyzed with fluorescence microscopy to determine the emission spectrum and localization of the fluorescence signal. Next, these neutrophils were stimulated with different degranulation agents to determine the localization of fluorescence. Lastly, isolated neutrophil lysates of clozapine users were separated by SDS-PAGE and evaluated. Clozapine-associated fluorescence ranged from 420 nm to 720 nm, peaking at 500-550 nm. Fluorescence was localized in a large number of small loci, suggesting granular localization of the signal. Neutrophil degranulation induced by Cytochalasin B/fMLF reduced fluorescence, whereas platelet-activating factor (PAF)/fMLF induced degranulation did not, indicating that the fluorescence originates from a secretable substance in azurophilic granules. SDS-PAGE of isolated neutrophil lysates revealed a fluorescent 14kDa band, suggesting that neutrophil fluorescence is likely to be originated from a 14kDa protein/peptide fragment. We conclude that clozapine-associated fluorescence in neutrophils is originating from a 14kDa soluble protein (fragment) present in azurophilic granules of neutrophils. This protein could be an autofluorescent protein already present in the cell and upregulated by clozapine, or a protein altered by clozapine to express fluorescence. Future studies should further explore the identity of this protein and its potential role in the pathophysiology of clozapine-induced agranulocytosis.


Mycotoxin production by pure fungal isolates analysed by means of an uhplc-ms/ms multi-mycotoxin method with possible pitfalls and solutions for patulin-producing isolates.
This study is the first report of applying an ultra high performance liquid chromatography/tandem mass spectrometric (UHPLC-MS/MS) multi-mycotoxin method to identify and quantify the mycotoxins produced by pure fungal isolates grown on Yeast Extract Sucrose (YES) agar. The method developed concerns a triple extraction procedure based on methanol, dichloromethane and ethyl acetate. The total extract was chromatographically separated on an UHPLC BEH C18 column and analyzed with a triple quadrupole mass spectrometer. Performance characteristics (specificity, linearity, possible matrix effects, recovery, repeatability, reproducibility and limit of detection) were evaluated by spiking experiments with blank agar plugs and the analytes. Verrucarol was used as internal standard. Recovery percentages varied between 56 and 125%, whereas the limit of detection ranged from 1 to 1,500 ng g(-1) with the exception of NIV, PAT and ZEA. The method was successfully applied for examining the in vitro mycotoxin production by Aspergillus fumigatus, A. flavus and A. niger. The mobile phases used for chromatographic separation were slightly modified when studying patulin-producing molds due to signal interference between this mycotoxin and an unknown metabolite. This modified method was successfully applied for Penicillium roqueforti, P. paneum and P. carneum grown on YES agar medium. Application of the multi-mycotoxin UHPLC-MS/MS method developed may be of great importance for studying the mycotoxin capacity of fungal isolates under varying growth conditions, in order to obtain a better insight into the conditions which induce or suppress mycotoxin production by pure fungal isolates or from a chemotaxonomic point of view.


[Prepubertal Hidradenitis suppurativa: Report of 2 clinical cases].
Hidradenitis suppurativa (HS) is an inflammatory follicular skin disease. It usually presents as recurrent, deep nodules in flexural apocrine gland bearing areas. It appears mainly in women, in the second and third decade of life. To present 2 cases of patients with prepuberal HS. A 10-year old female, Tanner stage I-II and obesity. History of 4 months of evolution with bilateral recurrent groin lesions that occasionally drain pus; HS Hurley stage i was diagnosed, and topical antibiotics and nutritional management were prescribed, with a good response. A 10 years old female, Tanner stage I-II and obesity. Since the age of 6 years, recurrent episodes of lesions in the inner side of the left thigh were observed, and multiple antibiotics with poor response were prescribed. HS Hurley stage i was diagnosed, and photodynamic therapy and nutritional management were used, with good response. The etiology of HS is unclear. Usually the presentation at early age is associated with a family history and more extensive compromise in the future. Treatment is difficult and depends on each case and severity.


[The psychological experience of the mothers whose babies were born deformed in the neonatological ward of the academic hospital center of Treichville (Côte-d'Ivoire)].
When a baby is born deformed, his birth breaks up plans his family has made for his life as well as for the family itself. So, our objective was to describe the experience undergone by the mothers who gave birth to babies with serious deformities. A prospective and descriptive study was carried out during 12 months about 35 mothers whose babies were born seriously deformed. The data were collected from newborn's medical file and from a well-conducted interview with volunteered mothers. The incidence of the major deformities was 1.4% and the antenatal diagnosis was carried out on only 6 cases. The announcement of deformities in the 30 cases discovered at birth by the clinical staff brought about a shock among mothers. In fact, 28 mothers were disappointed, while 23 experienced fear and 10 others felt guilty. Six mothers thought in terms of aborting, followed by 25 mothers who without any psychological aid felt lonely. Furthermore, 30 mothers suffered from a lack of communication with nurses and with medical staff concerning deformities. The anxiety of mothers was linked, respectively to fear of their husband (33 cases), to the social environment (35 cases) and to the health care (10 cases). Mothers facing congenital deformity experienced painful and violent emotional distress. Therefore, the emphasis must be put on the improvement of the neonatal diagnosis and of relationship between physicians and parents in order to achieve a close support toward mothers.


Skin cancer--primary and secondary prevention (information campaigns and screening)--with a focus on children & sunbeds.
Solar and artificial (sunbed) UV-exposure is the main risk factor for the development of epithelial skin cancer (basal cell carcinoma, BCC, and squamous cell carcinoma, SCC) as well for malignant melanoma (MM). UV exposure in childhood and adolescence is especially important. Therefore, adequate methods of primary prevention have continuously to be used and to be developed further to target these age-groups in order to reduce the risks of intensive UV-exposure. Primary prevention can effectively be combined with secondary prevention (early detection, screening) to reduce the burden of skin cancer and to decrease incidence, morbidity and mortality.


Hot spot identification method based on Andrews curves: an application on the COVID-19 crisis effects on caregiver distress in neurocognitive disorder.
Identifying and locating areas - hot spots - that present high concentration of observations in a high-dimensional data set is crucial in many data processing and analysis methods and techniques, since observations that belong to the same hot spot share information and behave in a similar way. A useful tool towards that aim is the reduction of the data dimensionality and the graphical representation of them. In the present paper, a new method to identify and locate hot spots is proposed, based on the Andrews curves. Simulations results demonstrate the performance of the proposed method, which is also applied to a high-dimensional data set, regarding caregiver distress related to symptoms of people with neurocognitive disorder and to the mental effects of the recent outbreak of the COVID-19 pandemic.


Giant GABAB-mediated synaptic potentials induced by zinc in the rat hippocampus: paradoxical effects of zinc on the GABAB receptor.
The interaction of zinc with pre- and postsynaptic GABAB receptors was studied in adult rat hippocampal slices using intracellular recording in CA1 and CA3 pyramidal neurons. Zinc (50-300 microM) antagonized baclofen responses with a variable potency, whereas CGP-35348 (100 microM) or barium (300 microM) produced a more substantial and consistent inhibition. Zinc also induced giant GABAA-mediated depolarizing potentials (GDP) in these neurons. After blocking GABAA and excitatory synaptic transmission, monosynaptic hyperpolarizing inhibitory postsynaptic potentials (IPSP) mediated by GABAB receptors (IPSPB) were inhibited by CGP-35348 or barium; however, zinc increased the latency and prolonged the duration of the IPSPB and also induced the appearance of spontaneous giant GABAB-mediated hyperpolarizing potentials (GHP). In some cells, IPSPBs in zinc exhibited a multiphasic appearance. The early component was partially inhibited by 300 microM zinc and was followed by a late GHP. CGP-35348 at 100 microM inhibited the early monosynaptic IPSPB but not the GHP; however, at 300 microM both components were blocked. Paired-pulse inhibition of the IPSPB was used to assess the effect of zinc on presynaptic GABAB receptors. Neither the zinc-chelating agent CP94 (400 microM) nor zinc affected this phenomenon. CGP-35348, barium and polyvalent cations, such as cadmium, copper, cobalt, manganese, iron and aluminum, failed to induce giant potentials in hippocampal neurons. It is concluded that zinc is apparently unique in synchronizing the release of GABA to produce GDPs and GHPs.


Variation of magnitude and timing of wrist flexor stretch reflex across the full range of voluntary activation.
This paper reports an investigation of the magnitude and timing of the stretch reflex over the full range of activation of flexor carpi radialis. While it is well established that the magnitude of the reflex increases with the level of muscle activation, there have been few studies of reflex magnitude above 50% of maximum voluntary contraction (MVC) and virtually no study of the timing of the response in relation to activation level. Continuous small amplitude (approximately 2 degrees) perturbations were applied to the wrist of 12 normal subjects while they maintained contraction levels between 2.5-95% MVC, monitored via surface electromyography (EMG). Both narrow band (4-5 Hz) and broad band (0-10 Hz) stretch perturbations were employed. The gain (EMG output/stretch input) and phase advance of the reflex varied with the level of muscle activation in a similar manner for both types of stretch, but there were significant differences in the patterns of change due to stretch bandwidth. Consistent with previous studies, the group average reflex gain initially increased with muscle activation level and then saturated. Inspection of individual data, however, revealed that the gain reached a peak at about 60% MVC and then decreased at higher contraction levels, the pattern across the full range of activation being well described by quadratic functions (mean r2=0.82). This quadratic pattern has not been reported previously for the neural reflex response in any muscle but is consistent with the pattern that has been reliably observed in studies of the mechanical reflex response in lower limb muscles. In contrast to the pattern for reflex gain, the phase advance of the reflex (at a stretch frequency of 4.5 Hz) decreased linearly from approximately 130 degrees at the lowest contraction levels to approximately 50 degrees as maximum voluntary contraction was reached (mean r2=0.69). This decrease corresponds to a delay of 49 ms introduced centrally in reflex pathways. All subjects showed clearly defined quadratic functions relating reflex gain and linear functions relating reflex phase to activation level, but there were considerable individual differences in the slopes of these functions which point to systematic differences in synaptic behaviour of the motoneuron pool. Thus, there was wide inter-subject variation in both the contraction level at which the reflex gain reached a peak (31-69% MVC) and the highest target contraction level that could be sustained during reflex measurement (47-95% MVC). A high correlation between these variables (r2=0.78) suggests a linear relation between afferent support of contraction and muscle fatigability. The decline in reflex gain at high levels of muscle activation signals a failure of muscle afferent input and subjects in whom the gain reached a peak and declined early were unable to sustain higher target contraction levels. The results of the study show that both the timing and magnitude of the stretch reflex vary markedly over the full range of voluntary muscle activation. The pattern of variation may account for why the stretch reflex contributes most effectively to muscle mechanics over the lower half of the range of activation, while progressive reductions in both gain and phase advance at higher levels render the reflex mechanically less effective and make tremor more likely.


NMR resonance assignments of the four isoforms of the hazelnut allergen Cor a 1.04.
In large parts of Europe, Northern America and China people are suffering from allergies after consuming certain kinds of fruits and vegetables. Typical allergic symptoms range from scratching and itching of the throat to severe symptoms like rhino conjunctivitis and anaphylaxis. For hazelnuts (Corylus avellana), these allergies result from initial sensitization to the birch (Betula verrucosa) pollen allergen Bet v 1 and subsequent development of allergic cross-reactions to proteins that are similar in their three-dimensional structure to the sensitizing protein Bet v 1. The cross-reactive proteins in hazelnut are the four isoforms Cor a 1.04 with a molecular weight of about 17.5 kDa. Significant differences regarding the immunologic behavior of these proteins have been reported. In this work we assigned backbone and side chain 1H, 13C, and 15N chemical shifts of these four isoforms, Cor a 1.0401, Cor a 1.0402, Cor a 1.0403, and Cor a 1.0404 by solution NMR spectroscopy. The chemical shift data confirm the characteristic Bet v onefold for all four isoforms, consisting of seven β-strands that are separated by two short α-helices, along with a long C-terminal α-helix. These data provide the basis for a comparative structural and dynamic analysis of these proteins by NMR in order to characterize their different immunologic cross-reactivities on a molecular level.


Sex as a biological determinant in anthropometric, biochemical, and dietary changes during Ramadan intermittent fasting in healthy people: A systematic review.
Observing Ramadan intermittent fasting (RIF) is associated with different behavioral, dietary, and health-related outcomes among healthy and unwell people. Sex is a major biological determinant that affects various health outcomes and impacts the effectiveness of dietary and lifestyle modifications. This systematic review aimed to identify differences in health-related outcomes following the practice of RIF by the sex of study participants. A systematic search was conducted across several databases to qualitatively identify studies focused on dietary, anthropometric, and biochemical outcomes associated with RIF in females and males. Of 3870 retrieved studies, sex-based differences were reported in 29 studies that included 3167 healthy people (females n = 1558, 49.2%). Most differences between males and females were reported both before and during RIF. Sex differences were examined for 69 outcomes following RIF and included dietary factors (17 outcomes), anthropometrics (13 outcomes), and biochemical factors (39 outcomes), with the latter including metabolic, hormonal, regulatory, inflammatory, and nutrition-related biochemical markers. Sex-based differences were observed in the examined dietary, anthropometric, and biochemical outcomes associated with the observance of RIF. More attention needs to be directed toward including both sexes in studies focused on the impact of observing RIF and differentiating outcomes based on sex.


Neuronal ceroid lipofuscinosis in a German Shorthaired Pointer associated with a previously reported CLN8 nonsense variant.
Two littermate German Shorthaired Pointers, a male and a female, were adopted as puppies from an animal shelter. Both puppies developed normally until approximately 11 months of age when the male began to exhibit neurological signs including ataxia, vision loss, and behavioral changes indicative of cognitive decline. These signs increased in severity over time. The female remained neurologically normal and healthy. The affected dog was euthanized at approximately 21 months of age. Autofluorescent cytoplasmic storage bodies were detected in neurons in unstained tissue sections from the cerebellum, the cerebrum, and the retina. Electron micrographs of these storage bodies showed that they were membrane bound and that most contained tightly packed aggregates of membranous whorls along with a variety of other ultrastructural features. This ultrastructure, along with the autofluorescence and the clinical signs supported a diagnosis of neuronal ceroid lipofuscinosis (NCL). Unlike earlier investigated forms of canine NCL with causal alleles in ATP13A2, TPP1, MFSD8 and CLN5 that had autofluorescent cytoplasmic storage bodies in cardiac muscle, no autofluorescence was detected in cardiac muscle from the affected German Shorthaired Pointer. A 39-fold average coverage whole genome sequence indicated that the affected German Shorthaired Pointer was homozygous for the A allele of a G > A transversion at position 30,895,648 chromosome 37. This 37:30895648G > A mutation created a CLN8 termination codon that had been previously reported to cause NCL in a mixed breed dog with Australian Shepherd and Australian Cattle Dog ancestry. This nonsense allele was heterozygous in the clinically normal female sibling, while archived DNA samples from 512 other German Shorthaired Pointers were all homozygous for the reference allele. The affected German Shorthaired Pointer and the previously diagnosed mixed breed dog with the same nonsense mutation shaired an identical homozygous haplotype that extended for 4.41 Mb at the telomeric end of chromosome 37, indicating the both dogs inherited the nonsense mutation from a common ancestor.


Repair of cranial defects with teflon: a method of cranioplasty in monkeys.
Magnetic resonance imaging demonstrated the need for cranioplasty in experimental neurobehavioral studies with non-human primates. Postoperatively temporal lobes showed substantial deformation of the neocortex due to pressure from the overlying muscle. A new method of cranioplasty using teflon to cover a cranial defect has been developed. Teflon is easily shaped and fitted into place. This method is safe, allows for the natural shape of the brain, provides protection, and is compatible with imaging techniques. Cranioplasty with teflon should be considered whenever craniotomy is necessary for accessing the brain.


The non-apoptotic function of Caspase-8 in negatively regulating the CDK9-mediated Ser2 phosphorylation of RNA polymerase II in cervical cancer.
Cervical cancer is the fourth most frequently diagnosed and fatal gynecological cancer. 15-61% of all cases metastasize and develop chemoresistance, reducing the 5-year survival of cervical cancer patients to as low as 17%. Therefore, unraveling the mechanisms contributing to metastasis is critical in developing better-targeted therapies against it. Here, we have identified a novel mechanism where nuclear Caspase-8 directly interacts with and inhibits the activity of CDK9, thereby modulating RNAPII-mediated global transcription, including those of cell-migration- and cell-invasion-associated genes. Crucially, low Caspase-8 expression in cervical cancer patients leads to poor prognosis, higher CDK9 phosphorylation at Thr186, and increased RNAPII activity in cervical cancer cell lines and patient biopsies. Caspase-8 knock-out cells were also more resistant to the small-molecule CDK9 inhibitor BAY1251152 in both 2D- and 3D-culture conditions. Combining BAY1251152 with Cisplatin synergistically overcame chemoresistance of Caspase-8-deficient cervical cancer cells. Therefore, Caspase-8 expression could be a marker in chemoresistant cervical tumors, suggesting CDK9 inhibitor treatment for their sensitization to Cisplatin-based chemotherapy.


Identification of a novel compound that inhibits both mitochondria-mediated necrosis and apoptosis.
In various pathological events, particularly in oxygen radical-mediated cell injury, both apoptosis and necrosis play essential roles. Apoptosis and some types of necrosis are induced via increases in mitochondrial membrane permeability, called mitochondrial outer membrane permeabilization (MOMP) and permeability transition pore (PTP) opening, respectively. To search for small compounds that inhibit both MOMP-mediated apoptosis and PTP-mediated necrosis, we performed a mitochondria-based high-throughput screening of a chemical library. We identified TMD#7538, a small compound that inhibits both MOMP and PTP opening. Consistent with the fact that this compound inhibited both apoptosis and necrosis, it efficiently suppressed H2O2-induced cell death in mouse embryonic fibroblasts and rat neonatal cardiomyocytes.


Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain.
Substantial evidence indicates involvement of microglia/macrophages in chronic neuropathic pain. However, the temporal-spatial features of microglial/macrophage activation and their pain-bound roles remain elusive. Here, we evaluated microglia/macrophages and the subtypes in the lumbar spinal cord (SC) and prefrontal cortex (PFC), and analgesic-anxiolytic effect of minocycline at different stages following spared nerve injury (SNI) in rats. While SNI enhanced the number of spinal microglia/macrophages since post-operative day (POD)3, pro-inflammatory MHCII+ spinal microglia/macrophages were unexpectedly less abundant in SNI rats than shams on POD21. By contrast, less abundant anti-inflammatory CD172a (SIRPα)+ microglia/macrophages were found in the PFC of SNI rats. Interestingly in naïve rats, microglial/macrophage expression of CD11b/c, MHCII and MHCII+/CD172a+ ratio were higher in the SC than the cortex. Consistently, multiple immune genes involved in anti-inflammation, phagocytosis, complement activation and M2 microglial/macrophage polarization were upregulated in the spinal dorsal horn and dorsal root ganglia but downregulated in the PFC of SNI rats. Furthermore, daily intrathecal minocycline treatment starting from POD0 for two weeks alleviated mechanical allodynia most robustly before POD3 and attenuated anxiety on POD9. Although minocycline dampened spinal MHCII+ microglia/macrophages until POD13, it failed to do so on cortical microglia/macrophages, indicating that dampening only spinal inflammation may not be enough to alleviate centralized pain at the chronic stage. Taken together, our data provide the first evidence that basal microglial/macrophage traits underlie differential region-specific responses to SNI and minocycline treatment, and suggest that drug treatment efficiently targeting not only spinal but also brain inflammation may be more effective in treating chronic neuropathic pain.


Hormone replacement therapy for survivors of breast and endometrial cancer.
Indirect evidence suggests that endogenous and exogenous estrogen does not influence the outcome of patients treated for breast or endometrial cancer. However, many reports have affirmed beneficial effects of hormone replacement therapy (HRT) in preventing multiple disease states and improving the quality of life of individual patients. Every practitioner of urogynecology understands the benefits of local and systemic therapy to women who suffer from urinary incontinence and/or loss of pelvic floor support. Thus, it seems appropriate to suggest that survivors of breast or endometrial cancer who request information on HRT for relief of their menopausal symptoms and for other benefits, of which patients are becoming increasingly aware, deserve a comprehensive explanation.


Polyphasic study of Chryseobacterium strains isolated from diseased aquatic animals.
Members of most Chryseobacterium species occur in aquatic environments or food products, while strains of some other species are pathogenic to humans and animals. A collection of 52 Chryseobacterium sp. strains isolated from diseased fish, one frog isolate and 22 reference strains were included in a polyphasic taxonomy study. Fourteen clusters of strains were delineated following the comparison of whole-cell protein profiles. Most of these clusters were confirmed when the phenotypic and RAPD profiles and the 16S rRNA gene sequences were compared. Fatty acid composition helped differentiate the Chryseobacterium strains from members of related genera. None of the fish isolates could be allocated to the two species previously reported from fish but two isolates belonged to C. joostei, while the frog isolate was identified as Elizabethkingia meningoseptica, a human pathogen previously included in the genus Chryseobacterium. Three clusters grouping from 3 to 13 isolates will probably constitute the core of new Chryseobacterium species but all other isolates occupied separate or uncertain positions in the genus. This study further demonstrated the overall high similarity displayed by most Chryseobacterium strains whatever the technique used and the resulting difficulty in delineating new species in the genus. Members of this bacterial group should be considered potential emergent pathogens in various fish and frog species, farming conditions and geographical areas.


Zinc in elderly people: effects of zinc supplementation on psychological dimensions in dependence of IL-6 -174 polymorphism: a Zincage study.
Zinc is relevant for psychological dimensions, which are altered in zinc deficiency, as in aging. Since zinc deficiency and the beneficial effect of zinc supplementation may be related to genotypes of IL-6 -174 polymorphism, the main goal was to examine psychological dimensions in relationship to plasma zinc and genetic background of IL-6 in healthy elderly subjects, recruited in Italy, Greece, and Poland, before and after zinc supplementation. On the basis of IL-6 -174 polymorphism, significant restoration occurs for PSS, especially in Greece and Poland, less for MMSE and GDS, after zinc supplementation, suggesting zinc is important in reducing stress in elderly people.