Protective effect of Luffa cylindrica Roemer against dexamethasone-induced muscle atrophy in primary rat skeletal muscle cells.
Glucocorticoids (GCs) are commonly used in the treatment of chronic inflammatory conditions. However, the administration of high doses and long-term use of GCs can induce muscle atrophy (MA) in patients, leading to a decline in quality of life and increased mortality. MA leads to protein degradation in skeletal muscle, resulting in a reduction of muscle mass. This process is triggered by GCs like dexamethasone (DEX), which induce the expression of E3 ubiquitin ligases, namely Atrogin-1 and muscle RING-finger protein-1 (MuRF1). In this study, we examined the anti-MA potential of Luffa cylindrica Roemer (LCR) on DEX-treated primary skeletal myotubes. Primary skeletal myotubes stimulated with LCR alone resulted in a significant upregulation of myotube development, characterized by an increase in both the number and diameter of myotubes. Contrastingly, combined treatment with LCR and DEX reduced the expression of Atrogin-1, while treatment with DEX alone induced the expression of MuRF1. Furthermore, LCR treatment successfully restored the number and diameter of myotubes that had been diminished by DEX treatment. These findings suggest that LCR holds potential for treating MA, as an accelerating effect on muscle development and anti-MA effects on primary skeletal muscle cells were observed.


Novel Two-Dimensional Porous Materials for Electrochemical Energy Storage: A Minireview.
Two dimensional (2D) porous materials have great potential in electrochemical energy conversion and storage. Over the past five years, our research group has focused on Simple, Mass, Homogeneous and Repeatable Synthesis of various 2D porous materials and their applications for electrochemical energy storage especially for supercapacitors (SCs). During the experimental process, through precisely controlling the experimental parameters, such as reaction species, molar ratio of different ions, concentration, pH value of reaction solution, heating temperature, and reaction time, we have successfully achieved the control of crystal structure, composition, crystallinity, morphology, and size of these 2D porous materials including transition metal oxides (TMOs), transition metal hydroxides (TMHOs), transition metal oxalates (TMOXs), transition metal coordination complexes (TMCCs) and carbon materials, as well as their derivatives and composites. We have also named some of them with CQU-Chen (CQU is the initialism of Chongqing University, Chen is the last name of Lingyun Chen), such as CQU-Chen-Co-O-1, CQU-Chen-Ni-O-H-1, CQU-Chen-Zn-Co-O-1, CQU-Chen-Zn-Co-O-2, CQU-Chen-OA-Co-2-1, CQU-Chen-Co-OA-1, CQU-Chen-Ni-OA-1, CQU-Chen-Gly-Co-3-1, CQU-Chen-Gly-Ni-2-1, CQU-Chen-Gly-Co-Ni-1, etc. The introduction of 2D porous materials as electrode materials for SCs improves the energy storage performances. These materials provide a large number of active sites for ion adsorption, supply plentiful channels for fast ion transport and boost electrical conductivity and facilitate electron transportation and ion penetration. The unique 2D porous structures review is mainly devoted to the introduction of our contribution in the 2D porous nanostructured materials for SC. Finally, the further directions about the preparation of 2D porous materials and electrochemical energy conversion and storage applications are also included.


Improved TV-CS Approaches for Inverse Scattering Problem.
Total Variation and Compressive Sensing (TV-CS) techniques represent a very attractive approach to inverse scattering problems. In fact, if the unknown is piecewise constant and so has a sparse gradient, TV-CS approaches allow us to achieve optimal reconstructions, reducing considerably the number of measurements and enforcing the sparsity on the gradient of the sought unknowns. In this paper, we introduce two different techniques based on TV-CS that exploit in a different manner the concept of gradient in order to improve the solution of the inverse scattering problems obtained by TV-CS approach. Numerical examples are addressed to show the effectiveness of the method.


Transverse testicular ectopia with persistent Muellerian duct syndrome.
A one-year-old boy was admitted with complaints of swelling in the left inguinoscrotal region and an empty right scrotum since birth. The inguinoscrotum contained two ovoid solid swellings one above the other. The swellings were testes like in feel, size and shape. The diagnosis was transverse testicular ectopia. The case was managed by surgery. Tissue from gonads, the tubular structures and the fallopian tubes were sent for histopathological examination for confirmation. This was a case of an otherwise normal male with transverse testicular ectopia with persistent Muellerian duct syndrome in the left inguinoscrotal hernial sac.


Local current injection into mesoscopic superconductors for the manipulation of quantum states.
We perform strategic current injection in a small mesoscopic superconductor and control the (non)equilibrium quantum states in an applied homogeneous magnetic field. In doing so, we realize a current-driven splitting of multiquanta vortices, current-induced transitions between states with different angular momenta, and current-controlled switching between otherwise degenerate quantum states. These fundamental phenomena form the basis for the electronic and logic applications discussed, and are confirmed in both theoretical simulations and multiple-small-tunnel-junction transport measurements.


Thermal quantitative sensory testing in healthy Dutch children and adolescents standardized test paradigm and Dutch reference values.
Quantitative sensory testing (QST) is often used to measure children's and adults' detection- and pain thresholds in a quantitative manner. In children especially the Thermal Sensory Analyzer (TSA-II) is often applied to determine thermal detection and pain thresholds. As comparisons between studies are hampered by the different testing protocols used, we aimed to present a standard protocol and reference values for thermal detection- and pain thresholds in children. Our standard testing protocol includes reaction time dependent and independent tests and takes about 14-18 min to complete. Reference values were obtained from a sample of 69 healthy term born children and adolescents with a median age of 11.2 years (range 8.2 to 17.9 years old). Seventy-one children were recruited and data of 28 males and 41 females was obtained correctly. We studied possible age and sex differences. This study provides Dutch reference values and presents a standard quantitative sensory testing protocol for children with an age from 8 years onwards. This protocol appeared to be feasible, since only two out of 71 participants were not able to correctly complete the protocol due to attention deficits and were therefore excluded. We found some significant age and sex differences: females were statistically significantly more sensitive for both cold and heat pain compared to males, and the youngest children (8-9 years old) were less sensitive to detect a warm stimulus. The youngest children tend to be more sensitive to heat pain in comparison to older participants, although the difference was not statistically significant. We present a feasible thermal quantitative sensory testing protocol for children and reference values that are easy to interpret and may serve as normative values for future studies.


Molecular Methods to Detect and Quantify Botryosphaeriaceae Inocula Associated With Grapevine Dieback in Australia.
Botryosphaeria dieback, caused by species of Botryosphaeriaceae, is an important grapevine trunk disease in Australia. Inocula produced by the pathogens are primarily dispersed by rain splash and wind and infect pruning wounds leading to cankers, dieback, and eventually death of vines. The objective of this study was to develop molecular tools to detect and quantify Botryosphaeriaceae inocula from the environment. These tools are essential for investigating spore dispersal patterns of Botryosphaeriaceae pathogens in Australian vineyards. DNA extraction protocols were evaluated and one modified protocol was found suitable for extracting Botryosphaeriaceae DNA from artificially and naturally inoculated Burkard volumetric spore sampler tapes. Multispecies primers and a hydrolysis probe for quantitative PCR (qPCR) were further developed to detect and quantify Botryosphaeriaceae inocula from environmental samples. Specificity tests showed that the multispecies primers were able to amplify the DNA of 10 Botryosphaeriaceae species (58 isolates) found in Australia while none of the 27 nontarget fungal species (90 isolates) tested were amplified. The qPCR assay was suitable for amplifying purified DNA, synthetic DNA fragments (gBlocks), and mixed DNA from spore trap tapes. The qPCR method developed in this study was shown to be rapid and sensitive in detecting Botryosphaeriaceae inocula from the environment using spore traps.


[Vertebral osteomyelitis caused by Rhodococcus equi in a three-and-half-month-old Dutch Warmblood foal].
Rhodococcus equi infection occurs worldwide and is especially a problem in foals, where it often causes colitis or pneumonia. Other organs are seldom affected, and their involvement is regarded as a complication of pneumonia and/or colitis. Vertebral osteomyelitis is one such rare complication and is probably caused by haematogenous spread from inflammatory lesions in the lungs and/or intestine. In rare cases, osteomyelitis can be caused by contamination of a wound. This case study describes a foal with vertebral osteomyelitis due to R. equi in which there were only minor inflammatory changes in a mesenteric lymph node.


Paraffin-Enabled Compressive Folding of Two-Dimensional Materials with Controllable Broadening of the Electronic Band Gap.
The capability to manipulate the size of the electronic band gap is of importance to semiconductor technology. Among these, a wide direct band gap is particularly helpful in optoelectronic devices due to the efficient utilization of blue and ultraviolet light. Here, we reported a paraffin-enabled compressive folding (PCF) strategy to widen the band gap of two-dimensional (2D) materials. Due to the large thermal expansion coefficient of paraffin, folded 2D materials can be achieved via thermal engineering of the paraffin-assisted transfer process. It can controllably introduce 0.2-1.3% compressive strain onto folded structures depending on the temperature differences and transfer the folding product to both rigid and soft substrates. Exemplified by MoS2, its folded multilayers demonstrated blue-shifts at direct gap transition peaks, six times stronger photoluminescence intensity, almost double mobility, and 20 times higher photoresponsivity over unfolded MoS2. This PCF strategy can attain controllable widening band gap of 2D materials, which will open up novel applications in optoelectronics.


Heterotopic Ossification in a Newborn: A Case Report.
Introduction: Heterotopic ossification is defined as the formation of trabecular bone that forms outside the normal sites of the skeletal structure, materializing in soft tissue where it does not usually exist. Methods/Case Report: This is a case report of a 27-day-old baby with a diagnosis of DiGeorge syndrome who developed heterotopic ossification on the dorsum of his right hand. Discussion: Heterotopic ossification in the pediatric population is a rare finding. Very few cases were published in the literature, and we find it important to increase the knowledge on such cases and discuss possible causes with the treatment used with our patient. Results: General treatments of heterotopic ossification include ruling out superimposed infection, physiotherapy to prevent joint involvement, warm compressors during the active phase of development of heterotopic ossification. If the swelling persists to the point that it interferes significantly with the functional capacity of the patient or becomes a cosmetic concern, the only treatment option remaining would be surgery.


The effect of local infection upon wound healing: an experimental study.
Local infection was introduced into rat abdominal wounds using a 10(8) bacterial/ml inoculum. Three groups of infection were used: Staphylococcus aureus, Pseudomonas aeruginosa and a combination group of Escherichia coli and Proteus mirabilis. Infection was shown to delay healing as judged by bursting tests. Fibroblast proliferation was depressed at the wound edges but there was an increase in the total amount of hydroxyproline present. Small vessel angiogenesis was increased in areas of abscess formation but larger vessels were commonly blocked by thrombus or distorted by surrounding inflamed tissue. The possible causes of these effects are discussed.


Molecular cloning and analysis of cDNA sequences derived from poly A+ RNA from barley endosperm: identification of B hordein related clones.
A collection of over 130 cDNA clones has been constructed in the bacterial plasmids pPH207 and pBR322 using as template the poly A+ RNA from membrane-bound polysomes of barley endosperm (cv. Sundance). Fifty four B hordein cDNA clones have been identified by cross-hybridization analysis and in vitro translation of plasmid-selected mRNAs. Hybridization of 11 of the B hordein cDNA clones to Northern blots of size-fractionated RNA indicated that the B hordein mRNA is ca. 1300 nucleotides long. One cDNA clone, pHvE-c16, has been partially sequenced and shown by comparison with C-terminal and other peptide sequences to be related to B1 hordein polypeptides. The results obtained from the analysis of the B hordein cDNA clones support the idea that the Hor 2 locus, which specifies the B hordeins, is complex and codes for a family of related mRNA species.


Fluorometric studies on the blood-retinal barrier in experimental animals.
Fluorophotometry was used to evaluate the blood-ocular barrier in rats following streptozocin-induced diabetes, experimental systemic hypertension, sodium iodate treatment, diet-induced galactosemia, and aldose reductase inhibitors. After administration of intravenous (IV) fluorescein sodium, diabetes, hypertension, or sodium iodate treatment resulted in an increased vitreous accumulation of IV fluorescein. Accumulation of dextran-labeled fluorescein (3,000 and 19,000 molecular weight [mol wt]) was not increased in diabetic or sodium iodate-treated animals. However, 3,000-mol wt dextran-labeled dye accumulated in the vitreous of hypertensive rats. The disappearance of fluorescein injected into the vitreous was significantly delayed in diabetic and sodium iodate-treated rats, whereas this rate was normal in hypertension animals. Galactosemia did not alter vitreous fluorophotometric measurements. Pretreatment for systemic effects with aldose reductase inhibitors did not correct the vitreous fluorophotometric measurements of diabetic rats.


Generation of nine induced pluripotent stem cell lines as an ethnic diversity panel.
Human induced pluripotent stem cells (iPSCs) provide a potentially unlimited source of differentiated cells from individuals with specific genetic backgrounds. Using self-replicative RNA reprogramming technology, we generated nine iPSC lines from endothelial progenitor cells (EPCs) derived from blood samples of three different ethnicities: Black or African American, Latino or Hispanic, and Non-Hispanic White. The resulting iPSC lines showed normal karyotype in large part, expressed pluripotency marker genes, and spontaneously differentiated in vitro into the three germ layers. These iPSC lines offer the potential to generate tissues with ethnic diversity, and thus afford a valuable tool for ethnic-related toxicological applications.


Birthing Consciousness as a Case of Adaptive Altered State of Consciousness Associated With Transient Hypofrontality.
In this article, I present the concept of "birthing consciousness," a psychophysical altered state of women that can occur during natural and undisturbed birth. I demonstrate that this altered state of consciousness (ASC) has phenomenological and cognitive features of hypofrontality; thus, birthing consciousness probably shares a similar brain mechanism to that postulated by the transient-hypofrontality theory (THT). I argue that until recently (with the advent of modern medical intervention), in evolutionary terms, women lacking the proclivity for this specific brain mechanism had a lower chance of reproducing successfully. Hence, I suggest a general and preliminary hypothesis concerning THT: Birthing consciousness is one example of an adaptive pain-induced ASC associated with transient hypofrontality.


RNF6 Promotes Colorectal Cancer by Activating the Wnt/β-Catenin Pathway via Ubiquitination of TLE3.
Gene amplification is a hallmark of cancer and is frequently observed in colorectal cancer. Previous whole-genome sequencing of colorectal cancer clinical specimens identified amplification of Ring finger protein 6 (RNF6), a RING-domain E3 ubiquitin ligase. In this study, we showed that RNF6 is upregulated in 73.5% (147/200) of patients with colorectal cancer and was positively associated with RNF6 gene amplification. Furthermore, RNF6 expression and its gene amplification were independent prognostic factors for poor outcome of patients with colorectal cancer. RNF6 promoted cell growth, cell-cycle progression, and epithelial-to-mesenchymal transition in colorectal cancer cells; RNF6 also promoted colorectal tumor growth and lung metastasis in mouse models. Mechanistic investigations revealed that RNF6 bound and ubiquitylated transducin-like enhancer of split 3 (TLE3), a transcriptional repressor of the β-catenin/TCF4 complex. RNF6-mediated degradation of TLE3 significantly suppressed the association of TLE3 with TCF4/LEF, which in turn led to recruitment of β-catenin to TCF4/LEF, triggering Wnt/β-catenin activation. Restoration of TLE3 expression abolished the oncogenic effects of RNF6. Taken together, these results demonstrate that RNF6 plays a pivotal oncogenic role in colorectal tumorigenesis.Significance: RNF6-mediated ubiquitination and degradation of TLE3 activates the Wnt/β-catenin pathway in colorectal carcinogenesis. Cancer Res; 78(8); 1958-71. ©2018 AACR.


Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells.
We recently cloned IRS-4, a new member of the insulin receptor substrate (IRS) family. In this study we have characterized IRS-4 in human embryonic kidney 293 cells, where it was originally discovered. IRS-4 was the predominant insulin-elicited phosphotyrosine protein in these cells. Subcellular fractionation revealed that about 50% of IRS-4 was located in cellular membranes, and immunofluorescence indicated that IRS-4 was concentrated at the plasma membrane. Immunoelectron microscopy conclusively established that a large portion of the IRS-4 was located at the cytoplasmic surface of the plasma membrane in both the unstimulated and insulin-treated states. IRS-4 was found to be associated with two src homology 2 (SH2) domain-containing proteins, phosphatidylinositol 3-kinase and Grb2, the adaptor to the guanine nucleotide exchange factor for Ras. On the other hand, no significant association was detected with two other SH2 domain proteins, the SH2-containing protein tyrosine phosphatase 2 and phospholipase Cgamma. Insulin-like growth factor I acting through its receptor was as effective as insulin in eliciting tyrosine phosphorylation of IRS-4, but interleukin 4 and epidermal growth factor were ineffective.


The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer.
MET overexpression and the EGFR T790M mutation are both associated with acquired resistance (AR) to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC). We characterized the frequency, underlying molecular mechanisms, and subsequent treatment for AR in MET overexpressing NSCLC patients with or without the T790M mutation. The study participants were 207 patients with advanced NSCLC and AR to EGFR-TKIs. The percentages of MET-, T790M- and MET/T790M-positive patients were 20.3% (42/207), 34.8% (72/207) and 6.8% (14/207), respectively. The disease control rate was 100% (5/5) for five patients with MET overexpression who received EGFR-TKIs plus a MET inhibitor. Among the MET/T790M-positive patients, seven received EGFR-TKIs plus a MET inhibitor and four received a T790M inhibitor, but no response was observed. The median post-progression survival (PPS) was 14.1, 24.5, and 10.7 months for MET-overexpressing, T790M-positive and MET/T790M-positive patients, respectively (P=0.044). c-Met, p-Met, ERBB3, and p-ERBB3 were highly expressed in MET-positive and MET/T790M-positive patients, but were poorly expressed in T790M-positive patients. EGFR, p-EGFR, AKT, p-AKT, MAPK, and p-MAPK were highly expressed in all three groups. These results suggest that MET/T790M-positive patients are at higher risk of AR to EGFR-TKIs, and have a worse PPS than patients with only MET overexpression or the T790M mutation alone. Clinical trials are needed to determine the best treatment for patients with both MET overexpression and the EGFR T790M mutation.


Ripening and genotype control stilbene accumulation in healthy grapes.
In grapes, stilbene synthesis occurs in the skin, and it is induced by biotic and abiotic stresses. To date, experimental evidence of a constitutive production of resveratrols in healthy grape is scarce and not conclusive. The aim of the present work was to investigate stilbene biosynthesis in healthy grapes both at biochemical and molecular levels. By measuring the concentration of resveratrols in ripe berries of 78 Vitis vinifera varieties for 3 years, we could identify significant differences among genotypes, providing the first tentative varietal classification based on resveratrol content. Furthermore, an increasing stilbene accumulation from veraison to ripening phase was also observed. Using real-time reverse transcription polymerase chain reaction and a berry-specific cDNA array, gene expression analysis was carried out on two distinct pools of berries belonging to the high and low resveratrol producers and on three berry developmental stages. The stilbene synthase, phenylalanine ammonia-lyase, and 4-coumarate-CoA ligase expression profiles showed an increasing concentration of these transcripts from véraison to maturity and a higher accumulation in the grape of high resveratrol producers. Macroarray data analysis revealed that high resveratrol levels are also accompanied by the up-regulation of genes involved in plant defense and the concomitant underexpression of genes related to the ripening process and to indole alkaloid synthesis.


Infrequent transmission of HIV-1 drug-resistant variants.
Transmission of drug-resistant variants is influenced by several factors, including the prevalence of drug resistance in the population of HIV-1-infected patients, HIV-1 RNA levels and transmission by recently infected patients. In order to evaluate the impact of these factors on the transmission of drug-resistant variants, we have defined the population of potential transmitters and compared their resistance profiles to those of newly infected patients. Sequencing of pol gene was performed in 220 recently infected patients and in 373 chronically infected patients with HIV-1 RNA >1000 copies/ml. Minimal and maximal drug-resistance profiles of potential transmitters were estimated by weighting resistance profiles of chronically infected patients with estimates of the Swiss HIV-1-infected population, the prevalence of exposure to antiviral drugs and the proportion of infections attributed to primary HIV infections. The drug-resistance prevalence in recently infected patients was 10.5% (one class drug resistance: 9.1%; two classes: 1.4%; three classes: 0%). Phylogenetic analysis revealed significant clustering for 30% of recent infections. The drug-resistance prevalence in chronically infected patients was 72.4% (one class: 29%; two classes: 27.6%; three classes: 15.8%). After adjustment, the risk of transmission relative to wild-type was reduced both for one class drug resistance (minimal and maximal estimates: odds ratio: 0.39, P<0.001; and odds ratio: 0.55, P=0.011, respectively), and for two to three class drug resistance (odds ratios: 0.05 and 0.07, respectively, P<0.001). Neither sexual behaviour nor HIV-1 RNA levels explained the low transmission of drug-resistant variants. These data suggest that drug-resistant variants and in particular multidrug-resistant variants have a substantially reduced transmission capacity.


Metformin inhibits TNF-alpha-induced IkappaB kinase phosphorylation, IkappaB-alpha degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation.
Metformin has been reported to reduce cardiovascular complications in diabetic patients. The purpose of the present study was to investigate the anti-inflammatory effects of metformin on endothelial cells and the related molecular mechanisms. Human umbilical vein endothelial cells (HUVEC) were used for the experiments. The effects of metformin on TNF-alpha-induced IL-6 production were investigated. Modulation of AMPK and related signal transduction pathways were also performed. TNF-alpha increased IL-6 secretion by HUVEC in a dose-dependent manner but inhibitors of NF-kappaB abolished the TNF-alpha-induced IL-6 production. Pre-treatment with metformin (100-1000 micromol/L) also inhibited TNF-alpha-induced IL-6 production, phosphorylation of IkappaB kinase (IKK) alpha/beta and IkappaB-alpha degradation. Metformin increased phosphorylation of AMP-activated kinase (AMPK) but wortmannin, a PI3K inhibitor, negated its effects on AMPK phosphorylation and TNF-alpha-induced IkappaB-alpha degradation. AICAR, a direct AMPK activator, had inhibitory effects on TNF-alpha-induced IL-6 production, similar to that of metformin. Transfection of siRNA against alpha1-AMPK eradicated the inhibitory effects of metformin on TNF-alpha-induced IL-6, implying the essential role of AMPK. Metformin had anti-inflammatory effects on endothelial cells and inhibited TNF-alpha-induced IKKalpha/beta phosphorylation, IkappaB-alpha degradation and IL-6 production in HUVEC. This effect was related to PI3K-dependent AMPK phosphorylation.


Hydrazinolysis of glycosphingolipids. A new method for preparation of N-deacylated (lyso) glycosphingolipids.
A useful method for N-deacylation of the ceramide moiety of glycosphingolipids has been developed. Galactosylceramide, glucosylceramide, lactosylceramide, and galactosyllactosylceramide were effectively deacylated by heating with anhydrous hydrazine at 150 degrees C for 15-25 h. The lyso-derivative as the deacylated product of the ceramide moiety of each glycosphingolipid was isolated by preparative silica gel thin layer chromatography with a 70-85% yield from the starting glycolipids. Hydrazine sulfate was an effective catalyst for the deacylation of the ceramide moiety. No dissociation of oligosaccharide moieties of the glycolipids on hydrazinolysis was confirmed by gas chromatographic analysis and N-acylation of these lysoderivatives. The free amino groups of the lysoglycosphingolipids can be combined with various kinds of probes giving useful derivatives for biochemical and immunological studies on glycosphingolipids.


Carotid endarterectomy in patients with asymptomatic intracranial aneurysm.
The patient with symptomatic extracranial carotid artery disease who, on angiography, is found to have a coexisting intracranial aneurysm presents a therapeutic dilemma. Relief of the carotid stenosis, with a potential increase in cerebral blood pressure, might increase the risk of aneurysm rupture. Conversely, repair of the aneurysm may be hazardous because of the low flow imposed by the carotid stenosis, particularly in the event of perioperative hypotension. We reviewed 19 patients treated with 20 carotid endarterectomies in the face of concurrent asymptomatic intracranial aneurysm. There were no instances of aneurysm rupture during the operation or the 30 days following operation. The literature reported to date consists of a total of 20 patients with only one incidence of aneurysm rupture in the postoperative period. We conclude that carotid endarterectomy is unlikely to precipitate rupture of an intracranial aneurysm during the operation or postoperative period.


Nuclear membrane fusion in fertilized Lytechinus variegatus eggs.
Fusion of apposed nuclear envelopes is frequently seen at telophase during postmitotic reorganization of the nucleus, but only rarely at other times in the cell cycle. We attempted to define an experimental system for studying changes in the nuclear envelope related to the cell cycle by varying the time of pronuclear apposition in fertilized Lytechinus variegatus eggs. This approach was based on the assumption that the period from fertilization to metaphase of the first cleavage division corresponds to the period from telophase to metaphase in the generalized cell cycle. The experimental approach used was to block the movement of the pronuclei with Colcemid and then to release this block at varying times after insemination by photochemically inactivating the Colcemid. The results show that apposed pronuclear envelopes can fuse from soon after insemination until the anticipated time of prometaphase. Fusion occurred in about 3 min as scored by light microscopy and this time did not vary significantly with the time after insemination. The potential for nuclear fusion is not restricted to pronuclei alone since diploid nuclei in binucleate cells could be fused using centrifugation in solutions of Colcemid to bring the nuclei into apposition. It is suggested that the potential for nuclear fusion is not necessarily related to the cell cycle and that modification of the nuclear envelope, possibly by association with chromatin or other fibrous material restricts nuclear fusion in most multinucleated cells.


Usefulness of cone beam computed tomography for odontogenic myxoma.
A case of odontogenic myxoma is reported as showing a cyst-like pattern with a partially thick but vague and unclear radiopaque border between the left mandibular second premolar and first molar on rotational panoramic radiography. Internal structure of the lesion displayed radiolucency with a sparse and coarse trabecular pattern. No expansion of bucco-lingual cortical bone was apparent. The radiographic pattern of odontogenic myxoma did not resemble a tennis racket-like or straight, curved and coarse septal appearance on panoramic radiography, but characteristic findings were noted on cone beam CT. Cone beam CT may prove extremely useful in clarifying detailed internal structure and the state of margins.


Thoracic intramedullary melanocytoma with long-term follow-up.
Melanocytomas are tumors of the neuraxis seen predominantly in adults. The authors report a case of a thoracic intramedullary melanocytoma with long-term follow-up of 8 years postsurgery. Melanocytomas, although rare, must be included in the differential diagnosis of intramedullary spinal cord tumors.


Effect of the contraceptive sponge on chlamydial infection, gonorrhea, and candidiasis. A comparative clinical trial.
To investigate the effect of the nonoxynol 9-impregnated contraceptive sponge on the incidence of chlamydial infection, gonorrhea, and candidiasis, we conducted a randomized comparative study among high-risk women in Bangkok, Thailand. The first (parallel) portion of the study covered 434 woman-weeks among sponge users and 494 woman-weeks among nonusers. As compared with women not using the sponge, sponge users were found to be less likely to become infected with chlamydia (relative rate, 0.67; 95% confidence interval, 0.42 to 1.07) and gonorrhea (relative rate, 0.31 [0.16 to 0.60]) but more likely to become infected with Candida (relative rate, 2.76 [0.96 to 7.98]). Women who continued in the study were crossed over to the alternate group, with former nonusers starting to employ the sponge and vice versa. The results of this second phase were similar to those of the larger parallel study. Overall, these results suggest that women using the sponge are protected against the two most common sexually transmitted pathogens, which are also those with the most serious health consequences. However, women using the sponge should be advised they may have an increased likelihood of a vaginal infection with Candida.


[Routes of approach to the vidian nerve (author's transl)].
The authors describe the various routes of approach to the deep recesses of the pterygo-maxillary fossa. A brief historical review indicates the importance of the work of Golding-Wood who started this type of surgery. Description of the personal technique of the authors via a trans-maxillary approach. Review of the endo-nasal approach of Poch-Vinals by cryotherapy and of M. Port mann by electro-coagulation. A parallel is then drawn between the trans-maxillary approach and the endo-nasal approach of Prades by dissection from the spheno-palatine orifice. The respective indications are discussed.


The effects of molybdenum water concentration on feedlot performance, tissue mineral concentrations, and carcass quality of feedlot steers,.
Thirty cross-bred steers (initial BW 452.0 ± 12.1 kg) were used to investigate the effects of Mo water concentration on performance, carcass characteristics, and mineral status of feedlot steers. The experimental design was a randomized complete block design. Steers were blocked by weight and then divided into 2 weight blocks each consisting of 15 steers. Steers were randomly assigned within block to one of 5 treatments (3 steers/treatment per block). Water treatments consisted of: 1) 0.0 µg/L, 2) 160 µg/L, 3) 320 µg/L, 4) 480 µg/L, and 5) 960 µg/L of supplemental Mo added as Na2MoO4 to the drinking water. Steers were housed in individual pens (steer = experimental unit) that contained individual 265 L water tanks for monitoring water intake. Steers were fed a growing diet for 28 d and then transitioned to a finishing diet. Block 1 steers were fed for a total of 151 d and block 2 steers were fed for a total of 112 d. Daily water intake was recorded for each steer. Steers were individually weighed on 2 consecutive days at the beginning and end of the experiment and interim weights and jugular blood samples were obtained every 28 d. Liver biopsies were obtained on d 0 and 84 from each steer within each block. Steers were transported to a commercial abattoir, slaughtered, and individual carcass data and liver samples were collected. Initial BW was used as a covariate for statistical analysis of data and significance was determined at P ≤ 0.05. No differences were observed for final BW (P > 0.98). Overall ADG (P > 0.91), DMI (P > 0.92), feed efficiency (P > 0.94), water intake (P > 0.40), hot carcass weight (P > 0.98), dressing percentage (P > 0.98), yield grade (P > 0.91), and marbling score (P > 0.29) did not differ across treatments. Lastly, no treatment differences were observed for liver concentrations of Cu (P > 0.93), Mo (P > 0.90) and Zn (P > 0.86) or plasma concentrations of Cu (P > 0.42), Mo (P > 0.43) and Zn (P > 0.62). These data indicate that water Mo concentration, within the range studied, had no impact on performance, mineral status, water intake, and carcass characteristics in feedlot steers.


Involvement of prolactin in the meloxicam-dependent inflammatory response of the gonadotropic axis to prolonged lipopolysaccharide treatment in anoestrous ewes.
An immune challenge can affect the reproductive process in females. Peripheral administration of bacterial endotoxin (lipopolysaccharide; LPS) decreases LH secretion and disrupts ovarian cyclicity. The aim of the present study was to determine the effects of a cyclo-oxygenase (COX)-2 inhibitor (meloxicam) on gonadotropin-releasing hormone (GnRH) and LH secretion in anoestrous ewes during systemic inflammation induced by LPS. LPS (400ngkg-1 per day) suppressed LH release. In three individuals, meloxicam (500μgkg-1, i.v.) abolished LPS-induced LH suppression. In another three ewes LH was ineffective. Similar changes were observed in hypothalamic GnRH expression. The effect of meloxicam depended on the circulating level of prolactin: meloxicam abolished inflammatory-dependent suppression of GnRH and LH secretion when plasma prolactin levels were similar to those in untreated animals, but was ineffective in those with elevated levels of prolactin. We conclude that COX-2 inhibitors minimise the negative effect of inflammation on the reproductive system but that this effect may be antagonised by prolactin.


Inhibition of histone deacetylase activity causes cell type-specific induction of the PDGF-B promoter only in the absence of activation by its enhancer.
There is a strong correlation between the acetylation status of nucleosomal histones and transcriptional activity. Here we show that the histone deacetylase inhibitor trichostatin A (TSA) activates reporter gene constructs driven by the human platelet-derived growth factor B (PDGF-B) gene promoter. This activation showed an inverse correlation with the cell type-specific transcriptional activities of the promoter. The TSA response was minimal in three tumor cell lines that exhibit high-level promoter activity. In JEG-3 choriocarcinoma cells, however, where the basal promoter activity is considerably lower, there was a strong response to TSA. This was in contrast to constructs that included a PDGF-B enhancer, which were refractory to TSA effects, indicating a possible function of the enhancer in modulating acetylation status. Analysis of PDGF-B promoter mutants with respect to TSA induction revealed no specific TSA-responsive element, but suggested that association of nonacetylated histones to the PDGF-B promoter may be a default process in the absence of enhancer activation. TSA treatment of JEG-3 cells, either alone or in combination with the demethylating agent 5-azacytidine, failed to activate the silenced endogenous PDGF-B transcript, however, which appears to be repressed by additional mechanisms.


Cingulate function in depression: a potential predictor of treatment response.
The relationship between pretreatment regional cerebral glucose metabolism and eventual antidepressant drug response was measured using positron emission tomography (PET) in hospitalized patients with unipolar depression. Rostral anterior cingulate metabolism uniquely differentiated eventual treatment responders from non-responders. Hypometabolism characterized non-responders when compared with controls, in contrast to responders who were hypermetabolic. Metabolism in no other region discriminated the two groups, nor did associated demographic, clinical or behavioral measures, including motor speed, cognitive performance, depression severity or illness chronicity. Cingulate hypermetabolism may represent an important adaptive response to depression and failure of this response may underlie poor outcome. A critical role for rostral cingulate area 24a/b in the limbic-cortical network involved in abnormal mood states is proposed.


Mediastinal fibrosis complicating histoplasmosis.
Mediastinal fibrosis, the most serious late complication of remote infection by Histoplasma capsulatum, is a thick, dense fibrotic capsule which surrounds a small mediastinal focus of old caseous adenitis. The fibrotic process may accrue over prolonged periods and extend within the lumina of critical mediastinal structures to produce complete occlusion. We summarized clinical and radiographic data for 71 patients with mediastinal fibrosis; the criteria for inclusion were the clinical demonstration of occlusion of major central airways (trachea or mainstem bronchus) or major vessels (pulmonary arteries or veins) and the absence of other disease processes which might cause such obstruction. We selected 65 patients who met these criteria from the medical literature of the last 40 years and report 6 new cases from our experience. The majority of patients were diagnosed between ages 20 and 40. The most common symptoms included hemoptysis, dyspnea, and cough. An accentuated pulmonic component of the second heart sound, wheezing, and localized murmur were among the physical findings reported. Radiographic abnormalities consisted of mass lesions and atelectasis or infiltrates, but were often nonspecific. Chest radiography was deceptively normal in some patients, even in the presence of major central airway or vascular occlusion, especially when the focus was subcarinal. Computed tomography has particular promise to depict the mediastinal abnormalities in this process. Surgery had minimal therapeutic benefit. Because of incomplete followup, the mortality of 30% in this series surely does not represent the true overall mortality of mediastinal fibrosis.


Modelling of long-term dynamic leaching tests applied to solidified/stabilised waste.
The paper aims at simulating the closed-system dynamic leaching of a cement-based monolith containing lead with the numerical reactive transport code HYTEC in a 3D-cylindrical geometry. The model considers, simultaneously, the chemical evolution of pore water, the progression of mineralogical alteration fronts, and the concomitant release of elements from the S/S waste. In good agreement with the experiment, element releases were found to be mainly controlled by either diffusion (Na, K, and, to a lesser extent, Cl), by surface dissolution (Ca, Si) or by a mixed evolution (Pb, SO4). All of the calculated mineralogical transformations take place in a thin layer beyond the monolith surface. Consequently, modelling of Ca, Si and SO4 releases was quite sensitive to the node size of the simulation grid and was improved by taking into account the increase of porosity and effective diffusion coefficient due to mineral dissolution in the leached layer. In agreement with experimental results, the deepest front corresponds under closed-system conditions to portlandite dissolution and calcium silicate hydrates CSH 1.8 transformation into CSH of lower Ca/Si ratio. A second, distinct and intermediate, front is made by ettringite dissolution. The network of CSH is globally preserved in the leached layer, complete dissolution occurring over a very small thickness only. Finally, hydrotalcite precipitation in the leached layer is expected by modelling due to pH drop.


Two quantitative trait loci on Sus scrofa chromosomes 1 and 7 affecting the number of vertebrae.
The objective of the research was to identify QTL affecting the number of vertebrae in swine, one of the major determining factors of growth and body composition. Previously, we reported a QTL for the number of vertebrae located on SSC1qter (terminal band of the q arm of SSC 1) in an F2 family produced by crossing a Göttingen miniature male with two Meishan females. Eight other swine families were subsequently produced by crosses between different breeds of European, Asian, and miniature pigs. In these families, the QTL on SSC1qter for the number of vertebrae was detected. Unlike the Asian alleles, all European alleles in this study had the effect of increasing the number of vertebrae by 0.44 to 0.69 and acted additively without dominance. The Göttingen miniature sire, for which we previously reported a smaller additive effect, seemed to be heterozygous at the QTL. In the present study, another QTL was found for the number of vertebrae on SSC7. This QTL was not fixed in the European pigs used as parents in our experimental families, and some of the European alleles increased the number of vertebrae. A half-sib analysis confirmed that this QTL was segregating in a commercial Large White population. Analysis in an F2 family in which the parental pigs were fixed for alternative alleles revealed that the effects of the QTL on SSC1 and on SSC7 were additive and similar in size. The two QTL acted independently without epistatic effects and explained an increase of more than two vertebrae.


Long-term humoral immunogenicity, safety and protective efficacy of inactivated vaccine against COVID-19 (CoviVac) in preclinical studies.
The unprecedented in recent history global COVID-19 pandemic urged the implementation of all existing vaccine platforms to ensure the availability of the vaccines against COVID-19 to every country in the world. Despite the multitude of high-quality papers describing clinical trials of different vaccine products, basic detailed data on general toxicity, reproductive toxicity, immunogenicity, protective efficacy and durability of immune response in animal models are scarce. Here, we developed a β-propiolactone-inactivated whole virion vaccine CoviVac and assessed its safety, protective efficacy, immunogenicity and stability of the immune response in rodents and non-human primates. The vaccine showed no signs of acute/chronic, reproductive, embryo- and fetotoxicity, or teratogenic effects, as well as no allergenic properties in studied animal species. The vaccine induced stable and robust humoral immune response both in form of specific anti-SARS-CoV-2 IgG and NAbs in mice, Syrian hamsters, and common marmosets. The NAb levels did not decrease significantly over the course of one year. The course of two immunizations protected Syrian hamsters from severe pneumonia upon intranasal challenge with the live virus. Robustness of the vaccine manufacturing process was demonstrated as well. These data encouraged further evaluation of CoviVac in clinical trials.


Mycobacterium avium-intracellulare-associated colitis in a patient with the acquired immunodeficiency syndrome.
A 40-year-old bisexual man with the acquired immunodeficiency syndrome developed abdominal pain and bloody diarrhea. At sigmoidoscopy, the mucosa of the rectum and sigmoid colon was edematous, erythematous, and friable, with multiple linear and oval erosions. Histologic examination of rectal biopsies demonstrated innumerable acid-fast bacilli free and within macrophages of the lamina propria. Mycobacterium avium-intracellulare was cultured from the rectal biopsy specimens. Pulmonary tissue and bone marrow cultures also demonstrated this organism. Therapy with several antimycobacterial agents resulted in improvement of symptoms. Among immunocompromised patients the spectrum of enteric pathogens causing colitis should be expanded to include Mycobacterium avium-intracellulare, a potentially treatable organism.


Chronic villitis in untreated neonatal alloimmune thrombocytopenia: an etiology for severe early intrauterine growth restriction and the effect of intravenous immunoglobulin therapy.
The objective of the study was to examine placental histopathology in intravenous immunoglobulin-treated and untreated neonatal alloimmune thrombocytopenia and correlate pathological findings with clinical outcomes. Placentas from 14 neonatal alloimmune thrombocytopenia-affected pregnancies were identified. Maternal antepartum treatment with intravenous immunoglobulin and pregnancy outcomes were abstracted from medical records. Placental histopathology and clinical outcomes were compared between intravenous immunoglobulin and no intravenous immunoglobulin treatment groups using Fisher's exact test. One subject, treated only after an intracranial hemorrhage (ICH) was diagnosed, was excluded from the analysis. P < .05 was considered significant. Untreated pregnancies demonstrated a lymphoplasmacytic chronic villitis not seen in the intravenous immunoglobulin-treated pregnancies (P = .005). Intrauterine growth restriction and intrauterine fetal demise occurred as frequently as ICH in the untreated group. No ICH, intrauterine growth restriction, or intrauterine fetal demises occurred in the treated group, although the P value was not significant. Chronic villitis is frequently manifest in neonatal alloimmune thrombocytopenia, with intravenous immunoglobulin alleviating this inflammatory immunologic response. We suspect a more universal role for the maternal antibody, such as fetal endothelial cell damage, in the sequelae of neonatal alloimmune thrombocytopenia.


Electron-Delocalization-Stabilized Photoelectrocatalytic Coupling of Methane by NiO-Polyoxometalate Sub-1 nm Heterostructures.
The oxidative coupling of methane to C2 oxygenates merits great scientific and technological potential yet remains a challenge due to its inferior selectivity. Subnanomaterials (SNMs) with "p-n-p-n"-type heteroconstructions feature enhanced external field coupling properties and tunable electronic structures, serving as promising catalysts for the selective partial oxidation of methane. Here we develop NiO-polyoxometalate (POM) subnanocoils with a thickness of 1.8 nm, showing excellent catalytic activity toward photoelectrochemical coupling of methane into a C2 product under mild conditions (1 bar, 25 °C) with a notable productivity (up to 4.48 mmol gcat-1 h-1) and a high selectivity (>99%). Under photoelectrochemical coupling, C-H bonds can be activated by NiO, and the resulted *COOH intermediates are stabilized by the delocalized electrons in POM clusters. The contiguous active sites of NiO and POM at the molecular level allow the in situ coupling of *COOH into oxalate. This work points out an economic way for the oxidation of methane under mild conditions and may enlighten the design of functional SNMs from fundamental standpoints.


Inflammation, malnutrition and vascular contraction in experimental chronic kidney disease.
Inflammation is a well-defined factor influencing the development of cardiovascular complications in chronic renal failure. The aim of this study was to examine systemic inflammatory state defined by the level of serum haptoglobin, local inflammation defined by monocyte chemoattractant protein-1 (MCP-1) level and arterial response to phenylephrine in different stages of renal failure. Experiments were performed on male Wistar rats, weighing 290-380 g. The rats were divided into 4 groups: I (control) was shame-operated (n=12); II underwent 1/2 nephrectomy (n=12); III, 3/4 nephrectomy (n=8); IV 5/6 nephrectomy (n=12). After 4 weeks, blood pressure (BP) in carotid artery was measured, and blood was collected for blood urea nitrogen, creatinine, albumin, haptoglobin and MCP-1. We compared the smooth muscle contractility after stimulation of alpha1-adrenoreceptor with phenylephrine in all groups. The constriction of artery was measured as the increase in perfusion pressure at a constant flow of the perfusion fluid. Cumulative response curves (CRCs) were obtained using the van Rossum method. We observed a significant shift of CRCs to the left in group III (calculated half-maximal contraction [EC50] was 1.55 x 10(-7) M/L vs. 7.71 x 10(-7) M/L in control) and a nonsignificant shift of CRCs to the left in group II (3.62 x 10(-7) M/L). Unexpectedly, rat tail arteries from the rats in the 5/6 nephrectomy group were characterized by diminished contraction response to phenylephrine (EC50 9.57 x 10-7 M/L). Systemic inflammation defined by haptoglobin level occurred in the 1/2 nephrectomy group and did not increase in more advanced stages of renal disease. Local inflammation (MCP-1 level) increased together with the renal failure progression. We found a positive correlation between MCP-1 level and haptoglobin only in the 5/6 nephrectomy group (r=0.65; p<0.01). The inflammatory state which affects vascular smooth muscle cells plays a key role in determining vascular contraction and resistant artery tone.


Variability in caries management decision-making in a dental school setting.
To assess variability in caries management decision-making by faculty and dental students. Understanding sources of variability during training can aid in implementing evidence-based clinical decision-making in caries management. A voluntary, anonymous survey including clinical scenarios was distributed online to dental students in their first (D1) and third-year (D3) of training, and to faculty in the Department of Cariology, Restorative Sciences and Endodontics. The response rate was 100% (108/108) for D1 students, 56% (73/130) for D3 students, and 39% (34/88; 12 full-time and 22 part-time) for faculty. D1 students, who were completing a cariology course, were in general more conservative in restorative thresholds for less severe caries lesions than D3 students and sometimes clinical faculty (e.g., for lesions at the DEJ, a significantly [p < 0.05] higher percentage of D3 students would restore these [53%] compared to D1 students and faculty [19% and 18%, respectively; p > 0.05]). For all groups, the threshold for doing restorative intervention was shifted toward less severe caries lesions as the caries risk increased (e.g., very few respondents would restore an occlusal lesion confined to enamel, with significantly [p < 0.05] less percentage of D1 students [lower risk scenario-LR = 4%; higher risk scenario-HR = 22%] compared to D3 students and faculty [LR = 15% and 18%; HR = 66% and 62%, respectively; p > 0.05]). Class lectures/preclinical instructors were the most important factor influencing decision-making for D1 students, versus clinical experiences/instructors for D3 students. Although the majority of respondents used best-evidence deciding caries management, there was variability in how to manage less severe lesions, with caries risk influencing clinical thresholds, and clinical experiences influencing students' decision-making over time.


Out of Sight, Out of Mind: Widespread Nuclear and Plastid-Nuclear Discordance in the Flowering Plant Genus Polemonium (Polemoniaceae) Suggests Widespread Historical Gene Flow Despite Limited Nuclear Signal.
Phylogenomic data from a rapidly increasing number of studies provide new evidence for resolving relationships in recently radiated clades, but they also pose new challenges for inferring evolutionary histories. Most existing methods for reconstructing phylogenetic hypotheses rely solely on algorithms that only consider incomplete lineage sorting (ILS) as a cause of intra- or intergenomic discordance. Here, we utilize a variety of methods, including those to infer phylogenetic networks, to account for both ILS and introgression as a cause for nuclear and cytoplasmic-nuclear discordance using phylogenomic data from the recently radiated flowering plant genus Polemonium (Polemoniaceae), an ecologically diverse genus in Western North America with known and suspected gene flow between species. We find evidence for widespread discordance among nuclear loci that can be explained by both ILS and reticulate evolution in the evolutionary history of Polemonium. Furthermore, the histories of organellar genomes show strong discordance with the inferred species tree from the nuclear genome. Discordance between the nuclear and plastid genome is not completely explained by ILS, and only one case of discordance is explained by detected introgression events. Our results suggest that multiple processes have been involved in the evolutionary history of Polemonium and that the plastid genome does not accurately reflect species relationships. We discuss several potential causes for this cytoplasmic-nuclear discordance, which emerging evidence suggests is more widespread across the Tree of Life than previously thought. [Cyto-nuclear discordance, genomic discordance, phylogenetic networks, plastid capture, Polemoniaceae, Polemonium, reticulations.].


Promising immunotherapies for esophageal cancer.
Esophageal cancer (EC) is the eighth most common cancer in the world, and the prognosis of EC is still poor. Although immunotherapy has been developed in melanoma and lung cancer, it is also expected to show efficacy in EC. Currently, several clinical trials are ongoing to evaluate the safety and efficacy of immunotherapies, immune checkpoint inhibitors, adoptive T cell transfer, and therapeutic cancer vaccines in EC. Areas covered: This review provides an overview and the status of immunotherapy in EC. Clinical significance of molecules related immune checkpoints, especially PD-1 and PD-L1 is presented and the designs, results and future directions of clinical trials using immunotherapy in EC are provided. Expert opinion: To bring immunotherapy to the forefront of treatment for EC, it is necessary to select patients who can obtain a high efficacy of immunotherapy and to also elucidate the correct timing for administration. Moreover, combination therapies of immunotherapy with existing chemotherapy or radiation or other immunotherapy with different mechanisms of action must be evaluated to achieve excellent outcomes in patients with EC.


Role of adjuvant chemotherapy in the treatment of invasive carcinoma of the urinary bladder.
The standard treatment for patients with muscle-invasive carcinoma of the urinary bladder is radical cystectomy. While radical cystectomy cures many patients with this tumor, almost 50% of them will develop metastatic disease. Adjuvant chemotherapy has been proposed for these patients in an attempt to reduce the probability of relapse and to improve survival. To assess whether adjuvant chemotherapy does benefit patients with muscle-invasive bladder cancer, we reviewed all phase II and III studies published in the English literature over the last 20 years. A review of all published reports was facilitated by the use of Medline computer search and by manual search of the Index Medicus. Several comparative, nonrandomized studies have indicated that adjuvant chemotherapy may prolong disease-free survival. Four randomized studies have been conducted and all had a suboptimal patient accrual. Three studies used a cisplatin-containing combination chemotherapy and included primarily patients with non-organ-confined transitional-cell carcinoma (TCC) of the bladder. All three studies indicated that adjuvant chemotherapy improved disease-free survival and two of them also showed improvement in event-free survival and overall survival, respectively. Published series have been unable to establish an undisputed benefit of adjuvant chemotherapy over radical cystectomy alone for muscle-invasive bladder cancer. The interpretation of the available data is compromised by several methodologic and statistical problems. Thus, adjuvant chemotherapy cannot be considered as a standard treatment for all patients with muscle-invasive carcinoma of the bladder. Well-designed prospective randomized studies are needed to clarify the role of adjuvant chemotherapy in this disease. However, outside a protocol setting, there is some evidence that patients with extravesical disease or with lymph node involvement may benefit from adjuvant treatment with cisplatin-based combination chemotherapy. No data support such an approach for patients with muscle-invasive but organ-confined bladder cancer.


Co-expression of ING4 and P53 enhances hypopharyngeal cancer chemosensitivity to cisplatin in vivo.
Hypopharyngeal cancer is a distinct type of malignant head and neck tumor, which exhibits low sensitivity to anti-cancer drugs. The importance of developing methods for reducing chemotherapy resistance, and improving and enhancing prognosis has previously been emphasized and is considered a challenge for effective clinical treatment of hypopharyngeal cancer. The current study investigated the effects of co‑expression of inhibitor of growth protein 4 (ING4) and P53, a tumor suppressor gene, on chemosensitivity to cisplatin in human hypopharyngeal cancer xenografts in vivo, and the potential molecular mechanisms involved. A tumor model was established by injecting athymic nude mice with FADU human hypopharyngeal cancer cells. Five days after intratumoral and peritumoral injections of an empty adenoviral vector (Ad), Ad‑ING4‑P53, cisplatin, or a combination of Ad‑ING4‑P53 and cisplatin (Ad‑ING4‑P53 + cisplatin) every other day for 5 days, the mice were euthanized and their tumors, livers, and kidneys were removed. The tumor weights were used to calculate the inhibition rate, and the expression levels of ING4 and P53 were detected by reverse transcription‑polymerase chain reaction. Additionally, apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling, and immunohistochemistry determined the levels ING4, P53, B‑cell lymphoma‑2 (Bcl‑2) and Bcl‑2 associated X protein (Bax) protein expression. The results demonstrated increased expression of ING4 and P53 in the Ad‑ING4‑P53 groups compared with PBS and Ad groups, indicating successful introduction of the genes into the tumor cells. Notably, the Ad‑ING4‑P53 + cisplatin group exhibited a higher inhibition rate compared with the four other groups. The results of immunohistochemistry analysis demonstrated that Bax expression was increased and Bcl‑2 was decreased in the Ad‑ING4‑P53 + cisplatin group. This suggested that the enhanced cisplatin chemosensitivity with Ad-ING4-P53 gene therapy in hypopharyngeal cancer xenografts may be associated with apoptosis induction through upregulation of Bax expression and downregulation of Bcl‑2. The results of the present study indicated that gene therapy combined with cisplatin treatment may be a promising treatment for human hypopharyngeal cancer.


Effects of swimming activity on the copulatory behavior of sexually active male rats.
Physical activity has long been associated with better sexual function. This study investigated the effects of moderate swimming exercise on the copulatory behavior of sexually potent male rats. Two sets of sexually potent male rats -highly active and moderately active- were identified depending on baseline sexual activity. Each of the two sets of rats was further randomly divided into two groups (swimming and sedentary). There were 16 rats in each of the four study groups (highly active swimming, highly active sedentary, moderately active swimming and moderately active sedentary). The copulatory behavior parameters and serum testosterone levels were measured and compared between the rats of the swimming and sedentary groups following a month long training period in which rats were made to swim for 1 h every alternate day. Swimming significantly improved the sexual performance of highly active rats, as indicated by increased intromission frequency and intromission ratio, compared with the sedentary controls. Swimming improved both sexual desire and performance, as indicated by reduced mount latency and increased intromission ratio, respectively, in swimming moderately active rats compared with the sedentary moderately active controls. Therefore, swimming activity improves the copulatory behavior of both highly active and moderately active male rats.


Quantum chemical methods for the investigation of photoinitiated processes in biological systems: theory and applications.
With the advent of modern computers and advances in the development of efficient quantum chemical computer codes, the meaningful computation of large molecular systems at a quantum mechanical level became feasible. Recent experimental effort to understand photoinitiated processes in biological systems, for instance photosynthesis or vision, at a molecular level also triggered theoretical investigations in this field. In this Minireview, standard quantum chemical methods are presented that are applicable and recently used for the calculation of excited states of photoinitiated processes in biological molecular systems. These methods comprise configuration interaction singles, the complete active space self-consistent field method, and time-dependent density functional theory and its variants. Semiempirical approaches are also covered. Their basic theoretical concepts and mathematical equations are briefly outlined, and their properties and limitations are discussed. Recent successful applications of the methods to photoinitiated processes in biological systems are described and theoretical tools for the analysis of excited states are presented.


Effect of LAMA4 on Prognosis and Its Correlation with Immune Infiltration in Gastric Cancer.
Laminin alpha 4 (LAMA4) is widely distributed in the basement membranes of various tissues. It can regulate cancer cell proliferation and migration. We investigated the effects of LAMA4 in gastric cancer (GC). LAMA4 expression patterns were analyzed in GC using the Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), and UALCAN. Correlations between LAMA4 expression and clinicopathological characteristics were evaluated using data from The Cancer Genome Atlas (TCGA). The survival analysis was examined using the Kaplan-Meier plotter and GEPIA and ascertained by multivariate Cox analysis. Genetic alterations and DNA methylation of LAMA4 were analyzed using cBioPortal and MethSurv. LinkedOmics was applied to identify coexpressed genes of LAMA4. The association between LAMA4 and infiltration of immune cells was explored using Tumor Immune Estimation Resource (TIMER) and GEPIA. LAMA4 was highly expressed in GC, and its upregulation significantly correlated with T classification (P = 0.040). LAMA4 expression was an independent risk factor for overall survival (OS, P = 0.033). Patients with genetic alterations of LAMA4 showed a significantly better disease-free survival (DFS, P = 0.022). Ten CpG sites of LAMA4 were significantly associated with prognosis in GC. The functions of LAMA4 and coexpression genes were mainly involved in extracellular matrix (ECM) receptor interaction. LAMA4 expression significantly correlated with infiltration of macrophages (P < 0.001), CD4+ T cells (P < 0.001), and dendritic cells (P < 0.001). Furthermore, LAMA4 expression was significantly associated with markers of M2 and tumor-associated macrophages (TAMs). LAMA4 expression was linked to GC prognosis and immune cell infiltration, indicating its potential use as a prognostic biomarker and therapeutic target.


[Brucella spp orchiepididymitis].
To report a brucellar orchiepididymitis case and to review the diagnosis and treatment of this pathology. We present the case of a 62 year old man presenting with fever, testicular pain and constitutional syndrome. The diagnosis was made after ultrasound, blood cultures and anamnesis. The treatment was Doxiciclin six weeks and teicoplanin, the second one was replaced with ciprofloxacin. It is important to make a correct anamnesis to the patient with orchiepididymitis to identify any risk factor for brucellosis. The diagnosis is confirmed with blood cultures. The oral antibiotics are enough to cure patients.


Characteristic MR and CT imaging findings of hepatobiliary paragonimiasis and their pathologic correlations.
Hepatobiliary paragonimiasis (HP) is not commonly encountered and may be confused with hepatobiliary tumors; however, computed tomography (CT) and magnetic resonance imaging (MRI) features of HP allow this entity to be distinguished from other diseases. To present the CT and MRI findings in patients with HP and to describe some specific imaging findings along with their pathological correlations. Imaging and clinical findings of 21 patients (9 boys/men and 12 girls/women; age range 3-67 years; mean age 40 years) who were diagnosed with HP were retrospectively evaluated. Among these patients, 16 underwent CT examination only, two had MR examination only, and three underwent both CT and MR. All patients underwent surgery, and the HP diagnosis was confirmed by the surgical and histopathologic results. Chronic abdominal pain or back pain was reported by 14 patients, severe abdominal pain with acute onset was reported by one patient, and six patients were asymptomatic and were discovered incidentally. Peripheral eosinophilia was present in 14 patients (14/21, 66.7%), and abnormal liver function tests were found in 16 patients (16/21, 76.2%). Of the 19 patients who underwent CT imaging, 17 patients showed multiple mixed hypodense lesions or multiple cysts with inlaying septation with separate irregular rims or circular enhancement on post-contrast CT images. Tunnel-shaped microabscesses and necrotic cavities were found in the lesions of 12 of those 17 patients. The other two patients showed smaller cystic masses. MRI showed faveolate T1 hypointense and T2 hyperintense areas in the liver parenchyma with rim or peripheral enhancement. Nodular or circular hyperintense materials were found scattered in the lesions on T1-weighted imaging. CT and MRI can reveal the radiological-pathological features of HP. Together with laboratory findings, MRI and CT findings may provide diagnostic clues, especially in endemic areas, that are very important for the selection of treatment methods.


[Primary tuberculous pleurisy. The course of 3 untreated cases].
Three patients with pleurisy, all exposed to tuberculosis (TB) in their environment, are presented. The etiology of the pleurisy was not initially uncovered and as the pleurisy resolved spontaneously, the patients were discharged from follow up after four to 21 months. Within two to 12 months hereafter, the patients showed up with post-primary tuberculosis: (case I) with miliary tuberculosis incl. meningeal tuberculosis, case II with apical lung tuberculosis and case III with extrapulmonary tuberculosis of the bones. After six months of combined anti-tuberculosis chemotherapy all patients recovered completely. Primary tuberculous pleurisy is known usually to be self-limited but the reactivation rate is high; up to 65% of the adult patients develop post-primary tuberculosis within five years, if not treated. Therefore, prompt diagnosis and treatment are important. Pleurisy in patients with TB in their environment should be intensively examined with cultures of all potentially diagnostic specimens; cultures from pleura fluid alone have a low diagnostic yield and diagnostic blind closed or thoracoscopic open biopsy from the pleura for cultures and histologic examination should be performed whenever possible. If the etiology is not found, the patient should be followed for at least five years.


[Not Available].
The changes of legal condition that the hospitals have had in these last years, have caused great problems also in the Archives' administration produced by those. In particular, there is a lamentation for lack of exact rules which regulate the preservation and the order of clinical fulders, although during these last years SIASO (Italian Society for Sanitary Hospital Archives) is working very much. Photographic supports or other things in place of paper documentation and the archives' administration of hospital institutions on behalf of a third party (records management) do not seem suitable and convenient solutions to safeguard documents that must not be considered from a bureaucratic point of view, but above all from a historical and cultural one.


Monte Carlo microdosimetry of 188Re- and 131I-labelled anti-CD20.
The radiolabelled monoclonal antibody anti-CD20 has the property of binding to the CD20 antigen expressed on the cell surface of B-lymphocytes, thus making it a useful tool in the treatment of non-Hodgkin's lymphoma. In this work, the event-by-event Monte Carlo code NOREC is used to calculate the single-event distribution function f(1)(z) in the cell nucleus using the beta spectra of the (188)Re and (131)I radionuclides. The simulated geometry consists of two concentric spheres representing the nucleus and the cell surface embedded in a semi-infinite water medium. An isotropic point source was placed on the cell surface to simulate the binding of the anti-CD20 labelled with either (188)Re or (131)I. The simulations were carried out for two combinations of cell surface and nucleus radii. A method was devised that allows one to calculate the contribution of betas of energy greater than 1 MeV, which cannot be simulated by the NOREC code, to the single-event distribution function. It is shown that disregarding this contribution leads to an overestimation of the frequency-mean specific energy of the order of 9-12%. In general, the antibody radiolabelled with (131)I produces single-event distribution functions that yield higher frequency-mean specific energies.


Identification of Load Categories in Rotor System Based on Vibration Analysis.
Rotating machinery is often subjected to variable loads during operation. Thus, monitoring and identifying different load types is important. Here, five typical load types have been qualitatively studied for a rotor system. A novel load category identification method for rotor system based on vibration signals is proposed. This method is a combination of ensemble empirical mode decomposition (EEMD), energy feature extraction, and back propagation (BP) neural network. A dedicated load identification test bench for rotor system was developed. According to loads characteristics and test conditions, an experimental plan was formulated, and loading tests for five loads were conducted. Corresponding vibration signals of the rotor system were collected for each load condition via eddy current displacement sensor. Signals were reconstructed using EEMD, and then features were extracted followed by energy calculations. Finally, characteristics were input to the BP neural network, to identify different load types. Comparison and analysis of identifying data and test data revealed a general identification rate of 94.54%, achieving high identification accuracy and good robustness. This shows that the proposed method is feasible. Due to reliable and experimentally validated theoretical results, this method can be applied to load identification and fault diagnosis for rotor equipment used in engineering applications.


Nasal disease in relation to fitness of a pilot.
The nasal cavity and sinus system is extensive but its examination is limited. Listening to breathing and respiration can afford useful clues to underlying abnormality. Examination of the nasal cavity may reveal the pale swollen mucosa of allergic rhinitis or the overdeveloped lining seen in perennial rhinorrhoea and hypertropic rhinitis. Localised hypertrophy gives rise to the nasal polyp which usually forms in the region of the ethmoid sinus. Atrophic rhinitis is a destructive condition of the nasal lining. Sinusitis may be open or closed, presenting with localised pain and displacement of the eye in the case of frontal or ethmoidal abscess or mucocoele. Deformities of the external nose or nasal septum are often encountered during examination. Epistaxis may be caused by bleeding simply from Kiesselbach's vessels, or may be an early feature of telangiectasia or cardiovascular diseases. Tumors are rarely found but include papillomata and the mucous membrane melanoma.


Unique Dual-Sites Boosting Overall CO2 Photoconversion by Hierarchical Electron Harvesters.
Low selectivity and poor activity of photocatalytic CO2 reduction process are usually limiting factors for its applicability. Herein, a hierarchical electron harvesting system is designed on CoNiP hollow nano-millefeuille (CoNiP NH), which enables the charge enrichment on CoNi dual active sites and selective conversion of CO2 to CH4 . The CoNiP serves as an electron harvester and photonic "black hole" accelerating the kinetics for CO2 -catalyzed reactions. Moreover, the dual sites form from highly stable CoONiC intermediates, which thermodynamically not only lower the reaction energy barrier but also transform the reaction pathways, thus enabling the highly selective generation of CH4 from CO2 . As an outcome, the CoNiP NH/black phosphorus with dual sites leads to a tremendously improved photocatalytic CH4 generation with a selectivity of 86.6% and an impressive activity of 38.7 µmol g-1 h-1 .


Thermodynamics of critical strange nonchaotic attractors.
The thermodynamic formalism is applied to dynamical attractors which have fractal geometry and on which all Lyapunov exponents are exactly zero. Such critical strange nonchaotic attractors (SNAs) which arise, for example, in the Harper system exhibit a static phase transition in the free energy. The Tsallis nonextensive entropy which is known to characterize the thermodynamics of systems with leading Lyapunov exponent zero is found to be subadditive for the critical states. These properties are shared by other quasiperiodic systems with critical SNAs.


The effects of race on peak oxygen consumption and survival in patients with systolic dysfunction.
The relationship of peak exercise oxygen consumption (VO(2)) to survival in black heart failure (HF) patients is not well established. We examined the effects of race on peak VO(2) values and survival in HF patients with systolic dysfunction. This study evaluated consecutive ambulatory HF patients who underwent symptom-limited stress tests with breath-by-breath expired gas analyses using ramped treadmill protocols. The relationship between cardiopulmonary exercise parameters and patient transplant-free survival was assessed by race. This study included 580 HF patients (mean age 52 +/- 12 years; 28% females; 22% blacks; mean left ventricular ejection fraction 26 +/- 12%; mean body mass index 28.7 +/- 5.4; 73% on beta-blocker). Black patients had a significantly lower peak VO(2) than white patients (14.2 +/- 5.2 versus 16.4 +/- 7.0; P < .0001), despite adjusting for identified covariates. However, there was no significant difference in the 1-year transplant-free survival between black and white HF patients (87% versus 85%; P = NS). Peak VO(2) was significantly associated with survival in both racial groups. Black HF patients had significantly lower peak VO(2), but yet had equivalent survival rates at 1 year. Further study is warranted to clarify the impact of these racial differences on the timing of cardiac transplantation black HF patients.


Introgression Threatens the Genetic Diversity of Quercus austrocochinchinensis (Fagaceae), an Endangered Oak: A Case Inferred by Molecular Markers.
Natural introgression can cause negative effects where rare species experience genetic assimilation and invade by their abundant congeners. Quercus austrocochinchinensis and Q. kerrii (subgenus Cyclobalanopsis) are a pair of closely related species in the Indo-China area. Morphological intermediates of the two species have been reported in this region. In this study, we used AFLP, SSR and two key leaf morphological diagnostic traits to study the two Q. austrocochinchinensis populations, two pure Q. kerrii and two putative hybrid populations in China. Rates of individual admixture were examined using the Bayesian clustering programs STRUCTURE and NewHybrids, with no a priori species assignment. In total, we obtained 151 SSR alleles and 781 polymorphic loci of AFLP markers. Population differentiation inferred by SSR and AFLP was incoherent with recognized species boundaries. Bayesian admixture analyses and principal coordinate analysis identified more hybrids and backcrossed individuals than morphological intermediates in the populations. SSR inferred a wide genetic assimilation in Q. austrocochinchinensis, except for subpopulation D2 in the core area of Xi-Shuang-Ban-Na Nature Reserve (XSBN). However, AFLP recognized more Q. austrocochinchinensis purebreds than SSR. Analysis using NewHybrids on AFLP data indicated that these hybridized individuals were few F2 and predominantly backcrosses with both parental species. All these evidences indicate the formation of a hybrid swarm at XSBN where the two species co-exist. Both AFLP and SSR recognized that the core protected area of XSBN (D2) has a high percentage of Q. austrocochinchinensis purebreds and a unique germplasm. The Hainan population and the other subpopulations of XSBN of the species might have lost their genetic integrity. Our results revealed a clear genetic differentiation in the populations and subpopulations of Q. austrocochinchinensis and ongoing introgression between Q. austrocochinchinensis and Q. kerrii at the disturbed contact areas. Combining the results from genetic and morphological analyses, the conservation of subpopulation D2 should be prioritized. Conservation and restoration of the integrity of tropical ravine rainforest is an important long-term goal for the successful conservation of Q. austrocochinchinensis. The fine-scale landscape might play an essential role in shaping the spatial patterns of hybridization. Further studies are needed to evaluate these patterns and dynamics.


Allee effects in tritrophic food chains: some insights in pest biological control.
Release of natural enemies to control pest populations is a common strategy in biological control. However, its effectiveness is supposed to be impaired, among other factors, by Allee effects in the biological control agent and by the fact that introduced pest natural enemies interact with some native species of the ecosystem. In this work, we devise a tritrophic food chain model where the assumptions previously raised are proved correct when a hyperpredator attacks the introduced pest natural enemy by a functional response type 2 or 3. Moreover, success of pest control is shown to be related to the release of large amounts (i.e., inundative releases) of natural enemies.


Artificial Intelligence (AI) and Robotics in Elderly Healthcare: Enabling Independence and Quality of Life.
We are being urged to redefine aging and only use positive terminology when discussing it. It is unacceptable to use a derogatory term like "aging tsunami." This is unfortunate because it comes at a time when geriatrics is precariously balancing itself. Geriatricians are growing far too slowly to supply an adequate number of medical professionals to meet the needs of the rapidly aging senior population. The global aging population poses significant challenges for healthcare systems and providing elderly care. In recent years, artificial intelligence (AI) and robotics have emerged as promising technologies to address these challenges by enabling independence and enhancing the quality of life for older adults. This review article examines the applications of AI and robotics in elderly care, focusing on their role in promoting independence, monitoring health, helping, and enhancing social interaction. The article also discusses the ethical considerations, challenges, and future directions in implementing AI and robotics in elderly care.


Weapons of mass destruction and the role of the neurosurgeon.
The desire to assist in a crisis should be tempered by a serious assessment of the technical preparation one has undertaken. Additionally, in the same way that a needs assessment is undertaken before prescribing a course of treatment, one should evaluate the actual staffing requirements of the situation. Many physician volunteers were turned away after the World Trade Center attacks because the overwhelming response of available medical personnel quickly exceeded the requirement. Finally, the duration and intensity of preparation should be based on a realistic evaluation of the likelihood of an event occurring that would necessitate use of the training. Before jumping into action in a situation in which weapons of mass destruction have been used, several issues must be addressed. Prior to the crisis, all professionals, neurosurgeons included, should ask how they can prepare themselves and their communities. During the crisis, neurosurgeons should evaluate their roles based on specialized triage training and experience, personal and equipment decontamination training, and the importance of neurosurgical skills. Finally, one should continually ask if there is anything he/she should be doing during the crisis in addition to performing neurosurgical tasks.


Patterns of eating and abstinence in women treated for bulimia nervosa.
The current study sought to determine whether there is an optimal pattern of eating leading to cessation of binge eating and purging in bulimic women. Data on the number of meals and snacks consumed were obtained from the Eating Disorders Examination (EDE) pretreatment and posttreatment, for individuals participating in a randomized controlled study comparing cognitive-behavioral therapy and interpersonal therapy. Records were available for 158 participants. The numbers of meals and snacks eaten from pretreatment to posttreatment increased significantly. A pattern of eating with at least 80 meals combined with at least 21 afternoon snacks within a 28-day period was associated with an abstinence rate of 70%. In contrast, for subjects having 72-80 meals, those having greater than 11 evening snacks have an abstinence rate of 4%. The critical elements of the pattern of eating related to abstinence appear to be the total number of meals consumed and the timing of snacks.


Spatial contacts and nucleosome step movements induced by the NURF chromatin remodeling complex.
The nucleosome remodeling factor NURF is a four-subunit, ISWI-containing chromatin remodeling complex that catalyzes nucleosome sliding in an ATP-dependent fashion, thereby modulating the accessibility of the DNA. To elucidate the mechanism of nucleosome sliding, we have investigated by hydroxyl radical footprinting how NURF makes initial contact with a nucleosome positioned at one end of a DNA fragment. NURF binds to two separate locations on the nucleosome: a continuous stretch of linker DNA up to the nucleosome entry site and a region asymmetrically surrounding the nucleosome dyad within the minor grooves, close to residues of the histone H4 tail that have been implicated in the activation of ISWI activity. Kinetic analysis reveals that nucleosome sliding occurs in apparent increments or steps of 10 bp. Furthermore, single nucleoside gaps as well as nicks about two helical turns before the dyad interfere with sliding, indicating that structural stress at this region assists the relative movement of DNA. These findings support a sliding model in which the position-specific tethering of NURF forces a translocating ISWI ATPase to pump a DNA distortion over the histone octamer, thereby changing the translational position of the nucleosome.


Specificity of polyamine requirements for the replication and maintenance of different double-stranded RNA plasmids in Saccharomyces cerevisiae.
We have shown previously that the M1 double-stranded (ds) RNA (i.e., the killer plasmid [KIL-k1]) that codes for a protein toxin requires spermidine or spermine for its replication. We now report that replication of two other ds RNA plasmids of yeast also requires polyamines: (i) M2 ds RNA [( KIL-k2]) and (ii) L-A-E, a ds RNA plasmid carrying the non-Mendelian genetic element [EXL]. Putrescine alone is sufficient to maintain L-A-E but is not sufficient to maintain either M1 ds RNA or M2 ds RNA, which require either spermidine or spermine. Once M1 or M2 or L-A-E is lost, it cannot be restored by the addition of polyamines. In contrast, L-A-HN, a ds RNA molecule that carries the cytoplasmic genes [HOK] and [NEX], is not lost during polyamine deprivation. It is striking that polyamine deprivation differentially affects L-A-E and L-A-HN, even though these two ds RNA molecules have more than 99% homology. L-C, which is the same size as L-A but very different in sequence, is also not lost on polyamine starvation.


A combination of depression and liver Qi stagnation and spleen deficiency syndrome using a rat model.
A syndrome (Zheng in Chinese) plays a critical role in disease identification, diagnosis, and treatment in traditional Chinese medicine (TCM). Clinically, the liver Qi stagnation and spleen deficiency syndrome (LQSSDS) is one of the most common syndrome patterns. Over the past few decades, several animal models have been developed to understand the potential mechanisms of LQSSDS, but until now, simulation of the syndrome is still unclear. Recently, several studies have confirmed that an animal model combining a disease and a syndrome is appropriate for simulating TCM syndromes. Overlapping previous studies have reported that depression is highly associated with LQSSDS; hence, we attempted to develop a rat model combining depression and LQSSDS. We exposed the rats to different durations of chronic unpredictable mild stress (CUMS). Subsequently, the evaluation indicators at macrolevel consisted of behavioral tests including open field test, sucrose preference test, and forced swim test, food intake, body weight, white adipose tissue, fecal water content, visceral hypersensitivity, and small bowel transit, and the evaluation indicators at microlevel included changes of hypothalamic-pituitary-adrenal axis. Serum D-xylose absorption was used to comprehensively confirm and assess whether the model was successful during the CUMS-induced process. The results showed that rats exposed to 6-week CUMS procedure exhibited significantly similar traits to the phenotypes of LQSSDS and depression. This study provided a new rat model for the LQSSDS and could potentially lead to a better understanding of the pathophysiology of LQSSDS and the development of new drugs for this syndrome.


Hemoglobin in a coacervate system.
Hemoglobin dissolved in a coacervate system shows the properties of a resuscitation fluid. In the coacervate system used, the equilibrium phase was the colloid rich phase. We propose a new definition of the coacervate phase to be that phase in a coacervate system which is most dissimilar to water in its physical chemical properties.


Velopharyngeal Closure and Resonance in Children Following Early Cleft Palate Repair: Outcome Measurement.
Introduction Timing of cleft palate repair and the method of speech outcome measurement in children with cleft lip and palate are much debated topics. The associated problems and quality of life in these children depend on the timing of the surgery. Aim The aim of this study was to investigate the velopharyngeal (VP) function and resonance parameters in children following early cleft palate repair. Method A total of 25 Kannada-speaking children with early repaired cleft palate were subjected to speech assessment and videofluoroscopic assessment. Perceptual speech parameters measured were severity of hypernasality and presence of nasal air emission. Videofluoroscopy was interpreted in terms of closure ratios to predict the severity of VP dysfunction. Results The analysis of videofluoroscopic images indicated that 48% of children had complete VP closure and 52% had perceptually normal resonance. A good correlation was found between the closure ratio and hypernasality. Conclusion Understanding the perceptual speech parameters and their structural correlates for outcome measurement will give better evidence for refining the existing treatment protocols. Data on a larger population are warranted for establishing predictors of optimum speech outcome.


Feline Mammary Cancer.
Feline mammary carcinoma (FMC) is similar to human breast cancer in the late age of onset, incidence, histopathologic features, biological behavior, and pattern of metastasis. Therefore, FMC has been proposed as a relevant model for aggressive human breast cancer. The goals of this study were to develop a nude mouse model of FMC tumor growth and metastasis and to measure the expression of genes responsible for lymphangiogenesis, angiogenesis, tumor progression, and lymph node metastasis in FMC tissues and cell lines. Two primary FMC tissues were injected subcutaneously, and 6 FMC cell lines were injected into 3 sites (subcutaneous, intratibial, and intracardiac) in nude mice. Tumors and metastases were monitored using bioluminescent imaging and characterized by gross necropsy, radiology, and histopathology. Molecular characterization of invasion and metastasis genes in FMC was conducted using quantitative real-time reverse transcription polymerase chain reaction in 6 primary FMC tissues, 2 subcutaneous FMC xenografts, and 6 FMC cell lines. The histologic appearance of the subcutaneous xenografts resembled the primary tumors. No metastasis was evident following subcutaneous injection of tumor tissues and cell lines, whereas lung, brain, liver, kidney, eye, and bone metastases were confirmed following intratibial and intracardiac injection of FMC cell lines. Finally, 15 genes were differentially expressed in the FMC tissues and cell lines. The highly expressed genes in all samples were PDGFA, PDGFB, PDGFC, FGF2, EGFR, ERBB2, ERBB3, VEGFD, VEGFR3, and MYOF. Three genes ( PDGFD, ANGPT2, and VEGFC) were confirmed to be of stromal origin. This investigation demonstrated the usefulness of nude mouse models of experimental FMC and identified molecular targets of FMC progression and metastasis.


Nationalistic Media Obsession With Olympic Medal Counts: The Case of the 2020 Tokyo Olympic Games.
Because Olympic medals are awarded to athletes representing an individual National Olympic Committee, it is natural for the media, and even the International Olympic Committee, to create a table indicating which nation has experienced the most athletic success. Problems, and even disagreements, arise when nations utilize different methods to count medals. The 2020 Tokyo Olympic Games, contested in 2021, provided a unique opportunity to observe how media organizations create a narrative around medal tables. American media outlets preferred to consistently show the United States at the top of the medal standings even though China had more gold medals for much of the Games' fortnight. Non-American media organizations took exception to that method of counting.


Susceptibility of multidrug-resistant human leukemia cell lines to human interleukin 2-activated killer cells.
Considering the possibility to overcome drug resistance by other treatment strategies than chemotherapy we investigated the susceptibility of three independently selected multidrug-resistant sublines of the T-lymphoblastoid leukemic cell line CCRF-CEM to lymphokine-activated killer (LAK) cells. We found that two of the multidrug-resistant sublines were significantly less susceptible targets to LAK cells. A third one, however, was as susceptible as the parental CCRF-CEM cell line. Moreover, a multidrug-resistant subline that reverted to an almost drug-sensitive phenotype was observed to be also revertant for resistance against LAK cells. We found an inverse relationship between the expression of the mdr1 gene (P-glycoprotein) and the susceptibility to LAK cells. Verapamil, a calcium channel blocker, while increasing the drug sensitivity of a multidrug-resistant subline, did not induce a reversal of the suppression of LAK susceptibility. The possibility of enhanced resistance to LAK cells of multidrug-resistant cells should be taken into account when one is looking for therapy strategies to overcome multidrug resistance.


Implicit Association Test Alone Is Not Sufficient to Increase Underrepresented Minority Representation in Physician Assistant Programs.
Physician assistant (PA) program matriculants are consistently less diverse than the US population. This study evaluates whether administration of an Implicit Association Test (IAT) to PA program admission committees is associated with changes in the likelihood of (1) receiving an admission interview, (2) receiving an offer of admission, and (3) matriculation of individuals underrepresented in medicine (URiM). Admission committees from 4 PA programs participated in an IAT before the 2019/2020 admissions cycle. Applicant outcome data (n = 5796) were compared with 2018/2019 cycle (n = 6346). Likelihood of URiM students receiving offers to interview, offers of admission, and matriculation were evaluated using random effects multiple logistic regression models. Fully adjusted random effects models included URiM status, year (control vs. intervention), multiplicative interaction terms between URiM and year, applicant age, and undergraduate grade point average (GPA) Secondary analyses examined associations of each race/ethnicity individually. Underrepresented in medicine status, age, and GPA were significantly associated with all admission outcomes ( P < .05). The intervention effect was not statistically significant. In sensitivity analyses examining each individual race rather than URiM status, our results did not importantly differ. Findings suggest admission committee member participation in IAT before admissions had no significant impact on the likelihood of admission of URiM students. This may suggest that making individuals aware of their implicit biases is not, in and of itself, sufficient to meaningfully affect the diversity of PA program admission metrics.


In vitro Activity of Meropenem-Vaborbactam versus Other Antibiotics Against Carbapenem-Resistant Escherichia coli from Southeastern China.
This study aimed to evaluate the in vitro activity of meropenem-vaborbactam (MVB) against a collection of carbapenem-resistant Escherichia coli (CREC) isolates and to compare the activity with other antibiotics with regard to different separation sites, carbapenem-resistant mechanisms, and sequence types (STs). A total of 58 CREC strains were used as the experimental strains from the First Affiliated Hospital of Wenzhou Medical University in southeastern China. The minimum inhibitory concentrations of MVB, ceftazidime-avibactam, and tigecycline against all the experimental strains were determined by the microdilution broth method. MVB exhibited higher antimicrobial activity (83% susceptibility) than that of other antibiotics, except for colistin and tigecycline. The susceptibility of CREC strains towards MVB varied with regard to carbapenem-resistant mechanisms and STs, especially in Klebsiella pneumoniae carbapenemase (KPC)-positive isolates and ST8 isolates. MVB exhibited considerably high activity against KPC-producing and ST8 CREC isolates. It has the great potential to be an alternative for the treatment of infections caused by CREC after determining the type of carbapenemase, the susceptibility to MVB and/or STs.