MicroRNA-373-3p inhibits the growth of cervical cancer by targeting AKT1 both in vitro and in vivo.
In this study, we aimed to investigate the function of microRNA-373-3p (miR-373-3p) in the pathogenesis of cervical cancer. Human and mouse cervical cancer cell lines were transfected with miR-373-3p mimic and inhibitor. Cell proliferation and viability were evaluated with Cell Counting Kit-8 (CCK-8) assay and Lactate Dehydrogenase (LDH) assay, respectively. The AKT1-targeting role of miR-373-3p was analyzed by qPCR and Western blot. Finally, a mouse xenograft cervical tumor model was adopted to study the in vivo effect of miR-373-3p on tumor growth and the expression of AKT1. Over-expression of miR-373-3p significantly reduced the proliferation of cervical carcinoma cell line in vitro. In addition, miR-373-3p overexpression also inhibited cervical cancer growth in tumor-bearing mice. Mechanistically, we found that AKT1 gene can be targeted by miR-373-3p. MiR-373-3p mimic decreased the mRNA and protein expression of AKT1, while the miR-373-3p inhibitor increased the level of AKT1 in cervical cancer cells. AKT1 overexpression rescued the proliferation of cervical cancer cells transfected with miR-373-3p. MiR-373-3p can serve as a novel anti-tumor microRNA in cervical cancer by targeting AKT1.


Smad2 decelerates re-epithelialization during gingival wound healing.
During periodontal regeneration, inhibition of gingival downgrowth is necessary to promote migration of mesenchymal cells into the defects. Transforming growth factor (TGF)-β is a pleiotropic cytokine that has numerous cell functions, including regulation of epithelial growth. Recent studies have shown that Smad2, a downstream transcription factor of TGF-β, plays crucial roles in wound healing in the epithelia. Therefore, we investigated the effects of Smad2 overexpression on re-epithelialization of gingival wounds. Transgenic mice overexpressing smad2 driven by the keratin 14 promoter (k14-smad2) were confirmed to have significant Smad2 phosphorylation in gingival basal epithelia. Punch wounds were made in the palatal gingiva, and wound healing was assessed histologically for 7 days. Re-epithelialization was significantly retarded on day 2, while collagen deposition was enhanced on day 7 in k14-smad2 compared with wild-type mice. Moreover, expression of keratin 16 (K16), an indicator of keratinocyte migration, was significantly inhibited in wound-edge keratinocytes in k14-smad2. The inhibition of K16 coincided with the induction of Smad2 in the corresponding epithelia, while BrdU incorporation was unaffected. These results indicated that Smad2 has inhibitory effects in regulating keratinocyte migration during gingival wound healing. TGF-β/Smad2 signaling mediating alteration of K16 expression must be tightly regulated during periodontal regeneration.


Local Therapy in Advanced Cholangiocarcinoma: A Review of Current Endoscopic, Medical, and Oncologic Treatment Options.
Endoscopic decompression of bile duct stenosis in unresectable cholangiocarcinoma (CC) may be difficult due to localization of the tumor, but it is important for pursuing oncologic treatment afterwards. Besides the initial diagnosis, jaundice and cholangitis are the most important indications for immediate endoscopic treatment. Endoscopic retrograde cholangiopancreatography is the favored approach for biliary access and stent placement. Hilar tumors are more difficult to treat and sometimes need higher endoscopic or radiologic expertise. In general, biliary decompression is accompanied by antibiotic treatment. Oncologic treatment of CC remains difficult, as it has to be interrupted when -infectious complications occur. For chemotherapy, a gemcitabine/cisplatin-based regime is favored. A validated -second-line treatment does not exist. Several therapeutic options are therefore offered to patients, including photodynamic therapy, selective internal radiotherapy, and high-dose radiotherapy. Exact treatment recommendations do not exist due to tumor rarity and lack of randomized controlled trials. In the present article, we take a look at current endoscopic, medical, and oncologic challenges from the endoscopist's point of view.


Expression and function of Neuregulin 1 and its signaling system ERBB2/3 in the enteric nervous system.
Neuregulin 1 (NRG1) is suggested to promote the survival and maintenance of the enteric nervous system (ENS). As deficiency in its corresponding receptor signaling complex ERBB2/ERBB3 leads to postnatal colonic hypo/aganglionosis we assessed the distributional and expressional pattern of the NRG1-ERBB2/ERBB3 system in the human colon and explored the neurotrophic capacity of NRG1 on cultured enteric neurons. Site-specific mRNA expression of the NRG1-ERBB2/3 system was determined in microdissected samples harvested from enteric musculature and ganglia. Localization of NRG1, ERBB2 and ERBB3 was determined by dual-label-immunohistochemistry using pan-neuronal and pan-glial markers. Morphometric analysis was performed on NRG1-stimulated rat enteric nerve cultures to evaluate neurotrophic effects. mRNA expression of the NRG1-ERBB2/3 system was determined by qPCR. Co-localization of NRG1 with neuronal or synaptic markers was analyzed in enteric nerve cultures stimulated with glial cell line-derived neurotrophic factor (GDNF). The NRG1 system was expressed in both neurons and glial cells of enteric ganglia and in nerve fibers. NRG1 significantly enhanced growth parameters in enteric nerve cell cultures and ErB3 mRNA expression was down-regulated upon NRG1 stimulation. GDNF negatively regulates ErbB2 and ErbB3 mRNA expression. The NRG1-ERBB2/3 system is physiologically present in the human ENS and NRG1 acts as a neurotrophic factor for the ENS. The down-regulation of ErbB3/ErbB2 in GDNF stimulated nerve cell cultures points to an interaction of both neurotrophic factors. Thus, the data may provide a basis to assess disturbed signaling components of the NRG1 system in enteric neuropathies.


Chinese cropland losses due to urban expansion in the past four decades.
Since 1970s, China has experienced the large-scale losses of croplands during urban expansion process, which has drawn great attentions to Chinese government. Although in-depth studies about cropland losses have been executed widely, relatively little attention has been paid to describe long term and high frequency influences of urban expansion on it and reveal its differences systematically. Based on remote sensing and GIS technology, we quantified, analyzed, and mapped cropland losses in China due to urban expansion from the national, administrative-level, population-size, and city scales. Results indicated that (1) Since the 1970s, croplands were the primary contributor to urban expansion in China, and their losses due to urban expansion underwent five obvious stages. The consciousness of cropland protection is being strengthened continuously and has developed from the initial to the deep execution stages. (2) Cropland losses were unbalanced in China, with the loss magnitude, rate, and influences on urban expansion positively related to the administrative-level and large population-size. That is, obvious losses always emerged in cities with high administrative-level and large population-size. (3) Seven basic trends of cropland losses were quantitatively recognized, which was conducive to the formulation of different policies or strategies for cropland protection for different cities.


Measurement of orientation and alignment moment relaxation by polarization spectroscopy: theory and experiment.
A diagrammatic perturbation theory description of one-color polarization spectroscopy (PS) is developed which emphasizes the significance of orientation and alignment tensor moments of the rotational angular momentum, and their collisional evolution. The influences of Doppler motion, velocity-changing collisions, decay of population, orientation and alignment, and nuclear hyperfine depolarization on the calculated PS signal are discussed. Illustrative simulations are presented of the evolution of the PS signal as a function of pump-probe laser delay. These are generated by a Monte Carlo integration of the derived equations for the signal electric field over typical experimental pump and probe laser temporal profiles and velocity distributions for a commonly studied system, the OH A 2Sigma+ -X 2Pi (0,0) band. These predictions are compared with a preliminary set of results obtained in an experimental apparatus designed for one-color polarization spectroscopy using independent pump and probe lasers. Measurements are presented using linearly polarized pump light on the Q1(2.5) transition of the OH A 2Sigma+ -X 2Pi (0,0) band with He as the collision partner. The decay of the experimental PS pump-probe signal is discussed with reference to inelastic collisional population transfer rates in the literature. It is concluded that the collisional depolarization of rotational alignment is rapid, with a rate approximately twice that of population transfer. This is consistent with previous measurements in atmospheric pressure flames. PS is shown to be a viable novel spectroscopic method for determining rotational angular momentum orientation and alignment relaxation rates, which are valuable quantities because they are sensitive probes of the forces involved in inelastic collisions.


Proactive interference and its release in short-term memory of mildly retarded adolescents.
Release from proactive interference in mildly retarded adolescents due to taxonomic shifts and rest periods prior to the final, critical-word triad was investigated. Interference accumulated rapidly across the first three trials; a shift in triad's taxonomic class on the final trial produced a substantial release (72 percent) from proactive interference. Although proactive interference dissipated when the interval between Trials 3 and 4 was increased to 120 seconds, the extent of recovery from proactive interference for the rest period plus taxonomic shift was no greater than a taxonomic shift alone. Results indicated that taxonomic category is a salient encoding dimension for retarded adolescents.


Triple pelvic osteotomy in Legg-Calvé-Perthes disease using a single anterolateral incision.
Pelvic osteotomy has a small role to play in the management of Legg-Calvé-Perthes disease. Residual acetabular dysplasia or incongruity can be corrected by rotational acetabuloplasty. In skeletally immature patients this can be performed by complete or incomplete innominate osteotomies. We present the case of a 12-year-old child with residual acetabular dysplasia, resulting from Legg-Calvé-Perthes disease, which was treated by a triple pelvic osteotomy performed by a small single anterolateral incision.


Bioinspired Rotation Microneedles for Accurate Transdermal Positioning and Ultraminimal-Invasive Biomarker Detection with Mechanical Robustness.
Microneedle permits transdermal biosensing and drug delivery with minor pain. However, accurate microneedle transdermal positioning with minimal skin deformation remains a significant technical challenge due to inhomogeneous skin topology and discontinuous force applied to the microneedle. Here, we introduce bioinspired rotation microneedles for in vivo accurate microneedle positioning as inspired by honeybees' stingers. We demonstrate the benefits of rotation microneedles in alleviating skin resistance through finite element analysis, full-thickness porcine validations, and mathematical derivations of microneedle-skin interaction stress fields. The max penetration force was mitigated by up to 45.7% and the force attenuation rate increased to 2.73 times in the holding stage after penetration. A decrease in max skin deflection and a faster deformation recovery introduced by rotation microneedles implied a more precise penetration depth. Furthermore, we applied the rotation microneedles in psoriasis mice, a monogenic disorder animal model, for minimally invasive biological sample extraction and proinflammatory cytokine monitoring. An ultrasensitive detection method is realized by using only one microneedle to achieve cytokine mRNA level determination compared to commonly required biopsies or blood collection. Thus, rotation microneedles permit a simple, rapid, and ultraminimal-invasive method for subcutaneous trace biological sample acquisition and subsequent point-of-care diagnostics with minimal damage to both microneedles and skins.


T cell receptors in autoimmune disease as targets for immune intervention.
The optimal form of treatment for an autoimmune disease should be highly specific, have few side effects, and allow treatment of clinically apparent disease. One target that could fulfill these requirements is the T cell receptor. To answer the question whether treatment of autoimmune disease is possible with anti-T cell receptor antibodies, the heterogeneity of T cell receptor elements utilized in the T cell mediated autoimmune disease experimental allergic encephalomyelitis was analyzed. The limited heterogeneity of these elements allowed prevention and treatment of clinical autoimmune disease with anti-T cell receptor monoclonal antibodies. These results and their potential value for other autoimmune diseases are discussed.


Effect of organic carbon on ammonia oxidizing bacteria in a mixed culture.
This study examined the effect of organic carbon (peptone vs. glucose) on two sequencing batch reactors performing simultaneous carbon oxidation and nitrification. Although each reactor had similar COD oxidation kinetics (0.029 and 0.036 mg COD mg VSS(-1) h(-1)), the Monod nitrification kinetics for the peptone-fed reactor (mu(m)=2.72 h(-1), K(s)=17.8 mg N L(-1)) were faster than for the glucose-fed reactor (mu(m)=0.868 h(-1), K(s)=26.5 mg L(-1)). The overall bacterial communities were profiled by 16S rRNA cloning and sequencing and revealed homology with a greater variety of bacteria from the peptone-fed reactor than the glucose-fed reactor. In addition, amoA cloning and sequencing, terminal restriction fragment length polymorphism, and fluorescent in situ hybridization experiments indicated greater AOB diversity and abundance in the peptone-fed reactor. This research provides evidence that the organic carbon source affects the make-up of the heterotroph community as well as AOB in mixed cultures.


Improving postharvest life, quality and bioactive compounds of strawberry fruits using spermine and spermidine.
Small fruits such as strawberries, are a good source of natural antioxidants. In recent decades, many efforts have been made to increase the shelf life of strawberries and maintain its nutritional value in post-harvest conditions. In the present study, the effects of spermine (Spm) and spermidine (Spd) (0, 1.0 and 1.5 mM) on the post-harvest life and quality of strawberry fruits during the 3rd, 6th, and 12th days of storage, were investigated. Applications of Spm and Spd decreased the rate of weight loss, fruit decay, soluble solids content, fruit juice pH and taste index during the storage period in compared to the control. However, titratable acids and vitamin C contents, tissue stiffness, phenolic compounds and antioxidant activity increased in compared to the control. These growth regulators prevented the aging and loss of bioactive compounds of the fruit by increasing the antioxidant activity and preventing the destruction of the fruit tissue. Among the studied treatments, applications of 1.5 mM of Spm and Spd were the most effective treatments to enhance the storage life and quality characters of strawberry fruits.


A dock and coalesce mechanism driven by hydrophobic interactions governs Cdc42 binding with its effector protein ACK.
Cdc42 is a Rho-family small G protein that has been widely studied for its role in controlling the actin cytoskeleton and plays a part in several potentially oncogenic signaling networks. Similar to most other small G proteins, Cdc42 binds to many downstream effector proteins to elicit its cellular effects. These effector proteins all engage the same face of Cdc42, the conformation of which is governed by the activation state of the G protein. Previously, the importance of individual residues in conferring binding affinity has been explored for residues within Cdc42 for three of its Cdc42/Rac interactive binding (CRIB) effectors, activated Cdc42 kinase (ACK), p21-activated kinase (PAK), and Wiskott-Aldrich syndrome protein (WASP). Here, in a complementary study, we have used our structure of Cdc42 bound to ACK via an intrinsically disordered ACK region to guide an analysis of the Cdc42 interface on ACK, creating a panel of mutant proteins with which we can now describe the complete energetic landscape of the Cdc42-binding site on ACK. Our data suggest that the binding affinity of ACK relies on several conserved residues that are critical for stabilizing the quaternary structure. These residues are centered on the CRIB region, with the complete binding region anchored at each end by hydrophobic interactions. These findings suggest that ACK adopts a dock and coalesce binding mechanism with Cdc42. In contrast to other CRIB-family effectors and indeed other intrinsically disordered proteins, hydrophobic residues likely drive Cdc42-ACK binding.


Urethral leiomyoma expressing estrogen receptors.
A case of urethral leiomyoma is presented. The patient was a 48-year-old female who was hospitalized with a 4-year history of a progressively enlarging urethral mass. Based on clinical diagnosis of benign urethral tumor, local excision was performed. Histological diagnosis was urethral leiomyoma and the tumor cells demonstrated immunoreactivity for estrogen receptors. We report our experience of a leiomyoma of the urethra expressing estrogen receptors.


Control of methicillin-resistant Staphylococcus aureus in a burn unit: role of nurse staffing.
We investigated retrospectively the spread of methicillin-resistant Staphylococcus aureus (MRS) in a burn unit. During 8 months, 34% of the patients acquired MRS, and transmission continued despite barrier isolation precautions and treatment of colonized personnel with topical intranasal antibiotics. Several findings suggested MRS was spread primarily by contact transmission involving personnel: case-control comparison showed burn size to be the major host risk factor for colonization; correlation analysis of environmental factors revealed a significant (p = 0.001) association of new cases with increased patient load and with staffing by overtime or temporary nurses; and environmental sampling yielded few colonies of MRS. The outbreak halted following implementation of control measures, among which assignment of separate nurses to colonized patients appeared to be essential. The association of different nurse staffing variables with persistence then eradication of MRS suggests nurse staffing may have been an important factor in staphylococcal transmission.


Confirmation of the protective role of proteins from S. typhimurium in infection of mice with their natural pathogen.
The protective role of proteins from S. typhi-murium in infection of mice with their natural pathogens was confirmed. Hyperimmunization with either toxic or detoxified proteins, from the same batch, induced the synthesis of strongly precipitating antiprotein antibodies, and the mice were protected against infections with 15-75 LD100 of S. typhimurium. Reinfection of the same animals with 300-500 LD100 of S. typhi-murium induced, in the vaccinated mice, the synthesis of only anti-protein antibodies precipitating in agar-gel.


Conditional Reprogramming Modeling of Bladder Cancer for Clinical Translation.
The use of advanced preclinical models has become increasingly important in drug development. This is particularly relevant in bladder cancer, where the global burden of disease is quite high based on prevalence and a relatively high rate of lethality. Predictive tools to select patients who will be responsive to invasive or morbid therapies (chemotherapy, radiotherapy, immunotherapy, and/or surgery) are largely absent. Patient-derived and clinically relevant models including patient-derived xenografts (PDX), organoids, and conditional reprogramming (CR) of cell cultures efficiently generate numerous models and are being used in both basic and translational cancer biology. These CR cells (CRCs) can be reprogrammed to maintain a highly proliferative state and reproduce the genomic and histological characteristics of the parental tissue. Therefore, CR technology may be a clinically relevant model to test and predict drug sensitivity, conduct gene profile analysis and xenograft research, and undertake personalized medicine. This review discusses studies that have utilized CR technology to conduct bladder cancer research.


Encapsulation and exfoliation of inorganic lamellar fillers into polycaprolactone by electrospinning.
The present paper reports, for the first time, the successful fabrication of layered double hydroxide (Mg-Al LDH)-reinforced polycaprolactone (PCL) nanofibers by electrospinning. Either the LDH in carbonate form or an LDH organically modified with 12-hydroxydodecanoic acid (LDH-HA) were incorporated into PCL and electrospun using a voltage of 20 KV. The LDH-HA was prepared by an ionic exchange reaction from pristine LDH and encapsulated into PCL from acetone solutions at 15 wt %. The morphological analysis showed pure PCL fibers with an average diameter of 600 +/- 50 nm, and this dimension was maintained in the fibers with LDH, with the inorganic component residing outside the fibers and not exfoliated. At variance, the fibers with the LDH-HA showed a significantly lower average diameter in the range of 350 +/- 50 nm, indicating the improved electrospinnability of PCL. Moreover, the inorganic lamellae were exfoliated, as shown by X-rays and residing inside the nanofibers as demonstrated by energy dispersive X-ray spectroscopy analysis. The structural parameters, such as degradation temperature and crystallinity, were investigated for all the samples and correlated with the electrospinning process.


Photoinduced Cyclizations of o-Diisocyanoarenes with Organic Diselenides and Thiols that Afford Chalcogenated Quinoxalines.
This study describes the syntheses of 2,3-bis(selanyl)quinoxalines via the photoinduced cyclizations of o-diisocyanoarenes with diaryl or dialkyl diselenides, in addition to providing a detailed discussion of the corresponding mechanism and revealing that the developed procedure can also be applied to prepare 2-thiolated quinoxaline derivatives from o-diisocyanoarenes and thiols. The developed technique does not need the use of additives or metal catalysts and features the advantages of a high conversion, a broad substrate scope, and mild reaction conditions, thereby rendering it a valuable addition to the quinoxaline synthesis toolbox.


Lack of association between allergic contact dermatitis and HLA antigens of the A and B series.
A previous study of patients with allergic contact dermatitis yielded results which supported the hypothesis that the presence of certain HLA antigens led to a predisposition to allergen-specific reactions and others to multiple contact sensitivity. The present study was performed to test this hypothesis. 129 patients sensitive to one allergen only (either chromium, nickel, formalin or balsam of Peru) and 83 patients sensitive to two or more allergens were HLA typed regarding the A and B loci. A series of 368 persons matched with regard to sex, age and place of residence were used as controls. A tendency towards an association between HLA B7 and contact allergy was observed. No other data confirming the hypothesis mentioned above were obtained. Among 37 patients who also had atopic diathesis a decreased frequency of HLA B7 was found.


Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11.
We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation.


Live imaging of developmental processes in a living meristem of Davidia involucrata (Nyssaceae).
Morphogenesis in plants is usually reconstructed by scanning electron microscopy and histology of meristematic structures. These techniques are destructive and require many samples to obtain a consecutive series of states. Unfortunately, using this methodology the absolute timing of growth and complete relative initiation of organs remain obscure. To overcome this limitation, an in vivo observational method based on Epi-Illumination Light Microscopy (ELM) was developed and tested with a male inflorescence meristem (floral unit) of the handkerchief tree Davidia involucrata Baill. (Nyssaceae). We asked whether the most basal flowers of this floral unit arise in a basipetal sequence or, alternatively, are delayed in their development. The growing meristem was observed for 30 days, the longest live observation of a meristem achieved to date. The sequence of primordium initiation indicates a later initiation of the most basal flowers and not earlier or simultaneously as SEM images could suggest. D. involucrata exemplarily shows that live-ELM gives new insights into developmental processes of plants. In addition to morphogenetic questions such as the transition from vegetative to reproductive meristems or the absolute timing of ontogenetic processes, this method may also help to quantify cellular growth processes in the context of molecular physiology and developmental genetics studies.


Ni Mg Mixed Metal Oxides for p-Type Dye-Sensitized Solar Cells.
Mg Ni mixed metal oxide photocathodes have been prepared by a mixed NiCl2/MgCl2 sol-gel process. The MgO/NiO electrodes have been extensively characterized using physical and electrochemical methods. Dye-sensitized solar cells have been prepared from these films, and the higher concentrations of MgO improved the photovoltage of these devices; however, there was a notable drop in photocurrent with increasing Mg(2+). Charge extraction and XPS experiments revealed that the cause of this was a positive shift in the energy of the valence band, which decreased the driving force for electron transfer from the NiO film to the dye and, therefore, the photocurrent. In addition, increasing concentrations of MgO increases the volume of pores between 0.500 and 0.050 μm, while reducing pore volumes in the mesopore range (less than 0.050 μm) and lowering BET surface area from approximately 41 down to 30 m(2) g(-1). A MgO concentration of 5% was found to strike a balance between the increased photovoltage and decreased photocurrent, possessing a BET surface area of 35 m(2) g(-1) and a large pore volume in both the meso- and macropore range, which lead to a higher overall power conversion efficiency than NiO alone.


Sulfhydryls and the in vitro polymerization of tubulin.
The free sulfhydryls of brain tubulin prepared by cyclic polymerization procedures both with and without glycerol have been examined. The average free sulfhydryl titer of tubulin prepared with glycerol (7.0 sulfhydryls/55,000 mol wt) is greater than that of tubulin prepared without glycerol (4.0 sulfhydryls/55,000 mol wt). Diamide, a sulfhydryl-oxidizing agent, inhibits the polymerization of tubulin. Diamide also disperses the 20S and 30S oligomers of tubulin seen in analytical ultracentrifuge patterns of tubulin solutions and, depending on the temperature at which diamide is added, converts all or part of the oligomeric material to 6S dimers. Electron microscopy demonstrates that diamide also destroys the 450-A ring structures characteristic of tubulin solutions. All diamide effects are reversible by the addition of 10 mM dithioerythreitol, a sulfhydryl-reducing agent. That diamide interacts with sulfhydryls on tubulin is directly demonstrated by a 50% decrease in the free sulfhydryl titer of tubulin measured after diamide treatment. Concentrations of CaCl2 which inhibit polymerization also decrease the free sulfhydryl titer of tubulin.


Patients with alcohol-related liver disease hospitalized during the COVID-19 pandemic experienced worse outcomes.
Psychosocial stressors related to the coronavirus-19 (COVID-19) pandemic increased alcohol consumption. The effect on patients with alcohol-related liver diseases remains unclear. Hospitalizations at a tertiary care center due to alcohol-related liver disease from March 1 through August 31 in 2019 (pre-pandemic cohort) and 2020 (pandemic cohort) were reviewed retrospectively. Differences in patient demographics, disease features, and outcomes were estimated in patients with alcoholic hepatitis utilizing T-tests, Mann-Whitney tests, Chi-square and Fisher Exact Tests and Anova models and logistic regression models in patients with alcoholic cirrhosis. 146 patients with alcoholic hepatitis and 305 patients with alcoholic cirrhosis were admitted during the pandemic compared to 75 and 396 in the pre-pandemic cohort. Despite similar median Maddrey Scores (41.20 vs. 37.45, p=0.57), patients were 25% less likely to receive steroids during the pandemic. Patients with alcoholic hepatitis admitted during the pandemic were more likely to have hepatic encephalopathy (0.13; 95% CI:0.01, 0.25), variceal hemorrhage (0.14; 95% CI:0.04, 0.25), require oxygen (0.11; 95% CI:0.01, 0.21), vasopressors (OR:3.49; 95% CI:1.27, 12.01) and hemodialysis (OR:3.70; 95% CI:1.22, 15.13). On average, patients with alcoholic cirrhosis had MELD-Na scores 3.77 points higher (95% CI:1.05, 13.46) as compared to the pre-pandemic and had higher odds of experiencing hepatic encephalopathy (OR:1.34; 95% CI:1.04, 1.73), spontaneous bacterial peritonitis (OR:1.88; 95% CI:1.03, 3.43), ascites (OR:1.40, 95% CI:1.10, 1.79), vasopressors (OR:1.68, 95% CI:1.14, 2.46) or inpatient mortality (OR:2.00, 95% CI:1.33, 2.99) than the pre-pandemic. Patients with alcohol-related liver disease experienced worse outcomes during the pandemic.


New solutions for type 2 diabetes mellitus: the role of pioglitazone.
Type 2 diabetes mellitus remains a significant burden to the Canadian healthcare system. Over 2 million Canadians have diabetes, with 85 to 90% having type 2 diabetes. Insulin resistance is a major pathophysiological mechanism in the development of type 2 diabetes. Insulin resistance can be defined as an impaired biological response to the metabolic and/or mitogenic effects of either exogenous or endogenous insulin. As a consequence of insulin resistance, type 2 diabetes is characterised by decreased glucose transport and utilisation at the level of muscle and adipose tissue and increased glucose production by the liver. The traditional oral agents used to treat type 2 diabetes clearly do not address the underlying insulin resistance responsible for the development of diabetes. Thiazolidinediones (TZDs) represent a relatively new class of oral hypoglycaemic medications that have been shown to reverse some of the metabolic processes believed responsible for the development of insulin resistance and, ultimately, type 2 diabetes. Research has demonstrated that TZDs activate peroxisome proliferator activator receptors, in particular, the gamma-receptor isoform. Pioglitazone is a TZD that reduces plasma glucose levels by increasing peripheral glucose utilisation and decreasing hepatic glucose production. Clinical studies with pioglitazone have demonstrated the following: absolute reductions in glycosylated haemoglobin of 0.8 to 2.6%; reductions in fasting plasma glucose of 1.7 to 4.4 mmol/L; an increase in high density lipoprotein cholesterol of 8.7 to 12.6%; and a decrease in triglycerides of 18.2 to 26.0%, with no significant effects on low density lipoprotein or total cholesterol.


Effect of subclinical, clinical and supraclinical doses of calcium channel blockers on models of drug-induced hepatotoxicity in rats.
Drug-related hepatotoxicity is the leading cause of acute liver failure, and hepatic problems are responsible for a significant number of liver transplantations and deaths worldwide. Calcium has been associated with various metabolic processes that lead to cell death and apoptosis, and increased cytosolic Ca(2+) has been implicated in hepatotoxicity. This study was designed to investigate the effects of calcium channel blockers (CCBs) on isoniazid-rifampicin, zidovudine and erythromycin-induced hepatotoxicity in rats. Treatment groups comprised control, hepatotoxicant, hepatotoxicant along with each of silymarin, nifedipine, verapamil and diltiazem at subclinical, clinical and supraclinical doses. A day to the end of treatment for each model, rats were subjected to the hexobarbitone-induced hypnosis test. On the last days of treatment, blood samples were collected and serum was analyzed for relevant biochemical parameters. Animals were sacrificed after blood collection and livers were harvested, and samples obtained for in vivo antioxidant indices assay and histopathology. The hepatotoxicants significantly increased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), as well as duration of sleep in the hypnosis test. These drugs significantly reduced the hepatic levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and increased the level of malondialdehyde (MDA). The CCBs at the various doses significantly reversed the effects of isoniazid-rifampicin, zidovudine and erythromycin. The results obtained in this study suggest that the CCBs possess hepatoprotective activity in drug-induced hepatotoxicity and may be beneficial at the subclinical and clinical doses.


The Recruitment and Activation of Plasminogen by Bacteria-The Involvement in Chronic Infection Development.
The development of infections caused by pathogenic bacteria is largely related to the specific properties of the bacterial cell surface and extracellular hydrolytic activity. Furthermore, a significant role of hijacking of host proteolytic cascades by pathogens during invasion should not be disregarded during consideration of the mechanisms of bacterial virulence. This is the key factor for the pathogen evasion of the host immune response, tissue damage, and pathogen invasiveness at secondary infection sites after initial penetration through tissue barriers. In this review, the mechanisms of bacterial impact on host plasminogen-the precursor of the important plasma serine proteinase, plasmin-are characterized, principally focusing on cell surface exposition of various proteins, responsible for binding of this host (pro)enzyme and its activators or inhibitors, as well as the fibrinolytic system activation tactics exploited by different bacterial species, not only pathogenic, but also selected harmless residents of the human microbiome. Additionally, the involvement of bacterial factors that modulate the process of plasminogen activation and fibrinolysis during periodontitis is also described, providing a remarkable example of a dual use of this host system in the development of chronic diseases.


The efficacy of acupuncture on menopausal symptoms (ACOM study): protocol for a randomised study.
Around 75% of menopausal women experience hot flushes (HF) and 10-20% of all postmenopausal women find this very distressing. The aim of this study is to evaluate the efficacy of acupuncture on moderate-to-severe menopausal symptoms in general and HF in particular. An un-blinded randomised trial (cross-over) with 1:1 allocation to early (intervention) versus late (control) acupuncture. The included women suffer from moderate-to-severe HF and will receive a weekly treatment during five consecutive weeks in the following predefined acupuncture points: CV-3, CV-4, LR-8, SP-6, SP-9. All acupuncturists will be medical doctors educated in acupuncture. The primary outcome is change in HF from baseline to week 6 measured by the HF scale from the MenoScores Questionnaire (MSQ). Secondary outcomes are change in other menopausal symptoms, in particular day and night sweats and menopausal-specific sleeping problems, also measured by other scales from the MSQ. A total of 68 patients must be enrolled to detect a relevant clinical reduction on the above MSQ scales. Both intention-to-treat and per-protocol analyses will be conducted; four or more treatments are considered adequate adherence. In the ACOM study, we explore the potential benefits of acupuncture on moderate-to-severe meno-pausal symptoms. The cross-over design offers the possi-bility of examining the legacy effect of acupuncture. The Idella Foundation, the University of Copenhagen and the Research Foundation of General Practice. Clinicaltrials NCT02746497.


Our initial learning curve in the enzymatic debridement of severely burned hands-Management and pit falls of initial treatments and our development of a post debridement wound treatment algorithm.
Excisional surgical debridement (SD) is still the gold standard in the treatment of deeply burned hands, though the intricate anatomy is easily damaged. Previous studies demonstrated that enzymatic debridement with the bromelain debriding agent NexoBrid® (EDNX) is more selective and thus can preserve viable tissue with excellent outcome results. So far no method paper has been published presenting different treatment algorithms in this new field. Therefore our aim was to close this gap by presenting our detailed learning curve in EDNX of deeply burned hands. We conducted a single-center prospective observational clinical trial treating 20 patients with deeply burned hands with EDNX. Different anaesthetic procedures, debridement and wound treatment algorithms were compared and main pitfalls described. EDNX was efficient in 90% of the treatments though correct wound bed evaluation was challenging and found unusual compared to SD. Post EDNX surprisingly the majority of the burn surface area was found overestimated (18 wounds). Finally we simplified our process and reduced treatment costs by following a modified treatment algorithm and treating under plexus anaesthesia bedside through a single nurse and one burn surgeon solely. Suprathel® could be shown to be an appropriate dressing for wound treatment after EDNX. Complete healing (less 5% rest defect) was achieved at an average of day 28. EDNX in deep burned hands is promising regarding handling and duration of the treatment, efficiency and selectivity of debridement, healing potential and early rehabilitation. Following our treatment algorithm EDNX can be performed easily and even without special knowledge in burn wound depth evaluation.


Pure Bilateral Perilunate Dislocation of the Carpus: An Uncommon Case in a Military Parachutist during a Jumping Accident.
Perilunate dislocations are uncommon injuries requiring high-energy trauma. They are responsible for serious lesions that can compromise the function of the limb. We report a case of pure bilateral perilunate dislocation in a parachutist while landing. The case involved a 30-year-old military officer of special forces who underwent closed trauma to both wrists following an automatic opening parachute jump. He had first consulted a garrison medical center where a wrist sprain had been treated. Given the persistence of the pain, he was referred to our clinic 2 months later. X-rays of the wrists showed bilateral perilunate dislocation, type 1 on the right and type 3 on the left, according to the Witvoët and Allieu classification. Surgery was indicated with 2 open scapholunate and lunotriquetral pins. The post-operative course was simple, with a complete resumption of professional activity after 9 months. Perilunate dislocations of the carpus are uncommon injuries that often go unnoticed. They can also occur after a parachute landing. Treatment must be surgical.


Plasmodium berghei: pulmonary oedema and changes in clotting and fibrinolysis during infection in mice.
Mice infected with Plasmodium berghei, during the ten days of infection, showed significant pulmonary oedema, delayed activated partial thromboplastin time, augmented plasma fibrinolytic activity, oscillations in fibrinogen and unchanged plasminogen levels. These alterations can be expected to cause the release of inflammatory peptides, leading to increased vascular permeability and the generation and/or maintenance of the pronounced pulmonary oedema affecting these animals.


Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy revisited: Genotype-phenotype correlations of all published cases.
The aim of this study was to evaluate the correlation between the various NOTCH3 mutations and their clinical and genetic profile, along with the presentation of a novel mutation in a patient. Here, we describe the phenotype of a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) harboring a novel mutation. We also performed an extensive literature research for NOTCH3 mutations published since the identification of the gene and performed a systematic review of all published cases with NOTCH3 mutations. We evaluated the mutation pathogenicity in a great number of patients with detailed clinical and genetic evaluation and investigated the possible phenotype-genotype correlations. Our patient harbored a novel mutation in the NOTCH3 gene, the c.3084 G > C, corresponding to the aminoacidic substitution p.Trp1028Cys, presenting with seizures as the first neurologic manifestation. We managed to find a correlation between the pathogenicity of mutations, severity of the phenotype, and age at onset of CADASIL. Significant differences were also identified between men and women regarding the phenotype severity. The collection and analysis of these scarce data published since the identification of NOTCH3 qualitatively by means of a systematic review and quantitatively regarding genetic profile and pathogenicity scores, highlight the significance of the ongoing trend of investigating phenotypic genotypic correlations.


Wnt and Kras signaling-dark siblings in lung cancer.
Aberrant Kras signaling is observed in a high percentage of human lung cancers while activating mutations in the Wnt/b-catenin signaling pathway are only rarely found. Our recent work has shown that the combined activation of both Kras and Wnt/b-catenin signaling leads to a dramatic increase in both tumor incidence and size. Moreover, lung tumors generated by the combined activation of both of these pathways exhibit a distinct phenotype similar to embryonic progenitors found in the developing lung. Thus, combinatorial activation of Kras and Wnt/b-catenin pathways leads to a significant increase in lung tumor formation characterized by a more progenitor like phenotype.


Induction of IL-10 synthesis by human keratinocytes through CD23 ligation: a cyclic adenosine 3',5'-monophosphate-dependent mechanism.
Ligation of the low affinity receptor for IgE, CD23/Fc epsilonRII, in human keratinocytes (HK) and monocytes induces the synthesis of proinflammatory cytokines (IL-6 and TNF-alpha), partly under the dependence of cAMP and nitric oxide pathways. Moreover, CD23 ligation induces IL-10 production in human monocytes. Since synthesis of IL-10 by HK is still a matter of debate, we investigate whether keratinocytes could produce IL-10 upon CD23 stimulation. Here, our data show that CD23 ligation induces significant IL-10 synthesis in HK, a phenomenon inhibited by cAMP antagonists, but not by inhibitors of the nitric oxide pathway. Accordingly, cAMP agonist induced significant IL-10 synthesis by HK, while nitric oxide-releasing chemical did not. Treatment of HK with anti-IL-10 mAb potentiated their CD23-mediated TNF-alpha synthesis. These data indicate that engagement of surface CD23 on human keratinocytes induces the synthesis of IL-10, which, in turn, down-regulates their proinflammatory response.


Incidence of HER2-expressing brain metastases in patients with HER2-null breast cancer: a matched case analysis.
The HER2-directed antibody-drug conjugate trastuzumab deruxtecan is active against lower levels of HER2 expression than prior-generation therapies. The rate of HER2 expression in brain metastases among patients with initially HER2-null breast cancer is undefined, and receptor discordance in advanced breast cancer with brain metastases may underestimate CNS response potential in the absence of brain metastasis sampling. In this cohort study including 136 patients with 401 samples scored according to ASCO/CAP guidelines, 15/28 patients (54%) with HER2-null primary breast cancer have detectable HER2 expression in subsequently resected brain metastases, a significant discordant population.


30 W-average-power femtosecond NIR laser operating in a flexible GHz-burst-regime.
Laser sources which produce GHz bursts of ultrashort pulses attract a lot of attention by demonstrating superior performance in material processing. Flexibility of the laser source in a selection of parameters for custom application is highly preferable. In this work, we demonstrate a very versatile method for burst formation using the active fiber loop (AFL). It allows forming GHz bursts containing from 2 up to approximately 2200 pulses in a burst (1000 ns burst width) with identical pulse separation and any predefined intra-burst pulse repetition rate (PRR). The burst pre-shaping by the amplification conditions in the AFL and by the modulation of transmission of the acousto-optic modulator was demonstrated. Industrial-grade ultrafast laser system was able to operate in the single-pulse and GHz-burst regimes. The laser system delivered high-quality 368 fs duration (FWHM) pulses of 15.3 µJ pulse energy and 30.6 W average output power at 2 MHz PRR in the single-pulse regime. In the GHz-burst operation regime, bursts of 2.2 GHz intra-burst repetition rate were formed and amplified to more than 30 W average output power with a burst energy up to 135 µJ at a burst repetition rate of 200 kHz. The sub-picosecond duration of pulses was obtained in the GHz-burst regime at different burst widths.


Does the preoperative neutrophil-to-lymphocyte ratio have a prognostic value in aneurysmal bone cysts?
The aim of this study was to evaluate the prognostic value of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-tomonocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in aneurysmal bone cysts (ABCs). Between February 2001 and August 2019, a total of 86 patients (44 males, 42 females; mean age: 21.5±15.2 years; range, 2 to 73 years) with a histologically confirmed diagnosis of ABCs who did not receive cancer treatment previously and had a minimum follow-up period of 24 months were retrospectively analyzed. Data including age, sex, side, tumor location, pre-treatment complete blood count analysis results, preferred surgical method, follow-up period, presence of recurrence, and date of recurrence were recorded. Preoperative NLR, LMR and PLR values were calculated in all patients. The mean follow-up was 56.7±13.5 (range, 24 to 179) months. Forty-one (47.7%) ABCs were located in the lower extremities, 36 (41.8%) in the upper extremities, and nine (10.4%) in the pelvic girdle. A statistically significant difference was detected in the NLR values according to recurrence status (p=0.023). The PLR and LMR values were not significant for area under the curve, while NLR values were significant for recurrence. The cut-off value was determined as 2.054. Those with an NLR of ≥2.054 were found to have a 4.561-fold higher risk of recurrence than those with an NLR of <2.054 (odds ratio [OR]=4.561). Our study results suggest that NLR, which is the pre-treatment inflammatory index, is a prognostic factor in patients with ABCs. Although NLR alone is not decisive in patients with elevated NLR, it can be used to evaluate the clinical prognosis and recommend an appropriate treatment strategy.


Purification and some properties of rabbit C1 inactivator.
C1 inactivator (C1 INA) was highly purified from rabbit serum. C1 INA thus purified was a single polypeptide chain with a molecular weight of 105,000 or 140,000, as estimated by SDS-polyacrylamide gel electrophoresis or gel filtration on Sephadex G-200, respectively. It inhibited rabbit and also human C1, when the C1 activities were measured in terms of hydrolyses of acetylglycyl-L-lysine methylester, N-alpha-acetyl-L-arginine methylester and N-alpha-acetyl-L-tyrosine ethylester. These properties showed that rabbit C1 INA bears a marked structural similarity to human C1 INA. Furthermore, rabbit C1 INA was capable of inhibiting similarly both rabbit C1s and its active fragment lacking a half of the H chain of C1s, indicating that deletion of a half of the H chain did not affect the susceptibility of C1s to the inhibitory activity of C1 INA.


Effects of eccentric overload bout on change of direction and performance in soccer players.
The aims of this study were to analyse the effects of eccentric overload training (EOT) on kinetic parameters during change of direction (COD) and performance related to sprinting and jumping abilities. 20 male soccer players performed 2 different protocols: 1) 5-min cycling warm-up and 2) 5-min cycling warm-up+YoYo half-squat exercise. The outcome measured included vertical ground reaction force (vGRF) and propulsive force (PvGRF), time to vGRF (T_vGRF) and propulsive force (T_PvGRF), contact time (CT), eccentric (ECC_IMP), concentric (CONC_IMP) and total (TOT_IMP) impulses and moments (Mx, My and Mz) during 2 COD tasks. Additionally, subjects performed a counter-movement jump (CMJ) and 20 m sprint tests. Results showed a substantial better improvement (likely to almost certainly) in vGRF (ES: 0.84), vAGRF (ES: 0.72), CT (ES: 0.48), My (ES: 0.35), Mz (ES: 0.44) and ECC_IMP (ES: 0.45) during crossover cutting maneuver, whereas during side-step cutting maneuver Time_ECC (ES: 0.68), CT (ES: 0.64), vGRF (ES: 0.48) and My (ES: 0.47) were substantially enhanced (likely). Furthermore, substantial better performance was found in CMJ (ES: 0.47; very likely) and 20 m (ES: 0.20; possibly). In conclusion, EOT produced a better muscle activation during 2 different COD tasks and greater sprinting and jumping performance.


[Short-term effects of fine particulate matter exposure on pulmonary function in healthy young adults: a time series study].
Objective: To explore the short-term effects of fine particulate matter (PM2.5) exposure on pulmonary function of healthy young adults in Beijing. Methods: In this time series study, twenty-four healthy young adults who living around Guanyuan area were investigated in Beijing. The follow-up study was lasted for 12 days in total from Nov. 28, 2016 to Dec. 9, 2016, and pulmonary spirometry and inpulse oscillometry parameters were measured daily. Air pollution data (including PM2.5, etc.) and meteorological data (temperature, humidity, etc.) were monitored based on Guanyuan monitoring site. The short-term effects of PM2.5 on pulmonary ventilation function and airway resistance of healthy young adults were analyzed by using generalized estimating equation (GEE). Results: In our study period, average daily concentration of PM2.5 were 100.7 μg/m(3). The single pollutant model showed that there were negative dose-response associations between PM2.5 concentration and forced vital capacity (FVC) and forced expiratory volume in one second (FEV(1)); and there were negatively correlated with daily mean level of PM2.5 lagged 0-1 days, and the strongest negative effect was in lag0. At lag0 day, each 10 μg/m(3) increase in PM2.5 concentration was associated with a significant decrease in FVC of 12.186 (95% CI: -15.573, -8.799) ml and in FEV(1) of 9.449 (95% CI: -13.265, -5.634) ml. Moreover, there were positive dose-response associations between PM2.5 concentration at lag0 to lag2 and peripheral resistance (Rp) , resonance frequency (Fres) and the fall in resistance between resistance at 5 Hz (R5) and resistance at 20 Hz (R20) (R(5-20)). And the strongest negative effect was in lag0. Each 10 μg/m(3) increase in PM2.5 concentration was associated with a significant increase in Rp of 2.444 (95% CI: 0.889, 3.999) Pa·L(-1)·s(-1) , Fres of 0.125 (95% CI: 0.082, 0.168) Hz and R(5-20) of 1.074 (95% CI: 0.444, 1.703) Pa·L(-1)·s(-1) at lag0 day. Conclusion: Short-term PM2.5 exposure has a negative and lagged effect on pulmonary function in healthy young adults.


Coalescence of inter: Osteotomy bone graft material inserted via separate transcrestal sinus osteotomies: A case report and concise review of the literature.
When multiple implants are to be placed, and a pneumatized sinus exists, the published reports suggest that the lateral window approach (LWA) is favored for sinus floor augmentation. Simultaneously, if a transcrestal sinus floor augmentation has been carried out (bone-added osteotome sinus floor elevation), the reports are restricted to single implant placement at any site. The aim of this study was to evaluate the clinical and radiographic outcomes at adjacent transcrestal sinus augmentation grafts using deproteinized bovine bone material, with the immediate placement of submerged adjacent implants, and so determining the fate of the graft material. The progressive loss of the inter-implant graft is reported for the LWA Technique. However, this novel coalescence method has shown a progressive increase in the inter-implant graft region, thus inferring a positive bony regeneration and remodelling at the region. These results indicate that the carrying out of a large scale study is warranted to confirm the efficacy of this technique.


The treatment and outcome analysis of primary squamous cell carcinoma of the thyroid.
Primary squamous cell carcinoma (SCC) of the thyroid is a rare disease. It usually presents with locally advanced disease and has an overall poor prognosis. In this study, we investigated the characteristics and outcomes of patients with SCC of the thyroid, and reported our experience with chemotherapy with lenvatinib in the treatment of SCC of the thyroid. The management outcome of 10 patients who had SCC of the thyroid between January 2000 and 2015 at Kyushu University Hospital or associated facilities was reviewed. There were 3 males and 7 females, ranging in age from 53 to 77 years. Extent of disease was staged as follows: stage IVA, 3 cases; stage IVB, 3 cases; stage IVC, 4 cases. Only tracheostomy was applied for 2 cases, surgical resection, such as total thyroidectomy and neck dissection, for the other 8 cases. Radiotherapy following surgical treatment was applied for 9 cases. Four patients started on oral lenvatinib due to recurrent or progressive SCC of the thyroid. The one year actuarial survival rate of patients was 22.7%. There was no 2-year survivor of all patients. Treatment should primarily be targeted at surgical resection with negative margins in patients with resectable disease. Lenvatinib may show promise to potentially extend survival.


Human gingiva-derived mesenchymal stem cells alleviate inflammatory bowel disease via IL-10 signalling-dependent modulation of immune cells.
Current evidence indicates that inflammatory bowel disease (IBD) is caused primarily by impaired mucosal immunity, resulting in an imbalance between epithelial barrier function and tissue inflammation. Human gingiva-derived mesenchymal stem cells (GMSCs) exhibit immunomodulatory and anti-inflammatory effects in a variety of immunity- and inflammation-associated diseases. However, the role of GMSCs in treating IBD has not been elucidated. Our study, therefore, examined the therapeutic effect and mechanism of GMSCs in a murine colitis model of IBD. Our results indicate that the infusion of GMSCs significantly prolonged survival and relieved symptoms. Phenotype analyses showed that the frequencies of NK1.1+ and CD11b+ cells, as well as CD4 T cells in the spleen, were suppressed in GMSC-treated mice compared with the PBS- or fibroblast-treated control groups. Additionally, GMSC treatment markedly increased the numbers of interleukin (IL)-10+ regulatory T cells, reduced the secretion of pro-inflammatory cytokines, and increased production of anti-inflammatory cytokines. A mechanistic study revealed that anti-IL-10R antibody abolished the protective effect of GMSCs compared with mice treated with anti-IgG antibody. Thus, our results indicate that GMSCs play a critical role in alleviating colitis by modulating inflammatory immune cells via IL-10 signalling.


[Udder health management practices in dairy enterprises to reduce the incidence of bovine mastitis].
An effective programme to reduce mastitis on farm level focuses on both decreasing the rate of mastitis incidence and shortening the duration of existing infections. Therefore, the present paper deals with the identification of those evidence-based management practices which are known to reduce the mastitis incidence on farm level. Corresponding practices in the areas of personnel, breeding, husbandry, feeding and milking are presented and evaluated. As most factors evaluated here pose a "pathogen-specific" risk rather than a "general" one, any systematic measure designed to control mastitis in a given herd has to consider this by performing a structured risk analysis based on the specific bacteriological findings.


Stability of vertical magnetic chains.
A linear stability analysis is performed for a pair of coaxial vertical chains made from permanently magnetized balls under the influence of gravity. While one chain rises from the ground, the other hangs from above, with the remaining ends separated by a gap of prescribed length. Various boundary conditions are considered, as are situations in which the magnetic dipole moments in the two chains are parallel or antiparallel. The case of a single chain attached to the ground is also discussed. The stability of the system is examined with respect to three quantities: the number of balls in each chain, the length of the gap between the chains, and a single dimensionless parameter which embodies the competition between magnetic and gravitational forces. Asymptotic scaling laws involving these parameters are provided. The Hessian matrix is computed in exact form, allowing the critical parameter values at which the system loses stability and the respective eigenmodes to be determined up to machine precision. A comparison with simple experiments for a single chain attached to the ground shows good agreement.


Rab25 is responsible for phosphoinositide 3-kinase/AKT‑mediated cisplatin resistance in human epithelial ovarian cancer cells.
Rab25, a member of the Rab family of small guanosine triphosphatase, was reported to have an essential role in the development of human epithelial ovarian cancer. The present study demonstrated that Rab25 mediated the sensitivity of ovarian cancer to cisplatin, a first‑line chemotherapeutic agent for the treatment of ovarian cancer in the clinic. Overexpression of Rab25 and increased phosphoinositide 3‑kinase (PI3K)/AKT signaling were detected in cisplatin‑resistant SKOV‑3 cells compared with those in cisplatin‑sensitive ES‑2 cells. The results of the present study indicated that cisplatin resistance was primarily due to reduced G1 cell cycle arrest following cisplatin treatment in SKOV‑3 cells. By contrast, the corresponding phenomenon was not observed following treatment with a Rab25‑specific small interfering RNA or treatment with the PI3K/AKT inhibitor LY294002. Of note, inhibition of the PI3K/AKT pathway reduced Rab25 gene expression and sensitized SKOV‑3 cells to cisplatin. Furthermore, knockdown of Rab25 showed an effect comparable with blocking the PI3K/AKT pathway. In conclusion, the results of the present study demonstrated that PI3K/AKT and Rab25 significantly contributed to cisplatin resistance in human epithelial ovarian cancer; in addition, silencing Rab25 or inhibiting the PI3K/AKT pathway markedly increased the sensitivity of these cells to cisplatin.


Anti-Müllerian hormone (AMH) as a good predictor of time of menopause.
Anti-Müllerian hormone (AMH) in women is secreted by granulosa cells in late preantral and small antral follicles. AMH seems to be a very stable marker having some advantages over other biochemical and biophysical markers and is very useful in the assessment of ovarian reserve. AMH measurement may be used in cases of premature ovarian failure, including iatrogenic, due to treatment for cancer, hypogonadotropic hypogonadism, and lastly, in polycystic ovary syndrome (PCOS). It is also a very specific marker of ovarian tumors - folliculomas. According to outcomes of some studies, AMH seems to be highly predictive for the timing of menopause. There are mathematical models in which a single AMH measurement is used to predict the time of menopause even in very young women, many years before the last period.


All that glitters is not gold: a stereological study of human donor oocytes.
Here we report a quantitative analysis of human metaphase II (MII) oocytes from a 22-year-old oocyte donor, retrieved after ovarian-controlled hyperstimulation. Five surplus donor oocytes were processed for transmission electron microscopy (TEM), and a stereological analysis was used to quantify the distribution of organelles, using the point-counting technique with an adequate stereological grid. Comparisons between means of the relative volumes (Vv) occupied by organelles in the three oocyte regions, cortex (C), subcortex (SC) and inner cytoplasm (IC), followed the Kruskal-Wallis test and Mann-Whitney U-test with Bonferroni correction. Life cell imaging and TEM analysis confirmed donor oocyte nuclear maturity. Results showed that the most abundant organelles were smooth endoplasmic reticulum (SER) elements (26.8%) and mitochondria (5.49%). Significant differences between oocyte regions were found for lysosomes (P = 0.003), cortical vesicles (P = 0.002) and large SER vesicles (P = 0.009). These results were quantitatively compared with previous results using prophase I (GV) and metaphase I (MI) immature oocytes. In donor MII oocytes there was a normal presence of cortical vesicles, SER tubules, SER small, medium and large vesicles, lysosomes and mitochondria. However, donor MII oocytes displayed signs of cytoplasmic immaturity, namely the presence of dictyosomes, present in GV oocytes and rare in MI oocytes, of SER very large vesicles, characteristic of GV oocytes, and the rarity of SER tubular aggregates. Results therefore indicate that the criterion of nuclear maturity used for donor oocyte selection does not always correspond to cytoplasmic maturity, which can partially explain implantation failures with the use of donor oocytes.


[Reference ranges of gestational weight gain in Chinese population on the incidence of macrosomia: a multi-center cross-sectional survey].
Objective: To investigate the influence of gestational weight gain (GWG) on the incidence of macrosomia, and to establish the reference ranges of GWG based on the incidence of macrosomia. Methods: A multicenter, cross-sectional study was conducted. Totally, 112 485 women were recruited from 39 hospitals in 14 provinces in China. Totally, 61 149 cases were eligible with singleton pregnancies and non-premature deliveries. The associations of pre-pregnancy body mass index (BMI), GWG, newborn gender and gestational diabetes with macrosomia were analyzed with logistic regression. The normal GWG ranges were calculated in all maternal BMI subgroups, based on the normal incidence of macrosomia was set as the range of 5.0% to 10.0%. Results: In this study, the incidence of macrosomia was 7.46% (4 563/611 149). The macrosociam was positive related with maternal height, delivery week, pre-pregnancy BMI, GWG, gestational diabetes, primipara, and male babies significantly (P<0.05), based on unadjusted and adjusted logestic regression. The normal range of GWG 20.0-25.0, 10.0-20.0, 0-10.0 and 0-5.0 kg in subgroups of underweight (pre-pregnancy BMI<18.5 kg/m(2)), normal (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)) and obese (≥30.0 kg/m(2)), respectively. Conclusion: The reference range of GWG in China based on the incidence of macrosomia is established.


The role of physiotherapy after total knee arthroplasty in patients with haemophilia.
With the availability of clotting factor concentrates, advances in surgical techniques, better implant design, and improvements in postoperative management, total knee arthroplasty has become the treatment of choice for haemophilia patients suffering from end-stage haemophilic knee arthropathy. The success of this surgery is also dependent on close collaborations among the orthopaedic surgeon, the haematologist and the physiotherapist. Although haemophilic patients undergoing this surgery would likely benefit from a targeted rehabilitation programme, its specificities, modalities and limitations have thus far not been extensively studied. Employing the published data of rehabilitation after knee prosthesis in patients with osteoarthritis and haemophilic arthropathy along with clinical experience, the authors present a comprehensive and original review of the role of physiotherapy for patients with haemophilia undergoing knee arthroplasty.


Necrotizing enterocolitis in full-term or near-term infants: risk factors.
A retrospective case-control study of necrotizing enterocolitis (NEC) affecting infants weighing > 2,000 g at birth was performed to determine those factors which could contribute to the development of NEC. Twenty-four infants met the criteria of definite NEC. For each case the next 2 healthy newborns were matched as controls. When compared with the control group, NEC infants had a significantly higher frequency of prolonged rupture of membranes, chorioamnionitis, Apgar score < 7 at 1 and 5 min, respiratory problems, congenital heart disease, hypoglycemia, and exchange transfusions. Only 3 infants with NEC were healthy newborns with an unremarkable perinatal course before NEC. There were no differences in the frequency of preeclampsia, maternal diabetes, maternal drug abuse, meconium-stained amniotic fluid and polycythemia. These results indicate that most of these more mature infants have a predisposing factor before developing NEC.


Conservative treatment of eminentia intercondylaris fractures of the tibia in children.
Seventeen patients (16 children, 1 adolescent) were reviewed 31 months to 71 months after sustaining the common childhood fracture of the eminentia intercondylaris of the tibia. The aim was to assess long-term results and prognosis by clinical and radiological examination and to discover whether conservative treatment was adequate for type I and type II fractures according to Meyers and McKeever. Early improvement occurred in all patients after conservative treatment, but long-term results were not satisfactory in displaced fractures,which were treated with closed reduction and immobilization in extension. Therefore, anatomic reduction and rigid fixation should be obtained for displaced fractures of the eminentia intercondylaris of the tibia.


Weight history over a forty-year time period.
Mortality and disease risk assessments consider body mass index (BMI), among other parameters. Nowadays optimal BMI is discussed controversially as risk assessments are usually performed using BMI of arbitrarily chosen age points. A more comprehensive approach could be based on BMI history. However, longitudinal studies investigating BMI are rare. To determine pragmatically different weight history patterns over forty years. Longitudinal study with four follow-ups over forty years, elucidating risk factors for peripheral vessel diseases as the original goal. There were 343 male subjects whose weight was measured both at baseline and at follow-ups. Based on pragmatic methods the following eight patterns were found: "stable" (24.8%), "stable and increasing" (28.6%), "stable and decreasing" (9.0%), "hill" (10.0%), "valley" (7.0%), "yo-yo" (14.0%), continually "increasing" (6.4%%), and continually "decreasing" (0.3%). In subjects over 45 years at baseline, stable patterns were most frequent (42%), and descending patterns became more prominent. The determination of different weight history patterns in a longitudinal study is possible with the use of a pragmatic procedure. Applying such weight history patterns to the mortality risk assessment of overweight could add new aspects to that risk assessment.


Genotyping of Toxoplasma gondii strain directly from human CSF samples of congenital toxoplasmosis clinical case.
This report describes a case of congenital toxoplasmosis in a newborn in Southern Italy. A pregnant mother had been admitted at the 20th week of her pregnancy on account of pharyngodynia and laterocervical lymphadenopathy. Although serological testing of the mother's serum documented a seroconversion with positive IgG and IgM anti-Toxoplasma antibodies during II trimester, the woman refused to perform prenatal diagnosis for congenital toxoplasmosis. Fetal ultrasound scan already showed mild asymmetrical triventricular hydrocephaly and cerebral calcifications. After birth, real-time PCR on cerebrospinal fluid and blood samples of the newborn showed a positive result for 529bp-repeat element DNA of T. gondii, In addition brain magnetic resonance imaging and computed tomography showed a characteristic diffuse brain tissue loss associated with hydrocephalus. For the first time molecular characterization of T. gondii isolate was performed directly from the newborn's CSF samples by using nested-PCR-RFLP of sag-2 and pk1 genes. The PCR-RLFP analysis revealed that the isolate belongs to the clonal type II, the predominant lineage causing human toxoplasmosis, as confirmed by DNA sequencing.


Three molecular subtypes and a five-gene signature for hepatocellular carcinoma based on m7G-related classification.
The current research investigated the heterogeneity of hepatocellular carcinoma (HCC) based on the expression of N7-methylguanosine (m7G)-related genes as a classification model and developed a risk model predictive of HCC prognosis, key pathological behaviors and molecular events of HCC. The RNA sequencing data of HCC were extracted from The Cancer Genome Atlas (TCGA)-live cancer (LIHC) database, hepatocellular carcinoman database (HCCDB) and Gene Expression Omnibus database, respectively. According to the expression level of 29 m7G-related genes, a consensus clustering analysis was conducted. The least absolute shrinkage and selection operator (LASSO) regression analysis and COX regression algorithm were applied to create a risk prediction model based on normalized expression of five characteristic genes weighted by coefficients. Tumor microenvironment (TME) analysis was performed using the MCP-Counter, TIMER, CIBERSORT and ESTIMATE algorithms. The Tumor Immune Dysfunction and Exclusion algorithm was applied to assess the responses to immunotherapy in different clusters and risk groups. In addition, patient sensitivity to common chemotherapeutic drugs was determined by the biochemical half-maximal inhibitory concentration using the R package pRRophetic. Three molecular subtypes of HCC were defined based on the expression level of m7G-associated genes, each of which had its specific survival rate, genomic variation status, TME status and immunotherapy response. In addition, drug sensitivity analysis showed that the C1 subtype was more sensitive to a number of conventional oncolytic drugs (including paclitaxel, imatinib, CGP-082996, pyrimethamine, salubrinal and vinorelbine). The current five-gene risk prediction model accurately predicted HCC prognosis and revealed the degree of somatic mutations, immune microenvironment status and specific biological events. In this study, three heterogeneous molecular subtypes of HCC were defined based on m7G-related genes as a classification model, and a five-gene risk prediction model was created for predicting HCC prognosis, providing a potential assessment tool for understanding the genomic variation, immune microenvironment status and key pathological mechanisms during HCC development.


Vitreous Fatty Amides and Acyl Carnitines Are Altered in Intermediate Age-Related Macular Degeneration.
Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics. We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0. Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values < 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values < 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (-0.55-fold), and succinic acid (-1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment. Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced, suggesting that altered metabolites related to fatty amides and acyl carnitines and energy metabolism may be implicated in the etiology of AMD.


Autogenous and xenogeneic bone grafts for the bone regeneration. A literature review.
The aim of this article is to investigate 2 groups of biomaterials widely used in the surgical procedures for bone regeneration in dentistry: autograft and xenograft bone. An insufficient bone volume is the main condition for the long life stability of osteointegrated implants. Thanks to the numerous surgical procedures and fervent research, the possibility to rebuild the bone is now much more predictable than in the past. This has provided the clinician with more solutions to handle complex situations. In the last decade, the demand for regenerative surgery for functional and aesthetic reasons has increased. The autogenous bone graft is considered the gold standard material for any regeneration procedures, because of its main properties: it is osteogenetic, osteoinductive and osteoconductive. The autogenous bone can be harvested from 2 different sites: the intraoral and the extraoral sites. Intraoral donor site are the symphysis of the mandible, the mandibular ramus and the maxillary tuberosity. Extraoral donor site are the iliac crest, the tibia and the skull. The xenogeneic bone graft is a graft that has been taken from a donor of another species. These natural materials, thanks to their chemical-physical characteristics similar to those of the human bone, show great osteoconductive properties.


Right mini-thoracotomy for left maze with transesophageal echo guidance.
Minimally invasive surgery (MIS) is widening with the development of new specialized instrumentation, allied with improved surgical experience and techniques, some of which have shown to be effective for the ablation of atrial fibrillation (AF). These developments enable us to achieve a so-called 'ideal procedure', epicardially on beating hearts, with less operative risk, high cure rates and rapid patient recovery. Epicor (St Jude Medical, Sunnyvale, CA, USA) low profile (LP) system is a device using high intensity focused ultrasound (HIFU). We describe the use of this technology for ablation of AF through MIS approach using transesophageal echocardiography (TEE) to pilot the ablation on mitral isthmus. Ten patients underwent monolateral small thoracotomy, through the 4th intercostal space. HIFU was carried out in all cases to create an epicardial box lesion of the pulmonary veins (PVs) and mitral isthmus. TEE was employed to guide the positioning of the ablation device on mitral isthmus, in all patients. There were no mortalities or major complications, including pacemaker implantation. One patient had postoperative atrial tachycardia and was cardioverted before hospital discharge. Three patients had a postoperative AF and were scheduled for cardioversion after three months, and one patient spontaneously revealed a normal sinus rhythm (SR). During the follow-up period, all patients recorded a normal SR. We consider Epicor LP system safe and effective for AF ablation through a single right minimal invasive approach.


Angiotensin II-induced upregulation of SGLT1 and 2 contributes to human microparticle-stimulated endothelial senescence and dysfunction: protective effect of gliflozins.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduced cardiovascular risk in type 2 diabetes patients independently of glycemic control. Although angiotensin II (Ang II) and blood-derived microparticles are major mediators of cardiovascular disease, their impact on SGLT1 and 2 expression and function in endothelial cells (ECs) and isolated arteries remains unclear. ECs were isolated from porcine coronary arteries, and arterial segments from rats. The protein expression level was assessed by Western blot analysis and immunofluorescence staining, mRNA levels by RT-PCR, oxidative stress using dihydroethidium, nitric oxide using DAF-FM diacetate, senescence by senescence-associated beta-galactosidase activity, and platelet aggregation by aggregometer. Microparticles were collected from blood of patients with coronary artery disease (CAD-MPs). Ang II up-regulated SGLT1 and 2 protein levels in ECs, and caused a sustained extracellular glucose- and Na+-dependent pro-oxidant response that was inhibited by the NADPH oxidase inhibitor VAS-2780, the AT1R antagonist losartan, sotagliflozin (Sota, SGLT1 and SGLT2 inhibitor), and empagliflozin (Empa, SGLT2 inhibitor). Ang II increased senescence-associated beta-galactosidase activity and markers, VCAM-1, MCP-1, tissue factor, ACE, and AT1R, and down-regulated eNOS and NO formation, which were inhibited by Sota and Empa. Increased SGLT1 and SGLT2 protein levels were observed in the rat aortic arch, and Ang II- and eNOS inhibitor-treated thoracic aorta segments, and were associated with enhanced levels of oxidative stress and prevented by VAS-2780, losartan, Sota and Empa. CAD-MPs promoted increased levels of SGLT1, SGLT2 and VCAM-1, and decreased eNOS and NO formation in ECs, which were inhibited by VAS-2780, losartan, Sota and Empa. Ang II up-regulates SGLT1 and 2 protein expression in ECs and arterial segments to promote sustained oxidative stress, senescence and dysfunction. Such a sequence contributes to CAD-MPs-induced endothelial dysfunction. Since AT1R/NADPH oxidase/SGLT1 and 2 pathways promote endothelial dysfunction, inhibition of SGLT1 and/or 2 appears as an attractive strategy to enhance the protective endothelial function.


Case Report: A Novel Variant c.2262+3A>T of the SCN5A Gene Results in Intron Retention Associated With Incessant Ventricular Tachycardias.
Objective: Voltage-gated sodium channel Nav1.5 encoded by the SCN5A gene plays crucial roles in cardiac electrophysiology. Previous genetic studies have shown that mutations in SCN5A are associated with multiple inherited cardiac arrhythmias. Here, we investigated the molecular defect in a Chinese boy with clinical manifestations of arrhythmias. Methods: Gene variations were screened using whole-exome sequencing and validated by direct Sanger sequencing. A minigene assay and reverse transcription PCR (RT-PCR) were performed to confirm the effects of splice variants in vitro. Western blot analysis was carried out to determine whether the c.2262+3A>T variant produced a truncated protein. Results: By genetic analysis, we identified a novel splice variant c.2262+3A>T in SCN5A gene in a Chinese boy with incessant ventricular tachycardias (VT). This variant was predicted to activate a new cryptic splice donor site and was identified by in silico analysis. The variant retained 79 bp at the 5' end of intron 14 in the mature mRNA. Furthermore, the mutant transcript that created a premature stop codon at 818 amino acids [p.(R818*)] could be produced as a truncated protein. Conclusion: We verified the pathogenic effect of splicing variant c.2262+3A>T, which disturbed the normal mRNA splicing and caused a truncated protein, suggesting that splice variants play an important role in the molecular basis of early onset incessant ventricular tachycardias, and careful molecular profiling of these patients will be essential for future effective personalized treatment options.


Effects of ovarian endometriotic fluid exposure on fertilization rate of mouse oocytes and subsequent embryo development.
Accidental exposure of oocyte/cumulus complex to endometriotic fluid is not uncommon during oocyte retrieval. Only two studies were available on this subject and they gave conflicting results. In this study, we used a mouse model to evaluate the effect of controlled exposure of oocytes to ovarian endometriotic fluid. Mouse oocytes/cumulus complexes (n = 862) were divided into 4 groups, and were exposed to endometriotic fluid (group 1), pooled sera from subjects without endometrioma (group 2), phosphate-buffered saline (group 3), and fertilization medium (controls). After five minutes, oocytes were washed and inseminated. Embryo development was observed daily. The quality of hatching blastocysts was assessed by counting the number of inner cell mass (ICM) and trophectoderm (TE) cells. The fertilization, cleavage and blastocyst formation rates in the four groups were not statistically different. The proportions of hatching/hatched blastocysts from fertilized oocytes in groups 1 and 2 were significantly lower than those in group 3 and controls (P = 0.015). Hatching blastocysts from all groups showed no significant difference in the number of ICM and TE cells. Exposure of mouse oocytes/cumulus complexes to endometriotic fluid had subtle detrimental effects on subsequent blastocyst development. However, one should be cautious in projecting the results of this study to contaminated human oocytes in a clinical setting.


Norepinephrine-induced blood pressure rise and renal vasoconstriction are not attenuated by enalapril treatment in microalbuminuric IDDM.
In non-diabetic subjects, an attenuated systemic norepinephrine (NE) responsiveness may contribute to the mechanisms of action of angiotensin-converting enzyme (ACE) inhibitor treatment. We determined whether ACE inhibitor treatment influences systemic and renal haemodynamic responsiveness to exogenous NE, as well as urinary albumin excretion during NE, in microalbuminuric insulin-dependent diabetic (IDDM) patients, representing a patient category that benefits by strict blood pressure control. In seven microalbuminuric IDDM patients, systemic and renal responsiveness to NE, infused at individually determined threshold [deltamean arterial pressure (MAP)=0 mmHg], 20% pressor (deltaMAP=4 mmHg) and pressor (deltaMAP=20 mmHg) doses, were compared before and after 8 weeks treatment with enalapril, 10 mg daily. Blood glucose was clamped at 5 mmol/l and insulin was infused at 30 mU/kg/h. Enalapril decreased MAP (P<0.05) and microalbuminuria (P<0.05), whereas effective renal plasma flow (ERPF) increased (P<0.01) and glomerular filtration rate remained unaltered. The filtration fraction tended to decline (P=0.09). The ACE inhibitor-induced fall in MAP disappeared at NE pressor dose, and the overall mean increase in MAP in response to NE was even higher with than without enalapril (P<0.05). After enalapril, the ERPF remained higher at all NE doses (P<0.05), but the magnitude of the NE-induced fall in ERPF was not altered by ACE inhibition treatment. Overnight urinary albumin excretion fell with ACE inhibition (P<0.05), but this effect was not seen during NE infusion. The angiotensin II/active renin ratio and serum aldosterone levels remained lower with enalapril at all NE doses (P<0.05). Enalapril does not attenuate systemic and renal vascular responsiveness to exogenous NE in microalbuminuric IDDM despite adequate inhibition of the renin-angiotensin-aldosterone system. These findings suggest that the effect of NE on vasoconstriction is not counteracted effectively by ACE inhibition treatment alone.


Plasmonic nanosensors for pharmaceutical and biomedical analysis.
The detection and identification of clinical biomarkers with related sensitivity have become a source of considerable concern for biomedical analysis. There have been increasing efforts toward the development of single-molecule analytical platforms to overcome this concern. The latest developments in plasmonic nanomaterials include fascinating advances in energy, catalyst chemistry, optics, biotechnology, and medicine. Nanomaterials can be successfully applied to biomolecule and drug detection in plasmonic nanosensors for pharmaceutical and biomedical analysis. Plasmonic-based sensing technology exhibits high sensitivity and selectivity depending on surface plasmon resonance (SPR) or localized surface plasmon resonance (LSPR) phenomena. In this critical paper, we offer an overview of the methodology of the SPR, LSPR, surface-enhanced Raman scattering (SERS), surface-enhanced infrared absorption (SEIRA), surface-enhanced fluorescence (SEF), and plasmonic nanoplatforms advanced for pharmaceutical and biomedical applications. First of all, we present here a brief discussion of the above trends. We have devoted the last section to the explanation of SPR, LSPR, SERS, SEIRA, and SEF platforms, which have found a wide range of applications, and reviewed recent advances for biomedical and pharmaceutical analysis.


Acute Epstein - Barr virus hepatitis without mononucleosis syndrome: a case report.
Elevated liver enzymes accompanied by Infectious Mononucleosis syndrome are widely seen in primary Epstein-Barr virus infection while acute symptomatic hepatitis without typical presentations of EBV is extremely rare. In the following report, we present a patient with acute isolated hepatitis due to laboratory confirmed Epstein-Barr virus.


Women's self-management of chronic illnesses in the context of caregiving: a grounded theory study.
Uncover how women self-manage their own chronic illness while taking care of a dependent relative. International policies place special emphasis in promoting interventions addressed to control, prevent and care for people with chronic health conditions. Self-management is a crucial part of this care. Caregivers are more prone to have chronic illness than non-caregivers. They are confronted with dilemmas about taking care of themselves while taking care of their dependent relative and the rest of their families. Caregivers articulate strategies to enable them to focus their energy on caring. Qualitative study using constructivist grounded theory. Thirty-nine women caregivers with a chronic illness participated in the study. Twenty-three semi-structured interviews and two focus groups were carried out between April 2010-December 2011. Data were analysed using grounded theory procedures. Self-management helps women caregivers with a chronic illness to balance the demands of their own illness and those of the dependent relative. They self-manage their illness by self-regulating the treatment, by regulating their strength and by controlling their emotions. Women caregivers integrate effectively and creatively the management of their chronic illnesses within the complexities of family care. This renders their health needs invisible and reaffirms them as capable caregivers. Identifying self-management strategies of women caregivers allow health professionals to acknowledge and reinforce effective self-care measures and to deter those that are ineffective and lessen their quality of life.


Cardiopulmonary arrest on arrival due to penetrating trauma.
The aim of this study was to clarify the outcome of patients with cardiopulmonary arrest on arrival due to penetrating trauma (PT-CPA) and to establish the treatment strategy. The clinical course of 29 patients with PT-CPA over the past 10 years was examined. We have taken three approaches to these patients: (i) an aggressive treatment strategy; (ii) an in-hospital system supporting this aggressive resuscitation; and (iii) the pre-hospital emergency medical service (EMS) system in our city. Although the return of spontaneous circulation (ROSC) was established in 59% of patients, only 17% survived for 7 days, 14% were discharged, and 7% were neurologically intact. Of 10 patients showing pulseless electrical activity (PEA) on the scene, ROSC was established in 100% and 30% were discharged; however, of 12 patients showing asystole, ROSC was established in 33% and no patient could be discharged. There was no difference in the time interval from the arrival at the emergency department to ROSC between discharged patients and patients who died. The time interval from collapse to arrival at the emergency department in discharged patients and patients who went to the intensive care unit was shorter than that of patients who died in the emergency department with and without ROSC. We cannot decide to give up and terminate resuscitation in any PT-CPA patients and cannot define salvageable patients. However, our data show that 30-min resuscitation is thought to be relevant and that we should not give up on resuscitation because of the time interval without ROSC after arrival at the hospital.


Raman Optical Activity Reveals Carotenoid Photoactivation Events in the Orange Carotenoid Protein in Solution.
The orange carotenoid protein (OCP) plays an important role in photoprotection in cyanobacteria, which is achieved by the photoconversion from the orange dark state (OCPO) to the red active state (OCPR). Using Raman optical activity (ROA), we studied the conformations of the carotenoid chromophore in the active sites of OCPO and OCPR. This ROA measurement directly observed the chromophore conformation of native OCP in solution, and the measurement of OCPR first demonstrated the ROA spectroscopy for the transient species. For OCPO, the spectral features of ROA were mostly reproduced by the quantum chemical calculation based on the crystal structure of the OCP. Within the spatial resolution (∼2 Å), a slight modification of the polyene-chain distortion improved the agreement between the observed and calculated ROA spectra. While the crystal structure of OCPR is not available, the ROA spectrum of OCPR was reproduced by using the crystal structure of red carotenoid protein (RCP), an OCPR proxy. The present results showed that the chromophore conformations in the crystal structures of OCP and RCP hold true for OCPO and OCPR in solution. Particularly, ROA spectroscopy of the native OCPR provides a direct support for the 12 Å translocation of chromophore in the photoactivation, which was proposed by X-ray crystallography using RCP [R. L. Leverenz, M. Sutter, et al. Science 2015, 348, 1463-1466].


Synthesis of 2,6-Dimethoxy-p-aminophenol from Hardwood Lignin.
Although the multiple functional groups in biomass offer notable chances for producing high-value chemicals, most of the current studies focused on the (deep) defunctionalization of biomass and its derivates. Herein, we present a catalytic approach to valorize birch wood lignin with maintaining the methoxy and hydroxy groups in the final product (i. e., 2,6-dimethoxy-p-aminophenol), which has applications in different sectors such as pharmaceuticals. The proved approach involves four steps with a high yield (19.8 wt % on the basis of used lignin) to 2,6-dimethoxy-p-aminophenol. The native lignin in birch wood was first converted using alkaline aerobic oxidation in the presence of copper ions toward high-yield syringaldehyde, which was then selectively oxidized toward 2,6-dimethoxy-1,4-benzoquinone using H2 O2 and V2 O5 . Oximation of 2,6-dimethoxy-1,4-benzoquinone can selectively form 2,6-dimethoxy-1,4-benzoquinone-4-oxime, which can be quantitatively hydrogenated toward 2,6-dimethoxy-p-aminophenol. This work highlights the unique potential of biomass and its derivates for the sustainable production of high-value products with exploring the value of inherent functional groups.


The role of probiotics in gastrointestinal disease.
Patients with intestinal failure often have diarrhea for a variety of reasons. Treatment of diarrhea has centered on the use of antidiarrheal medications and antibiotic therapy. Recently, there has been interest in the oral administration of probiotics for these patients with small bowel bacterial overgrowth, inflammatory bowel disease, and radiation enteritis. This paper reviews the studies that have used probiotics to treat patients with short bowel syndrome and gastrointestinal disorders. Additionally, some of the specific issues regarding probiotics are addressed.


Alimentary Canal of the Adult Blow Fly, Chrysomya megacephala (F.) (Diptera: Calliphoridae)-Part I: Ultrastructure of Salivary Glands.
The salivary gland ultrastructure of the adult male blow fly, Chrysomya megacephala (F.) (Diptera: Calliphoridae), was investigated at the ultrastructural level using light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The salivary glands are paired structures composed of a single median deferent duct bifurcated into two long, narrow efferent ducts connected to the coiled tubular glands. The SEM image of the gland surface revealed that the basal lamina is relatively smooth in general, but the whole surface appeared as a trace of rough swollen insertion by intense tracheal ramification. Ultrastructurally, the salivary gland is enclosed within the basal lamina, and interdigitation cytoplasmic extensions were apparent between the adjacent gland cells. The basement membrane appeared infoldings that is similar to the complex of the labyrinth channel. The cytoplasm characteristic of the gland revealed high activity, based on the abundance of noticeable secretory granules, either singly or in an aggregated reservoir. In addition, mitochondria were found to intersperse among rich parallel of arrays rough endoplasmic reticulum. Thick cuticle, which was well-delineated and electron dense, apically lined the gland compartments, with discontinuity of the double-layer cuticle revealing a trace of secretion discharged into the lumen. Gross anatomy of the adult salivary gland was markedly different from that of the third instar of the same species, and structural dissimilarity is discussed briefly.


Sudden cardiac death in young athletes: preparticipation screening for underlying cardiovascular abnormalities and approaches to prevention.
The study of sudden cardiac death (SCD) in athletes has received more interest in the medical and lay press over the past few years. Professional athletes represent ideals of fitness and health, and the sudden death of prominent athletes can come as a shock. Underlying occult cardiovascular disorders are the most common cause of SCD in athletes. Unfortunately, because these disorders rarely present clinically, their initial manifestation is often a fatal event. Due to this, much attention has turned to both primary and secondary prevention. Primary prevention includes preparticipation screening and secondary prevention includes having automatic external defibrillators available at sporting events. This article summarizes the most common causes of athletic-related cardiac arrest and evaluates the screening methods used to screen for these conditions. The general sentiment is that we need to more effectively identify athletes who are at risk for SCD, but how to do so using an efficient screening system and in a cost-effective manner have not been determined.


Severe hypothermia in transported pullets: case study of its occurrence, diagnosis and treatment using active external rewarming technique.
Sixty pullets, aged 17 weeks, were presented when presumed to be 'dead' after being exposed to wet-cold weather transportation. The birds appeared unconscious and their feathers were soaking wet, and with a body rigid and cold to touch. The aim of the study was to resuscitate the hypothermic pullets. Blood samples were obtained and core body temperature recorded before and after rewarming. The birds were resuscitated using active external rewarming technique. Blood samples revealed significant (P < 0.05) decreases in the concentrations of serum electrolytes of Na, Cl, K, Ca and P; and renal function and activities of the serum enzymes of AST, ALT, ALP and CRT decreased compared to baseline reference normal values. Colonic temperature, recorded through the cloacae, revealed a temperature of 29 ± 0.4°C. The presumptive diagnosis was severe hypothermia. Treatment of the pullets using active external rewarming technique for 7 to 10 h resulted in successful restoration of all the behavioural, biochemical and colonic temperature responses to normal values. The treatment resulted in a complete recovery of all the birds with no signs of illness at 4-week follow-up. To the best of our knowledge, this study is one of the first reports to evaluate the behavioural and biochemical responses of pullets accidentally exposed to severe hypothermia, and successful treatment of the birds using active external rewarming technique.